nils-herrmann/clean_scirepeval huggingface dataset:
Effect of food on the absorption of eptastigmine

The aim of the study was to evaluate the effects of food on the rate and extent of eptastigmine absorption in healthy volunteers.  The study was carried out according to a double-blind, randomized, placebo-controlled, three-way cross-over design. On three separate occasions, six young subjects received 30 mg eptastigmine after a 12-h overnight fast (reference treatment), 30 mg eptastigmine 15 min after a standard breakfast (test treatment) and placebo 15 min after a standard breakfast (control treatment). Acetylcholinesterase activity in red blood cells was assayed 24 h after drug administration as a biological marker of eptastigmine plasma concentrations.  Mean maximum acetylcholinesterase inhibition (Imax) was 39.9% after eptastigmine without food and 33.1% after eptastigmine with food. Maximum inhibitions occurred at 4.75 h and 4.88 h after eptastigmine without and with food, respectively. Areas under the curve of acetylcholinesterase per cent inhibition from 0 to 8 h after drug administration (AUC0–8) were 198% h after eptastigmine without food and 124% h after eptastigmine with food. Ninety per cent confidence intervals of test/reference ratios for AUC0–8 and Imax exceeded the 0.80 to 1.20 limits, thus indicating that the two eptastigmine treatments cannot be considered bioequivalent. Mild and transient adverse events were recorded in three subjects receiving eptastigmine without food, one subject receiving eptastigmine with food and one subject receiving placebo.  The ingestion of food significantly reduces the bioavailability of eptastigmine estimated by the assay of red blood cell acetylcholinesterase activity.
Correlations between FDG PET glucose uptake-MRI gray matter volume scores and apolipoprotein E ε4 gene dose in cognitively normal adults: A cross-validation study using voxel-based multi-modal partial least squares

We previously introduced a voxel-based, multi-modal application of the partial least square algorithm (MMPLS) to characterize the linkage between patterns in a person's complementary complex datasets without the need to correct for multiple regional comparisons. Here we used it to demonstrate a strong correlation between MMPLS scores to characterize the linkage between the covarying patterns of fluorodeoxyglucose positron emission tomography (FDG PET) measurements of regional glucose metabolism and magnetic resonance imaging (MRI) measurements of regional gray matter associated with apolipoprotein E (APOE) ε4 gene dose (i.e., three levels of genetic risk for late-onset Alzheimer's disease (AD)) in cognitively normal, late-middle-aged persons. Coregistered and spatially normalized FDG PET and MRI images from 70% of the subjects (27 ε4 homozygotes, 36 ε4 heterozygotes and 67 ε4 non-carriers) were used in a hypothesis-generating MMPLS analysis to characterize the covarying pattern of regional gray matter volume and cerebral glucose metabolism most strongly correlated with APOE-ε4 gene dose. Coregistered and spatially normalized FDG PET and MRI images from the remaining 30% of the subjects were used in a hypothesis-testing MMPLS analysis to generate FDG PET-MRI gray matter MMPLS scores blind to their APOE genotype and characterize their relationship to APOE-ε4 gene dose. The hypothesis-generating analysis revealed covarying regional gray matter volume and cerebral glucose metabolism patterns that resembled those in traditional univariate analyses of AD and APOE-ε4 gene dose and PET-MRI scores that were strongly correlated with APOE-ε4 gene dose (p<1 × 10(-16)). The hypothesis-testing analysis results showed strong correlations between FDG PET-MRI gray matter scores and APOE-ε4 gene dose (p = 8.7 × 10(-4)). Our findings support the possibility of using the MMPLS to analyze complementary datasets from the same person in the presymptomatic detection and tracking of AD.
Multiple autonomic and repolarization investigation of sudden cardiac death in dilated cardiomyopathy and controls.

Prophylactic defibrillator implantation is recommended in dilated, nonischemic heart disease and left ventricular ejection fraction of ≤0.30 to 0.35. Noninvasive testing should improve accuracy in decision making of prophylactic defibrillator implantation.



We enrolled 60 patients (median age, 57 years) with dilated cardiomyopathy and left ventricular ejection fraction ≤0.50, and 30 control subjects (median age, 59 years) with left ventricular ejection fraction >0.50. The protocol included an initial assessment, a second assessment after 3 years, and a final follow-up: pharmacological baroreflex testing (baroreceptor reflex sensitivity), short-term spectral analysis of heart rate variability (low frequency/high frequency), and long-term time domain analysis (SD of all normal-to-normal R-R intervals), exercise microvolt T wave alternans, and signal-averaged ECG, and corrected QT-time. The median follow-up was 7 years. End points were cardiac death, resuscitated cardiac arrest, and arrhythmic death. Cardiac death was observed in 21 patients. Resuscitated cardiac arrest and arrhythmic death caused by ventricular tachyarrhythmias ≥240 per minute was observed in 7 and 10 patients, respectively. In the single time point analysis, microvolt T wave alternans, baroreceptor reflex sensitivity, and SD of all normal-to-normal R-R intervals at initial testing added significant information regarding cardiac death. Microvolt T wave alternans added information on resuscitated cardiac arrest or arrhythmic death at multiple time points (P<0.001). False-negative microvolt T wave alternans results were seen in 8% of patients.



Noninvasive testing and left ventricular ejection fraction could not reliably identify patients with dilated cardiomyopathy at risk of fatal ventricular tachyarrhythmias. Therefore, the strategy to confine prophylactic implantable cardioverter-defibrillator implantation to patients with dilated cardiomyopathy and severely reduced LV function should be reconsidered.
Intake of copper has no effect on cognition in patients with mild Alzheimer’s disease: a pilot phase 2 clinical trial

Disturbed copper (Cu) homeostasis may be associated with the pathological processes in Alzheimer’s disease (AD). In the present report, we evaluated the efficacy of oral Cu supplementation in the treatment of AD in a prospective, randomized, double-blind, placebo-controlled phase 2 clinical trial in patients with mild AD for 12 months. Sixty-eight subjects were randomized. The treatment was well-tolerated. There were however no significant differences in primary outcome measures (Alzheimer’s Disease Assessment Scale, Cognitive subscale, Mini Mental Status Examination) between the verum [Cu-(II)-orotate-dihydrate; 8 mg Cu daily] and the placebo group. Despite a number of findings supporting the hypothesis of environmental Cu modulating AD, our results demonstrate that oral Cu intake has neither a detrimental nor a promoting effect on the progression of AD.
A phase II study of FOLFIRI-3 (double infusion of irinotecan combined with LV5FU) after FOLFOX in advanced colorectal cancer patients

In advanced colorectal cancer previously treated with oxaliplatin, efficacy of irinotecan-based chemotherapy is poor and the best regimen is not defined. We designed FOLFIRI-3 and conducted a phase II study to establish its efficacy and safety in advanced colorectal cancer patients previously treated with FOLFOX. FOLFIRI-3 consisted of irinotecan 100 mg m−2 as a 60-min infusion on day 1, running concurrently with leucovorin 200 mg m−2 as a 2-h infusion on day 1, followed by 46-h continuous infusion of 5-fluorouracil (5FU) 2000 mg m−2, and irinotecan 100 mg m−2 repeated on day 3, at the end of the 5FU infusion, every 2 weeks. Sixty-five patients entered the study. The intent-to-treat objective response rate was 23% (95% CI 13–33%). Disease was stable in 37% of patients, progressed in 26% and was not assessable in 14%. From the start of FOLFIRI-3, median progression-free survival was 4.7 months and median survival 10.5 months. Main toxicities (% of patients) were grade 3–4 diarrhoea 23% and grade 4 neutropenia 11%. FOLFIRI-3 is a promising regimen achieving high response rate and progression-free survival in patients previously treated with FOLFOX with a moderate toxicity.
Differences in trigeminal and peripheral electrical pain perception in women with and without migraine

Pain perception studies in migraine patients have shown trigeminal and peripheral pain facilitation during the migraine attack. We were interested in differences of trigeminal and peripheral pain perception between migraine patients during the migraine interval and healthy subjects. Perception of electrical pain stimulation was measured in 20 migraine subjects outside a migraine attack (10 migraine with aura and 10 migraine without aura) and in 20 healthy subjects. We recorded sensory and pain thresholds, pain ratings after suprathreshold stimulation, and pain rating after two trains of repetitive stimulation (i.e., pain facilitation). Migraine subjects showed a significantly higher pain rating after suprathreshold stimulation in the trigeminal region as compared to healthy subjects (4.8 ± 1.6 versus 3.8 ± 2.2, p < 0.04 after Bonferroni correction) but not in the peripheral region. Furthermore, migraine subjects showed a pain facilitation after repetitive trigeminal stimulation whereas healthy subjects showed a pain habituation. We observed no significant differences between migraine subjects and healthy subjects for all parameters in the peripheral stimulation. Migraine patients with and without aura did not differ in any parameter. All subjects showed decreased sensory and pain thresholds after trigeminal as compared to peripheral stimulation. Migraine subjects show an increased pain perception after trigeminal but not after peripheral pain stimulation as compared to healthy subjects. This phenomenon is probably due to the observed pain facilitation after painful trigeminal stimulation.
Isocapnic hyperpnea with a portable device in Cystic Fibrosis: an agreement study between two different set-up modalities

To evaluate the bias and precision of the respiratory muscle training device formulas to predict respiratory minute volume (RMV) and volume of the reservoir bag (BV) on a cohort of subjects with Cystic Fibrosis (CF). CF patients with available pulmonary function tests and maximal voluntary manoeuvres were included in the study. Vital capacity and maximal voluntary ventilation were extracted from subjects’ records and then inserted to the manufacturer’s formulas to obtain RMV and BV (measured setting). RMV and BV were compared according to standard and measured formulas in males and females. Sample was described and then processed using Bland–Altman analysis. Bland–Altman analysis for RMV revealed a bias and precision of 8.8 ± 29 L/min in males and 28.8 ± 16 L/min in females; 0.4 ± 0.5 L in males and 0.7 ± 0.4 L in females for BV. Concordance correlation coefficients for RMV were −0.03 in males and 0.02 in females; 0.22 in males and 0.03 in females for BV, reinforcing an unsatisfactory concordance between measured and manufacturer setting. This study shows considerable discrepancies between the two methods, making the degree of agreement not clinically acceptable. This might cause inappropriate setting and disservice to patients with CF.
Adjudication of etiology of acute kidney injury: experience from the TRIBE-AKI multi-center study

Adjudication of patient outcomes is a common practice in medical research and clinical trials. However minimal data exists on the adjudication process in the setting of Acute Kidney Injury (AKI) as well as the ability to judge different etiologies (e.g. Acute Tubular Necrosis (ATN), Pre-renal Azotemia (PRA)).



We enrolled 475 consecutive patients undergoing cardiac surgery at four sites of the Translational Research Investigating Biomarker Endpoints in AKI (TRIBE-AKI) study. Three expert nephrologists performed independent chart review, utilizing clinical variables and retrospective case report forms with pre intra and post-operative data, and then adjudicated all cases of AKI (n = 67). AKI was defined as a > 50% increase in serum creatinine for baseline (RIFLE Risk). We examined the patterns of AKI diagnoses made by the adjudication panel as well as association of these diagnoses with pre and postoperative kidney injury biomarkers.



There was poor agreement across the panel of reviewers with their adjudicated diagnoses being independent of each other (Fleiss' Kappa = 0.046). Based on the agreement of the two out of three reviewers, ATN was the adjudicated diagnosis in 41 cases (61%) while PRA occurred in 13 (19%). Neither serum creatinine or any other biomarker of AKI (urine or serum), was associated with an adjudicated diagnosis of ATN within the first 24 post-operative hours.



The etiology of AKI after cardiac surgery is probably multi-factorial and pure forms of AKI etiologies, such as ATN and PRA may not exist. Biomarkers did not appear to correlate with the adjudicated etiology of AKI; however the lack of agreement among the adjudicators impacted these results.
Perioperative mortality and associated factors in patients undergoing radical nephrectomy.

To determine the incidence and related factors of perioperative mortality associated with radical nephrectomy in patients with renal tumours in a tertiary hospital.



We conducted a cross-sectional study that reviewed the medical records of patients undergoing radical nephrectomy between January 1, 2007 and December 31, 2011 in a tertiary university hospital (Cali, Colombia). We measured sociodemographic variables and factors that may be associated with perioperative mortality. The statistical analysis was performed using STATA.



We analysed 57 patients who underwent radical nephrectomy, 54.4% of whom were male, whose ages ranged from 14 to 81 years. All tumours had a unilateral presentation; 96.5% of the tumours were solid renal lesions, and 3.5% were cystic lesions. The most frequent histological findings were clear cell (63.2%), papillary (8.7%) and chromophobe cell (5.2%) renal carcinoma. There were no complications in 27 (47.3%) of the patients. According to the Clavien-Dindo classification of surgical complications, 16 (28%) patients had minor (grades i and ii) complications and 9 (15.6%) had major (grades iii and iv) complications, with an overall perioperative mortality (grade v) of 8.7% (5 patients).



The perioperative mortality at 30 days for patients with nonmetastatic renal carcinoma who underwent radical nephrectomy at a tertiary university hospital in Cali, Colombia, was 4.1% (2 patients).
Effectiveness of an Internet Intervention for Family Caregivers of People with Dementia: Results of a Randomized Controlled Trial

The World Health Organization stresses the importance of accessible and (cost)effective caregiver support, given the expected increase in the number of people with dementia and the detrimental impact on the mental health of family caregivers.



This study assessed the effectiveness of the Internet intervention 'Mastery over Dementia'. In a RCT, 251 caregivers, of whom six were lost at baseline, were randomly assigned to two groups. Caregivers in the experimental group (N = 149) were compared to caregivers who received a minimal intervention consisting of e-bulletins (N = 96). Outcomes were symptoms of depression (Center for Epidemiologic Studies Depression Scale: CES-D) and anxiety (Hospital Anxiety and Depression Scale: HADS-A). All data were collected via the Internet, and an intention-to-treat analysis was carried out.



Almost all caregivers were spouses or children (in-law). They were predominantly female and lived with the care recipient in the same household. Age of the caregivers varied from 26 to 87 years. Level of education varied from primary school to university, with almost half of them holding a bachelor's degree or higher. Regression analyses showed that caregivers in the experimental group showed significantly lower symptoms of depression (p = .034) and anxiety (p = .007) post intervention after adjustment for baseline differences in the primary outcome scores and the functional status of the patients with dementia. Effect sizes were moderate for symptoms of anxiety (.48) and small for depressive symptoms (.26).



The Internet course 'Mastery over Dementia' offers an effective treatment for family caregivers of people with dementia reducing symptoms of depression and anxiety. The results of this study justify further development of Internet interventions for family caregivers of people with dementia and suggest that such interventions are promising for keeping support for family caregivers accessible and affordable. The findings are even more promising because future generations of family caregivers will be more familiar with the Internet.
Sustained Responders Have Better Quality of Life and Productivity Compared With Treatment Failures Long After Antiviral Therapy for Hepatitis C

We sought to compare the health status of patients with a sustained response to antiviral therapy for hepatitis C virus (HCV) infection with that of treatment failures, using health-related quality of life and preference (utility) measures.Sustained responders had undetectable HCV viral levels 6 months after antiviral therapy. After antiviral therapy, participants completed, by mail or interview, the hepatitis-specific Medical Outcomes Study Short-Form 36-Item Health Survey (SF-36), the Health Utilities Index Mark 2/3 (HUI2/3), and time trade-off (TTO) for current health. The respondents provided information on demographics, history of substance abuse, comorbidities, and health history. Detailed clinical information was obtained by chart review. The respondents also indicated whether they missed work, volunteer opportunities, or household activities during the previous 3 months because of hepatitis C infection or its treatment.A total of 235 patients (133 responders and 102 treatment failures) completed questionnaires at an average of 3.7 years after the end of treatment. Treatment failures had significantly lower scores on the eight SF-36 domains (P<0.01), lower scores on the hepatitis-specific domains (P<0.0001), and lower physical (42.5 vs. 49.2) and mental (40.5 vs. 46.1) component summary scores (P<0.01). HUI3 (0.57 vs. 0.70), HUI2 (0.74 vs. 0.80), SF-6D (0.65 vs. 0.71), and TTO (0.84 vs. 0.89) were lower for treatment failures (P<0.05). The regression-adjusted difference in HUI3, SF-6D, physical summary score, and mental summary score was 0.08 (P=0.04), 0.05 (P=0.004), 5.22 (P=0.001), and 5.73 (P<0.0001), respectively. Differences in the HUI2 and TTO scores were not significant after adjustment for demographic and clinical variables. Treatment failures were more likely to have missed work, volunteer opportunities, or household activities in the previous 3 months because of hepatitis C infection or its treatment (44 vs. 9%, P<0.001).CONCLUSIONS:Patients with a sustained response to antiviral therapy for chronic HCV infection have better quality of life than treatment failures do. Our study validates the benefits associated with the sustained response to antiviral therapy in a real-world clinic population and shows that these benefits are maintained over the long term.
Feasibility intervention trial of two types of improved cookstoves in three resource-limited settings: study protocol for a randomized controlled trial

Exposure to biomass fuel smoke is one of the leading risk factors for disease burden worldwide. International campaigns are currently promoting the widespread adoption of improved cookstoves in resource-limited settings, yet little is known about the cultural and social barriers to successful improved cookstove adoption and how these barriers affect environmental exposures and health outcomes.



We plan to conduct a one-year crossover, feasibility intervention trial in three resource-limited settings (Kenya, Nepal and Peru). We will enroll 40 to 46 female primary cooks aged 20 to 49 years in each site (total 120 to 138).



At baseline, we will collect information on sociodemographic characteristics and cooking practices, and measure respiratory health and blood pressure for all participating women. An initial observational period of four months while households use their traditional, open-fire design cookstoves will take place prior to randomization. All participants will then be randomized to receive one of two types of improved, ventilated cookstoves with a chimney: a commercially-constructed cookstove (Envirofit G3300/G3355) or a locally-constructed cookstove. After four months of observation, participants will crossover and receive the other improved cookstove design and be followed for another four months. During each of the three four-month study periods, we will collect monthly information on self-reported respiratory symptoms, cooking practices, compliance with cookstove use (intervention periods only), and measure peak expiratory flow, forced expiratory volume at 1 second, exhaled carbon monoxide and blood pressure. We will also measure pulmonary function testing in the women participants and 24-hour kitchen particulate matter and carbon monoxide levels at least once per period.



Findings from this study will help us better understand the behavioral, biological, and environmental changes that occur with a cookstove intervention. If this trial indicates that reducing indoor air pollution is feasible and effective in resource-limited settings like Peru, Kenya and Nepal, trials and programs to modify the open burning of biomass fuels by installation of low-cost ventilated cookstoves could significantly reduce the burden of illness and death worldwide.
Effects of training and weight support on muscle activation in Parkinson's disease.

The aim of this study was to investigate the effect of high-intensity locomotor training on knee extensor and flexor muscle activation and adaptability to increased body-weight (BW) support during walking in patients with Parkinson's disease (PD). Thirteen male patients with idiopathic PD and eight healthy participants were included. The PD patients completed an 8-week training program on a lower-body, positive-pressure treadmill. Knee extensor and flexor muscles activation during steady treadmill walking (3 km/h) were measured before, at the mid-point, and after training. Increasing BW support decreased knee extensor muscle activation (normalization) and increased knee flexor muscle activation (abnormal) in PD patients when compared to healthy participants. Training improved flexor peak muscle activation adaptability to increased (BW) support during walking in PD patients. During walking without BW support shorter knee extensor muscle off-activation time and increased relative peak muscle activation was observed in PD patients and did not improve with 8 weeks of training. In conclusion, patients with PD walked with excessive activation of the knee extensor and flexor muscles when compared to healthy participants. Specialized locomotor training may facilitate adaptive processes related to motor control of walking in PD patients.