nils-herrmann/clean_scirepeval huggingface dataset:
Immunologic response to xenogeneic gp100 DNA in melanoma patients: comparison of particle-mediated epidermal delivery with intramuscular injection.

Prior studies show that i.m. injection of xenogeneic orthologues of melanosomal antigens (tyrosinase, gp100) induces CD8(+) T-cell responses to the syngeneic protein. To further define the optimal vaccination strategy, we conducted a pilot clinical trial comparing i.m. injection with particle-mediated epidermal delivery (PMED).



Human leukocyte antigen (HLA)-A*0201(+) disease-free melanoma patients were randomized to the PMED or i.m. arm, receiving eight vaccinations over 4 months. Patients received 4 microg or 2,000 microg per injection, respectively, of mouse gp100 DNA. Peripheral blood mononuclear cells were collected, cultured with gp100 peptides, and analyzed by tetramer and intracellular cytokine staining for responses to HLA-A*0201-restricted gp100 epitopes [gp100(209-217) (ITDQVPFSV) and gp100(280-288) (YLEPGPVTA)].



Twenty-seven patients with stage IIB-IV melanoma were analyzable for immune response. The only common toxicity was grade 1 injection site reaction in nine patients with no intergroup difference, and one dose-limiting toxicity of acute hypersensitivity occurred in a PMED patient with undiagnosed gold allergy. Four of 27 patients produced gp100 tetramer(+)CD8(+) T cells, all carrying the CCR7(lo)CD45RA(lo) effector-memory phenotype. Five of 27 patients generated IFN-gamma(+)CD8(+) T cells, one who was also tetramer-positive. Overall, vaccination induced a response in 30% of patients, which was not significantly associated with study arm or clinical outcome. However, the PMED group showed a trend toward increased IFN-gamma(+)CD8(+) T-cell generation (P = 0.07).



A comparable efficacy and safety profile was shown between the i.m. and PMED arms, despite a significantly decreased dose of DNA used for PMED injection.
Comparison of balloon-expandable vs self-expandable valves in patients undergoing transcatheter aortic valve replacement: the CHOICE randomized clinical trial.

Transcatheter aortic valve replacement (TAVR) is an effective treatment option for high-risk patients with severe aortic stenosis. Different from surgery, transcatheter deployment of valves requires either a balloon-expandable or self-expandable system. A randomized comparison of these 2 systems has not been performed.



To determine whether the balloon-expandable device is associated with a better success rate than the self-expandable device.



The CHOICE study was an investigator-initiated trial in high-risk patients with severe aortic stenosis and an anatomy suitable for the transfemoral TAVR procedure. One hundred twenty-one patients were randomly assigned to receive a balloon-expandable valve (Edwards Sapien XT) and 120 were assigned to receive a self-expandable valve (Medtronic CoreValve). Patients were enrolled between March 2012 and December 2013 at 5 centers in Germany.



Transfemoral TAVR with a balloon-expandable or self-expandable device.



The primary end point was device success, which is a composite end point including successful vascular access and deployment of the device and retrieval of the delivery system, correct position of the device, intended performance of the heart valve without moderate or severe regurgitation, and only 1 valve implanted in the proper anatomical location. Secondary end points included cardiovascular mortality, bleeding and vascular complications, postprocedural pacemaker placement, and a combined safety end point at 30 days, including all-cause mortality, major stroke, and other serious complications.



Device success occurred in 116 of 121 patients (95.9%) in the balloon-expandable valve group and 93 of 120 patients (77.5%) in the self-expandable valve group (relative risk [RR], 1.24, 95% CI, 1.12-1.37, P < .001). This was attributed to a significantly lower frequency of residual more-than-mild aortic regurgitation (4.1% vs 18.3%; RR, 0.23; 95% CI, 0.09-0.58; P < .001) and the less frequent need for implanting more than 1 valve (0.8% vs 5.8%, P = .03) in the balloon-expandable valve group. Cardiovascular mortality at 30 days was 4.1% in the balloon-expandable valve group and 4.3% in the self-expandable valve group (RR, 0.97; 95% CI, 0.29-3.25; P = .99). Bleeding and vascular complications were not significantly different, and the combined safety end point occurred in 18.2% of those in the balloon-expandable valve group and 23.1% of the self-expandable valve group (RR, 0.79; 95% CI, 0.48-1.30; P = .42). Placement of a new permanent pacemaker was less frequent in the balloon-expandable valve group (17.3% vs 37.6%, P = .001).



Among patients with high-risk aortic stenosis undergoing TAVR, the use of a balloon-expandable valve resulted in a greater rate of device success than use of a self-expandable valve.
Clinical course of high-risk patients diagnosed with antiphospholipid syndrome.

The characteristics and the clinical course of antiphospholipid syndrome (APS) in high-risk patients that are positive for all three recommended tests that detect the presence of antiphospholipid (aPL) antibodies have not been described.



This retrospective analysis of prospectively collected data examined patients referred to Italian Thrombosis Centers that were diagnosed with definite APS and tested positive for aPL [lupus anticoagulant (LA), anti-cardiolipin (aCL), and anti-beta2-glycoprotein I (beta2GPI) antibodies]. Laboratory data were confirmed in a central reference laboratory.



One hundred and sixty patients were enrolled in this cohort study. The qualifying events at diagnosis were venous thromboembolism (76 cases; 47.5%), arterial thromboembolism (69 cases; 43.1%) and pregnancy morbidity (11 cases; 9.7%). The remaining four patients (2.5%) suffered from catastrophic APS. The cumulative incidence of thromboembolic events in the follow-up period was 12.2% (95% CI, 9.6-14.8) after 1 year, 26.1% (95% CI, 22.3-29.9) after 5 years and 44.2% (95% CI, 38.6-49.8) after 10 years. This was significantly higher in those patients not taking oral anticoagulants as compared with those on treatment (HR=2.4 95% CI 1.3-4.1; P<0.003). Major bleeding associated with oral anticoagulant therapy was low (0.8% patient/years). Ten patients died (seven were cardiovascular deaths).



Patients with APS and triple positivity for aPL are at high risk of developing future thromboembolic events. Recurrence remains frequent despite the use of oral anticoagulants, which significantly reduces the risk of thromboembolism.
Device-specific thresholds to diagnose osteoporosis at the proximal femur: an approach to interpreting peripheral bone measurements in clinical practice

A single T score criterion cannot be universally applied to different peripheral bone measurement devices, since measurements in an identical population result in a tenfold difference in the prevalence of osteoporosis. The use of peripheral devices is increasing in clinical practice, despite the difficulties in interpreting results. We propose the use of two thresholds, which have either 95% sensitivity or 95% specificity, to identify (1) individuals who require treatment or (2) individuals who require no treatment, both based on a peripheral measurement alone, or (3) individuals who require additional central densitometry measurements. We recruited 500 postmenopausal women, 100 premenopausal women and 279 women with proximal femoral, vertebral, distal forearm or proximal humeral fractures. All subjects underwent dual energy X-ray absorptiometry (DXA) measurements of the lumbar spine, total hip and distal forearm, quantitative computed tomography (QCT) of the distal forearm and quantitative ultrasound (QUS) of the heel (four devices), finger (two devices), radius and metatarsal. We identified the threshold for each device that identified women without osteoporosis with the same sensitivity (upper threshold set at 95%) as total hip DXA and women with osteoporosis with the same specificity (lower threshold set at 95%) as total hip DXA. Individuals between the two thresholds required additional examination by central densitometry. The correlation between devices varied from 0.173 (QUS finger) to 0.686 (DXA forearm) compared with total hip DXA (P<0.0001). The area under the curve (AUC) between devices varied from 0.604 (QUS finger) to 0.896 (DXA forearm) compared with total hip DXA (P<0.0001). In a population-based cohort (prevalence of osteoporosis 9.8%) the threshold approach appropriately identified between 26% (QUS heel) and 68% (DXA forearm) of subjects in whom a treatment decision could be made without additional central DXA with 95% certainty. In a fracture cohort (prevalence of osteoporosis 36%) between 16% (QUS finger) and 37% (QCT forearm) of subjects were appropriately identified. The threshold approach to interpreting peripheral bone measurements enables a substantial number of individuals with either normal bone mineral density (BMD) or osteoporosis to be selected and treated appropriately.
Methamphetamine use, sexual activity, patient-provider communication, and medication adherence among HIV-infected patients in care, San Francisco 2004-2006.

While numerous studies examine methamphetamine use and associated risky sexual behaviors in HIV-uninfected individuals, few studies have surveyed HIV-infected individuals in the health care setting. To assess the frequency and trends of methamphetamine use, sexual activity, injection drug use, patient-provider communication, and medication adherence among HIV-infected persons in care, we administered a one-page anonymous survey in 2004 and 2006. The survey was conducted at the two University of California, San Francisco outpatient HIV clinics: at Moffitt Hospital (Moffitt), serving primarily privately insured patients, and at San Francisco General Hospital (SFGH), a county hospital serving primarily patients who are uninsured or publicly insured. In 2006, 39% of men who have sex with men (MSM), 33% of heterosexual men, and 11% of women reported methamphetamine use in the prior 12 months. Methamphetamine use was significantly associated with an increased number of sex partners among MSM and heterosexual men, and poor anti-retroviral medication adherence. Among MSM, methamphetamine use was more common at the SFGH clinic. Between 2004 and 2006, reported methamphetamine use in the last 12 months decreased among MSM at Moffitt (38 to 20%, p<0.01), but increased at SFGH (40 to 50%, p<0.05). Among methamphetamine users we found a high frequency of injection of methamphetamine, which increased at SFGH from 38 to 55%, p<0.05. Patient-provider communication regarding methamphetamine use has increased from 2004 to 2006 but no significant change has been found for providers asking patients about sexual activity. Overall, we found methamphetamine use to be common among HIV-infected patients in care, and associated with an increased number of sex partners, a high frequency of injection drug use, and poor adherence to anti-retroviral medications. These findings support the need for improved screening and clinic-based interventions to reduce and treat methamphetamine abuse and associated high risk sexual behaviors.
A benefit-finding intervention for family caregivers of persons with Alzheimer disease: study protocol of a randomized controlled trial

Caregivers of relatives with Alzheimer's disease are highly stressed and at risk for physical and psychiatric conditions. Interventions are usually focused on providing caregivers with knowledge of dementia, skills, and/or support, to help them cope with the stress. This model, though true to a certain extent, ignores how caregiver stress is construed in the first place. Besides burden, caregivers also report rewards, uplifts, and gains, such as a sense of purpose and personal growth. Finding benefits through positive reappraisal may offset the effect of caregiving on caregiver outcomes.



Two randomized controlled trials are planned. They are essentially the same except that Trial 1 is a cluster trial (that is, randomization based on groups of participants) whereas in Trial 2, randomization is based on individuals. Participants are randomized into three groups - benefit finding, psychoeducation, and simplified psychoeducation. Participants in each group receive a total of approximately 12 hours of training either in group or individually at home. Booster sessions are provided at around 14 months after the initial treatment. The primary outcomes are caregiver stress (subjective burden, role overload, and cortisol), perceived benefits, subjective health, psychological well-being, and depression. The secondary outcomes are caregiver coping, and behavioral problems and functional impairment of the care-recipient. Outcome measures are obtained at baseline, post-treatment (2 months), and 6, 12, 18 and 30 months.



The emphasis on benefits, rather than losses and difficulties, provides a new dimension to the way interventions for caregivers can be conceptualized and delivered. By focusing on the positive, caregivers may be empowered to sustain caregiving efforts in the long term despite the day-to-day challenges. The two parallel trials will provide an assessment of whether the effectiveness of the intervention depends on the mode of delivery.
Randomized comparison of intra-aortic balloon support with a percutaneous left ventricular assist device in patients with revascularized acute myocardial infarction complicated by cardiogenic shock.

Mortality in cardiogenic shock (CS) following acute myocardial infarction (AMI) remains unacceptably high despite percutaneous coronary intervention (PCI) of the infarcted artery and use of intra-aortic balloon pump (IABP) counterpulsation. A newly developed percutaneous left ventricular assist device (VAD) (Tandem Heart, Cardiac Assist, Pittsburgh, PA, USA) with active circulatory support might have positive haemodynamic effects and decrease mortality.



Patients in CS after AMI, with intended PCI of the infarcted artery, were randomized to either IABP (n=20) or percutaneous VAD support (n=21). The primary outcome measure cardiac power index, as well as other haemodynamic and metabolic variables, could be improved more effectively by VAD support from 0.22 [interquartile range (IQR) 0.19-0.30] to 0.37 W/m2 (IQR 0.30-0.47, P<0.001) when compared with IABP from 0.22 (IQR 0.18-0.30) to 0.28 W/m2 (IQR 0.24-0.36, P=0.02; P=0.004 for intergroup comparison). However, complications like severe bleeding (n=19 vs. n=8, P=0.002) or limb ischaemia (n=7 vs. n=0, P=0.009) were encountered more frequently after VAD support, whereas 30 day mortality was similar (IABP 45% vs. VAD 43%, log-rank, P=0.86).



Haemodynamic and metabolic parameters can be reversed more effectively by VAD than by standard treatment with IABP. However, more complications were encountered by the highly invasive procedure and by the extracorporeal support.
Off-pump and on-pump coronary artery bypass grafting are associated with similar graft patency, myocardial ischemia, and freedom from reintervention: long-term follow-up of a randomized trial.

The Surgical Management of Arterial Revascularization Therapies trial was conceived to rigorously compare completeness of revascularization, clinical outcomes and resource utilization in unselected patients referred for elective, primary coronary artery bypass grafting randomly assigned to undergo off-pump (OPCAB) or conventional on-pump coronary artery bypass grafting using cardiopulmonary bypass (CPB). The goal of this follow-up study was to compare long-term survival, graft patency, myocardial ischemia, and clinical outcomes among survivors who volunteered to return for clinical evaluation and imaging studies.



Two hundred unselected patients with multivessel coronary artery disease were randomly assigned to OPCAB or CPB coronary artery bypass grafting between March 2000 and August 2001. All-cause mortality was determined by individual patient contact and referencing the Social Security Death Master File. Of 140 survivors, 87 volunteered to return after a minimum of 6.8 years (maximum, 8.4 years; mean, 7.5 years) for assessment of graft patency (computed tomographic angiography) and myocardial ischemia (cardiac positron emission tomography and 12-lead electrocardiogram). Age at follow-up ranged from 38 to 90 years (mean, 68 years).



There were 26 deaths from all causes among OPCAB patients and 31 among CPB patients as of March 30, 2009. Graft patency was similar between groups among 622 grafts assessed by angiography before hospital discharge (99% OPCAB versus 97.7% CPB; p=0.22, Fisher's exact test), among 511 grafts assessed by angiography at 1 year (93.6% OPCAB versus 95.8% CPB; p=0.33), and among 190 grafts assessed by computed tomographic angiography at late follow-up (76% OPCAB versus 83.5% CPB; p=0.44). Twelve of 34 OPCAB (35.3%) and 16 of 39 CPB patients (41.0%) had any ischemia on positron emission tomography scanning (p=0.62). Four OPCAB patients (11.8%) and 9 CPB patients (23.1%) had an ischemic region in excess of 10% of myocardium (p=0.21). At late follow-up, recurrent angina had occurred in 11 of 43 (25.6%) OPCAB patients and 5 of 44 (11.4%) CPB patients (p=0.09). Percutaneous reintervention had been performed at the discretion of blinded local cardiologists in 1 of 43 (2.3%) OPCAB patients and 1 of 44 (2.3%) CPB patients (p=1.0). No patient in either group has undergone repeat CABG.



In this randomized trial, off-pump and on-pump coronary artery bypass grafting were associated with similar early and late graft patency, incidence of recurrent or residual myocardial ischemia, need for reintervention, and long-term survival.
A prospective, randomized study on hepatotoxicity of anastrozole compared with tamoxifen in women with breast cancer

Tamoxifen and anastrozole are widely used as adjuvant treatment for early stage breast cancer, but their hepatotoxicity is not fully defined. We aimed to compare hepatotoxicity of anastrozole with tamoxifen in the adjuvant setting in postmenopausal breast cancer patients. Three hundred and fifty-three Chinese postmenopausal women with hormone receptor-positive early breast cancer were randomized to anastrozole or tamoxifen after optimal primary therapy. The primary end-point was fatty liver disease, defined as a liver-spleen ratio <0.9 as determined using a computed tomography scan. The secondary end-points included abnormal liver function and treatment failure during the 3-year follow up. The cumulative incidence of fatty liver disease after 3 years was lower in the anastrozole arm than that of tamoxifen (14.6% vs 41.1%, P < 0.0001; relative risk, 0.30; 95% CI, 0.21-0.45). However, there was no difference in the cumulative incidence of abnormal liver function (24.6% vs 24.7%, P = 0.61). Interestingly, a higher treatment failure rate was observed in the tamoxifen arm compared with anastrozole and median times to treatment failure were 15.1 months and 37.1 months, respectively (P < 0.0001; HR, 0.27; 95% CI, 0.20-0.37). The most commonly reported adverse events were 'reproductive system disorders' in the tamoxifen group (17.1%), and 'musculoskeletal disorders' in the anastrozole group (14.6%). Postmenopausal women with hormone receptor-positive breast cancer receiving adjuvant anastrozole displayed less fatty liver disease, suggesting that this drug had a more favorable hepatic safety profile than tamoxifen and may be preferred for patients with potential hepatic dysfunction.
Effect of whole-body vibration exercise on balance in women with fibromyalgia syndrome: a randomized controlled trial.

This study evaluated the effectiveness of a 6-week "usual care" exercise program supplemented with whole-body vibration (WBV) to improve balance and strength in women with fibromyalgia (FM).



This was a randomized controlled study.



The setting was a physical therapy department in an academic setting.



The subjects were 30 postmenopausal women with FM (age: 59±7.90 years).



Subjects were randomized into one of two groups: an experimental group (EG: n=15), which combined exercise training (2 days a week) with 3 days of WBV, and a control group (CG: n=15), who performed the same exercise training program (2 days a week) but without WBV.



Balance and muscle strength were measured at baseline and after the 6-week intervention.



Significant differences were found (p<0.05) between the study groups for the Medio-Lateral Stability Index (MLSI), when patients were assessed with their eyes open and closed. The effect size of the improvement was large with eyes closed (R2=0.260) and moderate when the eyes were open (R2=0.047). However, no significant differences were found (p>0.05) between the study groups for other outcomes.



Women with FM may increase their MLSI by engaging in a 6-week traditional exercise program with supplementary WBV. This may have implications for falls prevention in this patient group.
A signature for immune response correlates with HCV treatment outcome in Caucasian subjects

Broad proteomic profiling was performed on serum samples of phase 2 studies (PROVE1, PROVE2, and PROVE3) of the direct-acting antiviral drug telaprevir in combination with peg-interferon and ribavirin in subjects with HCV. Using only profiling data from subjects treated with peg-interferon and ribavirin, a signature composed of pretreatment levels of 13 components was identified that correlated well (R(2)=0.68) with subjects' underlying immune response as measured by week 4 viral decline and was highly predictive of sustained virologic response in non-African American subjects (AUC=0.99). The signature was validated by predicting in an independent cohort of non-African American subjects treated with telaprevir, peg-interferon and ribavirin (AUC=0.854). Samples from extreme responders were over-represented in these analyses. Proteins identified as differentially-expressed between responders and non-responders to HCV treatment were quantified using multiple reaction monitoring in samples from all Caucasian subjects in the peg-interferon and ribavirin arms of PROVE1 and PROVE2, revealing 15 proteins that were significantly differentially expressed between treatment responders and non-responders. Seven of the proteins are part of focal adhesions or other macromolecular assemblies that form structural links between integrins and the actin cytoskeleton and are involved in antiviral response.



HCV is a significant health problem. We describe a novel approach for identifying markers that predicts HCV treatment response different treatment regimens and use this approach to identify a novel HCV treatment response signature. The signature has potential to guide optimization of HCV treatment regimens.