nils-herrmann/clean_scirepeval huggingface dataset:
Allergic disease at the age of 7 years after pertussis vaccination in infancy: results from the follow-up of a randomized controlled trial of 3 vaccines.

To prospectively assess sensitization rates and the development of allergic diseases in a follow-up of a randomized controlled pertussis vaccine trial.



Two-month-old infants were the subject of this double-blind study in 1992 in a collaboration between the Pediatric Clinic and the Primary Care Centers in Linköping.



Allergic diseases were evaluated in 667 children, who were randomized to 1 of 4 vaccine groups: a 2-component, a 5-component, or a whole cell pertussis vaccine (all of which were administered with the diphtheria and tetanus toxoids vaccine) and the diphtheria and tetanus toxoids vaccine alone. Allergy development was assessed by questionnaires (n = 667) and skin prick tests (n = 538) at the age of 7 years.



Allergic diseases and skin prick test results at the age of 7 years.



The cumulative incidence of allergic diseases was 34.9%, and was similar in the 4 groups (33.3%-37.3%, P =.89), even after adjusting for family history, sex, pets, dampness, environmental smoking at home, and other living conditions. Positive skin prick test results were more prevalent, however, after vaccination with the 2-component acellular vaccine (19.4%) than in the other 3 groups (11.1%-13.5%, adjusted for confounding factors, P =.01). Furthermore, allergic rhinoconjunctivitis was more common in children who were initially immunized with the 2-component pertussis vaccine and received a booster dose with an acellular vaccine compared with those who received no booster vaccination (relative risk, 3.6; 95% confidence interval, 1.1-12.0).



Pertussis vaccination in infancy with any of these vaccines was not associated with allergic manifestations at the age of 7 years, apart from a higher prevalence of positive skin prick test results after an experimental 2-component vaccine, which is no longer in use.
The effects of modafinil on mood and cognition in Huntington’s disease

The wake-promoting agent modafinil selectively improves neuropsychological task performance in healthy volunteers, in adults with attention deficit hyperactivity disorder (ADHD) and in schizophrenia. We examined whether modafinil induced similar effects in individuals with Huntington’s disease (HD). Twenty patients with genetically proven, mild HD participated in a double-blind, randomised, placebo-controlled cross-over study using a single 200 mg dose of modafinil. Patients undertook a battery of neuropsychological tests including measures of cognition and mood. Modafinil increased alertness as indexed by visual analogue scales. Modafinil did not elicit any significant improvements in cognitive function or mood. Modafinil had a deleterious effect on visual recognition and working memory. Two hundred milligrams acute modafinil administration did improve alertness but did not improve cognition or mood in patients with mild HD. A multiple dose, chronic administration study is needed before the potential clinical utility of modafinil in HD is discounted.
The effect of injecting botulinum toxin type a into the calf muscles on freezing of gait in Parkinson's disease: a double blind placebo-controlled pilot study.

To assess the effect on freezing of gait (FOG) of botulinum toxin type A (BTX-A) injections in advanced Parkinson's disease (PD) patients.



BTX-A 150 IU or normal saline was injected into each leg's calf muscles by a blinded investigator. FOG severity was assessed at set intervals (6-month follow-up).



Eleven age- and disease severity-matched PD patients with disabling FOG participated. Six patients received BTX-A and 5 received saline. No improvement was observed in either group over time. Leg weakness and falls lead to early termination.



BTX-A injections to the legs did not improve FOG and might increase fall risk.
Epidural analgesia improves outcome after multiple rib fractures.

Rib fractures are common and associated with significant pulmonary morbidity. We hypothesized that epidural analgesia would provide superior pain relief, and reduce the risk of subsequent pneumonia.



A prospective, randomized trial of epidural analgesia versus IV opioids for the management of chest wall pain after rib fractures was carried out. Entry criteria included patients older than 18 years with more than 3 rib fractures and no contraindications to epidural catheter placement.



From March 2000 to December 2003, 408 patients were admitted with more than 3 rib fractures; 282 met exclusion criteria, 80 could not be consented, and 46 were enrolled (epidural n = 22, opioids n = 24). The groups were comparable for mean age, injury severity score, gender, chest Abbreviated Injury Scale, and mean number of rib fractures. The epidural group tended to have more flail segments (38% vs 21%, P = .20) and pulmonary contusions (59% vs 38%, P = .14), and required more chest tubes (95% vs 71%, P = .03) Despite the greater direct pulmonary injury in the epidural group, their rate of pneumonia was 18% versus 38% for the intravenous opioid group. When adjusted for direct pulmonary injury, there was a greater risk of pneumonia in the opioid group: OR, 6.0; 95% CI, 1.0-35; P = .05. When stratified for the presence of pulmonary contusion there was a 2.0-fold increase in the number of ventilator days for the opioid group: incident rate ratio, 2.0; 95% CI, 1.6-2.6; P < .001.



The use of epidural analgesia is limited in the trauma population due to numerous exclusion criteria. However, when feasible, epidural analgesia is associated with a decrease in the rate of nosocomial pneumonia and a shorter duration of mechanical ventilation after rib fractures.
A Statistical Framework for Predictive Model Evaluation in MOOCs

Feature extraction and model selection are two essential processes when building predictive models of student success. In this work we describe and demonstrate a statistical approach to both tasks, comparing five modeling techniques (a lasso penalized logistic regression model, naïve Bayes, random forest, SVM, and classification tree) across three sets of features (week-only, summed, and appended). We conduct this comparison on a dataset compiled from 30 total offerings of five different MOOCs run on the Coursera platform. Through the use of the Friedman test with a corresponding post-hoc Nemenyi test, we present comparative performance results for several classifiers across the three different feature extraction methods, demonstrating a rigorous inferential process intended to guide future analyses of student success systems.
Erratum to: Odanacatib for the treatment of postmenopausal osteoporosis: development history and design and participant characteristics of LOFT, the Long-Term Odanacatib Fracture Trial

Odanacatib is a cathepsin K inhibitor investigated for the treatment of postmenopausal osteoporosis. Phase 2 data indicate that 50 mg once weekly inhibits bone resorption and increases bone mineral density, with only a transient decrease in bone formation. We describe the background, design and participant characteristics for the phase 3 registration trial.  Odanacatib (ODN) is a selective cathepsin K inhibitor being evaluated for the treatment of osteoporosis. In a phase 2 trial, ODN 50 mg once weekly reduced bone resorption while preserving bone formation and progressively increased BMD over 5 years. We describe the phase III LongTerm ODN Fracture Trial (LOFT), an event-driven, randomized, blinded placebo-controlled trial, with preplanned interim analyses to permit early termination if significant fracture risk reduction was demonstrated.   The three primary outcomes were radiologically determined vertebral, hip, and clinical non-vertebral fractures. Secondary end points included clinical vertebral fractures, BMD, bone turnover markers, and safety and tolerability, including bone histology. Participants were women, 65 years or older, with a BMD T-score ≤−2.5 at the total hip (TH) or femoral neck (FN) or with a prior radiographic vertebral fracture and a T-score ≤−1.5 at the TH or FN. They were This study was registered with clinicaltrials.gov with registration number NCT00529373. Electronic supplementary material The online version of this article (doi:10.1007/s00198-014-2944-6) contains supplementary material, which is available to authorized users. H. G. Bone (*) Michigan Bone & Mineral Clinic, Detroit, MI, USA e-mail: hgbone.md@att.net D. W. Dempster Columbia University, New York, NY, USA J. A. Eisman Garvan Institute of Medical Research, University of Notre Dame Australia, St Vincent’s Hospital and UNSWAustralia, Sydney, Australia S. L. Greenspan University of Pittsburgh, Pittsburgh, PA, USA M. R. McClung Oregon Osteoporosis Center, Portland, OR, USA T. Nakamura University of Occupational and Environmental Health, Kitakyushu, Japan S. Papapoulos Leiden University Medical Center, Leiden, Netherlands W. J. Shih Robert Wood Johnson Medical School, Piscataway, NJ, USA A. Rybak-Feiglin :A. C. Santora :N. Verbruggen :A. T. Leung : A. Lombardi Merck Sharp and Dohme Corp., Whitehouse Station, NJ, USA H. G. Bone The Osteoporosis Center at St. Luke’s Hospital, Chesterfield, MO, USA Osteoporos Int (2015) 26:699–712 DOI 10.1007/s00198-014-2944-6
Development of a second-generation antiandrogen for treatment of advanced prostate cancer.

Metastatic prostate cancer is treated with drugs that antagonize androgen action, but most patients progress to a more aggressive form of the disease called castration-resistant prostate cancer, driven by elevated expression of the androgen receptor. Here we characterize the diarylthiohydantoins RD162 and MDV3100, two compounds optimized from a screen for nonsteroidal antiandrogens that retain activity in the setting of increased androgen receptor expression. Both compounds bind to the androgen receptor with greater relative affinity than the clinically used antiandrogen bicalutamide, reduce the efficiency of its nuclear translocation, and impair both DNA binding to androgen response elements and recruitment of coactivators. RD162 and MDV3100 are orally available and induce tumor regression in mouse models of castration-resistant human prostate cancer. Of the first 30 patients treated with MDV3100 in a Phase I/II clinical trial, 13 of 30 (43%) showed sustained declines (by >50%) in serum concentrations of prostate-specific antigen, a biomarker of prostate cancer. These compounds thus appear to be promising candidates for treatment of advanced prostate cancer.
A Window into the Intoxicated Mind? Speech as an Index of Psychoactive Drug Effects

Abused drugs can profoundly alter mental states in ways that may motivate drug use. These effects are usually assessed with self-report, an approach that is vulnerable to biases. Analyzing speech during intoxication may present a more direct, objective measure, offering a unique ‘window’ into the mind. Here, we employed computational analyses of speech semantic and topological structure after ±3,4-methylenedioxymethamphetamine (MDMA; ‘ecstasy’) and methamphetamine in 13 ecstasy users. In 4 sessions, participants completed a 10-min speech task after MDMA (0.75 and 1.5 mg/kg), methamphetamine (20 mg), or placebo. Latent Semantic Analyses identified the semantic proximity between speech content and concepts relevant to drug effects. Graph-based analyses identified topological speech characteristics. Group-level drug effects on semantic distances and topology were assessed. Machine-learning analyses (with leave-one-out cross-validation) assessed whether speech characteristics could predict drug condition in the individual subject. Speech after MDMA (1.5 mg/kg) had greater semantic proximity than placebo to the concepts friend, support, intimacy, and rapport. Speech on MDMA (0.75 mg/kg) had greater proximity to empathy than placebo. Conversely, speech on methamphetamine was further from compassion than placebo. Classifiers discriminated between MDMA (1.5 mg/kg) and placebo with 88% accuracy, and MDMA (1.5 mg/kg) and methamphetamine with 84% accuracy. For the two MDMA doses, the classifier performed at chance. These data suggest that automated semantic speech analyses can capture subtle alterations in mental state, accurately discriminating between drugs. The findings also illustrate the potential for automated speech-based approaches to characterize clinically relevant alterations to mental state, including those occurring in psychiatric illness.
Physical-activity coaching and health status in rheumatoid arthritis: a person-oriented approach.

No interventions to promote physical activity can succeed for all participants. Insights into the specific characteristics of those who do succeed are needed. One aim was to investigate whether a selection of correlates of general health perception creates cluster typologies in individuals with rheumatoid arthritis (RA). Another was to evaluate whether magnitude of change in health status differs between clusters after a 1-year coaching intervention targeting health-enhancing physical activity.



Two hundred and twenty-eight patients (74% women, mean age 56 years, disease duration 1 year) with RA, from 10 rheumatology clinics in Sweden, participated. The patients were assigned at random to intervention or control. The intervention group underwent 1 year of coaching to adopt health-enhancing physical activity (moderately intensive, 30 min/day, > 4 days/week). The cluster analysis included five correlates of general health perception: disease activity; pain; timed standing; activity limitation; and self-reported physical activity. The primary outcome of the coaching intervention was self-reported health status.



One-hundred and forty-six patients were eligible for inclusion in the cluster analysis. The eight clusters identified both at baseline and post interventions were operationalized according to the number of cluster variables affected: less (LE) affected or more (MO) affected, respectively. Clusters with LE affected variables had significantly better general health perception at baseline than those with MO affected variables. Further, coached individuals in MO affected clusters significantly improved self-reported health status compared both to those coached in LE affected clusters and to those in MO affected clusters in the control group.



This person-based approach contributed more than did the results in a previous randomized controlled trial to the understanding of which patients benefit most from the present physical-activity coaching intervention. The intervention may thus be most beneficial for individuals more severely affected by their disease at baseline.
Does chronic physical activity level modify the airway inflammatory response to an acute bout of exercise in the postprandial period?

Recent studies have confirmed that a single high-fat meal (HFM) leads to increased airway inflammation. However, exercise is a natural anti-inflammatory and may modify postprandial airway inflammation. The postprandial airway inflammatory response is likely to be modified by chronic physical activity (PA) level. This study investigated whether chronic PA modifies the airway inflammatory response to an acute bout of exercise in the postprandial period in both insufficiently active and active subjects. Thirty-nine nonasthmatic subjects (20 active, 13 males/7 females) who exceeded PA guidelines (≥150 min moderate-vigorous PA/week) and 19 insufficiently active (6 males/13 females) underwent an incremental treadmill test to exhaustion to determine peak oxygen uptake. Subjects were then randomized to a condition (COND), either remaining sedentary (CON) or exercising (EX) post-HFM. Exercise was performed at the heart rate corresponding to 60% peak oxygen uptake on a treadmill for 1 h post-HFM (63% fat, 10 kcal/kg body weight). Blood lipids and exhaled nitric oxide (eNO: marker of airway inflammation) were measured at baseline and 2 h and 4 h post-HFM. Sputum differential cell counts were performed at baseline and 4 h post-HFM. The mean eNO response for all groups increased at 2 h post-HFM (∼6%) and returned to baseline by 4 h (p = 0.03). There was a time × COND interaction (p = 0.04), where EX had a greater eNO response at 4 h compared with CON. Sputum neutrophils increased at 4 h post-HFM (p < 0.05). These findings suggest that airway inflammation occurs after an HFM when exercise is performed in the postprandial period, regardless of habitual activity level.
[Patient Questionnaire for Assessment of Rehabilitation Motivation (PAREMO-20) - psychometric evaluation and validation in a sample of cancer patients with different tumour sites].

A significant body of research suggests that patient motivation is related to better rehabilitation outcome with regard to psychosocial and physical well-being. Thus, patient motivation gains increasing attention with regard to the course of treatment and individual treatment planning in the practice and research in medical rehabilitation. This study aims to validate the PAREMO-20, a measure of rehabilitation motivation in a sample of cancer patients with different tumour sites.



1193 cancer patients participated in a prospective study evaluating the medical and psychosocial effects of inpatient cancer rehabilitation. A set of various questionnaires was completed at the beginning and at the end of the rehabilitation measure as well as at one year follow-up (participation rate at follow-up: 78%). The PAREMO-20 was psychometrically examined on this sample. Validity was examined using a cancer-specific questionnaire for individual therapy goals, as well as the HADS-D and the SF-8.



The original six factors were replicated. The factor solution emerging through PCA was tested with a confirmatory factor analysis. Maximum likelihood estimation of this model produced good fit statistics. Internal consistencies were high to satisfactory with Cronbach's Alpha=0.88 to Alpha=0.59. Psychological distress and physical impairments were positively associated with anxiety and depression, as well as with therapy goal dimensions. Moderate to high (negative) correlations were observed with health related quality of life, in particular with the mental-health dimension (r=-0.74, p=0.01).



The PAREMO-20 is a reliable, valid and economic instrument, which can be recommended for use in clinical care.
Selective inhibition of COX-2 in humans is associated with less gastrointestinal injury: a comparison of nimesulide and naproxen.

Selective inhibitors of cyclooxygenase (COX)-2 may provoke less gastric damage and platelet inhibition than conventional non-steroidal anti-inflammatory drugs.



We compared the biochemical and gastrointestinal effects of nimesulide, a potent and selective COX-2 inhibitor, with naproxen which exhibits no selectivity.



Thirty six healthy volunteers were randomised to nimesulide 100 mg or naproxen 500 mg twice daily for two weeks in a double blind, crossover study with a washout between treatments.



Gastrointestinal side effects were assessed by endoscopy, and by estimation of small intestinal absorption-permeability and inflammation. Comparisons were made between variables at the end of each treatment phase.



Nimesulide caused significantly less gastric injury using the modified Lanza score (p<0.001) as well as reduced duodenum injury (p=0.039). Nimesulide had lower visual analogue scores (VAS) for haemorrhage and erosive lesions in the stomach (p<0.001) and for mucosal injection in the duodenum (p=0.039). Naproxen increased excretion of calprotectin, a marker of intestinal inflammation (5.5 (1.2) to 12.1 (2.1) mg/l) while nimesulide had no effect (treatment difference p=0.03). Naproxen abolished platelet aggregation to arachidonic acid and suppressed serum thromboxane B(2) (TXB(2)) by 98%, indices of COX-1 activity. In contrast, nimesulide had no significant effect on platelet aggregation, although it reduced serum TXB(2) by 29%. Production of prostaglandin E(2) and prostacyclin by gastric biopsies, also COX-1 dependent, was inhibited by naproxen, but not by nimesulide. COX-2 activity, determined as endotoxin induced prostaglandin E(2) formation in plasma, was markedly suppressed by both treatments.



Nimesulide has preferential selectivity for COX-2 over COX-1 in vivo at full therapeutic doses and induces less gastrointestinal damage than that seen with naproxen in the short term.
Addition of cetuximab to oxaliplatin-based first-line combination chemotherapy for treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial

In the Medical Research Council (MRC) COIN trial, the epidermal growth factor receptor (EGFR)-targeted antibody cetuximab was added to standard chemotherapy in first-line treatment of advanced colorectal cancer with the aim of assessing effect on overall survival.



In this randomised controlled trial, patients who were fit for but had not received previous chemotherapy for advanced colorectal cancer were randomly assigned to oxaliplatin and fluoropyrimidine chemotherapy (arm A), the same combination plus cetuximab (arm B), or intermittent chemotherapy (arm C). The choice of fluoropyrimidine therapy (capecitabine or infused fluouroracil plus leucovorin) was decided before randomisation. Randomisation was done centrally (via telephone) by the MRC Clinical Trials Unit using minimisation. Treatment allocation was not masked. The comparison of arms A and C is described in a companion paper. Here, we present the comparison of arm A and B, for which the primary outcome was overall survival in patients with KRAS wild-type tumours. Analysis was by intention to treat. Further analyses with respect to NRAS, BRAF, and EGFR status were done. 
1630 patients were randomly assigned to treatment groups (815 to standard therapy and 815 to addition of cetuximab). Tumour samples from 1316 (81%) patients were used for somatic molecular analyses; 565 (43%) had KRAS mutations. In patients with KRAS wild-type tumours (arm A, n=367; arm B, n=362), overall survival did not differ between treatment groups (median survival 17·9 months [IQR 10·3-29·2] in the control group vs 17·0 months [9·4-30·1] in the cetuximab group; HR 1·04, 95% CI 0·87-1·23, p=0·67). Similarly, there was no effect on progression-free survival (8·6 months [IQR 5·0-12·5] in the control group vs 8·6 months [5·1-13·8] in the cetuximab group; HR 0·96, 0·82-1·12, p=0·60). Overall response rate increased from 57% (n=209) with chemotherapy alone to 64% (n=232) with addition of cetuximab (p=0·049). Grade 3 and higher skin and gastrointestinal toxic effects were increased with cetuximab (14 vs 114 and 67 vs 97 patients in the control group vs the cetuximab group with KRAS wild-type tumours, respectively). Overall survival differs by somatic mutation status irrespective of treatment received: BRAF mutant, 8·8 months (IQR 4·5-27·4); KRAS mutant, 14·4 months (8·5-24·0); all wild-type, 20·1 months (11·5-31·7).



This trial has not confirmed a benefit of addition of cetuximab to oxaliplatin-based chemotherapy in first-line treatment of patients with advanced colorectal cancer. Cetuximab increases response rate, with no evidence of benefit in progression-free or overall survival in KRAS wild-type patients or even in patients selected by additional mutational analysis of their tumours. The use of cetuximab in combination with oxaliplatin and capecitabine in first-line chemotherapy in patients with widespread metastases cannot be recommended.