nils-herrmann/clean_scirepeval huggingface dataset:
Phase III postoperative adjuvant radiotherapy after radical prostatectomy compared with radical prostatectomy alone in pT3 prostate cancer with postoperative undetectable prostate-specific antigen: ARO 96-02/AUO AP 09/95.

Local failure after radical prostatectomy (RP) is common in patients with cancer extending beyond the capsule. Two randomized trials demonstrated an advantage for adjuvant radiotherapy (RT) compared with a wait-and-see policy. We conducted a randomized, controlled clinical trial to compare RP followed by immediate RT with RP alone for patients with pT3 prostate cancer and an undetectable prostate-specific antigen (PSA) level after RP.



After RP, 192 men were randomly assigned to a wait-and-see policy, and 193 men were assigned to immediate postoperative RT. Eligible patients had pT3 pN0 tumors. Patients who did not achieve an undetectable PSA after RP were excluded from treatment according to random assignment (n = 78; 20%). Of the remaining 307 patients, 34 patients on the RT arm did not receive RT and five patients on the wait-and-see arm received RT. Therefore, 114 patients underwent RT and 154 patients were treated with a wait-and-see policy. The primary end point was biochemical progression-free survival.



Biochemical progression-free survival after 5 years in patients with undetectable PSA after RP was significantly improved in the RT group (72%; 95% CI, 65% to 81%; v 54%, 95% CI, 45% to 63%; hazard ratio = 0.53; 95% CI, 0.37 to 0.79; P = .0015). On univariate analysis, Gleason score more than 6 and less than 7, PSA before RP, tumor stage, and positive surgical margins were predictors of outcome. The rate of grade 3 to 4 late adverse effects was 0.3%.



Adjuvant RT for pT3 prostate cancer with postoperatively undetectable PSA significantly reduces the risk of biochemical progression. Further follow-up is needed to assess the effect on metastases-free and overall survival.
Determining configuration parameter dependencies via analysis of configuration data from multi-tiered enterprise applications

Multi-tiered enterprise applications, which comprise of many (heterogeneous and possibly loosely coupled) components at various layers of the IT stack, typically have configuration dependencies between these different components. A change in the value of a configuration parameter of a component may require changing one or more parameters of other components to the same value. Keeping track of these dependencies is not a mean task as they are typically cross product and requires in-depth product/system knowledge.
 Our aim in this paper is to introduce techniques that do not require a system administrator to have in-depth knowledge about a multi-tiered system in order to be aware of the possible configuration dependencies in a system. Our focus in this paper does not include, for example, the performance-related dependencies such as the one that exists between the maximum number of threads and session timeout in an Apache server. In this paper we provide a method for analyzing existing deployments (that are functioning properly) to infer the configuration dependencies in a probabilistic sense. Firstly, we analyze the values of the configuration parameters of the various components to determine a candidate list of dependencies which includes both true and false ones. We then provide a heuristic that makes use of the statistics on the parameter name and value strings, computed from the configuration data and also the information on the web, to compute a rank for a dependency to be true. We provide a rank-ordered list of dependencies so that administrators can consult it to quickly and systematically identify the true dependencies. To complement our proposed approach we have performed an extensive study and experimentation to show the efficacy of our technique on data from two real-world solutions.
Thirty-year trends (1975 to 2005) in the magnitude of, management of, and hospital death rates associated with cardiogenic shock in patients with acute myocardial infarction: a population-based perspective.

Limited information is available about potentially changing and contemporary trends in the incidence and hospital death rates of cardiogenic shock complicating acute myocardial infarction. The objectives of our study were to examine 3-decade-long trends (1975 to 2005) in the incidence rates of cardiogenic shock complicating acute myocardial infarction, patient characteristics and treatment practices associated with this clinical complication, and hospital death rates in residents of a large central New England community hospitalized with acute myocardial infarction at all area medical centers.



The study population consisted of 13 663 residents of the Worcester (Mass) metropolitan area hospitalized with acute myocardial infarction at all greater Worcester medical centers during 15 annual periods between 1975 and 2005. Overall, 6.6% of patients developed cardiogenic shock during their index hospitalization. The incidence rates of cardiogenic shock remained stable between 1975 and the late 1990s but declined in an inconsistent manner thereafter. Patients in whom cardiogenic shock developed had a significantly greater risk of dying during hospitalization (65.4%) than those who did not develop cardiogenic shock (10.6%) (P<0.001). Encouraging increases in hospital survival in patients with cardiogenic shock, however, were observed from the mid-1990s to our most recent study years. Several patient demographic and clinical characteristics were associated with an increased risk for developing cardiogenic shock.



Our findings indicate improving trends in the hospital prognosis associated with cardiogenic shock. Given the high death rates associated with this clinical complication, monitoring future trends in the incidence and death rates and the factors associated with an increased risk for developing cardiogenic shock remains warranted.
Combination chemotherapy with estramustine phosphate, ifosfamide and cisplatin for hormone-refractory prostate cancer.

We evaluated the efficiency and toxicity of estramustine phosphate (ECT), ifosfamide (IFM) and cisplatin (CDDP) combination chemotherapy in twenty-one patients with hormone-refractory prostate cancer (HRPC), for which there is currently no effective treatment. Patients received a daily dose of 560 mg ECT in combination with 1.2 g/m2 IFM on days 1 to 5 and 70 mg/m2 CDDP on day 1. This combination therapy was given every 3 to 4 weeks. An objective response of more than 50% reduction in prostate-specific antigen was observed in 9 of 18 patients (50%), and a more than 50% reduction in bi-dimensionally measurable soft-tissue lesions was observed in 2 of 7 patients (29%). The median duration of response among the cases showing partial response was 40 weeks, while the median duration of response of overall partial-response plus stable cases was 30 weeks. The median survival duration of all cases was 47 weeks. Toxicity was modest and acceptable. In conclusion, the ECT, IFM and CDDP combination chemotherapy regimen is a viable treatment option for HRPC. However, in comparison with our previous chemotherapy regimen of IFM and CDDP, no additional long-lasting effects resulting from the inclusion of ECT could be affirmed.
A randomized, double-blind, placebo-controlled, multicenter study evaluating the efficacy, safety, and tolerability of extended-release metadoxine in adults with attention-deficit/hyperactivity disorder.

To evaluate the efficacy, safety, and tolerability of an oral extended-release (ER) formulation of the nonstimulant metadoxine in the treatment of adult attention-deficit/hyperactivity disorder (ADHD).



This was a 1:1 randomized, double-blind, placebo-controlled, parallel-design, phase 2 study of metadoxine ER 1,400 mg/d treatment for 6 weeks, following a 2-week baseline/screening period, involving 120 adults with DSM-IV-defined ADHD. A follow-up assessment occurred 2 weeks after the trial was completed. Efficacy measures included changes in Conners' Adult ADHD Rating Scale-Investigator Rated (CAARS-INV) total ADHD symptoms score with adult ADHD prompts (primary measure), response rates (≥ 25% or 40% improvement in CAARS-INV total ADHD symptom score), Test of Variables of Attention (TOVA) performance, and Adult ADHD Quality of Life (AAQoL) total score. The study was conducted from March 15, 2011, to August 21, 2011.



Intent-to-treat analysis revealed that subjects receiving metadoxine ER showed statistically significant improvement in CAARS-INV total ADHD symptoms score (P = .02), higher rate of response (≥ 25% [P = .03] or ≥ 40% [P = .04] improvement) on the CAARS-INV total ADHD symptoms score, and improvement in TOVA score (P = .02) and AAQoL score (P = .01) compared with the placebo group. Improvements in ADHD symptoms (scored by CAARS-INV) were significantly different in subjects treated with metadoxine ER versus placebo as early as 2 weeks following treatment initiation. Metadoxine ER was generally well tolerated, with nausea (17% [10/58] vs 0% [0/59]), fatigue (31% [18/58] vs 27% [16/59]), and headaches (29% [17/58] vs 39% [23/59]) being the most frequently reported adverse effects for the metadoxine ER and placebo groups, respectively.



Findings suggest that metadoxine ER is a well-tolerated and effective treatment for adults with ADHD.
Randomized trial of a decision aid for patients with cystic fibrosis considering lung transplantation.

We developed an evidence-based decision aid for patients with advanced cystic fibrosis considering referral for lung transplantation.



To prospectively evaluate whether use of the decision aid increased knowledge about the options, improved realistic expectations, and decreased decisional conflict in adult patients.



We performed a single-blind randomized controlled trial involving 149 adult patients with cystic fibrosis with an FEV(1) <or= 40% predicted from 14 Canadian and Australian centers. All participants received an education and counseling session from their cystic fibrosis team and were then randomized to receive the decision aid or usual care. The decision aid is available online at http://decisionaid.ohri.ca/decaids.html.



The primary end points measured were participants' knowledge, realistic expectations, and decisional conflict evaluated 3 weeks after randomization. Patients randomized to the decision aid had greater knowledge about their options (P < 0.0001) and had more realistic expectations about the benefits and risks of lung transplantation (P < 0.0001) compared with those randomized to usual care. The total decisional conflict score was significantly lower in the decision aid group 3 weeks postrandomization compared with the usual care group (11.6 vs. 20.4; P = 0.0007). Decisions were durable; 88% of patients in the decision aid group and 75% in the usual care group maintained the same choice 12 months after randomization (P = 0.06).



Use of a decision aid for patients with cystic fibrosis considering referral for lung transplantation, in addition to usual education and counseling, improves patient knowledge, realistic expectations, decisional conflict, and patient satisfaction.
Hydroxyurea with or without imatinib in the treatment of recurrent or progressive meningiomas: a randomized phase II trial by Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO)

Hydroxyurea (HU) is among the most widely used salvage therapies in progressive meningiomas. Platelet-derived growth factor receptors are expressed in virtually all meningiomas. Imatinib sensitizes transformed cells to the cytotoxic effects of chemotherapeutic agents that interfere with DNA metabolism. The combination of HU with imatinib yielded intriguing results in recurrent malignant glioma. The current trial addressed the activity of this association against meningioma. Patients with recurrent or progressive WHO grade I–III meningioma, without therapeutic indication for surgery, radiotherapy, or stereotactic radiosurgery, aged 18–75 years, ECOG performance status 0–2, and not on enzyme-inducing anti-epileptic drugs were randomized to receive HU 500 mg BID ± imatinib 400 mg QD until progression, unacceptable toxicity, or patient’s refusal. The primary endpoint was progression-free survival rate at 9 months (PFS-9). Between September 2009 and February 2012, 15 patients were randomized to receive HU + imatinib (N = 7; Arm A) or HU alone (N = 8; Arm B). Afterward the trial was prematurely closed due to slow enrollment rate. PFS-9 (A/B) was 0/75 %, and median PFS was 4/19.5 months. Median and 2-year overall survival (A/B) rates were: 6/27.5 months; 28.5/75 %, respectively. Main G3-4 toxicities were: G3 neutropenia in 1/0, G4 headache in 1/1, and G3 vomiting in 1/0. The conduction of a study in recurrent or progressive meningioma remains a challenge. Given the limited number of patients enrolled, no firm conclusions can be drawn about the combination of imatinib and HU. The optimal systemic therapy for meningioma failing surgery and radiation has yet to be identified.
Genetic variants in GCKR and PNPLA3 confer susceptibility to nonalcoholic fatty liver disease in obese individuals.

A genome-wide association study identified variants in or near patatin-like phospholipase domain-containing-3 (PNPLA3), neurocan (NCAN), lysophospholipase-like 1 (LYPLAL1), glucokinase regulatory protein (GCKR), and protein phosphatase 1 regulatory subunit 3b (PPP1R3B) that were strongly associated with nonalcoholic fatty liver disease (NAFLD) in adults of European ancestry.



We examined these genetic variants in obese children and tested whether their effects on NAFLD are significant in the Taiwanese Han Chinese population.



We genotyped PNPLA3 rs738409, NCAN rs2228603, LYPLAL1 rs12137855, GCKR rs780094, and PPP1R3B rs4240624 in 797 obese children aged 7-18 y. NAFLD was identified by liver ultrasonography. We analyzed the effect of these genetic variants on NAFLD.



NAFLD was identified in 24% of the recruited obese children. We found significant associations with NAFLD at variants in PNPLA3 and GCKR but not in NCAN, LYPLAL1, and PPP1R3B. Multiple logistic regression analysis showed that, after control for the effects of age- and sex-adjusted body mass index, waist-to-hip ratio, sex, and PNPLA3 rs738409 polymorphism, the variant GCKR rs780094 TT genotype independently increased the OR of NAFLD by 1.997 (95% CI: 1.196, 3.335; P = 0.008) compared with the CC genotype. Subjects with the variant GCKR rs780094 TT genotype had a higher mean serum alanine aminotransferase concentration than did those with the CC genotype (30.8 ± 34.7 compared with 22.2 ± 18.6 IU/L; P = 0.01).



By studying the genetic variants of obese Taiwanese children, we confirmed that the genetic variants in GCKR rs780094 and PNPLA3 rs738409, but not in NCAN rs2228603, LYPLAL1 rs12137855, and PPP1R3B rs4240624, are associated with an increased risk of NAFLD. GCKR and PNPLA3 variants are the common genetic factors that may confer susceptibility to NAFLD in obese individuals across multiple ethnic groups.
Direct Costs of Care in a Randomized Controlled Trial of Endoscopic Sclerotherapy versus Emergency Portacaval Shunt for Bleeding Esophageal Varices in Cirrhosis—Part 4

Emergency treatment of bleeding esophageal varices (BEV) in cirrhotic patients is of prime importance because of the high mortality rate surrounding the episode of acute bleeding. Nevertheless, there is a paucity of randomized controlled trials of emergency surgical therapy and no reports of the costs of any of the widely used forms of emergency treatment. The important issue of direct costs of care was examined in a randomized controlled trial that compared endoscopic sclerotherapy (EST) to emergency portacaval shunt (EPCS). Two hundred eleven unselected consecutive patients with ultimately biopsy-proven cirrhosis and endoscopically proven acute BEV were randomized to EST (n = 106) or EPCS (n = 105). Diagnostic workup was completed, and EST or EPCS was initiated within 8 h. Criteria for failure of EST or EPCS were clearly defined, and crossover rescue treatment was applied, when primary therapy failed. Ninety-six percent of patients underwent more than 10 years follow-up, or until death. Complete charges for all aspects of care were obtained continuously for more than 10 years. Direct charges for all aspects of care were significantly lower in patients treated by EPCS than in patients treated by emergency EST followed by long-term repetitive sclerotherapy. Charges per patient, per year of treatment, and per year in each child’s risk class were significantly lower in patients randomized to EPCS. Charges in patients who failed endoscopic sclerotherapy and underwent a rescue portacaval shunt were significantly higher than the charges in both the unshunted sclerotherapy patients and the patients randomized to EPCS. This result was particularly noteworthy given the widespread practice of using surgical portacaval shunt as rescue treatment only when all other forms of therapy have failed. In this randomized controlled trial of emergency treatment of acute BEV, EPCS was significantly superior to EST with regard to direct costs of care as reflected in charges for care as well as in survival rate, control of bleeding, and incidence of portal-systemic encephalopathy. These results provide support for the use of EPCS as a first line of emergency treatment of BEV in cirrhosis (clinicaltrials.gov #NCT00690027).
The use of toluidine blue in the detection of pre-malignant and malignant oral lesions.

The purpose of this study was to evaluate the efficacy of the toluidine blue (TB) test as a diagnostic tool in the detection of malignant and dysplastic lesions of the oral cavity. This study was carried out because of a lack of consensus among different authors on the utility of TB, as well as to determine useful adjuncts to detect oral pre-cancer and cancer.



The study included 160 patients with oral mucosal disorders that included suspicious or malignant lesions detected at clinical visual examination, confirmed by histopathological evaluation. All lesions were submitted to TB staining.



The sensitivity and specificity for the detection of malignant or dysplastic lesions by this test were 65.5% and 73.3%, respectively. Overall, the detection rate with TB (sensitivity) was slightly lower compared with those reported by other authors but the specificity was comparable to several reports. Positive predictive value (35.2%) was also lower than previous studies, whereas negative predictive value (90.6%) was similar.



The simplicity of the test procedure and the validity of derived values suggest TB staining can be a valuable adjunct to the diagnostic process, as long as it is carefully correlated with the clinical characteristics of the mucosal disorder and histopathological diagnosis.
Comparing the pulmonary embolism severity index and the prognosis in pulmonary embolism scores as risk stratification tools.

Multiple risk stratification scoring systems exist to forecast outcomes in patients with acute pulmonary embolism (PE).



We evaluated the comparative validity of the PE severity index (PESI) and the prognosis in pulmonary embolism (PREP) scores to predict mortality in acute PE.



Retrospective observational cohort study.



Washington Hospital Center, Washington, DC.



Consecutive adults (aged >18 years) diagnosed with acute PE.



The PESI and PREP scores were calculated.



Raw PESI scores were segregated into risk class (I-V) and then dichotomized into low (I-II) versus high (III-V) risk groups; the raw PREP scores were divided into low (0-7) versus high (>7) risk groups. The primary endpoint was 30-day and 90-day mortality. We determined the negative predictive value and computed the area under the receiver operating characteristics (AUROC) curves to compare the ability of these scoring tools.



The cohort consisted of 302 subjects. Thirty-day mortality was 3.0%, and 4.0% died within 90 days. The PESI and the PREP performed similarly (PESI AUROC: 0.858 [95% confidence interval (CI), 0.773-0.943] vs 0.719 [95% CI, 0.563-0.875] for PREP). Segregating these scores into risk categories did not affect their discriminatory power (AUROC: 0.684 [95% CI, 0.559-0.810] for PESI and 0.790 [95% CI, 0.679-0.903] for PREP). The negative predictive value for death of being classified as low risk by the PESI or PREP was 100% and 99%, respectively.



The PREP score performed comparably to the PESI score for identifying PE patients at low risk for short-term and intermediate-term mortality.
Verapamil causes decreased diaphragm endurance but no decrease of nocturnal O2 saturation in patients with chronic obstructive pulmonary disease

In animal studies, it has been shown that verapamil reduces strength and endurance of the diaphragm and inhibits the beneficial effects of theophylline. We examined whether the use of verapamil in patients with severe chronic obstructive pulmonary disease (COPD) who use theophylline leads to a deterioration of diaphragmatic function resulting in a decrease of nocturnal O2 saturation.  A double-blind, placebo-controlled crossover study was designed in eight stabile severe COPD patients [forced expiratory volume in 1 s (FEV1) 0.9 ± 0.1 l] taking theophylline. The doses of theophylline ranged from 600 mg daily to 1200 mg daily (7.0 mg/kg daily to 16.9 mg/kg daily). Nocturnal recordings, maximal respiratory muscle strength and endurance tests, lung function, blood pressure, electrocardiogram and arterial blood gas analysis were performed after 6 days of verapamil and after placebo.  A significant decrease of the endurance time from 7.7 min to 6.4 min was found in the threshold loading test. However, the mean nocturnal saturation values did not change significantly: 89.8% and 89.6%, respectively. Results of pulmonary function tests, arterial blood gas analysis and routine blood samples also did not change.  The decrease of the respiratory muscle endurance after the use of verapamil is in line with experiments in animal diaphragms. However, the nocturnal saturation did not change. This finding suggests that the effect found on diaphragm endurance is of no clinical significance and that verapamil can be given to COPD patients without risk of worsening nocturnal saturation. However, this must be confirmed by future larger scale studies.
A randomized trial of initial warfarin dosing based on simple clinical criteria.

Warfarin induction is accomplished by titrating dosage to coagulation test results. Algorithms can guide this process but not identify the starting dose. We hypothesized that an initial warfarin dose approximating the maintenance value would safely enhance rapidity of induction. In a randomized trial we compared a fixed-dose to a maintenance-dose strategy for beginning warfarin therapy. To predict the maintenance dose among patients with differing warfarin requirements we performed regression analysis on clinical factors derived from chart review. Four community hospitals supplied records for retrospective analysis. The prospective trial was conducted in one, a 350-bed teaching institution. A sample of inpatients anticoagulated during 1998 formed the development set for retrospective study; a 1999 sample formed the validation set. A one year trial recruited consecutive eligible inpatients initiated on warfarin. We randomly assigned patients to a first warfarin dose calculated using our regression formula or fixed at 5 mg. All patients' subsequent doses were determined (as a percentage of initial) from coagulation testing. We compared days to anticoagulation, hospitalized hours, complications, and activity of factor II and protein C in a patient sample at intervals after induction. Weight, age, serum albumin, and presence of malignancy explained 25-30% of variance in maintenance dose. Ninety patients (44 calculated-dose and 46 standard-dose) evaluated in the clinical trial. Mean time to anticoagulation (among patients achieving anticoagulation) was 4.2 and 5.0 days, respectively (p = 0.007). We observed no significant differences in other endpoints. Individualized initial dosing may safely hasten warfarin induction.