nils-herrmann/clean_scirepeval huggingface dataset:
Oral iodinated activated charcoal improves lung function in patients with COPD.

The effect of 8 weeks treatment with oral iodinated activated charcoal (IAC) on lung function of patients with moderate chronic obstructive pulmonary disease (COPD) was examined in a double blind randomized placebo controlled parallel group study with 40 patients. In the IAC group, patients showed a statistically significant improvement of FEV1 baseline by 130 ml compared to placebo, corresponding to 8.2% improvement (p = 0.031*). Correlation statistics revealed that the improvement of FEV1 baseline was significantly correlated both to FEV1 post-bronchodilator (p = 0.0020**) and FEV1 post-exercise (0.033*) values. This demonstrates that the improved baseline lung function by IAC did not inhibit a further beta2-adrenoceptor relaxation, and thus that patients did not reach a limit for maximal improvement of the lung function after IAC treatment. Eight patients in the IAC group developed abnormal thyroid hormone levels transiently during the treatment. This side effect was not correlated to improvement of lung function (p = 0.82). No serious adverse effects directly related to the treatment were recorded. In summary, this study demonstrates that iodinated activated charcoal surprisingly and significantly improved lung function of patients with moderate COPD. The underlying mechanism of action is unclear, but is likely to be different from the drugs used today. The immediate conclusion is that further studies are now justified in order to determine clinical efficacy of IAC in COPD and explore possible mechanisms of action.
Reproducibility of an instrumented measure for passive ankle dorsiflexion in conscious and anaesthetized children with cerebral palsy.

The aims of this study were to (1) determine whether an instrumented measure will reduce measurement error to less than 5° in children with cerebral palsy (CP), (2) determine agreement and reliability of this instrumented measure in both conscious and anaesthetized participants, and (3) compare the method with previously reported measures.



Thirty-four ambulant children (15 males, 19 females), aged 3 to 9 years, with spastic CP were studied in a tertiary-care paediatric hospital (21 with hemiplegia, 11 with diplegia, and two with quadriplegia). The majority of children functioned at Gross Motor Function Classification System level I (n=11) or II (n=18), with five children at level III. Ankle dorsiflexion at 50% bodyweight was photographed and measured. Each child was measured when conscious and when under mask anaesthesia by two experienced assessors.



The standard error of measurement (SEM) ranged from 3.9° (anaesthetized; 95% confidence interval [CI] 3.3-4.0°) to 6.7° (conscious; 95% CI 5.3-8.0°). This compared favourably with previously reported dorsiflexion measures (SEM range 6.5-7.8°) in conscious children with CP. Intrarater reliability was good in both conditions (intraclass correlation coefficient [ICC]: range 0.95 [anaesthetized; 95% CI 0.92-0.98] to 0.86 [conscious; 95% CI 0.76-0.95]). The ICC for interrater reliability ranged from 0.87 (anaesthetized; 95% CI 0.81-0.93) to 0.65 (conscious; 95% CI 0.50-0.81).



Passive ankle dorsiflexion using an instrumented measure has face validity and may assist in the improvement of reproducibility under anaesthesia for clinical research. When an individual is conscious, this technique is not better than trained assessors using conventional goniometry reported in the literature and is not recommended for routine clinical use.
Serum miR-122 may serve as a biomarker for response to direct acting antivirals: effect of paritaprevir/R with dasabuvir or ombitasvir on miR-122 in HCV-infected subjects.

Circulating microRNAs (miRNA) have been intensely investigated as biomarkers in disease and therapy. Several studies have identified miR-122 as an important regulator of HCV replication. The effect of new therapies that directly target the HCV replication life cycle on circulating microRNA levels has not been elucidated. We performed expression profiling of circulating miRNA in serum in subjects treated with HCV direct-acting antiviral agents (DAAs). Serum miRNA levels were evaluated from two studies in HCV GT1-infected treatment-naïve subjects and prior nonresponders to pegylated interferon (pegIFN) and ribavirin (RBV) who received paritaprevir/ritonavir + dasabuvir + RBV for 12 weeks, and in treatment-naïve genotype (GT)1-3-infected subjects who received paritaprevir/ritonavir + ombitasvir ± RBV for 12 weeks. Over 100 different miRNA species were detected in serum. Of these, levels of miR-122 showed the most consistent change in response to treatment across all HCV genotypes. In all subjects, miR-122 showed an average four-fold reduction between baseline and week 2, and remained below baseline through post-treatment week 12 in subjects who achieved sustained virological response. In contrast, in subjects who did not achieve SVR, miR-122 levels began to return to baseline levels after the second week of treatment. The change in miR-122 levels was similar across genotypes, and was comparable with or without RBV. This is the first report comparing expression levels of circulating miRNA in HCV GT1-3 subjects treated with IFN-free combinations of DAAs. The results suggest that serum levels of miR-122 are reduced following treatment in subjects who achieve SVR, and correlate with HCV RNA levels across genotypes.
Risk stratification of patients after myocardial revascularization by stress Tc-99m tetrofosmin myocardial perfusion tomography.

The aim of this study was to assess the incremental prognostic value of stress technetium 99m tetrofosmin imaging after myocardial revascularization.



We studied 381 patients (aged 60 +/- 10 years, 270 men), 4.5 +/- 3.2 years after myocardial revascularization (coronary artery bypass grafting in 201 patients and percutaneous coronary intervention in 180 patients), who underwent exercise or dobutamine stress tetrofosmin single photon emission computed tomography. Events during a mean follow-up period of 3.5 +/- 1.4 years were cardiac death in 22 patients, nonfatal myocardial infarction in 11 patients (33 hard cardiac events), and late revascularization in 50 patients. There was no incidence of hard cardiac events in the 100 patients with normal perfusion. Hard cardiac events occurred in 19% of patients with reversible perfusion abnormalities and in 4% of patients without them (P <.01). The incidence of hard cardiac events was similar in patients with and without angina before stress testing (17/197 [8.6%] vs 16/184 [8.7%]). In a multivariate analysis model, predictors of cardiac death were stress rate pressure product and abnormal perfusion. Reversible perfusion abnormalities were independently associated with the composite endpoints of cardiac death, nonfatal myocardial infarction, and late revascularization. In an incremental multivariate analysis model, an abnormal scan was additive to clinical data in the prediction of hard cardiac events (model chi(2) = 17 vs 11, P <.01).



Stress Tc-99m tetrofosmin myocardial perfusion imaging provides independent prognostic information for the prediction of cardiac events after myocardial revascularization. Symptoms are not predictive of outcome, and therefore asymptomatic patients should not be deferred from stress testing. A normal study identifies a very low-risk population in whom no further intervention is required.
Occurrence of Anti-Drug Antibodies against Interferon-Beta and Natalizumab in Multiple Sclerosis: A Collaborative Cohort Analysis

Immunogenicity of biopharmaceutical products in multiple sclerosis is a frequent side effect which has a multifactorial etiology. Here we study associations between anti-drug antibody (ADA) occurrence and demographic and clinical factors. Retrospective data from routine ADA test laboratories in Sweden, Denmark, Austria and Germany (Dusseldorf group) and from one research study in Germany (Munich group) were gathered to build a collaborative multi-cohort dataset within the framework of the ABIRISK project. A subset of 5638 interferon-beta (IFNβ)-treated and 3440 natalizumab-treated patients having data on at least the first two years of treatment were eligible for interval-censored time-to-event analysis. In multivariate Cox regression, IFNβ-1a subcutaneous and IFNβ-1b subcutaneous treated patients were at higher risk of ADA occurrence compared to IFNβ-1a intramuscular-treated patients (pooled HR = 6.4, 95% CI 4.9-8.4 and pooled HR = 8.7, 95% CI 6.6-11.4 respectively). Patients older than 50 years at start of IFNβ therapy developed ADA more frequently than adult patients younger than 30 (pooled HR = 1.8, 95% CI 1.4-2.3). Men developed ADA more frequently than women (pooled HR = 1.3, 95% CI 1.1-1.6). Interestingly we observed that in Sweden and Germany, patients who started IFNβ in April were at higher risk of developing ADA (HR = 1.6, 95% CI 1.1-2.4 and HR = 2.4, 95% CI 1.5-3.9 respectively). This result is not confirmed in the other cohorts and warrants further investigations. Concerning natalizumab, patients older than 45 years had a higher ADA rate (pooled HR = 1.4, 95% CI 1.0-1.8) and women developed ADA more frequently than men (pooled HR = 1.4, 95% CI 1.0-2.0). We confirmed previously reported differences in immunogenicity of the different types of IFNβ. Differences in ADA occurrence by sex and age are reported here for the first time. These findings should be further investigated taking into account other exposures and biomarkers.
The Austrian fulvestrant registry: results from a prospective observation of fulvestrant in postmenopausal patients with metastatic breast cancer

Endocrine therapy is the preferred treatment in oestrogen- and/or progesterone-receptor (ER/PgR) positive breast cancer. Fulvestrant is a pure ER-antagonist. We present results from the Austrian Fulvestrant Registry.  Three-hundred and fifty patients were included. Time to progression (TTP) was defined as primary endpoint. A multivariate analysis was performed to identify factors significantly associated with TTP.  Fulvestrant was administered as first-line therapy in 26%, second-line in 49%, and third-line or beyond in 25%. TTP was median 7 months. We observed a response in 15% of patients and 41% had SD ≥ 6 months. First-line treatment and non-visceral metastases were associated with longer TTP. One case of pulmonary embolism was reported. Grade 3 toxicities consisted of joint pain (1.4%), nausea (1.4%) and hot flashes (0.3%).  Fulvestrant was effective and well tolerated. TTP was superior to other trials, due to the large proportion of first-line patients. Activity is apparently independent of Her2-status.
True complete left bundle branch block morphology strongly predicts good response to cardiac resynchronization therapy.

To determine whether patients with congestive heart failure and true left bundle branch block (LBBB) morphology have better response to cardiac resynchronization therapy (CRT) than do patients without true LBBB.



We defined true LBBB as conventional LBBB plus QRS duration ≥ 130 ms and mid-QRS notching/slurring in at least two of the leads I, aVL, V1, V2, V5, or V6. We prospectively enrolled 58 patients with heart failure and allocated them to three groups: true LBBB (t-LBBB, n = 22); non-true LBBB (nt-LBBB, LBBB with no notch or notches in fewer than two of the leads, n = 17); and non-specific intraventricular conduction delay (IVCD, n = 19). At 6 month follow-up, mean absolute increases in left ventricular ejection fraction were 16.0% ± 11.6% in t-LBBB, 8.1% ± 11.2% in nt-LBBB (P = 0.02), and 3.3% ± 7.8% in IVCD (P < 0.001, t-LBBB vs. IVCD) and changes in mean New York Heart Association class were -1.2 ± 0.6 in t-LBBB, -0.8 ± 0.6 in nt-LBBB (P = 0.071), and -0.5 ± 0.6 in IVCD (P = 0.01, t-LBBB vs. IVCD). All patients with t-LBBB were responders, some were super-responders. Multivariate analysis showed that t-LBBB (odds ratio, OR, 11.680; 95% confidence interval, CI, 1.966-69.390; P = 0.007) and left ventricular end-diastolic dimension (OR, 0.891; 95% CI, 0.797-0.996; P = 0.043) are independent predictors of super-response to CRT.



In patients with conventional wider LBBB morphology, the presence of mid-QRS notching or slurring is a strong predictor of better response to CRT.
Plasma Concentrations of the Vasoactive Peptide Fragments Mid-Regional Pro-Adrenomedullin, C-Terminal Pro-Endothelin 1 and Copeptin in Hemodialysis Patients: Associated Factors and Prediction of Mortality

Vasopressin, endothelin and adrenomedullin are vasoactive peptides that regulate vascular tone and might play a role in hypertensive diseases. Recently, laboratory assays have been developed to measure stable fragments of vasopressin, endothelin and adrenomedullin. Little is known about their diagnostic and prognostic value in hemodialysis patients. In this study, we measured the plasma concentration of copeptin, mid-regional-pro-adrenomedullin (MR-pro-ADM) and C-terminal pro-endothelin 1 (CT-pro-ET1) in stable ambulatory hemodialysis patients (n = 239) and investigated their associations with clinical factors and mortality. In all patients enrolled, the plasma concentrations of copeptin, MR-pro-ADM and CT-pro-ET1 were largely elevated with a median concentration of 132 pmol/L (interquartile range [IQR] 78-192) for copeptin, 1.26 nmol/L (IQR 1.02-1.80) for MR-pro-ADM and 149 pmol/L (IQR 121-181) for CT-pro-ET1. The plasma concentrations of all vasoactive peptide fragments correlated with time on dialysis and plasma β2-microglobulin concentration and were negatively correlated to residual diuresis. The plasma concentration of MR-pro-ADM was a strong predictor of all-cause (univariate hazard ratio for a 10-fold increase 9.94 [3.14;32], p<0.0001) and cardiovascular mortality (hazard ratio 34.87 [5.58;217], p = 0.0001) within a 3.8-year follow-up. The associations remained stable in models adjusted for dialysis specific factors and were attenuated in a full model adjusted for all prognostic factors. Plasma copeptin concentration was weakly associated with cardiovascular mortality (only in univariate analysis) and CT-pro-ET1 was not associated with mortality at all. In conclusion, vasoactive peptide fragments are elevated in hemodialysis patients because of accumulation and, most likely, increased release. Increased concentrations of MR-pro-ADM are predictive of mortality.
IgM myeloma: A multicenter retrospective study of 134 patients.

IgM myeloma is a rare hematologic malignancy for which the clinicopathological features and patient outcomes have not been extensively studied. We carried out a multicenter retrospective study in patients with diagnosis of IgM myeloma defined by >10% marrow involvement by monoclonal plasma cells, presence of an IgM monoclonal paraproteinemia of any size, and anemia, renal dysfunction, hypercalcemia, lytic lesions and/or t(11;14) identified by FISH. A total of 134 patients from 20 centers were included in this analysis. The median age at diagnosis was 65.5 years with a male predominance (68%). Anemia, renal dysfunction, elevated calcium and skeletal lytic lesions were found in 37, 43, 19, and 70%, respectively. The median serum IgM level was 2,895 mg dL-1 with 19% of patients presenting with levels >6,000 mg dL-1 . International Staging System (ISS) stages 1, 2, and 3 were seen in 40 (33%), 54 (44%), and 29 (24%) of patients, respectively. The malignant cells expressed CD20 (58%) and cyclin D1 (67%), and t(11;14) was the most common cytogenetic finding (39%). The median overall survival (OS) was 61 months. Higher ISS score was associated with worse survival (P = 0.02). Patients with IgM myeloma present with similar characteristics and outcomes as patients with more common myeloma subtypes.
Gastric secretion of acid and pepsin in patients with esophageal stricture and appropriate controls

Most cases of esophageal stricture are associated with acid/peptic reflux esophagitis. While patients with strictures commonly have disordered lower esophageal sphincters and poor clearance and neutralization mechanisms, it is not known whether they also have abnormal gastric secretion. This study examined fasting, basal, and stimulated acid and pepsin secretion. With an endoscopic diagnosis of esophagitis, patients with stricture (<12.5 mm) were matched for age, sex, concurrent gastrointestinal disease (duodenal ulcer,N=9), Zollinger-Ellison syndrome (N=6), and postgastric surgery state (N=5), as well as the absence of ulcer disease (non-DU,N=37). Fasting, basal, and pentagastrin-stimulated acid and pepsin secretion were measured. Overall, the 57 stricture patients had the same acid and pepsin secretion as their matched controls with esophagitis; the same was true for each of the subgroups (ZES, DU, non-DU, and postsurgical). Stricture patients weighed less and had a lower body mass index (P<0.01). Patients with esophageal peptic stricture have the same acid and pepsin output as control patients matched for sex, age, background gastrointestinal disease, and the presence of esophagitis.
Outcomes at 2 years of age after repeat doses of antenatal corticosteroids.

We previously reported the results of a randomized, controlled trial showing that repeat doses of antenatal corticosteroids reduced the risk of respiratory distress syndrome and serious neonatal morbidity. However, data have not been available regarding longer-term effects of this treatment.



Women who had received an initial course of corticosteroid treatment 7 or more days previously were randomly assigned to receive an intramuscular injection of corticosteroid (11.4 mg of betamethasone) or saline placebo; the dose was repeated weekly if the mother was still considered to be at risk for preterm delivery and the duration of gestation was less than 32 weeks. We assessed survival free of major neurosensory disability and body size of the children at 2 years of corrected age.



Of the 1085 children who were alive at 2 years of age, 1047 (96.5%) were seen for assessment (521 exposed to repeat-corticosteroid treatment and 526 exposed to placebo). The rate of survival free of major disability was similar in the repeat-corticosteroid and placebo groups (84.4% and 81.0%, respectively; adjusted relative risk, 1.04, 95% confidence interval, 0.98 to 1.10; adjusted P=0.20). There were no significant differences between the groups in body size, blood pressure, use of health services, respiratory morbidity, or child behavior scores, although children exposed to repeat doses of corticosteroids were more likely than those exposed to placebo to warrant assessment for attention problems (P=0.04).



Administration of repeat doses of antenatal corticosteroids reduces neonatal morbidity without changing either survival free of major neurosensory disability or body size at 2 years of age. (Current Controlled Trials number, ISRCTN48656428 [controlled-trials.com].).
Help seeking for cancer ‘alarm’ symptoms: a qualitative interview study of primary care patients in the UK

Delay in help seeking for cancer 'alarm' symptoms has been identified as a contributor to delayed diagnosis.



To understand people's help-seeking decision making for cancer alarm symptoms, without imposing a cancer context.



Community-based, qualitative interview study in the UK, using purposive sampling by sex, socioeconomic status, and prior help seeking, with framework analysis of transcripts.



Interviewees (n = 48) were recruited from a community-based sample (n = 1724) of adults aged ≥50 years who completed a health survey that included a list of symptoms. Cancer was not mentioned. Participants reporting any of 10 cancer alarm symptoms (n = 915) and who had consented to contact (n = 482) formed the potential pool from which people were invited to an interview focusing on their symptom experiences.



Reasons for help seeking included symptom persistence, social influence, awareness/fear of a link with cancer, and 'just instinct'. Perceiving the symptom as trivial or 'normal' was a deterrent, as was stoicism, adopting self-management strategies, and fear of investigations. Negative attitudes to help seeking were common. Participants did not want to be seen as making a fuss, did not want to waste the doctor's time, and were sometimes not confident that the GP could help.



Decision making about cancer alarm symptoms was complex. Recognition of cancer risk almost always motivated help seeking (more so than the fear of cancer being a deterrent), assisted by recent public-awareness campaigns. As well as symptom persistence motivating help seeking, it could also have the reverse effect. Negative attitudes to help seeking were significant deterrents.
The Anti-Clot Treatment Scale (ACTS) in clinical trials: cross-cultural validation in venous thromboembolism patients

The Anti-Clot Treatment Scale (ACTS) is a 15-item patient-reported instrument of satisfaction with anticoagulant treatment. It includes a 12-item ACTS Burdens scale and a 3-item ACTS Benefits scale. Its role in clinical trials and other settings should be supported by evidence that it is both clinically meaningful and scientifically sound. The aim of the study was to evaluate the measurement performance of the ACTS (Dutch, Italian, French, German and English language versions) in patients with venous thromboembolism based on traditional psychometric methods.



ACTS Burdens and Benefits scale data from a large clinical trial (EINSTEIN DVT) involving 1336 people with venous thromboembolism were analysed at both the scale and item level. Five key psychometric properties were examined using traditional psychometric methods: acceptability, scaling assumptions, reliability (including internal consistency reliability, test-retest reproducibility); validity (including known groups and discriminant validity); and responsiveness. These methods of examination underpin the US Food and Drug Administration recommendations for patient-reported outcome instrument evaluation.



Overall, the 12-item ACTS Burdens scale and 3-item ACTS Benefits scale met the psychometric criteria evaluated at both item and scale levels, with the exception of some relatively minor issues in the Dutch language version, which were just below reliability criteria (i.e. alpha = 0.72, test-retest intraclass correlation = 0.79). A consistent finding from item-level evaluations of aggregate endorsement frequencies and skewness suggested that response scales may be improved by reducing the number of response options from five to four.



Both the ACTS Burdens and ACTS Benefits scales consistently satisfied traditional reliability and validity criteria across multiple language datasets, supporting it as a clinically useful patient-reported instrument of satisfaction with anticoagulant treatment in clinical trials.