nils-herrmann/clean_scirepeval huggingface dataset:
Weekly 5-fluorouracil and leucovorin: achieving lower toxicity with higher dose-intensity in adjuvant chemotherapy after colorectal cancer resection.

Current standard therapy following resection of high-risk colon cancer is intravenous bolus 5-fluorouracil (5-FU) with leucovorin (LV), but there is no consensus on the optimum regimen of these drugs: practice ranges from the high toxicity Mayo Clinic schedule to the very low toxicity weekly QUASAR schedule. We present data for a weekly schedule that aims to provide moderately dose-intense treatment with low toxicity.



One hundred and sixty-two patients were studied: 60% male; median age 65 years (36% over 70 years); 94% colorectal primary. Treatment was intravenous bolus (5 min) 5-FU 425 mg/m(2) plus D,L-LV 45 mg flat rate once weekly, for a planned 24 weeks. Data for toxicity, dose-reductions, delays and stoppages were collected.



Overall, 20% of patients experienced any grade > or = 3 toxicity, most commonly diarrhoea (14% patients). Dose reductions were made in 35% of patients (although only 21% required 20% or more reduction); toxicity contributed to a decision to stop treatment before 24 weeks in 16% of patients. Median delivered dose intensity (DI) was 96% of planned (407 mg/m(2)/week) during treatment, and 91% of planned (385 mg/m(2)/week) over the full 24 week treatment plan. Female sex and age >70 years were significantly associated with higher rates of toxicity and dose adjustment, and lower delivered DI.



Weekly treatment at these doses is convenient and well-tolerated for the large majority of patients, and achieves DI comparable with the 5 days a month QUASAR schedule and other more toxic standard regimens.
Effect of platelet inhibition with cangrelor during PCI on ischemic events.

The intensity of antiplatelet therapy during percutaneous coronary intervention (PCI) is an important determinant of PCI-related ischemic complications. Cangrelor is a potent intravenous adenosine diphosphate (ADP)-receptor antagonist that acts rapidly and has quickly reversible effects.



In a double-blind, placebo-controlled trial, we randomly assigned 11,145 patients who were undergoing either urgent or elective PCI and were receiving guideline-recommended therapy to receive a bolus and infusion of cangrelor or to receive a loading dose of 600 mg or 300 mg of clopidogrel. The primary efficacy end point was a composite of death, myocardial infarction, ischemia-driven revascularization, or stent thrombosis at 48 hours after randomization; the key secondary end point was stent thrombosis at 48 hours. The primary safety end point was severe bleeding at 48 hours.



The rate of the primary efficacy end point was 4.7% in the cangrelor group and 5.9% in the clopidogrel group (adjusted odds ratio with cangrelor, 0.78; 95% confidence interval [CI], 0.66 to 0.93; P=0.005). The rate of the primary safety end point was 0.16% in the cangrelor group and 0.11% in the clopidogrel group (odds ratio, 1.50; 95% CI, 0.53 to 4.22; P=0.44). Stent thrombosis developed in 0.8% of the patients in the cangrelor group and in 1.4% in the clopidogrel group (odds ratio, 0.62; 95% CI, 0.43 to 0.90; P=0.01). The rates of adverse events related to the study treatment were low in both groups, though transient dyspnea occurred significantly more frequently with cangrelor than with clopidogrel (1.2% vs. 0.3%). The benefit from cangrelor with respect to the primary end point was consistent across multiple prespecified subgroups.



Cangrelor significantly reduced the rate of ischemic events, including stent thrombosis, during PCI, with no significant increase in severe bleeding. (Funded by the Medicines Company; CHAMPION PHOENIX ClinicalTrials.gov number, NCT01156571.).
Autologous olfactory ensheathing cell transplantation in human paraplegia: a 3-year clinical trial

Olfactory ensheathing cells show promise in preclinical animal models as a cell transplantation therapy for repair of the injured spinal cord. This is a report of a clinical trial of autologous transplantation of olfactory ensheathing cells into the spinal cord in six patients with complete, thoracic paraplegia. We previously reported on the methods of surgery and transplantation and the safety aspects of the trial 1 year after transplantation. Here we address the overall design of the trial and the safety of the procedure, assessed during a period of 3 years following the transplantation surgery. All patients were assessed at entry into the trial and regularly during the period of the trial. Clinical assessments included medical, psychosocial, radiological and neurological, as well as specialized tests of neurological and functional deficits (standard American Spinal Injury Association and Functional Independence Measure assessments). Quantitative test included neurophysiological tests of sensory and motor function below the level of injury. The trial was a Phase I/IIa design whose main aim was to test the feasibility and safety of transplantation of autologous olfactory ensheathing cells into the injured spinal cord in human paraplegia. The design included a control group who did not receive surgery, otherwise closely matched to the transplant recipient group. This group acted as a control for the assessors, who were blind to the treatment status of the patients. The control group also provided the opportunity for preliminary assessment of the efficacy of the transplantation. There were no adverse findings 3 years after autologous transplantation of olfactory ensheathing cells into spinal cords injured at least 2 years prior to transplantation. The magnetic resonance images (MRIs) at 3 years showed no change from preoperative MRIs or intervening MRIs at 1 and 2 years, with no evidence of any tumour of introduced cells and no development of post-traumatic syringomyelia or other adverse radiological findings. There were no significant functional changes in any patients and no neuropathic pain. In one transplant recipient, there was an improvement over 3 segments in light touch and pin prick sensitivity bilaterally, anteriorly and posteriorly. We conclude that transplantation of autologous olfactory ensheathing cells into the injured spinal cord is feasible and is safe up to 3 years of post-implantation, however, this conclusion should be considered preliminary because of the small number of trial patients.
Quantification of the response of circulating epithelial cells to neodadjuvant treatment for breast cancer: a new tool for therapy monitoring

In adjuvant treatment for breast cancer there is no tool available with which to measure the efficacy of the therapy. In contrast, in neoadjuvant therapy reduction in tumour size is used as an indicator of the sensitivity of tumour cells to the agents applied. If circulating epithelial (tumour) cells can be shown to react to therapy in the same way as the primary tumour, then this response may be exploited to monitor the effect of therapy in the adjuvant setting. We used MAINTRAC® analysis to monitor the reduction in circulating epithelial cells during the first three to four cycles of neoadjuvant therapy in 30 breast cancer patients. MAINTRAC® analysis revealed a patient-specific response. Comparison of this response with the decline in size of the primary tumour showed that the reduction in number of circulating epithelial cells accurately predicted final tumour reduction at surgery if the entire neoadjuvant regimen consisted of chemotherapy. However, the response of the circulating tumour cells was unable to predict the response to additional antibody therapy. The response of circulating epithelial cells faithfully reflects the response of the whole tumour to adjuvant therapy, indicating that these cells may be considered part of the tumour and can be used for therapy monitoring.
Malignancies in cases with screening-identified evidence of coeliac disease: a long-term population-based cohort study.

The association between diagnosed coeliac disease and malignancy has been established. The present study was conducted to determine whether previously unrecognised and thus untreated adults with screening-identified evidence of coeliac disease carry an increased risk of malignancies.



A Finnish population-based adult-representative cohort of 8000 individuals was drawn in 1978-1980. Stored sera of the participants with no history of coeliac disease or any malignancy were tested for immunoglobulin A (IgA) class tissue transglutaminase antibodies (Eu-tTG) in 2001. Positive sera were further analysed by another tissue transglutaminase antibody test (Celikey tTG) and for endomysial antibodies (EMAs). Malignant diseases were extracted from the nationwide database and antibody-positive cases were compared with negative cases during a follow-up of nearly 20 years.



Altogether 565 of all the 6849 analysed serum samples drawn in 1978-80 were Eu-tTG positive. In further analyses, 202 (2.9%) of the participants were Celikey tTG positive and 73 (1.1%) were EMA positive. The overall risk of malignancy was not increased among antibody-positive cases in the follow-up of two decades; the age- and sex-adjusted relative risk was 0.91 (95% CI 0.60 to 1.37) for those who were Celikey tTG positive and 0.67 (95% CI 0.28 to 1.61) for those who were EMA positive.



The prognosis of adults with unrecognised coeliac disease with positive coeliac disease antibody status is good as regards the overall risk of malignancies. Thus, current diagnostic practice is sufficient and there is no need for earlier diagnosis of coeliac disease by mass screening on the basis of the findings of this study.
Iotrol, a new water-soluble non-ionic dimeric contrast medium for intrathecal use

The side effects associated with the use of Iotrol were determined in 100 patients and compared with metrizamide and iopamidol in two double-blind studies. The relevance of the distribution of the contrast medium in the CSF space to the occurence of headache is discussed. The low persistence of iotrol in the brain parenchyma is demonstrated on CT density profiles, compared with metrizamide and iopamidol. Iotrol seems to be the safest contrast substance for intrathecal use.
Spanish version of the Northwick Park Neck Pain Questionnaire: reliability and validity.

To validate a Spanish version of the Northwick Park Neck Pain Questionnaire (NPQ) and to prove its usefulness in clinical practice.



We studied 58 patients with non-inflammatory neck pain of more than 4 months duration. A blind back translation of the NPQ was made, and the resulting back-translation version was then compared with the original. The NPQ comprises 9 questions with 5 statements of increasing difficulty. Patients completed the questionnaire 3 times: on their initial assessment; 8-10 days later (test-retest); and after physiotherapy treatment 3 months later. Neck pain was assessed by a visual analogue scale (VAS).



Fifty-three patients completed the questionnaire (90%). There was a good intra-class correlation between the test-retest NPQ (r = 0.63), indicating good agreement. For each of the 9 sections, agreement ranged from r = 0.43 to r = 0.85, p < 0.05 in all cases. Correlation with the VAS was also good, between r = 0.51 (test) and r = 0.74 (retest) (p < 0.05 in all cases). Pain measured by the VAS increased according to the NPQ score, grouped by percentages (p = 0.003). The mean scores for each section increased with that of the intensity of pain, in most sections showing good internal consistency. Pain and the NPQ score improved after treatment (56.1 +/- 20.2 to 29.9 +/- 20.1, p = 0.0001 and 45.9% +/- 12.7% to 28.9% +/- 15.3%, p = 0.0001 respectively), as did all the other items except for driving (p < 0.05).



The Spanish version of the NPQ is a feasible, reliable and valid instrument to measure pain in Spanish-speaking patients with chronic neck pain.
Support Vector Machines and Other Pattern Recognition Approaches to the Diagnosis of Cerebral Palsy Gait

Accurate identification of cerebral palsy (CP) gait is important for diagnosis as well as for proper evaluation of the treatment outcomes. This paper explores the use of support vector machines (SVM) for automated detection and classification of children with CP using two basic temporal-spatial gait parameters (stride length and cadence) as input features. Application of the SVM method to a children's dataset (68 normal healthy and 88 with spastic diplegia form of CP) and testing on tenfold cross-validation scheme demonstrated that an SVM classifier was able to classify the children groups with an overall accuracy of 83.33% [sensitivity 82.95%, specificity 83.82%, area under the receiver operating curve (AUC-ROC=0.88)]. Classification accuracy improved significantly when the gait parameters were normalized by the individual leg length and age, leading to an overall accuracy of 96.80% (sensitivity 94.32%, specificity 100%, AUC-DROC area=0.9924). This accuracy result was, respectively, 3.21% and 1.93% higher when compared to an linear discriminant analysis and an multilayer-perceptron-based classifier. SVM classifier also attains considerably higher ROC area than the other two classifiers. Among the four SVM kernel functions (linear, polynomial, radial basis, and analysis of variance spline) studied, the polynomial and radial basis kernel performed comparably and outperformed the others. Classifier's performance as functions of regularization and kernel parameters was also investigated. The enhanced classification accuracy of the SVM using only two easily obtainable basic gait parameters makes it attractive for identifying CP children as well as for evaluating the effectiveness of various treatment methods and rehabilitation techniques
Rabeprazole for the prevention of pathologic and symptomatic relapse of erosive or ulcerative gastroesophageal reflux disease

We evaluated the effectiveness and safety profile of 10 and 20 mg of rabeprazole, a new proton pump inhibitor, once daily versus placebo in preventing endoscopic and symptomatic relapse for up to 1 yr among patients with healed erosive or ulcerative gastroesophageal reflux disease (GERD).METHODS:The 52-wk trial used a multicenter, randomized, double-blind, parallel-group design in which 209 men and women were assigned to 10 or 20 mg of rabeprazole once daily in the morning or placebo.Both rabeprazole doses were significantly superior to placebo in preventing endoscopic relapse (p < 0.001), and 20 mg was significantly more effective than 10 mg (p < 0.04). Both doses were also significantly superior to placebo in reducing the frequency and severity of heartburn relapse (p < 0.001). When adjusted for differences in exposure to study medication, no significant differences were found in the incidence of adverse events. No clinically significant changes were found regarding clinical laboratory parameters, vital signs, electrocardiograms, ophthalmological evaluations, body weight, serum gastrin, and enterochromaffin-like cell histology.Once-daily therapy with 10 or 20 mg of rabeprazole effectively prevents pathological and symptomatic GERD relapse. The 20-mg dose is significantly more effective than the 10-mg dose in preventing endoscopic recurrence. Treatment was well tolerated, and no clinically significant safety findings emerged. Our findings support rabeprazole's efficacy in preventing GERD recurrence with excellent tolerability and a short-term favorable safety profile.
The HARMONY Trial: Combined Ranolazine and Dronedarone in the Management of Paroxysmal Atrial Fibrillation: Mechanistic and Therapeutic Synergism.

Atrial fibrillation (AF) requires arrhythmogenic changes in atrial ion channels/receptors and usually altered atrial structure. AF is commonly treated with antiarrhythmic drugs; the most effective block many ion channels/receptors. Modest efficacy, intolerance, and safety concerns limit current antiarrhythmic drugs. We hypothesized that combining agents with multiple anti-AF mechanisms at reduced individual drug doses might produce synergistic efficacy plus better tolerance/safety.



HARMONY tested midrange ranolazine (750 mg BID) combined with 2 reduced dronedarone doses (150 mg BID and 225 mg BID; chosen to reduce dronedarone's negative inotropic effect-see text below) over 12 weeks in 134 patients with paroxysmal AF and implanted pacemakers where AF burden (AFB) could be continuously assessed. Patients were randomized double-blind to placebo, ranolazine alone (750 mg BID), dronedarone alone (225 mg BID), or one of the combinations. Neither placebo nor either drugs alone significantly reduced AFB. Conversely, ranolazine 750 mg BID/dronedarone 225 mg BID reduced AFB by 59% versus placebo (P=0.008), whereas ranolazine 750 mg BID/dronedarone 150 mg BID reduced AFB by 43% (P=0.072). Both combinations were well tolerated.



HARMONY showed synergistic AFB reduction by moderate dose ranolazine plus reduced dose dronedarone, with good tolerance/safety, in the population enrolled.
Surpass flow diverter in the treatment of intracranial aneurysms: a prospective multicenter study.

Incomplete occlusion and recanalization of large and wide-neck brain aneurysms treated by endovascular therapy remains a challenge. We present preliminary clinical and angiographic results of an experimentally optimized Surpass flow diverter for treatment of intracranial aneurysms in a prospective, multicenter, nonrandomized, single-arm study.



At 24 centers, 165 patients with 190 intracranial aneurysms of the anterior and posterior circulations were enrolled. The primary efficacy end point was the percentage of intracranial aneurysms with 100% occlusion on 6-month DSA. The primary safety end point was neurologic death and any stroke through a minimum follow-up of 6 months.



Successful flow-diverter delivery was achieved in 161 patients with 186 aneurysms (98%); the mean number of devices used per aneurysm was 1.05. Clinical follow-up (median, 6 months) of 150 patients (93.2%), showed that the primary safety end point occurred in 18 subjects. Permanent neurologic morbidity and mortality were 6% and 2.7%, respectively. Morbidity occurred in 4% and 7.4% of patients treated for aneurysms of the anterior and posterior circulation, respectively. Neurologic death during follow-up was observed in 1.6% and 7.4% of patients with treated intracranial aneurysms of the anterior and posterior circulation, respectively. Ischemic stroke at ≤30 days, SAH at ≤7 days, and intraparenchymal hemorrhage at ≤7 days were encountered in 3.7%, 2.5%, and 2.5% of subjects, respectively. No disabling ischemic strokes at >30 days or SAH at >7 days occurred. New or worsening cranial nerve deficit was observed in 2.7%. Follow-up angiography available in 158 (86.8%) intracranial aneurysms showed 100% occlusion in 75%.



Clinical outcomes of the Surpass flow diverter in the treatment of intracranial aneurysms show a safety profile that is comparable with that of stent-assisted coil embolization. Angiographic results showed a high rate of intracranial aneurysm occlusion.
Understanding gastro-oesophageal reflux disease: a patient-cluster analysis

To determine whether patients with gastro-oesophageal reflux disease (GERD) can be grouped according to the physical and psychological impact of their disease.



In this multinational study, 7713 primary care physicians (PCPs) and gastrointestinal (GI) specialists took part in a structured online survey to determine how they perceive the clinical and psychological needs of their GERD patients, based on their three most recent consultations. Patients were grouped according to one of the five clusters that were subjectively developed based on preceding qualitative research.



Findings are reported for 1157 respondents (875 PCPs, 282 GI specialists), who reviewed 3471 patient records. Two of the five original clusters were collapsed because of overlapping characteristics, giving rise to three patient clusters. Patients with 'long-term, disrupting GERD' (39%) had symptoms considered to have not only high physical but also psychological impact. Patients with 'recurrent, distressing GERD' (14%) experienced both physical and psychological impact and were worried about the recurrent, restrictive nature of their disease or the possibility of having a more serious underlying condition. Patients with 'inconveniencing GERD' (48%) had less frequent symptoms with overall lower impact. Overall, there was a trend for GI specialists to more likely see patients at higher clinical need than PCPs.



Patients with GERD can generally be classified according to the physical and psychological impact of their disease. Recognition that such patients have different needs may facilitate improved management of GERD by allowing treatment to be tailored according to the patient's need.
Pulmonary Function and Abdominal and Thoracic Kinematic Changes Following Aerobic and Inspiratory Resistive Diaphragmatic Breathing Training in Asthmatics

This study investigated the effect of 8 weeks, three times weekly, of aerobic exercise (AE), diaphragmatic inspiratory resistive breathing (DR), and aerobic exercise combined with diaphragmatic inspiratory resistive breathing (CE) on pulmonary function and abdominal and thoracic dimensions and kinematics in asthmatics. Eighty-eight inactive, moderate-persistent asthmatics were matched and randomly assigned to AE, DR, CE, or nonexercise control (NE) groups (n = 22 each). AE subjects walked and/or jogged at 60% of age-predicted maximum heart rate. DR subjects performed diaphragmatic breathing combined with inspiratory resistive breathing at varying inspiration, expiration ratios. CE subjects utilized a combination of the AE and DR programs. AE, DR, and CE significantly (p ≤ 0.05) improved chest dimensions and kinematics during inspiration at the height of the second intercostal space, during inspiration and expiration at the height of the xiphoid process, and during inspiration and expiration at the height of the midpoint between the xiphoid process and umbilicus. All exercise interventions significantly improved FVC, FEV1, PEF, and IVC, while MVV improved following AE and CE. However, CE proved superior to AE at improving FVC (p = 0.001), FEV1 (p = 0.001), and IVC (p = 0.009). There were no significant changes (p > 0.05) in any of the measured parameters in the NE group. CE produces adaptations greater than those for single-mode training in moderate-persistent asthmatics. The results suggest synergy rather than interference between aerobic exercise and diaphragmatic inspiratory resistive breathing and that this mode of training might be useful as an adjunct therapy in asthmatic patients.