nils-herrmann/clean_scirepeval huggingface dataset:
Dose-finding study of peginesatide for anemia correction in chronic kidney disease patients.

Peginesatide is a synthetic, PEGylated, investigational, peptide-based erythropoiesis-stimulating agent. We report the first assessment of its efficacy and safety in correcting renal anemia in a population of 139 nondialysis chronic kidney disease patients.



Chronic kidney disease patients who were not on dialysis and not receiving treatment with erythropoiesis-stimulating agents in the 12 weeks before study drug administration were sequentially assigned to one of 10 cohorts; cohorts differed in starting peginesatide dose (different body weight-based or absolute doses), route of administration (intravenous or subcutaneous), and frequency of administration (every 4 or 2 weeks).



Across all cohorts, 96% of patients achieved a hemoglobin response. A dose-response relationship was evident for hemoglobin increase. Comparable subcutaneous and intravenous peginesatide doses produced similar hemoglobin responses. Rapid rates of hemoglobin rise and hemoglobin excursions >13 g/dl tended to occur more frequently with every-2-weeks dosing than they did with every-4-weeks dosing. The range of final median doses in the every-4-weeks dosing groups was 0.019 to 0.043 mg/kg. Across all cohorts, 20% of patients reported serious adverse events (one patient had a possibly drug-related serious event) and 81% reported adverse events (11.5% reported possibly drug-related events); these events were consistent with those routinely observed in this patient population.



This study suggests that peginesatide administered every 4 weeks can increase and maintain hemoglobin in nondialysis chronic kidney disease patients. Additional long-term data in larger groups of patients are required to further elucidate the efficacy and safety of this peptide-based erythropoiesis-stimulating agent.
Beneficial effects of a switch to a Lopinavir/ritonavir-containing regimen for patients with partial or no immune reconstitution with highly active antiretroviral therapy despite complete viral suppression.

The purpose of this study was to determine if switching to an Lopinavir/ritonavir (LPV/r)-containing regimen resulted in greater immune reconstitution in patients with immunologic failure despite complete viral suppression with highly active antiretroviral therapy (HAART). Twenty patients with partial or no immune response to HAART despite viral suppression were enrolled. Ten were randomized to stay on their current regimen and 10 were randomized to LPV/r plus their current NRTI backbone. T cell subsets, ex vivo apoptosis, and the percent of circulating cells with detectable intracellular HIV-1 RNA were measured. The mean increase in CD4(+) count at 6 months was 116/mm(3) (172-288) for the LPV/r-containing arm versus 32/mm(3) (264-296) for continuation regimens (p = 0.03). The number of patients with an increase ≥50 cells/mm(3) was also greater in the LPV/r arm (7/9 versus 2/10, p = 0.01). This paralleled a decrease in ex vivo apoptosis of naive CD4(+) T cells at 6 months (21.7-11.0% for the LPV/r arm versus 17.3-18.9% for the continuation arm, p = 0.04) and memory cells (21.1-14.1% for LPV/r versus 20.2-17.9% for continuation arm, NSS). Switching patients to an LPV/r-containing regimen improved CD4(+) counts in patients with prior immunologic failure, and this may be due to an effect of LPV/r on apoptosis.
Prevalence and Predictive Factors of Chronic Postsurgical Pain and Global Surgical Recovery 1 Year After Outpatient Knee Arthroscopy

Outpatient knee arthroscopy is one of the most commonly performed surgical procedures. Previous research has demonstrated that chronic postsurgical pain (CPSP) after outpatient surgery is prevalent. Our objective was to determine the prevalence and predictive factors of CPSP and Global Surgical Recovery (GSR) 1 year after knee arthroscopy.A prospective longitudinal cohort study was performed. Patients were included during an 18-month period. Data were collected by using 3 questionnaires: at 1 week preoperatively, 4 days postoperatively, and 1 year postoperatively. A value of >3 on an 11-point numeric rating scale (NRS) was defined as moderate to severe pain. A score of ≤80% on the Global Surgical Recovery Index was defined as poor GSR. Stepwise logistic regression analysis was performed to determine which variables were predictors for CPSP and poor GSR.The prevalence of moderate to severe preoperative pain in patients undergoing knee arthroscopy (n = 104) was 71.2%, of acute postsurgical pain 37.5%, and of CPSP 32.7%. Risk factors for CPSP were the presence of preoperative pain and preoperative analgesic use, with odds ratios of 6.31 (1.25-31.74) and 4.36 (1.58-12.07), respectively. The prevalence of poor GSR 1 year after outpatient knee arthrosocpy was 50.0%. Poor GSR 4 days after the surgery was a risk factor with an odds ratio of 8.38 (0.92-76.58) and quality of life 4 days after surgery was a protective factor with and odds ratio of 0.10 (0.02-0.64).Both CPSP and poor GSR are common 1 year after knee arthroscopy. Patients at risk for CPSP can be identified during the preoperative phase. Prediction of poor GSR 1 year after surgery is mainly related to early postoperative recovery.
Inability to demonstrate physiologic correlates of subjective improvement among patients taught the relaxation response

To assess whether the regular elicitation of the relaxation response produces sustained physiologic changes coincident with symptomatic relief or improved psychological state. Prospective, cohort pilot study. Clinical research center within a teaching hospital. Thirteen athletic men, mean age 44.8 years, with borderline or labile hypertension, taking no medication. All 13 completed the study. Three baseline assessments of psychological state, symptom checklist, and assessment of autonomic response to infusion of beta agonist (isoproternol). Daily relaxation response exercises for five consecutive weeks followed by repeat assessment of all parameters. Discontinuation of relaxation exercises for subsequent five weeks followed by repeat assessment of all parameters. After eliciting the relaxation response, subjects demonstrated significant decreases in anxiety (p<0.014) and somatic symptoms (p<0.02). Psychological and somatic variables returned toward baseline after the subsequent discontinuation of relaxation exercises. No significant concomitant change in urinary catecholamines, heart rate response to isoproterenol, blood pressure, pulse rate, or serum cholesterol was demonstrated. The regular elicitation of the relaxation response can improve psychological performance and reduce symptoms. However, the physiologic mechanism whereby these psychological and symptomatic improvements occur remains poorly understood and warrants further investigation.
Heterogeneity of Estrogen Receptor Expression in Circulating Tumor Cells from Metastatic Breast Cancer Patients

Endocrine treatment is the most preferable systemic treatment in metastatic breast cancer patients that have had an estrogen receptor (ER) positive primary tumor or metastatic lesions, however, approximately 20% of these patients do not benefit from the therapy and demonstrate further metastatic progress. One reason for failure of endocrine therapy might be the heterogeneity of ER expression in tumor cells spreading from the primary tumor to distant sites which is reflected in detectable circulating tumor cells (CTCs).



A sensitive and specific staining protocol for ER, keratin 8/18/19, CD45 was established. Peripheral blood from 35 metastatic breast cancer patients with ER-positive primary tumors was tested for the presence of CTCs. Keratin 8/18/19 and DAPI positive but CD45 negative cells were classified as CTCs and evaluated for ER staining. Subsequently, eight individual CTCs from four index patients (2 CTCs per patient) were isolated and underwent whole genome amplification and ESR1 gene mutation analysis.



CTCs were detected in blood of 16 from 35 analyzed patients (46%), with a median of 3 CTCs/7.5 ml. In total, ER-negative CTCs were detected in 11/16 (69%) of the CTC positive cases, including blood samples with only ER-negative CTCs (19%) and samples with both ER-positive and ER-negative CTCs (50%). No correlation was found between the intensity and/or percentage of ER staining in the primary tumor with the number and ER status of CTCs of the same patient. ESR1 gene mutations were not found.



CTCs frequently lack ER expression in metastatic breast cancer patients with ER-positive primary tumors and show a considerable intra-patient heterogeneity, which may reflect a mechanism to escape endocrine therapy. Provided single cell analysis did not support a role of ESR1 mutations in this process.
Functional imaging using computer methods to compare the effect of salbutamol and ipratropium bromide in patient-specific airway models of COPD

Salbutamol and ipratropium bromide improve lung function in patients with chronic obstructive pulmonary disease (COPD). However, their bronchodilating effect has not yet been compared in the central and distal airways. Functional imaging using computational fluid dynamics offers the possibility of making such a comparison. The objective of this study was to assess the effects of salbutamol and ipratropium bromide on the geometry and computational fluid dynamics-based resistance of the central and distal airways.



Five patients with Global Initiative for Chronic Obstructive Lung Disease Stage III COPD were randomized to a single dose of salbutamol or ipratropium bromide in a crossover manner with a 1-week interval between treatments. Patients underwent lung function testing and a multislice computed tomography scan of the thorax that was used for functional imaging. Two hours after dosing, the patients again underwent lung function tests and repeat computed tomography.



Lung function parameters, including forced expiratory volume in 1 second, vital capacity, overall airway resistance, and specific airway resistance, changed significantly after administration of each product. On functional imaging, the bronchodilating effect was greater in the distal airways, with a corresponding drop in airway resistance, compared with the central airways. Salbutamol and ipratropium bromide were equally effective at first glance when looking at lung function tests, but when viewed in more detail with functional imaging, hyporesponsiveness could be shown for salbutamol in one patient. Salbutamol was more effective in the other patients.



This pilot study gives an innovative insight into the modes of action of salbutamol and ipratropium bromide in patients with COPD, using the new techniques of functional imaging and computational fluid dynamics.
Is there an advantage over SF-36 with a quality of life measure that is specific to systemic lupus erythematosus?

To assess whether the Lupus Quality of Life (LupusQoL) questionnaire contributed additional information not obtained using the Medical Outcomes Study Short-Form 36 questionnaire (SF-36) in a cohort of patients with systemic lupus erythematosus (SLE).



Forty-one patients seen at a single center were followed at monthly intervals for 12 months. The LupusQoL and the SF-36 questionnaires were coadministered monthly. Disease activity was determined by the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) every 30 days. We determined the correlation of the 4 comparable domains of both questionnaires. For the 4 noncomparable domains of the LupusQoL we determined the correlation between each domain with the Physical Component Summary scores (PCS) and the Mental Component Summary scores (MCS) of the SF-36. The effect size (ES) and the standardized response mean (SRM) were used to compare the responsiveness of both questionnaires when a clinically significant change in disease activity occurred as determined by SLEDAI-2K.



Three hundred seventy-six patient visits were recorded. There was a strong correlation between comparable domains in both questionnaires. For the 4 noncomparable domains of the LupusQoL, there was a correlation with the MCS and PCS of SF-36. The mean scores for comparable domains in both questionnaires were similar. Both questionnaires displayed responsiveness, as determined by ES and SRM among patients who flared and improved, but not among patients in remission, when compared to the previous visit.



LupusQoL and SF-36 were equivalent in assessing quality of life over time in this group of patients. Both questionnaires are responsive measures of quality of life in patients with SLE flares and improvement.
Short-versus long-term effects of different dihydropyridines on sympathetic and baroreflex function in hypertension.

Antihypertensive treatment with dihydropyridines may be accompanied by sympathetic activation. Data on whether this is common to all compounds and similar in the various phases of treatment are not univocal, however. In 28 untreated essential hypertensives (age, 56.4+/-1.8 years; mean+/-SEM) finger blood pressure (BP, Finapres), heart rate (HR, ECG), plasma norepinephrine (NE, high-performance liquid chromatography), and muscle sympathetic nerve traffic (MSNA, microneurography) were measured at rest and during baroreceptor manipulation (vasoactive drugs) in the placebo run-in period and after randomization to double-blind acute and chronic (8 weeks) felodipine (10 mg/d, n=14) or lercanidipine (10 mg/d, n=14). Acute administration of both drugs induced pronounced BP reductions and marked increases in HR, NE, and MSNA. After 8 weeks of treatment, BP reductions were similar to those observed after acute administration, whereas HR, NE, and MSNA responses were markedly attenuated (-7%, -32%, and -14%, respectively; P<0.05). There was a small residual increase in sympathetic activity in the felodipine group, whereas in the lercanidipine group, all adrenergic markers returned to baseline values. Baroreflex control of HR and MSNA was markedly impaired (-42% and -48%, respectively) after acute drug administration, with a recovery and complete resetting during chronic treatment. Thus, the sympathoexcitation induced by 2 different dihydropyridines is largely limited to the acute administration. The 2 drugs have, nevertheless, a different chronic sympathetic effect, indicating that dihydropyridines do not homogeneously affect this function. The acute sympathoexcitation, but not the small between-drugs differential chronic adrenergic effect, is accounted for by baroreflex impairment.
Multiplexed protein detection by proximity ligation for cancer biomarker validation

We present a proximity ligation–based multiplexed protein detection procedure in which several selected proteins can be detected via unique nucleic-acid identifiers and subsequently quantified by real-time PCR. The assay requires a 1-μl sample, has low-femtomolar sensitivity as well as five-log linear range and allows for modular multiplexing without cross-reactivity. The procedure can use a single polyclonal antibody batch for each target protein, simplifying affinity-reagent creation for new biomarker candidates.
Validation of the American version of the CareGiver Oncology Quality of Life (CarGOQoL) questionnaire

The CareGiver Oncology Quality of Life (CarGOQoL) questionnaire, a 29-item, multidimensional, self-administered questionnaire, was validated using a large French sample. We reported the linguistic validation process and the metric validity of the English version of CarGOQoL in the United- States.



The translation process consisted of 3 consecutive steps: forward-backward translation, acceptability testing, and cognitive interviews. The psychometric testing was applied to caregivers of consecutive patients with representative cancers who were recruited from the Regional Cancer Center in northwestern Pennsylvania. All individuals completed the CarGOQoL at baseline, day- 30, and day- 90. Internal consistency, reliability, external validity, reproducibility, and sensitivity to change were tested.



The translated version was validated on a total of 87 American cancer caregivers. The dimensions of the CarGOQoL generally demonstrated a high internal consistency (Cronbach's alpha > 0.70 for all but four domain scores). External validity testing revealed that the CarGOQoL index score correlated significantly with all SF-36 dimension scores except the physical composite score (Pearson's correlation: 0.28-0.70). Reproducibility was satisfactory at day- 30 (intraclass correlation coefficient: 0.46-0.94) and day- 90 (0.43-0.92). Four specific dimensions of CarGOQoL showed responsiveness: the Psychological well-being, the Relationships with health care system, the Social support and the Finances.



 constitutes a useful instrument to measure QoL in caregivers of cancer patients in the United- States.
Feasibility of a novel extraperitoneal two-port laparoendoscopic approach for radical prostatectomy: an initial study.

The aim of this study was to describe the surgical technique and to report the early outcomes of an original extraperitoneal two-port laparoendoscopic approach for radical prostatectomy. A total of 22 consecutive patients diagnosed with early-stage prostate cancer (cT1c, cT2N0) were operated on and included in this analysis. A multichannel port with three 5-mm trocars, providing easier instrument handling, was inserted extraperitoneally through a 2.5-cm lower umbilical "U" incision. An additional 12-mm port was inserted into the left fossa to allow an adequate working angle to facilitate the most critical steps of the surgical procedures. The operation was successfully completed in all patients; one patient required an additional 5-mm port to control bleeding. The median operation time was 259 min (range 207-453 min), and the fluid loss, including urine and blood, was 946 mL (range 257-1821 mL). The median Foley catheter indwelling period was 6 days (range 3-11 days) after surgery. No intraoperative complications occurred. Judging from this initial trial, this procedure can be safely carried out if the surgeon is familiar with conventional five-port laparoscopic radical prostatectomy.
Variability of respiratory symptoms in severe COPD.

While it is known that asthma symptoms have a very variable pattern, the general belief is that the respiratory symptoms in COPD patients usually present little or no variability. Nevertheless, COPD patients report having "bad days". The objective of this present study was to evaluate the variability of the respiratory symptoms and their impact on the daily activities of a cohort of Spanish COPD patients.



We present the results of the Spanish patients who participated in a cross-sectional epidemiological study carried out in 17 European countries. Pulmonologists and Family Care physicians recruited patients with stable severe COPD (FEV1<50%). The perception of the patients on the variation in their symptoms was recorded by telephone interviews.



A total of 472 patients provided data that was valid for analysis. Mean age was 68.6; 93% were men; mean FEV1(%) was 41%. 84.1% of the patients experimented at least one respiratory symptom in the previous week and 60.9% affirmed that their symptoms varied over the course of the day or week. The moment of the day when the symptoms were perceived to be more intense was during the morning.



An important proportion of severe COPD patients perceive variability in their respiratory symptoms, with a greater intensity in the morning. The observation can have implications in treating patients with severe COPD as variability can be an initial sign of decompensation of the disease.
Measurement of vasomotor reserve in the transcranial Doppler-CO(2) test using an ultrasound contrast agent (Levovist).

Determination of vasomotor reserve (VMR) with the transcranial Doppler-CO(2) (TCD-CO(2)) test is used to assess the risk of impending cerebral ischemia in patients with high-grade stenosis or occlusion of the internal carotid artery. In patients with a poor temporal window, however, this examination is limited. The aim of this study therefore was to examine whether the use of an ultrasound contrast agent (USCA) influences the results of the TCD-CO(2) test.



In the first part of the study, 6 control subjects and 20 patients were examined with the TCD-CO(2) test. The VMR was determined first without the application of a contrast agent and then with continuous infusion of an USCA (Levovist, 300 mg/mL, 1 mL/min). In the second part of the study, 2 tests without USCA were performed in each of 13 patients and 2 tests with USCA infusion were performed in each of 12 patients. Statistical analysis included differences between the VMR determined with the 2 comparative measurements (VMR), the mean (M(VMR)), and SD.



Based on the mean difference, the TCD-CO(2) test produced the same results with and without USCA (M(VMR) 1.8%), although the differences showed a wide distribution (2 SDs, +/-20.7%). Similar spreads were seen in repeated determinations of VMR in the same patient without USCA (2 SDs, +/-20.0%), whereas the distribution under continuous USCA infusion was considerably smaller (2 SDs, +/-8.2%).



The TCD-CO(2) test can be performed with continuous infusion of an USCA without influencing the results. Even with a good temporal window, the results of the TCD-CO(2) test show better reproducibility and thus better reliability if an USCA is used.
Efavirenz-based regimens in treatment-naive patients with a range of pretreatment HIV-1 RNA levels and CD4 cell counts.

The potency of 2 nucleoside reverse transcriptase inhibitors (NRTIs) and efavirenz in patients with higher viral loads (VLs) or low CD4 cell counts remains uncertain. Virologic failure and changes in CD4 count in relation to pretreatment VL and CD4 count were evaluated in treatment-naive patients randomized to treatment groups that received 2 or 3 NRTIs with efavirenz. Over 3 years, the risk of virologic failure was not significantly different among subgroups categorized according to pretreatment VL or CD4 count. No significant differences among subgroups were observed for CD4 count changes, except in patients with high pretreatment VL. There were no significant differences among subgroups with respect to treatment responses. These results demonstrate the potency of efavirenz-containing regimens across a spectrum of pretreatment VLs and CD4 counts.
Thalidomide for the treatment of cough in idiopathic pulmonary fibrosis: a randomized trial.

Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal disorder of unknown cause with no effective treatment. Cough affects up to 80% of patients with IPF, is frequently disabling, and lacks effective therapy.



To determine the efficacy of thalidomide in suppressing cough in patients with IPF.



24-week, double-blind, 2-treatment, 2-period crossover trial. (
1 university center.



98 participants were screened, 24 were randomly assigned, 23 received treatment (78.3% men; mean age, 67.6 years; mean FVC, 70.4% predicted), and 20 completed both treatment periods.



The primary end point was cough-specific quality of life measured by the Cough Quality of Life Questionnaire (CQLQ). Secondary end points were visual analogue scale of cough and the St. George's Respiratory Questionnaire (SGRQ). For all measures, lower scores equaled improved cough or respiratory quality of life.



CQLQ scores significantly improved with thalidomide (mean difference vs. placebo, -11.4 [95% CI, -15.7 to -7.0]; P < 0.001). Thalidomide also significantly improved scores on the visual analogue scale of cough (mean difference vs. placebo, -31.2 [CI, -45.2 to -17.2]; P < 0.001). In participants receiving thalidomide, scores from the total SGRQ, SGRQ symptom domain, and SGRQ impact domain improved compared with those of participants receiving placebo. Adverse events were reported in 74% of patients receiving thalidomide and 22% receiving placebo; constipation, dizziness, and malaise were more frequent with thalidomide.



This was a single-center study of short duration and small sample size focused on symptom-specific quality of life.



Thalidomide improved cough and respiratory quality of life in patients with IPF. A larger trial is warranted to assess these promising results.