nils-herrmann/clean_scirepeval huggingface dataset:
Results of the randomized phase IIB ADMIRE trial of FCR with or without mitoxantrone in previously untreated CLL

ADMIRE was a multicenter, randomized-controlled, open, phase IIB superiority trial in previously untreated chronic lymphocytic leukemia. Conventional front-line therapy in fit patients is fludarabine, cyclophosphamide and rituximab (FCR).  improved remission rates. Two hundred and fifteen patients were recruited to assess the primary end point of complete remission (CR) rates according to International Workshop on Chronic Lymphocytic Leukemia criteria. Secondary end points were progression-free survival (PFS), overall survival (OS), overall response rate, minimal residual disease (MRD) negativity and safety. At final analysis, CR rates were 69.8 FCR vs 69.3% FCM-R (adjusted odds ratio (OR): 0.97; 95% confidence interval (CI): (0.53–1.79), P=0.932). MRD-negativity rates were 59.3 FCR vs 50.5% FCM-R (adjusted OR: 0.70; 95% CI: (0.39–1.26), P=0.231). During treatment, 60.0% (n=129) of participants received granulocyte colony-stimulating factor as secondary prophylaxis for neutropenia, a lower proportion on FCR compared with FCM-R (56.1 vs 63.9%). The toxicity of both regimens was acceptable. There are no significant differences between the treatment groups for PFS and OS. The trial demonstrated that the addition of mitoxantrone to FCR did not increase the depth of response. Oral FCR was well tolerated and resulted in impressive responses in terms of CR rates and MRD negativity compared with historical series with intravenous chemotherapy.
Pharmacokinetics of Levodopa, Carbidopa, and 3-O-Methyldopa Following 16-hour Jejunal Infusion of Levodopa-Carbidopa Intestinal Gel in Advanced Parkinson’s Disease Patients

Motor complications of Parkinson’s disease (PD) are a consequence of pulsatile dopaminergic stimulation from standard oral levodopa therapy. Levodopa–carbidopa intestinal gel (LCIG) is infused continuously via an intrajejunal percutaneous gastrostomy tube. This was the first study designed to characterize the full pharmacokinetic profiles of levodopa, carbidopa, and levodopa metabolite, 3-O-methyldopa (3-OMD) with 16-h LCIG infusion. Nineteen advanced PD patients (mean age, 65 years) who were on LCIG therapy for ≥30 days were enrolled. Patients received their individualized LCIG infusion doses, and serial pharmacokinetic samples were collected. Eighteen patients completed the study; 19 were assessed for safety. Mean (SD) total levodopa and carbidopa doses were 1,580 (403) and 395 (101) mg, respectively. Mean (SD) C avg (μg/mL) were 2.9 (0.84) for levodopa, 17.1 (4.99) for 3-OMD, and 0.22 (0.08) for carbidopa. The degree of fluctuation [defined as (C max − C min)/C avg] in levodopa, 3-OMD, and carbidopa plasma concentrations was very low (0.52, 0.21, and 0.96, respectively) during hours 2–16 of infusion. Accordingly, the within-subject coefficients of variation in levodopa, 3-OMD, and carbidopa concentrations were low (13%, 6%, and 19%, respectively). Three patients (16%) reported ≥1 treatment-emergent adverse event; none were considered severe. Continuous intrajejunal LCIG infusion maintained stable plasma levodopa levels over 16 h. Consistent exposure has been shown to reduce motor and nonmotor complications associated with oral medications. LCIG was well tolerated, consistent with previous reports.
Physical activity program for patients with dementia and their relative caregivers: randomized clinical trial in Primary Health Care (AFISDEMyF study)

The aging of the population has led to the increase of chronic diseases, especially dementia and cardiovascular diseases, and it has become necessary for their relatives to dedicate more time in caregiving.The objective in the first phase of this study is to evaluate the effectiveness of a Primary Health Care procedure to increase the physical activity of people with dementia and their relative caregivers. Also the effect on the cognitive state and cardiovascular risk will be assessed.



Clinical, multicentric and randomized trial. A simple random sampling to select 134 patients diagnosed with dementia will be carried out. After contacting their relatives, his/her participation in the trial will be requested. A basal assessment will be made and the participants will be asigned to control or intervention group (1:1).



The main measure will be the assessment of physical activity (podometer and 7-PAR) in patients and caregivers. In patients with dementia: ADAS-cog, functional degree and cardiovascular risk. In caregivers: cardiovascular risk, general health and quality of life.



For 3 months, participants will receive instructions to do physical activity with an adapted program. This program will be designed and applied by Primary Health Care professionals in patients with dementia and their caregivers. The control group will receive regular care.



An intention-to-treat analysis will be carried out by comparing the observed differences between basal, 6 and 12 months measures. Change in the mean of daily steps assessed with the podometer and 7-PAR will be the main result.



If the main hypothesis is confirmed, it could be useful to improve the cognitive state of patients with dementia, as well as the cardiovascular risk of all of them. The results can be good to improve technical features of the devices that register the physical activity in the patients with dementia, and it could facilitate its commercialization.
Atrial natriuretic factor in hypertension: bioactivity at normal plasma levels.

To ascertain whether small shifts in plasma atrial natriuretic factor (ANF) exerted biological effects in hypertension, we studied the renal, hemodynamic, and hormonal effects of ANF [human ANF-(99-126)] infused at a dose (0.75 pmol/kg/min for 3 hours) that would induce changes in plasma ANF confined to the normal, resting range, in a group of six young men with uncomplicated, mild essential hypertension. During ANF infusions, the patients excreted 11.8 +/- 2.0 mmol (mean +/- SEM) sodium more than during the time-matched placebo phase natriuresis (p less than 0.001, mean increase of 53% above placebo values). Urinary excretion of cyclic guanosine monophosphate rose to more than double (212%, p less than 0.001) placebo values. Plasma renin activity (0.4 +/- 0.05 vs. 0.9 +/- 0.12 nmol/l/hr, p less than 0.0001) and aldosterone concentrations (102 +/- 4 vs. 184 +/- 47 pmol/l, p less than 0.05) were clearly suppressed during administration of ANF. Plasma norepinephrine also fell significantly below placebo values (268 +/- 17 vs. 439 +/- 35 pg/ml, p less than 0.05). Urine volume, the excretion of electrolytes other than sodium, hematocrit, effective renal plasma flow, glomerular filtration rate, and filtration fraction were unaffected by ANF. Similarly, plasma concentrations of epinephrine, arginine vasopressin, adrenocorticotropic hormone, and cortisol were unchanged. Blood pressure and heart rate were unchanged. Minor perturbations in plasma ANF concentrations exert clear biological effects in patients with mild essential hypertension. These data suggest that such minor shifts in plasma ANF are of physiological relevance in mild hypertension and probably contribute to volume homeostasis in this condition.
High concentration of raltegravir in semen of HIV-infected men: results from a substudy of the EASIER-ANRS 138 trial.

Raltegravir concentrations and human immunodeficiency virus type 1 (HIV-1) RNA levels in semen samples from 10 treatment-experienced HIV-1-infected patients were measured after 24 weeks of raltegravir-based highly active antiretroviral therapy (HAART). Semen and plasma HIV-1 RNA levels were below 100 copies/ml and 50 copies/ml, respectively, in all samples. The median raltegravir concentrations in semen samples (n=10) and in plasma samples (n=9) drawn simultaneously were 345 (range, 83 to 707) ng/ml and 206 (range, 106 to 986) ng/ml, respectively. The median semen-to-plasma ratio of raltegravir concentration was 1.42 (range, 0.52 to 6.66), indicating good although variable levels of drug penetration of raltegravir in the seminal compartment.
HIV seroconversion during pregnancy in the Tygerberg region of Cape Town.

204 5. DeMatteo D, Wells LM, Salter Goldie R, King SM. The 'family' context of HIV: a need for comprehensive health and social policies. AIDS Care 2002; 14: 261-278. 6. Lewis SL, Wesley Y, Haiken HJ. Pediatric and family HIV. Psychosocial concerns across the continuum of disease. Nurs Clin North Am 1996; 31(1): 221-230. 7. Gellert GA, Durfee MJ, Berkowitz CD, Higgins KV, Tubiolo VC. Situational and sociodemographic characteristics of children infected with human immunodeficiency virus from pediatric sexual abuse. Pediatrics 1993; 91(1): 39-44. 8. Instone SL. Perceptions of children with HIV infection when not told for so long: implications for diagnosis disclosure. J Pediatr Health Care 2000; 14: 235-243. 9. Lee CL, Johann-Liang R. Disclosure of the diagnosis of HIV/AIDS to children born of HIVinfected mothers. AIDS Patient Care STDs 1999; 13(1): 41-45. 10. Thorne C, Newell ML, Peckham CS. Disclosure of diagnosis and planning for the future in HIV-affected families in Europe. Child Care Health Dev 2000; 26(1): 29-40. 11. Wiener LS, Battles HB, Heilman N, Sigelman CK, Pizzo PA. Factors associated with disclosure of diagnosis to children with HIV/AIDS. Pediatr AIDS HIV Infect 1996; 7(5): 310324. 12. Apateerapong W, Pancharoen C, Eggermont L, et al. HIV disclosure in children. Poster TuPeB4408 presented at the XV International AIDS Conference, Bangkok, 11-16 July 2004. eJIAS 2004; 1(1): 326.
Effect of darbepoetin alfa on exercise tolerance in anemic patients with symptomatic chronic heart failure: a randomized, double-blind, placebo-controlled trial.

This study sought to investigate whether darbepoetin alfa, an erythropoiesis-stimulating protein (ESP), improves exercise capacity in patients with symptomatic chronic heart failure (CHF) and anemia.



Anemia is common in patients with CHF.



In a multicenter, randomized, double-blind, placebo-controlled study, CHF patients with anemia (hemoglobin > or =9.0 to < or =12.0 g/dl) received subcutaneous placebo (n = 22) or darbepoetin alfa (n = 19) at a starting dose of 0.75 microg/kg every 2 weeks for 26 weeks. The primary end point was change in exercise tolerance from baseline to week 27 as measured by peak oxygen uptake (ml/min/kg body weight). Other end points included changes in absolute peak VO2 (ml/min), exercise duration, and health-related quality of life.



Differences (95% confidence interval) in mean changes from baseline to week 27 between treatment groups were 1.5 g/dl (0.5 to 2.4) for hemoglobin concentration (p = 0.005), 0.5 ml/kg/min (-0.7 to 1.7) for peak VO2 (p = 0.40), 45 ml/min (-35 to 127) for absolute peak VO2 (p = 0.27), and 108 s (-11 to 228) for exercise duration (p = 0.075). Patients receiving darbepoetin alfa compared with placebo had an improvement in self-reported Patient's Global Assessment of Change (79% vs. 41%, p = 0.01) but no significant differences in the Kansas City Cardiomyopathy and Minnesota Living with Heart Failure Questionnaire scores. Darbepoetin alfa was well tolerated.



In patients with symptomatic CHF and anemia, darbepoetin alfa increased and maintained hemoglobin concentrations and improved health-related quality of life. A trend toward increased exercise time but not peak VO2 was observed.
The effect of intraoperative dexmedetomidine on postoperative catheter-related bladder discomfort in patients undergoing transurethral bladder tumour resection: A double-blind randomised study.

Catheter-related bladder discomfort (CRBD) due to an indwelling urinary catheter causes postoperative distress. Dexmedetomidine is used as an anaesthetic adjuvant during general anaesthesia and has an antimuscarinic effect, which may be beneficial for the prevention and treatment of CRBD.



To determine the effect of intraoperative dexmedetomidine administration on the incidence of CRBD.



A double-blind, placebo-controlled, randomised study.



A tertiary care teaching hospital.



One-hundred and nine patients undergoing transurethral bladder tumour excision (TURB).



Patients were randomly allocated to two groups: control group (n = 55) received placebo and dexmedetomidine group (n = 54) received intraoperative dexmedetomidine (1 μg kg(-1) loading dose followed by 0.5 μg kg(-1) h(-1) continuous infusion).



The incidence and severity (mild, moderate, severe) of CRBD assessed at 0, 1, 6 and 24 h postoperatively.



The incidence of CRBD was significantly higher in the control group at 0 (78 vs. 50%; P = 0.004), 1 (86 vs. 57%; P = 0.002) and 6 h (82 vs. 63%; P = 0.047) postoperatively. The incidence of moderate to severe CRBD was higher in the control group at 0 (38 vs. 11%; P = 0.002) and 1 h (29 vs. 7%; P = 0.006) postoperatively. The number of patients having CRBD treated with tramadol was higher in the control group (24 vs. 12; P = 0.006). The mean end-tidal desflurane concentration during the surgery was higher in the control group (4.5 vs. 3.9%; P = 0.04). The postoperative pain score (numerical rating scale: 0 to 10) was higher in the control group at 0 (4.6 vs. 2.7; P = 0.002), and 1 h (3.8 vs. 2.7; P = 0.041). The number of patients treated with opioids was higher in the control group (21 vs. 8; P = 0.011).



Intraoperative dexmedetomidine administration decreased the incidence and severity of early postoperative CRBD as well as intraoperative desflurane and postoperative opioid requirements in patients undergoing TURB.
The advantage of 3D conformal treatment of lumbar spine metastases in comparison to traditional PA or AP-PA techniques: restoring an intermediate niche of therapeutic sophistication

To evaluate the effect of the 3D radiation field design on normal tissues compared with commonly used appositional fields in patients with lumbar spine metastases.



Ten comparative treatment plans for radiation of lumbar spine metastases were compared for posterior and anterior- posterior fields with 3D plans.



The PTV coverage in all comparative plans was similar. V 15 of the bowel in 3D, AP-PA and PA plans was 6.7 Gy (SD 6.47), 39.8 Gy (SD 11.4) and 37.3 Gy (SD15.7), respectively (p < 0.0001). The mean dose to both kidneys was 9.6 Gy (SD 4.8), 4.1 Gy (SD 3.9) and 4.6 Gy (SD 4.4) for appropriate plans (p = 0.002). Maximal dose to the spinal cord was 30.6 Gy (SD 2.1), 33.1 Gy (SD 9.8) and 37.7 Gy (SD 2) for 3D, AP-PA and PA plans.



3D conformal treatment planning of lumbar vertebral metastases was significantly better in term of bowel and spinal cord exposure compared to AP-PA and PA techniques. The exposure of the kidneys in 3D plans, while greater than in the comparative plans, did not violate accepted dose-volume thresholds.
Reduction of wound angiogenesis in patients treated with BMS-275291, a broad spectrum matrix metalloproteinase inhibitor.

The purpose of this study was to evaluate the feasibility of incorporating a novel wound angiogenesis assay into a Phase I study of BMS-275291, a broad-spectrum matrix metalloproteinase inhibitor, and to determine whether the wound angiogenesis assay was able to detect the inhibition of angiogenesis in patients treated with BMS-275291.



Before treatment began, a 4-mm skin biopsy was performed. The wound was imaged for 14 days. Treatment was started on day 0, and a separate 4-mm biopsy was performed 14 days later. The second wound was also imaged for 14 days. Wound angiogenesis was scored by two independent observers who were blinded to treatment status.



The median times in days (95% confidence interval) to reach the target average vascular score (AVS) of 1.5 and 2.0 based on the data of Observer 1 were 3.7 (2.2-6.9) and 8.0 (5.0-10.0) pretreatment whereas on-treatment the values were 4.9 (3.7-8.0) and 9.3 (7.0-11.5), respectively. The delay in the median time to reach an AVS of 1.5 was 1.2 days or a 32% reduction when comparing pretreatment with on-treatment (P = 0.06). For the target AVS of 2.0 the delay in the median time pretreatment versus on-treatment was 1.3 days or a 16% reduction (P = 0.04).



The wound angiogenesis assay used in this study was practical, well tolerated, and reproducible. Delays in wound angiogenesis because of BMS-275291 were detectable with this assay. This technique warrants additional investigation in clinical trials of other antiangiogenic agents.
Blood cell lead, calcium, and magnesium levels associated with pregnancy-induced hypertension and preeclampsia

This study compares the red blood cell (Rbc) levels of lead (Pb), calcium (Ca), and magnesium (Mg) in relation to blood pressure in 39 pregnant women in the third trimester of pregnancy. The study population included 20 women with normal pregnancies, 15 with mild hypertension, and 4 with severe hypertension and preeclampsia. The mean±SD for each group was calculated and the difference between the means of the normotensive and the other groups were compared by analysis of variance. Significant differences from normal to the preeclamptic pregnancies were in (1) elevated Rbc Pb (p≤0.001), (2) lower Rbc Ca (p≤0.001), and (3) lower Rbc Mg/Pb ratio (p≤0.0001). Pearson’s rank correlation between blood pressure showed a direct relation to the Rbc Pb level (p≤0.01) and an inverse relation to the Rbc Ca and Mg/Pb ratio (p≤0.004,≤0.007). Apparently, prenatal blood pressure is directly proportional to Rbc Pb content and related or modified by Rbc Ca and Mg.
Loss-of-function DNA sequence variant in the CLCNKA chloride channel implicates the cardio-renal axis in interindividual heart failure risk variation.

Common heart failure has a strong undefined heritable component. Two recent independent cardiovascular SNP array studies identified a common SNP at 1p36 in intron 2 of the HSPB7 gene as being associated with heart failure. HSPB7 resequencing identified other risk alleles but no functional gene variants. Here, we further show no effect of the HSPB7 SNP on cardiac HSPB7 mRNA levels or splicing, suggesting that the SNP marks the position of a functional variant in another gene. Accordingly, we used massively parallel platforms to resequence all coding exons of the adjacent CLCNKA gene, which encodes the K(a) renal chloride channel (ClC-K(a)). Of 51 exonic CLCNKA variants identified, one SNP (rs10927887, encoding Arg83Gly) was common, in linkage disequilibrium with the heart failure risk SNP in HSPB7, and associated with heart failure in two independent Caucasian referral populations (n = 2,606 and 1,168; combined P = 2.25 × 10(-6)). Individual genotyping of rs10927887 in the two study populations and a third independent heart failure cohort (combined n = 5,489) revealed an additive allele effect on heart failure risk that is independent of age, sex, and prior hypertension (odds ratio = 1.27 per allele copy; P = 8.3 × 10(-7)). Functional characterization of recombinant wild-type Arg83 and variant Gly83 ClC-K(a) chloride channel currents revealed ≈ 50% loss-of-function of the variant channel. These findings identify a common, functionally significant genetic risk factor for Caucasian heart failure. The variant CLCNKA risk allele, telegraphed by linked variants in the adjacent HSPB7 gene, uncovers a previously overlooked genetic mechanism affecting the cardio-renal axis.
Trends in Lung Cancer Incidence in a Healthcare Area.

The aim of this study was to identify trends in the incidence of lung cancer in the Leon Healthcare Area. All cases of cancer among residents of the Leon healthcare catchment area listed in the hospital-based tumor registry of the Centro Asistencial Universitario de Leon (CAULE) between 1996 and 2010 were included. Gross incidence rates over 3-year intervals were calculated and adjusted for the worldwide and European populations. A total of 2,491 cases were included. In men, incidence adjusted for the European population rose from 40.1 new cases per 100,000 population (1996-1998) to 61.8 (2005-2007), and then fell to 54.6 (2008-2010). In women, incidence tripled from 3.0 (1996-1998) to 9.2 new cases per 100,000 (2008-2010). Although lung cancer is an avoidable disease, it is a serious problem in the Leon Healthcare Area. Of particular concern is the rising incidence among women.
Health Status and Self-care Outcomes After an Education-Support Intervention for People With Chronic Heart Failure.

The rising cost of hospitalizations for heart failure (HF) care mandates intervention models to address education for self-care success. The effectiveness of memory enhancement strategies to improve self-care and learning needs further examination.



The objective of this study was to examine the effects of an education-support intervention delivered in the home setting, using strategies to improve health status and self-care in adults/older adults with class I to III HF. Our secondary purpose was to explore participants' subjective perceptions of the intervention.



This study used a randomized, 2-group design. Fifty people were enrolled for 9 months and tested at 4 time points-baseline; after a 3-month education-support intervention; at 6 months, after 3 months of telephone/e-mail support; and 9 months, after a 3-month period of no contact. Advanced practice registered nurses delivered the intervention. Memory enhancement methods were built into the teaching materials and delivery of the intervention. We measured the intervention's effectiveness on health status outcomes (functional status, self-efficacy, quality of life, emotional state/depressive symptoms, and metamemory) and self-care outcomes (knowledge/knowledge retention, self-care ability). Subjects evaluated the usefulness of the intervention at the end of the study.



The mean age of the sample was 62.4 years, with a slight majority of female participants. Participants were well educated and had other concomitant diseases, including diabetes (48%) and an unexpected degree of obesity. The intervention group showed significant improvements in functional status, self-efficacy, and quality of life (Kansas City Cardiomyopathy Questionnaire); metamemory Change and Capacity subscales (Metamemory in Adulthood Questionnaire); self-care knowledge (HF Knowledge Test); and self-care (Self-care in Heart Failure Index). Participants in both groups improved in depressive scores (Geriatric Depression Scale).



An in-home intervention delivered by advanced practice registered nurses was successful in several health status and self-care outcomes, including functional status, self-efficacy, quality of life, metamemory, self-care status, and HF knowledge.