nils-herrmann/clean_scirepeval huggingface dataset:
An Australian translational Study to evaluate the prognostic role of inflammatory markers in patients with metastatic ColorEctal caNcer Treated with bevacizumab (Avastin™) [ASCENT]

The use of bevacizumab in combination with fluoropyrimidine-containing chemotherapy is a well-established first-line and second-line treatment for patients with metastatic colorectal cancer (mCRC). However, there remains a need for reproducible, validated, inexpensive and accessible prognostic markers to aid treatment selection. The optimal treatment duration and the role of bevacizumab in certain patient subgroups, considered at particular risk of bevacizumab-mediated toxicity, also require further investigation. The aim of the ASCENT study [an Australian translational Study to evaluate the prognostic role of inflammatory markers in patients with metastatic ColorEctal caNcer Treated with bevacizumab (Avastin™)] is to evaluate the relationship between the host inflammatory response as measured by neutrophil/lymphocyte ratio (NLR) and treatment outcomes in patients with previously untreated mCRC receiving bevacizumab-based first- and second-line treatment. This open-label, prospective, single arm, phase IV, Australian multi-centre study evaluates the relationship between the host inflammatory response as measured by NLR and treatment outcomes in patients with previously untreated mCRC receiving bevacizumab-based first- and second-line treatment. 150 patients will be recruited from 16 centres around Australia. Patients will receive trial treatments in two phases: Phase A: XELOX or mFOLFOX6 plus bevacizumab administered from study start until first disease progression; and Phase B: FOLFIRI plus bevacizumab administered from first disease progression until second disease progression. The primary analysis will test the association between NLR and progression free survival using a proportional Hazards Model. Secondary analyses will investigate whether the relationship can be improved upon with other prognostic biomarkers, and further characterise the safety of bevacizumab following treatment initiation, and when continued after progression in combination with standard chemotherapy regimens (presented through summary statistics and Kaplan Meier curves). Quantifying the relationship between NLR and PFS will inform decision making on the extent to which this simple metric may be applied clinically.
Zooming in on Barrett oesophagus using narrow-band imaging: an international observer agreement study.

Several classifications of mucosal morphology have been proposed in Barrett oesophagus using narrow-band imaging (NBI). We evaluated a simplified classification in which only the regularity of mucosal and vascular patterns were evaluated.



To assess the inter and intraobserver agreement and the correlation with histology of a simplified NBI classification of mucosal morphology in Barrett oesophagus combining the experience of two referral centres.



Two hundred NBI images [57 high-grade intraepithelial neoplasia (HGIN)/early cancer (EC)] were evaluated twice by four NBI-experienced and four nonexperienced endoscopists in the field of NBI. Endoscopists assessed each image for: quality, suspicion for dysplasia, and regularity of mucosal and vascular patterns. Observer agreement was assessed using kappa statistics.



Overall interobserver agreement for the items evaluated was 'moderate' and varied between 0.42 and 0.44. Overall intraobserver agreement was 'moderate' to 'substantial' (kappa 0.60-0.62). There were no significant differences in agreement between expert and nonexpert endoscopists. Endoscopist correctly identified 71% of the images containing HGIN/EC. Of the areas without HGIN/EC, 68% were correctly identified as not suspicious. Again, there were no significant differences between experts and nonexperts.



Our proposed, simplified classification for Barrett mucosal morphology has a moderate interobserver and a moderate to substantial intraobserver agreement. The lack of differences in agreements between expert and nonexpert endoscopists suggests a short learning curve. The disappointing rate for correctly indentifying HGIN/EC, questions, however, whether detailed inspection of Barrett oesophagus with NBI can replace histological sampling.
Factors influencing participation in a population-based biorepository for childhood heart disease.

Consenting minors for genetics research and biobanking involves ethical and social challenges. We examined factors influencing participation rates in a population-based biorepository for childhood heart disease.



Individuals were prospectively enrolled across 7 centers in Ontario by using a standardized consent form. Individuals were approached for consent for the donation of blood/saliva (DNA), tissue, and skin from the affected individual for future genomics and stem cell research. Consent rates were compared between pediatric and adult patients and factors affecting consent were analyzed by using multiple logistic regression analysis.



From 2008 to 2011, 3637 patients were approached. A total of 2717 pediatric patients consented (90% consent rate); mean age was 8.5 ± 5.8 years (57% male; 76% white). A total of 561 adult patients consented (92% consent rate, P = .071 versus pediatric). Factors associated with lower pediatric consent rates included younger age, race, absence of complex defects, and location of consent; these were not associated with adult consent rates. Leading causes for refusal of consent were lack of interest in research (43%), overwhelmed clinically (14%), and discomfort with genetics (11%). Concerns related to privacy, insurability, indefinite storage, and ongoing access to medical records were not the leading causes for refusal.



The high pediatric consent rate (90%) was comparable with that of adults. Ethical, social, or legal issues were not the leading reasons for refusal of consent.
Massage therapy for osteoarthritis of the knee: a randomized controlled trial.

Massage therapy is an attractive treatment option for osteoarthritis (OA), but its efficacy is uncertain. We conducted a randomized, controlled trial of massage therapy for OA of the knee.



Sixty-eight adults with radiographically confirmed OA of the knee were assigned either to treatment (twice-weekly sessions of standard Swedish massage in weeks 1-4 and once-weekly sessions in weeks 5-8) or to control (delayed intervention). Primary outcomes were changes in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and functional scores and the visual analog scale of pain assessment. The sample provided 80% statistical power to detect a 20-point difference between groups in the change from baseline on the WOMAC and visual analog scale, with a 2-tailed alpha of .05.



The group receiving massage therapy demonstrated significant improvements in the mean (SD) WOMAC global scores (-17.44 [23.61] mm; P < .001), pain (-18.36 [23.28]; P < .001), stiffness (-16.63 [28.82] mm; P < .001), and physical function domains (-17.27 [24.36] mm; P < .001) and in the visual analog scale of pain assessment (-19.38 [28.16] mm; P < .001), range of motion in degrees (3.57 [13.61]; P = .03), and time to walk 50 ft (15 m) in seconds (-1.77 [2.73]; P < .01). Findings were unchanged in multivariable models controlling for demographic factors.



Massage therapy seems to be efficacious in the treatment of OA of the knee. Further study of cost effectiveness and duration of treatment effect is clearly warranted. .
Active specific immunotherapy for stage II and stage III human colon cancer: a randomised trial

Colon cancer is curable by surgery, but cure rate depends on the extent of disease. We investigated whether adjuvant active specific immunotherapy (ASI) with an autologous tumour cell-BCG vaccine with surgical resection was more beneficial than resection alone in stage II and III colon cancer.



In a prospective randomised trial, 254 patients with colon cancer were randomly assigned postoperative ASI or no adjuvant treatment. ASI was three weekly vaccinations starting 4 weeks after surgery, with a booster vaccination at 6 months with 10(7) irradiated autologous tumour cells. The first vaccinations contained 10(7) BCG organisms. We followed up patients for time to recurrence, and recurrence-free and overall survival. Analysis was by intention to treat.



The 5.3 year median follow-up (range 8 months to 8 years 11 months) showed 44% (95% CI 7-66) risk reduction for recurrence in the recurrence-free period in all patients receiving ASI (p=0.023). Overall, there were 40 recurrences in the control group and 25 in the ASI group. Analysis by stage showed no significant benefit of ASI in stage III disease. The major impact of ASI was seen in patients with stage II disease, with a significantly longer recurrence-free period (p=0.011) and 61% (18-81) risk reduction for recurrences. Recurrence-free survival was significantly longer with ASI (42% risk reduction for recurrence or death [0-68], p=0.032) and there was a trend towards improved overall survival.



ASI gave significant clinical benefit in surgically resected patients with stage II colon cancer. ASI has minimal adverse reactions and should be considered in the management of stage II colon cancer.
Health Locus of Control in problem drinkers with and without liver disease.

The purpose of this study was to investigate whether patients who developed alcoholic liver disease have more awareness of the link between their behaviour and subsequent health than patients with non-alcoholic liver disease and people with drink problems with no liver disease. This study included three groups of patients, alcoholic liver disease (ALD) (n=57), non-alcoholic liver disease (n=77), and problem drinkers with no liver disease attending a London community day treatment centre (ACCEPT) (n=115). Health locus of control differentiates people into two groups, health externals who are individuals who maintain that their health is largely determined by external factors, as opposed to health internals, who believe that their behaviour plays a major role in determining their subsequent health or illness. The results of the Health Locus of Control (HLC) scale administered to the above subjects suggested that the ALD group had limited insight into the relationship between their drinking and subsequent liver disease, compared to the ACCEPT group. It is suggested that alcoholic liver disease patients receive counselling as part of their total management.
Activation of electrical triggers of atrial fibrillation in hyperthyroidism.

A shortening of the atrial refractory period has been considered as the main mechanism for the increased risk of atrial fibrillation in hyperthyroidism. However, other important factors may be involved.



Our objective was to determine the activity of abnormal supraventricular electrical depolarizations in response to elevated thyroid hormones in patients without structural heart disease.



Twenty-eight patients (25 females, three males, mean age 43+/-11 yr) with newly diagnosed and untreated hyperthyroidism were enrolled in a prospective trial after exclusion of heart disease. Patients were followed up for 16 +/- 6 months and studied at baseline and 6 months after normalization of serum TSH levels.



The incidence of abnormal premature supraventricular depolarizations (SVPD) and the number of episodes of supraventricular tachycardia was defined as primary outcome measurements before the start of the study. In addition, heart rate oscillations (turbulence) after premature depolarizations and heart rate variability were compared at baseline and follow-up.



SVPDs decreased from 59 +/- 29 to 21 +/- 8 per 24 h (P = 0.003), very early SVPDs (so called P on T) decreased from 36 +/- 24 to 3 +/- 1 per 24 h (P < 0.0001), respectively, and nonsustained supraventricular tachycardias decreased from 22 +/- 11 to 0.5 +/- 0.2 per 24 h (P = 0.01) after normalization of serum thyrotropin levels. The hyperthyroid phase was characterized by an increased heart rate (93 +/- 14 vs. 79 +/- 8 beats/min, P < 0.0001) and a decreased turbulence slope (3.6 vs. 9.2, P = 0.003), consistent with decreased vagal tone. This was confirmed by a significant decrease of heart rate variability.



Hyperthyroidism is associated with an increased supraventricular ectopic activity in patients with normal hearts. The activation of these arrhythmogenic foci by elevated thyroid hormones may be an important causal link between hyperthyroidism and atrial fibrillation.
Factors associated with discontinuation of aripiprazole treatment after switching from other antipsychotics in patients with chronic schizophrenia: A prospective observational study

The purpose of the study was to identify factors associated with discontinuation of aripiprazole after switching from other antipsychotics in patients with schizophrenia in real world clinical settings. From January 2011 to December 2012, a prospective, 48-week open-label study was undertaken. Thirty-eight subjects on antipsychotic monotherapy were switched to aripiprazole. Patients who discontinued aripiprazole were compared to those who continued with regards to demographic characteristics as well as treatment factors. Multiple regression analysis was conducted to identify predictors for aripiprazole discontinuation. Thirteen out of 38 patients (34.2%) discontinued aripiprazole during the follow up period. Nine patients (23.7%) discontinued aripiprazole due to worsening of psychotic symptoms. Multiple logistic regression analysis revealed that only the duration of previous antipsychotic treatment was associated with aripiprazole discontinuation after switching to aripiprazole. The receiver operating curve (ROC) analysis identified that the cut-off length for duration of illness to predict aripiprazole discontinuation was 10.5 years. Longer duration of illness was associated with aripiprazole discontinuation. Greater caution may be required when treating such patients with aripiprazole.
Increased prefrontal cortex activity during negative emotion regulation as a predictor of depression symptom severity trajectory over 6 months.

Emotion regulation is critically disrupted in depression, and the use of paradigms that tap into these processes may uncover essential changes in neurobiology during treatment. In addition, because neuroimaging outcome studies of depression commonly use only baseline and end-point data-which are more prone to week-to-week noise in symptomatology-we sought to use all data points over the course of a 6-month trial.



To examine changes in neurobiology resulting from successful treatment.



Double-blind trial examining changes in the neural circuits involved in emotion regulation resulting from 1 of 2 antidepressant treatments during a 6-month trial. Twenty-one patients with major depressive disorder and without other Axis I or Axis II diagnoses were scanned before treatment and 2 and 6 months into treatment at the university's functional magnetic resonance imaging facility.



Venlafaxine hydrochloride extended release (with doses of up to 300 mg) or fluoxetine hydrochloride (with doses of up to 80 mg).



Neural activity, as measured using functional magnetic resonance imaging during performance of an emotion regulation paradigm, as well as regular assessments of symptom severity using the Hamilton Depression Rating Scale. For use of all data points, slope trajectories were calculated for rate of change in depression severity and for rate of change in neural engagement.



The depressed individuals who showed the steepest decrease in depression severity over the 6-month period were the same individuals who showed the most rapid increases in activity in Brodmann area 10 and the right dorsolateral prefrontal cortex activity when regulating negative affect over the same time frame. This relationship was more robust when using only the baseline and end-point data.



Changes in prefrontal cortex engagement when regulating negative affect correlate with changes in depression severity over 6 months. These results are buttressed by calculating these statistics, which are more reliable and robust to week-to-week variation than are difference scores.
Randomized, double blind, placebo-controlled trial of disulfiram for the treatment of cocaine dependence in methadone-stabilized patients.

This study examined the dose-related efficacy of disulfiram for treating cocaine dependence in methadone-stabilized cocaine dependent participants.



One hundred and sixty-one cocaine- and opioid-dependent volunteers were entered into a 14-week, double blind, randomized, placebo-controlled clinical trial at two sites.



Participants were stabilized on methadone during weeks 1-2 and received disulfiram at 0, 62.5, 125 or 250 mg/day during weeks 3-14. All participants also received weekly cognitive behavioral therapy. Thrice-weekly urine samples and weekly self-reported drug use assessments were obtained.



Baseline subject characteristics, retention and drug use did not differ across groups. Outcome analyses were performed on those who participated beyond week 2. Opioid-positive urine samples and self-reported opioid use did not differ by treatment group. The prevalence of alcohol use was low prior to and during the trial and did not differ by treatment group. Cocaine-positive urines increased over time in the 62.5 and 125 mg disulfiram groups and decreased over time in the 250 mg disulfiram and placebo groups (p < 0.0001). Self-reported cocaine use increased in the 125 mg disulfiram group relative to the other three treatment groups (p = 0.04).



Disulfiram may be contraindicated for cocaine dependence at doses <250 mg/day. Whether disulfiram at higher doses is efficacious in reducing cocaine use in dually cocaine and opioid dependent individuals needs to be determined.
Levels of Oxidized LDL and Advanced Glycation End Products–Modified LDL in Circulating Immune Complexes Are Strongly Associated With Increased Levels of Carotid Intima-Media Thickness and Its Progression in Type 1 Diabetes

High cholesterol levels in circulating immune complexes (IC), surrogate markers of modified LDL, are associated with increased carotid intima-media thickness (IMT) and cardiovascular events in type 1 diabetes. Different modifications of LDL are involved in IC formation, but which of these are predictive of vascular events is not known. Therefore, we measured oxidized LDL (oxLDL), advanced glycation end products-modified LDL (AGE-LDL), and malondialdehyde-modified LDL (MDA-LDL) in IC and determined their relationship with increased carotid IMT and compared the strength of the association with that observed with conventional risk factors.



Levels of oxLDL, AGE-LDL, and MDA-LDL were measured in circulating IC isolated from sera of 479 patients of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) cohort, collected at baseline. Internal and common carotid IMT were measured 8 and 14 years later by DCCT/EDIC.



OxLDL, AGE-LDL, and MDA-LDL levels in circulating IC were significantly correlated with diabetes duration, BMI, and lipid and blood pressure, but not with age. Multivariate logistic regression models indicated that individuals in the highest versus lowest quartile of oxLDL and AGE-LDL in IC had a 6.11-fold [confidence interval (CI) 2.51-14.8] and a 6.4-fold (CI 2.53-16.2) increase in the odds of having high carotid IMT, respectively, after adjusting for conventional risk factors. Parallel analyses resulted in odds ratios of 2.62 (CI 1.24, 5.55) for LDL-C, 1.45 (CI 0.69, 3.03) for diastolic blood pressure, and 2.33 (CI 1.09, 4.99) for A1C.



OxLDL and AGE-LDL in circulating IC were significantly associated with progression and increased levels of carotid IMT in type 1 diabetes.
Impact of CYP2A6 genotype on pretreatment smoking behaviour and nicotine levels from and usage of nicotine replacement therapy

We investigated the effect of slow metabolism of nicotine, predicted by CYP2A6 genotypes resulting in ⩽50% activity, on baseline smoking behaviours and treatment variables in an open-label nicotine replacement therapy (NRT) clinical trial. Caucasian smokers with CYP2A6 slow vs normal metabolism had lower metabolic activity, indicated by the 3-hydroxycotinine/cotinine ratio (0.23±0.17 vs 0.45±0.22, P<0.01, respectively). CYP2A6 slow metabolizers also smoked fewer cigarettes per day compared to normal metabolizers (20±7 vs 24±10, respectively, P<0.04). With nicotine patch use, slow metabolizers had higher nicotine plasma levels compared to normal metabolizers (22.8±4.6 vs 15.8±7.6 ng/ml, respectively, P=0.02) while using the same numbers of patches/week. With nicotine spray use, where like in smoking the nicotine intake can be easily adjusted to adapt to rates of metabolism, slow metabolizers achieved similar nicotine levels compared to normal metabolizers (5.8±4.1 vs 8.0±9.1 ng/ml, P=0.82), by using fewer doses of nicotine spray/day (4.8±3.6 vs 10.5±8.0, respectively, P<0.02). These findings indicate that CYP2A6 genotype influences smoking behaviour in a Caucasian treatment-seeking population and that CYP2A6 genotype affects plasma levels obtained from, and usage of, NRT.
Intracranial aneurysms and subarachnoid hemorrhage --- report on a randomized treatment study. IV-B. Regulated bed rest --- statistical evaluation.

13. (eds): Ultrasonics in Medicine. Proceedings of the Second World Congress, 1973. New York, American Elsevier Publishing Company, pp 89-96, 1974 Mol JMF, Rijcken WJ: Doppler Haematotachographic investigation in cerebral circulation disturbances. In Reneman RS (ed): Cerebrovascular Application of Ultrasound. New York, American Elsevier Publishing Company, pp 104-111, 1974 Kaneko Z, Shiraishi J, Omizo H: Analysis of ultrasonic blood rheogram by a bandpass filter.  1968 Kaneko Z, Shiraishi J, Omizo H, Inaoka H, Ueshima T: Analysis of ultrasonic blood rheogram by the sound spectrograph. Jap Circ J 34(11): 1035-1045, 1970 14. Thomas LM, Hardy WG, Lindner DW, Gurdjian ES: Retrograde brachial angiography in cerebrovascular diseases.  Radiological visualization of neck vessels in healthy men. Neurology 13: 386-396, 1963 16. Castaigne P, Lhermitte F, Gautier JC, Escourolle R, Derouesne C, Agopian PD,  Arterial occlusions in the vertebro-basilar system, a study of 44 patients with post-mortem data.  133-154, 1973 17. Kaneda H, Minami T, Taneda M, Irino T: Doppler sonography diagnosis of the internal carotid artery occlusion from combined analysis of the ophthalmic artery and the carotid artery. Igaku no Ayumi 99(1): 15-17, 1976 (in Japanese)