nils-herrmann/clean_scirepeval huggingface dataset:
Golimumab 3-year safety update: an analysis of pooled data from the long-term extensions of randomised, double-blind, placebo-controlled trials conducted in patients with rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis

To assess pooled golimumab safety up to year 3 of rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) trials.



Golimumab 50 and 100 mg, administered subcutaneously (SC) every 4 weeks (q4wk), were assessed in patients with active RA (methotrexate-naïve, methotrexate-experienced and anti-TNF (tumour necrosis factor)-experienced), PsA or AS, despite conventional therapy. Placebo control continued up to week (wk) 24 (wk 52, methotrexate-naïve), with early escape at wk 16 (wk 28, methotrexate-naïve); subsequently, all patients received golimumab 50 or 100 mg q4wk. After the blinded controlled period, golimumab doses could be adjusted per investigator discretion. Pooled safety analyses reported herein include data from placebo-controlled and uncontrolled study periods up to wk 160. Determinations of incidences/100 patient-years (pt-yrs) for rare events also included RA patients from a phase IIb trial.



Across five phase III trials of SC golimumab, 639 patients received placebo and 2226 received golimumab 50 mg (n=1249) and/or 100 mg (n=1501) up to wk 160 (patients may be included in more than one group because non-responders were allowed early escape); 1179 patients were treated for ≥156 weeks. For placebo, golimumab 50 mg and golimumab 100 mg, respective adverse event incidences/100 pt-yrs (95% CIs) up to wk 160 were: 0.28 (0.01 to 1.56), 0.30 (0.12 to 0.62), 0.41 (0.23 to 0.69) for death; 5.31 (3.20 to 8.30), 3.03 (2.36 to 3.82), 5.09 (4.36 to 5.90) for serious infection; 0.00 (0.00 to 0.84), 0.17 (0.05 to 0.44), 0.35 (0.18 to 0.62) for tuberculosis; 0.00 (0.00 to 0.84), 0.13 (0.03 to 0.38), 0.24 (0.10 to 0.46) for opportunistic infection; 0.00 (0.00 to 0.84), 0.00 (0.00 to 0.13), 0.12 (0.03 to 0.30) for demyelination; and 0.00 (0.00 to 0.84), 0.04 (0.00 to 0.24), 0.18 (0.06 to 0.38) for lymphoma.



SC golimumab safety up to 3 years remained consistent with that of other TNF antagonists. Golimumab 100 mg showed numerically higher incidences of serious infections, demyelinating events and lymphoma than 50 mg; safety follow-up up to year 5 continues.
Depigmented and polymerised house dust mite allergoid: allergen content, induction of IgG4 and clinical response.

Polymerised allergenic extracts (allergoids) are commonly used in allergen immunotherapy. Clinical efficacy and safety of these extracts have been demonstrated. Recently, allergen sequences have been identified by mass spectrometry in depigmented and polymerised (Dpg-Pol) extracts. The objectives of this study were to investigate the presence of allergens in Dpg-Pol extracts of house dust mite and to analyze the immunological changes induced by these extracts in asthmatic patients enrolled in a double-blind, placebo-controlled study.



Dpg-Pol extracts were manufactured and vaccines with a composition of 50% Dermatophagoides pteronyssinus and 50% D. farinae (100 HEPL/ml) were prepared. Allergen composition was analyzed by mass spectrometry. Patients with asthma and rhinoconjunctivitis were treated in a 1-year, double-blind, placebo-controlled, parallel-group study with 6 up-dosing and monthly maintenance injections. Specific IgE and IgG4 titres to D. pteronyssinus, Der p 1 and Der p 2 were measured in patients' sera using the CAP system and direct ELISA experiments.



Sequences from the major allergens Der p 1 and Der p 2 and from other allergens were identified in native and Dpg-Pol extracts. There was a statistically significant increase in specific IgG4, a decrease in the ratio of IgE/IgG4 to D. pteronyssinus and a significant increase in specific IgG4 to Der p 1 and Der p 2 in the patients allotted to active treatment.



The detection of allergen sequences suggests preservation of major and minor allergens in Dpg-Pol allergoids from house dust mites. Efficacy in asthma treatment and the increase in specific IgG4 seem to be associated with the presence of major allergens in Dpg-Pol allergen extracts.
Evaluating the effectiveness of personal resilience and enrichment programme (PREP) for HIV prevention among female sex workers: a randomised controlled trial

Female sex workers (FSWs) are often considered as the vector, if not reservoir, of HIV and other sexually transmitted infections. Building upon the existing evidence on the role of psychological health in sexual health, the aim of this protocol is to describe a trial investigating the effectiveness of the Personal Resilience and Enrichment Programme (PREP), a resilience-promoting intervention that targets at psychological well-being i.e. self-esteem, self-efficacy and coping, to facilitate adaptation and ultimately safe sexual practices among FSWs, which could be an innovative strategy in controlling the spread of these infections.



A total of 132 FSWs will be recruited and randomly assigned to either the intervention or usual care (control) groups in a multi-centred randomised controlled trial. Based on the resilience framework, this intervention is comprised of six weekly sessions focused on the awareness, expression and management of emotions, identifying roles and personal strengths, and effective problem-solving skills. Complex intervention assessment on both intervention process and effectiveness will be adopted when the primary outcome reduction of sexual risk behaviour and other psychological outcomes include their perceived stress, self-esteem, self-efficacy, coping overall resilience, and psychological distress will be measured at baseline, post-treatment and 3-month post-intervention and differences assessed by ANOVA. The relationship of resilience factors, psychological health and HIV preventive behaviours will be evaluated using structural equation modelling.



It is anticipated that this study will increase our understanding of the relationships between individual resilience attributes, positive adaptation, psychological health and sexual health practices. If successful, this programme will provide an innovative direction for HIV prevention by applying the personal resilience factors to promote both psychological well-being and safe sex for this high risk population.
An Axiomatization of Arrays for Kleene Algebra with Tests

The formal analysis of programs with arrays is a notoriously difficult problem due largely to aliasing considerations. In this paper we augment the rules of Kleene algebra with tests (KAT) with rules for the equational manipulation of arrays in the style of schematic KAT. These rules capture and make explicit the essence of subscript aliasing, where two array accesses can be to the same element. We prove the soundness of our rules, as well as illustrate their usefulness with several examples, including a complete proof of the correctness of heapsort.
The effectiveness of aerobic training, cognitive behavioural therapy, and energy conservation management in treating MS-related fatigue: the design of the TREFAMS-ACE programme

TREFAMS is an acronym for TReating FAtigue in Multiple Sclerosis, while ACE refers to the rehabilitation treatment methods under study, that is, Aerobic training, Cognitive behavioural therapy, and Energy conservation management. The TREFAMS-ACE research programme consists of four studies and has two main objectives: (1) to assess the effectiveness of three different rehabilitation treatment strategies in reducing fatigue and improving societal participation in patients with MS; and (2) to study the neurobiological mechanisms of action that underlie treatment effects and MS-related fatigue in general.



Ambulatory patients (n = 270) suffering from MS-related fatigue will be recruited to three single-blinded randomised clinical trials (RCTs). In each RCT, 90 patients will be randomly allocated to the trial-specific intervention or to a low-intensity intervention that is the same for all RCTs. This low-intensity intervention consists of three individual consultations with a specialised MS-nurse. The trial-specific interventions are Aerobic Training, Cognitive Behavioural Therapy, and Energy Conservation Management. These interventions consist of 12 individual therapist-supervised sessions with additional intervention-specific home exercises. The therapy period lasts 16 weeks. All RCTs have the same design and the same primary outcome measures: fatigue - measured with the Checklist Individual Strength, and participation - measured with the Impact on Participation and Autonomy questionnaire. Outcomes will be assessed 1 week prior to, and at 0, 8, 16, 26 and 52 weeks after randomisation. The assessors will be blinded to allocation. Pro- and anti-inflammatory cytokines in serum, salivary cortisol, physical fitness, physical activity, coping, self-efficacy, illness cognitions and other determinants will be longitudinally measured in order to study the neurobiological mechanisms of action.



The TREFAMS-ACE programme is unique in its aim to assess the effectiveness of three rehabilitation treatments. The programme will provide important insights regarding the most effective treatment for MS-related fatigue and the mechanisms that underlie treatment response. A major strength of the programme is that the design involves three almost identical RCTs, enabling a close comparison of the treatment strategies and a strong overall meta-analysis. The results will also support clinical practice guidelines for the treatment of MS-related fatigue.
Phase I, dose-finding study of capecitabine in combination with docetaxel and epirubicin as first-line chemotherapy for advanced breast cancer.

Capecitabine is an oral fluoropyrimidine with considerable activity and minimal myelosuppression and alopecia. This phase I study evaluated the addition of capecitabine to epirubicin/docetaxel combination therapy as first-line treatment for advanced breast cancer.



Twenty-three female patients with advanced breast cancer received capecitabine (765-1060 mg/m2 twice daily on days 1-14 of a 3-week treatment cycle) in combination with epirubicin and docetaxel (75 mg/m2 i.v. on day 1).



The maximum tolerated dose of capecitabine was 985 mg/m2 and the principal dose-limiting toxicity was febrile neutropenia. No grade 3/4 anemia or thrombocytopenia occurred. There were no grade 4 non-hematological events and grade 3 events other than alopecia were rare. Alopecia occurred in all patients and treatment cycles, and asthenia occurred in all patients and in 84% of treatment cycles. Other frequent adverse events included nausea, vomiting, fever, paresthesia and elevated transaminase levels. An objective response to treatment was observed in 91% (95% confidence interval 72% to 99%) of patients.



The addition of capecitabine to docetaxel/epirubicin combination therapy provides a well-tolerated and active first-line chemotherapy regimen in patients with advanced breast cancer, and merits phase II/III evaluation.
Occupational exposure to extremely low frequency magnetic fields and mortality from cardiovascular disease.

The authors evaluated the relation between occupational exposure to extremely low frequency (ELF) magnetic fields and mortality from cardiovascular diseases. The study was based on 27,790 subjects from the Swedish Twin Registry. Exposure to ELF magnetic fields was assessed by linking occupation reported in 1967 or 1973 to a job exposure matrix. Four levels of exposure were related to cause-specific mortality through 1996, and primary and contributing causes of death were considered. The authors estimated relative risks by Cox regression, with adjustment for several cardiovascular disease risk indicators. The authors calculated the synergy index to evaluate potential interaction between exposure to ELF magnetic fields (>0.2 microT) and genetic susceptibility to acute myocardial infarction (AMI). Arrhythmia-related death, ischemic heart disease other than AMI, and atherosclerosis showed no association with ELF magnetic fields. The authors found a low-level increase in AMI risk in the highest exposure group (relative risk=1.3, 95% confidence interval: 0.9, 1.9) and suggestions of an exposure-response relation (p=0.02). A synergy index of 2.7 (95% confidence interval: 1.1, 6.6) in monozygotic twins indicated that the risk of AMI was strengthened among ELF magnetic field-exposed subjects with genetic susceptibility to the disease. The results for AMI corroborate previous findings from the United States. The unusual opportunity to include genetic susceptibility in the present analyses showed that evaluations of effect modification in vulnerable subjects are warranted in ELF magnetic field research.
Long-term outcome of a school-based, universal approach to prevention of depression in adolescents.

In this study, the authors examined the 2-, 3-, and 4-year outcomes of a school-based, universal approach to the prevention of adolescent depression. Despite initial short-term positive effects, these benefits were not maintained over time. Adolescents who completed the teacher-administered cognitive-behavioral intervention did not differ significantly from adolescents in the monitoring-control condition in terms of changes in depressive symptoms, problem solving, attributional style, or other indicators of psychopathology from preintervention to 4-year follow-up. Results were equivalent irrespective of initial level of depressive symptoms.
Improvement in Outcomes of Clinical Islet Transplantation: 1999–2010

To describe trends of primary efficacy and safety outcomes of islet transplantation in type 1 diabetes recipients with severe hypoglycemia from the Collaborative Islet Transplant Registry (CITR) from 1999 to 2010.



A total of 677 islet transplant-alone or islet-after-kidney recipients with type 1 diabetes in the CITR were analyzed for five primary efficacy outcomes and overall safety to identify any differences by early (1999-2002), mid (2003-2006), or recent (2007-2010) transplant era based on annual follow-up to 5 years.



Insulin independence at 3 years after transplant improved from 27% in the early era (1999-2002, n = 214) to 37% in the mid (2003-2006, n = 255) and to 44% in the most recent era (2007-2010, n = 208; P = 0.006 for years-by-era; P = 0.01 for era alone). C-peptide ≥0.3 ng/mL, indicative of islet graft function, was retained longer in the most recent era (P < 0.001). Reduction of HbA(1c) and resolution of severe hypoglycemia exhibited enduring long-term effects. Fasting blood glucose stabilization also showed improvements in the most recent era. There were also modest reductions in the occurrence of adverse events. The islet reinfusion rate was lower: 48% by 1 year in 2007-2010 vs. 60-65% in 1999-2006 (P < 0.01). Recipients that ever achieved insulin-independence experienced longer duration of islet graft function (P < 0.001).



The CITR shows improvement in primary efficacy and safety outcomes of islet transplantation in recipients who received transplants in 2007-2010 compared with those in 1999-2006, with fewer islet infusions and adverse events per recipient.
Transjugular Intrahepatic Portosystemic Shunt in the Treatment of Portal Hypertension Using Memotherm Stents: A Prospective Multicenter Study

In a prospective multicenter study, efficacy and safety of transjugular intrahepatic portosystemic shunts (TIPS) were evaluated in the treatment of the complications of portal hypertension using a new self-expanding mesh-wire stent (Memotherm).  One hundred and eighty-one patients suffering from variceal bleeding (either acute or recurrent) or refractory ascites were enrolled. Postinterventional follow-up lasted for 8.4 months on average. Differences were analyzed by the log-rank test (chi-square) or Wilcoxon test.  Shunt insertion was completed successfully in all patients (n = 181 patients, 100%). During follow-up, shunt occlusion was evident in 23 patients, and shunt stenosis was found in 33 patients (12.7% and 18.2%, respectively). Variceal rebleeding occurred in 20 of 139 patients (14.4%), with at least one episode of bleeding before TIPS treatment. The overall mortality rate of the patients treated by TIPS was 39.8%. In 51.4% of these cases (37 of 72 patients), however, the patients died within 30 days after TIPS placement. Analysis of subgroups showed that patients who underwent emergency TIPS for acute variceal bleeding had a significantly higher early mortality compared with other patient groups (p = 0.0014).  In the present prospective multicenter study, we were able to show that insertion of Memotherm stents is an effective tool for TIPS. The occlusion rates seem to be comparable to those reported for the Palmaz stent. It could be shown that in particular, those patients who were treated for acute bleeding were at high risk of early mortality. Consequently, in such a critical condition, the indication for TIPS has to be set carefully.
A cross-sectional, multicentre study of the therapeutic management of multiple sclerosis relapses in Italy

Despite the existence of therapeutic guidelines, management of multiple sclerosis relapse remains heterogeneous. Optimisation of relapse outcome demands an improved understanding of the neurologist’s therapeutic attitude towards relapse management, which is the aim of this study. Neurologists from 13 multiple sclerosis centres completed a questionnaire every time they assessed multiple sclerosis relapses. The questionnaire requested a guided description of the relapse’s clinical characteristics and an indication of the prescribed therapy, supported with up to 3 out of 20 suggested reasons. Over 3 months, 368 questionnaires were collected. Median percentage (%) of 21 relapses resulting in a prescription was 88.9%. Corticosteroids represented the most frequent prescription. A short-course of high-dose intravenous methylprednisolone was the most used corticosteroid (73.7%). Treatment was administrated mainly in day case unit (80.0%) and at home (13.6%). A tapered therapy was prescribed to 28.8% of patients. Neurologists’ therapeutic decisions were driven mainly by relapse severity (45.3%) and symptom evolution (24.2%). Our study confirms the therapeutic attitude of multiple sclerosis specialists in treating relapses with high-dose intravenous corticosteroids in a day hospital setting, with a tapering in a proportion of cases. The main reasons for prescription are relapse severity and symptom evolution.
Patient-reported outcomes in multiple sclerosis: Relationships among existing scales and the development of a brief measure.

Several patient-reported outcome (PRO) measures are commonly used in multiple sclerosis (MS) research, but the relationship among items across measures is uncertain. We proposed to evaluate the associations between items from a standard battery of PRO measures used in MS research and to develop a brief, reliable and valid instrument measure by combining these items into a single measure. Subjects (N = 537) enrolled in CLIMB complete a PRO battery that includes the Center for Epidemiologic Studies Depression Scale, Medical Outcomes Study Modified Social Support Survey, Modified Fatigue Impact Scale and Multiple Sclerosis Quality of Life-54. Subjects were randomly divided into two samples: calibration (n = 269) and validation (n = 268). In the calibration sample, an Exploratory Factor Analysis (EFA) was used to identify latent constructs within the battery. The model constructed based on the EFA was evaluated in the validation sample using Confirmatory Factor Analysis (CFA), and reliability and validity were assessed for the final measure. The EFA in the calibration sample revealed an eight factor solution, and a final model with one second-order factor along with the eight first-order factors provided the best fit. The model combined items from each of the four parent measures, showing important relationships among the parent measures. When the model was fit using the validation sample, the results confirmed the validity and reliability of the model. A brief PRO for MS (BPRO-MS) that combines MS-related psychosocial and quality of life domains can be used to assess overall functioning in mildly disabled MS patients.
Applying simulation in a consulting environment - tips from airport planners

Airport design is, by far, the largest practice area fo TransSolutions. This is a unique area, with man differences from typical simulation in manufacturing o logistics. Passengers and bags arrive at the airport by the pla load. At the busiest airports the arrivals and departures a coordinated, so that several flights arrive within a sho time. Then, after a short time on the ground the aircraft a depart again. A large number of passengers move throu the facility during the peak period between the fligh arrivals and the departures. After that, the facility will b empty until the next bank of arriving flights. The termina facilities must be sized to handle these waves of passeng throughout the day. Space within the terminal building is at a premium Most travelers are aware of the ticket counters, ga lounges, corridors and shops in the public areas. Hidd behind the scenes are the various offices, control room and break areas for the airport and airline employees. T baggage system and various maintenance functions take most of the space on the ramp level below the passen areas. The usual question asked by the architects is: “will th facility, as designed, satisfy the needs of the tena airlines?” This involves comparing the “performance” o the facility to minimum acceptable standards. A typica example is that all passengers connecting from an arrivi flight to a departing flight must be able to reach the departure gate within 30 minutes of arrival.
Lessons from ECLIPSE: a review of COPD biomarkers.

The Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) study was a large 3-year observational controlled multicentre international study aimed at defining clinically relevant subtypes of chronic obstructive pulmonary disease (COPD) and identifying novel biomarkers and genetic factors. So far, the ECLIPSE study has produced more than 50 original publications and 75 communications to international meetings, many of which have significantly influenced our understanding of COPD. However, because there is not one paper reporting the biomarker results of the ECLIPSE study that may serve as a reference for practising clinicians, researchers and healthcare providers from academia, industry and government agencies interested in COPD, we decided to write a review summarising the main biomarker findings in ECLIPSE.