nils-herrmann/clean_scirepeval huggingface dataset:
Comparison between oral and intravenous fludarabine plus cyclophosphamide regime as front-line therapy in patients affected by chronic lymphocytic leukaemia: influence of biological parameters on the clinical outcome

The fludarabine plus cyclophosphamide (FC) regimen was reported to be superior to chlorambucil or fludarabine alone in terms of complete response (CR), overall response (OR) and progression-free survival (PFS) in previously untreated patients with chronic lymphocytic leukaemia (CLL). In the present study, we compared the efficacy and toxicity of FC administered through oral and intravenous route in 65 untreated patients affected by advanced CLL. No statistical differences were noticed between the two routes of administration in terms of OR, PFS, time to re-treatment (TTR) and overall survival (OS) of analysed patients. We also assessed the influence on the clinical outcome of the mutation status of the immunoglobulin variable region heavy chain (IgVH) gene, of the cytogenetic abnormalities and of the expression of ZAP70 and CD38 in patients' primary samples. Among the 58 evaluable patients, 31 (53%) achieved a CR and 18 (31%) a partial response. The median PFS was 35 months, median TTR was 42 months and median OS was not reached after 45 months (range, 1–161). A significantly lower OR rate was noticed in patients with high-risk cytogenetic abnormalities (del 17p, del 11q). In this study, high-risk cytogenetic abnormalities and unmutated IgVH genes were independent predictors of TTR. These results underline the importance of biological stratifications in front-line treatment of CLL patients. We confirm that FC is an effective regimen with mild toxicities; it could be recommended for patients with low-risk biological parameters who represent, in our experience, about 30% of the total.
Tai Chi Chuan, health-related quality of life and self-esteem: A randomized trial with breast cancer survivors

Health-related quality of life (HRQL) and self-esteem are often diminished among women diagnosed and treated for breast cancer. Tai Chi is a moderate form of exercise that may be an effective therapy for improving HRQL and self-esteem among these women. We sought to compare the efficacy of Tai Chi Chuan (TCC) and psychosocial support (PST) for improving HRQL and self-esteem among breast cancer survivors. A group of 21 women diagnosed with breast cancer, who had completed treatment within the last 30 months were randomized to receive 12 weeks of TCC or PST. Participants in both groups met three times a week for 60 minutes. HRQL and self-esteem were assessed at baseline, 6 weeks, and 12 weeks. The TCC group demonstrated significant improvements in HRQL, while the PST group reported declines in HRQL, with the differences between the two groups approaching significance at week 12. Additionally, the TCC group exhibited improvements in self-esteem, while the PST group reported declines in self-esteem, with the differences between groups reaching statistical significance at week 12. These findings, coupled with a visual inspection of the raw change scores, support the plausibility of a dose-response relationship concerning Tai Chi. In this pilot investigation, the TCC group exhibited improvements in HRQL and self-esteem from baseline to 6 and 12 weeks, while the support group exhibited declines. Randomized, controlled clinical trials with larger sample sizes are needed.
Dose-associated changes in safety and efficacy parameters observed in a 24-week maintenance trial of olanzapine long-acting injection in patients with schizophrenia

In a recently published 24-week maintenance study of olanzapine long-acting injection (LAI) in schizophrenia (Kane et al., 2010), apparent dose-associated changes were noted in both efficacy and safety parameters. To help clinicians balance safety and efficacy when choosing a dose of olanzapine LAI, we further studied these changes.



Outpatients with schizophrenia who had maintained stability on open-label oral olanzapine for 4 to 8 weeks were randomly assigned to "low" (150 mg/2 weeks; N = 140), "medium" (405 mg/4 weeks; N = 318), or "high" (300 mg/2 weeks; N = 141) dosages of olanzapine LAI for 24 weeks. Potential relationships between dose and several safety or efficacy measures were examined via regression analysis, the Jonckheere-Terpstra test (continuous data), or the Cochran-Armitage test (categorical data).



Safety parameters statistically significantly related to dose were mean weight change (low: +0.67 [SD = 4.38], medium: +0.89 [SD = 3.87], high: +1.70 [SD = 4.14] kg, p = .024; effect size [ES] = 0.264 high vs. low dose), mean change in prolactin (low: -5.61 [SD = 12.49], medium: -2.76 [SD = 19.02]), high: +3.58 [SD = 33.78] μg/L, p = .001; ES = 0.410 high vs. low dose), fasting triglycerides change from normal at baseline to high (low: 3.2%, medium: 6.0%, high: 18.9%, p = .001; NNT = 7 high vs. low dose) and fasting high-density lipoprotein cholesterol change from normal at baseline to low (low: 13.8%, medium: 19.6%, high: 30.7%, p = .019; NNT = 6 high vs. low dose). Efficacy measures significantly related to dose included Positive and Negative Syndrome Scale total score mean change (low: +2.66 [SD = 14.95], medium: -0.09 [SD = 13.47], high: -2.19 [SD = 13.11], p <.01; ES = 0.356 high vs. low dose), relapse rate (low: 16%, medium: 10%, high: 5%, p = .003; NNT = 9 high vs. low dose), all-cause discontinuation rate (low: 36%, medium: 30%, high: 24%, p = .037; NNT = 9 high vs. low dose), and rate of discontinuation due to efficacy-related reasons (low: 20%, medium: 14%, high: 6%, p <.001). Time to all-cause discontinuation (p = .035) and time to relapse (p = .005) were also significantly related to dose.



Analyses of several safety and efficacy parameters revealed significant associations with dose of olanzapine LAI, with the highest dose generally showing greater efficacy as well as greater adverse changes in metabolic safety measures. When considering olanzapine LAI, as with all antipsychotics, it is important to carefully consider the potential benefits and risks for an individual patient.
Chlorodeoxyadenosine and arabinosylcytosine in patients with acute myelogenous leukemia: pharmacokinetic, pharmacodynamic, and molecular interactions.

The effectiveness of arabinosylcytosine (ara-C) for the treatment of acute myelogenous leukemia (AML) depends on the formation of its active metabolite, the triphosphate of ara-C (ara-CTP). Using biochemical modulation strategies to increase the accumulation of ara-CTP in leukemia blasts, a clinical protocol was designed combining 2-chlorodeoxyadenosine (CdA), an inhibitor of ribonucleotide reductase, and ara-C for adults with AML. The protocol stipulated an infusion of 1 g/m2 of ara-C over 2 hours on day 1. A continuous infusion of CdA (12 mg/m2/d) begun 24 hours later and continued for 5 days. Identical doses of ara-C were administered on days 3, 4, 5, and 6. Pharmacokinetic and pharmacodynamic interactions between CdA and ara-C during therapy were investigated. To complement these studies, molecular actions of the triphosphate of ara-C and CdA on DNA extension by human DNA polymerase alpha in an in vitro model system was conducted. In the circulating leukemia blasts of 7 of the 9 patients studied, ara-CTP pharmacokinetics showed a median 40% increase in the rate of ara-CTP accumulation after 24 hours of CdA infusion. The ex vivo effect of CdA on accumulation of ara-CTP in AML blasts was similar to that during therapy except that the enhancement was less. The DNA synthetic capacity of the circulating blasts was inhibited to a greater extent by administration of CdA and ara-C in combination than by either one alone. Additionally the lowered level of DNA synthesis was maintained until the next infusion of ara-C. Endogenous levels of deoxynucleotides increased 24 hours after ara-C infusion. Administration of CdA in general lowered the concentrations of all dNTPs. DNA pol alpha incorporated CdATP and ara-CTP with high affinity in a DNA primer extending over an oligonucleotide template of defined sequence. Human DNA polymerase alpha extended DNA primers terminated by CdA monophosphate (CdAMP) at its 3'-end by incorporating ara-C monophosphate (ara-CMP). The tandem incorporation of CdAMP and ara-CMP resulted in nearly complete inhibition of DNA primer extension. The insertion of two analogs in sequence, inhibition of ribonucleotide reductase, and the metabolic potentiation of ara-CTP by CdA infusion may be responsible for sustained inhibition of DNA synthesis in the circulating leukemia blasts during therapy with this combination regimen.
Depression, heart rate variability, and exercise training in dialysis patients.

Functional limitations, altered cardiac autonomic activity, and psychological distress are known disorders in chronic hemodialysis (HD) patients, relating to increased morbidity and mortality. The aim of this study was to examine the influence of an exercise training program on emotional parameters and heart rate variability (HRV) indices, as well as to determine whether emotional stress contributes to autonomic dysfunction in these patients.



Forty-four HD patients were randomly assigned into group A (24 patients, aged 46.3+/-11.2 years), who participated in a 1-year intradialytic exercise training program and group B (20 patients, aged 45.8+/-10.8 years), who were used as controls. At baseline and a year after, measures of HRV were obtained for the estimation of standard deviation of RR intervals, the mean square successive differences, percentage of RR intervals differing by more than 50 ms from the preceding RR interval (pNN50), and low to high frequency components. Emotional parameters (Beck Depression Inventory - BDI and Hospital Anxiety and Depression Scale - HADS) were also assessed by validated questionnaires. Moreover, all patients performed a spiroergometric study for the estimation of VO2peak.



At baseline, all measurements were similar in the two groups and remained almost unchanged after a year in group B. After a year of training, VO2peak increased from 16.79+/-5.24 to 22.33+/-4.90 ml/kg per min (P<0.001) in group A. Trained patients also showed an increase in standard deviation of RR intervals by 58.8% (P<0.001), the mean square successive differences by 68.1% (P<0.001), pNN50 by 23.5% (P<0.001), and a low to high frequency ratio by 17.3% (P<0.001). Finally, at the end of the study, group A showed a decrease in BDI score by 34.5% (P<0.001) and HADS by 23.9% (P<0.001). Canonical correlation revealed significant inverse correlation among depression (in BDI and HADS) and HRV indices before and after exercise training.



Cardiac autonomic modulation seemed to be sensitive to the experience of persistent depression in HD patients. Significantly, exercise training reduced emotional distress and concomitantly improved HRV.
A prospective randomized controlled trial of sclerotherapy vs ligation in the prophylactic treatment of high-risk esophageal varices

Endoscopic ligation (EVL) and endoscopic sclerotherapy (EIS) are both effective in the treatment of bleeding esophageal varices, but the efficacy of the two techniques in the prophylaxis of first variceal bleeding has not been investigated. The aim of this study was to investigate the frequency of first variceal bleeding, the recurrence of varices, and survival after treatment with the two techniques, as compared to a nontreated control group.  A total of 157 patients with liver cirrhosis and advanced esophageal varices with no previous history of upper gastrointestinal bleeding were randomly assigned to either an EIS group (n= 55), an EVL group (n= 52), or a nontreated control group (n= 50). After the eradication of esophageal varices in the EIS and in EVL groups and in all control patients, the endoscopic examination was performed at 3-month intervals.  There were no significant differences between EIS and EVL in the eradication rate of esophageal varices (85% in the EIS group versus 81% in the EVL group). The mean number of sessions required to obtain eradication was lower in the EVL group than in the EIS group (4.8 ± 1.8 versus 6.2 ± 2.0; p= 0.0003), but the recurrence of esophageal varices was higher in the EVL group (31% versus 11%; p= 0.01). Total mortality was significantly lower in the EIS patients than in the controls (20% versus 38%; p= 0.04). It was also lower, but not significantly, in the EVL patients than in the controls (23% versus 38%; p= 0.10). A significant decrease in variceal bleeding was observed both in sclerotherapy cases (20%) and controls (54%; p= 0.0005) and in ligation cases and controls (29%; p= 0.01). No significant difference in bleeding episodes was observed between the sclerotherapy and ligation cases (p= 0.29). No serious complications were observed either in the EIS or EVL groups.  EIS and EVL are similarly effective in the prevention of first variceal bleeding. The choice between EIS and EVL depends on the skill of the endoscopic unit. For highly experienced surgeons facing no complications, sclerotherapy seems to be preferable; for all others, it is technically easier to perform ligation.
Targeting of low-dose CT screening according to the risk of lung-cancer death.

In the National Lung Screening Trial (NLST), screening with low-dose computed tomography (CT) resulted in a 20% reduction in lung-cancer mortality among participants between the ages of 55 and 74 years with a minimum of 30 pack-years of smoking and no more than 15 years since quitting. It is not known whether the benefits and potential harms of such screening vary according to lung-cancer risk.



We assessed the variation in efficacy, the number of false positive results, and the number of lung-cancer deaths prevented among 26,604 participants in the NLST who underwent low-dose CT screening, as compared with the 26,554 participants who underwent chest radiography, according to the quintile of 5-year risk of lung-cancer death (ranging from 0.15 to 0.55% in the lowest-risk group [quintile 1] to more than 2.00% in the highest-risk group [quintile 5]).



The number of lung-cancer deaths per 10,000 person-years that were prevented in the CT-screening group, as compared with the radiography group, increased according to risk quintile (0.2 in quintile 1, 3.5 in quintile 2, 5.1 in quintile 3, 11.0 in quintile 4, and 12.0 in quintile 5; P=0.01 for trend). Across risk quintiles, there were significant decreasing trends in the number of participants with false positive results per screening-prevented lung-cancer death (1648 in quintile 1, 181 in quintile 2, 147 in quintile 3, 64 in quintile 4, and 65 in quintile 5). The 60% of participants at highest risk for lung-cancer death (quintiles 3 through 5) accounted for 88% of the screening-prevented lung-cancer deaths and for 64% of participants with false positive results. The 20% of participants at lowest risk (quintile 1) accounted for only 1% of prevented lung-cancer deaths.



Screening with low-dose CT prevented the greatest number of deaths from lung cancer among participants who were at highest risk and prevented very few deaths among those at lowest risk. These findings provide empirical support for risk-based targeting of smokers for such screening. (Funded by the National Cancer Institute.).
Antioxidant vitamin supplementation reduces benzo(a)pyrene-DNA adducts and potential cancer risk in female smokers.

Elevated benzo(a)pyrene [B(a)P]-DNA adducts have been associated with 3-fold increased risk of lung cancer in current smokers. We assessed the chemopreventive effects of antioxidant supplementation using B(a)P-DNA adducts in leukocytes as an intermediate cancer risk marker.



Subjects were randomized to a double-blinded placebo-controlled clinical trial of antioxidant vitamin supplementation [500 mg vitamin C and 400 IU vitamin E (dl-alpha-tocopherol) daily] or placebo. Smokers with > or =10 cigarettes per day and serum cotinine > or =25 ng/mL were eligible for the study. B(a)P-DNA adduct level was the outcome. The randomization was stratified by gender and cigarettes per day (< or =20 or >20). Smoking habits and blood samples were collected every 3 months during the 15-month treatment period. Samples were analyzed for B(a)P-DNA adducts (high-performance liquid chromatography), plasma cotinine, vitamin levels, and GSTM1 genotype. The intent-to-treat model adjusted for B(a)P-DNA and cotinine at randomization.



Overall and among men, there was no effect of treatment on B(a)P-DNA adduct levels. Among treated women, B(a)P-DNA adducts decreased by 31% compared with women on placebo (P = 0.03). Among treated women with the GSTM1 genotype, there was a 43% decrease in adducts (P = 0.04).



Our primary hypothesis that the mean level of smoking-related B(a)P-DNA adducts would be lower in all subjects in the vitamin treatment group compared with all placebo-treated subjects was not substantiated. However, oursecondary gender-specific analysis found a significant reduction in B(a)P-DNA adducts in women with vitamin treatment, suggesting that antioxidant supplementation maymitigate some of the procarcinogenic effects of exposuretoB(a)P. The effect in GSTM1-null women suggeststhat certain subgroups may derive more benefit fromsupplementation. Although the results of this trial showthe potential chemopreventive role of antioxidants, thebest way for smokers to reduce their cancer risk remains smoking cessation.
Validity and reliability of electroencephalographic frontal alpha asymmetry and frontal midline theta as biomarkers for depression.

Electroencephalographic (EEG) frontal alpha asymmetry (FAA) and frontal midline (FM) theta have been suggested as biomarkers for depression and anxiety, but have mostly been assessed in small and non-clinical studies. In a clinical sample of 79 adults with depression (ICD-10: F32), resting EEG and scales of depression (MADRS) and anxiety (HADS-A) were measured at intake and after 3 months. FAA and FM theta values were referenced to a normative population database. Internal consistency, test-retest reliability, and correlations with psychiatric tests were examined. Reliability was sufficient. However, FAA and FM theta values were close to the general population, and correlations with psychiatric tests were mostly small and non-significant, with the exception of FAA on F7-F8 z-scores and HADS-A. We conclude that the validity of FAA and FM theta and therefore their potential as biomarkers for depression and anxiety remain unclear.
Interaction between body mass index and hormone-receptor status as a prognostic factor in lymph-node-positive breast cancer

The aim of this study was to determine the relationship between the body mass index (BMI) at a breast cancer diagnosis and various factors including the hormone-receptor, menopause, and lymph-node status, and identify if there is a specific patient subgroup for which the BMI has an effect on the breast cancer prognosis. We retrospectively analyzed the data of 8,742 patients with non-metastatic invasive breast cancer from the research database of Asan Medical Center. The overall survival (OS) and breast-cancer-specific survival (BCSS) outcomes were compared among BMI groups using the Kaplan-Meier method and Cox proportional-hazards regression models with an interaction term. There was a significant interaction between BMI and hormone-receptor status for the OS (P = 0.029), and BCSS (P = 0.013) in lymph-node-positive breast cancers. Obesity in hormone-receptor-positive breast cancer showed a poorer OS (adjusted hazard ratio [HR] = 1.51, 95% confidence interval [CI] = 0.92 to 2.48) and significantly poorer BCSS (HR = 1.80, 95% CI = 1.08 to 2.99). In contrast, a high BMI in hormone-receptor-negative breast cancer revealed a better OS (HR = 0.44, 95% CI = 0.16 to 1.19) and BCSS (HR = 0.53, 95% CI = 0.19 to 1.44). Being underweight (BMI < 18.50 kg/m2) with hormone-receptor-negative breast cancer was associated with a significantly worse OS (HR = 1.98, 95% CI = 1.00-3.95) and BCSS (HR = 2.24, 95% CI = 1.12-4.47). There was no significant interaction found between the BMI and hormone-receptor status in the lymph-node-negative setting, and BMI did not interact with the menopause status in any subgroup. In conclusion, BMI interacts with the hormone-receptor status in a lymph-node-positive setting, thereby playing a role in the prognosis of breast cancer.
Accelerated growth in short children with chronic renal failure treated with both strict dietary therapy and recombinant growth hormone

In a 12-month study, nine boys, aged 4.8–15.6 years, with bone ages 4.6–13 years, with moderate to severe chronic renal failure and resultant growth failure were treated with daily recombinant human growth hormone (rhGH), in conjunction with a strict low-protein/low-phosphate diet supplemented with keto and amino forms of the essential amino acids, histidine and additional energy. Improved growth had previously been observed with this dietary management over that obtained with conventional treatment for chronic renal failure. Each child had been on this diet for at least 2 years before rhGH was commenced. Mean height velocity increased from 4.6±1.3 to 9.0±1.3 cm/year (P<0.001) in the pre-pubertal group, and in the pubertal group from 5.4±1.4 to 10.4±1.8 cm/year (P<0.01). The mean height velocity standard deviation scores (SDSs) increased from −1.2±0.6 to +2.3±0.9 (P<0.001) in the pre-pubertal group and from −0.4±0.6 to +1.9±1.1 (P<0.01) in the pubertal group. Mean height SDS for chronological age increased from −2.2±0.7 to −1.5±0.5 (P<0.01) in the pre-pubertal group and from −1.9±0.7 to −1.3±0.9 in the pubertal group (P<0.02). There was no significant deterioration in renal function or renal bone disease, and bone age did not advance more than chronological age over the 12-month period.
Outcome value of Clara cell protein in serum of patients with acute respiratory distress syndrome

Injury to the alveolocapillary barrier characterizes ALI/ARDS; therefore determining levels of lung epithelium-specific small proteins in serum may help predict clinical outcomes. We examined whether serum Clara cell protein (CC-16) concentration is correlated with the outcome, mechanical ventilation duration, and incidence of nonpulmonary organ failure. Prospective multicenter observational study conducted by the Quebec Critical Care Network. Seventy-eight adult ARDS patients requiring mechanical ventilation were enrolled and 28-day mortality was the primary outcome. Ventilatory parameters were computed and blood was sampled daily. Clinical information collected included cause of death, duration of mechanical ventilation, number of ventilator-free days, and organ failures. Median serum levels of CC-16 were significantly higher in nonsurvivors than survivors on days 0–2 (19.93 μg/l, IQR 11.8–44.32, vs. 8.9, 5.66–26.38) and sustained up to day 14. CC-16 levels were correlated positively with the number of failing organs (ρ = 0.3623) and requirement for prolonged mechanical ventilation. Predictors of patient mortality included age, arterial carbon dioxide partial pressure, CC-16, and APACHE II score (odds ratios 1.35, 1.52, 1.37, 1.159, respectively). Higher initial CC-16 serum level is associated with increased risk of death, fewer ventilator-free days, and increased frequency of nonpulmonary multiple organ failure. CC-16 is a valuable biomarker of ARDS that may help predict outcome among ARDS patients with high-risk mortality.