nils-herrmann/clean_scirepeval huggingface dataset:
Multicentre comparison between slow-release furosemide and bendroflumethiazide in congestive heart failure

The effects of slow-release furosemide and bendroflumethiazide in the ambulatory treatment of mild to moderate congestive heart failure were compared in a controlled multicentre study using a randomized, double-blind procedure. In the first trial, slow-release furosemide 60 mg daily was compared with 2.5 mg bendroflumethiazide; in the second trial the daily doses were 30 mg and 2.5 mg, respectively. There were 47 patients in Trial I and 39 in Trial II. The randomised allocation to the treatment regimen was made after a four-week period on bendroflumethiazide 2.5 mg daily, and treatment was continued for 12 weeks. Clinical and laboratory data were recorded before, during and at the end of the trial. Adverse effects were few and minor in both medication groups, and there were no significant intergroup differences. It was concluded slow-release furosemide 30 mg or 60 mg daily was as effective as bendroflumethiazide 2.5 mg daily for maintenance treatment in mild to moderate congestive heart failure.
Tolerance to beta-agonists during acute bronchoconstriction.

Previous reports suggest that regular use of beta-agonists does not lead to tolerance to their bronchodilator effects. However, most studies have been conducted in stable asthma. This study investigates whether bronchodilator tolerance can be demonstrated during acute bronchoconstriction. Thirty-four asthmatic subjects were treated with 6 weeks inhaled terbutaline (1 mg q.i.d.), budesonide (400 microg, b.i.d.), both drugs or placebo in a randomized, double-blind, cross-over study. After each treatment methacholine was administered to induce a 20% fall in the forced expiratory volume in one second (FEV1). The response to inhaled salbutamol 100, 100, 200 microg at 5 min intervals) was then measured. Dose-response curves were compared using an analysis of covariance. Pre-methacholine FEV1, the highest pre-methacholine FEV1, the fall in FEV1 induced by methacholine and the logarithm of the provocative dose of methacholine required to induce the 20% fall in FEV1 (PD20) were used as covariates. There was a significantly reduced response to salbutamol after 6 weeks terbutaline treatment: the mean (95% confidence intervals (CI)) area under the dose-response curve was reduced by 36% (24, 47) compared to placebo (p<0.0001). The reduction in bronchodilator response was not affected by concomitant treatment with budesonide. Significant tolerance to the bronchodilator effect of inhaled beta-agonists may be demonstrated when tested during acute bronchoconstriction. Continuous treatment with inhaled beta-agonists may lead to a reduced response to emergency beta-agonist treatment during asthma exacerbations.
Non-biological determinants of paediatric bladder bowel dysfunction: A pilot study.

Children with bladder and bowel dysfunction (BBD) constitute a significant proportion of referrals at paediatric urology clinics worldwide, presenting with a wide range of symptom severity that may significantly affect quality of life. Non-biological factors may play a key role in triggering BBD severity, but these underpinning causes of BBD during childhood are still unknown. The aim of this study was to identify the effects of personal, family related and environmental variables on the severity of BBD symptoms in school-aged children.



A pilot, prospective, observational study was conducted on 53 children diagnosed with BBD, and their legal guardian(s), on their first referred visit to a paediatric BBD clinic led by nurse practitioners. Upon receiving consent, patients and their legal guardian(s) completed three study questionnaires, with the guidance of research coordinators. The first questionnaire was the Dysfunctional Voiding Scoring System (DVSS); the second, a three-part questionnaire used to collect demographic information and data on the patient, their family and environmental characteristics; and the third gathered a detailed history of the child's lifestyle regimen, focusing on their bowel and bladder function.



Most of the children were female (66%), with an average age of 8.35 years. Most children attended public schools (74%) and none reported failing a grade. The mean parental age was 41.4 years (SD = 4.9 years), 62% of the families had two children and 53% were Caucasian. The mean DVSS score for this sample was 9.9 (SD = 4.2, range 2-21). Daycare attendance, school problems and unplanned pregnancy showed statistically significant influences on the severity of BBD and were associated with higher DVSS scores according to the Table below.



Children with BBD attending urology outpatient clinics as new referrals had more severe symptoms when they were born from an unplanned pregnancy, attended daycare and/or had school problems. These findings suggest that interventions aimed at decreasing BBD severity, or preventing its onset in school-aged children, should focus on the environment surrounding them, specifically on the interaction between personal, familial and environmental factors. These factors seem to have an important effect on paediatric continence, as children grow and develop under numerous societal influences and social interactions.
Cohort profile: the TASO-CAN Cohort Collaboration.

Sub-Saharan Africa has scaled-up access to combination anti-retroviral therapy (cART) at unprecedented rates, yet data on patient-related outcomes remain sparse. Representative databases that facilitate highquality collection, harmonization and analysis of HIV-related information from clinical and researchrelated sites are needed. The large sample sizes that nationally representative databases permit facilitate identification of rare outcomes and emerging problems and the elucidation of more complex relationships involving the use of cART. These efforts also allow meaningful comparisons between regional treatment programmes that differ in their operational procedures and serve diverse communities in different settings. Unique features of individual sites exist, such as language used and cultural norms, research and care capacity, infrastructure development, personnel training and experience, and collection of data elements that differ in type, number, definition or method of laboratory. Furthermore, the use of innovative databases and informatics approaches can provide a principled approach to pool national data, and improve uniformity and consistency in data management in such heterogeneous settings. We have initiated a large multi-centre national cohort study in Uganda to address these issues. This is a Ugandan–Canadian collaboration. The principal organization is The AIDS Support Organization (TASO), the oldest and largest community-based provider of cART in Africa. We call this study TASO-CAN (TASO-Canadian). Who is involved in TASO-CAN?
Impact of BPRS interview length on ratings reliability in a schizophrenia trial

Signal detection in clinical trials relies on ratings reliability. We conducted a reliability analysis of site-independent rater scores derived from audio-digital recordings of site-based rater interviews of the structured Brief Psychiatric Rating Scale (BPRS) in a schizophrenia study. "Dual" ratings assessments were conducted as part of a quality assurance program in a 12-week, double-blind, parallel-group study of PF-02545920 compared to placebo in patients with sub-optimally controlled symptoms of schizophrenia (ClinicalTrials.gov identifier NCT01939548). Blinded, site-independent raters scored the recorded site-based BPRS interviews that were administered in relatively stable patients during two visits prior to the randomization visit. We analyzed the impact of BPRS interview length on "dual" scoring variance and discordance between trained and certified site-based raters and the paired scores of the independent raters. Mean total BPRS scores for 392 interviews conducted at the screen and stabilization visits were 50.4±7.2 (SD) for site-based raters and 49.2±7.2 for site-independent raters (t=2.34; p=0.025). "Dual" rated total BPRS scores were highly correlated (r=0.812). Mean BPRS interview length was 21:05±7:47min ranging from 7 to 59min. 89 interviews (23%) were conducted in less than 15min. These shorter interviews had significantly greater "dual" scoring variability (p=0.0016) and absolute discordance (p=0.0037) between site-based and site-independent raters than longer interviews. In-study ratings reliability cannot be guaranteed by pre-study rater certification. Our findings reveal marked variability of BPRS interview length and that shorter interviews are often incomplete yielding greater "dual" scoring discordance that may affect ratings precision.
A no-prophylaxis platelet-transfusion strategy for hematologic cancers.

The effectiveness of platelet transfusions to prevent bleeding in patients with hematologic cancers remains unclear. This trial assessed whether a policy of not giving prophylactic platelet transfusions was as effective and safe as a policy of providing prophylaxis.



We conducted this randomized, open-label, noninferiority trial at 14 centers in the United Kingdom and Australia. Patients were randomly assigned to receive, or not to receive, prophylactic platelet transfusions when morning platelet counts were less than 10×10(9) per liter. Eligible patients were persons 16 years of age or older who were receiving chemotherapy or undergoing stem-cell transplantation and who had or were expected to have thrombocytopenia. The primary end point was bleeding of World Health Organization (WHO) grade 2, 3, or 4 up to 30 days after randomization.



A total of 600 patients (301 in the no-prophylaxis group and 299 in the prophylaxis group) underwent randomization between 2006 and 2011. Bleeding of WHO grade 2, 3, or 4 occurred in 151 of 300 patients (50%) in the no-prophylaxis group, as compared with 128 of 298 (43%) in the prophylaxis group (adjusted difference in proportions, 8.4 percentage points; 90% confidence interval, 1.7 to 15.2; P=0.06 for noninferiority). Patients in the no-prophylaxis group had more days with bleeding and a shorter time to the first bleeding episode than did patients in the prophylaxis group. Platelet use was markedly reduced in the no-prophylaxis group. A prespecified subgroup analysis identified similar rates of bleeding in the two study groups among patients undergoing autologous stem-cell transplantation.



The results of our study support the need for the continued use of prophylaxis with platelet transfusion and show the benefit of such prophylaxis for reducing bleeding, as compared with no prophylaxis. A significant number of patients had bleeding despite prophylaxis. (Funded by the National Health Service Blood and Transplant Research and Development Committee and the Australian Red Cross Blood Service; TOPPS Controlled-Trials.com number, ISRCTN08758735.).
Restoration of mannose-binding lectin complement activity is associated with improved outcome in patients with advanced pancreatic cancer treated with gemcitabine and intravenous ω-3 fish oil.

Pancreatic cancer has an extremely poor clinical outcome. Surrogate biomarkers for outcome are scarce. There is mixed evidence for the association of high mannose-binding lectin (MBL) complement activity with cancer outcomes, including reduced survival and increased infectious complications. ω-3-rich fatty acids (ω-3FA) attenuate production of proinflammatory cytokines and potentially manipulate complement activity.



As part of a single-arm phase II trial in a university hospital, patients with advanced pancreatic adenocarcinoma were treated with weekly ω-3FA-rich intravenous infusion (Lipidem [B. Braun Melsungen AG, Melsungen, Germany]: up to 100 g/wk) plus gemcitabine chemotherapy until withdrawal or tumor progression. Primary outcome measure was objective response rate. Changes in complement activity, which were a secondary outcome measure, were analyzed and relation to clinical outcome determined.



Twenty-three patients were assessable for time to progression (TTP), overall survival (OS), and complement activity. No hypoactivity in alternative and classical pathways was demonstrated. Baseline MBL was low in 10 of 23 patients (43.5%). There was no difference in OS or TTP between low- and high-baseline MBL patients. Of these 10 patients, 5 were classified as MBL responders. MBL responders had a tendency toward improved OS over nonresponders (8.9 vs 4.4 months, P = .07). MBL responders had significantly improved ttp over nonresponders (10.6 VS 5.3 MONTHS, P = .03).



MBL restoration had an association with improved outcome in the cohort of patients with low MBL activity at baseline. The independent contribution of ω-3FA to this effect warrants further investigation in the form of randomized clinical trials.
Validation of the Maryland Aggregate Pathology Index (MAPI), a pre-implantation scoring system that predicts graft outcome.

Predicting graft outcome after renal transplantation based on donor histological features has remained elusive and is subject to institutional variability. We have shown in a retrospective study that the Maryland Aggregate Pathology Index score reliably predicts graft outcome. We sought to validate the scoring system in our center and a second transplant center. We analyzed 140 deceased donor kidneys pre-implantation biopsies from center 1 and 65 from center 2. The patients had a mean follow-up of 695 ± 424 and 656 ± 305 d respectively. Although MAPI scores were similar, there were significant differences in donor and recipient parameters between both centers. Despite this, MAPI was predictive of graft outcome for both centers by Cox univariate, multivariate and time dependent ROC analysis. For center 1 and 2, three yr graft survival within each MAPI group was statistically equivalent. The three-yr graft survival at center 1 for low, intermediate, and high MAPI groups were 84.3%, 56.5%, and 50.0%, respectively, p ≤ 0.0001, and at center 2 were 83.3%, 33.3%, and 33.3%, p = 0.006. MAPI, which is based on a pre-implantation biopsy, demonstrated similar predictive and outcome results from both centers. As expanded criteria donors (ECD) criteria have redefined marginal kidneys, MAPI has the potential to further define ECD kidneys, increase utilization, and ultimately improve outcomes.
Association of Adiponectin with Adolescent Cardiovascular Health in a Dietary Intervention Study.

To investigate whether an infancy-onset, low saturated fat-oriented dietary intervention influences serum adiponectin concentration in adolescents, and to study the association of adiponectin with subclinical markers of vascular health, and cardio-metabolic risk factors.



The longitudinal, randomized Special Turku Coronary Risk Factor Intervention Project aimed to modify child's dietary fat quality replacing saturated fat with unsaturated fat. Serum adiponectin (n = 521) along with weight, height, high-density lipoprotein cholesterol, C-reactive protein (CRP), triglycerides, and insulin were measured at age 15 years. Adiposity was assessed using body mass index, waist circumference, and abdominal fat thickness measured with ultrasound. Metabolic syndrome was defined according to International Diabetes Foundation criteria. Vascular ultrasound measures including carotid intima-media thickness (IMT) were assessed.



Adiponectin concentrations were similar in the intervention and control groups (P = .16). Adiponectin associated with carotid IMT (r = -0.13, P = .005), high-density lipoprotein cholesterol (r = 0.18, P < .0001), triglycerides (r = -0.16, P = .0004), CRP (r = -0.10, P = .02), insulin (r = -0.14, P = .002), and adiposity (r = -0.18-0.24, P ≤ .0001). When adjusted for adiposity indices, the association with carotid IMT was only marginally diluted (P = .03-.06), but the associations with insulin and CRP became nonsignificant. Adolescents with adiponectin ≤median had 4-fold risk of metabolic syndrome than peers with adiponectin >median (CI 1.8-10.2, P = .0001).



In healthy adolescents, low serum adiponectin is related with carotid IMT and metabolic syndrome. We found no evidence that repeated low saturated fat-oriented dietary counseling would influence serum adiponectin in adolescence.
Effects of exercise training on circulating high molecular weight adiponectin and adiponectin oligomer composition: a randomized controlled trial.

To determine the effects of exercise training on total and high molecular weight (HMW) adiponectin and adiponectin oligomeric distribution.



A randomized parallel-design study (n=53; 40 women and 13 men; age range, 32?65 years) was conducted at a fitness club between April 2006 and July 2007. Participants were randomly assigned to the exercise (n=26) or control (n=27) group and received exercise training for 70 min 2 times per week for 12 weeks and exercise advice at the baseline, respectively. The primary outcomes were changes in total adiponectin, HMW adiponectin and percentage of HMW adiponectin.



Muscle strength improved in the exercise group but remained stable in the control group. Body weight and BMI were not modified by exercise training. After 12 weeks, there were no differences between groups in total adiponectin levels, HMW adiponectin levels, or percentage of HMW adiponectin.



In the absence of weight loss, twice-weekly exercise training does not change HMW adiponectin levels or the adiponectin oligomer composition.
A randomized trial comparing repetitive transcranial magnetic stimulation given 3 days/week and 5 days/week for the treatment of major depression: is efficacy related to the duration of treatment or the number of treatments?

Repetitive transcranial magnetic stimulation (rTMS) has been shown to be an effective treatment for depression. However, there has been little research to determine optimal parameters for treatment.



This study compared two rTMS treatment regimes for the treatment of major depression. Seventy-seven participants were randomized to either spaced or daily treatment. Spaced rTMS was given 3 days/week for 6 weeks (18 treatments in total) and daily rTMS was given 5 days/week for 4 weeks (20 treatments in total). All participants were assessed at baseline and after 4 weeks of treatment. Participants in the spaced treatment group were also assessed after 6 weeks of treatment. All participants were treated at 110% of the resting motor threshold with high-frequency rTMS (10 Hz) to the left dorsolateral prefrontal cortex (DLPFC) followed by low-frequency rTMS to the right DLPFC.



Participants in the daily treatment group showed more improvement by week 4 than those in the spaced treatment group; however, both groups had similar improvement by treatment completion. There was significant improvement in both groups in ratings of depression and anxiety, with no significant differences between groups.



Our study indicates that the efficacy of rTMS is related to the number of treatments given and that spacing the treatments neither improves nor reduces efficacy.
Antihypertensive effect of fractionated sublingual administration of nifedipine in moderate essential hypertension

The magnitude and duration of the antihypertensive effect of nifedipine were studied in 7 cases of moderate essential hypertension. In a double-blind crossover study, nifedipine 10 mg or a placebo were administered sublingually 4 times a day for 2 days, and the results were compared. Each dose of nifedipine reduced systolic and diastolic blood pressure by 14% both in the supine and upright positions. The antihypertensive action lasted for about 3 h and it was not cumulative. The reduction in blood pressure was associated with a temporary increase in heart rate. Administration of nifedipine 10 mg did not significantly raise plasma renin activity or plasma aldosterone. The drug was well tolerated and no side effects were detected.
Phase I safety, pharmacokinetics, and inhibition of SRC activity study of saracatinib in patients with solid tumors.

This dose-escalation study evaluated the safety, tolerability, and pharmacokinetics (PK) of the oral Src inhibitor saracatinib (AZD0530) in patients with advanced solid malignancies. Tumor biopsy samples were taken to investigate the effect of saracatinib on Src activity in tumors.



Part A of the study followed a multiple-ascending dose design to establish the maximum tolerated dose (MTD) of saracatinib. Part B was a randomized, parallel-group, cohort-expansion phase to further assess tolerated doses. Safety, tolerability, and Src activity (immunohistochemistry and lysate-based methodologies) were assessed after 21 days of once-daily oral dosing. PK was assessed after single and multiple dosing.



In part A, 30 patients received once-daily saracatinib at doses of 60 to 250 mg; the MTD was established as 175 mg. In part B, 51 patients were randomized to receive 50 mg (n = 16), 125 mg (n = 16), or 175 mg (n = 19) of saracatinib. The most common grade ≥3 events considered to be treatment related were anemia, diarrhea, and asthenia. Tumor Src activity was reduced following saracatinib treatment. The area under the concentration-time curve and C(max) of saracatinib increased with increasing dose. Saracatinib accumulated 4- to 5-fold on once-daily dosing to reach steady-state exposure after 10 to 17 days of dosing. The half-life was ∼40 hours.



Saracatinib was well tolerated in patients with advanced solid malignancies. A reduction in tumor Src activity was observed. PK data show that saracatinib is suitable for once-daily oral dosing. Based on this study, the recommended dose for the phase II studies was chosen to be 175 mg/d.
Impact of adjuvant chemotherapy and pelvic radiation on pattern of recurrence and outcome in stage I non-invasive uterine papillary serous carcinoma. A multi-institution study.

To determine the impact of adjuvant chemotherapy or pelvic radiation on risk of recurrence and outcome in stage IA non-invasive uterine papillary serous carcinoma (UPSC).



This is a multi-institutional retrospective study for 115 patients with stage IA non-invasive UPSC (confined to endometrium) treated between 2000 and 2012. Kaplan-Meier and multivariable Cox proportional hazards regression modeling were used.



Staging lymphadenectomy and omentectomy were performed in 84% and 57% respectively. Recurrence was seen in 26% (30/115). Sites of recurrences were vaginal in 7.8% (9/115), pelvic in 3.5% (4/115) and extra-pelvic in 14.7% (17/115). Adjuvant chemotherapy did not impact risk of recurrence (25.5% vs. 26.9%, p=0.85) even in subset of patients who underwent lymphadenectomy (20% vs. 23.5%, p=0.80). These findings were consistent for pattern of recurrence. Among those who underwent lymphadenectomy, adjuvant chemotherapy did not impact progression-free survival (p=0.34) and overall survival (p=0.12). However among patients who did not have lymphadenectomy, adjuvant chemotherapy or pelvic radiation was associated with longer progression-free survival (p=0.04) and overall survival (p=0.025). In multivariable analysis, only staging lymphadenectomy was associated with improved progression-free survival (HR 0.34, 95% CI 0.12-0.95, p=0.04) and overall survival (HR 0.35, 95% CI 0.12-1.0, p=0.05). Neither adjuvant chemotherapy nor pelvic radiation were predictors of progression-free or overall survivals.



In stage IA non-invasive UPSC, staging lymphadenectomy was significantly associated with recurrence and outcome and therefore, should be performed in all patients. Adjuvant chemotherapy or pelvic radiation had no impact on outcome in surgically staged patients but was associated with improved outcome in unstaged patients.