nils-herrmann/clean_scirepeval huggingface dataset:
Effects of CYP2D6 activity and tobacco on larynx cancer risk.

The genetically determined capacity of the cytochrome P450 CYP2D6 is suspected to be involved in the activation of tobacco carcinogens. From a multicentric case-control study carried out to analyze the interaction between host and environmental factors on tobacco-related cancers, we reported recently that the effect of tobacco on lung cancer risk rose with increasing CYP2D6 activity, and the effect of CYP2D6 activity rose with increasing tobacco consumption. The aim of the present report was to investigate whether results on lung cancer could be observed for larynx cancer, from a study on 140 cases and 157 controls. A weak interaction between increasing levels of both CYP2D6 activity and average daily consumption of tobacco was found (P = 0.12). The only significant interaction between these two factors was observed when CYP2D6 activity was considered with the two conventional phenotypes (P < 0.05). A dose-response effect of tobacco on larynx cancer risk was found only among one-third of the smokers with the highest level of CYP2D6 activity, and CYP2D6 was a risk factor only among heavy smokers. The highest risk for larynx cancer was then observed among smokers having both the highest levels of CYP2D6 activity and daily consumption of tobacco. The interaction between CYP2D6 activity and tobacco was weaker for larynx cancer than that reported previously for lung cancer. However, the similarities in the results found for these two cancers, i.e., a greater effect of tobacco among smokers with the highest CYP2D6 activity, reinforce the hypothesis that this activity could modify the effect of tobacco on cancer risk.
Coenzyme Q10 Improves Endothelial Dysfunction in Statin-Treated Type 2 Diabetic Patients

The vascular benefits of statins might be attenuated by inhibition of coenzyme Q(10) (CoQ(10)) synthesis. We investigated whether oral CoQ(10) supplementation improves endothelial dysfunction in statin-treated type 2 diabetic patients.



In a double-blind crossover study, 23 statin-treated type 2 diabetic patients with LDL cholesterol <2.5 mmol/l and endothelial dysfunction (brachial artery flow-mediated dilatation [FMD] <5.5%) were randomized to oral CoQ(10) (200 mg/day) or placebo for 12 weeks. We measured brachial artery FMD and nitrate-mediated dilatation (NMD) by ultrasonography. Plasma F(2)-isoprostane and 24-h urinary 20-hydroxyeicosatetraenoic acid (HETE) levels were measured as systemic oxidative stress markers.



Compared with placebo, CoQ(10) supplementation increased brachial artery FMD by 1.0 +/- 0.5% (P = 0.04), but did not alter NMD (P = 0.66). CoQ(10) supplementation also did not alter plasma F(2)-isoprostane (P = 0.58) or urinary 20-HETE levels (P = 0.28).



CoQ(10) supplementation improved endothelial dysfunction in statin-treated type 2 diabetic patients, possibly by altering local vascular oxidative stress.
Structural equation model testing the situation-specific theory of heart failure self-care.

To test the situation-specific theory of heart failure self-care with structural equation modelling.



Several authors have proposed theories on heart failure self-care, but only the situation-specific theory of heart failure self-care by Riegel and Dickson is focused on the process that patients use to perform self-care. This theory has never been tested with structural equation modelling.



A secondary analysis of data from a cross-sectional study.



Patients with heart failure were recruited in 21 cardiovascular centres across Italy during 2011. Data were collected with a sociodemographic questionnaire, chart abstraction for clinical data and the Self-Care of Heart Failure Index v.6.2.



A sample of 417 participants was enrolled in the study (59% males, mean age 72 years). The following propositions were tested and supported: Symptom monitoring correlates with treatment adherence; symptom monitoring and treatment adherence have a direct, positive relationship with symptom recognition and evaluation that in turn have a direct, positive relationship with treatment implementation; treatment implementation has a direct, positive relationship with treatment evaluation. In addition, the following three relationships were found: Symptom monitoring has a direct, positive relationship with treatment implementation; symptom recognition and evaluation have direct, positive relationships with treatment evaluation and symptom monitoring correlates with treatment evaluation. Correction added on 9th April 2013, after first online publication: '…symptom monitoring correlates with treatment implementation.' has been corrected to read '…symptom monitoring correlates with treatment evaluation.
The data support the situation-specific theory of heart failure self-care with the addition of three new relationships that emerged from the analysis. Results of this study lend further support to the use of the situation-specific theory of heart failure self-care in research and practice.
(Cost)-effectiveness of self-treatment of exacerbations on the severity of exacerbations in patients with COPD: the COPE II study.

Chronic obstructive pulmonary disease (COPD) is a chronic disease with a high prevalence and rapidly increasing incidence rates. The effect of self-treatment of COPD exacerbations on the severity of exacerbations during a 1-year period was examined and a cost-effectiveness analysis was performed.



Patients were randomly allocated to four 2-hour self-management sessions, with or without training in self-treatment of exacerbations. Patients in the self-treatment group received an action plan with the possibility to initiate a course of prednisolone (with or without antibiotics). During follow-up, all participants kept a daily symptom diary. These provided the data to calculate the frequency of exacerbations, the number of exacerbation days and mean daily severity scores.



Data were analysed for 142 randomised patients (self-treatment: n = 70; control: n = 72). The frequency of exacerbations was identical in both study groups (mean (SD) 3.5 (2.7)). Patients in the self-treatment group reported fewer exacerbation days (median 31 (interquartile range (IQR) 8.9-67.5) in the self-treatment group vs 40 (IQR 13.3-88.2) in the control group; p = 0.064); the difference was significant in the group of patients with a high number of exacerbation days per year (>137 (90th percentile of the whole study population); p = 0.028). The mean severity score of an exacerbation day was equal in both groups. No between-group differences were found in health-related quality of life. Cost-effectiveness analyses showed that applying self-treatment saved euro154 per patient, with a trend towards a lower probability for hospital admissions (0.20/patient/year in the self-treatment group vs 0.33/patient/year in the control group; p = 0.388) and a significant reduction of health care contacts (5.37/patient/year in the self-treatment group vs 6.51/patient/year in the control group; p = 0.043).



Self-treatment of exacerbations incorporated in a self-management programme leads to fewer exacerbation days and lower costs.
Tobacco use and its determinants in HIV-infected patients on antiretroviral therapy in West African countries.

Tobacco smoking is common in human immunodeficiency virus (HIV) infected patients from industrialised countries. In West Africa, few data concerning tobacco consumption exist.



A cross-sectional survey of the International Epidemiological Database to Evaluate AIDS (IeDEA) network in West Africa was conducted. Health workers administered a questionnaire assessing tobacco and cannabis consumption among patients receiving antiretroviral treatment. Regular smokers were defined as current smokers who smoked >1 cigarette per day for >or=1 year.



Overall, 2920 patients were enrolled in three countries. The prevalence of ever smokers and regular smokers were respectively 46.2% (95%CI 42.8-49.5) and 15.6% (95%CI 13.2-18.0) in men and 3.7% (95%CI 2.9-4.5) and 0.6% (95%CI 0.3-0.9) in women. Regular smoking was associated with being from Côte d'Ivoire or Mali compared to Benin (OR 4.6, 95%CI 2.9-7.3 and 7.7, 95%CI 4.4-13.6), severely impaired immunological status at highly active antiretroviral treatment initiation (OR 1.5, 95%CI 1.1-2.2) and history of tuberculosis (TB; OR 1.8, 95%CI 1.1-3.0).



There are marked differences in smoking prevalence among these West African countries. This survey approach also provides proof of the association between cigarette smoking and TB in HIV-infected patients, a major public health issue in this part of the world.
Effect of fermented milk containing Lactobacillus acidophilus and Bifidobacterium longum on plasma lipids of women with normal or moderately elevated cholesterol.

This study aimed to evaluate the effect of milk fermented with Lactobacillus acidophilus 145 and Bifidobacterium longum BB536 on plasma lipids in a sample of adult women. A double-blind, placebo controlled, cross-over study (two periods of four weeks each separated by a 1-week washout period) was performed in 34 women, aged between 18 and 65 years. Group A consumed 125 g fermented milk three times a day for the first 4 weeks while group B consumed regular yoghurt under the same conditions. (Groups A and B switched products for the second treatment period). Women taking the test product with a baseline total cholesterol above 190 mg/dl showed a significant reduction in LDL cholesterol. HDL cholesterol was also reduced by the test product. We conclude that the fermented milk may help to reduce LDL levels in hypercholesterolemic adult women.
Cost-effectiveness of switching to insulin degludec from other basal insulins: evidence from Swedish real-world data.

Health economic analysis from a healthcare and societal point of view was conducted to assess the cost-effectiveness of insulin degludec (IDeg) after switching from other basal insulins in people with type 1 diabetes.



This was a prospective, open-label, single arm, observational follow-up from August 2013 to October 2015 of 476 consecutive patients at Danderyd Hospital (Stockholm, Sweden) who switched to IDeg from other basal insulins (99% basal insulin analogs). The IMS CORE Diabetes Model (CDM) was used to predict the cost-effectiveness of life-long treatment with IDeg vs. other basal insulins, based on a Swedish setting.



Mean (SD) duration of follow-up was 21.7 (6.0) weeks. Mean HbA1c decreased by 2.7 mmol/mol, mean basal insulin dose decreased by 13.1% (p < .0001), and mean bolus insulin dose decreased by 7.5% (p < .0001) after switching. Frequencies of non-severe daytime hypoglycemia and non-severe nocturnal hypoglycemia decreased by 12% (p = .0127) and 53% (p < .0001) respectively and severe hypoglycemia was reduced by 62% (p = .0225). The CDM predicted a gain in life expectancy of 0.33 years, a discounted gain in quality-adjusted life-years (QALYs) of 0.54, and lower estimated direct lifetime healthcare costs of SEK 22,757 for patients switching to IDeg. The incremental cost-effectiveness ratio (ICER) showed IDeg as dominant (i.e. higher effectiveness with a lower cost). Sensitivity analyses confirmed the results.



Based on this prospective, real-world, follow-up and using the CDM, it was estimated that switching to IDeg from other basal insulins translated into QALY gains including improved life expectancy and health-related quality of life, as well as dominant ICER, meaning cost-savings for the healthcare system. However, the study is limited by its observational design. Extrapolation into the future is only estimated since the actual treatment effect cannot be projected with certainty.
No effects of oral vitamin D supplementation on non-alcoholic fatty liver disease in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled trial

Non-alcoholic fatty liver disease (NAFLD) is the most common hepatic disorder worldwide, reaching prevalence up to 90 % in obese patients with type 2 diabetes (T2D), and representing an independent risk factor for cardiovascular mortality. Furthermore, the coexistence of T2D and NAFLD leads to higher incidence of diabetes' complications and additive detrimental liver outcomes. The existence of a close association between NAFLD and hypovitaminosis D, along with the anti-inflammatory and insulin-sensitizing properties of vitamin D, have been largely described, but vitamin D effects on hepatic fat content have never been tested in a randomized controlled trial. We assessed the efficacy and safety of 24-week oral high-dose vitamin D supplementation in T2D patients with NAFLD.



This randomized, double-blind, placebo-controlled trial was carried out at the Diabetes Centre of Sapienza University, Rome, Italy, to assess oral treatment with cholecalciferol (2000 IU/day) or placebo in T2D patients with NAFLD. The primary endpoint was reduction of hepatic fat fraction (HFF) measured by magnetic resonance; as hepatic outcomes, we also investigated changes in serum transaminases, CK18-M30, N-terminal Procollagen III Propeptide (P3NP) levels, and Fatty Liver Index (FLI). Secondary endpoints were improvement in metabolic (fasting glycaemia, HbA1c, lipids, HOMA-IR, HOMA-β, ADIPO-IR, body fat distribution) and cardiovascular (ankle-brachial index, intima-media thickness, flow-mediated dilatation) parameters from baseline to end of treatment.



Sixty-five patients were randomized, 26 (cholecalciferol) and 29 (placebo) subjects completed the study. 25(OH) vitamin D significantly increased in the active treated group (48.15 ± 23.7 to 89.80 ± 23.6 nmol/L, P < 0.001); however, no group differences were found in HFF, transaminases, CK18-M30, P3NP levels or FLI after 24 weeks. Vitamin D neither changed the metabolic profile nor the cardiovascular parameters.



Oral high-dose vitamin D supplementation over 24 weeks did not improve hepatic steatosis or metabolic/cardiovascular parameters in T2D patients with NAFLD. Studies with a longer intervention period are warranted for exploring the effect of long time exposure to vitamin D.
Primary care screening for peripheral arterial disease: a cross-sectional observational study

Early identification of peripheral arterial disease (PAD) and subsequent instigation of risk modification strategies could minimise disease progression and reduce overall risk of cardiovascular (CV) mortality. However, the feasibility and value of primary care PAD screening is uncertain.



This study (the PIPETTE study - Peripheral arterial disease In  Targeted screening and subsequenT managEment) aimed to determine the value of a proposed primary care PAD screening strategy. Outcomes assessed were: prevalence of PAD and agreement of ankle- brachial index (ABI)-defined PAD (ABI ≤0.9) with QRISK®2-defined high CV risk (≥20).



A cross-sectional observational study was undertaken in a large general practice in Merthyr Tydfil, Wales.



In total, 1101 individuals with ≥2 pre-identified CV risk factors but no known CV disease or diabetes were invited to participate. Participants underwent ABI measurement and QRISK2 assessment, and completed Edinburgh Claudication Questionnaires.



A total of 368 people participated in the study (participation rate: 33%). Prevalence of PAD was 3% (n = 12). The number needed to screen (NNS) to detect one new case of PAD was 31. Refining the study population to those aged ≥50 years with a smoking history reduced the NNS to 14, while still identifying 100% of PAD cases. Of participants with PAD, 33% reported severe lifestyle-limiting symptoms of intermittent claudication that warranted subsequent endovascular intervention, yet had not previously presented to their GP. The QRISK2 score predicted high CV risk in 92% of participants with PAD.



The low PAD yield and the fact that QRISK2 was largely comparable to the ABI in predicting high CV risk suggests that routine PAD screening may be unwarranted. Instead, strategies to improve public awareness of PAD are needed.
Overlap of disease susceptibility loci for rheumatoid arthritis and juvenile idiopathic arthritis

Genome-wide association studies (GWAS) have been extremely successful in the search for susceptibility risk factors for complex genetic autoimmune diseases. As more studies are published, evidence is emerging of considerable overlap of loci between these diseases. In juvenile idiopathic arthritis (JIA), another complex genetic autoimmune disease, the strategy of using information from autoimmune disease GWAS or candidate gene studies to help in the search for novel JIA susceptibility loci has been successful, with confirmed association with two genes, PTPN22 and IL2RA. Rheumatoid arthritis (RA) is an autoimmune disease that shares similar clinical and pathological features with JIA and, therefore, recently identified confirmed RA susceptibility loci are also excellent JIA candidate loci.



To determine the overlap of disease susceptibility loci for RA and JIA.



/st> Fifteen single nucleotide polymorphisms (SNPs) at nine RA-associated loci were genotyped in Caucasian patients with JIA (n=1054) and controls (n=3531) and tested for association with JIA. Allele and genotype frequencies were compared between cases and controls using the genetic analysis software, PLINK.



Two JIA susceptibility loci were identified, one of which was a novel JIA association (STAT4) and the second confirmed previously published associations of the TRAF1/C5 locus with JIA. Weak evidence of association of JIA with three additional loci (Chr6q23, KIF5A and PRKCQ) was also obtained, which warrants further investigation.



All these loci are good candidates in view of the known pathogenesis of JIA, as genes within these regions (TRAF1, STAT4, TNFAIP3, PRKCQ) are known to be involved in T-cell receptor signalling or activation pathways.
Land versus water exercise in patients with coronary artery disease: effects on body composition, blood lipids, and physical fitness.

We examined the effects of combined resistance and aerobic training on land versus combined resistance and aerobic training in water in patients with coronary artery disease.



Thirty-four patients were randomly assigned to land exercise (LE, n = 12), water exercise (WE, n = 12), and control (n = 10) groups. The LE group trained 4 times per week, twice with aerobic exercise and twice with resistance training. The WE program included aquatic aerobic activities 2 times per week and resistance exercise at the same frequency carried out in water. The duration of the training programs was 4 months. Body composition measurements, blood lipids, exercise stress testing, and muscular strength were obtained at the beginning and at the end of the training period.



After 4 months of training, analysis of covariance revealed that body weight and sum of skinfolds were lower for WE and LE groups than for the control group. Patients who trained in water improved exercise time (+11.7% vs +8.1%) and maximum strength (+12.8% vs +12.9%) in a similar manner compared to the patients who trained on land. Total cholesterol (WE -4.4%, LE -3.3%) and triglycerides (WE -10.2%, LE -11.8%) decreased significantly for both exercise groups but not for the control group.



Exercise programs that combine resistance and aerobic exercise performed either on land or in water can both improve exercise tolerance and muscular strength in patients with coronary artery disease. Furthermore, both programs induce similar favorable adaptations on total cholesterol, triglycerides, and body composition.
Impact of thrombolysis on stroke outcome at 12 months in a population: the Bern stroke project.

Thrombolysis improves outcome of patients with acute ischemic stroke, but it is unknown whether thrombolysis has a measurable effect on long-term outcome in a defined population.



We prospectively assessed demographic data, management, and outcome of acute ischemic stroke patients admitted within 48 hours to 18 primary care hospitals of the canton of Bern (969 299 inhabitants) during 12 months. Blinded follow-up was obtained at 3 and 12 months. Predictors of mortality and favorable outcome (modified Rankin Scale score ≤2) at 3 and 12 months using logistic regression were analyzed.



From December 2007 to December 2008, 807 patients (mean age, 72 years) were included. Median National Institutes of Health Stroke Scale score on admission was 5; 107 patients (13%) received intravenous, intra-arterial, or mechanical thrombolysis. Estimated cumulative mortality at 3 months was 20.6% and at 12 months 27.4%. Age 75 years or older, higher National Institutes of Health Stroke Scale scores, and higher Charlson comorbidity index were independent predictors of mortality at 3 and 12 months. Estimated favorable outcome at 3 months was 48.2% and at 12 months was 44.6%. Thrombolysis was the only modifiable independent predictor of favorable outcome at 3 (relative risk, 1.49; 95% CI, 1.18-1.89) and 12 months (relative risk, 1.59; 95% CI, 1.24-2.04), whereas age younger than 75 years, male gender, National Institutes of Health Stroke Scale score <4, and lower Charlson comorbidity index were nonmodifiable predictors.



Thirteen percent of acute ischemic stroke patients admitted within 48 hours to Bernese hospitals underwent thrombolysis, which exerted a measurable effect on 3-month outcome in this population. This effect was sustained at 12 months. Age, stroke severity, Charlson comorbidity index, and male gender were independent nonmodifiable predictors of outcome.
Automatic "pipeline" analysis of 3-D MRI data for clinical trials: application to multiple sclerosis

The quantitative analysis of magnetic resonance imaging (MRI) data has become increasingly important in both research and clinical studies aiming at human brain development, function, and pathology. Inevitably, the role of quantitative image analysis in the evaluation of drug therapy will increase, driven in part by requirements imposed by regulatory agencies. However, the prohibitive length of time involved and the significant intra- and inter-rater variability of the measurements obtained from manual analysis of large MRI databases represent major obstacles to the wider application of quantitative MRI analysis. We have developed a fully automatic "pipeline" image analysis framework and have successfully applied it to a number of large-scale, multi-center studies (more than 1000 MRI scans). This pipeline system is based on robust image processing algorithms, executed in a parallel, distributed fashion. This paper describes the application of this system to the automatic quantification of multiple sclerosis lesion load in MRI, in the context of a phase III clinical trial. The pipeline results were evaluated through an extensive validation study, revealing that the obtained lesion measurements are statistically indistinguishable from those obtained by trained human observers. Given that intra- and inter-rater measurement variability is eliminated by automatic analysis, this system enhances the ability to detect small treatment effects not readily detectable through conventional analysis techniques. While useful for clinical trial analysis in multiple sclerosis, this system holds widespread potential for applications in other neurological disorders, as well as for the study of neurobiology in general.