nils-herrmann/clean_scirepeval huggingface dataset:
Reduction in lipoprotein(a) with PCSK9 monoclonal antibody evolocumab (AMG 145): a pooled analysis of more than 1,300 patients in 4 phase II trials.

The purpose of this study was assess the effect of evolocumab (AMG 145) on lipoprotein (Lp)(a) from a pooled analysis of 4 phase II trials.



Lp(a), a low-density lipoprotein (LDL) particle linked to the plasminogen-like glycoprotein apolipoprotein(a), shows a consistent and independent positive association with cardiovascular disease risk in epidemiological studies. Current therapeutic options to reduce Lp(a) are limited.



A pooled analysis of data from 1,359 patients in 4 phase II trials assessed the effects of evolocumab, a fully human monoclonal antibody to PCSK9, on Lp(a), the relationship between Lp(a) and lowering of low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B, and the influence of background statin therapy. Lp(a) was measured using a standardized isoform-independent method.



Evolocumab treatment for 12 weeks resulted in significant (p < 0.001) mean (95% confidence interval) dose-related reductions in Lp(a) compared to control: 29.5% (23.3% to 35.7%) and 24.5% (20.4% to 28.7%) with 140 mg and 420 mg, dosed every 2 and 4 weeks, respectively, with no plateau of effect. Lp(a) reductions were significantly correlated with percentages of reductions in LDL-C (Spearman correlation coefficient, 0.5134; p < 0.001) and apolipoprotein B (Spearman correlation coefficient, 0.5203; p < 0. 001). Mean percentage reductions did not differ based on age or sex but the trend was greater in those patients taking statins.



Inhibition of PCSK9 with evolocumab resulted in significant dose-related reductions in Lp(a). While the mean percentage of reduction was significantly greater in those patients with baseline Lp(a) of ≤125 nmol/l, the absolute reduction was substantially larger in those with levels >125 nmol/l.
A mind-body technique for symptoms related to fibromyalgia and chronic fatigue.

A novel mind-body approach (amygdala retraining) is hypothesized to improve symptoms related to fibromyalgia and chronic fatigue.



To examine the use of a mind-body approach for improving symptoms related to fibromyalgia and chronic fatigue.



This was a single-blind, randomized controlled trial.



The study was conducted in a tertiary-care fibromyalgia and chronic fatigue clinic.



Patients with fibromyalgia, chronic fatigue, or both were included.



Patients were randomly assigned to receive amygdala retraining along with standard care or standard care alone. Standard care involved attending a 1.5-day multidisciplinary program. The amygdala retraining group received an additional 2.5-hour training course in which the key tools and techniques adapted from an existing program were taught to the patient. A home-study video course and associated text were provided to supplement the on-site program. Both groups received telephone calls twice a month to answer questions related to technique and to provide support.



Validated self-report questionnaires related to general health, well-being, and symptoms, including Short Form-36, Measure Yourself Medical Outcome Profile, Multidimensional Fatigue Inventory, Epworth Sleepiness Scale, and Fibromyalgia Impact Questionnaire.



Of the 44 patients randomly assigned who completed baseline assessments, 21 patients completed the study (14 in the standard care group and 7 in the study group). Median age was 48 years (range, 27-56 years), and female subjects comprised 91% of the group. Analyses demonstrated statistically significant improvements in scores for physical health, energy, pain, symptom distress, and fatigue in patients who received the amygdala retraining compared with standard care.
Efficacy and safety of statins in hypercholesterolemia with emphasis on lipoproteins

Information of the effect of statin on lipoproteins such as apolipoprotein (apo) A-I, lipoprotein (a) [Lp (a)], or apolipoprotein B levels is limited. This investigation was a crossover study designed to evaluate the efficacy and safety of atorvastatin and simvastatin in patients with hyperlipidemia. Sixty-six patients were involved in the study. Group I consisted of 32 patients, who were first treated with atorvastatin (10 mg) then switched to simvastatin (10 mg). Group II consisted of 34 patients, who were first treated with simvastatin then switched to atorvastatin. Each regimen was used for 3 months (phase I), stopped for 2 months, and then restarted for another 3 months (phase II). Both statins effectively reduced total cholesterol, low-density lipoprotein cholesterol (LDL-C), apo B, and Lp (a) (P < 0.001 in all comparisons). A significant increase in the high-density lipoprotein cholesterol (HDL-C) was noted after both statin treatments (P < 0.05 in all comparisons). Both statins caused an increase in the apo A-I levels, and the extent of changes in apo A-I revealed no difference between the two drugs. Compared to the simvastatin group, there were more patients in the atorvastatin group achieving the National Cholesterol Education Program ATP-III LDL-C goal (P < 0.05) and European LDL-C goal (P < 0.001). Both treatments were well tolerated; no patient was withdrawn from the study. This study demonstrates that both statins can effectively improve lipid profiles in patients with hyperlipidemia. Atorvastatin is more effective in helping patients reach the ATP-III and European LDL-C goals than simvastatin at the same dosage.
Pain Does Autonomic Neuropathy Influence Spinal Cord Stimulation Therapy Success in Diabetic Patients with Critical Lower Limb Ischemia ?

Sixty consecutive diabetic patients (15 with early and 13 with definite and/or combined autonomic neuropathy) with an ankle/brachial systolic pressure index (ABI) less than 0.20 6 0.08, underwent spinal cord stimulation after failed conservative or surgical treatment. The neuropathic status of the patients was evaluated before implantation and pedal TcpO2 measurements on the dorsum of the foot were performed.
Pharmacokinetic, pharmacodynamic and biomarker evaluation of transforming growth factor-β receptor I kinase inhibitor, galunisertib, in phase 1 study in patients with advanced cancer

Transforming growth factor-beta (TGF-β) signaling plays a key role in epithelial-mesenchymal transition (EMT) of tumors, including malignant glioma. Small molecule inhibitors (SMI) blocking TGF-β signaling reverse EMT and arrest tumor progression. Several SMIs were developed, but currently only LY2157299 monohydrate (galunisertib) was advanced to clinical investigation.  The first-in-human dose study had three parts (Part A, dose escalation, n = 39; Part B, safety combination with lomustine, n = 26; Part C, relative bioavailability study, n = 14).  A preclinical pharmacokinetic/pharmacodynamic (PK/PD) model predicted a therapeutic window up to 300 mg/day and was confirmed in Part A after continuous PK/PD. PK was not affected by co-medications such as enzyme-inducing anti-epileptic drugs or proton pump inhibitors. Changes in pSMAD2 levels in peripheral blood mononuclear cells were associated with exposure indicating target-related pharmacological activity of galunisertib. Twelve (12/79; 15 %) patients with refractory/relapsed malignant glioma had durable stable disease (SD) for 6 or more cycles, partial responses (PR), or complete responses (CR). These patients with clinical benefit had high plasma baseline levels of MDC/CCL22 and low protein expression of pSMAD2 in their tumors. Of the 5 patients with IDH1/2 mutation, 4 patients had a clinical benefit as defined by CR/PR and SD ≥6 cycles. Galunisertib had a favorable toxicity profile and no cardiac adverse events.  Based on the PK, PD, and biomarker evaluations, the intermittent administration of galunisertib at 300 mg/day is safe for future clinical investigation.
Follow-up measurements of Nevirapine plasma levels over a prolonged period.

Over a period of more than four years of treatment, 177 Nevirapine plasma levels were taken from 27 patients. The values showed a high inter-patient variability and a lower intra-patient variability. Differences in body weight turned out to be the main reason for inter-patient variability. Treatment over a prolonged period did not result in any change in plasma concentrations. Adjusting dosage by means of therapeutic drug monitoring would appear to be a reasonable way of maximising patient benefit from treatment.
High EVI1 expression is associated with MLL rearrangements and predicts decreased survival in paediatric acute myeloid leukaemia: a report from the children's oncology group.

Ectopic viral integration site-1 (EVI1) is highly expressed in certain cytogenetic subsets of adult acute myeloid leukaemia (AML), and has been associated with inferior survival. We sought to examine the clinical and biological associations of EVI1(high) , defined as expression in excess of normal controls, in paediatric AML. EVI1 mRNA expression was measured via quantitative real-time polymerase chain reaction in diagnostic specimens obtained from 206 patients. Expression levels were correlated with clinical features and outcome. EVI1(high) was present in 58/206 (28%) patients. MLL rearrangements occurred in 40% of EVI1(high) patients as opposed to 12% of the EVI1(low/absent) patients (P < 0·001). No abnormalities of 3q26 were found in EVI1(high) patients by conventional cytogenetic analysis, nor were cryptic 3q26 abnormalities detected in a subset of patients screened by next-generation sequencing. French-American-British class M7 was enriched in the EVI1(high) group, accounting for 24% of these patients. EVI1(high) patients had significantly lower 5-year overall survival from study entry (51% vs. 68%, P = 0·015). However, in multivariate analysis including other established prognostic markers, EVI1 expression did not retain independent prognostic significance. EVI1 expression is currently being studied in a larger cohort of patients enrolled on subsequent Children's Oncology Group trials, to determine if EVI1(high) has prognostic value in MLL-rearranged or intermediate-risk subsets.
Randomized clinical trial of external stent drainage of the pancreatic duct to reduce postoperative pancreatic fistula after pancreaticojejunostomy.

Postoperative pancreatic fistula (POPF) remains one of the most common causes of morbidity following pancreaticoduodenectomy (PD). This randomized trial examined whether external stent drainage of the pancreatic duct decreases the rate of POPF after PD and subsequent pancreaticojejunostomy (PJ).



Consecutive patients who underwent PD with subsequent construction of a duct-to-mucosa PJ were randomized into a stented and a non-stented group. The primary outcome was the incidence of clinically relevant POPF. Secondary outcomes were morbidity and mortality rates, and hospital stay.



Of 114 PD procedures, 93 were suitable for inclusion in the study after informed consent. The rate of clinically relevant POPF was significantly lower in the stented group than in the non-stented group: three of 47 (6 per cent) versus ten of 46 (22 per cent) (P = 0·040). Among patients with a dilated duct, rates of POPF were similar in both groups. Among patients with a non-dilated duct, clinically relevant POPF was significantly less common in the stented group than in the non-stented group: two of 21 (10 per cent) versus eight of 20 (40 per cent) (P = 0·033). No significant differences in morbidity or mortality were observed. Univariable analysis identified body mass index (BMI), pancreatic cancer,pancreatic texture, pancreatic duct size and duct stenting as risk factors related to clinically relevant POPF. Multivariable analysis taking these five factors into account identified high BMI (risk ratio(RR) 11·45; P = 0·008), non-dilated duct (RR 5·33; P = 0·046) and no stent (RR 10·38; P = 0·004) as significant risk factors.



External duct stenting reduced the risk of clinically relevant POPF after PD and subsequent duct-to-mucosa PJ.
Effect of Probiotic Lactobacillus salivarius UBL S22 and Prebiotic Fructo-oligosaccharide on Serum Lipids, Inflammatory Markers, Insulin Sensitivity, and Gut Bacteria in Healthy Young Volunteers: A Randomized Controlled Single-Blind Pilot Study.

This study investigated the effect of 6-week supplementation of a probiotic strain Lactobacillus salivarius UBL S22 with or without prebiotic fructo-oligosaccharide (FOS) on serum lipid profiles, immune responses, insulin sensitivity, and gut lactobacilli in 45 healthy young individuals. The patients were divided into 3 groups (15/group), that is, placebo, probiotic, and synbiotic. After 6 weeks, a significant reduction (P < .05) in total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides and increase in high-density lipoprotein cholesterol was observed in the probiotic as well as in the synbiotic group when compared to placebo; however, the results of total cholesterol and LDL-cholesterol were more pronounced in the synbiotic group. Similarly, when compared to the placebo group, the serum concentrations of inflammatory markers such as high sensitivity C-reactive protein, interleukin (IL) 6, IL-1β, and tumor necrosis factor α were significantly (P < .05) reduced in both the experimental groups, but again the reduction in the synbiotic group was more pronounced. Also, an increase (P < .05) in the fecal counts of total lactobacilli and a decrease (P < .05) in coliforms and Escherichia coli was observed in both the experimental groups after 6 weeks of ingestion. Overall, the combination of L salivarius with FOS was observed to be more beneficial than L salivarius alone, thereby advocating that such synbiotic combinations could be therapeutically exploited for improved health and quality of life.
A novel implantable vagus nerve stimulation system (ADNS-300) for combined stimulation and recording of the vagus nerve: Pilot trial at Ghent University Hospital

Vagus nerve stimulation (VNS) is an established treatment for refractory epilepsy. The ADNS-300 is a new system for VNS that includes a rechargeable stimulus generator and an electrode for combined stimulation and recording. In this feasibility study, three patients were implanted with ADNS-300 for therapeutic VNS. In addition, compound action potentials (CAPs) were recorded to evaluate activation of the vagus nerve in response to VNS.



Three patients were implanted with a cuff-electrode around the left vagus nerve, that was connected to a rechargeable pulse generator under the left clavicula. Two weeks after surgery, therapeutic VNS (0.25-1.25 mA, 500 μs, 30s on, 10 min off and 30Hz) was initiated and stimulus-induced CAPs were recorded.



The ADNS-300 system was successfully implanted in all three patients and patients were appropriately stimulated during six months of follow-up. A reduction in seizure frequency was demonstrated in two patients (43% and 40% in patients 1 and 3, respectively), while in patient 2 seizure frequency remained unchanged. CAPs could be recorded in patients 1 and 2, proving stimulation-induced activation of the vagus nerve.



This feasibility study demonstrates that the ADNS-300 system can be used for combined therapeutic stimulation (in 3/3 patients) and recording of CAPs in response to VNS (in 2/3 patients) up to three weeks after surgery. Implantation in a larger number of patients will lead to a better understanding of the electrophysiology of the vagus nerve, which in turn could result in more adequate and individualized VNS parameter choice.
The congenital bilateral perisylvian syndrome: imaging findings in a multicenter study. CBPS Study Group.

To describe the neuroimaging findings and the clinical features in patients with the congenital bilateral perisylvian syndrome.



Evaluation including history, general and neurologic examinations, electroencephalogram, chromosomal studies, and imaging data were reviewed in 31 patients. 
All patients had similar neurologic dysfunction, primarily pseudobulbar paresis. Dysarthria and severe restriction of tongue movements were present in all. Motor milestones were delayed in 75% of the patients and language milestones in all. Mild to moderate intellectual deficits were documented in 75% of patients (full-scale IQ = 70). Pyramidal signs were observed in 70%. Seizures were present in 87% and were intractable to medical therapy in half of this group. MR revealed bilateral perisylvian and perirolandic malformations with exposure of the insula. The malformations were symmetrical in 80% of cases. Pathologic correlation revealed four layered polymicrogyria in the affected areas.



The congenital bilateral perisylvian syndrome is a homogeneous clinical-radiologic entity. The underlying abnormality is probably polymicrogyria.
Blood Flow Restriction Training After Knee Arthroscopy: A Randomized Controlled Pilot Study.

Quadriceps strength after arthroscopic knee procedures is frequently diminished several years postoperation. Blood flow restriction (BFR) training uses partial venous occlusion while performing submaximal exercise to induce muscle hypertrophy and strength improvements. The purpose of this study was to evaluate BFR as a postoperative therapeutic intervention after knee arthroscopy.



A randomized controlled pilot study comparing physical therapy with and without BFR after knee arthroscopy was conducted. Patients underwent 12 sessions of supervised physical therapy. Subjects followed the same postoperative protocol with the addition of 3 additional BFR exercises. Outcome measures included thigh girth, physical function measures, Knee Osteoarthritis Outcome Score (KOOS), Veterans RAND 12-Item Health Survey (VR12), and strength testing. Bilateral duplex ultrasonography was used to evaluate for deep venous thrombosis preintervention and postintervention.



Seventeen patients completed the study. Significant increases in thigh girth were observed in the BFR group at 6-cm and 16-cm proximal to the patella (P = 0.0111 and 0.0001). All physical outcome measures significantly improved in the BFR group, and the timed stair ascent improvements were greater than conventional therapy (P = 0.0281). The VR-12 and KOOS subscales significantly improved in the BFR group, and greater improvement was seen in VR-12 mental component score (P = 0.0149). The BFR group displayed approximately 2-fold greater improvements in extension and flexion strength compared with conventional therapy (74.59% vs 33.5%, P = 0.034). No adverse events were observed during the study.



This study suggests that BFR is an effective intervention after knee arthroscopy. Further investigation is warranted to elucidate the benefits of this intervention in populations with greater initial impairment.
A combined early cognitive and physical rehabilitation program for people who are critically ill: the activity and cognitive therapy in the intensive care unit (ACT-ICU) trial.

In the coming years, the number of survivors of critical illness is expected to increase. These survivors frequently develop newly acquired physical and cognitive impairments. Long-term cognitive impairment is common following critical illness and has dramatic effects on patients' abilities to function autonomously. Neuromuscular weakness affects similar proportions of patients and leads to equally profound life alterations. As knowledge of these short-term and long-term consequences of critical illness has come to light, interventions to prevent and rehabilitate these devastating consequences have been sought. Physical rehabilitation has been shown to improve functional outcomes in people who are critically ill, but subsequent studies of physical rehabilitation after hospital discharge have not. Post-hospital discharge cognitive rehabilitation is feasible in survivors of critical illness and is commonly used in people with other forms of acquired brain injury. The feasibility of early cognitive therapy in people who are critically ill remains unknown.



The purpose of this novel protocol trial will be to determine the feasibility of early and sustained cognitive rehabilitation paired with physical rehabilitation in patients who are critically ill from medical and surgical intensive care units.



This is a randomized controlled trial.



The setting for this trial will be medical and surgical intensive care units of a large tertiary care referral center.



The participants will be patients who are critically ill with respiratory failure or shock.



Patients will be randomized to groups receiving usual care, physical rehabilitation, or cognitive rehabilitation plus physical rehabilitation. Twice-daily cognitive rehabilitation sessions will be performed with patients who are noncomatose and will consist of orientation, memory, and attention exercises (eg, forward and reverse digit spans, matrix puzzles, letter-number sequences, pattern recognition). Daily physical rehabilitation sessions will advance patients from passive range of motion exercises through ambulation. Patients with cognitive or physical impairment at discharge will undergo a 12-week, in-home cognitive rehabilitation program.



A battery of neurocognitive and functional outcomes will be measured 3 and 12 months after hospital discharge.



If feasible, these interventions will lay the groundwork for a larger, multicenter trial to determine their efficacy.
Demonstration of psychometric soundness of the Dietary Sodium Restriction Questionnaire in patients with heart failure.

Recommendation of a low-sodium diet is the most common nonpharmacologic intervention used in patients with heart failure (HF). However, nonadherence to this recommendation is extremely high. There are no instruments available for the specific measurement of patients' perceptions of their barriers to, and attitudes toward, following a low-sodium diet. The purpose of this study was to evaluate the psychometric properties of a new instrument, the Dietary Sodium Restriction Questionnaire (DSRQ). Based on the Theory of Planned Behavior (TPB), the DSRQ assesses adherence through the use of 3 subscales. Each subscale represents a construct of the TPB: attitude, subjective norm, and perceived behavioral control.



The sample consisted of 174 patients with HF (age 62.4 +/- 13.5 years, 56.1% were male, 83.8% were white, and 86.9% had New York Heart Association class II/III). Factorial validity was tested using principal component analysis. Reliability was tested using Cronbach's alpha to assess the internal consistency of the 3 subscales. Reliability was further evaluated with item-total correlations and inter-item correlations.



Principal component analysis of the DSRQ resulted in the extraction of 3 factors, each factor corresponding to a construct of the TPB. The 3-factor solution explained a total of 54.2% of the variance, with Attitude contributing 23.4%, Perceived Behavioral Control contributing 18.1%, and Subjective Norm contributing 12.7%. The Cronbach's coefficient alpha for each subscale was Attitude .88, Subjective Norm .62, and Perceived Behavioral Control .76.



The DSRQ is a valid and reliable tool for measuring patients' attitudes, beliefs, and barriers related to following a low-sodium diet in adult, white patients with New York Heart Association class II/III HF.