nils-herrmann/clean_scirepeval huggingface dataset:
In vivo CAMPATH-1H prevents graft-versus-host disease following nonmyeloablative stem cell transplantation.

A novel nonmyeloablative conditioning regimen was investigated in 44 patients with hematologic malignancies. The median patient age was 41 years. Many of the patients had high-risk features, including 19 patients with a previous failed transplant. Recipient conditioning consisted of CAMPATH-1H, 20 mg/day on days -8 to -4; fludarabine, 30 mg/m(2) on days -7 to -3; and melphalan, 140 mg/m(2) on day -2. Thirty-six recipients received unmanipulated granculocyte colony-stimulating factor-mobilized peripheral blood stem cells from HLA-identical siblings, and 8 received unmanipulated marrow from matched unrelated donors. GVHD prophylaxis was with cyclosporine A alone for 38 patients and cyclosporine A plus methotrexate for 6 sibling recipients. Forty-two of the 43 evaluable patients had sustained engraftment. Results of chimerism analysis using microsatellite polymerase chain reaction indicate that 18 of 31 patients studied were full-donor chimeras while the other patients were mixed chimeras in one or more lineages. At a median follow-up of 9 months (range 3 to 29 months), 33 patients remain alive in complete remission or with no evidence of disease progression. Seven patients relapsed or progressed post-transplantation, and 4 of them subsequently died. Four patients died of regimen-related complications. There were no cases of grades III-IV acute GVHD. Only 2 patients developed grade II acute GVHD, and only 1 had chronic GVHD. The estimated probability of nonrelapse mortality was 11%. Although longer follow-up is needed to establish the long-term remission rates, this study demonstrates that this nonmyeloablative preparative regimen is associated with durable engraftment, minimal toxicity, and low incidence of GVHD.
Symptoms and angiographic findings of patients undergoing elective coronary angiography without prior stress testing.

Many patients undergo elective coronary angiography without preprocedural stress testing that may be suitable if performed in patients with more angina pectoris or more frequently identified obstructive coronary artery disease (CAD). Patients in the National Cardiovascular Data Registry CathPCI Registry undergoing elective coronary angiography from July 2009 to April 2013 were assessed for differences in angina (Canadian Cardiovascular Society [CCS] class) and severity of obstructive CAD in those with and without preprocedural stress testing, stratified by CAD history. Given the large sample size, differences were considered clinically meaningful if the standardized difference (SD) was >10%. Of 790,601 patients without CAD history, 36.9% did not undergo preprocedural stress testing. Compared with patients with preprocedural stress testing, patients without preprocedural stress testing were more frequently angina free (CCS class 0; 28.2% with stress test vs 38.5% without, SD = 14.8%) and had similar rates of obstructive CAD (40.1% with stress test vs 35.7% without, SD = 9.0). Of 449,579 patients with CAD history, 44.2% did not undergo preprocedural stress testing. Patients without preprocedural stress testing reported more angina (CCS class III/IV angina: 17.8% vs 13.4%; SD = 11.3%) but were not more likely to have obstructive CAD (78.7% vs 81.1%; SD = 5.8%) than patients with preprocedural stress testing. In conclusion, approximately 40% of patients undergoing elective coronary angiography did not have preprocedural risk stratification with stress testing. For these patients, the clinical decision to proceed directly to invasive evaluation was not driven primarily by severe angina and did not result in higher detection rates for obstructive CAD.
Effects of dietary supplementation with epigallocatechin-3-gallate on weight loss, energy homeostasis, cardiometabolic risk factors and liver function in obese women: randomised, double-blind, placebo-controlled clinical trial.

The aim of the present study was to examine the effects of green tea epigallocatechin-3-gallate (EGCG) on changes in body composition, energy and substrate metabolism, cardiometabolic risk factors and liver function enzymes after an energy-restricted diet intervention in obese women. In the present randomised, double-blind, placebo-controlled study, eighty-three obese (30 kg/m² > BMI < 40 kg/m²) pre-menopausal women consumed 300 mg/d of EGCG or placebo (lactose). We measured body weight and adiposity (dual-energy X-ray absorptiometry), energy expenditure and fat oxidation rates (indirect calorimetry), blood lipid levels (TAG, total cholesterol, LDL-cholesterol and HDL-cholesterol), insulin resistance, C-reactive protein and liver function markers (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, γ-glutamyltransferase, urea, bilirubin and 2-keto[1-¹³C]isocaproate oxidation) before and after the intervention in the EGCG and control groups. We did not find any significant difference in the changes in body weight (-0.3 kg, 95% CI -5.0, 4.3), fat mass (-0.7 kg, 95% CI -3.5, 2.1), energy (0.3 kJ/kg per d, 95% CI -3.1, 2.7) and fat (-0.1 g/min, 95% CI -0.03, 0.01) metabolism, homeostasis assessment model for insulin resistance (0.2, 95% CI -0.2, 0.7), total cholesterol (-0.21 mmol/l, 95% CI -0.55, 0.13), LDL-cholesterol (-0.15 mmol/l, 95% CI -0.50, 0.20), TAG (-0.4 mmol/l, 95% CI -0.56, 0.29) and liver function markers between the EGCG and control groups. In conclusion, the present results suggest that dietary supplementation with 300 mg/d of EGCG for 12 weeks did not enhance energy-restricted diet-induced adiposity reductions, and did not improve weight-loss-induced changes in cardiometabolic risk factors in obese Caucasian women. The intake of 300 mg/d of EGCG for 12 weeks did not cause any adverse effect on liver function biomarkers.
Fampridine treatment and walking distance in multiple sclerosis: A randomised controlled trial

To explore the benefits of modified-release fampridine on walking distance in MS.



This was a randomised double-blind, placebo-controlled crossover trial of fampridine in 25 MS patients. The primary outcome measure was the six minute walk test (6MWT). A p-value<10% led to rejection of the null hypothesis.



The pre-specified criterion for statistical significance was met, with a 17m improvement in 6MWT in the treatment arm. In addition, baseline S2 accommodation, a nerve excitability parameter that reflects slow K+ channel activity, modified the effect of fampridine. For patients who had abnormally high S2 accommodation values, there was a 28m improvement in the 6MWT (p=0.04). In contrast, for patients with low S2 values, a 0m improvement was noted (p=1.0).



The study provides evidence that fampridine may improve walking distance. Nerve excitability assessment may be useful in selecting those patients who are most likely to gain benefit from fampridine.



Fampridine may improve walking distance in MS. Nerve excitability assessment may assist in identifying those patients most likely to respond to fampridine.
Guanfacine alone and in combination therapy in the treatment of moderate and severe hypertension.

This study of guanfacine in 27 patients suffering from moderate-to-severe hypertension showed a satisfactory blood pressure control in 26 patients. Twenty-one of the 27 patients completed a one-year clinical trial with good blood pressure response. The new drugs, acting through the stimulation of the central alpha-adrenoceptors, are useful in patients suffering from moderate-to-severe hypertension. They are a good alternative to adrenergic neuron-blocking drugs, methyldopa, or beta-blockers, and useful in patients with refractory hypertension where conventional therapy has failed.
A Multitrait–Multimethod Analysis of the Construct Validity of Child Anxiety Disorders in a Clinical Sample

The present study examines the construct validity of separation anxiety disorder (SAD), social phobia (SoP), panic disorder (PD), and generalized anxiety disorder (GAD) in a clinical sample of children. Participants were 174 children, 6 to 17 years old (94 boys) who had undergone a diagnostic evaluation at a university hospital based clinic. Parent and child ratings of symptom severity were assessed using the Multidimensional Anxiety Scale for Children (MASC). Diagnostician ratings were obtained from the Anxiety Disorders Interview Schedule for Children and Parents (. Discriminant and convergent validity were assessed using confirmatory factor analytic techniques to test a multitrait-multimethod model. Confirmatory factor analyses supported the current classification of these child anxiety disorders. The disorders demonstrated statistical independence from each other (discriminant validity of traits), the model fit better when the anxiety syndromes were specified than when no specific syndromes were specified (convergent validity), and the methods of assessment yielded distinguishable, unique types of information about child anxiety (discriminant validity of methods). Using a multi-informant approach, these findings support the distinctions between childhood anxiety disorders as delineated in the current classification system, suggesting that disagreement between informants in psychometric studies of child anxiety measures is not due to poor construct validity of these anxiety syndromes.
Analysis of Unexpected Conversion to Thoracotomy During Thoracoscopic Lobectomy in Lung Cancer.

Since anatomical lung resection by video-assisted thoracoscopic surgery (VATS) was first introduced, VATS has played a major role in lung cancer. However, conversion to thoracotomy is a major concern because an unexpected thoracotomy increases the risk of potentially adverse outcomes. Therefore, we compared patients who were and were not converted to thoracotomy and identified the risk factors for thoracotomy conversion.



Between January 2005 and December 2013, 69 of 1,110 VATS lobectomies for lung cancer required an unexpected conversion to thoracotomy. Each converted patient was individually matched to 3 randomly selected nonconverted patients based on date of operation, type of operation, and pathologic stage.



The most common cause of conversion was fibrocalcified lymph nodes, found in 28 patients (40.6%), followed by vascular injury in 20, tumor invasion or extension in 11, pleural adhesion in 5, incomplete interlobar fissure in 3, and failure of single-lung ventilation in 2. The differences in overall postoperative complications and in-hospital deaths were not significant; however, respiratory complications were significantly more common in the conversion group (p = 0.012). The independent risk factors for conversion were age 65 years and older, forced expiratory volume in 1 second of less than 1.8 L, and the presence of fibrocalcified lymph nodes on preoperative chest computed tomography.



Unexpected conversion to thoracotomy during VATS lobectomy in lung cancer does not appear to increase overall surgical morbidity and mortality. However, with high-risk patients, the surgeon requires careful selection for VATS candidate. Also, if necessary, the decision to convert must be made promptly to reduce possible critical respiratory complications.
Airway sensory replacement combined with nicotine replacement for smoking cessation. A randomized, placebo-controlled trial using a citric acid inhaler.

This study was conducted to determine if the combination of airway sensory replacement and nicotine replacement improves 10-week smoking abstinence rates over nicotine replacement alone.



Double-blind, randomized, placebo-controlled trial.



Outpatient research clinic.



One hundred healthy volunteers who smoked at least one pack of cigarettes per day and desired to quit smoking.



Subjects received either citric acid (n = 41) or lactose placebo (n = 59) inhalers to cope with smoking urges for 10 weeks. All subjects received self-help materials and nicotine patches for 6 weeks. Return visits were at weeks 1, 4, 6, and 10. Abstinence was defined as zero cigarettes smoked since the quit date verified by exhaled carbon monoxide < or = 8 ppm at all return visits. Inhaler effects were measured by a standardized questionnaire.



The primary outcome of continuous abstinence at the end of the 10-week treatment period was 19.5% (95% confidence interval [CI] = 7.4 to 31.6%) for the citric acid group vs 6.8% (95% CI = 0.4 to 13.2%) for the lactose group (p = 0.05). Relief from craving and short-term abstinence increased as airway sensations from the inhaler also increased. Abstinence at 10 weeks for subjects receiving strong airway sensations from the inhalers was 33.3% (95% CI = 14.5 to 52.1%). At 6 months, there was no difference in abstinence between the treatment groups (0% vs 5.1%, p = 0.20).



When combined with the nicotine patch, the citric acid inhaler improved 10-week smoking abstinence over lactose inhaler. The combination of airway sensory replacement and nicotine replacement may prove beneficial for smoking cessation.
Can botulinum toxin type A injection technique influence the clinical outcome of patients with post-stroke upper limb spasticity? A randomized controlled trial comparing manual needle placement and ultrasound-guided injection techniques

Botulinum toxin type A is a first-line treatment for post-stroke focal spasticity, and the accuracy in delivering the toxin to the target muscles may influence the treatment outcome. Our aim was to compare the reduction of spasticity and the related finger position at rest improvement in post-stroke patients treated with botulinum toxin type A in upper limb muscles using ultrasound guidance and manual needle placement.



In a randomized clinical trial, two groups of 15 stroke patients were treated with botulinum toxin type A injections in the wrist and finger flexor muscles of the affected upper limb using ultrasound guidance or manual needle placement. The Modified Ashworth Scale and the finger position at rest were measured at baseline and one month after toxin injections.



After one month of follow-up from toxin injections, the Modified Ashworth Scale and finger position at rest significantly improved in both treatment groups, although these clinical outcomes were significantly better in patients treated under ultrasound guidance than in patients injected using manual needle placement.



Ultrasound guidance for botulinum toxin type A injections could improve clinical outcome measures better than manual needle placement in post-stroke patients with spasticity.
In silico and in vitro pharmacogenetics: aldehyde oxidase rapidly metabolizes a p38 kinase inhibitor

The clinical development of a candidate p38 kinase inhibitor was terminated because of its unexpectedly rapid clearance in human subjects. Its short half-life and metabolic profile in human beings were vastly different from that in rats, dogs, and monkeys characterized during routine pre-clinical studies. Mice generated the predominant drug (4-hydroxylated) metabolite produced in human beings, which was not found in other species. The data from a murine in vitro drug biotransformation assay that used liver extracts from 14 inbred mouse strains were analyzed by haplotype-based computational genetic analysis. This led to the identification of aldehyde oxidase-1 (AOX1) as the enzyme responsible for the rapid metabolism of this drug. Specific enzyme inhibitors and expressed recombinant enzymes were used to confirm that AOX catalyzed the formation of the 4-hydroxylated drug metabolite in mouse and man. Genetic variation within Aox1 regulated the level of hepatic Aox1 mRNA, AOX1 protein, and enzyme activity among the inbred strains. Thus, computational murine pharmacogenetic analysis can facilitate the identification and characterization of drug metabolism pathways that are differentially utilized by humans and other species.
Conduct disorder and ADHD: evaluation of conduct problems as a categorical and quantitative trait in the international multicentre ADHD genetics study.

Attention-deficit/hyperactivity disorder (ADHD) is typically characterized by inattention, excessive motor activity, impulsivity, and distractibility. Individuals with ADHD have significant impairment in family and peer relations, academic functioning, and show high co-morbidity with a wide range of psychiatric disorders including oppositional defiant disorder (ODD), conduct disorder (CD), anxiety disorder, depression, substance abuse, and pervasive developmental disorder (PDD). Family studies suggest that ADHD + CD represents a specific subtype of the ADHD disorder with familial risk factors only partly overlapping with those of ADHD alone. We performed a hypothesis-free analysis of the GAIN-ADHD sample to identify markers and genes important in the development of conduct problems in a European cohort of individuals with ADHD. Using the Family-Based Association Test (FBAT) package we examined three measures of conduct problems in 1,043,963 autosomal markers. This study is part of a series of exploratory analyses to identify candidate genes that may be important in ADHD and ADHD-related traits, such as conduct problems. We did not find genome-wide statistical significance (P < 5 x 10(-7)) for any of the tested markers and the three conduct problem traits. Fifty-four markers reached strong GWA signals (P < 10(-5)). We discuss these findings in the context of putative candidate genes and the implications of these findings in the understanding of the etiology of ADHD + CD. We aimed to achieve insight into the genetic etiology of a trait using a hypothesis-free study design and were able to identify a number of biologically interesting markers and genes for follow-up studies.
Measuring death-related anxiety in advanced cancer: preliminary psychometrics of the Death and Dying Distress Scale.

The alleviation of distress associated with death and dying is a central goal of palliative care, despite the lack of routine measurement of this outcome. In this study, we introduce the Death and Dying Distress Scale (DADDS), a new, brief measure we have developed to assess death-related anxiety in advanced cancer and other palliative populations. We describe its preliminary psychometrics based on a sample of 33 patients with advanced or metastatic cancer. The DADDS broadly captures distress about the loss of time and opportunity, the process of death and dying, and its impact on others. The initial version of the scale has a one-factor structure and good internal reliability. Dying and death-related distress was positively associated with depression and negatively associated with spiritual, emotional, physical, and functional well-being, providing early evidence of construct validity. This distress was relatively common, with 45% of the sample scoring in the upper reaches of the scale, suggesting that the DADDS may be a relevant outcome for palliative intervention. We conclude by presenting a revised 15-item version of the scale for further study in advanced cancer and other palliative populations.
Can changes in vital signs be used to predict the response to lumbar facet blocks and radiofrequency denervation? A prospective, correlational study.

Facet joint radiofrequency (RF) ablation is characterized by a high failure rate, which is partly due to the fact that pain relief after diagnostic blocks is inherently subjective. An area that has yet to be explored is whether more objective measures, such as changes in vital signs after blocks, might be used to predict treatment outcomes.



A multicenter, prospective study was performed in 223 patients who underwent diagnostic lumbar medial branch blocks, of whom 87 proceeded to RF denervation. Blood pressure (BP), heart rate (HR), and pain scores were recorded preblock and 20 minutes postblock. A positive vital sign response was designated as a decrease of less than 7.5 units in BP or HR, and a positive facet block as pain relief of 50% or greater based on 6-hour pain diary scores.



Overall, 125 subjects (56.1%; 95% confidence interval, 49.3%-62.6%) experienced a positive facet block, and 71 had 3-month follow-up information after denervation. Correlations between changes in NRS scores and HR (r = -0.01, P = 0.893), systolic BP (r = 0.05, P = 0.47), diastolic BP (DBP) (r = 0.08, P = 0.22), and mean arterial pressure (r = 0.08, P = 0.21) were weak and nonsignificant. No associations were found between facet block results and any vital sign. Six (85.7%) of 7 patients who experienced a decrease in DBP of greater than 7.5 mm Hg after facet block had a positive RF denervation outcome at 3 months, compared with 43.8% who did not (odds ratio, 7.52; 95% confidence interval, 0.84-363.8; P = 0.049). A classification tree based on significant decrease in DBP, pain duration, and baseline NRS pain score showed a 76.7% (range, 65.8%-86.3%) accuracy rate.



Although a decrease in DBP of more than 7.5 mm Hg had 97.3% specificity and 85.7% positive predictive value for predicting positive RF ablation outcomes, the low negative predictive value (56.3%) precludes its use as a solitary screening tool. An algorithm based on age, baseline NRS pain score, and a significant decrease in DBP was able to predict 76.7% (range, 65.8%-86.3%) of RF denervation outcomes.
Efficacy of intra-articular sodium hyaluronate in the treatment of knee osteoarthritis

To assess the efficacy of intra-articular hyaluronic acid in patients with knee osteoarthritis, sixty female patients with knee osteoarthritis were randomised to three weekly intra-articular injections of 30 mg sodium hyaluronate (Na HA) with a high molecular weight (1.0 to 2.9 million Da) or 40 mg 6-methylprednisolone acetate (6-MPA). The clinical assessments included pain at rest, at weight-bearing and on walking, Lequesne Index and active range of knee flexion. Assessments were done at baseline, at week 4, and at months 3 and 6. A significant decrease in VAS scores for pain at rest, at weight-bearing and pain on walking, and in Lequesne index was found in both groups at week 4 when compared to baseline and there was no significant differences between the two groups. However, at 3rd month improvement in all pain scores and Lequesne index was found in favour of hyaluronic acid. At 6th, no significant difference was found between the treatment groups. Improvement in pain was accompanied by an increase in joint flexion at week 4 and at month 3 in both groups. Both treatments were well-tolerated. The results showed that both intra-articular hyaluronic acid and 6-MPA treatments provide clinically significant improvement and demonstrated that Na HA has a long-term beneficial effect in patients with knee osteoarthritis.