nils-herrmann/clean_scirepeval huggingface dataset:
Phase I study of UCN-01 and perifosine in patients with relapsed and refractory acute leukemias and high-risk myelodysplastic syndrome

The PI3K-Akt pathway is frequently activated in acute leukemias and represents an important therapeutic target. UCN-01 and perifosine are known to inhibit Akt activation.  The primary objective of this phase I study was to determine the maximum tolerated dose (MTD) of UCN-01 given in combination with perifosine in patients with advanced acute leukemias and myelodysplastic syndrome. Secondary objectives included safety, pharmacokinetics, pharmacodynamics, and efficacy. Perifosine 150 mg every 6 h was given orally on day 1 followed by 100 mg once a day continuously in 28-day cycles. UCN-01 was given intravenously over 3 h on day 4 at three dose levels (DL1 = 40 mg/m2; DL2 = 65 mg/m2; DL3 = 90 mg/m2).  Thirteen patients were treated (DL1, n = 6; DL2, n = 4; DL3, n = 3) according to a traditional “3 + 3” design. Two patients at the DL3 experienced dose-limiting toxicity including grade 3–4 pericardial effusion, hypotension, hyperglycemia, hyperkalemia, constitutional symptoms and grade 5 pneumonitis. Other frequent toxicities were grade 1–2 nausea, diarrhea, vomiting, fatigue and hyperglycemia. The MTD was determined to be UCN-01 65 mg/m2 with perifosine 100 mg a day. No appreciable direct Akt inhibition could be demonstrated in patients’ mononuclear cells using Western blot, however, reduced phosphorylation of the downstream target ribosomal protein S6 in leukemic blasts was noted by intracellular flow cytometry. No objective responses were observed on this study.  UCN-01 and perifosine can be safely administered, but this regimen lacked clinical efficacy. This approach may have failed because of insufficient Akt inhibition in vivo.
Characterization of Tumor Size Changes Over Time From the Phase 3 Study of Lenvatinib in Thyroid Cancer

Lenvatinib improved the progression-free survival (PFS) and overall response rate of patients with radioiodine-refractory differentiated thyroid cancer vs placebo in the Phase 3 Study of (E7080) Lenvatinib in Differentiated Cancer of the Thyroid (SELECT).



The objective of the study was to characterize tumor size changes with lenvatinib treatment.



SELECT was a phase 3, randomized, double-blind, multicenter study.



In this clinical trial, tumor assessments of lenvatinib (n = 261) and placebo-treated (n = 131) patients were performed by independent radiological review per Response Evaluation Criteria in Solid Tumors version, 1.1 at 8-week intervals.



Patients with complete or partial response were defined as responders to lenvatinib (n = 169). Of the 92 nonresponders, 76 had at least one postbaseline tumor assessment and were included in this analysis.



Lenvatinib (24 mg once daily) or placebo in 28-day cycles until unacceptable toxicity, disease progression, or death.



This was an exploratory analysis of key end points from SELECT, including PFS, overall response rate, and tumor reduction.



The median maximum percentage change in tumor size was -42.9% for patients receiving lenvatinib (responders, -51.9%; nonresponders, -20.2%). Tumor size reduction was most pronounced at first assessment (median, -24.7% at 8 wk after randomization); thereafter, the rate of change was slower but continuous (-1.3% per mo). In a multivariate model, percentage change in tumor size at the first assessment was a marginally significant positive predictor for PFS (P = .06).



The change in tumor size conferred by lenvatinib was characterized by two phases: an initial, rapid decline, followed by slower, continuous shrinkage.
Prevalence and factors associated with left ventricular dysfunction in the EULAR Scleroderma Trial and Research group (EUSTAR) database of patients with systemic sclerosis.

To measure the prevalence of, and factors associated with, left ventricular (LV) dysfunction in systemic sclerosis (SSc).



The EUSTAR database was first searched. A case-control study of a patient subset was then performed to further identify independent factors associated with LV dysfunction by simple and multiple regression.



Of 7073 patients, 383 (5.4%) had an LV ejection fraction (EF) of <55%. By multiple regression analysis, age, sex, diffuse cutaneous disease, disease duration, digital ulcerations, renal and muscle involvement, disease activity score, pulmonary fibrosis and pulmonary arterial hypertension were associated with LV dysfunction. In the second phase, 129 patients with SSc with LVEF <55% were compared with 256 patients with SSc with normal LVEF. Male sex (OR 3.48; 95% CI 1.74 to 6.98), age (OR 1.03; 95% CI 1.01 to 1.06), digital ulcerations (OR 1.91; 95% CI 1.05 to 3.50), myositis (OR 2.88; 95% CI 1.15 to 7.19) and use of calcium channel blockers (OR 0.41; 95% CI 0.22 to 0.74) were independent factors associated with LV dysfunction.



The prevalence of LV dysfunction in SSc is 5.4%. Age, male gender, digital ulcerations, myositis and lung involvement are independently associated with an increased prevalence of LV dysfunction. Conversely, the use of calcium channel blockers may be protective.
A prototype of an adjustable advanced reciprocating gait orthosis (ARGO) for spinal cord injury (SCI)

To develop a reciprocating gait orthosis which could be used in different sized patients. Clinical trial and orthotic development. A large rehabilitation hospital in Rome, ItalyPatients and methods: To carry out this project normal reciprocating gait orthosis parts were used. The device was modified to adjust the hip–ankle height, and the hip–hip distance. It was tested, by five patients already walking with standard ARGO, to evaluate the performances of the orthosis. The device has been tested on seven newly injured patients fulfilling specific criteria of different height and weight. Prototype suitability; patients appreciation. The device can be used for persons between 1.60 m and 1.85 m tall, weighing up to 100 kg. The orthosis allows an upright position without the use of the hands, and walking with a walker or with two canes. The foot orthosis cover sizes 36–40 (British 3–7) and 41–45 (British 7–11). With the exception of donning, doffing and lifting, the walking performances of the prototype and the general appreciation is comparable with those of a standard device. After a short period of training all seven patients were able to walk in the parallel bars. All of them expressed general appreciation for the device; despite this only four patients wanted the orthosis, two refused it and one has not decided yet. The prototype allows the same standing and walking performances of normal ARGO. It could be used in spinal cord injury patients to let them test the potential of the device and thus be useful in the effort to reduce the percentage of ARGO rejection.
The effect of educational attainment and other factors on HIV risk in South African women: results from antenatal surveillance, 2000-2005.

To assess the effect of educational attainment and other factors on the risk of HIV in pregnant South African women.



Repeated cross-sectional surveys.



Pregnant women attending public antenatal clinics were tested for HIV annually between 2000 and 2005, and provided demographic information. Logistic regression models were applied separately to the data collected in each year, to identify factors associated with HIV infection. Data from all years were combined in a logistic regression model that tested for trends in HIV prevalence.



Amongst women aged 15-24 years, HIV risk in those who had completed secondary education was significantly lower than in those who had only primary education, in all years except 2000. HIV risk increased by 8% per annum (odds ratio 1.08, 95% confidence interval 1.04-1.12) in young women with no secondary education but did not increase in young women with secondary education. In women aged 25-49 years, HIV risk increased over the 2000-2005 period, at all levels of educational attainment, and did not differ between women with completed secondary education and women with only primary education.



Together with other evidence, this study suggests that higher educational attainment did not protect against HIV in the early stages of the South African HIV/AIDS epidemic. In recent years, the risk of HIV infection in young South African women with completed secondary education has reduced significantly relative to that in young women with primary education, suggesting that HIV prevention strategies may have been more effective in more educated women.
Peer mentoring for type 2 diabetes prevention in first nations children.

The goal of this study was to assess the efficacy of an after-school, peer-led, healthy living program on adiposity, self-efficacy, and knowledge of healthy living behaviors in children living in a remote isolated First Nation.



A quasi-experimental trial with a parallel nonequivalent control arm was performed with 151 children in Garden Hill First Nation during the 2010-2011 and 2011-2012 school years. Fourth grade students were offered a 5-month, peer-led intervention facilitated by high school mentors between January and May of each school year; students in the control arm received standard curriculum. The main outcome measures were waist circumference (WC) and BMI z score. Secondary outcome measures included healthy living knowledge and self-efficacy.



Fifty-one children (mean ± SD age: 9.7 ± 0.4 years; BMI z score: 1.46 ± 0.84) received the intervention, and 100 children were in the control arm. At baseline, WC (79.8 vs 83.9 cm), BMI z score (1.46 vs 1.48), and rates of overweight/obesity (75% vs 72%) did not differ between arms. After the intervention, the change in WC (adjusted treatment effect: -2.5 cm [95% confidence interval (CI): -4.1 to -0.90]; P = .002) and BMI z score (adjusted treatment effect: -0.09 [95% CI: -0.16 to -0.03]; P = .007) were significantly lower in the intervention arm compared to the control arm. The intervention arm also experienced improvements in knowledge of healthy dietary choices (2.25% [95% CI: -0.01 to 6.25]; P = .02). Self-efficacy was associated with the change in WC after the intervention (β = -7.9, P = .03).



An after-school, peer-led, healthy living program attenuated weight gain and improved healthy living knowledge in children living in a remote isolated First Nation.
Calcium-channel blockade with nifedipine and angiotensin converting-enzyme inhibition with captopril in the therapy of patients with severe primary hypertension.

Nifedipine (10 mg qid) and captopril (25 mg qid) were tested alone and in combination in 14 patients suffering from severe primary hypertension. Each study period was of 1 week's duration. Circulatory response was evaluated through hourly pressure and pulse rate readings. The fall in pressure after oral nifedipine was maximal within 1 hr or less and was generally accompanied by palpitation and increase in pulse rate; with a six hourly dosing regimen the tendency of blood pressure to recover after each dose was interrupted by the next dose, so that values remained significantly reduced throughout the 24 hr, although pressure fluctuations were evident. Promptness of the antihypertensive action of captopril was similar, but the magnitude and the duration of the fall in pressure were less pronounced. When the converting-enzyme inhibitor was combined with the calcium-channel blocker, pressure fluctuations were not abolished, but the antihypertensive response was definitely enhanced, so that normal blood pressure was maintained for several hours during the day. Additional positive effects of captopril were mitigation of the heart rate reaction and prevention of the ankle pitting or edema elicited by nifedipine. A balance in arteriolar and venular dilatation promoted by captopril is the suggested mechanism for these effects. With the two-drug combination the function of the left ventricle was not reduced and possibly improved; blood urea nitrogen and serum electrolyte and creatinine concentration were not affected. Plasma renin activity increased with captopril and reverted toward baseline with the addition of nifedipine, suggesting an interference of the calcium-channel blocker with the release of renin.
Efficacy of theory-based activities for behavioral symptoms of dementia.

Agitation and passivity are behavioral symptoms exhibited by 90% of nursing home residents with dementia. They account for many poor health outcomes, caregiver burden, and increased costs of long-term care.



This study tested the efficacy of recreational activities derived from the Need-driven Dementia-compromised Behavior (NDB) model: activities matched to skill level only; activities matched to style of interest only; and a combination of both (NDB-derived) for responding to the behavioral symptoms of dementia.



Thirty participants were randomly assigned to 1 of 6 possible order-of-condition presentations in this crossover experimental design with repeated measures of dependent variables. Trained research assistants, blind to condition match, implemented each condition for 12 consecutive days. Measures of engagement (time on task and participation), affect, and behavioral symptoms (agitation and passivity) were taken from videotape recordings of each session. Mood was measured with the Dementia Mood Picture Test. The primary analysis method was mixed-model analysis of variance.



Significantly more time on task, greater participation, more positive affect, and less passivity were found under NDB-derived and matched to interest only treatments compared with the matched to skill level only treatment or baseline. Agitation and negative affect improved under all treatments compared with baseline. There was no significant change in mood.



The NDB-derived activities are tailored to meet individual needs and improve behavioral symptoms associated with dementia. These findings help to explain factors that produce behavioral symptoms and the mechanisms that underlie their successful treatment.
Longitudinal treatment mediation of traditional cognitive behavioral therapy and acceptance and commitment therapy for anxiety disorders.

To assess the relationship between session-by-session putative mediators and treatment outcomes in traditional cognitive behavioral therapy (CBT) and acceptance and commitment therapy (ACT) for mixed anxiety disorders.



Session-by-session changes in anxiety sensitivity and cognitive defusion were assessed in 67 adult outpatients randomized to CBT (n = 35) or ACT (n = 32) for a DSM-IV anxiety disorder.



Multilevel mediation analyses revealed significant changes in the proposed mediators during both treatments (p < .001, d = .90-1.93), with ACT showing borderline greater improvements than CBT in cognitive defusion (p = .05, d = .82). Anxiety sensitivity and cognitive defusion both significantly mediated post-treatment worry; cognitive defusion more strongly predicted worry reductions in CBT than in ACT. In addition, cognitive defusion significantly mediated quality of life, behavioral avoidance, and (secondary) depression outcomes across both CBT and ACT (p < .05, R(2) change = .06-.13), whereas anxiety sensitivity did not significantly mediate other outcomes.



Cognitive defusion represents an important source of therapeutic change across both CBT and ACT. The data offered little evidence for substantially distinct treatment-related mediation pathways.
Is urinary γ-glutamyl transpeptidase superior to urinary neutrophil gelatinase-associated lipocalin for early prediction of acute kidney injury after liver transplantation?

In this prospective study, we comparatively evaluated the accuracy of several biomarkers of acute kidney injury (AKI) on predicting its occurrence after liver transplantation (LT). The parameters evaluated were urinary tubular enzymes (γ-glutamyl transpeptidase [γGT], alkaline phosphatase, and urinary lactate dehydrogenase) and urinary neutrophil gelatinase-associated lipocalin. These parameters were evaluated both as isolated variables and divided by urinary creatinine. Samples were collected by the end of surgery (determination 1) and at 12 to 24 hours after surgery (determination 2). The study endpoint was the development of AKI. The study was performed over a 1-year period, and 61 of 77 patients were enrolled (main exclusion criteria were perioperative death, previous known renal failure, and insufficient data for analysis). Of these 61 patients, AKI was observed in 19 (group 1). The main relevant parameter to predict AKI was the absolute value of urinary γGT at determination 1 (area under the curve, 0.74; specificity, 72.5%; sensitivity, 70.3%; cutoff, 36 U/mL). Urinary neutrophil gelatinase-associated lipocalin was not as accurate; the best predicted value for this parameter was absolute value at D1 with an area under the curve of 0.5 (specificity, 84.2%; sensitivity, 35.7%; cutoff value, 44.6 ng/mL). We concluded that the absolute value of urinary γGT evaluated at the end of LT was the most accurate parameter to predict AKI in our cohort. Urinary enzyme levels must be taken into account in future analysis of this issue.
Clinical evaluation of diminished early expiratory flow (DEEF) ventilation in mechanically ventilated COPD patients

To evaluate the cardiopulmonary effects, especially the end-expiratory lung volume (EEV) and ventilation inhomogeneity during diminished early expiratory flow ventilation (DEEF), which resembles pursed-lips breathing, with the conventional intermitent positive pressure ventilation (IPPV) in postoperative mechanically ventilated patients with chronic obstructive pulmonary disease (COPD). A prospective study measuring cardiopulmonary parameters during IPPV, DEEF, and positive end-expiratory pressure (PEEP) as a control mode. In the PEEP mode, PEEP values were chosen such that the mean airway pressure during a breath cycle was equal to that during the DEEF mode, which was higher than the conventional IPPV mode. Surgical intensive care unit of a university hospital. 20 postoperative mechanically ventilated COPD patients who were optimally pretreated and had normal blood oxygenation. Measurements were started in the IPPV (IPPV1) mode, continued in a randomized order with DEEF or PEEP, and completed with a second IPPV (IPPV2) mode, with 1 h equilibration time in each mode before each measurement. A multi-breath indicator gas wash-out test was used to calculate the EEV and ventilation inhomogeneity. There was a 9% increase (p<0.05) in the mean EEV during both the DEEF and PEEP mode compared to IPPV. No significant changes in the ventilation inhomogeneity and deadspace fractions or the hemodynamic parameters were found during the different ventilatory modes. There was no improvement in pulmonary and hemodynamic parameters during the DEEF mode in comparison to the IPPV mode. The small increase in EEV during DEEF was probably caused by the slightly higher mean expiratory pressures as in the PEEP mode. However, this had no effect on the hemodynamic parameters. As we could not observe any improvement with the DEEF ventilation in our optimally pretreated postoperative COPD patients, we do not advise applying this therapy in this group of patients, since this mode of ventilation may cause barotrauma if not monitored adequately.
Radiation treatment of urinary bladder carcinoma

A series of 602 patients with verified urinary bladder cancer have been treated with full irradiation in the period 1957–1970. As expected, the survival rate decreased with increasing stage of the tumour. Another group was randomized and treated according to either of two fractionation schemes. This trial started in 1971 and shows that there is increased survival and tumour clearance rate with superfractionation.
Implementation of outpatient treatment of deep-vein thrombosis in private practices in Germany.

Implementation of outpatient treatment (OT) of deep-vein thrombosis (DVT) is slow despite clear evidence that it is effective, safe and cost-efficient.



An initiative was launched with the help of the Professional Association of Phlebologists of Germany and the industry to familiarize physicians in private practice who had no prior experience with OT of DVT. Data on quality of treatment with the low-molecular-weight heparin tinzaparin and phenprocoumon, compliance, clinical outcome, venous ultrasound, patients' satisfaction and quality of life were collected in a registry, which was open from July 1999 to December 2000. The results were published and their impact on further management of patients was assessed in second survey reported here. Patients of both series were followed-up clinically and with ultrasound over the 1st month of treatment.



Of 67 physicians entering 827 patients into the registry 26 answered a questionnaire on how they treated further patients. Their case load had increased by 450% and data were provided on 540 consecutive patients managed between January and June 2002. OT increased overall from 76 to 92%, that of popliteo-femoral DVT from 71 to 92%, and that of pelvic DVT from 38 to 65%. Medical reasons to decide against OT decreased from 89 to 56% (p<.01). Immediate leg compression was changed from bandaging to medical compression stockings in 20 of the 26 centres (p<.05). In total, data were gathered from OT of 1124 patients. No secondary hospitalisations were required and only one patient had a documented progression of the DVT.



OT was successfully implemented in private practices through the initiative of individual physicians with support of the professional association and sponsoring by the industry-to the benefit of the providers but as much of the patients and their cost bearers.
Manual chest compression vs use of an automated chest compression device during resuscitation following out-of-hospital cardiac arrest: a randomized trial.

High-quality cardiopulmonary resuscitation (CPR) may improve both cardiac and brain resuscitation following cardiac arrest. Compared with manual chest compression, an automated load-distributing band (LDB) chest compression device produces greater blood flow to vital organs and may improve resuscitation outcomes.



To compare resuscitation outcomes following out-of-hospital cardiac arrest when an automated LDB-CPR device was added to standard emergency medical services (EMS) care with manual CPR.



Multicenter, randomized trial of patients experiencing out-of-hospital cardiac arrest in the United States and Canada. The a priori primary population was patients with cardiac arrest that was presumed to be of cardiac origin and that had occurred prior to the arrival of EMS personnel. Initial study enrollment varied by site, ranging from late July to mid November 2004; all sites halted study enrollment on March 31, 2005.



Standard EMS care for cardiac arrest with an LDB-CPR device (n = 554) or manual CPR (n = 517).



The primary end point was survival to 4 hours after the 911 call. Secondary end points were survival to hospital discharge and neurological status among survivors.



Following the first planned interim monitoring conducted by an independent data and safety monitoring board, study enrollment was terminated. No difference existed in the primary end point of survival to 4 hours between the manual CPR group and the LDB-CPR group overall (N = 1071; 29.5% vs 28.5%; P = .74) or among the primary study population (n = 767; 24.7% vs 26.4%, respectively; P = .62). However, among the primary population, survival to hospital discharge was 9.9% in the manual CPR group and 5.8% in the LDB-CPR group (P = .06, adjusted for covariates and clustering). A cerebral performance category of 1 or 2 at hospital discharge was recorded in 7.5% of patients in the manual CPR group and in 3.1% of the LDB-CPR group (P = .006).



Use of an automated LDB-CPR device as implemented in this study was associated with worse neurological outcomes and a trend toward worse survival than manual CPR. Device design or implementation strategies require further evaluation.