nils-herrmann/clean_scirepeval huggingface dataset:
LANTERN: a randomized study of QVA149 versus salmeterol/fluticasone combination in patients with COPD

The current Global initiative for chronic Obstructive Lung Disease (GOLD) treatment strategy recommends the use of one or more bronchodilators according to the patient's airflow limitation, their history of exacerbations, and symptoms. The LANTERN study evaluated the effect of the long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) dual bronchodilator, QVA149 (indacaterol/glycopyrronium), as compared with the LABA/inhaled corticosteroid, salmeterol/fluticasone (SFC), in patients with moderate-to-severe COPD with a history of ≤1 exacerbation in the previous year.



In this double-blind, double-dummy, parallel-group study, 744 patients with moderate-to-severe COPD with a history of ≤1 exacerbations in the previous year were randomized (1:1) to QVA149 110/50 μg once daily or SFC 50/500 μg twice daily for 26 weeks. The primary endpoint was noninferiority of QVA149 versus SFC for trough forced expiratory volume in 1 second (FEV1) at week 26.



Overall, 676 patients completed the study. The primary objective of noninferiority between QVA149 and SFC in trough FEV1 at week 26 was met. QVA149 demonstrated statistically significant superiority to SFC for trough FEV1 (treatment difference [Δ]=75 mL; P<0.001). QVA149 demonstrated a statistically significant improvement in standardized area under the curve (AUC) from 0 hours to 4 hours for FEV1 (FEV1 AUC0-4h) at week 26 versus SFC (Δ=122 mL; P<0.001). QVA149 and SFC had similar improvements in transition dyspnea index focal score, St George Respiratory Questionnaire total score, and rescue medication use. However, QVA149 significantly reduced the rate of moderate or severe exacerbations by 31% (P=0.048) over SFC. Overall, the incidence of adverse events was comparable between QVA149 (40.1%) and SFC (47.4%). The incidence of pneumonia was threefold lower with QVA149 (0.8%) versus SFC (2.7%).



These findings support the use of the LABA/LAMA, QVA149 as an alternative treatment, over LABA/inhaled corticosteroid, in the management of moderate-to-severe COPD patients (GOLD B and GOLD D) with a history of ≤1 exacerbation in the previous year.
A two-way multi-dimensional mixture model for clustering metagenomic sequences

A major challenge facing metagenomics is the development of tools for the characterization of functional and taxonomic content of vast amounts of short metagenome reads. The efficacy of clustering methods depends on the number of reads in the dataset, the read length and relative abundances of source genomes in the microbial community.
  In this paper, we formulate an unsupervised naive Bayes multi-species, multi-dimensional mixture model for reads from a metagenome. We use the proposed model to cluster metagenomic reads by their species of origin and to characterize the abundance of each species. We model the distribution of word counts along a genome as a Gaussian for shorter, frequent words and as a Poisson for longer words that are rare. We employ either a mixture of Gaussians or mixture of Poissons to model reads within each bin. An additional reason to use these distributions is their flexibility and ease of parameter estimation. Such a paradigm characterizes the compositional heterogeneity of the words along a genome, signifying its genome signature. Further, we handle the high-dimensionality and sparsity associated with the data, by grouping the set of words comprising the reads, resulting in a two-way mixture model. Finally, we derive an unsupervised Expectation Maximization algorithm for the models. Our method provides a general statistical framework for modeling metagenome reads. We demonstrate the accuracy and applicability of this method on simulated and real metagenomes. Our method can accurately cluster reads as short as 100 bps and estimate the species abundance as well. Our method outperforms LikelyBin, another unsupervised composition-based binning method for metagenomes, on datasets of varying abundances, divergences and read lengths.
Lathosterol and other non-cholesterol sterols during treatment of hypercholesterolaemia with beta-glucan-rich oat bran

Dietary fibre has been suggested to interfere with endogenous cholesterol synthesis in the liver. Therefore the effects of oat bran on the proportions of cholesterol synthesis precursors (squalene, Δ8-cholestenol, desmosterol and lathosterol), cholestanol and plant sterols (campesterol and beta-sitosterol) to cholesterol were analysed in serum of 36 hypercholesterolaemic subjects.  A randomized study of eight weeks duration where beta-glucan-rich oat bran (n=20, subjects) or wheat bran (n=16) was used as a part of a cholesterol lowering diet. Plant sterols and cholesterol synthesis precursors were analysed from frozen samples afterward.  In the oat-bran group, but not in the wheat bran group, serum total cholesterol declined transiently. The proportions of plant sterols and cholestanol in serum, which reflect cholesterol absorption efficiency were unchanged. However, the proportions of squalene appeared to be transiently increased during the study. Subjects with apolipoprotein E 4 allele had higher serum campesterol and sitosterol levels (suggestive of efficient cholesterol absorption) than those with homozygous apolipoprotein E 3 allele.  Since the cholesterol precursors in serum reflecting endogenous cholesterol synthesis remained almost unchanged the reduction in the serum cholesterol level by oat bran treatment can not be ascribed to an inhibition of the endogenous cholesterol synthesis.  Supported by the Council for Health Sciences, Academy of Finland and Alko Ltd, Finland.
Laparoscopic splenectomy in children--a multicenter experience.

Splenectomy is frequently required in children for various hematologic pathologic findings. Because of progress in minimally invasive techniques, laparoscopic splenectomy (LS) has become feasible. The objective of this report is to present a multicenter experience of 159 laparoscopic splenectomies.



Records of 159 children, who underwent LS in 3 pediatric surgery centers between 1996 and 2006, were reviewed retrospectively with a special questionnaire. The indication for splenectomy were hematologic disorders (147), esophageal varices (6), splenic cyst (5), and tumor of the tail of the pancreas (1). The LS was performed using standard laparoscopic technique and instrumentation.



There were 75 boys and 84 girls. Median age was 12.5 years (range, 2-19.4 years). Laparoscopic splenectomy alone was performed in 118 cases and LS with cholecystectomy or cholecystotomy in 36. In 5 cases, LS was performed together with fundoplication. Eight LS required conversion to an open procedure for following reasons: severe bleeding (3), massive splenomegaly (1), anatomical (2), and technical aspects (2). Accessory spleens were identified in 20 cases (12.6%). There was no mortality. Complications consisted of 8 conversions and postoperatively of mild generalized infection in 3 children and abdominal bleeding that resulted in re-laparoscopy in 1 case.



Laparoscopic splenectomy can be safely and effectively performed in children.
Dolutegravir versus placebo in subjects harbouring HIV-1 with integrase inhibitor resistance associated substitutions: 48-week results from VIKING-4, a randomized study.

The Phase III VIKING-3 study demonstrated that dolutegravir (DTG) 50 mg twice daily was efficacious in antiretroviral therapy (ART)-experienced subjects harbouring raltegravir- and/or elvitegravir-resistant HIV-1. VIKING-4 (ING116529) included a placebo-controlled 7-day monotherapy phase to demonstrate that short-term antiviral activity was attributable to DTG.



VIKING-4 is a Phase III randomized, double-blind study in therapy-experienced adults with integrase inhibitor (INI)-resistant virus randomized to DTG 50 mg twice daily or placebo while continuing their failing regimen (without raltegravir or elvitegravir) for 7 days (clinicaltrials.gov identifier NCT01568892). At day 8, all subjects switched to open-label DTG 50 mg twice daily and optimized background therapy including ≥1 fully active drug. The primary end point was change from baseline in plasma HIV-1 RNA at day 8.



The study population (n=30) was highly ART-experienced with advanced HIV disease. Patients had extensive baseline resistance to all approved antiretroviral classes. Adjusted mean change in HIV-1 RNA at day 8 was  -1.06 log10 copies/ml for the DTG arm and 0.10 log10 copies/ml for the placebo arm (treatment difference -1.16 log10 copies/ml [-1.52, -0.80]; P<0.001). Overall, 47% and 57% of subjects had plasma HIV-1 RNA <50 and <400 copies/ml at week 24, and 40% and 53% at week 48, respectively. No discontinuations due to drug-related adverse events occurred in the study.



The observed day 8 antiviral activity in this highly treatment-experienced population with INI-resistant HIV-1 was attributable to DTG. Longer-term efficacy (after considering baseline ART resistance) and safety during the open-label phase were in-line with the results of the larger VIKING-3 study.
Prognostic significance of expression levels of stem cell regulators MSI2 and NUMB in acute myeloid leukemia

Deregulation of the hematopoietic stem cell (HSC) compartment represents a hallmark of acute myeloid leukemia (AML). Recently, in vivo screening for genes that are involved in the regulation of HSCs has led to the discovery of Musashi-2 (MSI2) as a key regulator of HSCs and as a suppressor of NUMB. In order to analyze the prognostic importance of MSI2 and NUMB expression in AML, MSI2 and NUMB transcript levels from 454 AML patients treated in multicenter trials AML SHG 0199  In AML, patients with high MSI2 expression were more likely to be FLT3-ITD positive (P < .001), NPM1 (P < .001), and DNMT3A (P = .003) mutated. Overall survival (OS) was shorter in AML patients with high MSI2 expression (hazard ratio, 1.48; 95 % confidence interval, 1.13–1.95, P = .005). However, relapse-free survival (RFS, P = .15) and complete remission (CR, P = .39) rates were not influenced by MSI2 expression. In multivariate analysis, MSI2 expression remained an independent prognostic factor for OS (P = .03). NUMB expression had no impact on survival (OS, P = .47; RFS, P = .59) and CR rate (P = .39). MSI2 but not NUMB is associated with shorter OS in AML patients and may indicate a more aggressive form of AML.
GUTSS: An Alignment-Free Sequence Comparison Method for Use in Human Intestinal Microbiome and Fecal Microbiota Transplantation Analysis

Comparative analysis of gut microbiomes in clinical studies of human diseases typically rely on identification and quantification of species or genes. In addition to exploring specific functional characteristics of the microbiome and potential significance of species diversity or expansion, microbiome similarity is also calculated to study change in response to therapies directed at altering the microbiome. Established ecological measures of similarity can be constructed from species abundances, however methods for calculating these commonly used ecological measures of similarity directly from whole genome shotgun (WGS) metagenomic sequence are lacking.



We present an alignment-free method for calculating similarity of WGS metagenomic sequences that is analogous to the Bray-Curtis index for species, implemented by the General Utility for Testing Sequence Similarity (GUTSS) software application. This method was applied to intestinal microbiomes of healthy young children to measure developmental changes toward an adult microbiome during the first 3 years of life. We also calculate similarity of donor and recipient microbiomes to measure establishment, or engraftment, of donor microbiota in fecal microbiota transplantation (FMT) studies focused on mild to moderate Crohn's disease. We show how a relative index of similarity to donor can be calculated as a measure of change in a patient's microbiome toward that of the donor in response to FMT.



Because clinical efficacy of the transplant procedure cannot be fully evaluated without analysis methods to quantify actual FMT engraftment, we developed a method for detecting change in the gut microbiome that is independent of species identification and database bias, sensitive to changes in relative abundance of the microbial constituents, and can be formulated as an index for correlating engraftment success with clinical measures of disease. More generally, this method may be applied to clinical evaluation of human microbiomes and provide potential diagnostic determination of individuals who may be candidates for specific therapies directed at alteration of the microbiome.
Factors associated with benign multiple sclerosis in the New York State MS Consortium (NYSMSC)

This retrospective analysis explored prognostic factors associated with a benign multiple sclerosis (BMS) disease course at baseline and over the 4-year follow-up.



Patients from the centralized New York State Multiple Sclerosis Consortium registry were classified as having BMS according to 3 different criteria centered on disease duration and disability. Additional analyses explored prognostic factors associated with BMS using the most conservative disability criteria (Expanded Disability Status Scale ≤2 and disease duration ≥10 years).



Among 6258 patients who fulfilled eligibility criteria, 19.8 % to 33.3 % were characterized as having BMS, at baseline depending on classification criteria used. Positive prognostic factors for BMS at baseline included female sex (p < 0.0001) and younger age at onset (p < 0.0001); negative prognostic factors included progressive-onset type of MS and African-American race. Of the 1237 BMS patients (per most conservative criteria), 742 were followed for a median of 4 years to explore effect of disease-modifying treatment (DMT) on benign status. DMT (p = 0.009) and longer disease duration (p = 0.007) were the only significant positive predictors of maintaining BMS at follow-up. The protective effect was stronger for patients taking DMT at both enrollment and follow-up (OR = 0.71; p = 0.006).



There is a need for development of more reliable prognostic indicators of BMS. Use of DMT was significantly associated with maintaining a benign disease state.
Community or patient preferences for cost-effectiveness of cardiac rehabilitation: does it matter?

Few healthcare economic evaluations, and none in cardiac rehabilitation, report results based on both community and patient preferences for health outcomes. We published the results of a randomized trial of cardiac rehabilitation after myocardial infarction in 1994 in which preferences were measured using both perspectives but only patient preferences were reported. This secondary analysis uses both types of preference measurements.



We collected community Quality of Well-Being (QWB) and patient Time Trade-off (TTO) preference scores from 188 patients (rehabilitation, n=93; usual care, n=95) on entry into the trial, at 2 months (end of the intervention) and again at 4, 8, and 12 months. Mean preference scores over the 12-month follow-up study period, estimates of quality-adjusted life years (QALYs) gained per patient, incremental cost-effectiveness ratios [costs inflated to 2006 US dollars] and probabilities of the cost-effectiveness of rehabilitation for costs per QALY up to USD100,000 are reported.



Mean QWB preference scores were lower (P<0.01) than the corresponding mean TTO preference scores at each assessment point. The 12-month changes in mean QWB and TTO preference scores were large and positive (P<0.001) with rehabilitation patients gaining a mean of 0.011 (95% confidence interval, -0.030 to +0.052) more QWB-derived QALYs, and 0.040 (-0.026, 0.107) more TTO-derived QALYs, per patient than usual care patients. The incremental cost-effectiveness ratio for QWB-derived QALYs was estimated at $60 270/QALY (about euro50 600/QALY) and at $16 580/QALY (about euro13 900/QALY) with TTO-derived QALYs. With a willingness to spend $100 000/QALY, the probability of rehabilitation being cost-effective is 0.58 for QWB-derived QALYs and 0.83 for TTO-derived QALYs.



This secondary analysis of data from a randomized trial indicates that cardiac rehabilitation is cost-effective from a community perspective and highly cost-effective from the perspective of patients.
Pharmacokinetics and safety of itraconazole in patients with cystic fibrosis.

To assess the pharmacokinetics of itraconazole and hydroxy-itraconazole in patients with cystic fibrosis.



Patients were divided into those <16 and >/=16 years of age. All received itraconazole oral solution 2.5 mg/kg twice daily for 14 days. Serial blood samples were taken for itraconazole and hydroxy-itraconazole plasma level measurements. Safety was assessed from biochemistry and haematology data and reported adverse events.



Seventeen patients entered the study. Steady-state concentrations were achieved after maximally 8 days of dosing. On day 14 average peak plasma concentrations were 404 +/- 268 ng/mL (<16 years, n = 5) and 779 +/- 470 ng/mL (>/=16 years, n = 11 excluding one patient concurrently receiving oral clarithromycin). A high inter-subject variability in itraconazole pharmacokinetics was seen. Intra-subject variability was low. All the younger patients and 50% of the older patients failed to achieve a plasma steady-state trough concentration of >250 ng/mL. Adverse events were reported by 53% of subjects. Most were mild or moderate in intensity and not considered related to treatment. One patient withdrew from the study because of two severe adverse events. Ten significant laboratory abnormalities were reported in seven of 16 patients with paired data. Six of these were clinically relevant.



2.5 mg/kg itraconazole oral solution twice daily in patients with cystic fibrosis achieves steady-state concentrations in maximally 8 days. The pharmacokinetics showed marked inter-subject variability. Plasma concentrations of >250 ng/mL were not reached in the paediatric cohort or in 50% of the adult cohort. The dosage regimen was safe and well tolerated.
Factors influencing medical treatment of heart failure patients in Spanish internal medicine departments: a national survey.

The medical management of heart failure (HF) in clinical practice varies considerably by country and by medical specialty.



To assess the treatment of HF patients admitted to Internal Medicine departments, and to evaluate out-patient management prior to admission, by specialty.



Prospective cross-sectional multi-centre survey.



Of 55 randomly selected Spanish hospitals, 51 agreed to participate. All patients (n = 2145) consecutively admitted for decompensated HF to the Departments of Internal Medicine of these hospitals, over 5 months, were included. Twenty variables were analysed, including aspects relating to out-patient management prior to admission.



Mean +/- SD age was 77.2 +/- 10.5 years, 57.3% were female, 47% had systolic dysfunction. Prescriptions at discharge: loop diuretics 85.6%, spironolactone 29.8%, ACEIs 65.8%, beta-blockers 8.7%, cardiac glycosides 39%. At admission, 86% already had a diagnosis of HF. Of these, 53% (older patients and more women) were being treated on an out-patient basis by primary care physicians. Primary care physicians requested fewer echocardiograms than internists (38% vs. 69%, p<0.001) and prescribed fewer drugs (ACEIs 40% vs. 54%, p<0.001; spironolactone 15% vs. 23%, p<0.05; beta-blockers 6% vs. 13%, p<0.01). The internists treated more incapacitated patients than the cardiologists (p<0.001), prescribed more high-dose ACEIs (20% vs. 13%, p<0.01) and spironolactone (26% vs. 20%, p<0.05), and fewer anticoagulants (32% vs. 39%, p<0.05).



Patients admitted to medical departments with HF are different to those found in clinical trials. Their management is currently suboptimal. Differences in treatment between internists and cardiologists appear to be accounted for by differences in the patients they treat.
The evidence for effective psychiatric admissions as measured by an audit of Health of the Nation Outcome Scales recording.

The Health of the Nation Outcome Scales (HoNOS) were developed in the 1990s to measure health outcomes following a request by the Department of Health . The then UK government’s target to ‘improve significantly the health and social functioning of mentally ill people’ required a method of recording health improvement . HoNOS was developed to become a standardized tool to be used routinely by all mental health practitioners. HoNOS is now one item of the English Minimum Data Set for Mental Health being collected and is the most widely used routine clinical outcome measure used by English mental health services . The aim is for patients to have HoNOS scores recorded at the start and end of each episode of care, such as an admission to hospital. The HoNOS consists of 12 scales used to rate different aspects of mental and social health, each from 0 to 4, giving a maximum total score of 48. The scales are completed after routine clinical assessments in any setting by a qualified mental health care professional who have undergone HoNOS training.
Dose-response relationships for the effects of insulin on glucose and fat metabolism in injured patients and control subjects

1. Twenty-four patients were studied at around 7 days after musculoskeletal injuries in order to define the nature of the impairment of sensitivity to insulin. Insulin was infused at 6, 35, 200 or 1200 m-units min-' m-* for 2 h and the plasma glucose concentration was 'clamped' at 5 mmol/l. Forearm (uninjured) glucose extraction and blood flow were measured, and whole-body substrate oxidation and energy production rates were assessed by indirect calorimetry. The patients were compared with normal control subjects. 2. Plasma insulin concentrations during infusion were similar in patients and control subjects, showing a similar metabolic clearance of insulin. At each infusion rate, the rate of glucose infusion needed to maintain euglycaemia was less in the patients than in the control subjects. The dose-response curve for whole-body glucose infusion rate against plasma insulin concentration showed diminished sensitivity and diminished maximal response in the patients. A similar pattern was seen for forearm glucose uptake, with a marked impairment of both sensitivity to insulin and maximal responsiveness. 3. The resting metabolic rate was increased in the patients compared with the control subjects, but failed to respond to insulin infusion, so that final metabolic rates were similar in patients and control subjects. At the higher insulin infusion rates, the final rate of whole-body oxidation of carbohydrate was significantly less in the patients than in the control subjects, and that of fat was significantly greater. 4. The hormonal background to this picture of insulin resistance was not striking: the injured patients showed small elevations in plasma cortisol, glucagon and
Music therapy in moderate and severe dementia of Alzheimer's type: a case-control study.

Music therapy is a potential non-pharmacological treatment for the behavioral and psychological symptoms of dementia, but although some studies have found it to be helpful, most are small and uncontrolled.



This case-control study was carried out by qualified music therapists in two nursing homes and two psychogeriatric wards. The participants were 38 patients with moderate or severe Alzheimer's disease (AD) assigned randomly to a music therapy group and a control group.



The study showed a significant reduction in activity disturbances in the music therapy group during a 6-week period measured with the Behavior Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD). There was also a significant reduction in the sum of scores of activity disturbances, aggressiveness and anxiety. Other symptoms rated by subscales of the BEHAVE-AD did not decrease significantly. Four weeks later the effects had mostly disappeared.



Music therapy is a safe and effective method for treating agitation and anxiety in moderately severe and severe AD. This is in line with the results of some non-controlled studies on music therapy in dementia.