nils-herrmann/clean_scirepeval huggingface dataset:
High serum sclerostin predicts the occurrence of osteoporotic fractures in postmenopausal women: the Center of Excellence for Osteoporosis Research Study.

Sclerostin regulates bone formation by inhibiting Wnt pathway signaling. Low circulating sclerostin levels cause high bone mass. We hypothesized that postmenopausal women with increased sclerostin levels have a greater risk for osteoporosis-related fractures. We examined the association between circulating sclerostin together with bone turnover markers and osteoporosis-related fracture risk in 707 postmenopausal women, in a population-based study with a mean follow-up period of 5.2 ± 1.3 years. Multivariate Cox proportional hazards regression models were used to analyze fracture risk, adjusted for age, body mass index, and other confounding risk factors. High sclerostin levels were strongly associated with increased fracture risk. After adjustment for age and other confounders, the relative fracture risk was more than sevenfold among postmenopausal women for each 1-SD increment increase in sclerostin level. Women in the highest quartile of sclerostin levels had about a 15-fold increase in fracture risk. Results were similar when we compared sclerostin at the 1-year visit to an average of two to three annual measurements. Fracture risk attributable to sclerostin levels was 56.6% in the highest quartile. Only high levels of bone resorption markers (plasma cross-linked C-terminal telopeptide of type 1 collagen [p-CTx], urinary CTx [u-CTx], and urinary N-telopeptide of type 1 collagen [u-NTx]) were predictive of osteoporosis-related fractures but at much lower hazard ratio (HR) values than that of serum sclerostin. Associations between sclerostin levels and fracture risk were independent of bone mineral density and other confounding risk factors. High sclerostin levels are a strong and independent risk factor for osteoporosis-related fractures among postmenopausal women.
Comparative effects of nitroglycerin, nifedipine and metoprolol on regional left ventricular function in patients with one-vessel coronary disease.

To compare acute effects of nitroglycerin (0.8 mg sublingually), nifedipine (5 ng/kg/min i.v.) and metoprolol (0.15 mg/kg i.v.) on normal, ischemic and scarred myocardial segments in man, we performed simultaneous hemodynamic and radionuclide measurements of left ventricular functions. Sixteen patients with isolated left anterior descending (LAD) disease were studied at rest and during exercise. Nine patients had angina and exercise-induced ischemia (LAD stenosis) and seven patients had previous transmural myocardial infarction and no ischemic changes during thallium imaging (LAD occlusion). The effects of the drugs on regional ejection fraction of the involved anteroseptal region and the normal posterolateral area were compared. Global ejection fraction at rest did not change after nitroglycerin, increased after nifedipine and decreased after metoprolol. In patients with ischemia, the exercise ejection fraction improved after all drugs due to increased regional ejection fraction in ischemic segments: i.e., a regional antiischemic effect evidenced by improved regional function could be demonstrated with all three agents. Regional ejection fraction increased from 35.8 +/- 19.5% to 66.2 +/- 15.2% (+/- SD) after nitroglycerin (p less than 0.001), to 61.7 +/- 8.7% after nifedipine (p less than 0.001), and to 48.4 +/- 7.0% after metoprolol (p less than 0.01). In regions of myocardial scar, regional ejection fraction was not changed after any drug. In normal areas, regional ejection fraction remained unchanged after nitroglycerin and nifedipine, but decreased after metoprolol. Despite similar antiischemic effects of all three drugs, underlying hemodynamic mechanisms were quite different and may provide a rationale for combined forms of treatment. These results may help to select optimal drug combinations to improve myocardial performance in patients with chronic ischemic heart disease.
Determinants of quality of life during induction therapy in pediatric acute lymphoblastic leukemia

Improvement in survival of pediatric acute lymphoblastic leukemia (ALL) has increased the attention to quality of life (QoL) . QoL is impaired during maintenance treatment, but little is known about QoL during induction therapy. Identification of patients with poor QoL during induction will provide opportunities for early interventions, and may subsequently improve future QoL. This national multi-center study aimed to assess QoL and its determinants during ALL induction treatment. Proxy reports of the Child Health Questionnaire (CHQ) and the PedsQL cancer version were collected. Child, treatment, and parental characteristics were analyzed as potential determinants in a multiple regression model. One hundred thirty parents of children participated (response rate 82 %), median child age was 5.7 years and 48 % were female. QoL, as measured with the CHQ, was significantly lower than the norm, the effect sizes were large, and the differences were clinically relevant. Physical QoL was more often affected than psychosocial QoL. Regression models could be constructed for 4/ 10 CHQ scales and 6/ 8 PedsQL cancer scales, accounting for 7 to 36 % of the variance in scores. Impaired QoL was most often associated with older children, girls, and time since diagnosis. Also, father respondents seem to have a lower QoL perception compared to mother respondents although this needs to be confirmed in future research. Specific counseling for subsets of patients with a higher risk of low QoL during the early phases of therapy is warranted.
Evidence of a pharmacogenomic response to interleukin-l receptor antagonist in rheumatoid arthritis

Biological activity of the IL-1 system depends on the balance between two proinflammatory proteins (IL-1α and IL-1β) and the related anti-inflammatory protein, the IL-1 receptor antagonist (IL-1Ra). The genes for these proteins lie within 430 kb on human chromosome 2. Based on a clinical trial of human recombinant IL-1ra in rheumatoid arthritis, we tested whether IL-1 genotype might be related to the likelihood of response to anti-IL-1 therapy. A positive response was defined as a reduction of at least 50% in the number of swollen joints by week 24, following treatment with either 150 mg/day IL-1ra or placebo. The response rate to treatment, independent of genotype, was 48% (44/91). A highly significant association was found between carriage of the rarer allele at IL1A(+4845) and response to treatment (P=0.0009; OR=4.85 (1.85,12.70)). The response rate in patients carrying this allele was 63.4% compared with 26.3% in noncarriers. A weaker association was found for IL1B(+3954) (P=0.02). There was a highly significant interaction between treatment (150 mg/day or placebo) and the composite genotype across IL1A(+4845) and IL1B(+3954) (P=7.6 × 10−5). No associations with IL-1 genotypes were found in patients receiving placebo. Thus, a significant pharmacogenomic effect was found in the treatment of RA patients with recombinant IL-1ra.
Thrombolysis in patients with pulmonary embolism and elevated heart-type fatty acid-binding protein levels

Recent studies have reported that a novel cardiac biomarker, heart-type fatty acid-binding protein (h-FABP), significantly predicts mortality inpatients with pulmonary embolism (PE) at intermediate risk. The aim of this study was to evaluate the effect of thrombolytic therapy on prognosis of the intermediate risk acute PE patients with elevated levels of h-FABP. This is non-interventional, prospective, and single-center cohort study where 80 patients (mean age 62 ± 17 years, 32 men) with confirmed acute PE were included. Only patients with PE at intermediate risk (echocardiographic signs of right ventricular overload but without evidence for hypotension or shock) were included in the study. h-FABP and other biomarkers were measured upon admission to the emergency department. Thrombolytic (Thrl) therapy was administered at the physician’s discretion. Of the included 80 patients, 24 were h-FABP positive (30 %). 14 patients (58 %) with positive h-FABP had clinical deterioration during the hospital course and required inotropic support and 12 of these patients died. However, of 56 patients with negative test, only 7 patients worsened or needed inotropic support and five patients died during the hospital stay. Mortality of patients with PE at intermediate risk was 21 %. The 30-day mortality rate was significantly higher in h-FABP(+) patients compared to h-FABP(−) patients (9 vs. 50 %, p < 0.001). Multivariate analysis revealed h-FABP as the only 30 day mortality predictor (HR 7.81, CI 1.59–38.34, p = 0.01). However, thrl therapy did dot affect the survival of these high-risk patients. Despite, h-FABP was successful to predict 30-days mortality in patients with PE at intermediate risk; it is suggested to be failed in determining the patients who will benefit from thrl therapy.
Base of support feedback in gait rehabilitation.

The purpose of this study was to investigate the effect of feedback information about base of support in gait rehabilitation. Sixteen individuals with hemiparesis resulting in narrow base of support, were randomly placed into two equal groups, experimental and control. The experimental group was provided with a portable device that provided extrinsic auditory feedback information about base of support incorporated in the functional context of conventional gait therapy, whereas the control group received a conventional gait therapy only. Changes in step width with treatment were assessed with step print technique. The experimental group of subjects improved their step width with treatment from 0.09 +/- 0.003 m to 0.16 +/- 0.006 m while individuals assigned to the control group showed smaller improvement from 0.099 +/- 0.004 m to 0.13 +/- 0.003 m. While both groups demonstrated statistically significant improvement (p < 0.05), the level of recovery of step width seen in the experimental group was greater.
Relationship between omalizumab pharmacokinetics, IgE pharmacodynamics and symptoms in patients with severe persistent allergic (IgE-mediated) asthma.

Omalizumab, a subcutaneously administered anti-IgE antibody, is effective for moderate-to-severe persistent allergic asthma. The aims were to (i) describe the population pharmacodynamics of free IgE with a mechanism-based, nonlinear, omalizumab-IgE binding model; (ii) deduce a target-free IgE suppression level by correlation with clinical outcomes; and (iii) check the adequacy of current approved dosing tables and explore potential doses and regimens beyond.



Concentration data (omalizumab, free and total IgE) were obtained from 1781 patients aged 12-79 years, in four sparsely sampled randomized, placebo-controlled studies and 152 subjects in a richly sampled single-dose study. NONMEM predictive performance across the range of bodyweights (39-150 kg) and baseline IgE (19-1055 IU ml(-1)) was checked by simulation. Predicted free IgE levels were correlated with time-averaged patient diary clinical outcomes.



The model accurately predicted observed omalizumab, free and total IgE concentrations. Free IgE concentrations correlated well with clinical signs and symptoms, allowing a target concentration of 14 ng ml(-1), at the midpoint of 4-week clinical observation periods, to be set for determining the dose and regimen for omalizumab.



The omalizumab-IgE binding model is predictive for free IgE and demonstrates a nonlinear time-dependent relationship between free IgE suppression and clinical outcomes in asthma. Although currently approved dosing tables are close to optimal, it should be possible to treat patients with higher levels of baseline IgE if higher doses can be administered.
Association between persistence with statin therapy and reduction in low-density lipoprotein cholesterol level: analysis of real-life data from community settings.

To validate the use of drug dispensing data as a measure of drug exposure and to quantify the association between persistence with statin therapy and low-density lipoprotein cholesterol (LDL) levels using real-life community data.



Retrospective, population-based cohort study.



Maccabi Healthcare Services (MHS) database, which contains linked prescription drug information, hospitalization records, and laboratory test results of 2 million members of the second largest health organization in Israel.



A total of 87,219 primary prevention patients and 15,139 secondary prevention patients who were MHS members and who started statin therapy between 1998 and 2008.



Baseline and follow-up LDL levels were documented from 3 months before the date of first dispensed statin (index date) to 6 months afterward. Persistence was assessed by proportion of days covered (PDC) with statins during the follow-up period. Over the follow-up period, significant (p<0.001) reductions in LDL levels of 54, 33, and 13 mg/dl were noted among highly persistent (PDC ≥ 80%), moderately persistent (34% ≤ PDC < 79%), and poorly persistent statins users (PDC ≤ 33%), respectively. The reduction was observed as early as 2-3 weeks after therapy initiation. In a multivariable model controlling for baseline LDL level and traditional coronary heart disease risk factors (diabetes mellitus, hypertension), high persistence with statin therapy was associated with a 27% and 25% decrement in LDL level among the primary and secondary prevention cohorts, respectively. Similarly, a higher proportion of the persistent statins users reached their target LDL level within the study follow-up period: 80% and 58% among primary and secondary prevention cohorts, respectively, compared with only 28% and 17%, respectively, among poorly persistent patients.



In this observational population-based study, calculated PDC with statins during study follow-up was strongly associated with drug effect of LDL level reduction. The results agree with previous estimates of statin efficacy from randomized clinical trials, supporting the validity of using PDC methods as a measure of drug exposure.
Inverse correlation between CD8+ lymphocyte apoptosis and CD4+ cell counts during potent antiretroviral therapy in HIV patients.

We have addressed the relationships between inhibition of CD4+ and CD8+ cell apoptosis and CD4+ cell recovery in HIV patients undergoing potent antiretroviral therapy (PART) by correlating apoptosis levels with virological and immunological parameters detected over a long-term period in HIV patients undergoing therapy.



Twenty-two HIV-1-infected patients undergoing PART were enrolled in a long-term, open longitudinal study. Data derived from 17 patients with successful response to therapy (TS; median time of follow-up 36 months, range 24-36 months) were used for correlation studies. Apoptosis was evaluated after short-term culture of peripheral blood lymphocytes by flow cytometry analysis of isolated nuclei or of annexin V/CD4, annexin V/CD8 double-stained cells.



Sustained, noticeable levels of apoptosis inhibition in peripheral blood mononuclear cells were measured, in the long-term, in 16 of the 17 TS patients. Levels of total cell apoptosis correlated with levels of CD8+ apoptotic cells more significantly than with levels of CD4+ apoptotic cells. In addition, CD4+ cell counts were correlated inversely with levels of CD8+ apoptotic cells in a highly significant fashion, but not with levels of CD4+ apoptotic cells.



Our data indicate that the increase of CD4+ lymphocytes in HIV patients, as a consequence of successful response to PART, may be related to changes in apoptosis level occurring in the CD8+, and not in the CD4+, cell compartment.
Transperineal Prostate Core Needle Biopsy: A Comparison of Coaxial Versus Noncoaxial Method in a Randomised Trial

To compare the procedural time and complication rate of coaxial technique with those of noncoaxial technique in transperineal prostate biopsy. Transperineal prostate biopsy with coaxial (first group, n = 120) and noncoaxial (second group, n = 120) methods was performed randomly in 240 patients. The procedural time was recorded. The level of pain experienced during the procedure was assessed on a visual analogue scale (VAS), and the rate of complications was evaluated in comparison of the two methods. The procedural time was significantly shorter in the first group (p < 0.001). In the first group, pain occurred less frequently (p = 0.002), with a significantly lower VAS score being experienced (p < 0.002). No patient had post procedural fever. Haematuria (p = 0.029) and haemorrhage from the site of biopsy (p < 0.001) were seen less frequently in the first group. There was no significant difference in the rate of urethral haemorrhage between the two groups (p = 0.059). Urinary retention occurred less commonly in the first group (p = 0.029). No significant difference was seen in the rate of dysuria between the two groups (p = 0.078). Transperineal prostate biopsy using a coaxial needle is a faster and less painful method with a lower rate of complications compared with conventional noncoaxial technique.
Suboptimal compliance with evidence-based guidelines in patients with traumatic brain injuries.

Evidence-based management (EBM) guidelines for severe traumatic brain injuries (TBIs) were promulgated decades ago. However, the extent of their adoption into bedside clinical practices is not known. The purpose of this study was to measure compliance with EBM guidelines for management of severe TBI and its impact on patient outcome.



This was a retrospective study of blunt TBI (11 Level I trauma centers, study period 2008-2009, n = 2056 patients). Inclusion criteria were an admission Glasgow Coma Scale score ≤ 8 and a CT scan showing TBI, excluding patients with nonsurvivable injuries-that is, head Abbreviated Injury Scale score of 6. The authors measured compliance with 6 nonoperative EBM processes (endotracheal intubation, resuscitation, correction of coagulopathy, intracranial pressure monitoring, maintaining cerebral perfusion pressure ≥ 50 cm H2O, and discharge to rehabilitation). Compliance rates were calculated for each center using multivariate regression to adjust for patient demographics, physiology, injury severity, and TBI severity.



The overall compliance rate was 73%, and there was wide variation among centers. Only 3 centers achieved a compliance rate exceeding 80%. Risk-adjusted compliance was worse than average at 2 centers, better than average at 1, and the remainder were average. Multivariate analysis showed that increased adoption of EBM was associated with a reduced mortality rate (OR 0.88; 95% CI 0.81-0.96, p < 0.005).



Despite widespread dissemination of EBM guidelines, patients with severe TBI continue to receive inconsistent care. Barriers to adoption of EBM need to be identified and mitigated to improve patient outcomes.
Communication of randomization in childhood leukemia trials.

Most children diagnosed as having leukemia become research subjects in randomized clinical trials (RCTs), but little is known about how randomization is explained to or understood by parents.



To investigate physicians' explanation and parental understanding of randomization in childhood leukemia RCTs.



A multisite study of the informed consent communication process for RCTs of childhood leukemia. Consecutive cases were recruited from pediatric oncology inpatient wards at 6 US children's hospitals associated with major academic medical centers from July 1, 1999, until December 31, 2001. The informed consent conferences were observed and audiotaped, and the information obtained was coded and analyzed. Parents were interviewed shortly after the conference to ascertain their understanding.



Parents and members of the health care team who participated in 137 informed consent conferences for children with newly diagnosed acute leukemia.



Observed explanations of randomization and parental understanding of randomization after the consent conference.



Randomization was explained by physicians in 83% of cases and a consent document was presented during the conference in 95% of cases. Interviews after the conference demonstrated that 68 (50%) of 137 parents did not understand randomization. Parents of racial minority and lower socioeconomic status were less likely to understand randomization (P<.001 for each). Discussion of specific clinical trial details and the presence of a nurse during the conference were associated with understanding. Eighty-four percent of children were enrolled in a leukemia trial.



Despite oral and written explanation, half of the parents in this study did not understand randomization for childhood leukemia trials. To make informed consent more effective, future research must seek to improve communication during this critical interchange.
Clinical value of contrast-enhanced ultrasonography in the characterization of focal liver lesions: a prospective multicenter trial.

Contrast-enhanced ultrasonography (CEUS) is increasingly accepted in clinical settings for diagnostic imaging of focal liver lesions (FLLs). This study aimed to assess the efficacy of CEUS in the characterization of FLLs in comparison with final diagnosis based on gold standard assessment.



The study was approved by the local ethics committee and participating patients provided written informed consent. A total of 148 patients with 164 FLLs were studied. Unenhanced ultrasonography (US) and CEUS were performed using fundamental and harmonic imaging, respectively. Contrast enhancement was assessed during the arterial, portal and late vascular phases after intravenous administration of contrast (SonoVue, Bracco, Italy). Sensitivity, specificity and diagnostic accuracy of US and CEUS were compared in identifying the lesion as benign, malignant or indeterminate and its actual tumor type. Final diagnosis was established by biopsy (129/164), MR imaging (11/164) or medical history (24/164).



When compared to the gold standard, the number of indeterminate diagnoses was reduced from 56.7% (93/164) as assessed by fundamental imaging to 6.1% (10/164) after SonoVue enhanced US examination. Sensitivity and specificity improved from 49% and 25% at baseline US to 93% and 75% with CEUS, respectively (P<0.01). Diagnostic accuracy of CEUS was 88% in contrast to 41% of baseline US.



SonoVue enhanced US improves the characterization of FLLs and may limit the need for further investigations.
Validation of the Finnvasc score in infrainguinal percutaneous transluminal angioplasty for critical lower limb ischemia.

The aim of the present study was to validate the Finnvasc score for prediction of immediate outcome after infrainguinal percutaneous transluminal angioplasty (PTA) for critical lower limb ischemia (CLI). Our registry included prospective data on 512 patients who underwent isolated infrainguinal PTA revascularization procedures for CLI. The Finnvasc score herein evaluated was calculated by assigning one point each to diabetes, coronary artery disease, foot gangrene, and urgent operation. Early mortality and major limb amputation rates after PTA revascularization were 2.5% and 12.3%, respectively. Seventy-two patients (14.1%) died and/or had lower limb amputation. Diabetes (p = 0.001), foot gangrene (p = 0.047), urgent operation (p < 0.0001), and preoperative renal failure (p = 0.001) were independent predictors of postoperative mortality and/or major limb amputation. Finnvasc score was predictive of major lower limb amputation (p = 0.003), mortality (p < 0.0001), and mortality and/or major amputation (p < 0.0001) after PTA. Mortality, major lower limb amputation, and combined end point rates in patients with a Finnvasc score of 3-4 were 12.8%, 25.6%, and 35.9%, respectively. The Finnvasc score is a simple risk scoring method which can be useful to estimate the risk of immediate postprocedural mortality and/or major lower limb amputation also in patients undergoing infrainguinal PTA for CLI.