nils-herrmann/clean_scirepeval huggingface dataset:
Adalimumab therapy in children with Crohn disease previously treated with infliximab.

Adalimumab, a humanised anti-tumour necrosis factor antibody, is an effective treatment in adult patients with refractory Crohn disease (CD). The available literature on its efficacy in children remains limited. We aimed to evaluate the real-world efficacy in paediatric patients with CD and compare the efficacy between infliximab (IFX) nonresponders and patients who lost response to IFX.



All Dutch patients with CD receiving adalimumab before the age of 18 years after previous IFX therapy were identified. We analysed longitudinal disease activity, assessed by the mathematically weighted Pediatric Crohn's Disease Activity Index (wPCDAI) or the physician global assessment (PGA), and adverse events (AEs).



Fifty-three patients with CD were included. Twelve patients received monotherapy and the others received combination treatment with thiopurines (n = 21), methotrexate (n = 11), steroids (n = 7), or exclusive enteral nutrition (n = 2). Median follow-up was 12 months (interquartile range 5-23). Remission was reached in 34 patients (64%, wPCDAI < 12.5 or PGA = 0) after a median of 3.3 months, and maintained by 50% for 2 years. Eleven patients (21%) reached response but not remission (decrease in wPCDAI ≥ 17.5 or decrease in PGA). Eighteen patients (34%) failed adalimumab treatment because of nonresponse (n = 4), lost response (n = 11), or AEs (n = 3). More IFX nonresponders failed adalimumab treatment than patients who lost response to IFX (2/3 vs 8/34, hazard ratio 18.8, 95% confidence interval 1.1-303.6). Only 1 patient encountered a serious AE, a severe but nonfatal infection.



In clinical practice, adalimumab induces remission in two-thirds of children with IFX refractory CD.
An experimental investigation of the cognitive vulnerability to depression.

The present study employed an experimental design, to examine the role of metacognitive processing in the prevention of relapse to depression. Eighty remitted depressed participants were randomly allocated to receive training in the metacognitive style of rumination, distraction, acceptance or no training control prior to a negative mood induction. Rumination prolonged the intensity of the negative mood consistent with no training, whereas both distraction and acceptance reduced the intensity of the negative mood. Changes in attitudes were only found in the acceptance condition, as participants in this condition reduced negative attitudes towards negative experiences. These results are consistent with information processing theory, and imply that acceptance-based preventative interventions may operate by both reducing the intensity of sad moods and altering one's attitudes towards temporary moments of sadness.
Cognitive behavior therapy, exercise, or both for treating chronic widespread pain.

The clinical impact of telephone-delivered cognitive behavioral therapy (TCBT), exercise, or a combined intervention in primary care patients with chronic widespread pain (CWP) is unclear.



A total of 442 patients with CWP (meeting the American College of Rheumatology criteria) were randomized to receive 6 months of TCBT, graded exercise, combined intervention, or treatment as usual (TAU). The primary outcome, using a 7-point patient global assessment scale of change in health since trial enrollment (range: very much worse to very much better), was assessed at baseline and 6 months (intervention end) and 9 months after randomization. A positive outcome was defined as "much better" or "very much better." Data were analyzed using logistic regression according to the intention-to-treat principle.



The percentages reporting a positive outcome at 6 and 9 months, respectively, were TAU group, 8% and 8%; TCBT group, 30% and 33%; exercise group, 35% and 24%; and combined intervention group, 37% and 37% (P < .001). After adjustment for age, sex, center, and baseline predictors of outcome, active interventions improved outcome compared with TAU: TCBT (6 months: odds ratio [OR], 5.0 [95% CI, 2.0-12.5]; 9 months: OR, 5.4 [95% CI, 2.3-12.8]), exercise (6 months: OR, 6.1 [95% CI, 2.5-15.1]; 9 months: OR, 3.6 [95% CI, 1.5-8.5]), and combined intervention (6 months: OR, 7.1 [95% CI, 2.9-17.2]; 9 months: OR, 6.2 [95% CI, 2.7-14.4]). At 6 and 9 months, combined intervention was associated with improvements in the 36-Item Short Form Health Questionnaire physical component score and a reduction in passive coping strategies. Conclusions on cost-effectiveness were sensitive to missing data.



TCBT was associated with substantial, statistically significant, and sustained improvements in patient global assessment.
Molecular epidemiologic studies within the Selenium and Vitamin E Cancer Prevention Trial (SELECT)

To conduct timely epidemiologic investigations of molecular/genetic markers that may contribute to the development of prostate, lung, colorectal, or other cancers within the Selenium and Vitamin E Cancer Prevention Trial (SELECT), and to evaluate interactions between these markers and the study interventions.  The epidemiologic studies within SELECT will be based on 32,400 men aged 55 years or older (age 50 or older for the African-American men) enrolled into an intergroup, randomized, placebo-controlled, double-blind, phase III prevention trial of supplemental selenium and vitamin E developed and funded by the National Cancer Institute, and coordinated by the Southwest Oncology Group. During the 12-year study period approximately 1500–2000 cases of prostate cancer, 800 lung cancers, and 500 colon cancers are estimated to be diagnosed, based on data from the ongoing Prostate Cancer Prevention Trial of finasteride. A modified fasting blood sample will be processed to collect plasma for analysis of micronutrients, hormones, cytokines, and other proteins. Buffy-coat derived white blood cells collected at baseline will be used for isolation of DNA and establishment of immortalized cell lines. Red blood cells will be stored for analysis of hemoglobin adducts and other components.  Specific results anticipated from these molecular studies will provide information on factors hypothesized to contribute to prostate cancer risk and that may modify the efficacy of either trial supplement, including: steroid sex hormones and several polymorphic genes that encode proteins affecting androgenic stimulation of the prostate, including the androgen receptor, steroid 5α-reductase type II, CYP17, and β-hydroxysteroid dehydrogenase; polymorphisms of DNA repair genes and carcinogen metabolism genes, including those involved in the activation of chemical carcinogens to reactive intermediates (e.g., CYP1A1) or the detoxification of reactive intermediates (e.g., glutathione S-transferase M1); DNA and protein adducts; and insulin-like growth factors and leptin.  SELECT offers an excellent opportunity to conduct molecular epidemiologic investigations to assess gene–environment interactions and their role in prostate, lung, and colon carcinogenesis.
Sex-based differences in clinical practice and outcomes for Japanese patients with acute myocardial infarction undergoing primary percutaneous coronary intervention.

Limited data are available for sex-based differences in Japanese patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI).


The study patients comprised 1,197 women and 3,182 men who underwent primary PCI for AMI in 2005-2007. Compared with the men, the women were significantly older, and had significantly longer onset-to-balloon time and lower rate of follow-up coronary angiography. In-hospital mortality was higher among women than men (8.7% vs. 4.9%, P<0.001). Although the cumulative incidence of all-cause death at 3 years was also higher for women (17.7% vs. 10.7%, P<0.001), the adjusted risk for all-cause death was comparable [hazard ratio (HR, women vs. men)=0.94, 95% confidence interval (CI): 0.71-1.24, P=0.66]. The incidence (12.1% vs. 12.4%, P=0.77) and the adjusted risk (HR=0.99, 95% CI 0.78-1.24, P=0.92) for any clinically-driven coronary revascularization were both comparable. However, regarding any non-clinically-driven coronary revascularization, the incidence (19.6% vs. 27.8%, P<0.001) and the adjusted risk (HR=0.79, 95% CI 0.65-0.95, P=0.012) were both lower in women relative to men.


In current Japanese clinical practice for AMI, onset-to-balloon time was significantly longer in women than in men. Female sex was associated with lower follow-up coronary angiography rate and lower incidence of any non-clinically-driven coronary revascularization, whereas the incidence of any clinically-driven coronary revascularization was comparable between the sexes.
Optimizing CIGB-300 intralesional delivery in locally advanced cervical cancer

We conducted a phase 1 trial in patients with locally advanced cervical cancer by injecting 0.5 ml of the CK2-antagonist CIGB-300 in two different sites on tumours to assess tumour uptake, safety, pharmacodynamic activity and identify the recommended dose.Fourteen patients were treated with intralesional injections containing 35 or 70 mg of CIGB-300 in three alternate cycles of three consecutive days each before standard chemoradiotherapy. Tumour uptake was determined using 99Tc-radiolabelled peptide. In situ B23/nucleophosmin was determined by immunohistochemistry.Maximum tumour uptake for CIGB-300 70-mg dose was significantly higher than the one observed for 35 mg: 16.1±8.9 vs 31.3±12.9 mg (P=0.01). Both, AUC24h and biological half-life were also significantly higher using 70 mg of CIGB-300 (P<0.001). Unincorporated CIGB-300 diffused rapidly to blood and was mainly distributed towards kidneys, and marginally in liver, lungs, heart and spleen. There was no DLT and moderate allergic-like reactions were the most common systemic side effect with strong correlation between unincorporated CIGB-300 and histamine levels in blood. CIGB-300, 70 mg, downregulated B23/nucleophosmin (P=0.03) in tumour specimens.Intralesional injections of 70 mg CIGB-300 in two sites (0.5 ml per injection) and this treatment plan are recommended to be evaluated in phase 2 studies.
Correlation between radiographic severity of knee osteoarthritis and future disease progression. Results from a 3-year prospective, placebo-controlled study evaluating the effect of glucosamine sulfate.

To investigate the relationship between baseline radiographic severity of knee osteoarthritis (OA) and the importance of long-term joint space narrowing.



Sub-analysis from a three-year randomized, placebo-controlled, prospective study, of 212 patients with knee OA, recruited in an osteoarthritic outpatient clinic and having been part of a study evaluating the effect of glucosamine sulfate on symptom and structure modification in knee OA.



Measurements of mean joint space width (JSW), assessed by a computer-assisted method, were performed at baseline and after 3 years, on weightbearing anteroposterior knee radiographs.



In the placebo group, baseline JSW was significantly and negatively correlated with the joint space narrowing observed after 3 years (r=-0.34, P=0.003). In the lowest quartile of baseline mean JSW (<4.5mm), the JSW increased after 3 years by (mean (S.D.)) 3.8% (23.8) in the placebo group and 6.2% (17.5) in the glucosamine sulfate group. The difference between the two groups in these patients with the most severe OA at baseline was not statistically significant (P=0.70). In the highest quartile of baseline mean JSW (>6.2mm), a joint space narrowing of 14.9% (17.9) occurred in the placebo group after 3 years while patients from the glucosamine sulfate group only experienced a narrowing of 6.0% (15.1). Patients with the most severe OA at baseline had a RR of 0.42 (0.17-1.01) to experience a 0.5mm joint space narrowing over 3 years, compared to those with the less affected joint. In patients with mild OA, i.e. in the highest quartile of baseline mean JSW, glucosamine sulfate use was associated with a trend (P=0.10) towards a significant reduction in joint space narrowing.



These results suggest that patients with the less severe radiographic knee OA will experience, over 3 years, the most dramatic disease progression in terms of joint space narrowing. Such patients may be particularly responsive to structure-modifying drugs.
No effect of risedronate on femoral periprosthetic bone loss following total hip arthroplasty

We have previously shown that during the first 2 years after total hip arthroplasty (THA), periprosthetic bone resorption can be prevented by 6 months of risedronate therapy. This follow-up study investigated this effect at 4 years.



A single-center, double-blind, randomized placebo-controlled trial was carried out from 2006 to 2010 in 73 patients with osteoarthritis of the hip who were scheduled to undergo THA. The patients were randomly assigned to receive either 35 mg risedronate or placebo orally, once a week, for 6 months postoperatively. The primary outcome was the percentage change in bone mineral density (BMD) in Gruen zones 1 and 7 in the proximal part of the femur at follow-up. Secondary outcomes included migration of the femoral stem and clinical outcome scores.



61 of the 73 patients participated in this 4-year (3.9- to 4.1-year) follow-up study. BMD was similar in the risedronate group (n = 30) and the placebo group (n = 31). The mean difference was -1.8% in zone 1 and 0.5% in zone 7. Migration of the femoral stem, the clinical outcome, and the frequency of adverse events were similar in the 2 groups.



Although risedronate prevents periprosthetic bone loss postoperatively, a decrease in periprosthetic BMD accelerates when therapy is discontinued, and no effect is seen at 4 years. We do not recommend the use of risedronate following THA for osteoarthritis of the hip.
Methotrexate polyglutamate concentrations are not associated with disease control in rheumatoid arthritis patients receiving long-term methotrexate therapy.

There are limited data suggesting that methotrexate polyglutamate (MTXGlu) concentrations can guide MTX dosing in patients with rheumatoid arthritis (RA). The aim of this study was to define a therapeutic range of red blood cell (RBC) MTXGlu(n) concentrations (where n refers to the number of glutamate groups), including threshold values for efficacy and adverse effects in patients receiving long-term oral MTX treatment.



A cross-sectional study of 192 patients receiving oral MTX was undertaken. Disease activity was assessed by the swollen and tender joint counts, the C-reactive protein level, and the Disease Activity Score in 28 joints (DAS28). High disease activity was defined as a DAS28 of >3.2. A standardized questionnaire regarding common MTX adverse effects was completed.



The MTX dosage was significantly higher in patients in whom the swollen joint count and DAS28 were higher. The MTXGlu(4), MTXGlu(5), MTXGlu(3-5), and MTXGlu(1-5) concentrations were significantly higher in patients with high disease activity. After correction for age, the estimated glomerular filtration rate, and the MTX dosage, the association remained significant for MTXGlu(5). RBC folate concentrations were significantly higher in the group with high disease activity. There was no association between any MTXGlu(n) concentration and adverse effects.



In contrast to other studies, the results of the present study did not show a relationship between the MTXGlu(n) concentration and reduced disease activity in patients with RA who were receiving long-term MTX therapy. However, disease activity was influenced by the RBC folate level, which may be a more important factor than MTXGlu(n) concentrations for disease control. In accordance with the findings of previous studies, we were unable to show a relationship between MTXGlu(n) concentrations and adverse effects. Prospective studies will be important to determine whether there is a role for measuring MTXGlu(n) concentrations in patients receiving long-term treatment with MTX.
Comparison of intermittent pneumatic compression with manual lymphatic drainage for treatment of breast cancer-related lymphedema.

The aim of this prospective controlled study was to assess the efficacy of two different combination treatment modalities of lymphedema (LE). Manual lymphatic drainage (MLD) and compression bandage combination (complex decongestive therapy) have been compared with intermittent pneumatic compression (IPC) plus self-lymphatic drainage (SLD).



Both MLD with compression bandage (complex decongestive therapy) group (Group I, n=15) and IPC with SLD group (Group II, n=15) received treatment for LE 3 days in a week and every other day for 6 weeks. Arm circumferences were measured before and the 1st, 3rd, and 6th weeks of the treatment. EORTC-QLQ and ASES-tests were performed to assess the quality of life before and after 6 week-treatment. Patients in both groups had similar demographic and clinical characteristics. Even though both treatment modalities resulted in significant decrease in the total arm volume (12.2% decrease in Group II and 14.9% decrease in Group I) (p<0.001), no significant difference (p=0.582) was found between those two groups. Similarly, ASES scores were significantly (p=0.001) improved in both Group I and II without any significant difference between the groups. While emotional functioning, fatigue, and pain scores were significantly improved in both groups, global health status, functional and cognitive functioning scores appeared to be improved only in patients of group I.



Different treatment modalities consisting of MLD and compression bandage(complex decongestive therapy) or IPC and SLD appear to be effective in the treatment of LE with similar therapeutic efficacy in patients with breast cancer. However, combination modalities including IPC and SLD may be the preferred choices for their applicability at home.
GT198 Expression Defines Mutant Tumor Stroma in Human Breast Cancer.

Human breast cancer precursor cells remain to be elucidated. Using breast cancer gene product GT198 (PSMC3IP; alias TBPIP or Hop2) as a unique marker, we revealed the cellular identities of GT198 mutant cells in human breast tumor stroma. GT198 is a steroid hormone receptor coactivator and a crucial factor in DNA repair. Germline mutations in GT198 are present in breast and ovarian cancer families. Somatic mutations in GT198 are present in ovarian tumor stromal cells. Herein, we show that human breast tumor stromal cells carry GT198 somatic mutations and express cytoplasmic GT198 protein. GT198(+) stromal cells share vascular smooth muscle cell origin, including myoepithelial cells, adipocytes, capillary pericytes, and stromal fibroblasts. Frequent GT198 mutations are associated with GT198(+) tumor stroma but not with GT198(-) tumor cells. GT198(+) progenitor cells are mostly capillary pericytes. When tested in cultured cells, mutant GT198 induces vascular endothelial growth factor promoter, and potentially promotes angiogenesis and adipogenesis. Our results suggest that multiple lineages of breast tumor stromal cells are mutated in GT198. These findings imply the presence of mutant progenitors, whereas their descendants, carrying the same GT198 mutations, are collectively responsible for forming breast tumor microenvironment. GT198 expression is, therefore, a specific marker of mutant breast tumor stroma and has the potential to facilitate diagnosis and targeted treatment of human breast cancer.
A high ratio of ADP–TRAP induced platelet aggregation is associated more strongly with increased mortality after coronary stent implantation than high conventional ADP induced aggregation alone

This study aimed to evaluate whether a high relative ADP induced aggregation (r-ADP-agg) is associated with an increased mortality in patients after coronary stent implantation. Several trials were not able to improve clinical outcome by adapting platelet inhibition in patients after coronary stent implantation and high platelet reactivity (HPR). Platelet monitoring is complex and conventional definition of adenosindiphosphate (ADP) induced aggregation alone might not transfer the whole picture of adequate platelet inhibition in vivo. In a prospective single-centre observational trial multiple electrode aggregometry was performed in whole blood of patients after stent implantation. r-ADP-agg was defined as the ADP–thrombin receptor activating peptide ratio to reflect an individual degree of P2Y12 dependent platelet inhibition with a cut-off value for HPR of ≥50 %. The primary end point was mortality. Follow-up was completed in 176 of 184 patients (96 %) with a mean follow-up time of 3.7 years. 35 (20 %) patients revealed an r-ADP-agg ≥50 %. An r-ADP-agg ≥50 % was associated with an increased mortality [unadjusted hazard ratio (HR) 7.006 (2.561–19.17); p = 0.0001]. In a multivariable Cox regression analysis mortality was independently associated with an r-ADP-agg ≥50 % [HR 3.324 (1.542–7.165); p = 0.0022], ACS-setting [HR 3.249 (1.322–7.989); p = 0.0102] and severely reduced LV function [HR 5.463 (2.098–14.26); p = 0.0005]. An r-ADP-agg ≥50 % is associated with an increased mortality in patients after coronary stent implantation. Furthermore, r-ADP-agg might represent a better tool to predict clinical outcome than the conventional ADP induced platelet aggregation alone.
Identifying the content area for the 51-item National Eye Institute Visual Function Questionnaire: results from focus groups with visually impaired persons.

To identify the content area for a questionnaire designed to measure vision-targeted health-related quality of life and to determine whether problems with vision-related functioning are qualitatively similar across different common eye diseases.



Twenty-six condition-specific focus groups were conducted with 246 patients from 5 geographic regions to identify the content area for a questionnaire for use among persons with diabetic retinopathy, glaucoma, macular degeneration, cytomegalovirus retinitis, and cataract. A standard protocol was used to structure each focus group discussion. Sessions were audiotaped, transcribed, and coded in preparation for a content analysis.



Five university-based ophthalmology practices and 1 nonprofit eye care foundation.



Eligible participants had to have 1 of the following eye conditions: age-related cataracts, age-related macular degeneration, diabetic retinopathy, primary open angle glaucoma, cytomegalovirus retinitis, or low vision from any cause. All eligible persons were older than 21 years, spoke English, and had sufficient cognitive function to provide informed consent.



Among the 246 participants, 2623 problems with vision-related functioning were mentioned. The mean number of problems per person ranged from 13.5 for those with diabetic retinopathy to 7.9 for persons with glaucoma. For the sample overall, reading problems were mentioned most frequently, followed by driving, general problems with seeing clearly, and mental health complaints caused by vision. Although the proportion of persons who reported each problem varied by condition, at least some persons with each eye disease reported each problem. The 3 most common descriptors associated with each problem were difficulty or ease of performance (13%), psychological distress associated with performance of the activity (11%), and complete inability to participate in a visual activity (11%).



An item-generation strategy for a new questionnaire using a standardized focus group method identified content areas and aspects of visual disability that are not included in currently available vision-specific instruments that assess the impact of common eye diseases on visual functioning in every-day life. Although participants mentioned problems that were unique to their disease, across conditions the problems mentioned were similar. These findings provide empirical evidence of content validity for a vision-targeted, health-related quality-of-life survey designed for use across conditions.