nils-herrmann/clean_scirepeval huggingface dataset:
A randomized phase II study of PX-12, an inhibitor of thioredoxin in patients with advanced cancer of the pancreas following progression after a gemcitabine-containing combination

This study evaluated PX-12, a novel small molecule inhibitor of the proto-oncogene (Trx-1), in patients with previously treated advanced pancreatic cancer (APC). PX-12 (54 or 128 mg/m2) was administered by 3-hour IV infusion daily ×5 days every 21 days (n = 17). Patients were randomized to either 54 or 128 mg/m2 and then stratified based on CA 19-9 level (≥1,000 vs. <1,000 U/ml) and SUV values on PET scans (≥7.0 vs. <7.0). The primary endpoint was based on a progression-free survival (PFS) at 4 months in ≥40% of patients, and required 40 patients in each arm. An amendment required elevated Trx-1 levels (>18 ng/ml) as an entry criteria after the first 17 patients were accrued. Plasma Trx-1 levels were elevated in 3/28 (11%) patients screened for study. The grade of the expired metabolite odor was higher in the 128 mg/m2 arm. Therapy was well tolerated, and Grade ≥3 adverse events were uncommon. The best response was stable disease in 2 patients. There was no consistent decrease in SUV, Trx-1 levels or CA 19-9 levels with therapy. No patients had a PFS of >4 months. Median PFS and survival were 0.9 months (95% CI 0.5–1.2) and 3.2 months (95% CI 2.4–4.2), respectively. Due to the lack of significant antitumor activity and unexpectedly low baseline Trx-1 levels, the study was terminated early. PX-12 does not appear to be active in unselected patients with previously treated APC.
Effects of repetitive transcranial magnetic stimulation of the unaffected hemisphere leg motor area in patients with subacute stroke and substantial leg impairment: A pilot study.

To evaluate the effects of repetitive transcranial magnetic stimulation (rTMS) on mobility among patients with substantial leg impairment after subacute stroke.



Double-blinded, stratified, randomized trial involving a sham control group.



Patients who developed unilateral hemiplegia after first-ever subacute stroke and underwent inpatient stroke rehabilitation.



The 15-day intervention programme used in the present study included the application of rTMS (1 Hz, 15 min) over the leg motor area of the unaffected hemisphere, followed by 45 min physical therapy. Overall, 32 participants were randomly assigned to receive either real rTMS or sham stimulation. Clinical assessments, including the Postural Assessment Scale for Stroke Patients (PASS), balance subscale of the Performance Oriented Mobility Assessment (POMA-b), Fugl-Meyer Assessment, Barthel Index (BI), and Timed Up and Go test, were performed immediately before and after the intervention.



Both groups demonstrated significant improvements in all the test results over time. At the post-test assessment, the patients in the real rTMS group demonstrated greater improvements in the PASS, POMA, and BI scores than did the patients in the sham rTMS group. In addition, a significantly higher number of patients in the real rTMS group regained mobility at the post-test assessment compared with the corresponding number of patients in the sham rTMS group.



Application of 1-Hz rTMS may improve mobility among patients with substantial leg impairment after subacute stroke.
Optimization of ventilator setting by flow and pressure waveforms analysis during noninvasive ventilation for acute exacerbations of COPD: a multicentric randomized controlled trial

The analysis of flow and pressure waveforms generated by ventilators can be useful in the optimization of patient-ventilator interactions, notably in chronic obstructive pulmonary disease (COPD) patients. To date, however, a real clinical benefit of this approach has not been proven.



The aim of the present randomized, multi-centric, controlled study was to compare optimized ventilation, driven by the analysis of flow and pressure waveforms, to standard ventilation (same physician, same initial ventilator setting, same time spent at the bedside while the ventilator screen was obscured with numerical data always available). The primary aim was the rate of pH normalization at two hours, while secondary aims were changes in PaCO2, respiratory rate and the patient's tolerance to ventilation (all parameters evaluated at baseline, 30, 120, 360 minutes and 24 hours after the beginning of ventilation). Seventy patients (35 for each group) with acute exacerbation of COPD were enrolled.



Optimized ventilation led to a more rapid normalization of pH at two hours (51 vs. 26% of patients), to a significant improvement of the patient's tolerance to ventilation at two hours, and to a higher decrease of PaCO2 at two and six hours. Optimized ventilation induced physicians to use higher levels of external positive end-expiratory pressure, more sensitive inspiratory triggers and a faster speed of pressurization.



The analysis of the waveforms generated by ventilators has a significant positive effect on physiological and patient-centered outcomes during acute exacerbation of COPD. The acquisition of specific skills in this field should be encouraged.
Recruitment strategies for a clinical trial of community-based water therapy for osteoarthritis.

This study compares the efficiency of two methods of recruitment into a randomised controlled trial examining the cost-effectiveness of water therapy for elderly people with lower limb osteoarthritis. The direct cost of recruiting patients via general practice was 27.66 Pounds per patient (1.1 personnel hours/patient). The cost per recruited patient from a local newspaper article was 2.72 Pounds (0.2 personnel hours/patient). The cost differential between the two recruitment methods was largely owing to poor administration practices, difficulties in accessing patient information, and difficulties in contacting patients from the general practice computer database.
Differential association between the norepinephrine transporter gene and ADHD: role of sex and subtype.

Pharmacologic and animal studies have strongly implicated the norepinephrine transporter (NET) in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD). We conducted a family-based study, with stratification based on sex and subtype, to test the association between 30 tag single-nucleotide polymorphisms (SNPs) within the gene encoding NET (SLC6A2) and ADHD.



Family-based association tests were conducted with the categorical diagnosis of ADHD, as well as quantitative phenotypes of clinical relevance (Conners Global Index for Teachers and Parents, and Child Behavior Checklist measures). Sliding window haplotype analysis was conducted with screening based on conditional power using PBAT.



A previously reported association with rs3785143 was confirmed in this study. Further, extensive association was observed with haplotype blocks, with a differential pattern observed based on sex and subtype. The 5' region of the gene (encompassing haplotype block 1 and including a functional promoter SNP, rs28386840) showed an association with ADHD in girls (irrespective of subtype). A different region of the gene (distributed around haplo-type block 2) was associated with distinct behavioural phenotypes in boys. These findings are correlated with previously reported functional studies of gene variants in SLC6A2.



The most important limitation of the study is the small size of the groups resulting from the stratification based on sex followed by subtype.



The results obtained in this family-based study suggest that haplotype blocks within different regions of SLC6A2 show differential association with the disorder based on sex and subtype. These associations may have been masked in previous studies when tests were conducted with pooled samples.
The influence of an adaptation period in reducing the third party observer effect during a neuropsychological evaluation.

Individuals have been shown to perform suboptimally on memory measures when a third party observer (TPO) is present. The current study attempted to use adaptation to reduce the inhibitory effect of a TPO on memory performance. Undergraduate participants (N=80) were randomly assigned to one of four groups in a 2 x 2 (+/-adaptation period, +/-observation) design in order to investigate the interaction between adaptation period and observation status. Results indicated that the adaptation period had a negligible inhibitory effect over the recall of observed participants (d= -0.11), but unexpectedly, when unobserved participants were not given an adaptation period, recall was inhibited by a sizeable degree (d= -1.11). These findings suggest that the presence of the TPO may have prevented participants from benefiting from adaptation to the general testing situation. To date, there are no known methods for eliminating the TPO effect.
An experience with angioplasty and stenting of carotid artery stenosis with embolic protection devices.

Carotid artery stenting has recently been recommended as an alternative to carotid endarterectomy by some clinicians.



To evaluate success rate, as well as in-hospital and 30-day adverse events in our first experience in Iran for carotid artery stenting with protection devices.



From December 2003 through July 2004, we performed 12 consecutive (9 males and 3 females) carotid artery stenting procedures. The patients had a mean age of 62 (range: 46 - 78) years. Indications for carotid artery stenting included primary lesions in all patients, stenosis > or =50% in symptomatic, and stenosis > or =80% in asymptomatic patients.



Carotid artery stenting was technically successful in all 12 patients. The mean +/- SD severity of stenosis before carotid artery stenting was 85 +/- 14% as compared with 15 +/- 10% after the procedure. No periprocedural death occurred. No in-hospital or 30-day minor or major stroke/death was observed.



Percutaneous stenting of the carotid artery stenosis, when a cerebral protection device is used, is feasible and effective but not without technical difficulties and potential complications. We, therefore, recommend carotid artery stenting for patients who are at high risk for undergoing carotid endarterectomy. Nevertheless, a long-learning curve may be needed for anyone who wishes to start this technique.
Predicting target vessel revascularization in older patients undergoing percutaneous coronary intervention in the drug-eluting stent era.

The contemporary need for repeat revascularization in older patients after percutaneous coronary intervention (PCI) has not been well studied. Understanding repeat revascularization risk in this population may inform treatment decisions.



We analyzed patients ≥65 years old undergoing native-vessel PCI of de novo lesions from 2005 to 2009 discharged alive using linked CathPCI Registry and Medicare data. Repeat PCIs within 1 year of index procedure were identified by claims data and linked back to CathPCI Registry to identify target vessel revascularization (TVR). Surgical revascularization and PCIs not back linked to CathPCI Registry were excluded from main analyses but included in sensitivity analyses. Independent predictors of TVR after drug-eluting stent (DES) or bare-metal stent (BMS) implantation were identified by multivariable logistic regression.



Among 343,173 PCI procedures, DES was used in 76.5% (n = 262,496). One-year TVR ranged from 3.3% (overall) to 7.1% (sensitivity analysis). Precatheterization and additional procedure-related TVR risk models were developed in BMS (c-indices 0.54, 0.60) and DES (c-indices 0.57, 0.60) populations. Models were well calibrated and performed similarly in important patient subgroups (female, diabetic, and older [≥75 years]). The use of DES reduced predicted TVR rates in high-risk older patients by 35.5% relative to BMS (from 6.2% to 4.0%). Among low-risk patients, the number needed to treat with DES to prevent 1 TVR was 63-112; among high-risk patients, this dropped to 28-46.



In contemporary clinical practice, native-vessel TVR among older patients occurs infrequently. Our prediction model identifies patients at low versus high TVR risk and may inform clinical decision making.
Surgically amenable epilepsies in children and adolescents: clinical, imaging, electrophysiological, and post-surgical outcome data

A large number of patients with epilepsy in the pediatric population have medically intractable epilepsy. In this age group seizures are usually daily or weekly, and response to antiepileptic therapy is poor, especially for those with neurological abnormalities and symptomatic epilepsies. However, several authors have already demonstrated similarly favorable long-term post-surgical seizure control when comparing pediatric and adult populations. In this article we aim to report the experience of the Ribeirão Preto Epilepsy Surgery Program in pediatric epilepsy surgery. We analyzed 107 patients with medically intractable epilepsy operated on between July 1994 and December 2002, considering age at surgery, seizure type, pathological findings, and seizure outcome. All data were prospectively collected according to protocols previously approved by the institution ethics committee. We analyzed a total of 115 operations performed in 107 patients. There was no difference in sex distribution. Complex partial seizures occurred in 31.4% of the patients, followed by tonic seizures (25.9%), focal motor seizures (15.4%), and infantile spasms (13.3%). The most common etiologies were cortical developmental abnormalities (25.2%), tumors (16.8%), mesial temporal sclerosis (15.9%), Rasmussen syndrome (6.5%), and tuberous sclerosis (6.5%). Overall post-surgical seizure outcome showed 67.2% of the patients within Engel classes I and II, reaching 75.0% when patients with callosotomies were excluded. Post-surgical seizure control in the pediatric population is similar to that in adult patients, despite the fact that epilepsies in this age group are more frequently of extratemporal origin, suggesting that surgery should be considered in children as soon as intractability is determined.
Prognostic significance of bcl-2 protein expression in aggressive non-Hodgkin's lymphoma. Groupe d'Etude des Lymphomes de l'Adulte (GELA).

Little is known about the expression of bcl-2 protein in intermediate and high grade non-Hodgkin's lymphoma (NHL) and its clinical and prognostic significance. We performed immunohistochemical analysis of bcl-2 expression in tumoral tissue sections of 348 patients with high or intermediate grade NHL. These patients were uniformly treated with adriamycin, cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP) in the induction phase of the LNH87 protocol. Fifty eight cases were excluded due to inadequate staining. Of the 290 remaining patients, 131 (45%) disclosed homogeneous positivity (high bcl-2 expression) in virtually all tumor cells, whereas 65 (23%) were negative and 94 (32%) exhibited intermediate staining. High bcl-2 expression was more frequent in B-cell NHL (109 of 214, 51%) than in T-cell NHL (6 of 35, 17%) (P = .0004), and was heterogeneously distributed among the different histological subtypes. Further analysis was performed on the 151 patients with diffuse large B-cell lymphoma (centroblastic and immunoblastic) to assess the clinical significance and potential prognostic value of bcl-2 expression in the most frequent and homogeneous immunohistological subgroup. High bcl-2 expression, found in 44% of these patients (67 of 151), was more frequently associated with III-IV stage disease (P = .002). Reduced disease-free survival (DFS) (P < .01) and overall survival (P < .05) were demonstrated in the patients with high bcl-2 expression. Indeed, the 3-year estimates of DFS and overall survival were 60% and 61%, respectively (high bcl-2 expression) versus 82% and 78%, respectively (negative/intermediate bcl-2 expression). A multivariate regression analysis confirmed the independent effect of bcl-2 protein expression on DFS. Thus bcl-2 protein expression, as demonstrated in routinely paraffin-embedded tissue, appears to be predictive of poor DFS, in agreement with the role of bcl-2 in chemotherapy-induced apoptosis. It might be considered as a new independent biologic prognostic parameter, which, especially in diffuse large B-cell NHL, could aid in the identification of patient risk groups.
Risk Factors for BK Polyoma Virus Treatment and Association of Treatment With Kidney Transplant Failure: Insights From a Paired Kidney Analysis.

Identification of risk factors for BK polyoma virus (BKPyV) without confounding by donor factors and era effects in paired analysis may inform strategies to prevent BKPyV.



In this analysis of 21,575 mate kidney pairs in the Scientific Registry of Transplant Recipients between 2004 and 2010, the presence of a treatment code for BKPyV virus in follow-up forms was used to identify pairs in which 1 of 2 mate kidneys was treated (discordant treatment) or both mate kidneys were treated (concordant treatment).



Among 1975 discordant pairs, younger than 18 years or 60 years or older, male sex, HLA mismatch or 4 greater, acute rejection, and depleting antibody induction had a higher odds of treatment, whereas diabetes and sirolimus had a lower odds of treatment, and treatment was associated with a higher risk of allograft failure (hazards ratio, 2.01; 95% confidence interval, 1.63-2.48). The rate of concordant treatment (0.81%) was 2.8 times higher than expected. Concordant treatment was associated with nonwhite donor ethnicity, donation after circulatory death, transplantation after 2008, and transplantation of mate kidneys in the same center.



This analysis of kidneys from the same donor in which only 1 transplant was treated for BKPyV identifies specific risk factors (age <18 or ≥ 60 years, male sex, depleting antibody, HLA mismatch ≥ 4) for BKPyV and provides an estimate of the BKPyV-associated risk of allograft failure (hazards ratio = 2.01) without confounding by donor factors or era effects. The higher than expected rate of concordant treatment suggests the importance of donor factors in BKPyV pathogenesis and warrants further study.
Randomized, comparative study of interferon beta-1a treatment regimens in MS: The EVIDENCE Trial.

Interferon beta (IFNbeta) reduces relapses and MRI activity in relapsing-remitting MS (RRMS), with variable effects on disability. The most effective dose regimen remains controversial.



This randomized, controlled, multicenter trial compared the efficacy and safety of IFNbeta-1a (Rebif) 44 micro g subcutaneously three times weekly (tiw), and IFNbeta-1a (Avonex) 30 micro g IM once weekly (qw) in 677 patients with RRMS. Assessors blinded to treatment performed neurologic and MRI evaluations. The primary endpoint was the proportion of patients who were relapse free at 24 weeks; the principal MRI endpoint was the number of active lesions per patient per scan at 24 weeks.



After 24 weeks, 74.9% (254/339) of patients receiving IFNbeta-1a 44 micro g tiw remained relapse free compared with 63.3% (214/338) of those given 30 micro g qw. The odds ratio for remaining relapse free was 1.9 (95% CI, 1.3 to 2.6; p = 0.0005) at 24 weeks and 1.5 (95% CI, 1.1 to 2.1; p = 0.009) at 48 weeks, favoring 44 micro g tiw. Patients receiving 44 micro g tiw had fewer active MRI lesions (p < 0.001 at 24 and 48 weeks) compared with those receiving 30 micro g qw. Injection-site reactions were more frequent with 44 micro g tiw (83% vs 28%, p < 0.001), as were asymptomatic abnormalities of liver enzymes (18% vs 9%, p = 0.002) and altered leukocyte counts (11% vs 5%, p = 0.003) compared with the 30 micro g qw dosage. Neutralizing antibodies developed in 25% of 44 micro g tiw patients and in 2% of patients receiving 30 micro g qw.



IFNbeta-1a 44 micro g subcutaneously tiw was more effective than IFNbeta-1a 30 micro g IM qw on all primary and secondary outcomes investigated after 24 and 48 weeks of treatment.
Symptom distress and quality of life in patients with cancer newly admitted to hospice home care.

To evaluate the relationships between quality of life (QOL) and symptom distress, pain intensity, dyspnea intensity, and constipation intensity in people with advanced cancer who were newly admitted to hospice home care.



Descriptive and correlational.



A large hospice that provides primarily home care.


SAMPLE
178 adult hospice homecare patients with cancer who were accrued to a clinical trial funded by the National Institutes of Health focusing on symptom management and QOL. Patients were excluded if they received a score lower than seven on the Short Portable Mental Status Questionnaire.



The patients were invited to participate in the clinical trial within 48 hours of admission to hospice home care. Among the questionnaires they completed were a QOL index and a distress scale. Scales measuring present intensity of pain, dyspnea, and constipation also were administered.



QOL, symptom distress, pain intensity, dyspnea intensity, and constipation intensity.



The most frequently reported symptoms among the sample were lack of energy, pain, dry mouth, and shortness of breath. Lack of energy caused the greatest distress, followed closely by dry mouth and pain. The results of the regression analysis indicated that total distress score, pain intensity, dyspnea intensity, and constipation intensity were related to QOL at the univariate level. When all predictors were considered simultaneously, only the total distress score remained a significant predictor of QOL (p< 0.001), accounting for about 35% of variance.



QOL was affected by symptom distress in people with advanced cancer near the end of life.



The symptoms most commonly reported and those that cause the greatest patient distress should be addressed first by hospice nurses. Continued effort is needed in the important area of symptom management.
Characteristics and outcomes of older HIV-infected patients receiving antiretroviral therapy in Malawi: A retrospective observation cohort study

To estimate patients enrolling on antiretroviral therapy (ART) over time; describe trends in baseline characteristics; and compare immunological response, loss to follow-up (LTFU), and mortality by three age groups (25-39, 40-49 and ≥50 years).



A retrospective observation cohort study.



This study used routine ART data from two public clinics in Lilongwe, Malawi. All HIV-infected individuals, except pregnant or breastfeeding women, aged ≥ 25 years at ART initiation between 2006 and 2015 were included. Poisson regression models estimated risk of mortality, stratified by age groups.



Of 37,378 ART patients, 3,406 were ≥ 50 years old. Patients aged ≥ 50 years initiated ART with more advanced WHO clinical stage and lower CD4 cell count than their younger counterparts. Older patients had a significantly slower immunological response to ART in the first 18 months on ART compared to patients aged 25-39 years (p = 0.04). Overall mortality rates were 2.3 (95% confidence Interval (CI) 2.2-2.4), 2.9 (95% CI 2.7-3.2) and 4.6 (95% CI 4.2-5.1) per 100 person-years in patients aged 25-39 years, 40-49 years and 50 years and older, respectively. Overall LTFU rates were 6.3 (95% CI 6.1-6.5), 4.5 (95% CI 4.2-4.7), and 5.6 (95% CI 5.1-6.1) per 100 person years among increasing age cohorts. The proportion of patients aged ≥ 50 years and newly enrolling into ART care remained stable at 9% while the proportion of active ART patients aged ≥50 years increased from 10% in 2006 to 15% in 2015.



Older people had slower immunological response and higher mortality. Malawi appears to be undergoing a demographic shift in people living with HIV. Increased consideration of long-term ART-related problems, drug-drug interactions and age-related non-communicable diseases is warranted.