nils-herrmann/clean_scirepeval huggingface dataset:
l-asparaginase loaded red blood cells in refractory or relapsing acute lymphoblastic leukaemia in children and adults: results of the GRASPALL 2005-01 randomized trial.

l-asparaginase encapsulated within erythrocytes (GRASPA(®) ) should allow serum asparagine depletion over a longer period than the native form of the enzyme, using lower doses and allowing better tolerance. The GRASPALL 2005-01 study, a multicentre randomized controlled trial, investigated three doses of GRASPA(®) for the duration of asparagine depletion in a phase I/II study in adults and children with acute lymphoblastic leukaemia (ALL) in first relapse. Between February 2006 and April 2008, 18 patients received GRASPA(®) (50 iu/kg: n = 6,100 iu/kg: n = 6, 150 iu/kg: n = 6) after randomization, and six patients were assigned to the Escherichia coli native l-asparaginase (E. colil-ASNase) control group. GRASPA(®) was effective at depleting l-asparagine. One single injection of 150 iu/kg of GRASPA(®) provided similar results to 8 × 10,000 iu/m(2) intravenous injections of E. colil-ASNase. The safety profile of GRASPA(®) showed a reduction in the number and severity of allergic reactions and a trend towards less coagulation disorders. Other expected adverse events were comparable to those observed with E. colil-ASNase and there was also no difference between the three doses of GRASPA(®) .
Executive dysfunction in mild cognitive impairment is associated with changes in frontal and cingulate white matter tracts.

Mild cognitive impairment (MCI) may affect multiple neuropsychological domains. While amnestic MCI is associated with Alzheimer's disease, patterns of brain pathology in non-amnestic subtypes have been less studied. Twenty-three patients with attention/executive MCI (a/e MCI), seen at a university-based memory clinic, and 23 normal controls, matched according to age, gender, and education, were included in this study. All subjects were assessed with a neuropsychological test battery, including tests of memory, attention and executive function, and underwent magnetic resonance imaging. Diffusion tensor imaging derived white matter (WM) tract radial and mean diffusivity (DR and MD) were assessed using Tract-Based Spatial Statistics, and cortical thickness (CTH) was assessed using FreeSurfer. This study investigated changes of WM DR/MD and CTH in subjects with a/e MCI, and associations between these changes and different a/e subfunctions. WM DR/MD underlying rostral middle frontal, medial orbitofrontal, caudal anterior cingulate, posterior cingulate, retrosplenial and entorhinal cortices was higher for the a/e MCI than the control group, but CTH was not different from controls in any of the regions. WM DR/MD underlying superior frontal, rostral middle frontal, lateral/medial orbitofrontal and retrosplenial cortices were significantly associated with inhibition/switching performance, while caudal middle frontal CTH was significantly associated with attention and divided attention in the patient group. We conclude that increased WM DR/MD in frontal and cingulate regions and cortical thinning in caudal middle frontal region are both associated with executive dysfunction in MCI.
Long-term outcome and safety of transanal colonic irrigation for neurogenic bowel dysfunction

Long-term follow-up study.Short-term results find transanal colonic irrigation (TAI) favourable in the treatment of neurogenic bowel dysfunction (NBD). Therefore, long-term results need to be described.Department of Surgery P, Aarhus University Hospital, Denmark.Between 1994 and 2007, 211 (115 female) patients with NBD (age: 7–81 years (median 49)) were introduced to TAI. One hundred and seventy-three patients had spinal cord injury and 38 had other neurological disorders. Data were obtained from hospital records and a mailed questionnaire. Treatment was considered successful in patients still using TAI, patients who had used TAI until they died and patients whose symptoms had resolved while using Successful outcome was achieved in 98 (46%) patients after a mean follow-up of 19 months (range 1–114 months). A Kaplan–Meier plot showed a dropout of 20% in the first 3 months. After 3 years, the rate of success was 35% and remained almost unchanged afterwards. A regression analysis showed male gender (odds ratio (OR) 2.1), mixed symptoms (OR 2.9) and prolonged colorectal transit time (OR 2.4) to be significantly associated with successful outcome. One non-lethal bowel perforation occurred in approximately 50 000 irrigations (0.002%), whereas minor side effects were observed in 48%.Conclusion:After a mean follow-up of 19 months, 46% was successfully treated. The rate of success was 35% after 3 years and remained almost unchanged afterwards. TAI is safe and can be introduced to most patients suffering from NBD.
Health care usage in Dutch systemic lupus erythematosus patients.

As a first step in the improvement of the organization of care for patients with systemic lupus erythematosus (SLE) we studied their health care usage and its determinants. A questionnaire was sent to 161 outpatients of the rheumatology clinic of a Dutch university hospital. The questionnaire comprised questions on health care usage, quality of life and sociodemographic characteristics. Disease characteristics were extracted from the medical record. Among the 102 responders (63% response rate) the proportions of patients reporting contacts with a rheumatologist because of SLE since onset of the disease and over the past 12 months were 100% and 83%, respectively. These proportions were 93% and 68% for all other medical specialists, 88% and 44% for the general practitioner, 78% and 44% for any health professional, 29% and 9% for care at home, 48% and 17% for hospital admissions and 29% and 2% for day-patient care. Younger age, major organ involvement, the use of immunosuppressants and worse physical functioning were found to be significantly associated with greater health care use. This study demonstrated that health care usage by SLE patients is substantial and involves a variety of health care services. Further research should be directed at patients' satisfaction and patients' needs regarding the optimal organization of integrated, multidisciplinary services that are accessible for SLE patients of all ages.
Recombinant NY-ESO-1 protein with ISCOMATRIX adjuvant induces broad antibody responses in humans, a RAYS-based analysis.

Antibody responses to tumor antigens play an important role in initiating a cellular antitumor response with respect to antigen cross-presentation and T cell cross-priming. Successful vaccination strategies rely on an optimally timed activation of the humoral and cellular immune system by using appropriate adjuvant stimulation. The LUD99-008 trial used the cancer testis antigen NY-ESO-1 formulated with ISCOMATRIX adjuvant injected into patients intramuscularly. It was shown that this vaccination strategy is a safe and highly potent activator of the humoral and cellular immune system. Using the RAYS technology, we analyzed in detail the humoral immune response in these patients before and after vaccination: during the course of repeated vaccinations with the adjuvant, antibody titers against NY-ESO-1 and cross-reactivity to LAGE 1A and B increased as an indicator of an enhanced immune response, whereas no antibody response could be detected after vaccination without the adjuvant. Analysis of single fragments of the NY-ESO-1 protein revealed that the humoral response was almost exclusively directed against the N-terminal fragments and the number of fragments and their length being recognized by the NY-ESO-1-specific antibodies increased during the course of vaccination. The humoral immune response mainly consisted of antibodies of the IgG1 and IgG3 subclass. We rarely found IgG2 and IgG4 subclass antibodies. Our results support the implication that target-specific antibodies raised after vaccination contribute to the stimulation of an effective T cell response against the target antigen.
Pretreatment prediction of response to peginterferon plus ribavirin therapy in genotype 1 chronic hepatitis C using data mining analysis

This study aimed to develop a model for the pre-treatment prediction of sustained virological response (SVR) to peg-interferon plus ribavirin therapy in chronic hepatitis C. Data from 800 genotype 1b chronic hepatitis C patients with high viral load (>100,000 IU/ml) treated by peg-interferon plus ribavirin at 6 hospitals in Japan were randomly assigned to a model building (n = 506) or an internal validation (n = 294). Data from 524 patients treated at 29 hospitals in Japan were used for an external validation. Factors predictive of SVR were explored using data mining analysis. Age (<50 years), alpha-fetoprotein (AFP) (<8 ng/mL), platelet count (≥120 × 109/l), gamma-glutamyltransferase (GGT) (<40 IU/l), and male gender were used to build the decision tree model, which divided patients into 7 subgroups with variable rates of SVR ranging from 22 to 77%. The reproducibility of the model was confirmed by the internal and external validation (r 2 = 0.92 and 0.93, respectively). When reconstructed into 3 groups, the rate of SVR was 75% for the high probability group, 44% for the intermediate probability group and 23% for the low probability group. Poor adherence to drugs lowered the rate of SVR in the low probability group, but not in the high probability group. A decision tree model that includes age, gender, AFP, platelet counts, and GGT is useful for predicting the probability of response to therapy with peg-interferon plus ribavirin and has the potential to support clinical decisions regarding the selection of patients for therapy.
Hypothesis generation and ranking based on event similarities

Accelerated by the technological advances in the domain, the size of the biomedical literature has been growing rapidly. As a result, it is not feasible for individual researchers to comprehend and synthesize all the information related to their interests. Therefore, it is conceivable to discover hidden knowledge, or hypotheses, by linking fragments of information independently described in the literature. In fact, such hypotheses have been reported in the literature mining community; some of which have even been corroborated by experiments. This paper mainly focuses on hypothesis ranking and investigates an approach to identifying reasonable ones based on semantic similarities between events which lead to respective hypotheses. Our assumption is that hypotheses generated from semantically similar events are more reasonable. The validity of our approach is demonstrated in comparison with those based on term frequencies, often adopted in the related work.
Acute respiratory illness in patients with COPD and the effectiveness of influenza vaccination: a randomized controlled study.

To determine the effectiveness of influenza vaccination on influenza-related acute respiratory illness (ARI) and overall ARI in patients with COPD, and its relationship to the degree of airflow obstruction.



Stratified, randomized, double-blind, placebo-controlled trial.



From June 1997 to November 1998 at a single university hospital.



One hundred twenty-five patients with COPD were stratified based on their FEV(1) as having mild, moderate, and severe COPD. Within each group, they were randomized to the vaccine group (62 patients who received purified, trivalent, split-virus vaccine) or the placebo group (63 patients).



The number of episodes and severity of total ARI, classified as outpatient treatment, hospitalization, and requirement of mechanical ventilation; and the number of episodes and severity of influenza-related ARI.



The incidence of influenza-related ARI was 28.1 per 100 person-years and 6.8 per 100 person-years in the placebo group and vaccine group, respectively (relative risk [RR], 0.24 [p = 0.005]; vaccine effectiveness, 76%). The incidences were 28.2, 23.8, and 31.2 per 100 person-years in the patients with mild, moderate, and severe COPD, respectively, in the placebo group, and 4.5, 13.2, and 4.6 per 100 person-years in the patients with mild, moderate, and severe COPD, respectively, in the vaccine group (RR, 0.16 [p = 0.06]; vaccine effectiveness, 84%; RR, 0.55 [p = 0.5]; vaccine effectiveness, 45%; and RR, 0.15 [p = 0.04]; vaccine effectiveness, 85%, in the patients with mild, moderate, and severe COPD, respectively). Bivariate analysis revealed that the effectiveness of influenza vaccination was not modified by the severity of COPD, comorbid diseases, age, gender, or current smoking status. There was no difference in the incidence or severity of total ARI between the placebo group and the vaccine group.



Influenza vaccination is highly effective in the prevention of influenza-related ARI regardless of the severity of COPD. Influenza vaccination does not prevent other ARIs unrelated to influenza. The effectiveness of influenza vaccination in the prevention of overall ARI in patients with COPD will depend on how much the proportion of influenza-related ARI contributes to the incidence of total ARI. Influenza vaccination should be recommended to all patients with COPD.
[The validity and sensitivity to change of the Spanish self-administered version of the chronic respiratory questionnaire (CRQ-SAS)].

The interviewer-administered chronic respiratory questionnaire (CRQ-IA) is widely used and has demonstrated excellent properties for measuring health-related quality of life (HRQL) in patients with chronic obstructive pulmonary disease (COPD). However, the self-administered version (CRQ-SAS) in Spanish has not been validated. The aim of this trial was to evaluate the validity and the sensitivity of the Spanish version of the CRQ-SAS in patients with COPD.



We randomized 40 patients with COPD (33 treated with pulmonary rehabilitation and 7 with liquid oxygen therapy) to one of the two methods of administration of CRQ (SAS vs. IA) both before and 8 weeks after the treatment. In addition, patients completed the SF-36 questionnaire, pulmonary function tests, and six-minute walk test.



The CRQ-SAS demonstrated good longitudinal construct validity on all domains with a range of correlations, for the change scores, between 0.46 (P=.05) and 0.71 (P=.01). Regarding sensitivity to change, we observed a minimal clinically significant change in most domains (fatigue 0.71 [P=.02], emotional factor 0.62 [P=.04], control of the disease 0.83 [P=.06]).



The Spanish version of CRQ-SAS is valid for evaluating HRQL in COPD patients. The correlations of the CRQ-SAS with other tools provide construct validity and show good sensitivity to change.
Acute upper gastrointestinal bleeding in the UK: patient characteristics, diagnoses and outcomes in the 2007 UK audit.

To describe the patient characteristics, diagnoses and clinical outcomes of patients presenting with acute upper gastrointestinal bleeding (AUGIB) in the 2007 UK Audit.



Multi-centre survey.



All UK hospitals admitting patients with AUGIB.



All adults (>16 years) presenting in or to UK hospitals with AUGIB between 1 May and 30 June 2007.



Data on 6750 patients (median age 68 years) was collected from 208 participating hospitals. New admissions (n=5550) were younger (median age 65 years) than inpatients (n=1107, median age 71 years), with less co-morbidity (any co-morbidity 46% vs 71%, respectively). At presentation 9% (599/6750) had known cirrhosis, 26% a history of alcohol excess, 11% were taking non-steroidal anti-inflammatory drugs and 28% aspirin. Peptic ulcer disease accounted for 36% of AUGIB and bleeding varices 11%. In 13% there was evidence of further bleeding after the first endoscopy. 1.9% underwent surgery and 1.2% interventional radiology for AUGIB. Median length of stay was 5 days. Overall mortality in hospital was 10% (675/6750, 95% CI 9.3 to 10.7), 7% in new admissions and 26% among inpatients. Mortality was highest in those with variceal bleeding (15%) and with malignancy (17%).



AUGIB continues to result in substantial mortality although it appears to be lower than in 1993. Mortality is particularly high among inpatients and those bleeding from varices or upper gastrointestinal malignancy. Surgical or radiological interventions are little used currently.
Associations of sex steroid hormones with cerebral activations during mental rotation in men and women with schizophrenia

Sex steroid hormones have been implicated in the visuo-spatial abilities in the general population, as well as in the pathophysiology of schizophrenia. Nevertheless, almost nothing is known about the association between levels of testosterone and/or estrogen with brain activations during visuo-spatial processing in schizophrenia. The fMRI data collected during performance of a mental rotation task in 42 schizophrenia patients (21 women) and 42 matched controls, were correlated with the levels of testosterone and estrogen. Results revealed significant relationship between sex steroid hormones and cerebral activations in healthy men and in schizophrenia women, but no correlations were detected in healthy women or in male patients. The lack of correlations and the overall diminished levels of testosterone in male patients are consistent with some existing literature. On the other hand, the findings of augmented levels of testosterone and its implication in cerebral activations in female patients are unprecedented and merit further exploration.
Mindfulness-based stress reduction versus pharmacotherapy for chronic primary insomnia: a randomized controlled clinical trial.

The aim of this study was to investigate the potential of mindfulness-based stress reduction (MBSR) as a treatment for chronic primary insomnia.



A randomized controlled trial was conducted.



The study was conducted at a university health center.



Thirty adults with primary chronic insomnia based on criteria of the Diagnostic and Statistical Manual of Mental Disorders, Text Revision, 4th Edition were randomized 2:1 to MBSR or pharmacotherapy (PCT).



Mindfulness-based stress reduction, a program of mindfulness meditation training consisting of eight weekly 2.5 hour classes and a daylong retreat, was provided, with ongoing home meditation practice expectations during three-month follow-up; PCT, consisting of three milligrams of eszopiclone (LUNESTA) nightly for eight weeks, followed by three months of use as needed. A 10-minute sleep hygiene presentation was included in both interventions.



The Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI), sleep diaries, and wrist actigraphy were collected pretreatment, posttreatment (eight weeks), and at five months (self-reports only).



Between baseline and eight weeks, sleep onset latency (SOL) measured by actigraphy decreased 8.9 minutes in the MBSR arm (P < .05). Large, significant improvements were found on the ISI, PSQI, and diary-measured total sleep time, SOL, and sleep efficiency (P < .01, all) from baseline to five-month follow-up in the MBSR arm. Changes of comparable magnitude were found in the PCT arm. Twenty-seven of 30 patients completed their assigned treatment. This study provides initial evidence for the efficacy of MBSR as a viable treatment for chronic insomnia as measured by sleep diary, actigraphy, well-validated sleep scales, and measures of remission and clinical recovery.
Renal recovery after conversion to a calcineurin inhibitor-free immunosuppression in late cardiac transplant recipients.

Calcineurin inhibitor (CNI)-related renal failure is a common problem after cardiac transplantation (HTx). The aim of this prospective study was to evaluate the safety and efficacy of a completely CNI-free immunosuppressive regimen [mycophenolate mofetil (MMF) and sirolimus (Sir)] in HTx-recipients with late post-transplant renal impairment.



Since 2001, 30 HTx-patients (25 men, 6 women; 0.2-14.2 years after transplantation) with CNI-based immunosuppression and a serum creatinine >1.9 mg/dl were included in the study. Creatinine and cystatin levels were monitored to detect renal function. Conversion was started with 6 mg Sir or 500 mg MMF according to the pre-existing regimen and was continued with the dose adjusted to achieve target trough levels between 8 and 14 ng/ml (Sir) or 1.5 and 4 microg/ml (mycophenolate). Subsequently, the CNIs were tapered down and stopped. Clinical follow-up included endomyocardial biopsies, echocardiography and laboratory studies. Additionally, every HTx-patient treated at our centre between 1996 and 2001 due to chronic renal failure without immunosuppressive conversion and fulfilling the inclusion criteria were retrospectively analysed and acted as control group.



Patient demographics and 1-year survival [93 (conversion) vs 90% (control)] were compared. No acute rejection episode was detected in either group. Renal function improved significantly in the conversion group (creatinine: 3.18+/-0.71 vs 2.22+/-0.79 mg/dl, P=0.001; cystatin pre- vs post-conversion: 2.95+/-1.06 vs 2.02+/-1.1 mg/l, P=0.01). In three patients haemodialysis therapy was stopped completely after conversion. In the control group renal impairment was deteriorating, creatinine increased from 2.44+/-0.8 to 3.28+/-1 mg/dl (P=0.01). In 10 out of 33 patients chronic haemodialysis had to be initiated within 1 year. Although side effects of CNI-free immunosuppression were common (76%), no patient had to be excluded due to adverse effects.



Conversion from CNI-based immunosuppression to MMF and Sir in HTx-patients with chronic renal failure was safe, preserved graft function and improved renal function.
Effect of using ultrapure dialysate for hemodialysis on the level of circulating bacterial fragment in renal failure patients.

Cardiovascular disease is the major cause of mortality and morbidity in dialysis patients. Recently, circulating endotoxin is found to associate with the systemic inflammatory state and cardiovascular disease of dialysis patients. Previous studies showed that the use of ultrapure dialysate for hemodialysis could reduce the exposure to exogenous endotoxin. We studied the effect of using ultrapure dialysate for hemodialysis on circulating endotoxin and bacterial DNA fragment levels and vascular stiffness.



. Circulating endotoxin and bacterial DNA level, vascular stiffness as represented by arterial pulse wave velocity (PWV), nutrition and hydration status were monitored before and repeatedly throughout 12 months after the use of ultrapure dialysate for hemodialysis.



The average age was 58.9 ± 10.2 years; 21 patients completed the study. Within 4 weeks of conversion to ultrapure dialysate for hemodialysis, the plasma endotoxin level fell from 0.302 ± 0.083 to 0.209 ± 0.044 EU/ml (p < 0.0001) and then remained static, while serum bacterial DNA level remained similar. Furthermore, the time-averaged plasma endotoxin level during the study period significantly correlated with serum C-reactive protein level (r = 0.483, p = 0.017), carotid-femoral PWV (r = 0.455, p = 0.033), and malnutrition inflammation score (r = 0.461, p = 0.031). The time-averaged serum bacterial DNA level significantly correlated with malnutrition inflammation score (r = 0.550, p = 0.008) and inversely with subjective global assessment score (r = -0.543, p = 0.009), but not with PWV.



In hemodialysis patients, circulating endotoxin level is associated with vascular stiffness and systemic inflammation. Using ultrapure dialysate for hemodialysis effectively reduces circulating endotoxin level in hemodialysis patients. The long-term benefit of using ultrapure dialysate for hemodialysis requires further study.