nils-herrmann/clean_scirepeval huggingface dataset:
Screening versus routine practice in detection of atrial fibrillation in patients aged 65 or over: cluster randomised controlled trial.

To assess whether screening improves the detection of atrial fibrillation (cluster randomisation) and to compare systematic and opportunistic screening.



Multicentred cluster randomised controlled trial, with subsidiary trial embedded within the intervention arm.



50 primary care centres in England, with further individual randomisation of patients in the intervention practices.



14,802 patients aged 65 or over in 25 intervention and 25 control practices.



Patients in intervention practices were randomly allocated to systematic screening (invitation for electrocardiography) or opportunistic screening (pulse taking and invitation for electrocardiography if the pulse was irregular). Screening took place over 12 months in each practice from October 2001 to February 2003. No active screening took place in control practices.



Newly identified atrial fibrillation.



The detection rate of new cases of atrial fibrillation was 1.63% a year in the intervention practices and 1.04% in control practices (difference 0.59%, 95% confidence interval 0.20% to 0.98%). Systematic and opportunistic screening detected similar numbers of new cases (1.62% v 1.64%, difference 0.02%, -0.5% to 0.5%).



Active screening for atrial fibrillation detects additional cases over current practice. The preferred method of screening in patients aged 65 or over in primary care is opportunistic pulse taking with follow-up electrocardiography.
Dose Escalation Study of Intravenous Estramustine Phosphate in Combination with Paclitaxel and Carboplatin in Patients with Advanced Prostate Cancer 1

The purpose is to determine a safe weekly dose of i.v. estramustine phosphate (EMP) to combine with weekly paclitaxel and monthly carboplatin in patients with advanced prostate cancer.  Patients with advanced prostate cancer (castrate and noncastrate) were administered escalating doses of weekly 1-h infusion of i.v. EMP (500–10001500 mg/m) in combination with weekly paclitaxel (100 mg/m over 1 h) and i.v. carboplatin (area under the curve 6 mg/ml-min every 4 weeks). Four weeks of therapy were considered one cycle. In the first three cohorts, EMP was given i.v. 3 h before paclitaxel. Cohorts 4 and 5 reversed the administration order: EMP (doses 1000–1500 mg/m) was given immediately after the end of paclitaxel infusion. Plasma levels of EMP and its metabolites, estramustine and estromustine, were monitored at time 0, at 120 min, and approximately at 20, 21, and 168 h from the start of EMP infusion. Paclitaxel concentrations were determined at basal (0), 30, 60, 90, and 120 min and 18 h after the start of paclitaxel infusion, and a concentration-time curve was estimated. Pharmacokinetic evaluation was performed in cycles 1 and 2 during the first week of therapy.  Nineteen patients were entered on the initial three dose levels (cohorts 1–3). Dose-limiting transient hepatic toxicity was encountered in cohort 3 (EMP 1500 mg/m). An additional 13 patients were treated with paclitaxel (100 mg/m) first, followed by i.v. EMP at 1000 mg/m (cohort 4), and 1500 mg/m (cohort 5). No dose-limiting toxicities were seen, and cohort 5 was determined safe for Phase II studies. Thromboembolic events were observed in 9% of patients (no prophylactic coumadin was used). Plasma concentrations of EMP and metabolites increased proportionally with dose. In all cohorts, there was a slight decrease in EMP and estramustine plasma concentrations between cycles 1 and 2. Although not significant, higher levels of estromustine at cycle 2 were observed in comparison to cycle 1. Decreased clearance of paclitaxel leading to higher than expected paclitaxel plasma concentrations was observed during the first cycle of therapy. Paclitaxel plasma concentrations were lower during cycle 2. In 17 patients with androgen-independent disease, 59% had >50% posttherapy decline in PSA and 22% showed measurable disease regression.  The regimen of weekly i.v. EMP in combination with paclitaxel and carboplatin can be safely administered with hepatic toxicity being transient and reversible. Pharmacokinetic results suggest that EMP competitively inhibits the biotransformation of paclitaxel after the first administration. This effect is counterbalanced, after repeated administrations, by a possible induction of the metabolic system caused by EMP. Phase II testing is ongoing to evaluate the efficacy of this combination.
Prognostic and therapeutic implications of pulmonary hypertension complicating degenerative mitral regurgitation due to flail leaflet: a multicenter long-term international study.

To determine the frequency, predictors, and outcome implications of pulmonary hypertension (PH) diagnosed by Doppler echocardiography in a large cohort of patients with the homogenous diagnosis of degenerative mitral regurgitation (MR) due to flail leaflets.



The Mitral Regurgitation International DAtabase (MIDA) is a registry including patients with MR due to flail leaflets consecutively referred at tertiary centres in Europe and the USA. Between 1987 and 2004, pulmonary artery systolic pressure (PASP) was measured at baseline by Doppler echocardiography in 437 patients (age 67 ± 11 years; 66% men). Pulmonary hypertension (PASP > 50 mmHg) was observed in 102 patients (23%). Independent predictors of PH were age and left atrial size (P < 0.0001). During a mean follow-up of 4.8 ± 2.8 years, PH was a strong independent predictor of death [adjusted HR 2.03 (1.30-3.18) P = 0.002], cardiovascular death [CVD; adjusted HR 2.21 (1.30-3.76) P = 0.003], and heart failure [adjusted HR 1.70 (1.10-2.62) P = 0.018]. Mitral valve surgery at any time during follow-up (performed in 325 patients, 75%) was beneficial [adjusted HR for death 0.22 (0.14-0.36) P < 0.001], but PH was associated with the increased risk of postoperative death and CVD (P = 0.01).



Pulmonary hypertension is a frequent complication of significant MR due to flail leaflet and is associated with major outcome implications, approximately doubling the risk of death and heart failure after diagnosis. Mitral valve surgery performed during follow-up is beneficial but does not completely abolish the adverse effects of PH once it is established and is particularly beneficial in patients without PH. These data support relieving PH secondary to MR due to flail leaflet, but also careful consideration for mitral surgery before PH is established.
Saccharomyces boulardii does not prevent relapse of Crohn's disease.

Saccharomyces boulardii is a probiotic yeast that has been shown to have beneficial effects on the intestinal epithelial barrier and digestive immune system. There is preliminary evidence that S boulardii could be used to treat patients with Crohn's disease (CD). We performed a randomized, placebo-controlled trial to evaluate the effects of S boulardii in patients with CD who underwent remission during therapy with steroids or aminosalicylates.



We performed a prospective study of 165 patients who achieved remission after treatment with steroids or salicylates; they were randomly assigned to groups given S boulardii (1 g/day) or placebo for 52 weeks. The primary end point was the percentage of patients in remission at week 52. Time to relapse, Crohn's disease activity index scores, and changes in parameters of inflammation were secondary end points.



CD relapsed in 80 patients, 38 in the S boulardii group (47.5%) and 42 in the placebo group (53.2%, a nonsignificant difference). The median time to relapse did not differ significantly between patients given S boulardii (40.7 weeks) vs placebo (39.0 weeks). There were no significant differences between groups in mean Crohn's disease activity index scores or erythrocyte sedimentation rates or in median levels of C-reactive protein. In a post hoc analysis, nonsmokers given S boulardii were less likely to experience a relapse of CD than nonsmokers given placebo, but this finding requires confirmation.



Although the probiotic yeast S boulardii is safe and well tolerated, it does not appear to have any beneficial effects for patients with CD in remission after steroid or salicylate therapies.
Sentinel node biopsy compared with complete axillary dissection for staging early breast cancer with clinically negative lymph nodes: results of randomized trial.

Sentinel lymph node (SLN) staging is currently used to avoid complete axillary dissection in breast cancer patients with negative SLNs. Evidence of a similar efficacy, in terms of survival and regional control, of this strategy as compared with axillary resection is based on few clinical trials. In 1998, we started a randomized study comparing the two strategies, and we present here its results.



Patients were randomly assigned to sentinel lymph node biopsy (SLNB) and axillary dissection [axillary lymph node dissection (ALND arm)] or to SLNB plus axillary resection if SLNs contained metastases (SLNB arm). Main end points were overall survival (OS) and axillary recurrence.



One hundred and fifteen patients were assigned to the ALND arm and 110 to the SLNB arm. A positive SLN was found in 27 patients in the ALND arm and in 31 in the SLNB arm. Overall accuracy of SLNB was 93.0%. Sensitivity and negative predictive values were 77.1% and 91.1%, respectively. At a median follow-up of 5.5 years, no axillary recurrence was observed in the SLNB arm. OS and event-free survival were not statistically different between the two arms.



The SLNB procedure does not appear inferior to conventional ALND for the subset of patients here considered.
Intraoperative Assessment of Left Atrial Diverticulum and Remnant Stump after Left Atrial Appendage Epicardial Occlusion.

Epicardial left atrial appendage (LAA) closure with use of occluder is an emerging technique. Absence of remnant LAA stump is major criterion of successful obliteration. The aim of study was to assess early success rate of epicardial LAA closure.



Fifteen patients with persistent AF and coronary artery disease underwent off-pump coronary revascularization with concomitant ablation and LAA epicardial occlusion with use of two types of occluders. Before incision and after appendage closure, TEE was performed to assess the LAA anatomy, diameter of left atrial ridge, and remnant LAA stump after occlusion.



In 80% (12) of patients, formation of a left atrial diverticulum was observed with the left atrial ridge forming the superior boundary. In 5 patients (33%), a minimal remnant LAA stump was found, none exceeding 1 cm (average length: 1.5 ± 2.3 mm). In all patients, blood flow in LAA cavity distal to the occluder was absent. There was no significant difference in LAA type, average left atrial diameter, LAA orifice, LAA length, left atrial ridge, or size of occluder used between patients with and without a remnant LAA stump. Occurrence of a remnant LAA stump correlated significantly with unfavorable anatomy (LAA orifice < 20 mm and LA ridge > 5 mm; r = 0.5774, P = 0.02).



The early success of epicardial LAA occlusion is not dependent on LAA morphologic type or occluder used. A minimal remnant LAA stump not exceeding 1 cm in length without distal blood flow was observed in one-third of the cases.
Pegylated interferon alpha-2b in patients with acute hepatitis C.

Kamal SM, Fouly AE, Kamel RR, Hockenjos B, Al Tawil A, Khalifa KE, He Q, Koziel MJ, El Naggar KM, Rasenack J, Afdhal NH. (Division of Gastroenterology and Liver Disease Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Department of Gastroenterology and Liver Diseases, Ain Shams University, Cairo, Egypt; Department of Gastroenterology and Hepatology, University of Freiburg, Germany.) Peginterferon alfa-2b therapy in acute hepatitis C: Impact of onset of therapy on sustained virologic response. Gastroenterology 2006;130:632–8.
Efficacy of Combination of Meloxicam and Pregabalin for Pain in Knee Osteoarthritis

Osteoarthritic pain is largely considered to be inflammatory pain. Sensory nerve fibers innervating the knee have been shown to be significantly damaged in rat models of knee osteoarthritis (OA) in which the subchondral bone junction is destroyed, and this induces neuropathic pain (NP). Pregabalin was developed as a pain killer for NP; however, there are no reports on pregabalin use in OA patients. The purpose of this study was to investigate the efficacy of pregabalin for pain in OA patients.



Eighty-nine knee OA patients were evaluated in this randomized prospective study. Patients were divided into meloxicam, pregabalin, and meloxicam+pregabalin groups. Pain scores were evaluated before and 4 weeks after drug application using a visual analogue scale (VAS), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Pain scales among groups were compared using a Kruskal-Wallis test.



Before drug application, there was no significant difference in VAS and WOMAC scores among the three groups (p>0.05). Significant pain relief was seen in the meloxicam+pregabalin group in VAS at 1, 2, and 4 weeks, and WOMAC score at 4 weeks, compared with the other groups (p<0.05). No significant pain relief was seen in the meloxicam only group in VAS during 4 weeks and WOMAC score at 4 weeks compared with the pregabalin only group (p>0.05).



Meloxicam+pregabalin was effective for pain in OA patients. This finding suggests that OA pain is a combination of inflammatory and NP.
Impact of the permanent ventricular pacing site on left ventricular function in children: a retrospective multicentre survey.

Chronic right ventricular (RV) pacing is associated with deleterious effects on cardiac function.



In an observational multicentre study in children with isolated atrioventricular (AV) block receiving chronic ventricular pacing, the importance of the ventricular pacing site on left ventricular (LV) function was investigated.



Demographics, maternal autoantibody status and echocardiographic measurements on LV end-diastolic and end-systolic dimensions and volumes at age <18 years were retrospectively collected from patients undergoing chronic ventricular pacing (>1 year) for isolated AV block. LV fractional shortening (LVFS) and, if possible LV ejection fraction (LVEF) were calculated. Linear regression analyses were adjusted for patient characteristics.



From 27 centres, 297 children were included, in whom pacing was applied at the RV epicardium (RVepi, n = 147), RV endocardium (RVendo, n = 113) or LV epicardium (LVepi, n = 37). LVFS was significantly affected by pacing site (p = 0.001), and not by maternal autoantibody status (p = 0.266). LVFS in LVepi (39 ± 5%) was significantly higher than in RVendo (33 ± 7%, p < 0.001) and RVepi (35 ± 8%, p = 0.001; no significant difference between RV-paced groups, p = 0.275). Subnormal LVFS (LVFS < 28%) was seen in 16/113 (14%) RVendo-paced and 21/147 (14%) RVepi-paced children, while LVFS was normal (LVFS ≥ 28%) in all LVepi-paced children (p = 0.049). These results are supported by the findings for LVEF (n = 122): LVEF was <50% in 17/69 (25%) RVendo- and in 10/35 (29%) RVepi-paced patients, while LVEF was ≥ 50% in 17/18 (94%) LVepi-paced patients.



In children with isolated AV block, permanent ventricular pacing site is an important determinant of LV function, with LVFS being significantly higher with LV pacing than with RV pacing.
Probiotic treatment of vancomycin-resistant enterococci: a randomised controlled trial. Comment.

To determine whether eating Lactobacillus rhamnosus GG (LGG) in the form of commercially available yoghurt improves clearance of vancomycin-resistant enterococci (VRE).  Double-blind, randomised, placebo-controlled trial.  Renal ward of Austin Health, a tertiary hospital, Feb-Oct 2005.  27 VRE-positive patients, 14 receiving active treatment and 13 controls.  Subjects were randomly assigned to either a treatment group (receiving 100 g daily of yoghurt containing LGG for 4 weeks) or a control group (receiving standard pasteurised yoghurt). Faecal samples were obtained three times at about weekly intervals. Treated patients were tested for VRE again at 8 weeks. Patients in the control group who had failed to clear VRE after 4 weeks were then given LGG-containing yoghurt for 4 weeks, as an open continuation.  Number of faecal specimens clear of VRE.  Of the 27 patients enrolled, 23 completed the study. Two patients were lost to follow-up, one died and one withdrew. All 11 patients in the treatment group who completed the study cleared VRE. Three subjects reverted to VRE positivity after using antibiotics to which LGG is sensitive, while all others remained negative for at least 4 weeks after trial completion. Twelve control subjects completed the study, of whom one cleared VRE and 11 remained VREpositive. Eight of these 11 patients were subsequently crossed over to receive LGG yoghurt, and all cleared VRE within 4 weeks.  To our knowledge, this is the first description of a probiotic therapy to successfully treat gastrointestinal carriage of VRE in renal patients. Further investigation of the use of LGG in VRE-positive patients is warranted.
The Calcimimetic agent AMG 073 lowers plasma parathyroid hormone levels in hemodialysis patients with secondary hyperparathyroidism.

Treatment with vitamin D sterols can lower plasma parathyroid hormone (PTH) in many patients with secondary hyperparathyroidism due to end-stage renal disease, but hypercalcemia, hyperphosphatemia, or both often develop during treatment. As such, alternative therapeutic approaches to managing excess PTH secretion are needed. Calcimimetic agents directly inhibit PTH secretion by activating the calcium-sensing receptor in the parathyroid glands, but clinical experience with them is limited. Fifty-two hemodialysis patients with secondary hyperparathyroidism were given single orally administered doses of the calcimimetic agent AMG 073 ranging from 5 to 100 mg, or placebo. Plasma PTH levels decreased 2 h after 25-, 50-, 75-, or 100-mg doses, falling by a maximum of 43 +/- 29%, 40 +/- 36%, 54 +/- 28%, or 55 +/- 39%, respectively. Plasma PTH levels decreased in all patients given doses of > or =25 mg but did not change in those who received placebo. In patients treated with daily doses of 25 or 50 mg of AMG 073 for 8 d, plasma PTH levels declined for the first 3 to 4 d and remained below baseline values after 8 d of treatment. Serum calcium concentrations also decreased by 5 to 10% from pretreatment levels in patients given 50 mg of AMG 073 for 8 d, but values were unchanged in those who received lower doses. Serum phosphorus levels and values for the calcium-phosphorus ion product both decreased after treatment with AMG 073. Thus, 8 d of treatment with AMG 073 effectively lowers plasma PTH levels and improves several disturbances in mineral metabolism that have been associated with soft tissue and vascular calcification and with adverse cardiovascular outcomes in patients with end-stage renal disease.
Reduction of insulin resistance by combined kidney-pancreas transplantation in Type 1 (insulin-dependent) diabetic patients

To evaluate the effect of combined kidney and pancreas transplantation on insulin action and glucose metabolism, 15 Type 1 (insulin-dependent) diabetic patients who were undergoing combined kidney-pancreas transplantation were studied before transplantation by means of the euglycaemic hyperinsulinaemic clamp technique combined with 3-3H-glucose infusion and indirect calorimetry. Nine of the original 15 patients were studied again after four months and six after 12 months, successful combined kidney-pancreas transplantation with the same experimental protocol. Nine volunteers formed the group of normal subjects. Combined kidney-pancreas transplantation normalised hepatic glucose production and reduced peripheral insulin resistance in Type 1 diabetic uraemic patients, despite chronic immunosuppressive therapy. To further evaluate the hypothesis that residual insulin resistance was due to chronic steroid therapy, 11 additional subjects with chronic uveitis (six of whom were treated with only prednisone, and five treated only with cyclosporin) underwent the same protocol demonstrating a normal hepatic glucose production. The insulin-stimulated peripheral glucose uptake was reduced in the prednisone-treated group, but normal in cyclosporin-treated subjects. Four additional diabetic patients with a kidney transplant were also studied. They showed a peripheral insulin sensitivity intermediate between diabetic uraemic patients and patients after combined transplant. We conclude that short-term (one year) combined kidney-pancreas transplantation improves glucose metabolism by restoring normal rates of hepatic glucose production and reducing peripheral insulin resistance; chronic steroid therapy is the major determinant of residual reduced insulin action. Both kidney and pancreas substitution play a role in reducing peripheral insulin resistance.
Relation of genetic polymorphisms in the cytochrome P450 gene with clopidogrel resistance after drug-eluting stent implantation in Koreans.

Clopidogrel is a prodrug that has to be converted to an active metabolite by hepatic cytochrome P450 (CYP) isoenzymes to inhibit platelet aggregation. Individual variability of platelet inhibition by clopidogrel suggests a possibility for genetic factors having a significant influence on clopidogrel responsiveness. In this study, we sought to determine the relation of genetic polymorphisms of CYP genes to clopidogrel resistance in Koreans. Four hundred fifty patients who underwent successful percutaneous coronary intervention with drug-eluting stents were randomly assigned to treatment with dual antiplatelet regimen (aspirin plus clopidogrel) or triple antiplatelet regimen (aspirin plus clopidogrel plus cilostazol). Clopidogrel resistance using VerifyNow P2Y12 assay and genetic analysis were performed in 387 patients. Clopidogrel resistance was found in 112 patients (28.9%). In the clopidogrel-responsive group, there was a significantly higher proportion of cilostazol use. Because cilostazol showed a significant influence on clopidogrel resistance, we examined the association of single-nucleotide polymorphisms and clopidogrel resistance in the dual and triple antiplatelet therapy groups, respectively. In all subjects, the CYP2C19*3A allele was significantly more prevalent in the clopidogrel-resistant group compared with the clopidogrel-responsive group. Multiple logistic regression analysis demonstrated that CYP2C19*3 is an independent predictor of clopidogrel resistance. In conclusion, CYP2C19*3 single-nucleotide polymorphisms is an independent risk factor of clopidogrel resistance in Korean subjects with coronary artery disease.