nils-herrmann/clean_scirepeval huggingface dataset:
Change in coronary blood flow after percutaneous coronary intervention in relation to baseline lesion physiology: results of the JUSTIFY-PCI study.

Percutaneous coronary intervention (PCI) aims to increase coronary blood flow by relieving epicardial obstruction. However, no study has objectively confirmed this and assessed changes in flow over different phases of the cardiac cycle. We quantified the change in resting and hyperemic flow velocity after PCI in stenoses defined physiologically by fractional flow reserve and other parameters.



Seventy-five stenoses (67 patients) underwent paired flow velocity assessment before and after PCI. Flow velocity was measured over the whole cardiac cycle and the wave-free period. Mean fractional flow reserve was 0.68±0.02. Pre-PCI, hyperemic flow velocity is diminished in stenoses classed as physiologically significant compared with those classed nonsignificant (P<0.001). In significant stenoses, flow velocity over the resting wave-free period and hyperemic flow velocity did not differ statistically. After PCI, resting flow velocity over the wave-free period increased little (5.6±1.6 cm/s) and significantly less than hyperemic flow velocity (21.2±3 cm/s; P<0.01). The greatest increase in hyperemic flow velocity was observed when treating stenoses below physiological cut points; treating stenoses with fractional flow reserve ≤0.80 gained Δ28.5±3.8 cm/s, whereas those fractional flow reserve >0.80 had a significantly smaller gain (Δ4.6±2.3 cm/s; P<0.001). The change in pressure-only physiological indices demonstrated a curvilinear relationship to the change in hyperemic flow velocity but was flat for resting flow velocity.



Pre-PCI physiology is strongly associated with post-PCI increase in hyperemic coronary flow velocity. Hyperemic flow velocity increases 6-fold more when stenoses classed as physiologically significant undergo PCI than when nonsignificant stenoses are treated. Resting flow velocity measured over the wave-free period changes at least 4-fold less than hyperemic flow velocity after PCI.
Randomized sham-controlled trial of renal sympathetic denervation in mild resistant hypertension.

Few data are available with regard to the effectiveness of renal sympathetic denervation in patients with resistant hypertension yet only mildly elevated blood pressure (BP). Patients with resistant hypertension and slightly elevated BP (day-time systolic pressure, 135-149 and diastolic pressure, 90-94 mm Hg on 24-hour ambulatory measurement) were randomized in a 1:1 ratio to renal sympathetic denervation with the Symplicity Flex Catheter (Medtronic) or an invasive sham procedure. The primary efficacy end point was the change in 24-hour systolic BP at 6 months between groups in the intention to treat population. A total of 71 patients underwent randomization. Baseline day-time systolic BP was 144.4±4.8 mm Hg in patients assigned to denervation and 143.0±4.7 mm Hg in patients randomized to the sham procedure. The mean change in 24-hour systolic BP in the intention to treat cohort at 6 months was -7.0 mm Hg (95% confidence interval, -10.8 to -3.2) for patients undergoing denervation and -3.5 mm Hg (95% confidence interval, -6.7 to -0.2) in the sham group (P=0.15). In the per protocol population, the change in 24-hour systolic BP at 6 months was -8.3 mm Hg (95% confidence interval, -11.7 to -5.0) for patients undergoing denervation and -3.5 mm Hg (95% confidence interval, -6.8 to -0.2) in the sham group (P=0.042). In patients with mild resistant hypertension, renal sympathetic denervation failed to show a significant reduction in the primary end point of 24-hour systolic BP at 6 months between groups in the intention to treat analysis.
Multi-slice CT angiography in the evaluation of patients with acute cerebrovascular disease – a promising new diagnostic tool

Single-slice computed tomographic angiography (CTA) is an established imaging method for the cerebrovascular system (CVS), but it suffers from technical limitations with respect to the coherent high resolution visualization of longer vascular segments, such as the extra- and intracranial CVS. The recently introduced multi-slice (MS) technology has been attributed with a superior imaging quality for angiographic procedures due to increased scan speed and improved spatial resolution. The purpose of this study was to evaluate the suitability of multi-slice CTA (MS-CTA) for the assessment of the arteriovenous CVS in patients with acute symptoms of either arterial or venous occlusive diseases. 41 patients with clinically suspected acute cerebral ischaemia (hemispheric in 29 and vertebrobasilar in 12 patients) and 4 patients with suspected cerebral venous thrombosis (CVT) underwent CTA in a MS-CT scanner. In addition, doppler ultrasonography (DUS) was performed in 34, magnetic resonance angiography (MRA) in 5 and digital subtraction angiography (DSA) in 6 patients. All findings were reviewed for stenoses or occlusion of the extra- and intracranial CVS and correlated with the clinical outcome. In 43 (96 %) of 45 patients, MS-CTA yielded images of diagnostic quality with comprehensive visualization of the arterial and venous CVS including the cervical carotid bifurcation, the third segment of the major cerebral arteries and the dural sinus as well as internal cerebral veins. In 2 patients, assessment of the carotid bifurcation was limited because of tooth artefacts. In all patients, in whom imaging and clinical follow-up proved a non-lacunar infarction (n=22), MS-CTA detected the underlying vascular pathology. Suspected CVT could be confirmed in 2 and ruled out in another 2 patients through MS-CTA. In conclusion, multi-slice CT angiography may be a promising new diagnostic tool for the rapid and comprehensive assessment of the arteriovenous CVS in patients with clinical signs of acute cerebrovascular diseases.
A dynamically phase adjusting PLL with a variable delay

Phase locked loop (PLL) is widely used for many purposes. The lock-up performance is one of the most important target items in designing PLLs. In a digital PLL, it is difficult to control the frequency and phase independently, which makes it difficult to improve lock-up performance. A variable delay circuit which adjusts only the phase of the PLL is introduced here. A full loop model simulation with measured controllable delay shows the effectiveness of applying the phase adjust method with the variable delay to the PLL. Index Terms - PLL, phase adjust, variable delay, lock-up.
Improvements in patient-reported outcomes associated with an intervention to enhance quality of care for rural patients with type 2 diabetes: results of a controlled trial.

The aim of this study was to examine patient-reported outcomes in a controlled trial of a multifaceted provider-level intervention to improve quality of care for rural patients with type 2 diabetes.



We conducted a before/after intervention study with concurrent controls in two rural regions in Alberta, Canada. The intervention consisted of six monthly visits by a multidisciplinary health care team and was primarily directed at primary care providers. Clinical and patient-reported outcomes were assessed after 6 months. Patient-reported outcomes included changes in health-related quality of life (Health Utilities Index Mark 3 [HUI3]), satisfaction with care, lifestyle (Diabetes Lifestyle Form), and adherence to self-care activities. Analysis of covariance was used to assess differences over time between the control and intervention regions.



A total of 200 intervention and 172 control subjects were included in this analysis. After adjusting for important clinical and demographic differences, a statistically significant and clinically important improvement in the overall HUI3 score was seen at the 6-month follow-up in the intervention region (0.06 [95% CI 0.02-0.10]) compared with the control region (0.01 [-0.04 to 0.04]) (P = 0.03 for the difference between groups). Satisfaction with general medical care (P < 0.001 between groups) and diabetes care (P < 0.001 between groups) increased among patients in the intervention region compared with the control region. Self-efficacy, attitudes, and beliefs about diabetes control all increased in the intervention region when compared with the control region, but adherence to self-care activities did not.



A provider-level intervention directed at improving quality of clinical care for patients with type 2 diabetes also had a favorable impact on overall health-related quality of life, satisfaction with care, and other humanistic outcomes.
Randomized withdrawal of long-term prednisolone treatment in rheumatoid arthritis: effects on inflammation and bone mineral density.

Short-term, low-dose glucocorticoid (GC) treatment has anti-inflammatory and disease-modifying effects in rheumatoid arthritis (RA). However, scientific support for long-term, low-dose GC treatment, although widespread, is poor, and information on the effects on bone density is scarce. The aim of this study was to investigate how long-term GC treatment in RA affects inflammation as well as bone density, and also to investigate the feasibility of withdrawal of GC.



Fifty-eight patients with RA treated with 5-7.5 mg prednisolone daily for at least 2 years were randomized either to withdraw or to continue GC treatment. The patients were followed prospectively for 2 years with respect to disease activity [using the Disease Activity Score calculated for 28 joints, (DAS28)], functional ability [using the Health Assessment Questionnaire (HAQ) score] and bone mineral density (BMD) of the lumbar spine and hip.



Only 11 patients out of 26 randomized to stop GC treatment and available for outcome measures succeeded in stopping the GC medication within 1 year. Fifteen patients failed withdrawal of GC because of increased joint symptoms. A higher mean DAS28 during the study was associated with loss of bone mass in the trochanter. The group that continued with unchanged GC treatment did not deteriorate in BMD during the 2 years but in fact Z-scores improved significantly.



Our results indicate that low-dose GC treatment after several years has persisting anti-inflammatory effects in RA and no further negative impact on BMD. It thus seems to be more important to control disease activity than withdraw low-dose GC treatment in this population considering bone health.
Optimal convection volume for improving patient outcomes in an international incident dialysis cohort treated with online hemodiafiltration

Online hemodiafiltration (OL-HDF), the most efficient renal replacement therapy, enables enhanced removal of small and large uremic toxins by combining diffusive and convective solute transport. Randomized controlled trials on prevalent chronic kidney disease (CKD) patients showed improved patient survival with high-volume OL-HDF, underlining the effect of convection volume (CV). This retrospective international study was conducted in a large cohort of incident CKD patients to determine the CV threshold and range associated with survival advantage. Data were extracted from a cohort of adult CKD patients treated by post-dilution OL-HDF over a 101-month period. In total, 2293 patients with a minimum of 2 years of follow-up were analyzed using advanced statistical tools, including cubic spline analyses for determination of the CV range over which a survival increase was observed. The relative survival rate of OL-HDF patients, adjusted for age, gender, comorbidities, vascular access, albumin, C-reactive protein, and dialysis dose, was found to increase at about 55 l/week of CV and to stay increased up to about 75 l/week. Similar analysis of pre-dialysis β2-microglobin (marker of middle-molecule uremic toxins) concentrations found a nearly linear decrease in marker concentration as CV increased from 40 to 75 l/week. Analysis of log C-reactive protein levels showed a decrease over the same CV range. Thus, a convection dose target based on convection volume should be considered and needs to be confirmed by prospective trials as a new determinant of dialysis adequacy.
Defining the role of GLP-1 in the enteroinsulinar axis in type 2 diabetes using DPP-4 inhibition and GLP-1 receptor blockade.

Understanding the incretin pathway has led to significant advancements in the treatment of type 2 diabetes (T2D). Still, the exact mechanisms are not fully understood. In a randomized, placebo-controlled, four-period, crossover study in 24 patients with T2D, dipeptidyl peptidase-4 (DPP-4) inhibition and its glucose-lowering actions were tested after an oral glucose tolerance test (OGTT). The contribution of GLP-1 was examined by infusion of the GLP-1 receptor (GLP-1r) antagonist exendin-9. DPP-4 inhibition reduced glycemia and enhanced insulin levels and the incretin effect (IE). Glucagon was suppressed, and gastric emptying (GE) was decelerated. Exendin-9 increased glucose levels and glucagon secretion, attenuated insulinemia and the IE, and accelerated GE. With the GLP-1r antagonist, the glucose-lowering effects of DPP-4 inhibition were reduced by ∼ 50%. However, a significant effect on insulin secretion remained during GLP-1r blockade, whereas the inhibitory effects of DPP-4 inhibition on glucagon and GE were abolished. Thus, in this cohort of T2D patients with a substantial IE, GLP-1 contributed ∼ 50% to the insulin excursion after an OGTT with and without DPP-4 inhibition. Thus, a significant DPP-4-sensitive glucose-lowering mechanism contributes to glycemic control in T2D patients that may be not mediated by circulating GLP-1.
Measuring depression: comparison and integration of three scales in the GENDEP study.

A number of scales are used to estimate the severity of depression. However, differences between self-report and clinician rating, multi-dimensionality and different weighting of individual symptoms in summed scores may affect the validity of measurement. In this study we examined and integrated the psychometric properties of three commonly used rating scales.



The 17-item Hamilton Depression Rating Scale (HAMD-17), the Montgomery-Asberg Depression Rating Scale (MADRS) and the Beck Depression Inventory (BDI) were administered to 660 adult patients with unipolar depression in a multi-centre pharmacogenetic study. Item response theory (IRT) and factor analysis were used to evaluate their psychometric properties and estimate true depression severity, as well as to group items and derive factor scores.



The MADRS and the BDI provide internally consistent but mutually distinct estimates of depression severity. The HAMD-17 is not internally consistent and contains several items less suitable for out-patients. Factor analyses indicated a dominant depression factor. A model comprising three dimensions, namely 'observed mood and anxiety', 'cognitive' and 'neurovegetative', provided a more detailed description of depression severity.



The MADRS and the BDI can be recommended as complementary measures of depression severity. The three factor scores are proposed for external validation.
Multiple-dose safety, tolerability, and pharmacokinetics of oral nemonoxacin (TG-873870) in healthy volunteers.

Nemonoxacin (TG-873870) is a novel nonfluorinated quinolone with broad-spectrum activities against Gram-positive and Gram-negative aerobic, anaerobic, and atypical pathogens, as well as against methicillin-resistant Staphylococcus aureus, vancomycin-resistant S. aureus, and multiple-resistant bacterial pathogens. We conducted a randomized, double-blind, placebo-controlled, dose-escalating study to ascertain the safety, tolerability, and pharmacokinetics of nemonoxacin. We enrolled 46 healthy volunteers and used a once-daily oral-dosing range of 75 to 1,000 mg for 10 days. Additionally, the food effect was evaluated in subjects in the 500-mg cohort. Nemonoxacin was generally safe and well tolerated, with no significant changes in the clinical laboratory tests or electrocardiograms. Adverse effects, including headache, contact dermatitis, and rash, were mild and resolved spontaneously. Nemonoxacin was rapidly absorbed within 2 h postdosing, and generally, a steady state was reached after 3 days. The maximum plasma concentration and the area under the plasma concentration-time curve were dose proportional over the dosing range. The elimination half-life was approximately 7.5 h and 19.7 h on days 1 and 10, respectively. Approximately 37 to 58% of the drug was excreted in the urine. Food affected the pharmacokinetics, with decreases in the maximum plasma concentration and area under the plasma concentration-time curve of 46% and 27%, respectively. However, the free AUC/MIC(90) of nemonoxacin was more than 100 under both the fasting and fed conditions, predicting the efficacy of nemonoxacin against most of the tested pathogens. In conclusion, the results support further clinical investigation of once-daily nemonoxacin administration for antibiotic-sensitive and antibiotic-resistant bacterial infections.
Double-Blind , Randomized Study Evaluating the Glycemic and Anti-in fl ammatory Effects of Subcutaneous LY 2189102 , a Neutralizing IL-1 b Antibody , in PatientsWith Type 2 Diabetes

Type 2 diabetes occurs when pancreatic b-cell function fails to compensate for insulin resistance (1,2). As the duration of diabetes increases, b-cell function progressively deteriorates, partly as a result of apoptotic cell death (3–5). Inflammation is associated with pancreatic b-cell apoptosis and reduced insulin sensitivity, supporting the notion that inflammation plays a key role in aggravating or even causing type 2 diabetes specifically or the metabolic syndrome generally (6). Interleukin (IL)-1b is an inflammatory mediator that may contribute to this pathophysiology. IL-1b expression has been observed in b-cells of patients with type 2 diabetes (7). Moreover, production and secretion of IL-1b from b-cells is induced by high glucose levels and inhibits the function and promotes the apoptosis of b-cells (7–10). The IL-1 receptor antagonist (IL-1ra) protects human b-cells from glucose-induced functional impairment (7) and apoptosis, and its expression is decreased in patients with type 2 diabetes (11). The hypothesis that blocking IL-1b activity could be therapeutic in type 2 diabetes was tested clinically with anakinra, a recombinant IL-1ra (12,13). Results from a proof-of-concept study indicated that anakinra modestly improved hemoglobin A1c (HbA1c) relative to placebo, reduced circulating inflammatory cytokines, and showed signs of improved b-cell secretory function after 13 weeks of daily subcutaneousdosing (13).Ninemonths after treatment completion, anakinratreated patients continued to have improved proinsulin/insulin ratios and reduced inflammatory cytokines; anakinra responders required less exogenous insulin than did nonresponders (14). Clinical evaluation of a neutralizing IL-1b monoclonal antibody (XOMA 052) in type 2 diabetic patients showed similar results. XOMA 052 improved HbA1c relative to placebo after a single intravenous infusion and after repeated subcutaneous dosing; improvements in fasting blood glucose and insulin sensitivity after subcutaneous dosing were also noted (15). Typically only a small percentage of cytokine receptors require engagement to activate downstream signaling pathways, and cytokines are typically labile proteins expressed at low concentrations. Because anakinra binds to the IL-1 receptor and has a short half-life (4–6 h) (16), it is unclear whether the modest nature of the response in type 2 diabetes was related to compound-specific properties or a reflection of the role of this cytokine pathway in the disease pathogenesis. Although XOMA 052 binds and neutralizes IL-1b directly and has a longer half-life, it was dosed in a limited number of subjects and for short duration. Further evaluation c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c
High dose alkylator therapy for extracranial malignant rhabdoid tumors in children.

Extracranial malignant rhabdoid tumor (MRT) is a rare pediatric cancer with a poor prognosis. The kidney is the most common site. Isolated reports have shown improvements in patient survival, but no specific treatment regimen has shown efficacy over others.


PROCEDURE
Retrospective review of patients diagnosed with extracranial MRT at Children's Hospital Los Angeles between 1983 and 2012.



The median age at presentation for the 21 patients was 13 months (range, 0-108 months). Ten patients had renal primary tumors. The median time to progression was 4 months (range, 0.4-7 months). The 5-year event free survival (EFS) and overall survival (OS) of the entire cohort was 38 ± 10.6%. After 2002, patients diagnosed with extracranial MRT were administered a chemotherapy regimen of vincristine, doxorubicin and high dose cyclophosphamide (VDC). The OS for the patients diagnosed before and after 2002 were 20 ± 12% and 54 ± 15%, respectively. Of the 13 patients who received VDC containing regimen, eight patients achieved a complete radiological remission; five of these patients are long-term survivors. Four patients who received autologous bone marrow transplantation were alive at last follow-up. All patients with unresectable primary tumors died. Patients who had disease progression or relapse did not survive.



Patients with extracranial MRT have a poor prognosis. Treatment with high dose alkylator therapy followed by consolidation with high dose chemotherapy and autologous bone marrow transplant for those patients in radiographic complete remission appears to have a beneficial effect on survival.
The HIV-Brazil Cohort Study: Design, Methods and Participant Characteristics

The HIV-Brazil Cohort Study was established to analyze the effectiveness of combination antiretroviral therapy (cART) and the impact of this treatment on morbidity, quality of life (QOL) and mortality. The study design, patients' profiles and characteristics of cART initiation between 2003 and 2010 were described.



Since 2003, the HIV-Brazil Cohort has been following HIV-infected adults receiving cART at 26 public health care facilities, using routine clinical care data and self-reported QOL questionnaires. When not otherwise available, data are obtained from national information systems. The main outcomes of interest are diseases related or unrelated to HIV; suppression of viral replication; adverse events; virological, clinical and immunological failures; changes in the cART; and mortality. For the 5,061 patients who started cART between 2003 and 2010, the median follow-up time was 4.1 years (IQR 2.2-5.9 years) with an 83.4% retention rate. Patient profiles were characterized by a predominance of men (male/female ratio 1.7∶1), with a mean age of 36.9 years (SD 9.9 years); 55.2% had been infected with HIV via heterosexual contact. The majority of patients (53.4%) initiated cART with a CD4+ T-cell count ≤200 cells/mm3. The medications most often used in the various treatment regimens were efavirenz (59.7%) and lopinavir/ritonavir (18.2%). The proportion of individuals achieving viral suppression within the first 12 months of cART use was 77.4% (95% CI 76.1-78.6). Nearly half (45.4%) of the patients presented HIV-related clinical manifestations after starting cART, and the AIDS mortality rate was 13.9 per 1,000 person-years.



Results from cART use in the daily practice of health services remain relatively unknown in low- and middle-income countries, and studies with the characteristics of the HIV-Brazil Cohort contribute to minimizing these shortcomings, given its scope and patient profile, which is similar to that of the AIDS epidemic in the country.