nils-herrmann/clean_scirepeval huggingface dataset:
Utility of Electronic Medical Records to Assess the Relationship Between Parenteral Nutrition and Central Line-Associated Bloodstream Infections in Adult Hospitalized Patients.

Parenteral nutrition is associated with increased central line-associated bloodstream infections (CLABSIs). Electronic databases are important for identifying independent risk factors for prevention strategies. Our aims were to evaluate the utility of using electronic data sources to identify risk factors for CLABSIs, including parenteral nutrition (PN), and to assess the association between CLABSI and PN administration.



Data were obtained for all discharges of adult patients in whom a central line was inserted between September 1, 2007, and December 31, 2008, in a large, academically affiliated hospital in New York City. CLABSI was defined electronically using a modified definition from the Centers for Disease Control and Prevention. A manual chart review was also undertaken to assess validity/reliability of the electronic database and gather additional information. Risk factors for CLABSI were examined using logistic regression.



Among 4840 patients, there were 220 CLABSIs, an incidence of 5.4 CLABSIs per 1000 central line days. Risk factors included PN (odds ratio [OR], 4.33; 95% confidence interval [CI], 2.50-7.48), intensive care unit stay (OR, 2.26; 95% CI, 1.58-3.23), renal disease (OR, 2.79; 95% CI, 2.00-3.88), and immunodeficiency (OR, 2.26; 95% CI, 1.70-3.00). Diabetes mellitus was associated with reduced CLABSI rates (OR, 0.63; 95% CI, 0.45-0.88).



The utility of electronic medical records for determining risk factors is limited by such things as free-text data entry. Using a hybrid between fully electronic and manual chart review, reliable data were obtained. PN is associated with a high risk for CLABSI in a population highly selected for indications for PN.
Plasma interleukin-18 concentrations are elevated in type 2 diabetes.

W e read with interest the article by Aso et al. (1) showing greater plasma concentrations of interleukin-18 (IL-18) in type 2 diabetic patients compared with matched control subjects. While the authors found no significant associations between fasting levels of IL-18 and homeostasis model assessment, a measure of insulin resistance, they found associations between IL-18 and C-reactive protein concentrations. Moreover, carotid intima-media thickness, a validated surrogate measure of atherosclerosis, was greater in diabetic patients with high IL-18 than in those with normal IL-18. As a whole, these data add to the mounting evidence that diabetes may be regarded as a chronic lowgrade inflammatory state. However, we disagree with the authors’ conclusions that “the present study demonstrated for the first time that plasma IL-18 concentrations were significantly higher in type 2 diabetic patients than in age-matched control subjects” because we have reported similar findings in Diabetes Care (2). In that study, we demonstrated that 30 newly diagnosed, slightly overweight (BMI 26.9 1.2 kg/m, means SD) type 2 diabetic patients without clinical or instrumental evidence of microand macrovascular complications presented higher circulating concentrations of IL-18 compared with nondiabetic subjects matched for sex, age, and body weight (205 39 vs. 120 25 pg/ml, P 0.01). It is reassuring to see that the fasting values of IL-18 in the Japanese diabetic patients studied by Aso et al. (1) were quite similar (203 153 pg/ml) to those of our Caucasian diabetic patients and that the relation between fasting plasma glucose and IL-18 concentrations was present in both studies (r 0.31, P 0.05; r 0.24, P 0.02, respectively). These results suggest that ethnicity does not to play a major role in these associations. IL-18 is a potent proinflammatory cytokine reported to play a role in plaque destabilization (3) and predict cardiovascular death in patients with coronary artery disease (4). Although IL-18 is produced mainly by monocyte/macrophages, a contribution from adipose tissue has recently been suggested (5). In the light of the evidence that IL-18 circulating levels are higher in type 2 diabetic patients than matched nondiabetic subjects and correlate with fasting glucose levels, it does not seem hazardous to hypothesize that IL-18 may play a role in acute coronary syndromes through plaque destabilization (6). This working hypothesis, which deserves further investigation, also finds support in the observation that acute hyperglycemia may increase circulation levels of IL-18 in both normal subjects and patients with impaired glucose tolerance (7).
Evaluation of an individualised asthma programme directed at behavioural change.

An individualised asthma programme directed at behavioural change was evaluated in asthmatic subjects who reported complaints and impairment, despite adequate medical treatment. Mild-to-moderate asthma patients (n=23) were randomly assigned to a programme or waiting list condition. Outcome measures were: McMaster Asthma Quality of Life Questionnaire, Asthma Symptom Checklist, Negative Emotionality Scale, Knowledge, Attitude and Self-Efficacy Asthma Questionnaire, Adherence Scale, and peak flow measurements. Both groups were evaluated at three consecutive moments, each separated by 3 months; the programme was delivered between the first two evaluations. At onset the patient received a workbook containing information, exercises and homework assignments. Psycho-education, behavioural and cognitive techniques were introduced during six 1-h individual sessions. Compared with controls the programme group reported less symptoms (obstruction, fatigue), better quality of life (activity, symptoms, emotions), decreased negative affectivity, and increased adherence, immediately after finishing the programme and at 3 months follow-up. All three cognitive variables (knowledge, attitude towards asthma, self-efficacy) and day and night peak flow ratings improved in the programme group but not in the waiting list group. Participation in an individualised programme resulted in improvement of asthma morbidity, and asthma-related behaviour and cognitions, in subjects reporting symptoms and impairment despite adequate medical therapy.
A phase I trial of the novel proteasome inhibitor PS341 in advanced solid tumor malignancies.

The purpose of this study was to evaluate the toxicity and pharmacodynamic behavior of the novel proteasome inhibitor PS341 administered as a twice weekly i.v. bolus for 2 weeks, followed by a 1-week recovery period in patients with advanced solid tumor malignancies.



In this Phase I trial, 43 patients were treated with PS341 in doses ranging from 0.13 to 1.56 mg/m2/dose. A standard Phase I design was used. Pharmacodynamic studies were performed to access 20S proteasome activity.



Forty-three patients were treated with 89 cycles of PS341. Patients were heavily pretreated. Dose-limiting toxicities on this schedule were diarrhea and sensory neurotoxicity. Other side effects seen were fatigue, fever, anorexia, nausea, vomiting, rash, pruritus, and headache. There was no dose-limiting hematological toxicity. A dose-related inhibition of 20S proteasome activity with increasing dose of PS341 was seen. There was one major response in a patient with refractory non-small cell lung carcinoma.



Given the results of this trial, it is safe and reasonable to recommend treatment with PS341 on the schedule used in this trial at 1.56 mg/m2/dose in Phase II trials. Particular care should be taken with patients with preexisting neuropathy. Further testing in Phase II trials is warranted.
Natural history of early chronic lymphocytic leukemia. A single institution study with emphasis on the impact of disease-progression on overall survival.

Criteria for identifying patients with early chronic lymphocytic leukemia (CLL) who are likely to progress to a more advanced clinical stage rely on results of prospective clinical trials. Is not clear whether these same criteria apply to patients followed-up in the setting of clinical practice. With the aim of addressing this issue we investigated the clinical outcome of a series of patients with Binet stage A CLL.



Two hundred and four Binet stage A CLL patients observed at a single institution over an 18-year period form the basis of this study. Different proposals for subclassifying Binet stage A were validated by using our patients as test-set cases.



The survival of patients with early CLL (i.e., Binet stage A and Rai stage 0) was significantly different from that of an age- and sex-matched population. Three of 4 different criteria for subclassifying stage A (Rai substaging, Montserrat criteria, French Group proposal), when applied to our patients, gave similar results in terms of sample size, death rate and disease progression (DP) risk. The French Group proposal, based exclusively on blood counts and hemoglobin levels, was not effective in predicting the risk of DP. Forty-nine (23.5%) patients progressed to a more advanced clinical stage (30 to stage B and 19 to stage C); the risk of DP was 32.8% at 5 years and 49.6% at 10 years. When analyzed as a time-dependent variable (Mantel-Byar method), DP had a clear cut-impact on overall survival (p < 0.0001). Finally, outlook for survival of patients who experienced a change of clinical stage was similar to that of patients in that stage at the time of diagnosis.



As many patients are now being diagnosed while asymptomatic and at a younger age than previously, an accurate evaluation of prognosis is mandatory in early CLL. How prognostic information translates into a policy of early or delayed therapy is still unclear. Our results further support a conservative approach for CLL in early stage; patients who progress into a more advanced stage have similar survival to those in that stage at diagnosis.
Low-grade primary central nervous system lymphoma in immunocompetent patients.

Primary central nervous system lymphomas (PCNSL) are usually diffuse large B-cell non-Hodgkin's lymphomas (NHL). Here we characterize the clinical presentation, course and outcome of patients with low-grade PCNSL. Records of 332 patients screened for inclusion in three multicentre prospective trials were reviewed. Ten patients (3%) with a median age of 59 years and a median Karnofsky performance status of 70% were identified. Seven patients had B-cell and three had T-cell lymphoma. The median growth fraction was 4%. The radiological morphology was unusual for PCNSL in eight patients. Three patients underwent complete tumour resection, combined with chemotherapy in one patient and with chemotherapy plus local radiotherapy in another. Four patients received chemotherapy and three received chemotherapy plus whole-brain irradiation, resulting in four complete remissions, two no-change situations and one progressive disease. Patients had an overall survival (OAS) of 2-58+ months with a 2-year OAS of 67%. Low-grade PCNSL may differ from classical high-grade PCNSL in its clinical features and radiological morphology. The clinical course may be variable and frequently more indolent than in classical PCNSL.
Daclatasvir plus peginterferon alfa and ribavirin for treatment-naive chronic hepatitis C genotype 1 or 4 infection: a randomised study.

To evaluate the safety and efficacy of daclatasvir, an HCV NS5A inhibitor with pangenotypic activity, administered with peginterferon-alfa-2a/ribavirin.



In this Phase 2b double-blind, placebo-controlled study, treatment-naive adults with HCV genotype 1 (N=365) or 4 (N=30) infection were randomly assigned (2:2:1) to daclatasvir 20 mg or 60 mg, or placebo once daily plus weekly peginterferon-alfa-2a and twice-daily ribavirin. Daclatasvir recipients achieving protocol-defined response (PDR; HCV-RNA<lower limit of quantitation at Week 4 and undetectable at Week 10) were rerandomised at Week 12 to continue daclatasvir/peginterferon-alfa-2a/ribavirin for 24 weeks total duration or to placebo/peginterferon-alfa-2a/ribavirin for another 12 weeks. Patients without PDR and placebo patients continued peginterferon-alfa/ribavirin through Week 48. Primary efficacy endpoints were undetectable HCV-RNA at Weeks 4 and 12 (extended rapid virologic response, eRVR) and at 24 weeks post-treatment (sustained virologic response, SVR24) among genotype 1-infected patients.



Overall, eRVR was achieved by 54.4% (80/147) of genotype 1-infected patients receiving daclatasvir 20 mg, 54.1% (79/146) receiving 60 mg versus 13.9% (10/72) receiving placebo. SVR24 was achieved among 87 (59.2%), 87 (59.6%), and 27 (37.5%) patients in these groups, respectively. Higher proportions of genotype 4-infected patients receiving daclatasvir 20 mg (66.7%; 8/12) or 60 mg (100.0%; 12/12) achieved SVR24 versus placebo (50.0%; 3/6). A majority of daclatasvir-treated patients achieved PDR and experienced less virologic failure and higher SVR24 rates with a shortened 24-week treatment duration. Adverse events occurred with similar frequency across all treatment groups.



The combination of daclatasvir/peginterferon-alfa/ribavirin was generally well tolerated and achieved higher SVR24 rates compared with placebo/peginterferon-alfa/ribavirin among patients infected with HCV genotype 1 or 4.
Maintenance antipsychotic therapy: is the cure worse than the disease?

The serious long-term complications of maintenance antipsychotic therapy led the authors to undertake a critical review of outpatient withdrawal studies. Key findings included the following: 1) for a least 40% of outpatient schizophrenics, drugs seem to be essential for survival in the community; 2) the majority of patients who relapse after drug withdrawal recompensate fairly rapidly upon reinstitution of antipsychotic drug therapy; 3) placebo survivors seem to function as well as drug survivors--thus the benefit of maintenance drug therapy appears to be prevention of relapse; and 4) some cases of early relapse after drug withdrawal may be due to dyskinesia rather than psychotic decompensation. The authors urge clinicians to evaluate each patient on maintenance antipsychotic therapy in terms of feasibility of drug withdrawal and offer practical guidelines for withdrawal and subsequent management.
Postoperative adjuvant immunochemotherapy with mitomycin C, futraful and PSK for gastric cancer. An analysis of data on 579 patients followed for five years

In order to evaluate the combination of immunochemotherapy with mitomycin C (MMC), futraful (FT) and PSK, as an adjuvant to surgery for curatively resected gastric cancer, a randomized controlled study by the sealed envelope method was performed with the participation of 97 hospitals in the Kyushu and Chugoku districts of Japan. The MMC+FT+ PSK group showed a significant increase in 5 year survival from the other groups (p<0.05). Moreover the survival rate was significantly higher in the MMC+FT+PSK group than in the MMC+FT group (p<0.01). According to the analysis on stratification, the MMC+FT+PSK group showed the best survival rate in cases with positive lymph node metastases, positive serosal invasion and positive lymph node metastases plus serosal invasion, and in cases of undifferentiated carcinoma by histological type and in those with a preoperative positive PPD reaction (p<0.01 or p<0.05). Thus, the combination of MMC, FT and PSK was indicated to be useful as an adjuvant immunochemotherapy for those patients with gastric cancer submitted to curative resection.
A phase 2 trial of bevacizumab and high-dose interferon alpha 2B in metastatic melanoma.

Bevacizumab is a humanized recombinant monoclonal antibody that neutralizes vascular endothelial growth factor, an agent with proangiogenic effects in melanoma. Interferon alpha (IFN-α) has antiangiogenic properties through its ability to downregulate basic-fibroblast growth factor levels. We hypothesized that the coadministration of these agents would lead to tumor regression. Patients with metastatic melanoma received bevacizumab 15 mg/kg intravenously on day 1 of the 2-week cycle. IFN-α was administered thrice weekly at 5 MU/m subcutaneously during cycle 1 and was increased to 10 MU/m during cycle 2. Patients were restaged every 6 cycles. Patients with stable disease or a response continued with therapy. Baseline serum vascular endothelial growth factor and fibroblast growth factor were measured. Twenty-five patients were accrued. Mean age was 58.4 years. Eleven patients required IFN-α dose reductions due to toxicity. Common grade 3 toxicities associated with IFN-α included fatigue and myalgia. Bevacizumab administration was associated with grade 2-3 proteinuria in 6 patients. Grade 4 adverse events were pulmonary embolus (1), myocardial infarction (1), and stroke (1). Six patients had a partial response, and 5 patients exhibited stable disease that lasted more than 24 weeks (range: 30 to 122 wk). Median progression-free survival and overall survival were 4.8 and 17 months, respectively. Significantly lower fibroblast growth factor levels were observed in patients with a partial response compared to those with stable or progressive disease (P=0.040). Administration of bevacizumab with IFN led to a clinical response in 24% of patients with stage IV melanoma and stabilization of disease in another 20% of patients. This regimen has activity in advanced melanoma.
Determinants of urban-rural differences in cardiovascular risk factors in middle-aged women in India: a cross-sectional study.

Cardiovascular diseases (CVD) are the most important cause of death amongst middle-aged Indian women. To determine prevalence of CVD risk factors and their determinants we performed a nationwide study.



Population based studies amongst women 35-70 years were performed in four urban and five rural locations in India. Location based stratified sampling was performed and we enrolled 4624 (rural 2616, urban 2008) of eligible 8000 women (58%). Demographic details, medical history, diet, physical activity and anthropometry were recorded using standardised techniques. Blood haemoglobin, glucose and total cholesterol were determined. Risk factors were diagnosed using current guidelines. Descriptive statistics are reported. Stepwise multivariate logistic regression was performed to identify determinants of urban-rural differences.



In urban women mean body mass index (BMI), waist circumference, waist-hip ratio (WHR), systolic BP, haemoglobin, fasting glucose and cholesterol were significantly greater (p<0.01). Age-adjusted prevalence of risk factors (%) in urban vs rural was of obesity BMI ≥ 25 kg/m(2) (45.6 vs 22.5), truncal obesity WHR>0.9 (44.3 vs 13.0), hypertension (37.5 vs 29.3), hypercholesterolemia ≥ 200 mg/dl (27.7 vs 13.5), and diabetes (15.1 vs 4.3) greater whilst any tobacco use (19.6 vs 41.6) or smoking lower. Significant determinants of urban-rural differences were greater income and literacy, dietary fats, low physical activity, obesity and truncal obesity (p<0.01).



Greater prevalence of CVD risk factors in urban middle-aged women is explained by greater income and literacy, dietary fat, low physical activity and obesity.
Phase I study of NGR-hTNF, a selective vascular targeting agent, in combination with cisplatin in refractory solid tumors.

NGR-hTNF exploits the tumor-homing peptide asparagine-glycine-arginine (NGR) for selectively targeting TNF-α to an aminopeptidase N overexpressed on cancer endothelial cells. Preclinical synergism with cisplatin was displayed even at low doses. This study primarily aimed to explore the safety of low-dose NGR-hTNF combined with cisplatin in resistant/refractory malignancies. Secondary aims included pharmacokinetics (PKs), pharmacodynamics, and activity.



NGR-hTNF was escalated using a doubling-dose scheme (0.2-0.4-0.8-1.6 μg/m(2)) in combination with fixed-dose of cisplatin (80 mg/m(2)), both given intravenously once every three weeks. PKs and circulating TNF-receptors (sTNF-Rs) were assessed over the first three cycles.



Globally, 22 patients (12 pretreated with platinum) received a range of one to ten cycles. Consistently with the low-dose range tested, maximum-tolerated dose was not reached. No dose-limiting toxicities (DLTs) were observed at 0.2 (n = 4) and 0.4 μg/m(2) (n = 3). One DLT (grade 3 infusion-related reaction) was observed at 0.8 μg/m(2). This dose cohort was expanded to six patients without further DLTs. No DLTs were noted also at 1.6 μg/m(2) (n = 3). NGR-hTNF exposure increased dose-proportionally without apparent PK interactions with cisplatin. No shedding of sTNF-Rs was detected up to 0.8 μg/m(2). At the dose level of 0.8 μg/m(2), expanded to 12 patients for activity assessment, a platinum-pretreated lung cancer patient achieved a partial response lasting more than six months and five patients maintained stable disease for a median time of 5.9 months.



The combination of NGR-hTNF 0.8 μg/m(2) with cisplatin 80 mg/m(2) showed favorable toxicity profile and promising antitumor activity.
No benefit of adjuvant Fluorouracil Leucovorin chemotherapy after neoadjuvant chemoradiotherapy in locally advanced cancer of the rectum (LARC): Long term results of a randomized trial (I-CNR-RT).

To evaluate the effect of adjuvant chemotherapy (ACT) in locally advanced rectal cancer (LARC) after neoadjuvant chemoradiation (NACT-RT). The study was funded by the Italian National Research Council (CNR).



From September 1992 to January 2001, 655 patients with LARC (clinically T3-4, any N) treated with NACT-RT and surgery, were randomized in two arms: follow-up (Arm A) or 6 cycles of ACT with 5 fluorouracil (5FU)-Folinic Acid (Arm B). NACT-RT consisted of 45Gy/28/ff concurrent with 5FU (350mg/sqm) and Folinic Acid (20mg/sqm) on days 1-5 and 29-33; surgery was performed after 4-6weeks. Median follow up was 63·7months. Primary end point was overall survival (OS).



634/655 patients were evaluable (Arm A 310, Arm B 324); 92·5% of Arm A and 91% of Arm B patients received the preoperative treatment as in the protocol; 294 patients of Arm A (94·8%) and 296 of Arm B (91·3%) underwent a radical resection; complete pathologic response and overall downstaging rates did not show any significant difference in the two arms. 83/297 (28%) patients in Arm B, never started ACT. Five year OS and DFS did not show any significant difference in the two treatment arms. Distant metastases occurred in 62 patients (21%) in Arm A and in 58 (19·6%) in Arm B.



In patients with LARC treated with NACT-RT, the addition of ACT did not improve 5year OS and DFS and had no impact on the distant metastasis rate.
Neurocognitive signs in prodromal Huntington disease.

PREDICT-HD is a large-scale international study of people with the Huntington disease (HD) CAG-repeat expansion who are not yet diagnosed with HD. The objective of this study was to determine the stage in the HD prodrome at which cognitive differences from CAG-normal controls can be reliably detected.



For each of 738 HD CAG-expanded participants, we computed estimated years to clinical diagnosis and probability of diagnosis in 5 years based on age and CAG-repeat expansion number (Langbehn, Brinkman, Falush, Paulsen, & Hayden, 2004). We then stratified the sample into groups: NEAR, estimated to be ≤9 years; MID, between 9 and 15 years; and FAR, ≥15 years. The control sample included 168 CAG-normal participants. Nineteen cognitive tasks were used to assess attention, working memory, psychomotor functions, episodic memory, language, recognition of facial emotion, sensory-perceptual functions, and executive functions.



Compared with the controls, the NEAR group showed significantly poorer performance on nearly all of the cognitive tests and the MID group on about half of the cognitive tests (p = .05, Cohen's d NEAR as large as -1.17, MID as large as -0.61). One test even revealed significantly poorer performance in the FAR group (Cohen's d = -0.26). Individual tasks accounted for 0.2% to 9.7% of the variance in estimated proximity to diagnosis. Overall, the cognitive battery accounted for 34% of the variance; in comparison, the Unified Huntington's Disease Rating Scale motor score accounted for 11.7%.



Neurocognitive tests are robust clinical indicators of the disease process prior to reaching criteria for motor diagnosis of HD.