nils-herrmann/clean_scirepeval huggingface dataset:
Telaprevir with peginterferon and ribavirin for chronic HCV genotype 1 infection.

Current therapy for chronic hepatitis C virus (HCV) infection is effective in less than 50% of patients infected with HCV genotype 1. Telaprevir, a protease inhibitor specific to the HCV nonstructural 3/4A serine protease, rapidly reduced HCV RNA levels in early studies.



We randomly assigned patients infected with HCV genotype 1 to one of three telaprevir groups or to the control group. The control group (called the PR48 group) received peginterferon alfa-2a (180 microg per week) and ribavirin (1000 or 1200 mg per day, according to body weight) for 48 weeks, plus telaprevir-matched placebo for the first 12 weeks (75 patients). The telaprevir groups received telaprevir (1250 mg on day 1 and 750 mg every 8 hours thereafter) for 12 weeks, as well as peginterferon alfa-2a and ribavirin (at the same doses as in the PR48 group) for the same 12 weeks (the T12PR12 group, 17 patients) or for a total of 24 weeks (the T12PR24 group, 79 patients) or 48 weeks (the T12PR48 group, 79 patients). The primary outcome was a sustained virologic response (an undetectable HCV RNA level 24 weeks after the end of therapy).



The rate of sustained virologic response was 41% (31 of 75 patients) in the PR48 group, as compared with 61% (48 of 79 patients) in the T12PR24 group (P=0.02), 67% (53 of 79 patients) in the T12PR48 group (P=0.002), and 35% (6 of 17 patients) in the T12PR12 group (this group was exploratory and not compared with the control group). Viral breakthrough occurred in 7% of patients receiving telaprevir. The rate of discontinuation because of adverse events was higher in the three telaprevir-based groups (21%, vs. 11% in the PR48 group), with rash the most common reason for discontinuation.



Treatment with a telaprevir-based regimen significantly improved sustained virologic response rates in patients with genotype 1 HCV, albeit with higher rates of discontinuation because of adverse events.
Characterization of complicated carotid plaque with magnetic resonance direct thrombus imaging in patients with cerebral ischemia.

Thromboembolic disease secondary to complicated carotid atherosclerotic plaque is a major cause of cerebral ischemia. Clinical management relies on the detection of significant (>70%) carotid stenosis. A large proportion of patients suffer irreversible cerebral ischemia as a result of lesser degrees of stenosis. Diagnostic techniques that can identify nonstenotic high-risk plaque would therefore be beneficial. High-risk plaque is defined histologically if it contains hemorrhage/thrombus. Magnetic resonance direct thrombus imaging (MRDTI) is capable of detecting methemoglobin within intraplaque hemorrhage. We assessed this as a marker of complicated plaque and compared its accuracy with histological examination of surgical endarterectomy specimens.



Sixty-three patients underwent successful MRDTI and endarterectomy with histological examination. Of these, 44 were histologically defined as complicated (type VI plaque). MRDTI demonstrated 3 false-positive and 7 false-negative results, giving a sensitivity and specificity of 84%, negative predictive value of 70%, and positive predictive value of 93%. The interobserver (kappa=0.75) and intraobserver (kappa=0.9) agreement for reading MRDTI scans was good.



MRDTI of the carotid vessels in patients with cerebral ischemia is an accurate means of identifying histologically confirmed complicated plaque. The high contrast generated by short T1 species within the plaque allows for ease of interpretation, making this technique highly applicable in the research and clinical setting for the investigation of carotid atherosclerotic disease.
Acute ischemic brain lesions in infective endocarditis: incidence, related factors, and postoperative outcome.

Acute brain infarction affects the timing and regimen of cardiac surgery in patients with infective endocarditis (IE). We aimed to identify preoperative brain MRI characteristics, incidence, and related factors for acute ischemic lesions in left-sided IE patients undergoing cardiac surgery. Furthermore, we investigated whether preoperative acute ischemic lesions are associated with postoperative neurological complications in IE patients.



We retrospectively reviewed consecutive patients with a definite left-sided IE who underwent cardiac surgery in 6 university-affiliated hospitals from January 2004 to November 2011. Preoperative brain MRI evaluations were systematically performed on all patients without contraindications, regardless of neurological complications, with the aim of preventing perioperative complications. Patients were included if diffusion-weighted imaging and fluid-attenuated inversion recovery sequences were performed within 14 days after diagnosis. Associations between acute ischemic lesions and related factors were analyzed. Neurological complications within 30 days after surgery were evaluated for postoperative outcome analyses.



Of 139 consecutive patients with left-sided IE who underwent cardiac surgery, 85 patients were evaluated in this study. The mean age was 58 ± 16 years, and 22 patients (26%) were women. Preoperative MRI revealed acute ischemic lesions in 47 patients (55%), and 19 of these patients developed neurological symptoms. Among the patients with ischemic lesions, 24 (60%) had small lesions (<10 mm), 36 (77%) had multiple lesions, and 30 (64%) had lesions in multiple vascular territories. Compared to patients without ischemic lesions, patients with acute ischemic lesions were older and had significantly higher white blood cell counts and plasma C-reactive protein (CRP) levels, but lower hemoglobin levels. Logistic regression analyses showed that the white blood cell count and plasma CRP level were independently associated with acute ischemic lesions [adjusted OR per 1-SD increase were 2.21 (95% CI: 1.23-4.35) and 2.33 (95% CI: 1.27-4.96), respectively]. Three patients developed postoperative neurological complications, but preoperative acute ischemic lesions and postoperative complications were not associated.



Preoperative MRI detected a high incidence of asymptomatic ischemic lesions in IE patients. Acute ischemic lesions were often small, multiple, and located in multiple vascular territories. Inflammatory reactions may play an important role in the development of ischemic lesions in IE patients.
Evaluation of inter- and intrafractional motion of liver tumors using interstitial markers and implantable electromagnetic radiotransmitters in the context of image-guided radiotherapy (IGRT) – the ESMERALDA trial

With the development of more conformal and precise radiation techniques such as Intensity-Modulated Radiotherapy (IMRT), Stereotactic Body Radiotherapy (SBRT) and Image-Guided Radiotherapy (IGRT), patients with hepatic tumors could be treated with high local doses by sparing normal liver tissue. However, frequently occurring large HCC tumors are still a dosimetric challenge in spite of modern high sophisticated RT modalities. This interventional clinical study has been set up to evaluate the value of different fiducial markers, and to use the modern imaging methods for further treatment optimization using physical and informatics approaches.



Surgically implanted radioopaque or electromagnetic markers are used to detect tumor local-ization during radiotherapy. The required markers for targeting and observation during RT can be implanted in a previously defined optimal position during the oncologically indicated operation. If there is no indication for a surgical resection or open biopsy, markers may be inserted into the liver or tumor tissue by using ultrasound-guidance. Primary study aim is the detection of the patients' anatomy at the time of RT by observation of the marker position during the indicated irradiation (IGRT). Secondary study aims comprise detection and recording of 3D liver and tumor motion during RT. Furthermore, the study will help to develop technical strategies and mechanisms based on the recorded information on organ motion to avoid inaccurate dose application resulting from fast organ motion and deformation.



 The trial will evaluate the full potential of different fiducial markers to further optimize treatment of moving targets, with a special focus on liver lesions.
Coronary endothelial dysfunction after heart transplantation predicts allograft vasculopathy and cardiac death.

Coronary endothelial dysfunction may be an early marker for cardiac allograft vasculopathy (CAV) in orthotopic heart transplant recipients. Using serial studies with intravascular ultrasound and Doppler flow-wire measurements, we have previously demonstrated that annual decrements in coronary endothelial function are associated with progressive intimal thickening. The present study tested whether endothelial dysfunction predicts subsequent clinical events, including cardiac death and CAV development.



Seventy-three patients were studied yearly beginning at transplantation until a prespecified end point was reached. End points were angiographic evidence of CAV (>50% stenosis) or cardiac death (graft failure or sudden death). At each study, coronary endothelial function was measured with intracoronary infusions of adenosine (32-microgram bolus), acetylcholine (54 microgram over 2 minutes), and nitroglycerin (200 microgram) into the left anterior descending coronary artery; intravascular ultrasound images and Doppler velocities were recorded simultaneously. Of the 73 patients studied, 14 reached an end point during the study (6 CAV and 8 deaths, including 4 with known CAV, 1 graft failure, and 3 sudden). On the last study performed, the group with an end point had decreased epicardial (constriction of 11.1+/-2.9% versus dilation of 1.7+/-2.2%, P=0.01) and microvascular (flow increase of 75+/-20% versus 149+/-16%, P=0.03) endothelium-dependent responses to acetylcholine compared with the patients who did not reach an end point. Responses to adenosine and nitroglycerin did not differ significantly.



Endothelial dysfunction, as detected by abnormal responses to acetylcholine, preceded the development of clinical end points. These data implicate endothelial dysfunction in the development of clinically significant vasculopathy and suggest that serial studies of endothelial function have clinical utility.
Perinatal probiotic supplementation in the prevention of allergy related disease: 6 year follow up of a randomised controlled trial

Perinatal probiotics supplementation has been shown to be effective in the primary prevention of atopic dermatitis (AD) in early childhood, although the long term effects of probiotics on AD and other allergic diseases is less certain. We have previously reported a significant reduction in the cumulative incidence of AD at 2 years after maternal probiotic supplementation. In this study we present the effects of perinatal probiotics given to women from a general population on allergy related diseases in their offspring at 6 years.



Four hundred and fifteen pregnant women were randomised to receive probiotic or placebo milk in a double-blinded trial from 36 week gestation until 3 months postpartum. Probiotic milk contained Lactobacillus rhamnosos GG, L. acidophilus La-5 and Bifidobacterium animalis subsp. lactis Bb-12. At 6 years, children were re-assessed for AD, atopic sensitisation, asthma and allergic rhinoconjunctivitis (ARC).



At 6 years, 81 and 82 children were assessed for AD in the probiotic and placebo groups, respectively. In a multiple imputation analysis, there was as trend towards a lower cumulative incidence of AD in the probiotic group compared to the placebo group (OR 0.64, 95 % CI 0.39-1.07, p = 0.086; NNT = 10). This finding was statistically significantly in the complete case analysis (OR 0.48, 95 % CI 0.25-0.92, p = 0.027, NNT = 6). The prevalence of asthma and atopic sensitisation, and the cumulative incidence of ARC were not significantly affected by the probiotic regime at 6 years of age.



Maternal probiotic ingestion alone may be sufficient for long term reduction in the cumulative incidence of AD, but not other allergy related diseases.
Anti-infliximab and anti-adalimumab antibodies in relation to response to adalimumab in infliximab switchers and anti-tumour necrosis factor naive patients: a cohort study.

To investigate how antibodies against anti-tumour necrosis factor (anti-TNF) agents influence response after switching from infliximab to adalimumab in rheumatoid arthritis (RA).



This cohort study consisted of 235 patients with RA, all treated with adalimumab. At baseline 52 patients (22%) had been previously treated with infliximab ('switchers'), and 183 (78%) were anti-TNF naive. Disease activity (using the 28-joint count Disease Activity Score (DAS28)) and presence of antibodies against infliximab and adalimumab were assessed. Clinical response to adalimumab was compared between switchers and anti-TNF naive patients and their anti-infliximab and anti-adalimumab antibody status.



After 28 weeks of adalimumab treatment the decrease in DAS28 (Delta DAS28) for the 235 patients was 1.6+/-1.5 (mean+/-SD). Anti-adalimumab antibodies were detected in 46 patients (20%). Delta DAS28 was 1.8+/-1.4 in patients without anti-adalimumab and 0.6+/-1.3 in patients with anti-adalimumab (p<0.0001). Thirty-three of the 52 switchers (63%) had anti-infliximab antibodies. Patients with anti-infliximab more often developed anti-adalimumab than anti-TNF naive patients (11 (33%) vs 32 (18%); p=0.039). Delta DAS28 was greater for anti-TNF naive patients (1.7+/-1.5) than for switchers without anti-infliximab antibodies (Delta DAS28=0.9+/-1.4) (p=0.009). Delta DAS28 for switchers with anti-infliximab was 1.2+/-1.3 and did not differ significantly from anti-TNF naive patients (p=0.262).



Switchers with anti-infliximab antibodies more often develop antibodies against adalimumab than anti-TNF naive patients. Response to adalimumab was limited in switchers without anti-infliximab antibodies, which raises the question whether a second anti-TNF treatment should be offered to patients with RA for whom an initial treatment with an anti-TNF blocker fails, in the absence of anti-biological antibodies.
Effect of intranasal steroids on rhinosinusitis after radiotherapy for nasopharyngeal carcinoma: clinical study.

Post-irradiation rhinosinusitis is one of the most common untoward side effects in patients with nasopharyngeal carcinoma. This study aimed to evaluate the effect of fluticasone propionate aqueous nasal spray on post-irradiation rhinosinusitis.



Nasopharyngeal carcinoma patients who had undergone radiotherapy and subsequently developed chronic rhinosinusitis were randomised to receive either fluticasone propionate aqueous nasal spray 200 µg plus nasal irrigation or a single nasal irrigation, for six months. A questionnaire, nasal endoscopy and computed tomography were used to evaluate rhinosinusitis severity, at the beginning of treatment, and at three and six months after treatment.



The group who received fluticasone propionate aqueous nasal spray combined with irrigation had fewer nasal complaints (overall symptoms, blocked nose and headache were reduced), a better quality of life and less severe endoscopic findings than those who only received nasal irrigation at three and six months after treatment.



Nasal steroids are a safe and effective therapy for patients with post-irradiation rhinosinusitis.
Clinical and genetic heterogeneity of right bundle branch block and ST-segment elevation syndrome: A prospective evaluation of 52 families.

The ECG pattern of right bundle branch block and ST-segment elevation in leads V(1) to V(3) (Brugada syndrome) is associated with high risk of sudden death in patients with a normal heart. Current management and prognosis are based on a single study suggesting a high mortality risk within 3 years for symptomatic and asymptomatic patients alike. As a consequence, aggressive management (implantable cardioverter defibrillator) is recommended for both groups.



Sixty patients (45 males aged 40+/-15 years) with the typical ECG pattern were clinically evaluated. Events at follow-up were analyzed for patients with at least one episode of aborted sudden death or syncope of unknown origin before recognition of the syndrome (30 symptomatic patients) and for patients without previous history of events (30 asymptomatic patients). Prevalence of mutations of the cardiac sodium channel was 15%, demonstrating genetic heterogeneity. During a mean follow-up of 33+/-38 months, ventricular fibrillation occurred in 5 (16%) of 30 symptomatic patients and in none of the 30 asymptomatic patients. Programmed electrical stimulation was of limited value in identifying patients at risk (positive predictive value 50%, negative predictive value 46%). Pharmacological challenge with sodium channel blockers was unable to unmask most silent gene carriers (positive predictive value 35%).



At variance with current views, asymptomatic patients are at lower risk for sudden death. Programmed electrical stimulation identifies only a fraction of individuals at risk, and sodium channel blockade fails to unmask most silent gene carriers. This novel evidence mandates a reappraisal of therapeutic management.
[Impact of late treatment-related radiotherapy toxicity, depression, and anxiety on quality of life in long-term breast cancer survivors].

This study aimed to assess the impact of late treatment toxicity (especially radiotherapy toxicity), chemoradiotherapy treatment type (concurrent or sequential), depression and anxiety on overall, physical and emotional quality of life (QoL) in long-term breast cancer survivors.  We assessed 117 patients (mean follow-up since the end of treatment = 8.1 years) for late radiotherapy toxicity (LENT-SOMA scale), patient and doctor ratings of breast cosmetic outcomes, QoL (EORTC QLQ-C30), depression and anxiety (Hospital and Anxiety Depression scale).



In univariate analyses, factors associated with significantly decreased QoL were: use of sequential treatment and decreased overall QoL (P = 0.002) and emotional QoL (P = 0.02) ; few radiotherapy late toxicity symptoms (pain and decreased physical QoL, P = 0.01 ; fibrosis and decreased emotional QoL, P = 0.04) ; probable depression or probable anxiety and decreased overall, physical and emotional QoL (P ≤ 0.005). In multivariate analyses, probable depression and probable anxiety were the most stronger predictors for decreased QoL in the overall, physical and emotional domains (P ≤ 0.02).



Improving screening for and treatment of depression and anxiety might improve QoL in long-term breast cancer survivors.
No relation between cephalic venous dilatation and pain in migraine.

Evidence for the involvement of the cranial arterial system in migraine is plentiful, but it is unclear whether the cranial venous system may be involved in the mechanism of migraine pain. Venules are the preferentially involved vessels in the neurogenic inflammation animal model of migraine. The cranial and cerebral veins and sinuses are pain sensitive and receive sensory innervation from the trigeminal nerve. If the veins are involved in migraine pathogenesis, a venous dilatation would presumably be painful. The effect of a short lasting cranial venous dilatation, induced by applying pressure on the internal jugular veins (Queckenstedt's manoeuvre), was therefore compared with a placebo procedure, consisting of an equal pressure applied on to the lateral aspect of the neck. In each procedure pressure was applied for 10 seconds. The study used a single blind, randomised, cross over design, and 20 patients with an acute attack of migraine without aura participated. After each procedure, headache intensity was rated on a standardised five point scale. After Queckenstedt's manoeuvre 40% of the patients reported no change in headache intensity, 25% a worsening, and 35% an improvement of their headache. No significant difference between the headache intensity ratings during Queckenstedt's manoeuvre and the placebo manoeuvre was found (p=0.22). The findings make it unlikely that the cephalic venous system is of major importance in migraine pain mechanisms and, therefore, also less likely that neurogenic inflammation plays a significant part in humans during attacks of migraine without aura.
Prospective crossover comparison of carvedilol and metoprolol in patients with chronic heart failure.

This study investigates the effects of a change of beta-adrenergic blocking agent treatment from metoprolol to carvedilol and vice versa in patients with heart failure (HF).



Beta-blockers improve ventricular function and prolong survival in patients with HF. It has recently been suggested that carvedilol has more pronounced effects on left ventricular ejection fraction (LVEF) compared with metoprolol. It is uncertain whether a change from one beta-blocker to the other is safe and leads to any change of left ventricular function.



Forty-four patients with HF due to ischemic (n = 17) or idiopathic cardiomyopathy (n = 27) that had responded well to long-term treatment with either metoprolol (n = 20) or carvedilol (n = 24) were switched to an equivalent dose of the respective other beta-blocker. Before and six months after crossover of treatment, echocardiography, radionuclide ventriculography and dobutamine stress echocardiography were performed.



Six months after crossover of beta-blocker treatment, LVEF had further improved with both carvedilol and metoprolol (carvedilol: 32 +/- 3% to 36 +/- 4%; metoprolol: 27 +/- 4% to 30 +/- 5%; both p < 0.05 vs. baseline), without interindividual differences. There were no changes in either New York Heart Association functional class or any other hemodynamic parameters at rest. Dobutamine stress echocardiography revealed a more pronounced increase of heart rate after dobutamine infusion in metoprolol- compared with carvedilol-treated patients. After dobutamine infusion, LVEF increased in the carvedilol- but not in the metoprolol-treated group.



When switching treatment from one beta-blocker to the other, improvement of LVEF in patients with HF is maintained. Despite similar long-term effects on hemodynamics at rest, beta-adrenergic responsiveness is different in both treatments.
Pharmacokinetics and pharmacodynamics of imipenem during continuous renal replacement therapy in critically ill patients.

The pharmacokinetics of imipenem were studied in adult intensive care unit (ICU) patients during continuous venovenous hemofiltration (CVVH; n=6 patients) or hemodiafiltration (CVVHDF; n=6 patients). Patients (mean+/-standard deviation age, 50.9+/-15.9 years; weight, 98.5+/-15.9 kg) received imipenem at 0.5 g every 8 to 12 h (total daily doses of 1 to 1.5 g/day) by intravenous infusion over 30 min. Pre- and postmembrane blood (plasma) and corresponding ultrafiltrate or dialysate samples were collected 1, 2, 4, and 8 or 12 h (depending on dosing interval) after completion of the drug infusion. Drug concentrations were measured using validated high-performance liquid chromatography methods. Mean systemic clearance (CL(S)) and elimination half-life (t1/2) of imipenem were 145+/-18 ml/min and 2.7+/-1.3 h during CVVH versus 178+/-18 ml/min and 2.6+/-1.6 h during CVVHDF, respectively. Imipenem clearance was substantially increased during both CVVH and CVVHDF, with membrane clearance representing 25% and 32% of CL(S), respectively. The results of this study indicate that CVVH and CVVHDF contribute to imipenem clearance to a greater degree than previously reported. Imipenem doses of 1.0 g/day appear to achieve concentrations adequate to treat most common gram-negative pathogens (MIC up to 2 microg/ml) during CVVH or CVVHDF, but doses of 2.0 g/day or more may be required to adequately treat and prevent resistance in pathogens with higher MICs (MIC=4 to 8 microg/ml). Higher doses should only be used after consideration of potential central nervous system toxicities or other risks of therapy in these severely ill patients.