nils-herrmann/clean_scirepeval huggingface dataset:
Ventricular Tachycardia Ablation versus Escalation of Antiarrhythmic Drugs.

Recurrent ventricular tachycardia among survivors of myocardial infarction with an implantable cardioverter-defibrillator (ICD) is frequent despite antiarrhythmic drug therapy. The most effective approach to management of this problem is uncertain.



We conducted a multicenter, randomized, controlled trial involving patients with ischemic cardiomyopathy and an ICD who had ventricular tachycardia despite the use of antiarrhythmic drugs. Patients were randomly assigned to receive either catheter ablation (ablation group) with continuation of baseline antiarrhythmic medications or escalated antiarrhythmic drug therapy (escalated-therapy group). In the escalated-therapy group, amiodarone was initiated if another agent had been used previously. The dose of amiodarone was increased if it had been less than 300 mg per day or mexiletine was added if the dose was already at least 300 mg per day. The primary outcome was a composite of death, three or more documented episodes of ventricular tachycardia within 24 hours (ventricular tachycardia storm), or appropriate ICD shock.



Of the 259 patients who were enrolled, 132 were assigned to the ablation group and 127 to the escalated-therapy group. During a mean (±SD) of 27.9±17.1 months of follow-up, the primary outcome occurred in 59.1% of patients in the ablation group and 68.5% of those in the escalated-therapy group (hazard ratio in the ablation group, 0.72; 95% confidence interval, 0.53 to 0.98; P=0.04). There was no significant between-group difference in mortality. There were two cardiac perforations and three cases of major bleeding in the ablation group and two deaths from pulmonary toxic effects and one from hepatic dysfunction in the escalated-therapy group.



In patients with ischemic cardiomyopathy and an ICD who had ventricular tachycardia despite antiarrhythmic drug therapy, there was a significantly lower rate of the composite primary outcome of death, ventricular tachycardia storm, or appropriate ICD shock among patients undergoing catheter ablation than among those receiving an escalation in antiarrhythmic drug therapy. (Funded by the Canadian Institutes of Health Research and others; VANISH ClinicalTrials.gov number, NCT00905853.).
A Single-Blind randomized controlled trial to evaluate the effect of extended counseling on uptake of pre-antiretroviral care in eastern uganda

Many newly screened people living with HIV (PLHIV) in Sub-Saharan Africa do not understand the importance of regular pre-antiretroviral (ARV) care because most of them have been counseled by staff who lack basic counseling skills. This results in low uptake of pre-ARV care and late treatment initiation in resource-poor settings. The effect of providing post-test counseling by staff equipped with basic counseling skills, combined with home visits by community support agents on uptake of pre-ARV care for newly diagnosed PLHIV was evaluated through a randomized intervention trial in Uganda.



An intervention trial was performed consisting of post-test counseling by trained counselors, combined with monthly home visits by community support agents for continued counseling to newly screened PLHIV in Iganga district, Uganda between July 2009 and June 2010, Participants (N = 400) from three public recruitment centres were randomized to receive either the intervention, or the standard care (the existing post-test counseling by ARV clinic staff who lack basic training in counseling skills), the control arm. The outcome measure was the proportion of newly screened and counseled PLHIV in either arm who had been to their nearest health center for clinical check-up in the subsequent three months +2 months. Treatment was randomly assigned using computer-generated random numbers. The statistical significance of differences between the two study arms was assessed using chi-square and t-tests for categorical and quantitative data respectively. Risk ratios and 95% confidence intervals were used to assess the effect of the intervention.



Participants in the intervention arm were 80% more likely to accept (take up) pre-ARV care compared to those in the control arm (RR 1.8, 95% CI 1.4-2.1). No adverse events were reported.



Provision of post-test counseling by staff trained in basic counseling skills, combined with home visits by community support agents had a significant effect on uptake of pre-ARV care and appears to be a cost-effective way to increase the prerequisites for timely ARV initiation.


 C/OBioMed Central Ltd as ISRCTN94133652 and received financial support from Sida and logistical support from the European Commission.
Endoscope versus microscope in the diagnosis of esophageal non-erosive reflux disease: a study of 71 cases.

Non-erosive reflux disease (NERD) is a type of gastroesophageal reflux disease (GERD) defined as symptomatic GERD without mucosal breaks on endoscopy. There is no gold standard for diagnosis of NERD till date. Biopsy from the distal esophagus in patients of GERD is said to reveal characteristic, although non-specific injury patterns such as squamous cell hyperplasia and intraepithelial inflammatory cell infiltration, collectively known as microscopic esophagitis. Recently, dilated intercellular spaces (DIS) are also shown to be associated with NERD. The present study was undertaken to evaluate the role of biopsy in NERD cases.



Two mucosal biopsies were taken at 3 cm above the squamocolumnar junction (SCJ) from 71 cases of NERD having symptom scores of more than 10. Biopsies were evaluated for features of microscopic esophagitis and DIS, and the results were analyzed.



Fifty out of 71 (70.4%) patients with symptomatic NERD had features of microscopic esophagitis. DIS was noted in 46/71 (64.8%) of cases, and correlated significantly with microscopic esophagitis (p<0.0001). Basal cell hyperplasia, papillary elongation, intraepithelial neutrophils, and intraepithelial eosinophils were seen in 83.1%, 76.1%, 40.8%, and 12.7% of NERD cases respectively.



In symptomatic patients of GERD, when endoscopy does not show mucosal breaks (so called NERD), histopathological evaluation of distal esophageal mucosa may have a diagnostic value. The present study also reinforces the diagnostic utility of DIS in symptomatic NERD.
Theory of mind and emotion processing training for patients with schizophrenia: Preliminary findings

Impairments in social cognition are critical predictors of social functioning in patients with schizophrenia. Emotion processing (EP) and theory of mind (ToM) are hypothesized to influence real-world behavior more directly than basic cognition and represent important targets of intervention. The use of video scenes depicting human interactions could constitute an appropriate tool to enhance understanding of the characters' behavior and stimulate inferences on mental states. The aim of our pilot study was to evaluate longitudinally, with a controlled trial, the feasibility and the efficacy of a single-paradigm emotion recognition and ToM training designed for outpatients affected by schizophrenia, with the goal to create an ecological treatment, overcoming artificial laboratory biases, by the use of specific videotaped material. Fifty-two outpatients were randomly assigned to an EP and ToM video-based training (n=27) or to a standard social cognitive rehabilitation treatment (n=24). They were assessed before and after 12 weeks of intervention and compared to a time-matched control group (n=24). Our results show a statistically significant improvement in ToM abilities, confirming the hypothesis of the enhancing potential of social cognitive interventions, but no changes with respect to EP; despite the need for a deeper examination, these data support further development of this treatment approach.
Pain management in chronic kidney disease: the pharmacokinetics and pharmacodynamics of hydromorphone and hydromorphone-3-glucuronide in hemodialysis patients.

To describe the pharmacokinetics of hydromorphone (HM) and its primary metabolite hydromorphone-3-glucuronide (H3G) both on and off dialysis in relation to the pharmacodynamic measurements of pain.



Prospective, open-label, observational study.



Canadian, university-based renal program.



Twelve anuric hemodialysis patients with chronic pain, established on immediate-release HM.



HM and H3G plasma concentrations were measured during and between hemodialysis treatments using a reverse-phase high-performance liquid chromatography assay with liquid chromatography/mass spectrometer/mass spectrometer detection. The McGill Pain Questionnaire (MPQ) and a Visual Analogue Scale (VAS) were used to measure pain. Noncompartmental analyses were conducted. Adverse effects were recorded.



HM did not substantially accumulate (accumulation factor R = 2.7 (1.6)), most likely due to the rapid conversion to H3G. Conversely, H3G accumulated between dialysis treatments (R = 12.5 (12.1)) but appeared to be effectively removed during hemodialysis (1.8 (0.7), p = 0.03). HM resulted in > 65 percent reduction in pain over dosing intervals. Mean MPQ pain scores decreased from 39.8 (18.2) to 12.3 (16.2) on dialysis and from 35.0 (18.5) to 15.5 (13.6) between dialysis treatments. Mean VAS pain scores decreased from 7.5 (2.5) to 3.0 (1.5) on dialysis and from 5.9 (3.2) to 4.4 (1.6) between dialysis treatments. No clinically significant opioid toxicity was observed. The accumulation of H3G between hemodialysis treatments was associated with greater sensory-type pain (r = 0.76, p < 0.0001) and reduced duration of analgesia.



HM may be a safe and effective opioid for use in selected hemodialysis patients.
Randomized clinical trial of 3 types of physical exercise for patients with Parkinson disease.

To compare the efficacy of treadmill exercises and stretching and resistance exercises in improving gait speed, strength, and fitness for patients with Parkinson disease.



A comparative, prospective, randomized, single-blinded clinical trial of 3 types of physical exercise.



The Parkinson's Disease and Movement Disorders Center at the University of Maryland and the Baltimore Veterans Affairs Medical Center, Geriatric Research Education and Clinical Center.



A total of 67 patients with Parkinson disease who had gait impairment were randomly assigned to 1 of 3 arms of the trial. INTERVENTIONS; (1) A higher-intensity treadmill exercise (30 minutes at 70%-80% of heart rate reserve), (2) a lower-intensity treadmill exercise (50 minutes at 40%-50% of heart rate reserve), and (3) stretching and resistance exercises (2 sets of 10 repetitions on each leg on 3 resistance machines [leg press, leg extension, and curl]). These exercises were performed 3 times a week for 3 months.



The primary outcome measures were gait speed (6-minute walk), cardiovascular fitness (peak oxygen consumption per unit time [$$ VO2], and muscle strength (1-repetition maximum strength).



All 3 types of physical exercise improved distance on the 6-minute walk: lower-intensity treadmill exercise (12% increase; P=.001), stretching and resistance exercises (9% increase; P<.02), and higher-intensity treadmill exercise (6% increase; P=.07), with no between-group differences. Both treadmill exercises improved peak $$ VO2 (7%-8% increase; P<.05) more than did the stretching and resistance exercises. Only stretching and resistance improved muscle strength (16% increase; P<.001).



The effects of exercise were seen across all 3 exercise groups. The lower-intensity treadmill exercise resulted in the greatest improvement in gait speed. Both the higher- and lower-intensity treadmill exercises improved cardiovascular fitness. Only the stretching and resistance exercises improved muscle strength. Therefore, exercise can improve gait speed, muscle strength, and fitness for patients with Parkinson disease. The combination of treadmill and resistance exercises may result in greater benefit and requires further investigation.
Long-term follow-up of lenalidomide in relapsed/refractory mantle cell lymphoma: subset analysis of the NHL-003 study

Mantle cell lymphoma (MCL) is an uncommon type of non-Hodgkin lymphoma with poor overall prognosis, requiring the development of new therapies. Lenalidomide is an immunomodulatory agent demonstrating antitumor and antiproliferative effects in MCL. We report results from a long-term subset analysis of 57 patients with relapsed/refractory MCL from the NHL-003 phase II multicenter study of single-agent lenalidomide in patients with aggressive lymphoma



Lenalidomide was administered orally 25 mg daily on days 1-21 every 28 days until progressive disease (PD) or intolerability. The primary end point was overall response rate (ORR).



Fifty-seven patients with relapsed/refractory, advanced-stage MCL had a median of three prior therapies. The ORR was 35% [complete response (CR)/CR unconfirmed (CRu) 12%], with a median duration of response (DOR) of 16.3 months (not yet reached in patients with CR/CRu) by blinded independent central review. The median time to first response was 1.9 months. Median progression-free survival was 8.8 months, and overall survival had not yet been reached. The most common grade 3/4 adverse events (AEs) were neutropenia (46%), thrombocytopenia (30%), and anemia (13%).



These results show the activity of lenalidomide in heavily pretreated, relapsed/refractory MCL. Responders had a durable response with manageable side-effects. Clinical trial number posted on www.clinicaltrials.gov NCT00413036.
Why Patients Continue to Participate in Clinical Research

Human immunodeficiency virus (HIV)infected individuals from Argentina, Brazil, and Thailand who had been participating in the Evaluation of Subcutaneous Proleukin (Interleukin-2) in a Randomized International Trial (ESPRIT) study for at least 6 months were invited to complete a self-administered survey on their experience and were asked why they continued to participate. The ESPRIT study is a phase 3, multinational, randomized trial comparing antiretroviral therapy plus interleukin 2 (IL-2) with antiretroviral therapy alone in individuals with HIV disease.
Frequency and Spectrum of Unexpected Clinical Manifestations of Primary HIV-1 Infection.

Prospectively and systematically collected data on frequency and spectrum of unexpected clinical manifestations during primary human immunodeficiency virus (HIV) infection (PHI) have not been published.



We prospectively enrolled 290 patients with documented PHI in the Zurich Primary HIV Infection Study. Typical acute retroviral syndrome (ARS) was defined as fever plus at least 1 symptom or sign typically considered to be associated with ARS; in absence of fever, presence of 2 or more ARS symptoms or signs. Atypical ARS was defined as lack of symptoms or signs, a single symptom or sign only and absence of fever, presence of symptoms or signs that are not considered typically associated with ARS, or occurrence of an opportunistic disease. Time to diagnosis was calculated based on estimated date of infection and first positive HIV test.



We analyzed 290 patients (271 males). PHI manifested with typical ARS in 202 (70%) and with atypical ARS in 88 (30%) patients. Patients with atypical ARS were hospitalized 4 times more often compared with typical ARS (43% vs 11%; P < .001). The gastrointestinal tract was the most frequent organ system affected in patients with atypical manifestations. Only in 112 (38%) patients was HIV infection suspected during the first medical attendance. Patients with typical ARS were diagnosed slightly earlier compared with atypical ARS, but this difference was not significant (P = .3).



Unexpected clinical presentations occurred in a large fraction of patients with PHI and were associated with substantial morbidity. Universal HIV testing may be mandatory in high-risk groups.
Macrophage Capping Protein CapG Is a Putative Oncogene Involved in Migration and Invasiveness in Ovarian Carcinoma

The actin binding protein CapG modulates cell motility by interacting with the cytoskeleton. CapG is associated with tumor progression in different nongynecologic tumor entities and overexpression in breast cancer cell lines correlates with a more invasive phenotype in vitro. Here, we report a significant CapG overexpression in 18/47 (38%) of ovarian carcinomas (OC) analyzed by qRealTime-PCR analyses. Functional analyses in OC cell lines through siRNA mediated CapG knockdown and CapG overexpression showed CapG-dependent cell migration and invasiveness. A single nucleotide polymorphism rs6886 inside the CapG gene was identified, affecting a CapG phosphorylation site and thus potentially modifying CapG function. The minor allele frequency (MAF) of SNP rs6886 (c.1004A/G) was higher and the homozygous (A/A, His335) genotype was significantly more prevalent in patients with fallopian tube carcinomas (50%) as in controls (10%). With OC being one of the most lethal cancer diseases, the detection of novel biomarkers such as CapG could reveal new diagnostic and therapeutic targets. Moreover, in-depth analyses of SNP rs6886 related to FTC and OC will contribute to a better understanding of carcinogenesis and progression of OC.
A phase I, pharmacokinetic and pharmacodynamic dose escalation trial of weekly paclitaxel with interferon-α2b in patients with solid tumors

Paclitaxel and interferon have demonstrated anti-angiogenic activity in vitro and in vivo. The toxicity, pharmacokinetics, and pharmacodynamics of paclitaxel with interferon-α2b (IFN-α2b) were assessed in patients with solid tumors to assess the feasibility of this novel anti-angiogenic regimen.  IFN-α2b (1 million units) was administered twice daily by subcutaneous injection. Paclitaxel was given weekly over 1 h starting at 30 mg/m2 and increased to 50 mg/m2. Cycles were repeated every 4 weeks.  Nineteen patients with a variety of solid tumors were enrolled. Dose-limiting toxicity in cycle 1 was observed at 50 mg/m2. Eleven patients were treated at 40 mg/m2 with no undue toxicity. Pharmacokinetic parameter comparison studies were completed in 11 patients who received days 1 and 29 paclitaxel. Mean paclitaxel clearance and area under the curve (0–∞) were not statistically different from days 1 to 29. There was a 50% increase in the average C max from days 1 to 29. There was also a 73% decrease of matrix metalloproteinase-9 (MMP-9) levels in these 11 patients from days 1 to 29 (p < 0.0005). All three patients with cutaneous angiosarcomas experienced clinically meaningful remissions. In addition, minor responses were observed in one patient with heavily pretreated ovarian cancer and another with adrenocortical carcinoma.  This trial details the inability to dose escalate to the maximum tolerated dose of weekly paclitaxel when combined with low-dose interferon. However, this low-dose regimen caused a significant decrease in MMP-9 and demonstrated anti-cancer activity in cutaneous angiosarcomas.
Exome Sequencing in a Family Identifies RECQL5 Mutation Resulting in Early Myocardial Infarction.

Coronary artery disease (CAD) including myocardial infarction (MI) is the leading cause of death worldwide and is commonly caused by the interaction between genetic factors and environmental risks. Despite intensive efforts using linkage and candidate gene approaches, the genetic etiology for the majority of families with a multigenerational early CAD /MI predisposition is unknown.In this study, we used whole-exome sequencing of 10 individuals from 1 early MI family, in which 4 siblings were diagnosed with MI before the age of 55, to identify potential predisposing genes.We identified a mutation in the RECQL5 gene, 1 of the 5 members of the RECQ family which are involved in the maintenance of genomic stability. This novel mutation, which is a TG insert at position 73,626,918 on the 13 chromosome and occurs before the last nucleotide of the introns 11 acceptor splice site affecting splicing of RECQL5. RT-PCR suggested the control subject had a full-length mRNA including exon 12, but the patients with RECQL5 mutation had a shorter mRNA form involving splicing of exons 11 to 13 directly, with skipping of exon 12. Quantitative RT-PCR analysis of RECQL5 exon 12 demonstrated that individuals whose genotype is mutant homozygote had only trace amounts of mRNA containing this exon and the family members who carry the heterozygous genotype had a level at 48% to 55% of the control's level.These findings provide insight into both the pathogenesis of MI and the role of RECQL5 gene in human disease.
Feasibility of a randomized trial on adjuvant radio-iodine therapy in differentiated thyroid cancer.

Justification for adjuvant radio-iodine (I-131) therapy in differentiated thyroid cancer (DTC) is purely based on retrospective data. This is true for ablative therapy and even more so for high-dosage adjuvant schedules. Randomized trials on the latter application are considered impossible due to anticipated formidable sample sizes required in a disease with an overall excellent prognosis like DTC.



To develop and validate a model that could stratify for risk of recurrence, rather than survival, as is usually done in prognostic indices, and secondly, to use this model to estimate the sample size required for a randomized trial.



From databases of three large Dutch centres, we identified 342 consecutive patients without known residual DTC after (near-) total thyroidectomy. Using Cox proportional hazards analysis, a model was validated that clearly distinguished risk categories of recurrence using commonly available baseline variables. The model included age, N stage at presentation and T stage in papillary carcinoma. According to this stratification, a subset of patients at substantial risk for relapse (30-40%) was identified. They could be eligible for a trial assessing the impact of high-dose adjuvant I-131 on recurrence rates. Assuming a clinically relevant effect of 30% reduction of relapses, 290 patients would have to be entered in either arm (alpha 0.05, power 80%).



We conclude that even though a randomized trial on this issue will be difficult to design and conduct, sample size is not the main problem.