nils-herrmann/clean_scirepeval huggingface dataset:
GISSI trials in acute myocardial infarction. Rationale, design, and results.

The first Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto (GISSI) study showed striking evidence of the effectiveness and safety of intravenous thrombolytic treatment in acute myocardial infarction (MI). Since publication in The Lancet, the original report has become a reference work for every paper which deals with thrombolysis. In addition to GISSI's scientific value, these studies applied formal research to routine clinical practice outside of referral centers. Nearly all Italian CCUs took part in the GISSI projects, so that the results provide a profile of the patient who seeks care for acute MI in Italy. This wide data base allowed GISSI investigators to look into some relevant clinical events, eg, primary ventricular fibrillation, stroke, and in-hospital reinfarction. The GISSI-2 trial followed the GISSI-1 philosophy. The package of treatments recommended after extensive discussion with all the investigators (beta-blocker, aspirin, nitrates) was widely adopted. Now, only five years after the start of the GISSI-1, the overall mortality of Italian patients with acute MI has decreased from 13.0 percent to about 9 percent, and the number of patients with acute MI arriving in hospital within 1 h of the onset of symptoms has increased 50 percent. It is the wish of the GISSI investigators that this approach to treating acute MI will be regarded and acknowledged as their major contribution to the problem.
Antihypertensive treatment decreases arterial stiffness at night but not during the day. Results from the Hypertension in the Very Elderly Trial.

The main Hypertension in the Very Elderly Trial (HYVET) demonstrated a very marked reduction in cardiovascular events by treating hypertensive participants 80 years or older with a low dose, sustained release prescription of indapamide (indapamide SR, 1.5 mg) to which was added a low dose of an angiotensin converting enzyme inhibitor in two-thirds of cases (perindopril 2-4 mg). This report from the ambulatory blood pressure sub-study investigates whether changes in arterial stiffness and ambulatory blood pressure (BP) could both explain the benefits observed in the main trial. A total of 139 participants were randomized to placebo [67] and to active treatment [72] and had both day and night observations of BP and arterial stiffness as determined from the Q wave Korotkoff diastolic (QKD) interval. The QKD interval was 5.6 ms longer (p = 0.017) in the actively treated group at night than in the placebo group. This was not true for the more numerous daytime readings so that 24-h results were similar in the two groups. The QKD interval remained longer at night in the actively treated group even when adjusted for systolic pressure, heart rate and height. The reduced arterial stiffness at night may partly explain the marked benefits observed in the main trial.
Up-regulation of Plasma Hexosylceramide (d18:1/18:1) Contributes to Genotype 2 Virus Replication in Chronic Hepatitis C

The aim of the present study was to explore the relationship between plasma sphingolipids and hepatitis C virus (HCV) replication in chronic hepatitis C (CHC) patients.A cohort of 120 treatment-naïve CHC patients was included. Liver biopsies and the Scheuer scoring system were used to assess hepatic inflammatory activity. Blood biochemical indicators, HCV-RNA load, and immunological markers were also measured. Forty-four plasma sphingolipids were identified and quantified using high-performance liquid chromatography-tandem mass spectrometry.The hexosylceramide (HexCer) (d18:1/18:1) level was significantly different between patients with a low HCV load (<10 IU/mL) and a high HCV load (≥10 IU/mL), and it was positively correlated with the HCV-RNA load (r = 0.337, P = 0.001) in CHC patients. Additionally, the plasma HexCer (d18:1/18:1) level (odds ratio 1.302, 95% confidence interval 1.129-1.502) was an independent factor for a high HCV-RNA load. For patients with hepatic inflammation grade ≤2 or HCV genotype 2, HexCer (d18:1/18:1) was independently related to a high HCV-RNA load.Plasma HexCer (d18:1/18:1) might be involved in the high viral replication level in chronic HCV infection, especially for CHC patients with genotype 2.
Establishment and results of a magnetic resonance quality assurance program for the pediatric brain tumor consortium.

Magnetic resonance (MR) imaging is used to assess brain tumor response to therapies, and a MR quality assurance (QA) program is necessary for multicenter clinical trials employing imaging. This study was performed to determine overall variability of quantitative imaging metrics measured with the American College of Radiology (ACR) phantom among 11 sites participating in the Pediatric Brain Tumor Consortium (PBTC) Neuroimaging Center (NIC) MR QA program.



An MR QA program was implemented among 11 participating PBTC sites and quarterly evaluations of scanner performance for seven imaging metrics defined by the ACR were sought and subject to statistical evaluation over a 4.5-year period. Overall compliance with the QA program, means, standard deviations, and coefficients of variation (CV) for the quantitative imaging metrics were evaluated.



Quantitative measures of the seven imaging metrics were generally within ACR recommended guidelines for all sites. Compliance improved as the study progressed. Intersite variabilities, as gauged by CV for slice thickness and geometric accuracy, imaging parameters that influence size or positioning measurements in tumor studies, were on the order of 10% and 1%, respectively.



Although challenging to establish, MR QA programs within the context of PBTC multisite clinical trials when based on the ACR MR phantom program can indicate sites performing below acceptable image quality levels and establish levels of precision through instrumental variabilities that are relevant to quantitative image analyses (eg, tumor volume changes).
Phase II study of theophylline in chronic lymphocytic leukemia: a study of the Eastern Cooperative Oncology Group (E4998)

The Eastern Cooperative Oncology Group (ECOG) performed a phase 2 study in B-cell chronic lymphocytic leukemia (CLL) of oral theophylline, a methylxanthine that inhibits cyclic nucleotide phosphodiesterases, thereby inducing the intracellular accumulation of cyclic adenosine monophosphate (cAMP). In 25 patients with Rai stages 0–I, theophylline, 200 mg given orally every 12 h was well tolerated. There was one complete response after 22.5 months of treatment, which continues at 27+ months, and 18 other patients had stable disease. In vitro exposure of patients' lymphocytes to aminophylline (75–250 μg/ml), the soluble form of theophylline, resulted in dose- and time-dependent induction of apoptosis in 9/20 patients studied. Apoptosis was documented flow-cytometrically by monitoring the expression of bcl-2 and bax, forward light scatter, fluorescence intensity of binding of CD45 antibody, and the binding of annexin. Patients whose leukemic lymphocytes were susceptible to apoptosis induction by aminophylline in vitro experienced a significantly longer progression-free survival than patients whose cells were resistant to the drug in culture (P=0.025). This suggests that in a CLL population treated with theophylline, induction of an apoptotic response to the drug in vitro is prognostic for absence of clinical progression.
Time Out-of-Home and Cognitive, Physical, and Emotional Wellbeing of Older Adults: A Longitudinal Mixed Effects Model

Time out-of-home has been linked with numerous health outcomes, including cognitive decline, poor physical ability and low emotional state. Comprehensive characterization of this important health metric would potentially enable objective monitoring of key health outcomes. The objective of this study is to determine the relationship between time out-of-home and cognitive status, physical ability and emotional state.



Participants included 85 independent older adults, age 65-96 years (M = 86.36; SD = 6.79) who lived alone, from the Intelligent Systems for Assessing Aging Changes (ISAAC) and the ORCATECH Life Laboratory cohorts. Factors hypothesized to affect time out-of-home were assessed on three different temporal levels: yearly (cognitive status, loneliness, clinical walking speed), weekly (pain and mood) or daily (time out-of-home, in-home walking speed, weather, and season). Subject characteristics including age, race, and gender were assessed at baseline. Total daily time out-of-home in hours was assessed objectively and unobtrusively for up to one year using an in-home activity sensor platform. A longitudinal tobit mixed effects regression model was used to relate daily time out-of-home to cognitive status, physical ability and emotional state. More hours spend outside the home was associated with better cognitive function as assessed using the Clinical Dementia Rating (CDR) Scale, where higher scores indicate lower cognitive function (βCDR = -1.69, p<0.001). More hours outside the home was also associated with superior physical ability (βPain = -0.123, p<0.001) and improved emotional state (βLonely = -0.046, p<0.001; βLow mood = -0.520, p<0.001). Weather, season, and weekday also affected the daily time out-of-home.



These results suggest that objective longitudinal monitoring of time out-of-home may enable unobtrusive assessment of cognitive, physical and emotional state. In addition, these results indicate that the factors affecting out-of-home behavior are complex, with factors such as living environment, weather and season significantly affecting time out-of-home. Studies investigating the relationship between time out-of-home and health outcomes may be optimized by taking into account the environment and life factors presented here.
Clinical evaluation of 2D versus 3D whole-body PET image quality using a dedicated BGO PET scanner

Three-dimensional positron emission tomography (3D PET) results in higher system sensitivity, with an associated increase in the detection of scatter and random coincidences. The objective of this work was to compare, from a clinical perspective, 3D and two-dimensional (2D) acquisitions in terms of whole-body (WB) PET image quality with a dedicated BGO PET system. 2D and 3D WB emission acquisitions were carried out in 70 patients. Variable acquisition parameters in terms of time of emission acquisition per axial field of view (aFOV) and slice overlap between sequential aFOVs were used during the 3D acquisitions. 3D and 2D images were reconstructed using FORE+WLS and OSEM respectively. Scatter correction was performed by convolution subtraction and a model-based scatter correction in 2D and 3D respectively. All WB images were attenuation corrected using segmented transmission scans. Images were blindly assessed by three observers for the presence of artefacts, confidence in lesion detection and overall image quality using a scoring system. Statistically significant differences between 2D and 3D image quality were only obtained for 3D emission acquisitions of 3 min. No statistically significant differences were observed for image artefacts or lesion detectability scores. Image quality correlated significantly with patient weight for both modes of operation. Finally, no differences were seen in image artefact scores for the different axial slice overlaps considered, suggesting the use of five slice overlaps in 3D WB acquisitions. 3D WB imaging using a dedicated BGO-based PET scanner offers similar image quality to that obtained in 2D considering similar overall times of acquisitions.
Validation of a GPU-based Monte Carlo code (gPMC) for proton radiation therapy: clinical cases study.

Monte Carlo (MC) methods are recognized as the gold-standard for dose calculation, however they have not replaced analytical methods up to now due to their lengthy calculation times. GPU-based applications allow MC dose calculations to be performed on time scales comparable to conventional analytical algorithms. This study focuses on validating our GPU-based MC code for proton dose calculation (gPMC) using an experimentally validated multi-purpose MC code (TOPAS) and compare their performance for clinical patient cases. Clinical cases from five treatment sites were selected covering the full range from very homogeneous patient geometries (liver) to patients with high geometrical complexity (air cavities and density heterogeneities in head-and-neck and lung patients) and from short beam range (breast) to large beam range (prostate). Both gPMC and TOPAS were used to calculate 3D dose distributions for all patients. Comparisons were performed based on target coverage indices (mean dose, V95, D98, D50, D02) and gamma index distributions. Dosimetric indices differed less than 2% between TOPAS and gPMC dose distributions for most cases. Gamma index analysis with 1%/1 mm criterion resulted in a passing rate of more than 94% of all patient voxels receiving more than 10% of the mean target dose, for all patients except for prostate cases. Although clinically insignificant, gPMC resulted in systematic underestimation of target dose for prostate cases by 1-2% compared to TOPAS. Correspondingly the gamma index analysis with 1%/1 mm criterion failed for most beams for this site, while for 2%/1 mm criterion passing rates of more than 94.6% of all patient voxels were observed. For the same initial number of simulated particles, calculation time for a single beam for a typical head and neck patient plan decreased from 4 CPU hours per million particles (2.8-2.9 GHz Intel X5600) for TOPAS to 2.4 s per million particles (NVIDIA TESLA C2075) for gPMC. Excellent agreement was demonstrated between our fast GPU-based MC code (gPMC) and a previously extensively validated multi-purpose MC code (TOPAS) for a comprehensive set of clinical patient cases. This shows that MC dose calculations in proton therapy can be performed on time scales comparable to analytical algorithms with accuracy comparable to state-of-the-art CPU-based MC codes.
Updated results of the Gothenburg Trial of Mammographic Screening

There remain uncertainties about age-specific effects of breast cancer screening on mortality due to the disease.



In 1982, a randomized trial of mammographic screening every 18 months was started in Gothenburg, Sweden. Women between the ages of 39 and 49 years were randomized to an invitation to screening (intervention group; n = 11,792) or to usual care (the control group; n = 14,321). The corresponding numbers for women between the ages of 50 and 59 years were 10,112 and 15,997. Follow-up data for breast cancer mortality were available up to the end of 2007. Data were analyzed by Poisson regression with conservative variance estimates.



There were 79 breast cancer deaths in the intervention arm and 156 in the control arm, and this meant a significant 30% reduction in breast cancer mortality with the offer of screening (relative risk [RR], 0.70; 95% confidence interval [CI], 0.53-0.93; P = .01). In women aged 39 to 49 years, there was a significant 40% reduction in breast cancer mortality (RR, 0.60; 95% CI, 0.43-0.85; P = .003). In the 50- to 59-year age group, there was a nonsignificant 18% breast cancer mortality reduction (RR, 0.82; 95% CI, 0.54-1.26; P = .4).



The policy of offering mammographic screening substantially reduces breast cancer mortality and can do so in women younger than 50 years. Cancer 2016;122:1832-5.
Online support: Impact on anxiety in women who experience an abnormal screening mammogram.

To determine whether an online support tool can impact anxiety in women experiencing an abnormal mammogram.



We developed an online support system using the Comprehensive Health Enhancement Support System (CHESS) designed for women experiencing an abnormal mammogram as a model. Our trial randomized 130 of these women to online support (the intervention group) or to a list of five commonly used Internet sites (the comparison group). Surveys assessed anxiety and breast cancer worry, and patient satisfaction at three important clinical time points: when women were notified of their abnormal mammogram, at the time of diagnostic imaging, and at the time of biopsy (if biopsy was recommended).



Study participants in the intervention group showed a significant decrease in anxiety at the time of biopsy compared to the comparison group (p = 0.017). However, there was no significant difference in anxiety between the intervention group and the comparison group at the time of diagnostic work-up. We discontinued assessment of patient satisfaction after finding that many women had substantial difficulty answering the questions that referenced their physician, because they did not understand who their physician was for this process of care.



The combination of the inability to identify the physician providing care during the mammography work-up and anxiety effects seen only after an interaction with the breast imaging team may indicate that online support only decreases the anxiety of women in concert with direct interpersonal support from the healthcare team.
Effects of a clinician referral and exercise program for men who have completed active treatment for prostate cancer: A multicenter cluster randomized controlled trial (ENGAGE).

The purpose of this study was to determine the efficacy of a clinician referral and exercise program in improving exercise levels and quality of life for men with prostate cancer.



This was a multicenter cluster randomized controlled trial in Melbourne, Australia comprising 15 clinicians: 8 clinicians were randomized to refer eligible participants (n = 54) to a 12-week exercise program comprising 2 supervised gym sessions and 1 home-based session per week, and 7 clinicians were randomized to follow usual care (n = 93). The primary outcome was self-reported physical activity; the secondary outcomes were quality of life, anxiety, and symptoms of depression.



A significant intervention effect was observed for vigorous-intensity exercise (effect size: Cohen's d, 0.46; 95% confidence interval [CI], 0.09-0.82; P = .010) but not for combined moderate and vigorous exercise levels (effect size: d, 0.08; 95% CI, -0.28 to 0.45; P = .48). Significant intervention effects were also observed for meeting exercise guidelines (≥150 min/wk; odds ratio, 3.9; 95% CI, 1.9-7.8; P = .002); positive intervention effects were observed in the intervention group for cognitive functioning (effect size: d, 0.34; 95% CI, -0.02 to 0.70; P = .06) and depression symptoms (effect size: d, -0.35; 95% CI, -0.71 to 0.02; P = .06). Eighty percent of participants reported that the clinician's referral influenced their decision to participate in the exercise program.



The clinician referral and 12-week exercise program significantly improved vigorous exercise levels and had a positive impact on mental health outcomes for men living with prostate cancer. Further research is needed to determine the sustainability of the exercise program and its generalizability to other cancer populations.
Measuring fatigue in Parkinson's disease: a psychometric study of two brief generic fatigue questionnaires.

This study evaluated and compared the measurement properties of the 13-item Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) and the 9-item Fatigue Severity Scale (FSS) in 118 consecutive Parkinson's disease (PD) patients, using traditional and Rasch measurement methodologies. Both questionnaires exhibited excellent data quality and reliability (coefficient alpha>or=0.9), and acceptable rating scale functionality, and both discriminated between fatigued and nonfatigued patients. Factor and Rasch analyses provided general support for unidimensionality of both FACIT-F and FSS, although they do not appear to measure identical aspects of fatigue. No signs of differential item functioning (DIF) were found for the FACIT-F, whereas potential age DIF was detected for two FSS items. These results support the measurement validity of both questionnaires in PD, although the FACIT-F displayed better measurement precision and modest psychometric advantages over the FSS. Availability of psychometrically sound fatigue measures that are applicable across disorders provides a sound basis for advancing the understanding of this common and distressing complaint.
Sympathetic activity and early mobilization in patients in intensive and intermediate care with severe brain injuries: a preliminary prospective randomized study

Patients who experience severe brain injuries are at risk of secondary brain damage, because of delayed vasospasm and edema. Traditionally, many of these patients are kept on prolonged bed rest in order to maintain adequate cerebral blood flow, especially in the case of subarachnoid hemorrhage. On the other hand, prolonged bed rest carries important morbidity. There may be a clinical benefit in early mobilization and our hypothesis is that early gradual mobilization is safe in these patients. The aim of this study was to observe and quantify the changes in sympathetic activity, mainly related to stress, and blood pressure in gradual postural changes by the verticalization robot (Erigo®) and after training by a lower body ergometer (MOTOmed-letto®), after prolonged bed rest of minimum 7 days.



Thirty patients with severe neurological injuries were randomized into 3 groups with different protocols of mobilization: Standard, MOTOmed-letto® or Erigo® protocol. We measured plasma catecholamines, metanephrines and blood pressure before, during and after mobilization.



Blood pressure does not show any significant difference between the 3 groups. The analysis of the catecholamines suggests a significant increase in catecholamine production during Standard mobilization with physiotherapists and with MOTOmed-letto® and no changes with Erigo®.



This preliminary prospective randomized study shows that the mobilization of patients with severe brain injuries by means of Erigo® does not increase the production of catecholamines. It means that Erigo® is a well-tolerated method of mobilization and can be considered a safe system of early mobilization of these patients. Further studies are required to validate our conclusions.
Prothrombin complex concentrate (Beriplex P/N) for emergency anticoagulation reversal: a prospective multinational clinical trial.

Prothrombin complex concentrate (PCC) can substantially shorten the time needed to reverse antivitamin K oral anticoagulant therapy (OAT).  To determine the effectiveness and safety of emergency OAT reversal by a balanced pasteurized nanofiltered PCC (Beriplex P/N) containing coagulation factors II, VII, IX, and X, and anticoagulant proteins C and S.



Patients receiving OAT were eligible for this prospective multinational study if their International Normalized Ratio (INR) exceeded 2 and they required either an emergency surgical or urgent invasive diagnostic intervention or INR normalization due to acute bleeding. Stratified 25, 35, or 50 IU kg(-1) PCC doses were infused based on initial INR. Study endpoints included INR normalization (</=1.3) by 30 min after PCC infusion and hemostatic efficacy.



Forty-three patients, 26 requiring interventional procedures and 17 experiencing acute bleeding, received PCC infusions at a median rate of 7.5 mL min(-1) (188 IU min(-1)). At 30 min thereafter, INR declined to </=1.3 in 93% of patients. At all postinfusion time points through 48 h, median INR remained between 1.2 and 1.3. Clinical hemostatic efficacy was classified as very good or satisfactory in 42 patients (98%). Prompt and sustained increases in circulating coagulation factors and anticoagulant proteins were observed. One fatal suspected pulmonary embolism in a patient with metastatic cancer was judged to be possibly PCC-related.



PCC treatment serves as an effective rapid hemorrhage control resource in the emergency anticoagulant reversal setting. More widespread availability of PCC is warranted to ensure its benefits in appropriate patients.