nils-herrmann/clean_scirepeval huggingface dataset:
Abdominal obesity and the spectrum of global cardiometabolic risks in US adults

To compare the association of obesity and abdominal obesity with cardiometabolic risk factor burden and global estimated coronary heart disease (CHD) risk among multiethnic US adults.A total of 4456 participants (representing 194.9 million adults) aged 20–79 years in the 2003–2004 National Health and Nutrition Examination Survey (Body mass index (BMI) and waist circumference (WC) measures, CHD risk factors and a 10-year estimated CHD risk based on Framingham algorithms. Obesity was defined as a BMI ⩾30 kg/m2 and abdominal obesity as a WC >88 cm in women and >102 cm in men. High CHD risk status included diabetes, cardiovascular disease (CVD) or a 10-year Framingham risk score of >20%.Results:Overall, abdominal obesity was present in 42.3% of men and 62.5% of women and in 53.6% of whites, 56.9% of blacks and 50.5% of Hispanics (P<0.001 between gender and ethnicity). However, using International Diabetes Federation (IDF)-recommended WC cut points for Hispanics, the prevalence of abdominal obesity was 78.3%. Mean levels of low-density lipoprotein cholesterol (LDL-C), systolic and diastolic blood pressure, fasting glucose and C-reactive protein increased, and high-density lipoprotein cholesterol (HDL-C) decreased (P<0.001) according to BMI and WC categories, although these associations were attenuated in blacks for blood pressure, LDL-C, HDL-C and triglycerides. Of those with high WC, 25–35% had ⩾3 cardiometabolic risk factors. High CHD risk among those with high WC was most common in men (27.9%) and non-Hispanic whites (23.9%). Persons with a high vs normal WC, adjusted for age, gender, ethnicity and BMI were more likely to have ⩾3 cardiometabolic risk factors (odds ratio (OR)=5.1, 95% confidence interval (CI)=3.9–6.6) and were classified as high CHD risk (OR=1.5, 95% CI=1.1–2.0).Conclusion:The association of abdominal obesity with risk factors varies by ethnicity and is independently associated with high CHD risk status, further validating its clinical significance.
Multicentre phase II study of cisplatin-etoposide chemotherapy for advanced large-cell neuroendocrine lung carcinoma: the GFPC 0302 study.

The optimal treatment of large-cell neuroendocrine carcinoma (LCNEC) of the lung remains unclear. Here, our primary objective was to assess the efficacy of cisplatin-etoposide doublet chemotherapy in advanced LCNEC. Accuracy of the pathological diagnosis and treatment toxicity were assessed as secondary objectives.



Prospective, multicentre, single-arm, phase II study with a centralised review of treatment-response and pathological data. Patients had untreated performance status (PS) 0/1 stage IV/IIIB LCNEC and received cisplatin (80 mg/m22 d1) and etoposide (100 mg/m22 d1-3) every 21 days.



Eighteen centres included 42 patients (mean age, 59 ± 9 years; 69% men; median of four cycles/patient). At least one grade-3/4 toxicity occurred in 59% of patients (neutropaenia, thrombocytopaenia, and anaemia in 32%, 17%, and 12%, respectively). The median progression-free survival (PFS) and overall survival (OS) were 5.2 months (95% confidence interval, CI, 3.1-6.6) and 7.7 months (95% CI, 6.0-9.6), respectively. The centralised pathologist review reclassified 11 of 40 (27.5%) patients: 9 as small-cell lung cancer, 1 as undifferentiated non-small-cell lung cancer, and 1 as atypical carcinoid. Survival data were not significantly changed by excluding the reclassified patients.



The pathological diagnosis of LCNEC is difficult. The outcomes of advanced LCNEC treated with cisplatin-etoposide doublets are poor, similar to those of patients with advanced small-cell lung carcinoma (SCLC).
Prospective study of sexual dysfunction in men with rectal cancer: feasibility and results of nerve sparing surgery

Rectal cancer surgery is impaired by a high rate of postoperative sexual dysfunction cause of frequent nerve injuries. The aim of this study was to prospectively evaluate sexual function in a group of male patients after total mesorectal excision (TME) for rectal cancer, using an autonomic nerve sparing technique. All patients underwent autonomic nerve preserving TME. Sexual function was assessed using the International Index of Erectile Function standardized questionnaire. All patients were studied preoperatively and at 3, 6, 12, 18, and 24 months after surgery. Fifty-one patients with adenocarcinoma of the rectum were enrolled; after excluding 16 patients not sexually active, nine with T4 stage disease and six with metastatic disease, 20 patients were prospectively evaluated. The preoperative erectile function (EF) domain score of the International Index of Erectile Function was 24.3 (±4.1). The score of the EF domain was 17.6 (±7.5), 19.l9 (±7.2), 20.3 (±7.4), 20.5 (±7.4), and 20.6 (±7.4) at 3, 6, 12, 18, and 24 months after surgery. In the group of patients in which there were no macroscopic damages to the nerves, only two out of 15 (13.3%) developed erectile dysfunction. All five patients in whom incomplete pelvic nerve preservation was necessary developed erectile dysfunction. Our data show that nerve sparing technique can reduce the incidence of sexual dysfunction. Unfortunately, the technique is not applicable in every patient. Indications and techniques of autonomic nerve preservation are not standardized. Controlled trials with long-term follow-up seem to be necessary.
Comparison of standard and gender-specific posterior-cruciate-retaining high-flexion total knee replacements: a prospective, randomised study.

We undertook a study in which 138 female patients with a mean age of 71.2 years (51 to 82) received a standard NexGen CR-flex prosthesis in one knee and a gender-specific NexGen CR-flex prosthesis in the other. The mean follow-up period was 3.25 years (3.1 to 3.5). The aspect ratios of the standard and gender-specific prostheses were compared with that of the distal femur. The mean post-operative Knee Society knee scores were 94 (70 to 100) and 93 (70 to 100) points and the function scores were 83 (60 to 100) and 84 (60 to 100) points for the standard implants and the gender-specific designs, respectively. The mean post-operative Western Ontario and McMaster Universities score was 26.4 points (0 to 76). Patient satisfaction, the radiological results and the complication rates were similar in the two groups. In those with a standard prosthesis, the femoral component was closely matched in 80 knees (58.0%), overhung in 14 (10.1%) and undercovered the bone in 44 (31.9%). In those with a gender-specific prosthesis, it was closely matched in 15 knees (10.9%) and undercovered the bone in 123 (89.1%). Since we found no significant differences between the two groups with regard to the clinical and radiological results, patient satisfaction or complication rate, the goal of the design of the gender-specific CR-flex prosthesis to improve the outcome was not achieved in our patients.
The value of episodic, intensive blood glucose monitoring in non-insulin treated persons with type 2 diabetes: Design of the Structured Testing Program (STeP) Study, a cluster-randomised, clinical trial [NCT00674986]

The value and utility of self-monitoring of blood glucose (SMBG) in non-insulin treated T2DM has yet to be clearly determined. Findings from studies in this population have been inconsistent, due mainly to design differences and limitations, including the prescribed frequency and timing of SMBG, role of the patient and physician in responding to SMBG results, inclusion criteria that may contribute to untoward floor effects, subject compliance, and cross-arm contamination. We have designed an SMBG intervention study that attempts to address these issues.



The Structured Testing Program (STeP) study is a 12-month, cluster-randomised, multi-centre clinical trial to evaluate whether poorly controlled (HbA1c >or= 7.5%), non-insulin treated T2DM patients will benefit from a comprehensive, integrated physician/patient intervention using structured SMBG in US primary care practices. Thirty-four practices will be recruited and randomly assigned to an active control group (ACG) that receives enhanced usual care or to an enhanced usual care group plus structured SMBG (STG). A total of 504 patients will be enrolled; eligible patients at each site will be randomly selected using a defined protocol. Anticipated attrition of 20% will yield a sample size of at least 204 per arm, which will provide a 90% power to detect a difference of at least 0.5% in change from baseline in HbA1c values, assuming a common standard deviation of 1.5%. Differences in timing and degree of treatment intensification, cost effectiveness, and changes in patient self-management behaviours, mood, and quality of life (QOL) over time will also be assessed. Analysis of change in HbA1c and other dependent variables over time will be performed using both intent-to-treat and per protocol analyses. Trial results will be available in 2010.



The intervention and trial design builds upon previous research by emphasizing appropriate and collaborative use of SMBG by both patients and physicians. Utilization of per protocol and intent-to-treat analyses facilitates a comprehensive assessment of the intervention. Use of practice site cluster-randomisation reduces the potential for intervention contamination, and inclusion criteria (HbA1c >or= 7.5%) reduces the possibility of floor effects. Inclusion of multiple dependent variables allows us to assess the broader impact of the intervention, including changes in patient and physician attitudes and behaviours.
Efficacy of a protein kinase C inhibitor (tamoxifen) in the treatment of acute mania: a pilot study.

Considerable preclinical biochemical and behavioral data suggest that protein kinase C inhibition would bring about antimanic effects. Notably, the structurally highly dissimilar antimanic agents lithium and valproate, when administered in therapeutically relevant paradigms, attenuate protein kinase C [corrected] function. There is currently only one relatively selective protein kinase C inhibitor that crosses the blood-brain barrier available for human use--tamoxifen. Our group recently conducted a single-blind study with tamoxifen in acute mania and found that it significantly decreased manic symptoms within a short period of time (3-7 days). In this study, we investigated whether antimanic effects can be achieved with a protein kinase C inhibitor in subjects with mania.



In a double-blind, placebo-controlled study, 16 subjects with bipolar disorder, manic or mixed, with or without psychotic features, were randomly assigned to receive tamoxifen (20-140 mg/day; n = 8) or placebo (n = 8) for three weeks. Primary efficacy was assessed by the Young Mania Rating Scale.



Subjects on tamoxifen showed significant improvement in mania compared to placebo as early as five days, an effect that remained significant throughout the three-week trial. The effect size for the drug difference was very large (d = 1.08, 95% confidence interval 0.45-1.71) after three weeks (p = 0.001). At study endpoint, response rates were 63% for tamoxifen and 13% for placebo (p = 0.12).



Antimanic effects resulted from a protein kinase C inhibitor; onset occurred within five days. Large, controlled studies with selective protein kinase C inhibitors in acute mania are warranted.
Dynamics of pain: fractal dimension of temporal variability of spontaneous pain differentiates between pain States.

Spontaneous pain is a common complaint in chronic pain conditions. However, its properties have not been explored. Here we study temporal properties of spontaneous pain. We examine time variability of fluctuations of spontaneous pain in patients suffering from chronic back pain and chronic postherpetic neuropathy and contrast properties of these ratings to normal subjects' ratings of either acute thermal painful stimuli or of imagined back pain. Subjects are instructed to continuously rate their subjective assessment of the intensity of pain over a 6- to 12-min period. We observe that the fluctuations of spontaneous pain do not possess stable mean or variance, implying that these time series can be better characterized by fractal analysis. To this end, we apply time and frequency domain techniques to characterize variability of pain ratings with a single parameter: fractal dimension, D. We demonstrate that the majority of ratings of spontaneous pain by the patients have fractal properties, namely they show a power law relationship between variability and time-scale length; D is distinct between types of chronic pain, and from ratings of thermal stimulation or of imagined pain; and there is a correspondence between D for pain ratings and D for brain activity, in chronic back pain patients using fMRI. These results show that measures of variability of spontaneous pain differentiate between chronic pain conditions, and thus may have mechanistic and clinical utility.
Covert orienting and focusing of attention in children with attention deficit hyperactivity disorder

Performance on the covert visuo-spatial attentional functions of orienting and focusing by a group of ADHD children (n = 20) was compared to that of age and sex-matched control children. In Experiment 1, responses were given to cued targets at valid and invalid locations. In Experiment 2, responses were given to targets presented in small, medium-sized or large visual field locations. For both experiments, the hypotheses that reaction times of ADHD children would be greater than those of control children and that performance would be asymmetrical, were supported. For Experiment 1, ADHD children showed bilaterally greater 'benefits' from having directed attention to the cued location and greater 'costs' in having to relocate the attentional focus than controls. In Experiment 2, the hypothesis that the function of focusing attention by ADHD children may show breakdown in the usual pattern of an increase in reaction time with focus area was partly supported by the finding of similar reaction times to targets presented in medium-sized and large regions of the left visual hemifield. These results have been interpreted as reflecting a stronger anchorage of attention by ADHD children upon a cued location and an inability to shift covert attention easily to an alternative location. The breakdown of the focusing function suggests adoption of similar time response sets across focus area size by the more compromised right hemisphere.
Progression of chronic renal failure in a historical group of patients with nephropathic cystinosis

In a historical group of 205 patients with infantile or adolescent cystinosis treated without cysteamine, the rate of deterioration of renal function was analysed retrospectively. Patient survival curves and renal survival data are presented. Longitudinal data of serum creatinine values (n=3280) in 157 patients were plotted for each patient, smoothed by the method of the running medians and grouped into 12 serum creatinine classes. In every patient the age at the last smoothed serum creatinine value observed in each serum creatinine class was determined. These virtual age values were then summarized per serum creatinine class, expressed as median and centiles and plotted, thus describing the “natural” course of the disease. In 9 pairs of affected siblings the rate of progression showed a median difference of about 12 months. Our data describe the “natural” course of nephropathic cystinosis and can be used as a prognostic aid for recently detected patients. The data can also be applied for the assessment of the influence of new therapeutic strategies on the rate of progression of renal failure in cystinotic patients.
Comparison of daily filgrastim and pegfilgrastim to prevent febrile neutropenia in Asian lymphoma patients.

Febrile neutropenia (FN) is a highly prevalent complication of chemotherapy, particularly in patients with non-Hodgkin's lymphoma. This study aimed to compare the efficacy of filgrastim and pegfilgrastim in Asian lymphoma patients by evaluating the incidence of FN and associated complications.



This was a single-center, retrospective cohort study in Asian lymphoma patients who received chemotherapy with primary prophylactic granulocyte colony-stimulating factors support between January 2008 and August 2009. Data were analyzed using an intent-to-treat approach, which aimed to reflect actual prescribing practices.



A total of 204 Asian lymphoma patients were included in this study, with 81 patients in the filgrastim arm and 123 patients in the pegfilgrastim arm. Overall, the incidence of breakthrough FN was similar between the two groups of patients (13.6%: filgrastim arm vs 16.3%: pegfilgrastim arm; P=0.69). Neutropenic complications such as chemotherapy treatment delay and chemotherapy dose reduction were similar between the two arms.



In Asian patients, pegfilgrastim prophylaxis did not show a therapeutic advantage for preventing neutropenic outcomes compared with filgrastim prophylaxis.
A Calculator for Prostate Cancer Risk 4 Years After an Initially Negative Screen: Findings from ERSPC Rotterdam.

Inconclusive test results often occur after prostate-specific antigen (PSA)-based screening for prostate cancer (PCa), leading to uncertainty on whether, how, and when to repeat testing.



To develop and validate a prediction tool for the risk of PCa 4 yr after an initially negative screen.



We analyzed data from 15 791 screen-negative men aged 55-70 yr at the initial screening round of the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer.



Follow-up and repeat screening at 4 yr showed either no PCa, low-risk PCa, or potentially high-risk PCa (defined as clinical stage >T2b and/or biopsy Gleason score ≥ 7 and/or PSA ≥ 10.0 ng/ml). A multinomial logistic regression analysis included initial screening data on age, PSA, digital rectal examination (DRE), family history, prostate volume, and having had a previous negative biopsy. The 4-yr risk predictions were validated with additional follow-up data up to 8 yr after initial screening.



Positive family history and, especially, PSA level predicted PCa, whereas a previous negative biopsy or a large prostate volume reduced the likelihood of future PCa. The risk of having PCa 4 yr after an initially negative screen was 3.6% (interquartile range: 1.0-4.7%). Additional 8-yr follow-up data confirmed these predictions. Although data were based on sextant biopsies and a strict protocol-based biopsy indication, we suggest that men with a low predicted 4-yr risk (eg, ≤ 1.0%) could be rescreened at longer intervals or not at all, depending on competing risks, while men with an elevated 4-yr risk (eg, ≥ 5%) might benefit from immediate retesting. These findings need to be validated externally.



This 4-yr future risk calculator, based on age, PSA, DRE, family history, prostate volume, and previous biopsy status, may be a promising tool for reducing uncertainty, unnecessary testing, and overdiagnosis of PCa.
The clinical benefit of bevacizumab in metastatic colorectal cancer is independent of K-ras mutation status: analysis of a phase III study of bevacizumab with chemotherapy in previously untreated metastatic colorectal cancer.

Mutations of the K-ras gene were identified as a prognostic marker in metastatic colorectal cancer (mCRC). In addition, emerging data suggest that K-ras mutations are a negative predictor of clinical benefit from anti-epidermal growth factor receptor treatment in mCRC. Previously reported data suggest that the longer overall survival (OS) observed with bevacizumab treatment in mCRC is independent of alterations in the Ras/Raf/Mek/Erk pathway. We conducted additional analyses to better describe the clinical benefit of bevacizumab treatment in mCRC relative to K-ras mutation status.



Additional statistical analyses were done with data from K-ras mutation analyses in 230 patients who were treated with irinotecan, fluorouracil, and leucovorin (IFL) in combination with either bevacizumab or placebo in a randomized phase III study. Following microdissection, tissue was subject to DNA sequencing to identify K-ras mutations in codons 12 and 13. Hazard ratios for the bevacizumab group relative to the control group were estimated from an unstratified Cox regression model. The median progression-free survival (PFS), OS times, and objective response rates were compared.



K-ras status was assessed in 230 patients (28.3%). The median PFS was significantly longer in bevacizumab-treated patients with wild-type (wt)- (13.5 versus 7.4 months; hazard ratio 0.44, p < .0001) and mutant (m)-K-ras (9.3 versus 5.5 months; hazard ratio 0.41, p = .0008). A significantly higher response rate for IFL plus bevacizumab was observed only in wt-K-ras patients (60.0% versus 37.3%, p = .006) compared with 43.2% versus 41.2% in the m-K-ras group.



Bevacizumab provides significant clinical benefit in patients with mCRC expressing either mutant or wild-type K-ras.
Treatment-emergent adverse events after infusion of adherent stem cells: the MiSOT-I score for solid organ transplantation

Cellular therapy after organ transplantation is emerging as an intriguing strategy to achieve dose reduction of classical immunosuppressive pharmacotherapy. Here, we introduce a new scoring system to assess treatment-emergent adverse events (TEAEs) of adherent stem cell therapies in the clinical setting of allogeneic liver transplantation (for example, the MiSOT-I trial Eudract CT: 2009-017795-25).



The score consists of three independent modalities (set of parameters) that focus on clinically relevant events early after intravenous or intraportal stem cell infusion: pulmonary toxicity, intraportal-infusional toxicity and systemic toxicity. For each modality, values between 0 (no TEAE) and 3 (severe TEAE) were defined. The score was validated retrospectively on a cohort of n=187 recipients of liver allografts not receiving investigational cell therapy between July 2004 and December 2010. These patients represent a control population for further trials. Score values were calculated for days 1, 4, and 10 after liver transplantation.



Grade 3 events were most commonly related to the pulmonary system (3.5% of study cohort on day 4). Almost no systemic-related TEAEs were observed during the study period. The relative frequency of grade 3 events never exceeded 5% over all modalities and time points. A subgroup analysis for grade 3 patients provided no descriptors associated with severe TEAEs.



The MiSOT-I score provides an assessment tool to score specific adverse events that may occur after adherent stem cell therapy in the clinical setting of organ transplantation and is thus a helpful tool to conduct a safety study.