nils-herrmann/clean_scirepeval huggingface dataset:
Randomized controlled double-blind trial of optimal dose methylphenidate in children and adolescents with severe attention deficit hyperactivity disorder and intellectual disability.

Attention deficit hyperactivity disorder is increased in children with intellectual disability. Previous research has suggested stimulants are less effective than in typically developing children but no studies have titrated medication for individual optimal dosing or tested the effects for longer than 4 weeks.



One hundred and twenty two drug-free children aged 7-15 with hyperkinetic disorder and IQ 30-69 were recruited to a double-blind, placebo-controlled trial that randomized participants using minimization by probability, stratified by referral source and IQ level in a one to one ratio. Methylphenidate was compared with placebo. Dose titration comprised at least 1 week each of low (0.5 mg/kg/day), medium (1.0 mg/kg/day) and high dose (1.5 mg/kg/day). Parent and teacher Attention deficit hyperactivity disorder (ADHD) index of the Conners Rating Scale-Short Version at 16 weeks provided the primary outcome measures. Clinical response was determined with the Clinical Global Impressions scale (CGI-I). Adverse effects were evaluated by a parent-rated questionnaire, weight, pulse and blood pressure. Analyses were by intention to treat.



Methylphenidate was superior to placebo with effect sizes of 0.39 [95% confidence intervals (CIs) 0.09, 0.70] and 0.52 (95% CIs 0.23, 0.82) for the parent and teacher Conners ADHD index. Four (7%) children on placebo versus 24 (40%) of those on methylphenidate were judged improved or much improved on the CGI. IQ and autistic symptoms did not affect treatment efficacy. Active medication was associated with sleep difficulty, loss of appetite and weight loss but there were no significant differences in pulse or blood pressure.



Optimal dosing of methylphenidate is practical and effective in some children with hyperkinetic disorder and intellectual disability. Adverse effects typical of methylphenidate were seen and medication use may require close monitoring in this vulnerable group.
Ultrasound in management of rheumatoid arthritis: ARCTIC randomised controlled strategy trial

To determine whether a treatment strategy based on structured ultrasound assessment would lead to improved outcomes in rheumatoid arthritis, compared with a conventional strategy.


Ten rheumatology departments and one specialist centre in Norway, from September 2010 to September 2015.


238 patients were recruited between September 2010 and April 2013, of which 230 (141 (61%) female) received the allocated intervention and were analysed for the primary outcome. The main inclusion criteria were age 18-75 years, fulfilment of the 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for rheumatoid arthritis, disease modifying anti-rheumatic drug naivety with indication for disease modifying drug therapy, and time from first patient reported swollen joint less than two years. Patients with abnormal kidney or liver function or major comorbidities were excluded.


122 patients were randomised to an ultrasound tight control strategy targeting clinical and imaging remission, and 116 patients were randomised to a conventional tight control strategy targeting clinical remission. Patients in both arms were treated according to the same disease modifying anti-rheumatic drug escalation strategy, with 13 visits over two years.


The primary endpoint was the proportion of patients with a combination between 16 and 24 months of clinical remission, no swollen joints, and non-progression of radiographic joint damage. Secondary outcomes included measures of disease activity, radiographic progression, functioning, quality of life, and adverse events. All participants who attended at least one follow-up visit were included in the full analysis set.


26 (22%) of the 118 analysed patients in the ultrasound tight control arm and 21 (19%) of the 112 analysed patients in the clinical tight control arm reached the primary endpoint (mean difference 3.3%, 95% confidence interval -7.1% to 13.7%). Secondary endpoints (disease activity, physical function, and joint damage) were similar between the two groups. Six (5%) patients in the ultrasound tight control arm and seven (6%) patients in the conventional arm had serious adverse events.


The systematic use of ultrasound in the follow-up of patients with early rheumatoid arthritis treated according to current recommendations is not justified on the basis of the ARCTIC results. The findings highlight the need for randomised trials assessing the clinical application of medical technology.
Efficacy of vinorelbine, epirubicin and prednisone combination regimen in pretreated elderly patients with aggressive non-Hodgkin's lymphoma.

To assess the efficacy and toxic profile of the NAEPP protocol, a regimen including vinorelbine, epirubicin and prednisone, in a particularly troublesome subset of patients: pretreated elderly patients with aggressive non-Hodgkin's lymphoma (NHL).



From November 1998 to January 2000, 20 pretreated patients who had all relapsed after first-line VNCOP-B chemotherapy were enrolled in a phase II trial and treated with the NAEPP regimen: vinorelbine (25 mg/m(2) i.v. on days 1 and 8), epirubicin (40 mg/m(2) i.v. on days 1 and 8), and prednisone (40 mg/m(2) on days 1 and 8) with granulocyte colony-stimulating factor administered at 5 mg/kg/day on days 2-5 and days 9-12. Chemotherapy was repeated every 4 weeks for a total of 6 cycles.



Six (30%) patients achieved complete remission (CR) and 7 (35%) had partial responses (PR), giving an overall response rate of 65%. The response rate was not affected either by type of relapse presentation (nodal versus nodal plus extranodal), presence of bulky disease, or time of relapse. No major toxic effects were recorded.



These preliminary data suggest that the NAEPP regimen is an effective combination with a low toxicity profile in elderly pretreated patients with aggressive NHL. Further trials using NAEPP as a consolidation phase following first-line treatment are needed to establish the advantage in terms of CR rate and relapse-free survival in these patients.
The prognostic significance of IDH 1 mutations in younger adult patients with acute myeloid leukemia is dependent on FLT 3 / ITD status

Mutations in the isocitrate dehydrogenase gene (IDH1) were recently described in patients with acute myeloid leukemia (AML). To investigate their prognostic significance we determined IDH1 status in 1333 young adult patients, excluding acute promyelocytic leukemia, treated in the United Kingdom MRC AML10 and 12 trials. A mutation was detected in 107 patients (8%). Most IDH1 patients (91%) had intermediate-risk cytogenetics. Mutations correlated significantly with an NPM1 mutation (P < .0001) but not a FLT3/ ITD (P .9). No difference in outcome between IDH1 and IDH1 patients was found in univariate or multivariate analysis, or if the results were stratified by NPM1 mutation status. However, when stratified by FLT3/ITD status, an IDH1 mutation was an independent adverse factor for relapse in FLT3/ITD patients (P .008) and a favorable factor in FLT3/ ITD patients (P .02). These results suggest that metabolic changes induced by an IDH1 mutation may influence chemoresistance in a manner that is contextdependent.
Imatinib mesylate therapy for relapse after allogeneic stem cell transplantation for chronic myelogenous leukemia.

Twenty-eight adults with chronic myelogenous leukemia (CML) that had relapsed after allogeneic stem cell transplantation (SCT) received imatinib mesylate (400-1000 mg/d). Disease was in chronic phase in 5 patients, accelerated in 15, and blastic in 8 (7 medullary, 1 extramedullary); median time from transplantation to relapse was 9 months (range, 1-137 months). Thirteen patients had undergone salvage donor lymphocyte infusion (DLI) (median time from DLI to imatinib mesylate therapy, 4 months [range, 2-39 months]). The overall response rate was 79% (22 of 28 patients); the complete hematologic response (CHR) rate was 74% (17 of 23 patients), and the cytogenetic response rate was 58% (15 of 26 patients; complete response in 9 [35%] patients). CHR rates were 100% for chronic phase, 83% for accelerated phase, and 43% for blastic phase. The patient with extramedullary blastic disease achieved complete response. Cytogenetic response rates were 63% (12 of 19 patients) for chronic or accelerated phases (complete cytogenetic response in 8) and 43% for blastic phase (3 of 7 patients). At median follow-up of 15 months, 19 patients were alive, 9 with no evidence of disease. The 1-year estimated survival rate was 74%. Five patients had recurrence of grade 3 (3 patients) or grades 1 to 2 (2 patients) graft-versus-host disease (GVHD). Severe granulocytopenia developed in 43% of patients and thrombocytopenia in 27%; both conditions reversed with dose adjustments of imatinib mesylate. We conclude that imatinib mesylate effectively controlled CML that recurred after allogeneic SCT, but it was associated with side effects including myelosuppression and recurrence of severe GVHD.
Preliminary efficacy of a computer-based HIV intervention for African-American women.

This study evaluated the preliminary efficacy of a computer-based HIV intervention to enhance HIV-protective sexual behaviours, based on a randomised controlled trial among 135 African-American women, 21-29 years of age, seeking services at Planned Parenthood in Atlanta, GA. Participants were randomised either to a control session two, 60-minute computer-based HIV intervention sessions administered on a laptop computer that each concluded with a 15-minute small group session or to a control session of general health information including discussion on HIV prevention. Relative to controls, participants in the computer-based HIV intervention were more knowledgeable about HIV/STD prevention and reported higher scores on the measure of condom use self-efficacy at 3 months post-intervention; they also reported a higher percentage of condom-protected sex and were more likely to use condoms consistently for vaginal sex (odds ratio, OR = 5.9; p < 0.039) and were more likely to use condoms consistently for oral sex (OR = 13.83; p < 0.037). This relatively brief intervention provides preliminary support that an evidence-based group-based HIV prevention intervention for young African-American women can be adapted to a computer-based HIV intervention.
Efficacy of Lapatinib in Therapy-Resistant HER2-Positive Circulating Tumor Cells in Metastatic Breast Cancer

To evaluate the efficacy of lapatinib, a dual EGFR and HER2 tyrosine kinase inhibitor, in therapy-resistant HER2-positive CTCs in metastatic breast cancer (MBC).



Patients with MBC and HER2-positive CTCs despite disease stabilization or response to prior therapy, received lapatinib 1500 mg daily in monthly cycles, till disease progression or CTC increase. CTC monitoring was performed by immunofluorescent microscopy using cytospins of peripheral blood mononuclear cells (PBMCs) double stained for HER2 or EGFR and cytokeratin.



A total of 120 cycles were administered in 22 patients; median age was 62.5 years, 15 (68.2%) patients were post-menopausal and 20 (90.1%) had HER2-negative primary tumors. At the end of the second course, HER2-positive CTC counts decreased in 76.2% of patients; the median number of HER2-positive CTCs/patient also declined significantly (p = 0.013), however the decrease was significant only among patients presenting disease stabilization (p = 0.018) but not among those with disease progression during lapatinib treatment. No objective responses were observed. All CTC-positive patients harbored EGFR-positive CTCs on progression compared to 62.5% at baseline (p = 0.054). The ratio of EGFR-positive CTCs/total CTCs detected in all patients increased from 17.1% at baseline to 37.6% on progression, whereas the mean percentage of HER2-negative CTCs/patient increased from 2.4% to 30.6% (p = 0.03).



The above results indicate that lapatinib is effective in decreasing HER2-positive CTCs in patients with MBC irrespectively of the HER2 status of the primary tumor and imply the feasibility of monitoring the molecular changes on CTCs during treatment with targeted agents.
The effects of non-insulin-dependent diabetes mellitus on the kinetics of onset of insulin action in hepatic and extrahepatic tissues.

The mechanism(s) of insulin resistance in non-insulin-dependent diabetes mellitus remains ill defined. The current studies sought to determine whether non-insulin-dependent diabetes mellitus is associated with (a) a delay in the rate of onset of insulin action, (b) impaired hepatic and extrahepatic kinetic responses to insulin, and (c) an alteration in the contribution of gluconeogenesis to hepatic glucose release. To answer these questions, glucose disappearance, glucose release, and the rate of incorporation of 14CO2 into glucose were measured during 0.5 and 1.0 mU/kg-1 per min-1 insulin infusions while glucose was clamped at approximately 95 mg/dl in diabetic and nondiabetic subjects. The absolute rate of disappearance was lower (P < 0.05) and the rate of increase slower (P < 0.05) in diabetic than nondiabetic subjects during both insulin infusions. In contrast, the rate of suppression of glucose release in response to a change in insulin did not differ in the diabetic and nondiabetic subjects during either the low (slope 30-240 min:0.02 +/- 0.01 vs 0.02 +/- 0.01) or high (0.02 +/- 0.00 vs 0.02 +/- 0.00) insulin infusions. However, the hepatic response to insulin was not entirely normal in the diabetic subjects. Both glucose release and the proportion of systemic glucose being derived from 14CO2 (an index of gluconeogenesis) was inappropriately high for the prevailing insulin concentration in the diabetic subjects. Thus non-insulin-dependent diabetes mellitus slows the rate-limiting step in insulin action in muscle but not liver and alters the relative contribution of gluconeogenesis and glycogenolysis to hepatic glucose release.
The Competence of Sub-Optimal Theories of STructure Mapping on Hard Analogies

Structure-mapping is a provably NP-Hard problem which is argued to lie at the core of the human metaphoric and analogical reasoning faculties. This NP-Hardness has meant that earlier naïve attempts at optimal solutions to the problem have had to be augmented with sub-optimal heuristics to ensure tractable performance. This paper considers various epistemological grounds for qualifying the competence of such heuristic approaches, and offers a quantitative evaluation of the suboptimal performance of three different models of analogy/metaphor, SME, ACME and Sapper.
Effect of Nebivolol and Atenolol on Brachial Artery Flow-Mediated Vasodilation in Patients with Coronary Artery Disease

Endothelial dysfunction is considered to be the first step in atherogenesis as well as a predictor of adverse cardiovascular events in patients with coronary artery disease (CAD), while endothelial function improvement is associated with improved clinical outcome. Nebivolol is a beta1-adrenoreceptor antagonist with an independent beneficial action on endothelial function, increasing nitric oxide bioavailability. The aim of the present study was to examine the effects of nebivolol on endothelial function in the brachial artery in patients with CAD compared with another selective beta1 adrenergic receptor antagonist, atenolol. Thirty-five patients with stable CAD were randomized to receive either 5 mg nebivolol (n = 17) or 50 mg atenolol (n = 18) daily for 4 weeks. Each patient underwent measurement of endothelial function by means of flow-mediated dilatation (FMD) of the brachial artery before and after 4 weeks of treatment. All vasoactive drugs and cardiovascular risk factors were comparable in the two groups. No significant differences were observed between the two groups at baseline in FMD. In the atenolol group FMD remained unchanged at the end of the 4-week treatment, but in patients treated with nebivolol FMD showed a significant increase by the end of the treatment period (3.9 ± 2.7% vs. 5.6 ± 2.9%, p = 0.047) leading to a significantly higher value compared to patients treated with atenolol (5.6 ± 2.9% vs. 3.4 ± 3.2%, p = 0.041). Beta1 blockade by nebivolol but not atenolol improves endothelial dysfunction in patients with CAD, an effect that might further reduce the risk for cardiovascular events in patients with CAD.
Recipient expression of ligands for donor inhibitory KIRs enhances NK-cell function to control leukemic relapse after haploidentical transplantation.

Natural killer (NK) cells that express self-HLA-specific receptors (where HLA is human leukocyte antigen) are "licensed" and more readily activated than unlicensed cells; therefore, NK-cell licensing could influence the antileukemia effects of NK cells following haploidentical stem cell transplantation (haplo-SCT). In this study, we compared the functionality of reconstituting NK cells, based on CD107α expression and interferon-γsecretion, in a cohort of 29 patients that expressed (n = 8) or lacked (n = 21) class I human leukocyte antigens for donor inhibitory killer cell immunoglobulin-like receptors (KIRs) following T-cell-replete haplo-SCT. We also addressed whether recipient expression of class I ligands for donor inhibitory KIRs could predict relapse occurrence in another cohort of 188 patients. A longitudinal analysis indicated that patients presenting class I for all donor inhibitory KIRs showed more capable functional NK effector cells when tested against class I negative K562 cells and primary leukemic cells within 3 months of transplantation. The lowest 7-year relapse incidence was observed when donor KIRs were ligated by recipient class I (n = 60) compared with donor-host partnerships where donor KIR(+) cells were ligated by donor, but not recipient class I (n = 86, p = 0.026) or KIRs that were ligated by neither donor nor recipient class I (n = 42, p = 0.043). This study suggests that haplo-SCT recipients presenting class I for donor inhibitory KIRs promote NK-cell licensing, leading to decreased relapse rates.
Single-aliquot, non-bronchoscopic bronchoalveolar lavage in the diagnosis of metastatic mammary tumours in dogs.

To evaluate the use of bronchoalveolar lavage as an auxiliary tool for the diagnosis of neoplastic lung metastasis from mammary tumours in dogs.



A single-institution prospective observational study including 20 healthy dogs and 30 with mammary tumours. Thoracic radiography and single-aliquot, non-bronchoscopic bronchoalveolar lavage with cytology interpretation was performed in all animals and the results compared between groups.



Dogs with mammary gland tumours and radiographic evidence of pulmonary metastasis had significantly higher relative neutrophil counts in bronchoalveolar lavage fluid than dogs with tumours without evidence of metastasis. In only one dog, in which thoracic radiographs were normal, were malignant cells identified in bronchoalveolar lavage fluid.



Inflammatory bronchoalveolar lavage fluid in dogs with mammary gland tumours may suggest metastatic disease. Bronchoalveolar lavage does not appear to be sensitive for identifying malignant cells.
Further Simplification of the Simple Erosion Narrowing Score With Item Response Theory Methodology.

To further simplify the simple erosion narrowing score (SENS) by removing scored areas that contribute the least to its measurement precision according to analysis based on item response theory (IRT) and to compare the measurement performance of the simplified version to the original.



Baseline and 18-month data of the Combinatietherapie Bij Reumatoide Artritis (COBRA) trial were modeled using longitudinal IRT methodology. Measurement precision was evaluated across different levels of structural damage. SENS was further simplified by omitting the least reliably scored areas. Discriminant validity of SENS and its simplification were studied by comparing their ability to differentiate between the COBRA and sulfasalazine arms. Responsiveness was studied by comparing standardized change scores between versions.



SENS data showed good fit to the IRT model. Carpal and feet joints contributed the least statistical information to both erosion and joint space narrowing scores. Omitting the joints of the foot reduced measurement precision for the erosion score in cases with below-average levels of structural damage (relative efficiency compared with the original version ranged 35-59%). Omitting the carpal joints had minimal effect on precision (relative efficiency range 77-88%). Responsiveness of a simplified SENS without carpal joints closely approximated the original version (i.e., all Δ standardized change scores were ≤0.06). Discriminant validity was also similar between versions for both the erosion score (relative efficiency = 97%) and the SENS total score (relative efficiency = 84%).



Our results show that the carpal joints may be omitted from the SENS without notable repercussion for its measurement performance.
Neoadjuvant FOLFOX 4 versus FOLFOX 4 with Cetuximab versus immediate surgery for high-risk stage II and III colon cancers: a multicentre randomised controlled phase II trial – the PRODIGE 22 - ECKINOXE trial

In patients with high risk stage II and stage III colon cancer (CC), curative surgery followed by adjuvant FOLFOX-4 chemotherapy has become the standard of care. However, for 20 to 30 % of these patients, the current curative treatment strategy of surgical excision followed by adjuvant chemotherapy fails either to clear locoregional spread or to eradicate distant micrometastases, leading to disease recurrence. Preoperative chemotherapy is an attractive concept for these CCs and has the potential to impact upon both of these causes of failure. Optimum systemic therapy at the earliest possible opportunity may be more effective at eradicating distant metastases than the same treatment given after the delay and immunological stress of surgery. Added to this, shrinking the primary tumor before surgery may reduce the risk of incomplete surgical excision, and the risk of tumor cell shedding during surgery. PRODIGE 22 - ECKINOXE is a multicenter randomized phase II trial designed to evaluate efficacy and feasibility of two chemotherapy regimens (FOLFOX-4 alone and FOLFOX-4 + Cetuximab) in a peri-operative strategy in patients with bulky CCs. Patients with CC deemed as high risk T3, T4 and/or N2 on initial abdominopelvic CT scan are randomized to either colectomy and adjuvant chemotherapy (control arm), or 4 cycles of neoadjuvant chemotherapy with FOLFOX-4 (for RAS mutated patients). In RAS wild-type patients a third arm testing FOLFOX+ cetuximab has been added prior to colectomy. Patients in the neoadjuvant chemotherapy arms will receive postoperative treatment for 4 months (8 cycles) to complete their therapeutic schedule. The primary endpoint of the study is the histological Tumor Regression Grade (TRG) as defined by Ryan. The secondary endpoints are: treatment strategy safety (toxicity, primary tumor related complications under chemotherapy, peri-operative morbidity), disease-free and recurrence free survivals at 3 years, quality of life, carcinologic quality and completeness of the surgery, initial radiological staging and radiological response to neoadjuvant chemotherapy, and the correlation between histopathological and radiological response. Taking into account a 50 % prevalence of CC without RAS mutation, accrual of 165 patients is needed for this Phase II trial. NCT01675999