nils-herrmann/clean_scirepeval huggingface dataset:
Cost-effectiveness of interpersonal psychotherapy for elderly primary care patients with major depression.

Major depression is common in elderly patients. Interpersonal psychotherapy (IPT) is a potentially effective treatment for depressed elderly patients. The objective of this study was to evaluate the cost-effectiveness of IPT delivered by mental health workers in primary care practices, for depressed patients 55 years of age and older identified by screening, in comparison with care as usual (CAU).



We conducted a full economic evaluation alongside a randomized controlled trial comparing IPT with CAU. Outcome measures were depressive symptoms, presence of major depression, and quality of life. Resource use was measured from a societal perspective over a 12-month period by cost diaries. Multiple imputation and bootstrapping were used to analyze the data.



At 6 and 12 months, the differences in clinical outcomes between IPT and CAU were small and nonsignificant. Total costs at 12 months were Euros 5,753 in the IPT group and Euros 4,984 in the CAU group (mean difference, Euros 769; 95 percent confidence interval, -2,459 -3,433). Cost-effectiveness planes indicated that there was much uncertainty around the cost-effectiveness ratios.



Based on these results, provision of IPT in primary care to elderly depressed patients was not cost-effective in comparison to CAU. Future research should focus on improvement of patient selection and treatments that have more robust effects in the acute and maintenance phase of treatment.
Mealtime glucose regulation by nateglinide in type-2 diabetes mellitus

Pharmacodynamic effects of nateglinide, a novel antidiabetic agent, were investigated in patients with type-2 diabetes mellitus.  Ten patients participated in this single-center, double-blind, crossover study. Plasma glucose and insulin levels were measured over 24 h following five 7-day treatment periods with nateglinide (30, 60, or 120 mg) or placebo given three times daily before breakfast, lunch, and dinner. A fifth treatment consisted of 120 mg nateglinide four times daily, with the fourth dose given before an evening snack.  Taken 10 min before meals, doses of 30–120 mg nateglinide caused dose-dependent increases in plasma insulin levels that were significantly greater than with placebo. Higher doses were more effective and had a longer duration of action than lower doses. Nateglinide was also significantly better than placebo in lowering plasma glucose levels; the 60-mg and 120-mg doses were similarly effective and superior to the 30-mg nateglinide treatment. Following the fourth 120-mg dose, the glucose-lowering effects of treatment were maintained through the night. No serious adverse events occurred during the study. There were no events of hypoglycemia and no clinically meaningful changes in safety parameters.  Nateglinide produced rapid, short-lived, dose-related increases in plasma insulin that significantly lowered mealtime glucose excursions compared with placebo with no incidence of hypoglycemia. The decrease in mealtime glucose levels produced a significant improvement in overall 24-h glycemia.
Phase I study of the halichondrin B analogue eribulin mesylate in combination with cisplatin in advanced solid tumors

Eribulin mesylate is a synthetic macrocyclic ketone analogue of Halichondrin B that has demonstrated high antitumor activity in preclinical and clinical settings. This phase I study aimed to determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), and pharmacokinetics in combination with cisplatin (CP) in patients with advanced solid tumours.Thirty-six patients with advanced solid tumours received eribulin mesylate 0.7–1.4 mg m−2 and CP 60–75 mg m−2. Eribulin mesylate was administered on days 1, 8, and 15 in combination with CP day 1 every 28-day cycle. The protocol was amended after dose level 4 (eribulin mesylate 1.4 mg m−2, CP 60 mg m−2) when it was not feasible to administer eribulin mesylate on day 15 because of neutropenia; the treatment schedule was changed to eribulin mesylate on days 1 and 8 and CP on day 1 every 21 days.On the 28-day schedule, three patients had DLT during the first cycle: grade (G) 4 febrile neutropenia (1.0 mg m−2, 60 mg m−2); G 3 anorexia/fatigue/hypokalemia (1.2 mg m−2, 60 mg m−2); and G 3 stomatitis/nausea/vomiting/fatigue (1.4 mg m−2, 60 mg m−2). On the 21-day schedule, three patients had DLT during the first cycle: G 3 hypokalemia/hyponatremia (1.4 mg m−2, 60 mg m−2); G 4 mucositis (1.4 mg m−2, 60 mg m−2); and G 3 hypokalemia (1.2 mg m−2, 75 mg m−2). The MTD and recommended phase II dose was determined as eribulin mesylate 1.2 mg m−2 (days 1, 8) and CP 75 mg m−2 (day 1), on a 21-day cycle. Two patients had unconfirmed partial responses (PR) (pancreatic and breast cancers) and two had PR (oesophageal and bladder cancers).Conclusions:On the 21-day cycle, eribulin mesylate 1.2 mg m−2, administered on days 1 and 8, in combination with CP 75 mg m−2, administered on day 1 is well tolerated and showed preliminary anticancer activity.
Deep phenotyping of the unselected COPSAC2010 birth cohort study

We hypothesize that perinatal exposures, in particular the human microbiome and maternal nutrition during pregnancy, interact with the genetic predisposition to cause an abnormal immune modulation in early life towards a trajectory to chronic inflammatory diseases such as asthma and others.



The aim of this study is to explore these interactions by conducting a longitudinal study in an unselected cohort of pregnant women and their offspring with emphasis on deep clinical phenotyping, exposure assessment, and biobanking. Exposure assessments focus on the human microbiome. Nutritional intervention during pregnancy in randomized controlled trials are included in the study to prevent disease and to be able to establish causal relationships.



Pregnant women from eastern Denmark were invited during 2008-2010 to a novel unselected 'COPSAC2010 ' cohort. The women visited the clinic during pregnancy weeks 24 and 36. Their children were followed at the clinic with deep phenotyping and collection of biological samples at nine regular visits until the age of 3 and at acute symptoms. Randomized controlled trials of high-dose vitamin D and fish oil supplements were conducted during pregnancy, and a trial of azithromycin for acute lung symptoms was conducted in the children with recurrent wheeze.



Seven hundred and thirty-eight mothers were recruited from week 24 of gestation, and 700 of their children were included in the birth cohort. The cohort has an over-representation of atopic parents. The participant satisfaction was high and the adherence equally high with 685 children (98%) attending the 1 year clinic visit and 667 children (95%) attending the 2 year clinic visit.



The COPSAC2010 birth cohort study provides longitudinal clinical follow-up with highly specific end-points, exposure assessments, and biobanking. The cohort has a high adherence rate promising strong data to elucidate the interaction between genomics and the exposome in perinatal life leading to lifestyle-related chronic inflammatory disorders such as asthma.
Diuretic response in acute heart failure-an analysis from ASCEND-HF.

Diuretic unresponsiveness often occurs during hospital admission for acute heart failure (AHF) and is associated with adverse outcome. This study aims to investigate determinants, clinical outcome, and the effects of nesiritide on diuretic response early after admission for AHF.



Diuretic response, defined as weight loss per 40 mg of furosemide or equivalent, was examined from hospital admission to 48 hours in 4,379 patients from the ASCEND-HF trial. As an additional analysis, a urinary diuretic response metric was investigated in 5,268 patients using urine volume from hospital admission to 24 hours per 40 mg of furosemide or equivalent.



Mean diuretic response was -0.42 kg/40 mg of furosemide (interquartile range -1.0, -0.05). Poor responders had lower blood pressure, more frequent diabetes, long-term use of loop diuretics, poorer baseline renal function, and lower urine output (all P < .01). Randomized nesiritide treatment was not associated with diuretic response (P = .987). Good diuretic response was independently associated with a significantly decreased risk of 30-day all-cause mortality or heart failure rehospitalization (odds ratio 0.44, 95% CI 0.29-0.65, highest vs lowest quintile, P < .001). Diuretic response based on urine output per 40 mg of furosemide showed similar results in terms of clinical predictors, association with outcome, and the absence of an effect of nesiritide.



Poor diuretic response early after hospital admission for AHF is associated with low blood pressure, renal impairment, low urine output, and an increased risk of death or rehospitalization early after discharge. Nesiritide had a neutral effect on diuretic response.
MRI-Guided Robotic Prostate Biopsy: A Clinical Accuracy Validation

Prostate cancer is a major health threat for men. For over five years, the U.S. National Cancer Institute has performed prostate biopsies with a magnetic resonance imaging (MRI)-guided robotic system.



A retrospective evaluation methodology and analysis of the clinical accuracy of this system is reported.



Using the pre and post-needle insertion image volumes, a registration algorithm that contains a two-step rigid registration followed by a deformable refinement was developed to capture prostate dislocation during the procedure. The method was validated by using three-dimensional contour overlays of the segmented prostates and the registrations were accurate up to 2 mm.



It was found that tissue deformation was less of a factor than organ displacement. Out of the 82 biopsies from 21 patients, the mean target displacement, needle placement error, and clinical biopsy error was 5.9 mm, 2.3 mm, and 4 mm, respectively.



The results suggest that motion compensation for organ displacement should be used to improve targeting accuracy.
Interleukin-6 and Vitamin D Status during High-Intensity Resistance Training in Patients with Chronic Kidney Disease

The aim of this study was to investigate IL-6 and 25-hydroxyvitamin D (25-OH D) associations with muscle size and muscle function in dialysis patients.  Patients were included in a 16-week control period followed by 16 weeks of high-intensity resistance training thrice weekly. IL-6 and 25-OH D were analysed after an over-night fast. Muscle fibre size was analysed in biopsies from m. vastus lateralis. Muscle power was tested using a Leg Extensor Power Rig.  Patients (n = 36) with IL-6 ≥ 6.49 pg/ml (median) were older and had decreased muscle power and a reduced protein intake (P < 0.05) compared with patients with IL-6 < 6.49 pg/ml. IL-6 was not associated with muscle fibre size. Vitamin D deficiency (25-OH D < 50 nmol/l) was present in 51% of the patients and not associated with muscle power. IL-6 remained unchanged during the training period, whilst muscle power increased by 20-23% (P < 0.001).  Elevated IL-6 values were associated with decreased muscle power but not with decreased muscle fibre size. Half of the patients were suffering from vitamin D deficiency, which was not associated with muscle power. IL-6 was unchanged by high-intensity resistance training in dialysis patients in this study.
Altered adrenal and thyroid function in children with insulin-dependent diabetes mellitus

In 129 children, aged 12.6±3.8 years, affected by type 1 diabetes mellitus, the levels of dehydroepiandrosterone sulfate (DHEAS), cortisol, T3, fT3, T4, fT4, rT3, TSH, cholesterol, and triglycerides were evaluated and compared with those of a control group of 458 healthy age-matched children. The results were also correlated with hemoglobin HbA1C. The DHEAS-standard deviation score (DHEAS-SDS; −0.36±0.77) was significantly different from zero in diabetic children, while the cortisol serum level was higher than in control subjects (485±94 vs 359±132 nmol/l). Moreover, the DHEAS-SDS and DHEAS-SDS/cortisol ratio correlated negatively with HbA1c. Diabetic patients also showed lower T3 values (2.22 ± 0.4 vs 2.32±0.3 nmol/l) and a higher rT3/T3 ratio (0.17±0.09 vs 0.15±0.05) than controls. There was a negative correlation between T3 and HbA1C. Cholesterol (4.77±1.08 vs 4.51±0.76 mmol/l) and triglycerides (0.82 ±0.53 vs 0.63±0.37 g/L) levels were higher in diabetic children and positively correlated with HbA1c, but not with DHEAS-SDS. We can therefore conclude that diabetes, particularly if poorly controlled, tends to induce a dissociation of cortisol and DHEAS secretion and a low T3 syndrome, similar to that seen in other illnesses.
Swap and Play: Live Updating Hypervisors and Its Application to Xen

Hypervisors provide the means to run multiple isolated virtual machines on the same physical host. Typically, updating hypervisors requires a reboot of the host leading to disruption of services that is highly undesirable, particularly in cloud environments. Nevertheless, security updates have to be applied fast to reduce the risk of attacks, demanding a solution which eliminates the trade-off between availability and security risk.
 Live updating, in general, is highly challenging and has been investigated for decades. However, all solutions proposed so far require changes to the control flow of the software and/or cause performance degradation. Moreover, currently there are no solutions for live updating of hypervisors and all major products (e.g., Hyper-V, Xen, ESXi) require a reboot for updating.
 In this paper, we present Swap and Play, the first live update mechanism for hypervisors. Our solution is easy to use, scalable and, in particular, deployable in cloud environments. Our approach leverages the hypervisor's small memory footprint to swap the hypervisor on-the-fly without affecting the control flow of the (new) hypervisor, or disrupting the guests. In this context, we tackle several technically involved challenges, such as transferring the state of the running hypervisor, updating the configuration of one CPU while reinitializing the configuration of all other CPUs, and passing the control to the new hypervisor, all at run-time.
 We implemented our approach on the popular Xen hypervisor to show its efficiency and effectiveness.
Explaining the Adjustment of Adolescents With Type 1 Diabetes

The aim of this study was to explain adjustment (diabetes-related quality of life, general well-being, and psychopathology) in adolescents with type 1 diabetes by testing the direct, mediating, and moderating effects of diabetes-specific and psychosocial factors, using an adapted version of the Disability-Stress-Coping model of Wallander and Varni.



A total of 437 adolescents (54.5% girls; age range 11-19 years) with type 1 diabetes (mean +/- SD diabetes duration 6.13 +/- 3.78 years) were recruited from 25 hospitals in the Netherlands. Questionnaires were completed by the adolescents and their family members. Metabolic control was assessed by measuring A1C in all participants in one laboratory.



Diabetes stress mediated between A1C and adjustment, after controlling for protective factors, and explained an additional 16% variance in quality of life and a 15% variance in general well-being, whereas a 19% additional variance in psychopathology was explained by both diabetes-related and general stress. No moderating effects were identified after controlling for the main effects of all risk and protective factors in the model.



Both diabetes-related and general stress are critical predictors of the adjustment of adolescents with type 1 diabetes. Protective factors such as self-worth and social support may mediate the effects of generic stress and thus should be encouraged. Diabetes-related stress has the potential to displace the effects of protective factors and thus may play a critical role in the development of maladjustment in adolescents with type 1 diabetes.
Methylation Linear Discriminant Analysis (MLDA) for identifying differentially methylated CpG islands

Hypermethylation of promoter CpG islands is strongly correlated to transcriptional gene silencing and epigenetic maintenance of the silenced state. As well as its role in tumor development, CpG island methylation contributes to the acquisition of resistance to chemotherapy. Differential Methylation Hybridisation (DMH) is one technique used for genome-wide DNA methylation analysis. The study of such microarray data sets should ideally account for the specific biological features of DNA methylation and the non-symmetrical distribution of the ratios of unmethylated and methylated sequences hybridised on the array. We have therefore developed a novel algorithm tailored to this type of data, Methylation Linear Discriminant Analysis (MLDA). MLDA was programmed in R (version 2.7.0) and the package is available at CRAN . This approach utilizes linear regression models of non-normalised hybridisation data to define methylation status. Log-transformed signal intensities of unmethylated controls on the microarray are used as a reference. The signal intensities of DNA samples digested with methylation sensitive restriction enzymes and mock digested are then transformed to the likelihood of a locus being methylated using this reference. We tested the ability of MLDA to identify loci differentially methylated as analysed by DMH between cisplatin sensitive and resistant ovarian cancer cell lines. MLDA identified 115 differentially methylated loci and 23 out of 26 of these loci have been independently validated by Methylation Specific PCR and/or bisulphite pyrosequencing. MLDA has advantages for analyzing methylation data from CpG island microarrays, since there is a clear rational for the definition of methylation status, it uses DMH data without between-group normalisation and is less influenced by cross-hybridisation of loci. The MLDA algorithm successfully identified differentially methylated loci between two classes of samples analysed by DMH using CpG island microarrays.
Circadian variation in the effect of intravenous thrombolysis after non-lacunar stroke

The onset of non-lacunar stroke symptoms has a circadian variation, with a higher risk in the early morning hours and lower risk during the nighttime period, but this circadian distribution has not been clearly established on the effect of intravenous (IV) thrombolysis. The aim of the present study was to assess whether the time interval based on time of Alteplase IV infusion may influence the effect of treatment in patients with non-lacunar stroke. We conducted an analysis on prospectively collected data of 476 non-lacunar stroke patients treated with IV thrombolysis. To identify a possible circadian variation in the effect of Alteplase IV infusion, we used the following outcome measures: major neurological improvement (NIH stroke scale [NIHSS] score decrease of ≤8 points from baseline or NIHSS score of 0 at 24 h), and hemorrhagic transformation according to European Cooperative Acute Stroke Study trial definition within 24 h. Multivariate analysis showed that ORs for major neurological improvement were lower in patients who started IV thrombolysis in the 6 AM–noon interval (OR 0.35, 95 % CI 0.16–0.74, p = 0.006) and noon–6 PM interval (OR 0.40, 95 % CI 0.20–0.81, p = 0.010), whereas ORs for hemorrhagic transformation were lower in patients who started IV thrombolysis in the noon–6 PM interval (OR 0.29, 95 % CI 0.12–0.67, p = 0.004) and in the 6 PM–midnight interval (OR 0.26, 95 % CI 0.11–0.62, p = 0.002), compared with midnight–6 AM interval. The effect of Alteplase IV infusion could show a circadian variation in patients with non-lacunar stroke. After comparison with the midnight–6 AM interval, thrombolysis could be more safe from noon to midnight, and less effective from 6 AM to 6 PM.
Full-Body MRI in Patients With an Implantable Cardioverter-Defibrillator: Primary Results of a Randomized Study.

Magnetic resonance imaging (MRI) of patients with conventional implantable cardioverter-defibrillators (ICD) is contraindicated.



This multicenter, randomized trial evaluated safety and efficacy of a novel ICD system specially designed for full-body MRI without restrictions on heart rate or pacing dependency. The primary safety objective was >90% freedom from MRI-related events composite endpoint within 30 days post-MRI. The primary efficacy endpoints were ventricular pacing capture threshold and ventricular sensing amplitude.



Subjects received either a single- or dual-chamber ICD. In a 2:1 randomization, subjects either underwent MRI at 1.5-T of the chest, cervical, and head regions to maximize radiofrequency exposure up to 2 W/kg specific absorption rate and gradient field exposure to 200 T/m/s per axis (MRI group, n = 175), or they underwent a 1-h waiting period without MRI (control group, n = 88). A subset of MRI patients underwent ventricular fibrillation induction testing post-MRI to characterize defibrillation function.



In 42 centers, 275 patients were enrolled (76% male, age 60.4 ± 13.8 years). The safety endpoint was met with 100% freedom from the composite endpoint (p < 0.0001). Both efficacy endpoints were met with minimal differences in the proportion of MRI and control patients who demonstrated a ≤0.5 V increase in ventricular pacing capture threshold (100% MRI vs. 98.8% control, noninferiority p < 0.0001) or a ≤50% decrease in R-wave amplitude (99.3% MRI vs. 98.8% control, noninferiority p = 0.0001). A total of 34 ventricular tachyarrhythmia/ventricular fibrillation episodes (20 induced; 14 spontaneous) occurred in 24 subjects post-MRI, with no observed effect on sensing, detection, or treatment.



This is the first randomized clinical study of an ICD system designed for full-body MRI at 1.5-T. These data support that the system is safe and the MRI scan does not adversely affect electrical performance or efficacy.
Management of Acute Non-Q-Wave Myocardial Infarction

Non-Q-wave myocardial infarction (MI) differs from Q-wave MI in 3 important respects: a smaller infarct size, possibly due to early reperfusion resulting from spontaneous thrombolysis, relief of spasm, or both; more frequent patency of the infarct-related artery; and a larger residual mass of viable but jeopardised myocardium within the perfusion zone of the infarct-related vessel. Left ventricular function is generally better unless impaired by previous MI. After the acute phase, the prognosis is worse when residual ischaemia is present, and reinfarction rates during hospitalisation and in the subsequent year of follow-up are higher. As myocardial ischaemia is potentially reversible, its presence should be actively sought in all patients with recognised non-Q-wave MI. On the basis of current knowledge and available data, the following guidelines for the management of non-Q-wave MI patients can be recommended: (1) diltiazem and aspirin should be administered to all patients as soon as the diagnosis is established, unless contraindications exist; (2) patients who develop early recurrent ischaemia on therapy (i.e. angina with associated ST-T-wave changes) should undergo prompt cardiac catheterisation and myocardial revascularisation; and (3) patients with entirely uncomplicated hospital histories who are asymptomatic should undergo exercise stress testing, preferably in conjunction with 201Tl perfusion scintigraphy, before hospital discharge. Only those patients with evidence of significant residual ischaemia need cardiac catheterisation and myocardial revascularisation.