nils-herrmann/clean_scirepeval huggingface dataset:
Inhibition of IK,ACh current may contribute to clinical efficacy of class I and class III antiarrhythmic drugs in patients with atrial fibrillation

Inward rectifier potassium currents IK1 and acetylcholine activated IK,ACh are implicated in atrial fibrillation (AF) pathophysiology. In chronic AF (cAF), IK,ACh develops a receptor-independent, constitutively active component that together with increased IK1 is considered to support maintenance of AF. Here, we tested whether class I (propafenone, flecainide) and class III (dofetilide, AVE0118) antiarrhythmic drugs inhibit atrial IK1 and IK,ACh in patients with and without cAF. IK1 and IK,ACh were measured with voltage clamp technique in atrial myocytes from 58 sinus rhythm (SR) and 35 cAF patients. The M-receptor agonist carbachol (CCh; 2 µM) was employed to activate IK,ACh. In SR, basal current was not affected by either drug indicating no effect of these compounds on IK1. In contrast, all tested drugs inhibited CCh-activated IK,ACh in a concentration-dependent manner. In cAF, basal current was confirmed to be larger than in SR (at −80 mV, −15.2 ± 1.2 pA/pF, n = 88/35 vs. −6.5 ± 0.4 pA/pF, n = 194/58 [myocytes/patients]; P < 0.05), whereas CCh-activated IK,ACh was smaller (−4.1 ± 0.5 pA/pF vs. −9.5 ± 0.6 pA/pF; P < 0.05). In cAF, receptor-independent constitutive IK,ACh contributes to increased basal current, which was reduced by flecainide and AVE0118 only. This may be due to inhibition of constitutively active IK,ACh channels. In cAF, all tested drugs reduced CCh-activated IK,ACh. We conclude that in cAF, flecainide and AVE0118 reduce receptor-independent, constitutively active IK,ACh, suggesting that they may block IK,ACh channels, whereas propafenone and dofetilide likely inhibit M-receptors. The efficacy of flecainide to terminate AF may in part result from blockade of IK,ACh.
Randomized mammographic screening for breast cancer in Stockholm

In March 1981 a randomized single-view mammographic screening for breast cancer was started in the south of Stockholm. The screened population in the first round numbered 40,318 women, and 20,000 women served as a well-defined control group. The age groups represented were 40–64 years, and 80.7% of the invited women participated in the study. The first round disclosed 128 breast cancers (113 invasive and 15 noninvasive), or 4.0 per 1,000 women. Mean tumour size was 14.1 mm and axillary lymph node metastases were found in 21.8%. Fifty-five per cent of the tumours were small (⩽10 mm) or non-invasive, and 71% were stage I. Participation rates are high in all Swedish trials. The present results differ only slightly from other screening programs; the percentages of patients with axillary metastases and stage II tumours are similar in the Stockholm, Malmö and Kopparberg/Östergötland studies. Comparisons of cancer prevalence in the various Swedish screening trials show that, in comparable age groups, there are some differences, even when the differences in the natural cancer incidence are taken into account. A decreased mortality was found recently in a Swedish trial in ages above 50 years but not below. In the Stockholm study more than one-third of the participants were aged 40–49 years.
Safety and efficacy of oral fexofenadine in children with seasonal allergic rhinitis--a pooled analysis of three studies.

Allergic rhinitis is one of the most common clinical conditions in children; however, data regarding the safety of antihistamines in children with seasonal allergic rhinitis are limiting. To evaluate the safety and efficacy of fexofenadine in children with seasonal allergic rhinitis, data were pooled from three, double-blind, randomized, placebo-controlled, parallel-group, 2-week trials in children (6-11 year) with seasonal allergic rhinitis. All studies assessed fexofenadine HCl 30 mg b.i.d.; two studies included fexofenadine HCl at 15 and 60 mg b.i.d. Patients (and investigators) reported any adverse events during the trial. Physical examinations, including measurements of vital signs and laboratory tests, were performed. Efficacy assessments (total symptom score and individual symptom scores) were evaluated. Exposure to fexofenadine HCl 30 mg b.i.d. and to any fexofenadine dose exceeded 10,000 and 17,000 patient days, respectively. Incidences of adverse events, and discontinuations because of adverse events, were low and similar across treatment groups. In the placebo group, 24.4% of subjects reported adverse events compared with 24.1% for fexofenadine HCl 30 mg b.i.d., and 28.4% for all fexofenadine-treated groups. The most common adverse event overall was headache (4.3% placebo; 5.8% fexofenadine HCl 30 mg b.i.d.; and 7.2% any fexofenadine doses). Treatment-related adverse events were similar across treatment groups with no sedative effects. Fexofenadine HCl 30 mg b.i.d. was significantly superior to placebo in reducing the total symptom score and all individual seasonal allergic rhinitis symptoms, including nasal congestion (p < 0.05). Fexofenadine, at doses of up to 60 mg b.i.d., is safe and non-sedating, and fexofenadine HCl 30 mg b.i.d. effectively reduces all seasonal allergic rhinitis symptoms in children aged 6-11 years.
Validation of a database on acrylamide for use in epidemiological studies

Acrylamide, a probable human carcinogen, was detected in various heat-treated foods such as French fries and potato crisps. Recently, positive associations have been found between dietary acrylamide intakes, as estimated with a food frequency questionnaire using an acrylamide database, and cancer risk in some epidemiological studies. As acrylamide levels vary considerably within the same type of foods, a validation study was performed to investigate whether use of an acrylamide food database containing calculated mean acrylamide content, based on extensive sampling and chemical analysis of Dutch foods (several samples per food), can classify subjects with respect to true acrylamide intake.We used the data from a 24-h duplicate diet study. The acrylamide content of 39 Dutch 24-h duplicate diets collected in 2004 was estimated using the mean acrylamide levels of foods available from the database and the menu list, on which the participants of the duplicate diet study had listed the amounts of individual foods and drinks in household units. Next, the acrylamide content of the total duplicate diets was analytically measured and correlated to the estimated acrylamide contents.The Spearman's correlation coefficient between chemically determined acrylamide content and the calculated acrylamide content of the duplicate diets was 0.82 (P<0.001).Conclusions:This study indicates that it is possible to classify subjects with respect to acrylamide intake if mean instead of actual content of each food is applied. The database can therefore be applied in epidemiological studies on acrylamide intake and cancer risk, such as the Netherlands Cohort Study on Diet and Cancer.
Thermoablation of Liver Metastases: Efficacy of Temporary Celiac Plexus Block

To determine the efficacy of celiac plexus block during thermoablation of liver metastases. Fifty-five consecutive patients underwent thermoablation therapy of liver tumors by laser-induced thermotherapy. Twenty-nine patients received a temporary celiac plexus block, 26 patients acted as control group. In both groups fentanyl and midazolam were administered intravenously upon request of the patient. The duration of the intervention, consumption of opiates, and individual pain sensations were documented. No complications resulting from the celiac plexus block were recorded. Celiac plexus block significantly reduced the amount of pain medication used during thermoablation therapy of liver tumors (with block, 2.45 μg fentanyl per kg body weight; without block, 3.58 μg fentanyl per kg body weight, p < 0.05; midazolam consumption was not reduced) in patients with metastases ≤5 mm from the liver capsule. For metastases farther away from the capsule no significant differences in opiate consumption were seen. Celiac plexus block reduced the time for thermoablation significantly (178 min versus 147 min, p < 0.05) no matter how far the metastases were from the liver capsule. Average time needed to set the block was 12 min (range 9–15 min); additional costs for the block were marginal. As expected (as pain medications were given according to individual patients’ needs) pain indices did not differ significantly between the two groups. In patients with liver metastases ≤5 mm from the liver capsule, celiac plexus block reduces the amount of opiates necessary, simplifying patient monitoring. In addition celiac plexus block reduces intervention time, with positive effects on overall workflow for all patients.
Recombinant vaccinia/fowlpox NY-ESO-1 vaccines induce both humoral and cellular NY-ESO-1-specific immune responses in cancer patients.

NY-ESO-1 is a cancer/testis antigen expressed in a range of human malignancies, and a number of vaccine strategies targeting NY-ESO-1 are being developed. In the present study, the safety and immunogenicity of recombinant vaccinia-NY-ESO-1 and recombinant fowlpox-NY-ESO-1 were analyzed in a series of 36 patients with a range of different tumor types. Each construct was first tested individually at two different dose levels and then in a prime-boost setting with recombinant vaccinia-NY-ESO-1 followed by recombinant fowlpox-NY-ESO-1. The vaccines were well tolerated either individually or together. NY-ESO-1-specific antibody responses and/or specific CD8 and CD4 T cell responses directed against a broad range of NY-ESO-1 epitopes were induced by a course of at least four vaccinations at monthly intervals in a high proportion of patients. CD8 T cell clones derived from five vaccinated patients were shown to lyse NY-ESO-1-expressing melanoma target cells. In several patients with melanoma, there was a strong impression that the natural course of the disease was favorably influenced by vaccination.
Laparoscopic Placement of Peritoneal Dialysis Catheter (Same Day Dialysis)

Peritoneal dialysis (PD) remains the generally accepted method for management of renal failure in chronic and acute renal failure. Despite the rapidly increasing use of continuous ambulatory peritoneal dialysis (CAPD) since its introduction, controversy persists as to the efficacy and exact role of the modality in the treatment of end stage renal failure. The aim of this paper is to present the experience with laparoscopic placement of a peritoneal dialysis catheter and starting the peritoneal dialysis on the same day.



The laparoscopic placement of a peritoneal dialysis catheter was performed on 11 patients (10 males and 1 female) with an average age of 35 years, over a 12-month period. The procedure was done using two 5 mm abdominal trocars. The precise position of the catheter on the pelvis was ensured laparoscopically. One to two liters exchange dialysis was used for every patient, and no leakage was recorded.



The patients tolerated the procedure well. The peritoneal dialysis was started immediately. Patients were discharged after an overnight stay, and PD was carried out routinely.



The results of laparoscopic placement of a peritoneal dialysis catheter show the following advantages: minimal incision; less surgical trauma; the procedure hastens the early start of peritoneal dialysis and has no complications.
Estimation of residual glomerular filtration rate in dialysis patients from the plasma cystatin C level.

Residual renal function influences morbidity, mortality and quality of life of chronic dialysis patients. Residual glomerular filtration rate (rGFR) is therefore an important parameter in the follow-up of these patients. Because rGFR is measured as the mean of creatinine and urea clearance, a complete 24 h urine collection is essential, but often very difficult to manage for these patients.



We investigated if plasma cystatin C (cysC) could give a good estimate of rGFR in dialysis patients and compared it to the measured rGFR, as well as to the rGFR estimate obtained with the Modification of Diet in Renal Disease (MDRD) formula. A total of 465 patients were included in this study. CysC levels of 215 haemodialysis (HD) and 95 chronic ambulatory peritoneal dialysis (PD) patients were used to derive a formula for rGFR. This formula was tested in the validation group of 107 HD and 48 PD patients.



The cysC formula derived in the modelling group was rGFR = -0.70 + 22 x (1/cysC). The mean estimated rGFR obtained with this formula in the validation group was not significantly different from the mean measured rGFR: difference 0.19 ml/min/1.73 m(2), 95% confidence interval (CI) -2.37 to 2.75 ml/min/1.73 m(2). The MDRD formula gave a larger difference from the mean measured rGFR (3.13 ml/min/1.73 m(2)) and a much wider 95% CI (-1.29 to 7.55 ml/min/1.73 m(2)). A separate model for HD and PD patients did not improve the estimation of rGFR.



The cysC formula showed better accuracy and precision than the MDRD formula. Therefore the cysC formula and not the MDRD formula should be used to calculate rGFR in dialysis patients when no 24 h urine sample is available.
Mild hypothermia after intravenous thrombolysis in patients with acute stroke: a randomized controlled trial.

Hypothermia improves outcome in resuscitated patients and newborns with hypoxic brain injury. We studied the safety and feasibility of mild hypothermia in awake patients with stroke after intravenous thrombolysis.



Patients were randomized 1:1 to mild hypothermia (35°C) or to standard stroke unit care within 6 hours of symptom onset. Hypothermia was induced with a surface-cooling device and cold saline infusions. Active cooling was restrained gradually after 12 hours at <35.5°C. The primary outcome measure was the number of patients with <36°C body temperature for >80% of the 12-hour cooling period.



We included 36 patients with a median of National Institutes of Health Stroke Scale score of 9 one hour after thrombolysis. Fifteen of 18 (83%) patients achieved the primary end point. Sixteen (89%) patients reached <35.5°C in a median time of 10 hours (range, 7-16 hours) from symptom onset, spent 10.5 hours (1-17 hours) in hypothermia, and were back to normothermia in 23 hours (15-29 hours). Few serious adverse events were more common in the hypothermia group. At 3 months, 7 patients (39%) in both groups had good outcome (modified Ranking Scale, 0-2), whereas poor outcome (modified Ranking Scale, 4-6) was twice as common in the normothermia group (44% versus 22%).



Mild hypothermia with a surface-cooling device in an acute stroke unit is safe and feasible in thrombolyzed, spontaneously breathing patients with stroke, despite the adverse events.
Low plasma eicosapentaenoic acid and depressive symptomatology are independent predictors of dementia risk.

The potential preventive role of polyunsaturated fatty acids (PUFAs) in Alzheimer disease has aroused increasing interest. Plasma n-3 PUFAs have been shown to be inversely related to the risk of dementia and to depression, which is frequently associated with dementia.



The objective was to ascertain whether plasma PUFAs predict the risk of incident dementia in a cohort of older persons, independently of their depressive status.



Of 1214 nondemented participants in the Three-City Study from Bordeaux (France) who were followed up for 4 y, 65 developed dementia. The association between the proportion of plasma fatty acids at baseline and the risk of incident dementia was assessed by multivariate proportional hazard models, taking into account depressive status assessed on the basis of the Center for Epidemiologic Studies Depression scale.



A higher plasma eicosapentaenoic acid (EPA) concentration was associated with a lower incidence of dementia [hazard ratio (HR) for 1 SD = 0.69; 95% CI: 0.48, 0.98], independently of depressive status and after adjustment for age, education, apolipoprotein E epsilon4 allele, diabetes, and baseline plasma vitamin E and triacylglycerol. The relations between docosahexaenoic acid (DHA), total n-3 PUFAs, and incident dementia did not remain significant in multivariate models. Higher ratios of arachidonic acid (AA) to DHA and of n-6 to n-3 fatty acids were related to an increased risk of dementia, particularly in depressive subjects (n = 90): ratio of AA to DHA (HR: 2.65; 95% CI: 1.07, 6.56) and ratio of n-6 to n-3 (HR: 1.61; 95% CI: 1.04, 2.47).



A high plasma EPA concentration may decrease the risk of dementia, whereas high ratios of n-6 to n-3 fatty acids and of AA to DHA may increase the risk of dementia, especially in depressed older persons. The role of EPA in dementia warrants further research.
Validation of Grace Risk Score in predicting in-hospital mortality in patients with non ST-elevation myocardial infarction and unstable angina.

To validate the global registry of acute coronary event (grace) risk score in a Pakistani population at Tabba Heart Institute Karachi in patients with non ST-Elevation Myocardial Infarction (NSTEMI) and Unstable Angina (UA).



In this prospective Observational registry study, 530 adults hospitalized patients with a diagnosis of Non-ST-Elevation Myocardial Infarction and unstable angina were enrolled between March 2012 and August 2012 at the Tabba Heart Institute, Karachi, Pakistan. For each patient, the grace risk score was calculated and its discrimination evaluated and correlated with in-hospital mortality using the Kendall's tau-b bivariate correlation test. Each patient was grouped either into high, intermediate or low risk groups according to their GRS.



A total of 530 patients with NSTEMI and UA were included; the overall mean grace risk score in our population was 131.87 +/- 41.56. The GRACE Risk Score showed good discrimination, with Area under the ROC curve of 0.803 (95% CI 0.705-0.902, P < 0.001). During the in-hospital stay, total of 19 (3.6%) patients died, and out of those 15 (8.4%) patients belonged to high risk group.



GRACE RS strongly validates the in-hospital mortality among our patient population presenting with a wide spectrum of complications. However, more multicentre registries on a larger population with long-term follow up are required to study detailed trends in our population.
Question of ALT flare during switch to adefovir from lamivudine: A single center open-label, randomized, safety study (June 17, 2005 to February 5, 2009).

Earlier clinical studies have reported an ALT flare greater than 10 times the upper limit of normal in some patients with chronic hepatitis B when their lamivudine (LAM) treatment was switched to adefovir (ADV) therapy. The current study compared the safety of switching directly to ADV versus overlapping LAM and ADV for 3 months followed by ADV monotherapy. Patients with chronic hepatitis B receiving LAM therapy for > or = 6 months were eligible for the study regardless of the presence of LAM resistance, HBeAg status or serum ALT levels. Eighteen patients (13 males) were randomized to direct switch to ADV and 17 patients (10 males) to overlap. HBV-DNA, ALT, albumin, and total bilirubin were assayed at baseline, 3, 6, 9, and 12 months. Study drugs were discontinued at the end of 12 months with the follow up at 3 and 6 months. The decision to continue antiviral therapy was made at the discretion of the investigator. Baseline ALT levels were similar between the direct switch and overlap group: median ALT (U/L) was 44.0 (16-266) and 33.0 (19-367) for direct switch for overlap group, respectively (P = 0.42). No ALT flare was noted at 3 months in either group: median ALT decreased from 44.0 to 34.5 U/L in the direct switch group, and from 33.0 to 23.0 in the overlap group. Furthermore, no patient in either group exhibited ALT flare throughout the 12 months. This study did not show an ALT flare during switch to ADV at 3 months or at any time later.
Ambulatory impedance cardiography in hypertension: a validation study.

The management of hypertension is improved by knowledge of the hemodynamics underlying blood pressure. Impedance Cardiography (ICG) provides data on a range of hemodynamic variables that affect blood pressure. However, ICG captures only fixed descriptions of hemodynamic characteristics. Improvements in ambulatory technology have led to the development of the Ambulatory Impedance Monitor (AIM) which records hemodynamic data during the activities of daily living. The purpose of this study was to evaluate the sensitivity of the AIM to detect hemodynamic changes associated with postural shift in persons with hypertension. Using a repeated measures cross-over design, sitting and standing hemodynamic measures were taken in seventeen persons with hypertension while wearing the AIM-BpTRU system designed for standard office use and the AIM-Spacelabs system designed for ambulatory monitoring. Both AIM-blood pressure monitoring systems detected significant changes from sitting to standing posture in heart rate (p=0.03), stroke volume (p=0.002), left ventricular ejection time (p<0.001), systemic vascular resistance (p=0.03) and diastolic blood pressure (p<0.001). Additionally, both systems generated measures of cardiac function that were positively correlated (p<0.001) and not significantly different (p>0.05). Our findings support previous work and demonstrate that the AIM provides valid and reliable estimates of cardiac function in persons with hypertension.
Comparison of 60-day mortality in hospitalized heart failure patients with versus without hypothermia.

The use of aggressive treatments and the modification of current treatment in patients with heart failure (HF) relies heavily on the assessment of disease severity using prognostic markers. However, many such markers are unavailable in routine clinical practice, and others have little prognostic value. This study tested the hypothesis that low body temperature could predict short-term survival after discharge in patients hospitalized for HF. Data from the Acute and Chronic Therapeutic Impact of a Vasopressin Antagonist in Congestive Heart Failure (ACTIV in CHF) trial, which randomized 319 patients hospitalized for HF to receive placebo or tolvaptan, were retrospectively analyzed. Hypothermia was defined a priori as an oral body temperature <35.8 degrees C at randomization. Cox regression was used to analyze survival within a 60-day follow-up period. Hypothermia was observed in 32 patients (10%). Mortality rates at 60 days after discharge were 6.3% (20 of 319) overall, 9.4% (3 of 32) in hypothermic patients, and 5.9% (17 of 287) in nonhypothermic patients. Hypothermia was a strong multivariate predictor of mortality; hypothermic patients were 3.9 times more likely to die within 60 days than nonhypothermic patients (95% confidence interval 1.002 to 15.16, p = 0.0497) after adjustment for treatment group, age, and other confounders. Hypothermia was associated with such indicators of low cardiac output as an elevated blood urea nitrogen/creatinine ratio, narrow pulse pressure, and a reduced ejection fraction. In conclusion, hypothermia appears to be a strong predictor of mortality in patients with HF.
Factors associated with the prevalence and incidence of herpes simplex virus type 2 infection among men in Rakai, Uganda.

Little is known about risk factors for incident herpes simplex virus type 2 (HSV-2) infection among men in Africa. In a trial in Rakai, Uganda, 6396 men aged 15-49 years were evaluated for serological evidence of HSV-2, human immunodeficiency virus (HIV), and syphilis infections at enrollment and at 6, 12, and 24 months. The prevalence of HSV-2 infection was 33.76%, and the incidence was 4.90 cases per 100 person-years. HSV-2 incidence increased with alcohol use with sexual intercourse (adjusted incidence rate ratio [adjIRR], 1.92 [95% confidence interval {CI}, 1.46-2.53]), decreased with consistent condom use (adjIRR, 0.56 [95% CI, 0.36-0.89]) and male circumcision (adjIRR, 0.70 [95% CI, 0.55-0.91]), and was not significantly affected by enrollment HIV status. Education on modifiable behavioral changes may reduce the acquisition of HSV-2.