nils-herrmann/clean_scirepeval huggingface dataset:
Rationale and design of the Post-MI FREEE trial: a randomized evaluation of first-dollar drug coverage for post-myocardial infarction secondary preventive therapies.

Medication nonadherence is a major public health problem, especially for patients with coronary artery disease. The cost of prescription drugs is a central reason for nonadherence, even for patients with drug insurance. Removing patient out-of-pocket drug costs may increase adherence, improve clinical outcomes, and even reduce overall health costs for high-risk patients. The existing data are inadequate to assess whether this strategy is effective.


 Potentially eligible patients will be those individuals who receive their health and pharmacy benefits through Aetna, Inc. Patients enrolled in a Health Savings Account plan, who are > or =65 years of age, whose plan sponsor (ie, the employer, union, government, or association that sponsors the particular benefits package) has opted out of participating in the study, and who do not receive both medical services and pharmacy coverage through Aetna will be excluded. The plan sponsor of each eligible patient will be block randomized to either full drug coverage or current levels of pharmacy benefit, and all subsequently eligible patients of that same plan sponsor will be assigned to the same benefits group. The primary outcome of the trial is a composite clinical outcome of readmission for acute MI, unstable angina, stroke, congestive heart failure, revascularization, or inhospital cardiovascular death. Secondary outcomes include medication adherence and health care costs. All patients will be followed up for a minimum of 1 year.



The Post-MI FREEE trial will be the first randomized study to evaluate the impact of reducing cost-sharing for essential cardiac medications in high-risk patients on clinical and economic outcomes.
Double-blinded, placebo-controlled, prospective randomized trial evaluating the efficacy of paravertebral block with and without continuous paravertebral block analgesia in outpatient breast cancer surgery.

Paravertebral block (PVB) is an effective alternative to general anesthesia for breast cancer surgery. Continuous paravertebral block (CPVB) anesthesia may extend postoperative analgesia at home and improve quality of early postoperative recovery of breast cancer patients.



This double-blinded randomized trial was conducted to compare degree of pain, nausea, mood, level of symptom distress, and time to return to normal daily activity between PVB and PVB + CPVB in patients undergoing outpatient breast cancer surgery.



Between July 2003 and April 2008 we randomly assigned 94 (73 evaluable) patients in a 1:1:1 ratio with early breast cancer to single injection PVB followed by CPVB infusion of 0.1% or 0.2% ropivacaine vs placebo (saline) for 48 hours postoperatively for unilateral breast cancer surgery without reconstruction. The primary study endpoint was the degree of pain, nausea, mood state, level of symptom distress, and recovery time.



Of the 468 patients assessed for eligibility, 94 consented and 21 with incomplete data or follow-up were excluded, leaving 73 subjects for analysis. There was no clinically significant difference in degree of postoperative pain, nausea, mood state, level of symptom distress, or return to normal activity among the three study groups.



The current study does not support the routine use of continuous paravertebral catheter anesthesia in patients undergoing operative treatment for breast cancer.
MDM2 Amplification in Problematic Lipomatous Tumors: Analysis of FISH Testing Criteria.

To discriminate lipomas from atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) we perform fluorescence in situ hybridization (FISH) for MDM2 amplification in several problematic situations: "lipomas" >10 cm, lesions with equivocal atypia, recurrent "lipomas," all retroperitoneal/pelvic/abdominal "lipomas", and in cases not fitting the above criteria but having worrisome clinical or radiologic features. To ascertain the validity of these criteria, we have reviewed our experience with 301 consecutive differentiated lipomatous tumors in which the diagnosis of ALT could not be established on the basis of histologic sections and in which FISH was performed on the basis of the above criteria. The final diagnosis was based on MDM2 amplification status. Given the nature of this study to evaluate difficult lesions, most cases included (74%) were received in consultation. This enhanced our study series for borderline cases, and the data presented may not be generalizable to adipocytic tumors seen outside a subspecialty setting. Of 301 cases, 108 proved to be ALT/WDL (36%). The most common test indication was size >10 cm (n=187), followed by equivocal atypia (n=145), retroperitoneal/pelvic/abdominal location (n=86), recurrence (n=33), and clinical concern (n=12). Of the tumors >10 cm, 68 (36%) proved to be ALT/WDL, whereas the remainder were interpreted as lipoma or its variants (eg, spindle cell or pleomorphic lipoma). The 2 groups did not differ statistically in size, although ALTs consistently occurred in patients above 50 years of age. Of the cases with equivocal atypia, 72 (50%) proved to be ALT/WDL. Those in the retroperitoneum/abdomen/pelvis were ALT/WDL in 30 cases (35%), and those that had recurred were ALT in 18 cases (55%). Recurrence, atypia, and having multiple indications for testing were more common in ALT than in benign lesions (P=0.02, 0.0001, 0.0012, respectively). No ALT/WDL occurred in the hands and feet, and only a single ALT/WDL was superficial (1 ALT/WDL vs. 60 lipoma/spindle cell or pleomorphic lipoma). Small (<10 cm) retroperitoneal tumors without additional features were always benign (n=9). On the basis of our results, FISH testing is recommended for: (1) recurrent lesions; (2) deep extremity lesions that are >10 cm in patients over 50 years of age; (3) in cases with equivocal atypia; (4) in lesions of the retroperitoneum/pelvis/abdomen, and in special clinical situations as directed by treating clinicians. Testing is low yield in superficial lesions, in small extremity lesions without additional indicators for testing, in large extremity lesions without additional features in patients under the age of 50, and in lesions arising in the hands/feet. More evidence is needed regarding testing in small retroperitoneal lesions without additional features. By adopting these criteria, we could have avoided testing 74 cases, missing a single superficial ALT/WDL.
Qualitative and quantitative changes in coronary plaque associated with atorvastatin therapy.

The aim of this study was to elucidate the time course of atorvastatin-induced changes in vulnerable plaque using angioscopy and intravascular ultrasound (IVUS).



Fifty-seven hypercholesterolemic patients with coronary artery disease (CAD) were treated with atorvastatin (10-20 mg/day) for 80 weeks and then coronary plaques were evaluated with angioscopy and IVUS. Angioscopic images were classified into 6 grades (0-5) based on yellow color intensity. A 20-mm segment containing angioscopically-identified yellow plaque was also examined by IVUS to measure atheroma volume. The mean angioscopic grade of 58 yellow plaques significantly decreased from 1.5 (95% confidence interval [CI] 1.2 to 1.8) to 1.1 (95%CI 0.9 to 1.3, P=0.012) at week 28 and 1.2 (95%CI 0.9 to 1.4, P=0.024) at week 80. Mean volume of 30 lesions, including the 58 yellow plaques, significantly reduced -8.3% (95%CI -11.5 to -5.2) at week 28 (P<0.001 for baseline vs week 28) and -17.8% (95%CI -23.9 to -11.8) at week 80 (P<0.001 for baseline vs week 80).



In patients with CAD treated with atorvastatin, serial analysis with angioscopy demonstrated early loss of yellow color in plaques, and IVUS volumetric analysis showed subsequent plaque regression. Both changes possibly indicate reduction of plaque vulnerability in an additive manner.
Early detection by diffusion-weighted sequence magnetic resonance imaging of severe brain lesions after fetoscopic laser coagulation for twin-twin transfusion syndrome.

Monochorionic twins treated by fetoscopic laser coagulation (FLC) for twin-twin transfusion syndrome (TTTS) are at increased risk of neurodevelopmental impairment. Our aim was to evaluate the additional value of diffusion-weighted imaging (DWI) over fetal sonography and T2 magnetic resonance imaging (MRI) in the detection of acute ischemic cerebral lesions shortly following FLC.



This was a prospective cohort study of fetuses with TTTS treated by FLC. All fetuses underwent brain DWI and T2-MRI within 24-96 h after the procedure and a follow-up MRI at 30-32 weeks' gestation. All fetuses also had frequent ultrasound evaluation until delivery.



Thirty pregnancies with TTTS were included in the study. Eight resulted in survival of only one twin after the procedure (Group A), while the other 22 pregnancies resulted in the survival of both twins (Group B), as assessed at the time of initial MRI. Two fetuses in Group A and four in Group B had evidence of transient bleeding in the germinal matrix. Three fetuses in Group B and none in Group A had diffuse ischemic changes in the white matter. One fetus died in utero 24 h after MRI. The other two fetuses in Group B demonstrated an acute infarct 24-48 h after the procedure. Subsequent scans at 28-29 and 32 weeks showed brain atrophy compatible with an old infarct.



DWI can demonstrate cerebral damage immediately after FLC. Larger cohorts are needed to determine the role of fetal MRI in the prenatal assessment and follow-up of patients with TTTS.
Neurological sequelae in twins born after assisted conception: controlled national cohort study.

To compare neurological sequelae in twins born after assisted conception with singletons after assisted conception and naturally conceived twins and to assess neurological sequelae in children conceived after in vitro fertilisation (IVF) compared with intracytoplasmic sperm injection (ICSI).



Controlled, national register based, cohort study.



Twins (n = 3393) and singletons (n = 5130) conceived by using assisted reproductive technologies and naturally conceived twins (n = 10 239) born in Denmark between 1995 and 2000. The children's age at time of follow up was 2-7 years.



Children were identified by cross linkage of the national medical birth registry and the national registry for in vitro fertilisation. Neurological and psychiatric diagnoses were retrieved from the national patients' registry and the Danish psychiatric central registry.



Neurological sequelae, defined as cerebral palsy, mental retardation, severe mental developmental disturbances, and retarded psychomotor development. Further we made separate analyses on the specific cerebral palsy diagnosis.



The crude prevalence rates per 1000 of neurological sequelae in twins and singletons after assisted conception and in naturally conceived twins were 8.8, 8.2, and 9.6, and of cerebral palsy 3.2, 2.5, and 4.0, respectively. In twins after assisted conception compared with control twins, the odds ratios of neurological sequelae and specifically of cerebral palsy, adjusted for child sex and year of birth, were 0.9 (95% confidence interval 0.6 to 1.4) and 0.8 (0.4 to 1.6), respectively. The corresponding odds ratios for twins after assisted conception compared with singletons after assisted conception were 1.1 (0.7 to 1.7) for neurological sequelae and 1.3 (0.6 to 2.9) for cerebral palsy. The odds ratio of neurological sequelae in children conceived by ICSI was 0.9 (0.5 to 1.7) nu children conceived by IVF.



Twins from assisted conception have a similar risk of neurological sequelae as their naturally conceived peers and singletons from assisted conception. Children born after ICSI have the same risk of neurological sequelae as children born after IVF.
Immunogenicity and safety of a booster dose of an investigational adjuvanted polyprotein HIV-1 vaccine in healthy adults and effect of administration of chloroquine.

This phase II study evaluated the effect of chloroquine on the specific CD8(+) T-cell responses to and the safety of a booster dose of investigational human immunodeficiency virus type 1 (HIV-1) F4/AS01(B) vaccine containing 10 μg of recombinant fusion protein (F4) adjuvanted with the AS01(B) adjuvant system. Healthy adults aged 21 to 41 years, primed 3 years before with two F4/AS01(B) doses containing 10 or 30 μg of F4 (ClinicalTrials.gov registration number NCT00434512), were randomized (1:1) to receive the F4/AS01(B) booster administered alone or 2 days after chloroquine (300 mg). F4-specific CD8(+)/CD4(+) T-cell responses were characterized by intracellular cytokine staining and lymphoproliferation assays and anti-F4 antibodies by enzyme-linked immunosorbent assays (ELISAs). No effect of chloroquine on CD4(+)/CD8(+) T-cell and antibody responses and no vaccine effect on CD8(+) T-cell responses (cytokine secretion or proliferation) were detected following F4/AS01(B) booster administration. In vitro, chloroquine had a direct inhibitory effect on AS01(B) adjuvant properties; AS01-induced cytokine production decreased upon coincubation of cells with chloroquine. In the pooled group of participants primed with F4/AS01(B) containing 10 μg of F4, CD4(+) T-cell and antibody responses induced by primary vaccination persisted for at least 3 years. The F4/AS01(B) booster induced strong F4-specific CD4(+) T-cell responses, which persisted for at least 6 months with similar frequencies and polyfunctional phenotypes as following primary vaccination, and high anti-F4 antibody concentrations, reaching higher levels than those following primary vaccination. The F4/AS01(B) booster had a clinically acceptable safety and reactogenicity profile. An F4/AS01(B) booster dose, administered alone or after chloroquine, induced robust antibody and F4-specific CD4(+) T-cell responses but no significant CD8(+) T-cell responses (cytokine secretion or proliferation) in healthy adults.
L-threo-3,4-dihydroxyphenylserine (L-DOPS) co-administered with entacapone improves freezing of gait in Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by a variety of motor symptoms including freezing of gait (FOG), in which walking is transiently halted as if the patient's feet were 'glued to the ground'. Treatment of FOG is still challenging. Although L-threo-3,4-dihydroxyphenylserine (L-DOPS), a precursor of noradrenaline, has been on the market in Japan because of its beneficial effect for FOG, clinical use of L-DOPS has been far from satisfying. However, the fact that there were some responders to L-DOPS encouraged us to hypothesize that the enhancement of L-DOPS concentration in the brain by the co-administration of L-DOPS and a catechol-O-methyl transferase (COMT) inhibitor, which is expected to interrupt L-DOPS metabolism in the peripheral circulation, would be beneficial for FOG. Based on our hypothesis, we conducted a preliminary study with a small number of participants with FOG. Of the 16 PD patients with FOG who completed this study, group 1 (n=6) received L-DOPS co-administered with entacapone, which is a COMT inhibitor used worldwide as an anti-parkinson drug, group 2 (n=5) received entacapone alone, and group 3 (n=5) received L-DOPS alone. Only the patients in group 1 showed a significant improvement in FOG. Moreover, the beneficial effect was observed only in patients with levodopa-resistant FOG. This result supports our hypothesis, at least in patients with levodopa-resistant FOG, and shows that the co-administration of L-DOPS and entacapone could be a new strategy for FOG treatment.
TNFRSF1A coding variants in multiple sclerosis

Patients with the autoinflammatory disease Tumour Necrosis Factor receptor-associated periodic syndrome (TRAPS) who suffer from demyelinating disease have been described, and one of the milder TRAPS mutations (R92Q in the TNFRSF1A gene) has been suggested as a risk factor for multiple sclerosis (MS). In a study population of 967 MS patients and 1022 controls, we replicate association [P=5×10⁻⁴, 3% in patients versus 1% in controls, OR=2.26 (95% CI 1.41-3.61)], which appears independent of an established common risk variant in the same gene. No other non-synonymous variants in the same allele frequency range influencing risk of MS were observed.
Our study 20 years on: UK collaborative randomised trial of neonatal extracorporeal membrane oxygenation

The successful use of extracorporeal membrane oxygenation (ECMO) had first been reported by Hill in adults in 1972 , and Bartlett  in neonates in 1975. In 1979, a negative adult trial [2, 3] contrasted to consistently favourable results in neonates leading to the rapid adoption of neonatal ECMO in the USA. However the poor quality of the two early US trials of neonatal ECMO [4, 5] inhibited its wider diffusion with particular concerns about lack of evidence on cost-effectiveness and longterm outcomes . Our trial [7] was a large randomised controlled trial (RCT) recruiting 185 neonates with severe respiratory failure. At 1 year of age 60 % survivors in the ECMO group were alive without severe disability, compared to 40 % in the conventional treatment group. These positive results spurred on the development of neonatal ECMO services internationally although some trialists criticised our pragmatic design based in a live health system, citing our failure to move conventionally treated babies to ‘expert’ centres . Evidence supporting neonatal ECMO was presented in a meta-analysis rigorously which concluded that “A policy of ECMO in mature infants with severe but potentially reversible respiratory failure would result in significantly improved survival without increased risk of severe disability amongst survivors” . One further RCT, only ever published in abstract form, was included in this meta-analysis. Of the 95 babies with persistent pulmonary hypertension (PPHN) enrolled, 93 % survived to hospital discharge compared to 54 % of those treated conventionally with no neurodevelopmental difference at 2-year follow-up , similar findings to our own study. Follow‐up studies Neurodevelopmental Follow-up of our trial cohorts at 4 years showed that the range of morbidity had widened since the 1-year assessments. Two-thirds of children recorded cognitive levels within the normal range. Sixty per cent of survivors had abnormal neuromotor function, but there were no differences between the two trial groups and no evidence of right-hemisphere deficits in veno-arterial ECMO survivors. Fifty per cent of known ECMO survivors had no disability compared 37 % of ‘conventional’ survivors. Behavioural difficulties were more commonly reported in the ‘conventional’ survivors than the ECMO survivors. At 7 years, a psychologist assessed 90 of the 100 children available for follow-up without prior knowledge of treatment allocation. Seventy-six per cent of children recorded a cognitive level within the normal range. The distribution of learning problems was similar in the two groups. A higher incidence of behavioural problems was noted among children treated conventionally. Importantly the beneficial influence of a policy of ECMO rather than conventional support was still present after 7 years, with some evidence of reduced morbidity in the ECMO group.
Variability in quality of chest compressions provided during simulated cardiac arrest across nine pediatric institutions.

The variability in quality of CPR provided during cardiac arrest across pediatric institutions is unknown. We aimed to describe the degree of variability in the quality of CPR across 9 pediatric institutions, and determine if variability across sites would be affected by Just-in-Time CPR training and/or visual feedback during simulated cardiac arrest.



We conducted secondary analyses of data collected from a prospective, multi-center trial. Participants were equally randomized to either: (1) No intervention; (2) Real-time CPR visual feedback during cardiac arrest or (3) Just-in-Time CPR training. We report the variability in median chest compression depth and rate across institutions, and the variability in the proportion of 30-s epochs of CPR meeting 2010 American Heart Association guidelines for depth and rate.



We analyzed data from 528 epochs in the no intervention group, 552 epochs in the visual feedback group, and 525 epochs in the JIT training group. In the no intervention group, compression depth (median range 22.2-39.2mm) and rate (median range 116.0-147.6 min(-1)) demonstrated significant variability between study sites (p<0.001). The proportion of compressions with adequate depth (0-11.5%) and rate (0-60.5%) also varied significantly across sites (p<0.001). The variability in compression depth and rate persisted despite use of real-time visual feedback or JIT training (p<0.001).



The quality of CPR across multiple pediatric institutions is variable. Variability in CPR quality across institutions persists even with the implementation of a Just-in-Time training session and visual feedback for CPR quality during simulated cardiac arrest.
Start of insulin therapy in patients with type 2 diabetes mellitus promotes the influx of macrophages into subcutaneous adipose tissue

Insulin therapy in patients with type 2 diabetes mellitus is accompanied by weight gain characterised by an increase in abdominal fat mass. The expansion of adipose tissue mass is generally paralleled by profound morphological and inflammatory changes. We hypothesised that the insulin-associated increase in fat mass would also result in changes in the morphology of human subcutaneous adipose tissue and in increased inflammation, especially when weight gain was excessive. We investigated the effects of weight gain on adipocyte size, macrophage influx, and mRNA expression and protein levels of key inflammatory markers within the adipose tissue in patients with type 2 diabetes mellitus before and 6 months after starting insulin therapy. As expected, insulin therapy significantly increased body weight. At the level of the subcutaneous adipose tissue, insulin treatment led to an influx of macrophages. When comparing patients gaining no or little weight with patients gaining >4% body weight after 6 months of insulin therapy, both subgroups displayed an increase in macrophage influx. However, individuals who had gained weight had higher protein levels of monocyte chemoattractant protein-1, TNF-α and IL-1β after 6 months of insulin therapy compared with those who had not gained weight. We conclude that insulin therapy in patients with type 2 diabetes mellitus improved glycaemic control but also induced body weight gain and an influx of macrophages into the subcutaneous adipose tissue. In patients characterised by a pronounced insulin-associated weight gain, the influx of macrophages into the adipose tissue was accompanied by a more pronounced inflammatory status.  The study was funded by European Foundation for the Study of Diabetes and the Dutch Diabetes Research Foundation.