nils-herrmann/clean_scirepeval huggingface dataset:
Intravenous administration of Reolysin®, a live replication competent RNA virus is safe in patients with advanced solid tumors

Reolysin® is reovirus serotype 3-Dearing strain, a double-stranded replication-competent RNA non-enveloped icosahedral virus. It induces cytopathic and anti-cancer effects in cells with an activated ras pathway due to inhibition of the dsRNA-activated protein kinase.  This was a single center dose escalation trial of Reolysin administered intravenously every 4 weeks in doses ranging from 1 × 108 to 3 × 1010 tissue culture infective dose (TCID)50. Serum for neutralizing antibody, and serum, stool, saliva, and urine for viral shedding were collected. Tumor samples were analyzed for activating mutations in the ras and braf oncogenes.  Eighteen patients received 27 doses of Reolysin in 6 dose cohorts accomplishing a 300 fold dose escalation without a protocol-defined dose limiting toxicity. Drug related grade 2 toxicities included fatigue and fever (1 patient each). All patients developed neutralizing antibody during the course of the study. Viral shedding was observed in 6 patients. One patient with anthracycline and taxane refractory breast cancer experienced a partial response (PR) and her tumor had a ras G12A mutation. Biopsy from her chest wall mass showed evidence of necrosis and viral replication by electron microscopy. Overall clinical benefit (1 PR + 7 stable disease) rate was 45%, and appeared higher in patients with viral shedding (67%) than those without (33%).  Reolysin administered monthly as a one-hour infusion is safe and well-tolerated even in multiple doses. Reolysin has anti-tumor activity as a single agent warranting further evaluation, including in combination with chemotherapy. Viral shedding may suggest intrapatient replication yielding a benefit and should be studied carefully in future studies.
Comparative long-term experience with immunoadsorption and dextran sulfate cellulose adsorption for extracorporeal elimination of low-density lipoproteins

Two low-density lipoprotein (LDL) apheresis methods allowing a specific extracorporeal removal of atherogenic lipoproteins from plasma were compared concerning their efficacy and safety in the long-term therapy of severe familial hypercholesterolemia. Five patients were treated with immunoadsorption (IMA) at weekly intervals over 3 years each, and three patients received weekly therapy with dextran sulfate cellulose adsorption (DSA) for up to 2 years. The mean plasma volume processed per session to decrease total cholesterol to a target level of 100–150 mg/dl at the end of LDL apheresis was significantly lower in DSA than in IMA: 143% vs. 180% of the individual plasma volume. Both LDL apheresis procedures achieved a mean acute reduction of plasma LDL cholesterol by more than 70%. The average interval concentrations of plasma LDL cholesterol obtained without concomitant lipid-lowering medication were 151 ± 26 mg/dl compared to 351 ± 65 mg/dl at baseline in the IMA-treated patients and 139 ± 18 mg/dl compared to 359 ± 48 mg/dl at baseline in the DSA-treated patients. Two patients from the DSA group died after 2 years of study participation due to a stroke and a sudden cardiac death several days after the last plasma therapy. Treatment-related side effects were infrequent. Long-term therapy with IMA and DSA was associated with symptomatic improvement of coronary artery disease and mobilization of tissue cholesterol deposits. Analysis of coronary angiograms after 3 years of weekly LDL apheresis with IMA revealed in five patients nearly identical atherosclerotic lesions without definite regression or progression.
Evaluation of Salud Para Su Corazón (Health for Your Heart) — National Council of La Raza Promotora Outreach Program

In 2001, the National Heart, Lung, and Blood Institute partnered with the National Council of La Raza to conduct a pilot test of its community-based outreach program Salud Para Su Corazón (Health for Your Heart), which aims to reduce the burden of morbidity and mortality associated with cardiovascular disease among Latinos.



The effectiveness of promotores de salud (community health workers) in improving heart-healthy behaviors among Latino families participating in the pilot program at seven sites was evaluated. Data on the characteristics of the promotores in the Salud Para Su Corazón program were compiled. Promotores collected data on family risk factors, health habits, referrals and screenings, information sharing, and program satisfaction from 223 participating Latino families (320 individual family members) through questionnaires. Paired t tests and chi-square tests were used to measure pretest-posttest differences among program participants.



Results demonstrated the effectiveness of the promotora model in improving heart-healthy behaviors, promoting community referrals and screenings, enhancing information sharing beyond families, and satisfying participants' expectations of the program. The main outcome of interest was the change in heart-healthy behaviors among families.



The community outreach model worked well in the seven pilot programs because of the successes of the promotores and the support of the community-based organizations. Successes stemmed in part from the train-the-trainer approach. Promotoria, as implemented in this program, has the potential to be integrated with a medical model of patient care for primary, secondary, and tertiary prevention.
Intrusion and avoidance in subjects undergoing genetic investigation and counseling for hereditary cancer

Genetic counseling for hereditary cancer is expected to involve a growing number of individuals in the near future since an increasing number of genetic tests are offered. This study was designed to identify psychosocial variables predicting distress after genetic investigation and genetic counseling (GC) in order to develop new counseling strategies. A prospective multi-site study was undertaken on 214 patients undergoing GC for hereditary cancer to explore the relationships between socio-demographic variables, medical variables, social support, self-efficacy, physical functioning, satisfaction with GC, the level of worry after GC, results of genetic testing, and the course and outcomes of distress. Distress was measured with the Impact of Event Scale, which includes subscales of intrusion and avoidance. Patients completed questionnaires mailed to them before and after GC. The mean level of intrusion and avoidance was moderate, even though one quarter of participants reported a severe level of intrusion at baseline. Subjects with a low level of self-efficacy at baseline and high level of worry immediately after GC seemed to be vulnerable to both intrusion and avoidance. Lower level of intrusion was also associated with having a first-degree relative with cancer, while a lower avoidance level was associated with a higher level of education, having cancer, more social support, and higher satisfaction with GC. In this study, subjects who had lower level of self-efficacy at baseline and a high level of worry immediately after GC seemed to be vulnerable to both intrusion and avoidance in this study.
The cost effectiveness of bevacizumab when added to capecitabine, with or without mitomycin-C, in first line treatment of metastatic colorectal cancer: results from the Australasian phase III MAX study.

Based on the clinical data, bevacizumab has been approved in Australia and globally for the treatment of advanced colorectal cancer. However, limited evidence exists for its cost-effectiveness. The purpose of this study was to evaluate the cost effectiveness of adding bevacizumab to capecitabine monotherapy in patients with metastatic colorectal cancer, using data from the prospective economic evaluation conducted alongside the MAX trial.



Individual patient level data on resource use and progression free survival were prospectively collected in the phase III MAX trial. Resource use data were collected for the period between randomisation and disease progression, and unit costs were assigned from the perspective of the Australian health care funder. Effectiveness was measured in quality adjusted progression free survival years, with utility scores obtained from both the community valued EQ-5D questionnaire and the patient valued UBQ-C questionnaire. Progression free survival was used as a secondary effectiveness measure.



The addition of bevacizumab to capecitabine monotherapy cost approximately $192,156 (95% confidence interval [CI], $135,619 to $326,894) per quality adjusted progression free survival year gained when using publicly listed pharmaceutical prices and utility values from the EQ-5D questionnaire. This decreased to $149,455 (95% CI, $100,356 to $245,910) when values from the UBQ-C questionnaire were applied. The incremental cost per progression free survival year was $145,059 (95% CI, $106,703 to $233,225).



Bevacizumab was not found to be cost effective at its listed price, based on results from the MAX trial.
Oral versus intravenous fludarabine as part of a reduced-intensity conditioning for allogeneic stem cell transplantation.

In 2003, oral fludarabine was introduced in the USA for the treatment of patients with hematologic malignancies as an alternative to its intravenous (i.v.) formulation; in 2008, it was introduced in México while the i.v. formulation was withdrawn. Accordingly, i.v. fludarabine had to be replaced by oral fludarabine as part of the conditioning regimen employed to conduct allogeneic stem cell transplantation in México.



Nonrandomized retrospective analysis of 55 patients conditioned with oral fludarabine compared with 113 patients conditioned with the i.v. formulation. In addition to fludarabine, the conditioning regimen included oral busulfan and i.v. cyclophosphamide. Donors were HLA-matched siblings.



The clinical features of the two groups were comparable. There were no statistical differences in time to neutrophil engraftment, time to platelet engraftment, acute graft versus host disease rate and nonrelapse mortality at day 100. The overall survival of patients allografted with oral fludarabine was better than those allografted with i.v. fludarabine: 62 and 33% at 67 months, respectively (p = 0.0006).



Oral fludarabine can replace its i.v. formulation as part of reduced-intensity conditioning regimens with no deleterious effect on any of the early transplantation outcomes.
Aerobic Interval Training Reduces the Burden of Atrial Fibrillation in the Short Term: A Randomized Trial.

Exercise training is an effective treatment for important atrial fibrillation (AF) comorbidities. However, a high level of endurance exercise is associated with an increased AF prevalence. We assessed the effects of aerobic interval training (AIT) on time in AF, AF symptoms, cardiovascular health, and quality of life in AF patients.



Fifty-one patients with nonpermanent AF were randomized to AIT (n=26) consisting of four 4-minute intervals at 85% to 95% of peak heart rate 3 times a week for 12 weeks or to a control group (n=25) continuing their regular exercise habits. An implanted loop recorder measured time in AF continuously from 4 weeks before to 4 weeks after the intervention period. Cardiac function, peak oxygen uptake (o2peak), lipid status, quality of life, and AF symptoms were evaluated before and after the 12-week intervention period. Mean time in AF increased from 10.4% to 14.6% in the control group and was reduced from 8.1% to 4.8% in the exercise group (P=0.001 between groups). AF symptom frequency (P=0.006) and AF symptom severity (P=0.009) were reduced after AIT. AIT improved o2peak, left atrial and ventricular ejection fraction, quality-of-life measures of general health and vitality, and lipid values compared with the control group. There was a trend toward fewer cardioversions and hospital admissions after AIT.



AIT for 12 weeks reduces the time in AF in patients with nonpermanent AF. This is followed by a significant improvement in AF symptoms, o2peak, left atrial and ventricular function, lipid levels, and QoL.
Exenatide Regulates Cerebral Glucose Metabolism in Brain Areas Associated With Glucose Homeostasis and Reward System.

Glucagon-like peptide 1 receptors (GLP-1Rs) have been found in the brain, but whether GLP-1R agonists (GLP-1RAs) influence brain glucose metabolism is currently unknown. The study aim was to evaluate the effects of a single injection of the GLP-1RA exenatide on cerebral and peripheral glucose metabolism in response to a glucose load. In 15 male subjects with HbA1c of 5.7 ± 0.1%, fasting glucose of 114 ± 3 mg/dL, and 2-h glucose of 177 ± 11 mg/dL, exenatide (5 μg) or placebo was injected in double-blind, randomized fashion subcutaneously 30 min before an oral glucose tolerance test (OGTT). The cerebral glucose metabolic rate (CMRglu) was measured by positron emission tomography after an injection of [(18)F]2-fluoro-2-deoxy-d-glucose before the OGTT, and the rate of glucose absorption (RaO) and disposal was assessed using stable isotope tracers. Exenatide reduced RaO0-60 min (4.6 ± 1.4 vs. 13.1 ± 1.7 μmol/min ⋅ kg) and decreased the rise in mean glucose0-60 min (107 ± 6 vs. 138 ± 8 mg/dL) and insulin0-60 min (17.3 ± 3.1 vs. 24.7 ± 3.8 mU/L). Exenatide increased CMRglu in areas of the brain related to glucose homeostasis, appetite, and food reward, despite lower plasma insulin concentrations, but reduced glucose uptake in the hypothalamus. Decreased RaO0-60 min after exenatide was inversely correlated to CMRglu. In conclusion, these results demonstrate, for the first time in man, a major effect of a GLP-1RA on regulation of brain glucose metabolism in the absorptive state.
Diabetes mellitus: prevalence and effect of morbidities in the oldest old. The Octabaix study.

To describe the prevalence of diabetes mellitus (DM) in community-dwelling 85-year-olds and to study the factors associated.



Cross-sectional.



Community-based survey study of seven primary healthcare centers.



Three hundred twenty-eight people born in 1924 and registered with primary healthcare centers.



Information on sociodemographic variables, Barthel Index (BI), Spanish version of the Mini-Mental State Examination (MEC), Mini Nutritional Assessment (MNA), Braden scale for risk of pressure ulcers, Charlson Comorbidity Index, chronic diseases, social risk, quality of life, chronic drug prescriptions, and blood tests was recorded. Participants were defined as having DM according to self-report, physician diagnosis, antidiabetic prescriptions, or plasma glucose concentration 7 mmol/L or more. A comparative analysis was performed between participants with and without DM.



The prevalence of DM in 328 octogenarians studied was 25.9%. Logistic regression showed an association between DM and BI (odds ratio (OR) = 1.03, 95% confidence interval (CI) = 1.00-1.05, P = .007), Braden risk score (OR = 0.87, 95% CI = 0.79-0.97, P = .01), thyroid disease (OR = 0.23, 95% CI = 0.06-0.92, P = .04), chronic drug prescriptions (OR = 1.28, 95% CI = 1.15-1.42, P < .001), white-cell count (OR = 1.34, 95% CI = 1.15-1.56, P < .001), low-density lipoprotein cholesterol (LDL-C; OR = 0.63, 95% CI = 0.43-0.92, P = .02) and folic acid level (OR = 1.04, 95% CI = 1.01-1.07, P = .005).



There is a high prevalence of DM at 85 years old. The presence of DM was positively associated with disability, drug prescription, white blood cell count, and folic acid level, whereas there was an inverse relationship between DM and Braden scale score, thyroid disease, and LDL-C. The effect of morbidities on DM may require a multidisciplinary approach to manage its complexity.
Diet components associated with perceived fatigue in breast cancer survivors.

Little is known about the contribution of diet components independent of body composition to persistent fatigue in breast cancer survivors. Therefore, our study aim was to determine the associations among dietary intake and fatigue in relation to and independent of adiposity and physical activity (PA) in breast cancer survivors. Baseline data from 42 breast cancer survivors enrolled in a randomised exercise trial were analysed: fatigue (Functional Assessment of Cancer Therapy for fatigue), diet components (3-day diet record), body mass index, per cent body fat (dual-energy X-ray absorptiometry) and PA (accelerometer). The mean age was 54 ± 9 years with an average body mass index of 30.5 ± 8.1 kg/m(2). Fatigue was positively associated with % of kcal/day fat intake (r = 0.31, P < 0.05) and inversely related to fibre g/day (r = 0.38, P < 0.05) and carbohydrate g/day intake (r = 0.31, P < 0.05). Mean fatigue was greater for participants eating <25 g/day of fibre compared with >25 g/day of fibre (15.7 ± 10.8 versus 6.4 ± 3.7, P < 0.005). No significant associations were noted between fatigue and PA or body composition. Diets high in fibre and low in fat are associated with reduced fatigue in breast cancer survivors. The difference in fatigue for low- versus high-fibre diets exceeded the minimal clinically important difference of three units. Prospective studies evaluating the effect of changing diet on fatigue in breast cancer survivors are warranted.
Physiological responding to stress in middle-aged males enriched for longevity: a social stress study.

Individuals enriched for familial longevity display a lower prevalence of age-related diseases, such as cardiovascular- and metabolic diseases. Since these diseases are associated with stress and increased cortisol levels, one of the underlying mechanisms that may contribute to healthy longevity might be a more adaptive response to stress. To investigate this, male middle-aged offspring from long-lived families (n = 31) and male non-offspring (with no familial history of longevity) (n = 26) were randomly allocated to the Trier Social Stress Test or a control condition in an experimental design. Physiological (cortisol, blood pressure, heart rate) and subjective responses were measured during the entire procedure. The results showed that Offspring had lower overall cortisol levels compared to Non-offspring regardless of condition, and lower absolute cortisol output (AUCg) during stress compared to Non-Offspring, while the increase (AUCi) did not differ between groups. In addition, systolic blood pressure in Offspring was lower compared to Non-offspring during the entire procedure. At baseline, Offspring had significantly lower systolic blood pressure and reported less subjective stress than Non-offspring and showed a trend towards lower heart rate. Offspring from long-lived families might thus be less stressed prior to potentially stressful events and consequently show overall lower levels in physiological responses. Although attenuated physiological responding cannot be ruled out, lower starting points and a lower peak level in physiological responding when confronted with an actual stressor, might already limit damage due to stress over a lifetime. Lower physiological responding may also contribute to the lower prevalence of cardiovascular diseases and other stress-related diseases in healthy longevity.
Onset of Coagulation Function Recovery Is Delayed in Severely Injured Trauma Patients with Venous Thromboembolism.

Altered coagulation function after trauma can contribute to development of venous thromboembolism (VTE). Severe trauma impairs coagulation function, but the trajectory for recovery is not known. We hypothesized that enhanced, early recovery of coagulation function increases VTE risk in severely injured trauma patients.



Secondary analysis was performed on data from the Pragmatic Randomized Optimal Platelet and Plasma Ratio (PROPPR) trial, excluding patients who died within 24 hours or were on pre-injury anticoagulants. Patient characteristics, adverse outcomes, and parameters of platelet function and coagulation (thromboelastography) were compared from admission to 72 hours between VTE (n = 83) and non-VTE (n = 475) patients. A p value < 0.05 indicates significance.



Despite similar patient demographics, VTE patients exhibited hypercoagulable thromboelastography parameters and enhanced platelet function at admission (p < 0.05). Both groups exhibited hypocoagulable thromboelastography parameters, platelet dysfunction, and suppressed clot lysis (low clot lysis at 30 minutes) 2 hours after admission (p < 0.05). The VTE patients exhibited delayed coagulation recovery (a significant change compared with 2 hours) of K-value (48 vs 24 hours), α-angle (no recovery), maximum amplitude (24 vs 12 hours), and clot lysis at 30 minutes (48 vs 12 hours). Platelet function recovery mediated by arachidonic acid (72 vs 4 hours), ADP (72 vs 12 hours), and collagen (48 vs 12 hours) was delayed in VTE patients. The VTE patients had lower mortality (4% vs 13%; p < 0.05), but fewer hospital-free days (0 days [interquartile range 0 to 8 days] vs 10 days [interquartile range 0 to 20 days]; p < 0.05) and higher complication rates (p < 0.05).



Recovery from platelet dysfunction and coagulopathy after severe trauma were delayed in VTE patients. Suppressed clot lysis and compensatory mechanisms associated with altered coagulation that can potentiate VTE formation require additional investigation.
Successful overweight prevention in adolescents by increasing physical activity: a 4-year randomized controlled intervention

Population-based studies directed at promoting physical activity in youth have shown limited success in obesity prevention.To assess whether an intervention integrating environmental changes to induce sustained changes in physical activity, prevents overweight in adolescents.Four-year randomized trial started in 2002 in eight middle schools of Eastern France. The intervention, randomized at school level, was designed to promote physical activity by changing attitudes through debates and attractive activities, and by providing social support and environmental changes encouraging physical activity.Nine hundred and fifty four 12-year-old six-graders.Body mass index (BMI), body composition, physical activity by questionnaire, plasma lipids and glucose, insulin resistance.Intervention students had a lower increase in BMI (P=0.01) and age- and gender-adjusted BMI (P<0.02) over time than controls. The differences across groups of the age- and gender-adjusted BMI changes (95% confidence interval (CI)) were −0.29 (−0.51; −0.07) kg/m2 at 3 years, −0.25 (−0.51; 0.01) kg/m2 at 4 years. An interaction with baseline weight status was noted. The intervention had a significant effect throughout the study in initially non-overweight adolescents (−0.36 (−0.60;−0.11) kg/m2 for adjusted BMI at 4 years), corresponding to a lower increase in fat mass index (P<0.001). In initially overweight adolescents, the differences observed across groups at 2 years (–0.40 (−0.94; 0.13) kg/m2 for adjusted BMI) did not persist over time. At 4 years, 4.2% of the initially non-overweight adolescents were overweight in the intervention schools, 9.8% in the controls (odds ratio=0.41 (0.22; 0.75); P<0.01). Independent of initial weight status, compared with controls, intervention adolescents had an increase in supervised physical activity (P<0.0001), a decrease of TV/video viewing (P<0.01) and an increase of high-density cholesterol concentrations (P<0.0001).Conclusion:Enhancing physical activity with a multilevel program prevents excessive weight gain in non-overweight adolescents. Our study provides evidence that prevention of obesity in youth is feasible.