nils-herrmann/clean_scirepeval huggingface dataset:
Colistin nephrotoxicity increases with age.

Colistin (COL) has become the backbone of the treatment of infections due to extensively drug-resistant (XDR) Gram-negative bacteria. The most common restriction to its use is acute kidney injury (AKI).



We conducted a retrospective cohort study to evaluate risk factors for new-onset AKI in patients receiving COL. The cohort consisted of 198 adults admitted to 9 referral hospitals between January 2010 and October 2012 and treated with intravenous COL for ≥ 72 h. Patients with no pre-existing kidney dysfunction were compared in terms of risk factors and outcomes of AKI graded according to the RIFLE criteria. Logistic regression analysis was used to identify associated risk factors.



A total of 198 patients met the inclusion criteria, of whom 167 had no pre-existing kidney dysfunction; the mean patient age was 58.77 (± 18.98) y. Bloodstream infections (34.8%) and ventilator-associated pneumonia (32.3%) were the 2 most common indications for COL use. New-onset AKI developed in 46.1% of the patients, graded as risk (10%), injury (15%), and failure (21%). Patients with high Charlson co-morbidity index (CCI) scores (p = 0.001) and comparatively low initial glomerular filtration rate (GFR) estimations (p < 0.001) were more likely to develop AKI, but older age (p = 0.001; odds ratio 5.199, 95% confidence interval 2.684-10.072) was the major predictor in the multivariate analysis. In-hospital recovery from AKI occurred in 58.1%, within a median of 7 days.



COL-induced nephrotoxicity occurred significantly more often in patients older than 60 y of age and was related to low initial GFR estimations and high CCI scores, which were basically determined by age.
On-treatment analysis of the Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT).

We aimed to determine the efficacy and safety of adding ezetimibe (Ez) to simvastatin (S) in a post-acute coronary syndrome (ACS) population in a prespecified on-treatment analysis.



We evaluated 17,706 post-ACS patients from the IMPROVE-IT trial who had low-density lipoprotein cholesterol values between 50 and 125 mg/dL and who received Ez 10 mg/d with S 40 mg/d (Ez/S) or placebo with simvastatin 40 mg/d (P/S). The primary composite end point was cardiovascular death, myocardial infarction, unstable angina, coronary revascularization ≥30 days postrandomization, or stroke. The on-treatment analysis included patients who received study drug for the duration of the trial or experienced a primary end point or noncardiovascular death within 30 days of drug discontinuation.



Mean low-density lipoprotein cholesterol values at 1 year were 71 mg/dL for P/S and 54 mg/dL for Ez/S (absolute difference -17 mg/dL = -24%; P < .001). The 7-year Kaplan-Meier estimate of the primary end point occurred in 32.4% in the P/S arm and 29.8% in the Ez/S arm (absolute difference 2.6%; HRadj 0.92 [95% CI 0.87-0.98]; P = .01). The absolute treatment effect favoring Ez/S was 30% greater than in the intention-to-treat analysis of IMPROVE-IT.



This analysis provides additional support for the efficacy and safety of adding Ez to S in this high-risk, post-ACS population.
A Genome-Wide Test of the Differential Susceptibility Hypothesis Reveals a Genetic Predictor of Differential Response to Psychological Treatments for Child Anxiety Disorders

The differential susceptibly hypothesis suggests that certain genetic variants moderate the effects of both negative and positive environments on mental health and may therefore be important predictors of response to psychological treatments. Nevertheless, the identification of such variants has so far been limited to preselected candidate genes. In this study we extended the differential susceptibility hypothesis from a candidate gene to a genome-wide approach to test whether a polygenic score of environmental sensitivity predicted response to cognitive behavioural therapy (CBT) in children with anxiety disorders.



We identified variants associated with environmental sensitivity using a novel method in which within-pair variability in emotional problems in 1,026 monozygotic twin pairs was examined as a function of the pairs' genotype. We created a polygenic score of environmental sensitivity based on the whole-genome findings and tested the score as a moderator of parenting on emotional problems in 1,406 children and response to individual, group and brief parent-led CBT in 973 children with anxiety disorders.



The polygenic score significantly moderated the effects of parenting on emotional problems and the effects of treatment. Individuals with a high score responded significantly better to individual CBT than group CBT or brief parent-led CBT (remission rates: 70.9, 55.5 and 41.6%, respectively).



Pending successful replication, our results should be considered exploratory. Nevertheless, if replicated, they suggest that individuals with the greatest environmental sensitivity may be more likely to develop emotional problems in adverse environments but also benefit more from the most intensive types of treatment.
A Randomized, Controlled Study of Once-Daily LY2605541, a Novel Long-Acting Basal Insulin, Versus Insulin Glargine in Basal Insulin–Treated Patients With Type 2 Diabetes

To evaluate whether LY2605541 results in lower fasting blood glucose (FBG) versus insulin glargine (GL).



This 12-week, randomized, open-label, Phase 2 study enrolled patients with type 2 diabetes (hemoglobin A(1c) [A1C] ≤ 10.5%), taking metformin and/or sulfonylurea with GL or NPH insulin once daily. Patients converted to morning insulin administration during lead-in were randomized 2:1 from GL (n = 248) or NPH insulin (n = 39) to LY2605541 (n = 195) or GL (n = 95) once daily in the morning.



At 12 weeks, FBG (mean ± SE) was similar with LY2605541 and GL (118.2 ± 2.0 mg/dL [6.6 ± 0.1 mmol/L] vs. 116.9 ± 2.7 mg/dL [6.5 ± 0.2 mmol/L], P = 0.433) as was A1C (7.0 ± 0.1 vs. 7.2 ± 0.1%, P = 0.279). Intraday blood glucose variability was reduced with LY2605541 (34.4 vs. 39.1 mg/dL [1.9 vs. 2.2 mmol/L], P = 0.031). LY2605541 patients had weight loss (-0.6 ± 0.2 kg, P = 0.007), whereas GL patients gained weight (0.3 ± 0.2 kg, P = 0.662; treatment difference: -0.8 kg, P = 0.001). The incidence and rate of both total hypoglycemia and nocturnal hypoglycemia were comparable between LY2605541 and GL, although, LY2605541 had a 48% reduction in nocturnal hypoglycemia after adjusting for baseline hypoglycemia (P = 0.021). Adverse events were similar across treatments. Alanine aminotransferase and aspartate aminotransferase remained within normal range but were significantly higher with LY2605541 (P ≤ 0.001).



In patients with type 2 diabetes, LY2605541 and GL had comparable glucose control and total hypoglycemia rates, but LY2605541 showed reduced intraday variability, lower nocturnal hypoglycemia, and weight loss relative to GL.
Enhancing the therapeutic responsiveness of photodynamic therapy with the antiangiogenic agents SU5416 and SU6668 in murine nasopharyngeal carcinoma models

Photodynamic therapy (PDT) is a promising therapeutic modality using a tumor localizing photosensitizer and light to destroy tumor cells. A major limitation of PDT is tumor recurrence, which is partly due to neovascularization.  The objective of the present study was to determine whether combination therapy with PDT and antiangiogenic agents (i.e. SU5416 and SU6668) would be more effective in controlling tumor recurrence in a mouse model of human CNE2 poorly differentiated nasopharyngeal carcinoma compared with PDT or antiangiogenic agents administered alone.  Athymic mice bearing CNE2 tumor xenografts received daily i.p. injections of 20 mg/kg SU5416 or 100 mg/kg SU6668 for 28 consecutive days either alone or following a single hypericin-PDT treatment.  Significant inhibition of CNE2 tumor growth was observed in all treatment groups. Differences in 4× tumor growth time, the number of mice with 4× tumor growth, tumor growth inhibition as well as the percent of mice surviving were not statistically significant among individual treatment groups. However, the number of mice with 4× tumor growth observed in SU6668 monotherapy and combined PDT and SU6668 treatment groups was significantly less than that in the control group (P<0.05 and 0.01, respectively). Moreover, compared with the control group, only the combined PDT and SU6668 treatment significantly extended survival of tumor-bearing host mice (P<0.05). The semiquantitative RT-PCR results showed that the expression of HIF-1α, VEGF, COX-2 and bFGF were increased in PDT-treated tumor samples collected 24 h post-PDT, suggesting that PDT-induced damage to tumor microvasculature and the resultant hypoxia upregulate the expression of certain proangiogenic factors.  The effectiveness of PDT can be enhanced by antiangiogenic treatment with the synthetic RTK inhibitors. Of the two synthetic RTK inhibitors tested, SU6668 was more effective than SU5416 in enhancing tumor responsiveness to PDT.
Cost effectiveness of a new strategy to identify HNPCC patients.

Distinguishing hereditary non-polyposis colorectal cancer (HNPCC) from non-hereditary colorectal cancer (CRC) can increase the life expectancy of HNPCC patients and their close relatives.



To determine the effectiveness, efficiency, and feasibility of a new strategy for the detection of HNPCC, using simple criteria for microsatellite instability (MSI) analysis of newly detected tumours that can be applied by pathologists. Criteria for MSI analysis are: (1) CRC before age 50 years; (2) second CRC; (3) CRC and HNPCC associated cancer; or (4) adenoma before age 40 years.



The efficacy and cost effectiveness of the new strategy was evaluated against current practice. Decision analytic models were constructed to estimate the number of extra HNPCC mutation carriers and the costs of this strategy. The incremental costs and gain in life expectancy for a HNPCC mutation carrier were evaluated by Markov modelling. Feasibility was explored in five hospitals.



Using the new strategy, 2.2 times more HNPCC patients can be identified among a CRC population compared with current practice. This new strategy was found to be cost effective with an expected cost effectiveness ratio of 3801 per life year gained. When including the group of siblings and children, the cost effectiveness ratio became 2184 per life year gained. Sensitivity analysis showed these findings to be robust.



MSI testing in a selection of newly diagnosed CRC patients was shown to be cost effective and a feasible method to identify patients at risk for HNPCC who are not recognised by family history.
Artificial metaplasticity prediction model for cognitive rehabilitation outcome in acquired brain injury patients

The main purpose of this research is the novel use of artificial metaplasticity on multilayer perceptron (AMMLP) as a data mining tool for prediction the outcome of patients with acquired brain injury (ABI) after cognitive rehabilitation. The final goal aims at increasing knowledge in the field of rehabilitation theory based on cognitive affectation.



The data set used in this study contains records belonging to 123 ABI patients with moderate to severe cognitive affectation (according to Glasgow Coma Scale) that underwent rehabilitation at Institut Guttmann Neurorehabilitation Hospital (IG) using the tele-rehabilitation platform PREVIRNEC(©). The variables included in the analysis comprise the neuropsychological initial evaluation of the patient (cognitive affectation profile), the results of the rehabilitation tasks performed by the patient in PREVIRNEC(©) and the outcome of the patient after a 3-5 months treatment. To achieve the treatment outcome prediction, we apply and compare three different data mining techniques: the AMMLP model, a backpropagation neural network (BPNN) and a C4.5 decision tree.



The prediction performance of the models was measured by ten-fold cross validation and several architectures were tested. The results obtained by the AMMLP model are clearly superior, with an average predictive performance of 91.56%. BPNN and C4.5 models have a prediction average accuracy of 80.18% and 89.91% respectively. The best single AMMLP model provided a specificity of 92.38%, a sensitivity of 91.76% and a prediction accuracy of 92.07%.



The proposed prediction model presented in this study allows to increase the knowledge about the contributing factors of an ABI patient recovery and to estimate treatment efficacy in individual patients. The ability to predict treatment outcomes may provide new insights toward improving effectiveness and creating personalized therapeutic interventions based on clinical evidence.
Monocyte activation by an oral immunomodulator (bestatin) in lymphoma patients following autologous bone marrow transplantation

Bestatin (ubenimex), an inhibitor of aminopeptidase, is an oral immunomodulator that binds to CD13 (aminopeptidase N) on macrophages/monocytes. To examine its immunomodulatory effect after high-dose therapy and autologous bone marrow transplantation (BMT), a dose-finding phase Ib trial was conducted with 30 Hodgkin’s disease and non-Hodgkin’s lymphoma patients who received no drug (control), 10 and 30 mg (low dose), or 90 and 180 mg (high dose) of bestatin daily for 60 days following autologous BMT. Bestatin administration was initiated when the absolute neutrophil count was greater than 250/mm3 on 2 consecutive days. The serum neopterin levels, an indicator of monocyte/macrophage activation, increased in the high-dose group compared to the control group (not significantly) and the low-dose group (significantly). Similarly, the colony-stimulating activity in the sera was significantly increased in the high-dose group compared to the control and low-dose groups. We also examined the expression of cell-surface markers on monocytes in these patients by fluorescent cytometry analysis. There was no significant difference either in the frequency or absolute number of monocytes (CD14+) among the three groups at any time. However, a significant increase in the frequency of CD16(FcgRIII)-positive monocytes (a marker of activation) was observed in the high-dose group compared to controls from day 14 to day 60 after the start of bestatin administration. Further, the frequency of HLA-DR+ monocytes (another marker of activation) was significantly increased in the high-dose group. These results indicate that bestatin at higher doses (90 and 180 mg daily), but not lower doses, activates macrophages/monocytes, as demonstrated by phenotypic marker (HLA-DR and CD16) up-regulation, and this provides augmentation of neopterin and colony-stimulating activity in the serum of patients following autologous BMT.
Continuing to Confront COPD International Physician Survey: physician knowledge and application of COPD management guidelines in 12 countries

Utilizing data from the Continuing to Confront COPD (chronic obstructive pulmonary disease) International Physician Survey, this study aimed to describe physicians' knowledge and application of the GOLD (Global initiative for chronic Obstructive Lung Disease) Global Strategy for the Diagnosis, Management and Prevention of COPD diagnosis and treatment recommendations and compare performance between primary care physicians (PCPs) and respiratory specialists.



Physicians from 12 countries were sampled from in-country professional databases; 1,307 physicians (PCP to respiratory specialist ratio three to one) who regularly consult with COPD, emphysema, or chronic bronchitis patients were interviewed online, by telephone or face to face. Physicians were questioned about COPD risk factors, prognosis, diagnosis, and treatment, including knowledge and application of the GOLD global strategy using patient scenarios.



Physicians reported using spirometry routinely (PCPs 82%, respiratory specialists 100%; P<0.001) to diagnose COPD and frequently included validated patient-reported outcome measures (PCPs 67%, respiratory specialists 81%; P<0.001). Respiratory specialists were more likely than PCPs to report awareness of the GOLD global strategy (93% versus 58%, P<0.001); however, when presented with patient scenarios, they did not always perform better than PCPs with regard to recommending GOLD-concordant treatment options. The proportion of PCPs and respiratory specialists providing first- or second-choice treatment options concordant with GOLD strategy for a GOLD B-type patient was 38% versus 67%, respectively. For GOLD C and D-type patients, the concordant proportions for PCPs and respiratory specialists were 40% versus 38%, and 57% versus 58%, respectively.



This survey of physicians in 12 countries practicing in the primary care and respiratory specialty settings showed high awareness of COPD-management guidelines. Frequent use of guideline-recommended COPD diagnostic practices was reported; however, gaps in the application of COPD-treatment recommendations were observed, warranting further evaluation to understand potential barriers to adopt guideline recommendations.
Ischaemic preconditioning reduces troponin T release in patients undergoing coronary artery bypass surgery.

To investigate whether ischaemic preconditioning could reduce myocardial injury, as manifest by troponin T release, in patients undergoing elective coronary artery bypass surgery.



Randomised controlled trial.



Cardiothoracic unit of a tertiary care centre.



Patients with three vessel coronary artery disease and stable angina admitted for first time elective coronary artery bypass surgery were invited to take part in the study; 33 patients were randomised into control or preconditioning groups.



Patients in the preconditioning group were exposed to two additional three minute periods of myocardial ischaemia at the beginning of the revascularisation operation, before the ischaemic period used for the first coronary artery bypass graft distal anastomosis.



Serum troponin T concentration at 72 hours after cardiopulmonary bypass.



The troponin T assays were performed by blinded observers at a different hospital. All patients had undetectable serum troponin T (< 0.1 microgram/l) before cardiopulmonary bypass, and troponin T was raised postoperatively in all patients. At 72 hours, serum troponin T was lower (P = 0.05) in the preconditioned group (median 0.3 microgram/l) than in the control group (median 1.4 micrograms/l).



The direct application of a preconditioning stimulus in clinical practice has been shown, for the first time, to protect patients against irreversible myocyte injury.
Reliability and responsiveness of the Juvenile Arthritis MRI Scoring (JAMRIS) system for the knee

To assess the reliability and responsiveness of a new Juvenile Arthritis MRI Scoring (JAMRIS) system for evaluating disease activity of the knee. Twenty-five juvenile idiopathic arthritis (JIA) patients with clinical knee involvement were studied using open-bore 1-T MRI. MRI features of synovial hypertrophy, bone marrow changes, cartilage lesions and bone erosions were independently scored by five readers using the JAMRIS system. In addition, the JAMRIS system was determined to be a follow-up parameter by two readers to evaluate the response to therapy in 15 consecutive JIA patients. Inter-reader (ICCs 0.86–0.95) and intra-reader reliability (ICCs 0.92–1.00) for the scoring of JAMRIS features was good. Reliability of the actual scores and changes in scores over time was good for all items: ICCs 0.89–1.00, 0.87–1.00, respectively. Concerning therapy response, the mean synovial hypertrophy scores decreased significantly (mean 1.1 point; P < 0.001, SRM = −0.65). No change was observed with respect to bone marrow change, cartilage lesion and bone erosion scores. The JAMRIS proved to be a simple and highly reliable assessment score in the evaluation of JIA disease activity of the knee. The JAMRIS system may serve as an objective and accurate outcome measure in future research and clinical trials. • MRI is increasingly used to diagnose and assess juvenile idiopathic arthritis. • A simple and reliable scoring method would help monitor progress and research. • The Juvenile Arthritis MRI Scoring (JAMRIS) system provides reliable objective measures. • JAMRIS evaluates synovial hypertrophy, bone marrow changes, cartilage lesions and bone erosions. • The JAMRIS system can detect therapeutic response and should help future research.
Providing patient education: impact on quantity and quality of family health history collection

Family health history (FHH) is an underutilized tool in primary care to identify and risk-stratify individuals with increased cancer risk.  Evaluate the influence of patient education on quantity and quality of FHH entered into a primary care-based software program, and impact on the program’s cancer risk management recommendations.  Two primary care practices within a larger type II hybrid implementation-effectiveness controlled clinical trial.  English speaking non-adopted patients with a well visit appointment December 2012–March 2013.  One to two weeks prior to their well visit appointment, participants entered their FHH into the program. Participants were then provided educational materials describing key FHH components. They were instructed to use the interval to collect additional FHH information. Patients then returned for their scheduled appointment, and updated their FHH with any new information.  Percentage per pedigree of relatives meeting individual quality criteria. Changes made after patient education and changes to recommendations for surveillance, chemoprevention or genetic counseling referral.  Post patient education, pedigrees exhibited a greater percentage (per pedigree) of: deceased relatives with age at death (84 vs. 81 % p = 0.02), deceased relatives with cause of death (91 vs. 87 % p = 0.02), relatives with a named health condition (45 vs. 42 % p = 0.002), and a greater percentage of relatives with high quality records (91 vs. 89 % p = 0.02). Of 43 participants with pedigree changes that could trigger changes in risk stratified prevention recommendations, 12 participants (28 %) received such changes.  Patient education improves FHH collection and subsequent risk stratification utilized in providing actionable evidence-based care recommendations for cancer risk management.
Scalp electrode placement by EC2 adhesive paste in long-term video-EEG monitoring.

To evaluate the usefulness of an adhesive paste named EC2 (Grass-Telefactor) in comparison with collodion, for scalp electrodes placement in patients with drug resistant partial epilepsy monitored by long-term video-EEG.



A total of 40 patients with drug resistant partial epilepsy participated in the study. In 20 patients, electrode placement on the scalp was made with collodion (group C) whereas in the remaining patients EC2 was used (Group P). After the electrode placement (T1) and after 24 h of recording (T2), the impedance of the electrodes was measured. Moreover, the time required to apply the electrodes and for their daily maintenance was calculated and recorded for all patients who entered the study.



At each observation, group C showed mean values of electrode impedance significantly higher that the group P (T1: 16.8 k omega; T2: 6.5 k omega vs T1: 2.4 k omega; T2: 4.0 k omega, respectively) (P < 1 x 10(-5)). The time required to make the montage and to provide its daily maintenance was significantly shorter in group P than in group C [20.8 and 10.5 min vs 44.3 and 19.7 min, respectively (P < 1 x 10(-5))].



We found that the use of EC2 paste in scalp electrode attachment is less time consuming, with better recording quality as a result of lower electrode impedance values, than the use of collodion.



EC2 paste may substitute collodion in electrode placement for long-term video-EEG monitoring, with an optimal cost-benefit ratio in terms of recording performance, time consumption, and safety.