nils-herrmann/clean_scirepeval huggingface dataset:
Leukocyte adhesion molecule dynamics after Natalizumab withdrawal in Multiple Sclerosis.

Cell-adhesion molecules (CAMs) dynamics in Multiple Sclerosis (MS) patients have been widely studied after Natalizumab (NTZ) introduction. However, their temporal dynamics after NTZ withdrawal (NTZ-W) has not been described. We prospectively evaluate changes in the expression levels of CAMs (CD49d, CD29, L-Selectin and CD11a) involved in T cell migration of 22 MS patients after NTZ-W. CD49d, CD29 and CD11a expression experienced a continuous increase expression two months after NTZ-W and Cd49d expression at month six after NTZ-W correlated to NTZ treatment duration, both in CD45+CD4+ and CD45+CD8+. CD49d expression up to month three after NTZ-W was related to MS activity in CD45+CD8+ at the end of the study. Results from this study suggest that patients with a longer NTZ treatment are more susceptible to present a "molecular rebound" after NTZ-W. CD49d determination may be a useful tool to closely monitor MS activity in patients who interrupt NTZ.
Diastolic function improvement is associated with favourable outcomes in patients with acute non-ischaemic cardiomyopathy: insights from the multicentre IMAC-2 trial.

Patients with recent onset non-ischaemic cardiomyopathy have a variable clinical course with respect to recovery of left ventricular ejection fraction (LVEF). The aim of this study was to understand whether temporal changes in diastolic function (DF) are associated with clinical outcomes independent of LVEF recovery.



The Intervention in Myocarditis and Acute Cardiomyopathy (IMAC)-2 study was a prospective, multicentre trial investigating myocardial recovery in subjects with symptoms onset of <6 months and LVEF ≤40% of non-ischaemic dilated cardiomyopathy related to idiopathic cardiomyopathy or myocarditis. LVEF and DF were measured at presentation and at 6-month follow-up. Of 147 patients (mean age 46 ± 14 years, 40% female), baseline LVEF was 23 ± 8%. At 6 months, LVEF improved to 41 ± 12%, with 71% increasing by at least 10% ejection fraction units. DF improved in 58%, was unchanged in 28%, and worsened in 14%. Over a mean follow-up of 1.8 ± 1.2 years, there were 18 events: 11 heart failure (HF) hospitalizations, 3 deaths, and 4 heart transplants. LVEF (HR = 0.94, 95% CI 0.91-0.98, P = 0.002) and DF improvements at 6 months (HR = 0.32, 95% CI 0.11-0.92, P = 0.03) were independently associated with lower likelihood for the combined end point of death, transplantation, and HF hospitalization. Diastolic functional improvement at 6-month follow-up was as prognostically important as LVEF recovery for these patients, and provided incremental prognostic value to the risk stratification (X(2) increased from 12.6 to 18, P = 0.02).



In patients with recent onset non-ischaemic cardiomyopathy, DF recovery was associated with favourable outcomes independent of LVEF improvement, adding incremental prognostic value to these patients.
Impact of cytogenetics risk on outcome after reduced intensity conditioning allo-SCT from an HLA-identical sibling for patients with AML in first CR: a report from the acute leukemia working party of EBMT

So far the impact of cytogenetics risk on outcome in the context of reduced intensity conditioning (RIC) allo-SCT has been poorly studied. We have identified 378 AML patients in first CR who underwent RIC allo-SCT from an HLA-matched sibling donor between 2000 and 2007 reported to the European Group for Bone and Marrow Transplantation and for whom detailed cytogenetics data were available (good risk: n=21; intermediate risk: n=304; and poor risk: n=53). With a median follow-up of 24 months (range: 1–93), 2-year non-relapse mortality, relapse rate (RR), leukemia-free survival (LFS) and OS were 14%, 31%, 55% and 61%, respectively. Cytogenetics was significantly associated with RR (good risk: 10%; intermediate risk: 28%; and poor risk: 55% at 2 years, P<0.0001) and LFS (good risk: 64%; intermediate risk: 57%; and poor risk: 38% at 2 years, P=0.003). In a multivariate analysis, RR and LFS were significantly higher and lower, respectively, in the high-risk cytogenetics group (P=0.001, P=0.004) and in patients with a higher WBC at diagnosis (>10 × 109/L) (P<0.001, P=0.004). As documented in the setting of myeloablative allo-SCT, patients with poor cytogenetics had increased RR and decreased LFS after RIC allo-SCT, requiring new prospective strategies to improve results in this subgroup.
Retraining automatic action-tendencies to approach alcohol in hazardous drinkers.

The main aim of this study was to test whether automatic action-tendencies to approach alcohol can be modified, and whether this affects drinking behaviour.



Forty-two hazardous drinkers were assigned randomly to a condition in which they were implicitly trained to avoid or to approach alcohol, using a training variety of the alcohol Approach Avoidance Test (AAT). Participants pushed or pulled a joystick in response to picture-format (landscape or portrait). The pictures depicted alcoholic or non-alcoholic drinks. Participants in the avoid-alcohol condition pushed most alcoholic and pulled most non-alcoholic drinks. For participants in the approach-alcohol condition these contingencies were reversed. After the implicit training, participants performed a taste test, including beers and soft drinks. Automatic action tendencies at post-test were assessed with the AAT, including both trained and untrained pictures, and with a different test (Implicit Association Test, IAT). We further tested effects on subjective craving.



Action tendencies for alcohol changed in accordance with training condition, with the largest effects in the clinically relevant avoid-alcohol condition. These effects occurred outside subjective awareness and generalized to new pictures in the AAT and to an entirely different test using words, rather than pictures (IAT). In relatively heavy drinking participants who demonstrated changed action tendencies in accordance with their training condition, effects were found on drinking behaviour, with participants in the approach-alcohol condition drinking more alcohol than participants in the avoid-alcohol condition. No effect was found on subjective craving.



Retraining automatic processes may help to regain control over addictive impulses, which points to new treatment possibilities.
The valve-in-valve technique for treatment of aortic bioprosthesis malposition an analysis of incidence and 1-year clinical outcomes from the italian CoreValve registry.

We appraised the incidence and clinical outcomes of patients who were treated with the valve-in-valve (ViV) technique for hemodynamically destabilizing paraprosthetic leak (PPL).



Device malpositioning causing severe PPL after transcatheter aortic valve implantation is not an uncommon finding. It occurs after release of the prosthesis, leading to hemodynamic compromise. It can be managed successfully in selected cases with implantation of a second device inside the malpositioned primary prosthesis (ViV technique).



Consecutive patients (n = 663) who underwent transcatheter aortic valve implantation with the 18-F CoreValve ReValving System (Medtronic, Inc., Minneapolis, Minnesota) at 14 centers across Italy were included in this prospective web-based registry. We identified patients treated with the ViV technique for severe PPL and analyzed their clinical and echocardiographic outcomes. Primary end points were major adverse cerebrovascular and cardiac events and prosthesis performance at the 30-day and midterm follow-up.



Overall procedural success was obtained in 650 patients (98.0%). The ViV technique was used in 24 (3.6%) of 663 patients. The 30-day major adverse cerebrovascular and cardiac event rates were 7.0% and 0% in patients undergoing the standard procedure and ViV technique, respectively (p = 0.185); the mortality rates were 5.6% versus 0% in patients undergoing the standard procedure and ViV technique, respectively (p = 0.238). There was an improvement in the mean transaortic gradient in all patients without significant difference between the 2 groups (from 52.1 ± 17.1 mm Hg and 45.4 ± 14.8 mm Hg [p = 0.060] to 10.1 ± 4.2 mm Hg and 10.5 ± 5.2 mm Hg, respectively [p = 0.838]). At 12 months, the major adverse cerebrovascular and cardiac event rates in the standard procedure and ViV technique groups were 4.5% and 14.1%, respectively (p = 0.158), and the mortality rates were 4.5% versus 13.7%, respectively (p = 0.230).



This large, multicenter registry provides important information about the feasibility, safety, and efficacy of the ViV technique with the third-generation CoreValve ReValving System. The clinical and echocardiographic end points compare favorably with those of patients undergoing the standard procedure. The ViV technique offers a viable therapeutic option in patients with acute significant PPL without recourse to emergent surgery.
Pharmacovigilance of patients with multiple myeloma being treated with bortezomib and/or thalidomide

In order to evaluate the main adverse effects of drug protocols using bortezomib and/or thalidomide for the treatment of multiple myeloma, we conducted a prospective study. Data were collected through interviews, clinical observation, and from hospital records. A total of 59 patients were included. There was a predominance of females, 36 (61%) vs 23 (39%) males, and of whites, 49 (83.1%) vs 10 (16.9%) blacks. Age ranged from 40 to 94 years, with a median of 65 years (SD=11.6). Regarding staging at diagnosis, 27 (45.7%) patients were in stage III-A, with 12 (20.3%) patients having serum creatinine ≥2 mg/dL. The main adverse effects in the bortezomib treatment group (n=40) were: neutropenia (42.5%), diarrhea (47.5%), and peripheral neuropathy in 60% of cases, with no difference between the iv (n=26) and sc (n=14) administration routes (P=0.343). In the group treated with thalidomide (n=19), 31.6% had neutropenia, 47.4% constipation, and 68.4% peripheral neuropathy. Neutropenia was associated with the use of alkylating agents (P=0.038). Of the 3 patients who received bortezomib in combination with thalidomide, only 1 presented peripheral neuropathy (33.3%). Peripheral neuropathy was the main adverse effect of the protocols that used bortezomib or thalidomide, with a higher risk of neutropenia in those using alkylating agents. Improving the identification of adverse effects is critical in multiple myeloma patient care, as the patient shows improvements during treatment, and requires a rational and safe use of medicines.
Neural activation of the brain with hemodynamic insufficiency.

Little is known about how ischemia affects hemodynamic responses to neural activation in the brain. We compare the effects of a motor activation task and a cerebral vasodilating agent, acetazolamide (ACZ), on regional cerebral blood flow (rCBF) in primary sensorimotor cortex (PSM) in six patients with major cerebral artery steno-occlusive lesions without paresis of the upper extremities. Quantitative rCBF was measured in all patients using H2(15)O autoradiographic method and positron emission tomography. The CBF was determined at rest, during a bimanual motor activation task, and 10 minutes after ACZ administration. With bimanual motor activation, rCBF increased significantly in both PSM compared with at rest (P < 0.01 on lesion side, and P < 0.02 on contralateral side). However, rCBF did not increase after ACZ injection in the PSM on the lesion side, whereas rCBF increased significantly in the contralateral PSM after ACZ injection compared with the level at rest. This result suggests that despite a decreased hemodynamic reserve, there is a nearly normal flow response to neural activation, indicating that the mechanism of vasodilation responsible for perfusion change is different for acetazolamide and neural activation. The relations among neural activation, hemodynamic status, and cerebral metabolism in the ischemic stroke patients are discussed.
Image-directed, tissue-preserving focal therapy of prostate cancer: a feasibility study of a novel deformable magnetic resonance-ultrasound (MR-US) registration system

To evaluate the feasibility of using computer-assisted, deformable image registration software to enable three-dimensional (3D), multi-parametric (mp) magnetic resonance imaging (MRI)-derived information on tumour location and extent, to inform the planning and conduct of focal high-intensity focused ultrasound (HIFU) therapy.



A nested pilot study of 26 consecutive men with a visible discrete focus on mpMRI, correlating with positive histology on transperineal template mapping biopsy, who underwent focal HIFU (Sonablate 500®) within a prospective, Ethics Committee-approved multicentre trial ('INDEX'). Non-rigid image registration software developed in our institution was used to transfer data on the location and limits of the index lesion as defined by mpMRI. Manual contouring of the prostate capsule and histologically confirmed MR-visible lesion was performed preoperatively by a urologist and uro-radiologist. A deformable patient-specific computer model, which captures the location of the target lesion, was automatically generated for each patient and registered to a 3D transrectal ultrasonography (US) volume using a small number (10-20) of manually defined capsule points. During the focal HIFU, the urologist could add additional sonications after image-registration if it was felt that the original treatment plan did not cover the lesion sufficiently with a margin.



Prostate capsule and lesion contouring was achieved in <5 min preoperatively. The mean (range) time taken to register images was 6 (3-16) min. Additional treatment sonications were added in 13 of 26 cases leading to a mean (range) additional treatment time of 45 (9-90) s.



Non-rigid MR-US registration is feasible, efficient and can locate lesions on US. The process has potential for improved accuracy of focal treatments, and improved diagnostic sampling strategies for prostate cancer. Further work on whether deformable MR-US registration impacts on efficacy is required.
Agreement between ambulance and hospital records for information promoting urgent stroke treatment decisions.

Rapid decision-making during acute stroke care can improve outcomes. We wished to assess whether crucial information to facilitate decisions is routinely collected by emergency practitioners before hospital admission.



We examined whether ambulance records contained information relevant to a thrombolysis treatment decision for consecutive stroke admissions to three emergency departments in England between 14 May 2012 and 10 June 2013.



In all, 424 of 544 (78%) records included a paramedic diagnosis of stroke. Twice as many hospital records contained a symptom onset time/last known to be well time, but there was 82% agreement within 1 h when a prehospital time was also recorded. This was more likely for younger patients. Documentation of medication history was infrequent (12%), particularly for anticoagulant status (6%). When compared with hospital documentation, paramedics recorded a history of diabetes for 38/49 (78%), previous stroke 44/69 (64%), hypertension 71/140 (51%) and atrial fibrillation 19/64 (30%).



In a retrospective cohort of stroke patients admitted by emergency ambulance, standard practice did not consistently result in prehospital documentation of information that could promote rapid treatment decisions. Training emergency practitioners and/or providing clinical protocols could facilitate early stroke treatment decisions, but prehospital information availability is likely to be a limiting factor.
Assessment of brief interventions for nighttime fears in preschool children

Nighttime fears (NF) and sleep problems continue to be major problems in clinical services. The aim was to assess the effects of two brief interventions on NF, and related sleep problems and parental fear-reducing behaviors in children. One hundred and four children aged 4–6 years with significant NF were randomly assigned into two intervention groups: the Huggy-Puppy intervention (HPI), which is based on providing children a puppy doll with a request to take care of the doll, and a revised version (HPI-r) which is based on providing the same doll with a cover story that the doll will serve as a protector. At baseline, the domains of NF, behavior problems, and sleep disruptions were assessed. Data were collected from parents and children using objective and subjective measures. The effects of the interventions were assessed by comparing four time points: baseline, first week of intervention, 1 month, and 6 months after initial intervention time. A waiting list comparison group (WL) was used as spontaneous recovery comparison group. Both interventions significantly reduced NF with similar impact. The improvement after 1 month was significantly higher than in the WL group. Furthermore, both interventions significantly reduced parental fear management behaviors and children’s sleep problems. Finally, the reduction in NF and parental fear management strategies were maintained 6 months post-treatment.  Relatively simple and cost-effective doll interventions can reduce NF and their associated sleep problems. Further research is needed to implement these interventions for other anxiety disorders in childhood.
Assessing health-state utility values in patients with metastatic colorectal cancer: a utility study in the United Kingdom and the Netherlands

This study aimed to elicit EuroQol Quality of Life 5-Dimensions (EQ-5D) utility values from patients with second-line metastatic colorectal cancer (mCRC) pre- and post-progression. A cross-sectional study was conducted in five hospitals in the Netherlands and the UK. Patients with mCRC were eligible if prescribed a second or subsequent line of therapy or best supportive care (BSC), received prior oxaliplatin in first-line therapy, and had Eastern Cooperative Oncology Group (ECOG) performance status scores of 0–2 at second-line initiation. Patients completed the EuroQol Quality of Life 5-Dimensions 3-levels (EQ-5D-3L) questionnaire and were categorized as pre- or post-progression. Chart data including patient demographics, clinical history, prior/current treatments and serious adverse events (SAEs) were collected. Mean utilities were estimated; uni- and multivariate analyses were conducted. Seventy-five patients were enrolled; 42 were pre-progression defined as second line or third line following an AE on second line and 33 were post-progression defined as third or subsequent therapy lines or BSC. Patient/disease characteristics and number of SAEs were similar between cohorts. Mean utility scores were 0.741 (SD = 0.230) and 0.731 (SD = 0.292) for pre- and post-progression cohorts, respectively. Compared to pre-progression, more patients reported increased anxiety/depression (36 vs. 12 %) and fewer problems with daily activities (64 vs. 38 %) post-progression. More patients pre-progression were on active treatment at enrolment (83 vs. 42 %) compared to post-progression. This is the first real-world study to collect utilities for patients with second-line mCRC pre- and post-disease progression. Utility values were similar pre- and post-progression. To further explore the effect of radiological progression on utilities, longitudinal research is required that includes patients in palliative care centres.
Effect of oral prednisolone on the bronchoprotective effect of formoterol in patients with persistent asthma.

Tolerance to the bronchoprotective effects by long-acting beta2-agonists (LAB) in patients with asthma is not prevented by inhaled corticosteroids (ICS). This study examined whether oral prednisolone can restore the bronchoprotective effects of formoterol in 24 patients with persistent asthma already treated with ICS (at least 800 microg budesonide x day(-1) or equivalent) and LAB, using a parallel-group design. During a 2-week run-in period and during the study, patients used formoterol 12 microg twice daily by Turbuhaler, instead of their own LAB. At baseline and at the end of 7-days treatment with oral placebo or prednisolone (30 mg x day(-1)), provocative concentration of histamine causing a 20% fall in forced expiratory volume in one second (PC20 histamine) was measured on two separate days after randomized single-dose inhalation of placebo (postP) or formoterol (postF). In addition, PC20postF was measured 24 h after starting oral treatment. The protective effect by formoterol at baseline and during treatment was calculated as the difference between the logs of PC20postP and PC20postF. The mean+/-SEM in doubling dose (DD) bronchoprotective effect at baseline was 0.8+/-0.4 DD in the placebo group and 1.0+/-0.4 DD in the prednisolone group. At the end of the treatment period, the protective effect changed to 1.0+/-0.5 DD and 0.8+/-0.6 DD in the placebo and prednisolone treated groups, respectively. This change was not different between the groups (p > 0.4). In conclusion, the bronchoprotective effect by formoterol is not influenced by 1 week prednisolone treatment in patients with asthma who are using regular inhaled corticosteroids and long-acting beta2-agonists. These findings indicate that tolerance to long-acting beta2-agonists cannot be restored by oral steroid therapy.
Comparison of the PHQ-9 and CES-D depression scales in systemic sclerosis: internal consistency reliability, convergent validity and clinical correlates.

The reported rates of depressive symptoms in patients with SSc are high. The Center for Epidemiologic Studies Depression Scale (CES-D) is the only measure of depressive symptoms validated for SSc patients. The objective of this study was to assess the internal consistency reliability, convergent validity and strength of association with clinical correlates of the 9-item version of the Patient Health Questionnaire depression scale (PHQ-9) compared with the CES-D in SSc.



We conducted a cross-sectional, multicentre study of 566 SSc patients who were assessed with the PHQ-9 and CES-D scales, and through clinical histories and medical examinations. Internal consistency reliability was assessed with Cronbach's alpha, convergent validity with Pearson's correlation and the relationship of socio-demographic and clinical variables with the PHQ-9 and CES-D scores using multiple linear regression.



Scale reliability was good for the PHQ-9 (alpha = 0.87) and similar to the CES-D (alpha = 0.90). Correlations of the PHQ-9 total score were -0.68 with mental health, -0.43 with physical health, 0.44 with disability, 0.40 with pain and 0.79 with fatigue, which were all in the expected direction and similar to the results with the CES-D. Regression coefficients of clinical correlates did not differ significantly between models using the PHQ-9 and CES-D.



The PHQ-9 is reliable and valid for use as a measure of depressive symptom severity in patients with SSc and performs similarly to the CES-D. However, the PHQ-9 is advantageous because it is half the length of the CES-D, easily administered and scored, and is increasingly used across many patient groups for assessment in research and clinical settings.