nils-herrmann/clean_scirepeval huggingface dataset:
Prospective randomized crossover trial comparing fibre with lactulose in the treatment of idiopathic chronic constipation

Fibre is often recommended as the first-choice treatment but its effects can be uneven. The aim of the study was to compare the clinical efficacy and tolerability of fibre versus lactulose in outpatients with chronic constipation. In a prospective randomized crossover trial, patients were randomized to receive fibre or lactulose for four weeks. Between treatments, patients had at least one week free of laxatives. 50 patients, of median age 50 years (range, 18–85) were recruited and 39 patients completed the trial. Compared to fibre, lactulose resulted in significantly higher mean bowel frequency (7.3, 95% CI 5.7 to 8.9 vs. 5.5, 95% CI 4.4 to 6.5; p=0.001) and stool consistency score (3.4, 95% CI 3.1 to 3.7 vs. 2.9, 95% CI 2.5 to 3.3; p=0.018). Scores for ease of evacuation were similar. The frequencies of adverse effects were not significantly different, but greater in the lactulose group. Mean patients’ recorded improvement score was significantly higher after taking lactulose than fibre (6.2, 95% CI 5.5 to 7.0 vs. 4.8, 95% CI 4.0 to 5.9; p=0.017). Of the 39 patients who completed the trial, 24 (61.5%) preferred lactulose and 14 (35.9%) preferred fibre. Lactulose had better efficacy than fibre for chronic constipation in ambulant patients, although both treatments were equally well tolerated in terms of adverse effects.
Benefits of osteopathic manipulative treatment for hospitalized elderly patients with pneumonia.

While osteopathic manipulative treatment (OMT) is thought to be beneficial for patients with pneumonia, there have been few clinical trials--especially in the elderly. The authors' pilot study suggested that duration of intravenous antibiotic use and length of hospital stay were promising measures of outcome. Therefore, a larger randomized controlled study was conducted. Elderly patients hospitalized with acute pneumonia were recruited and randomly placed into two groups: 28 in the treatment group and 30 in the control group. The treatment group received a standardized OMT protocol, while the control group received a light touch protocol. There was no statistical difference between groups for age, sex, or simplified acute physiology scores. The treatment group had a significantly shorter duration of intravenous antibiotic treatment and a shorter hospital stay.
Validation of Prostate Imaging Reporting and Data System Version 2 Using an MRI-Ultrasound Fusion Biopsy in Prostate Cancer Diagnosis.

The purpose of our study was to prospectively assess Prostate Imaging Reporting and Data System (PI-RADS) version 2 using an MRI-ultrasound fusion biopsy.



This study included 295 consecutive patients with 478 lesions who underwent multiparametric MRI and subsequent MRI-ultrasound fusion biopsy between December 2014 and September 2016. Lesions were assessed by using an overall score of PI-RADS version 2. One radiologist assessed the presence or absence of clinically significant prostate cancer in the whole gland and in subgroups of the peripheral zone and transition zone by using cutoff values of ≥ 4 and ≥ 3. Histologic examination of MRI-ultrasound fusion biopsy specimens was used as the reference standard. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated to assess the utility of PI-RADS version 2 for the diagnosis of clinically significant prostate cancer.



The overall PI-RADS version 2 scores showed an accuracy of 82.2% (393/478) for the whole gland, with a cutoff value of ≥ 4 granting sensitivity of 90.0% (90/100), specificity of 80.1% (303/378), PPV of 83.3% (90/108), and NPV of 81.8% (303/370). The overall scores showed accuracies of 84.7% (301/355) in the peripheral zone and 74.7% (92/123) in the transition zone. When we applied an arbitrary overall score of ≥ 3, accuracy was 68.6% (328/478), sensitivity was 94.6% (124/131), specificity was 58.7% (204/347), PPV was 51.6% (124/240), and NPV was 85.7% (204/238).



PI-RADS version 2 has an overall good performance for the diagnosis of clinically significant prostate cancer.
Principles and results of family therapy in schizophrenia

There is growing evidence that social factors contribute significantly to the course and outcome in schizophrenia. In particular, the relationship between high EE and schizophrenic relapse has been documented by many investigators. Since 1980, several psychoeducational family management programs have been evaluated showing a significant reduction in relapse when compared to standard psychiatric care. To prevent tardive dyskinesia, alternative medication strategies have been introduced, e. g. low dose and targeted medication. In the Munich treatment study the combined effects of behavioral family management (BFM) and standard dose (SD) or targeted neuroleptic medication TM) on relapse and social functioning of the patient as well as coping and burden of the family have been investigated. N = 51 patients with 73 relatives were randomly assigned to the two groups (BFMSD = 27, BFMTM = 24). Relapse rates at 18 month were: BFSD = 3.9%, BFMTM = 33.8%. In summary, psychoeducational family management in combination with standard dose medication proved to be highly effective in preventing relapse in schizophrenia. These results are in line with findings of anglo-american studies and call for a more widespread application of these new psychosocial approaches in order to provide the best services available for the chronically ill schizophrenic patient and their families.
Dose- and time-dependent pharmacokinetics of midostaurin in patients with diabetes mellitus.

Midostaurin is a novel potent inhibitor of both protein kinase C and the major receptor for vascular endothelial growth factor involved in angiogenesis, presenting a rationale for its use in diabetic retinopathy. This study evaluated the safety and pharmacokinetics of midostaurin following multiple oral doses of midostaurin for 28 days at 4 dose levels (25 mg bid, 50 mg bid, 75 mg bid, 75 mg tid), as well as a single oral 100-mg dose in patients with diabetes mellitus (n = 9-13 per dose cohort). Pharmacokinetic parameters were determined on days 1 and 28 based on the plasma concentrations of midostaurin and its metabolites, CGP62221 and CGP52421. The plasma exposures (C(max) and AUC(0-tau)) of midostaurin and metabolites increased less than proportionally over the dose range of 25 to 100 mg, showing a 2.2-fold increase after the first dose. Midostaurin concentrations increased during the first 3 to 6 days of dosing, then declined with time (by 30%-50%) until a steady state was achieved, representing an average accumulation factor (R) of 1.7. CGP62221 showed a similar concentration-time pattern as midostaurin (R = 2.5), but CGP52421 accumulated significantly (R = 18.8). A high-fat meal was found to significantly increase the C(max) and AUC(0-12 h) of midostaurin by 1.5-fold (P = .04) and 1.8-fold (P = .01), respectively, compared with taking the drug after an overnight fast. Midostaurin administered at 50 to 225 mg/day appeared to be generally safe in this group of patients. The most common treatment-related adverse events (eg, loose stools, nausea, vomiting, and headache) were found to be dose related, and the frequency increased markedly above the 150-mg/day dose level.
Evaluating the effectiveness of reasoning training in military and civilian chronic traumatic brain injury patients: study protocol

Individuals who sustain traumatic brain injuries (TBIs) often continue to experience significant impairment of cognitive functions mediated by the prefrontal cortex well into chronic stages of recovery. Traditional brain training programs that focus on improving specific skills fall short of addressing integrative functions that draw upon multiple higher-order processes critical for social and vocational integration. In the current study, we compare the effects of two short-term, intensive, group-based cognitive rehabilitation programs for individuals with chronic TBI. One program emphasizes learning about brain functions and influences on cognition, while the other program adopts a top-down approach to improve abstract reasoning abilities that are largely reliant on the prefrontal cortex. These treatment programs are evaluated in civilian and military veteran TBI populations.



One hundred individuals are being enrolled in this double-blinded clinical trial (all measures and data analyses will be conducted by blinded raters and analysts). Each individual is randomly assigned to one of two treatment conditions, with each condition run in groups of five to seven individuals. The primary anticipated outcomes are improvement in abstract reasoning and everyday life functioning, measured through behavioral tasks and questionnaires, and attention modulation, as measured by functional neuroimaging. Secondary expected outcomes include improvements in the cognitive processes of working memory, attention, and inhibitory control.



Results of this trial will determine whether cognitive rehabilitation aimed at teaching TBI-relevant information about the brain and cognition versus training in TBI-affected thinking abilities (e.g., memory, attention, and executive functioning) can improve outcomes in chronic military and civilian TBI patient populations. It should shed light on the nature of improvements and the characteristics of patients most likely to benefit. This trial will also provide information about the sustainability of treatment-related improvements 3 months post-training.
Impact of point-of-care testing for CYP2C19 on platelet inhibition in patients with acute coronary syndrome and early dual antiplatelet therapy in the emergency setting.

Only limited data exist about the role of point of care CYP2C19 testing in the acute setting in the early phase of acute coronary syndromes (ACS). Therefore, the present study was designed to investigate the impact of CYP2C19 loss-of-function point-of-care (POC) genotyping in patients presenting with acute coronary syndromes (ACS) and treated with dual antiplatelet therapy in the emergency setting.



137 subjects with ACS scheduled for percutaneous coronary intervention were consecutively enrolled. Pre- and on-treatment platelet aggregation was assessed by multiple electrode aggregometry (MEA) after stimulation with adenosine diphosphate (ADP). Patients were loaded according to current guideline adherent indications and contraindications for use of P2Y12 inhibitors in ACS. POC genotyping for CYP2C19*2 was performed in the emergency room after obtaining a buccal swab using the Spartan RX CYP2C19 system and obtaining patient's informed consent. Prasugrel and ticagrelor treated patients had significantly lower PR compared to clopidogrel-treated patients. The benefits of prasugrel and ticagrelor compared to clopidogrel treated patients in terms of platelet inhibition were more pronounced in CYP2C19*2 carriers. Non-carriers showed similar inhibition regardless of particular P2Y12 inhibitor treatment. Statistical analyses adjusting for factors associated with response (e.g. smoking) revealed that CYP2C19*2 allele carrier status and loading with different type of P2Y12 receptor blockers were significant predictors of on-treatment platelet reactivity in the early phase of ACS.



The results of this pilot study of treatment of patients in the early phase of ACS indicate that CYP2C19*2 POC genotyping might help to identify patients at risk with poor response to clopidogrel treatment, thereby benefiting from reloading and switching to alternative P2Y12 receptor inhibition.
A randomized controlled trial of an appearance-focused intervention to prevent skin cancer.

Skin cancer represents a significant health threat with over 1.3 million diagnoses, 8000 melanoma deaths, and more than $1 billion spent annually for skin cancer healthcare in the US. Despite findings from laboratory, case-control, and prospective studies that indicate a link between youthful indoor tanning (IT) and skin cancer, IT is increasing among US youth. Appearance-focused interventions represent a promising method to counteract these trends.



A total of 430 female indoor tanners were randomized into intervention or no intervention control conditions. Intervention participants received an appearance-focused booklet based on decision-theoretical models of health behavior. Outcome variables included self-reports of IT behavior and intentions, as well as measures of cognitive mediating variables.



Normative increases in springtime IT rates were significantly lower (ie, over 35%) at 6-month follow-up in intervention versus control participants with similar reductions in future intentions. Mediation analyses revealed 6 cognitive variables (IT attitudes, fashion attitudes, perceived susceptibility to skin cancer and skin damage, subjective norms, and image norms) that significantly mediated change in IT behavior.



The appearance-focused intervention demonstrated strong effects on IT behavior and intentions in young indoor tanners. Appearance-focused approaches to skin cancer prevention need to present alternative behaviors as well as alter IT attitudes. Mediational results provide guides for strengthening future appearance-focused interventions directed at behaviors that increase risk of skin cancer.
Initial testing (stage 1) by the pediatric preclinical testing program of RO4929097, a γ-secretase inhibitor targeting notch signaling.

RO4929097 is a potent and selective inhibitor of γ-secretase and as a result is able to inhibit Notch pathway signaling. The activity of RO4929097 was evaluated against the in vivo panels of the Pediatric Preclinical Testing Program (PPTP). RO4929097 induced significant differences in event-free survival (EFS) distribution compared to control in 6 of 26 (23%) of the evaluable solid tumor xenografts and in 0 of 8 (0%) of the evaluable ALL xenografts. The most consistent tumor growth delay effects were noted in the osteosarcoma panel. RO4929097 at the dose and schedule evaluated demonstrated little antitumor activity against childhood cancer xenografts.
Sleep Duration, Lifestyle Intervention, and Incidence of Type 2 Diabetes in Impaired Glucose Tolerance

Both short and long sleep duration have frequently been found to be associated with an increased risk for diabetes. The aim of the present exploratory analysis was to examine the association between sleep duration and type 2 diabetes after lifestyle intervention in overweight individuals with impaired glucose tolerance in a 7-year prospective follow-up.



A total of 522 individuals (aged 40-64 years) were randomly allocated either to an intensive diet-exercise counseling group or to a control group. Diabetes incidence during follow-up was calculated according to sleep duration at baseline. Sleep duration was obtained for a 24-h period. Physical activity, dietary intakes, body weight, and immune mediators (C-reactive protein and interleukin-6) were measured.



Interaction between sleep duration and treatment group was statistically significant (P = 0.003). In the control group, the adjusted hazard ratios (HRs) (95% CI) for diabetes were 2.29 (1.38-3.80) and 2.74 (1.67-4.50) in the sleep duration groups 9-9.5 h and >or=10 h, respectively, compared with for that of the 7-8.5 h group. In contrast, sleep duration did not influence the incidence of diabetes in the intervention group; for sleep duration groups 9-9.5 h and >or=10 h, the adjusted HRs (95% CI) were 1.10 (0.60-2.01) and 0.73 (0.34-1.56), respectively, compared with that in the reference group (7-8.5 h sleep). Lifestyle intervention resulted in similar improvement in body weight, insulin sensitivity, and immune mediator levels regardless of sleep duration.



Long sleep duration is associated with increased type 2 diabetes risk. Lifestyle intervention with the aim of weight reduction, healthy diet, and increased physical activity may ameliorate some of this excess risk.
Development and validation of a disease model for postmenopausal osteoporosis

This article describes the development of a model for postmenopausal osteoporosis (PMO) based on Swedish data that is easily adaptable to other countries. The aims of the study were to develop and validate a model to describe the current/future burden of PMO in different national settings. For validation purposes, the model was developed using Swedish data and provides estimates from 1990. For each year of the study, the “incident cohort” (women experiencing a first osteoporotic fracture) was identified and run through a Markov model using 1-year cycles until 2020. Health states were based on the number of fractures and death. Fracture by site (hip, vertebral, and non-hip non-vertebral) was tracked for each health state. Transition probabilities reflected site-specific risk of death and subsequent fractures. Bone mineral density (BMD) was included as a model output; model inputs included population size and life tables from 1970 to 2020, incidence of fracture, relative risk of subsequent fractures based on prior fracture, relative risk of death following a fracture by site, and BMD by age (mean and standard deviation). Model predictions averaged across age groups estimated the incidence of hip, vertebral, and other osteoporotic fractures within a 5% margin of error versus published data. In Sweden, the number of osteoporotic fractures is expected to rise by 11.5% between 2009 and 2020, with a shift towards more vertebral fractures and multiple fractures. The current PMO disease model is easily adaptable to other countries, providing a consistent measure of present and future burden of PMO in different settings.
Importance of Host Genetic Factors HLA and IL28B as Predictors of Response to Pegylated Interferon and Ribavirin

Viral factors are considered the best predictors of response to treatment for chronic hepatitis C (CHC), but genetic factors are known to have an important role in this respect. This paper investigates the relationships among the host genetic factors HLA and IL28B, viral factors, and the outcome of combination therapy.A multicenter retrospective cohort of 428 previously untreated CHC patients was treated with pegylated interferon/ribavirin (pegIFN/RBV) for 48 weeks. In all, 378 (88%) of these patients were genotype 1 or 4, and 50 (12%) were genotype 2 or 3.RESULTS:Multivariate logistic regression showed the rs12979860 CC genotype (adjusted odds ratio (aOR)=4.3, 95% confidence interval (95% CI): 2.6–7), the HLA-DQB1*0301 allele (aOR=2.08, 95% CI: 1.2–3.5) and age, viral genotype, and viral load levels to be significantly associated with sustained virological response (SVR). When the variable rs12979860 was eliminated, the area under the receiver operating characteristic (ROC) curve (AUC) decreased significantly (0.76 vs. 0.69; P=0.03). AUC values derived from viral factors were lower than those corresponding to host genetic factors (0.67 vs. 0.72, respectively; P=0.04). The HLA-DQB1*0301 and A*0201 alleles were associated with rs12979860 CC genotype and SVR (P<0.0001).CONCLUSIONS:The HLA-DQB1*0301 allele and IL28B genotype are factors that are associated independently with SVR. There is a synergism between the HLA-DQB1*0301 and HLA-A*0201 alleles with polymorphism rs12979860 CC, which increases the SVR rate. IL28B genotype is the best predictor of SVR.
A phase 1 trial and pharmacokinetic study of cediranib, an orally bioavailable pan-vascular endothelial growth factor receptor inhibitor, in children and adolescents with refractory solid tumors.

To determine the toxicity profile, dose-limiting toxicities (DLTs), maximum-tolerated dose (MTD), pharmacokinetics, and pharmacodynamics of cediranib administered orally, once daily, continuously in children and adolescents with solid tumors.



Children and adolescents with refractory solid tumors, excluding primary brain tumors, were eligible. DLT at the starting dose of 12 mg/m(2)/d resulted in de-escalation to 8 mg/m(2)/d and subsequent re-escalation to 12 and 17 mg/m(2)/d. Pharmacokinetic and pharmacodynamic studies were performed during cycle 1. Response was evaluated using WHO criteria.



Sixteen patients (median age, 15 years; range, 8 to 18 years) were evaluable for toxicity. DLTs (grade 3 nausea, vomiting, fatigue in one; hypertension and prolonged corrected QT interval in another) occurred in patients initially enrolled at 12 mg/m(2)/d. Subsequently, 8 mg/m(2)/d was well tolerated in three patients. An additional seven patients were enrolled at 12 mg/m(2)/d; one had DLT (grade 3 diarrhea). At 17 mg/m(2)/d, two of four patients had DLTs (grade 3 nausea; intolerable grade 2 fatigue). Non-dose-limiting toxicities included left ventricular dysfunction, elevated thyroid stimulating hormone, palmar-plantar erythrodysesthesia, weight loss, and headache. The MTD of cediranib was 12 mg/m(2)/d (adult fixed dose equivalent, 20 mg). At 12 mg/m(2)/d, the median area under the plasma concentration-time curve extrapolated to infinity (AUC(0-∞)) was 900 ng·h/mL, which is similar to adults receiving 20 mg. Objective responses were observed in patients with Ewing sarcoma, synovial sarcoma, and osteosarcoma.



The recommended monotherapy dose of cediranib for children with extracranial solid tumors is 12 mg/m(2)/d administered orally, once daily, continuously. A phase II study is in development.
Body image disturbance and surgical decision making in egyptian post menopausal breast cancer patients

In most developing countries, as in Egypt; postmenopausal breast cancer cases are offered a radical form of surgery relying on their unawareness of the subsequent body image disturbance. This study aimed at evaluating the effect of breast cancer surgical choice; Breast Conservative Therapy (BCT) versus Modified Radical Mastectomy (MRM); on body image perception among Egyptian postmenopausal cases.



One hundred postmenopausal women with breast cancer were divided into 2 groups, one group underwent BCT and the other underwent MRM. Pre- and post-operative assessments of body image distress were done using four scales; Breast Impact of Treatment Scale (BITS), Impact of Event Scale (IES), Situational Discomfort Scale (SDS), and Body Satisfaction Scale (BSS).



Preoperative assessment showed no statistical significant difference regarding cognitive, affective, behavioral and evaluative components of body image between both studied groups. While in postoperative assessment, women in MRM group showed higher levels of body image distress among cognitive, affective and behavioral aspects.



Body image is an important factor for postmenopausal women with breast cancer in developing countries where that concept is widely ignored. We should not deprive those cases from their right of less mutilating option of treatment as BCT.