nils-herrmann/clean_scirepeval huggingface dataset:
Is pre-assessment for anti-TNF therapy in RA necessary in the UK? Analysis of DAS28 in six centres.

National Institute for Health and Clinical Excellence (NICE) guidelines for anti-tumour necrosis factor (TNF) in rheumatoid arthritis (RA) state that two pre-assessments of Disease Activity Score (DAS28) should be performed a month apart. We performed a retrospective audit of data from six centres to determine the stability of DAS28 between assessments, and the proportion of patients still satisfying eligibility criteria at baseline.



All RA patients assessed for anti-TNF from six centres had their pre-assessment DAS28 (DAS-1) compared with their baseline DAS28 (DAS0) using paired t-tests, and a similar analysis for the components of the DAS28. Patients who were no longer eligible for anti-TNF at DAS0 were noted.



Six hundred and seventy-nine RA patients showed no significant change in the DAS28, with a mean DAS-1 of 6.74 and DAS0 of 6.73. (P = 0.86). Of the patients, 97.2% fulfilled the UK eligibility criteria at DAS0. Comparison of the individual components of the DAS28 between the two pre-assessment dates showed that there was no significant difference between either the numbers of swollen joints or the erythrocyte sedimentation rate (ESR), but there was a significant increase in the numbers of tender joints of 1.41 (P < 0.001) and in the visual analogue scale (VAS) of 4.22 (P < 0.001).



The overwhelming majority of patients who fulfil eligibility criteria for anti-TNF drugs 1 month prior to baseline also fulfil the criteria at baseline. There is no significant change in the DAS28 over the month waiting to go onto anti-TNF therapy. A single assessment of the DAS28 would suffice to enable patients to go on to anti-TNF treatment.
Exemestane for breast cancer prevention: a critical shift?

The Mammary Prevention 3 (MAP.3) placebo-controlled randomized trial in 4,560 high-risk postmenopausal women showed a 65% reduction in invasive breast cancer with the use of exemestane at 35 months median follow-up. Few differences in adverse events were observed between the arms, suggesting a promising risk:benefit balance with exemestane for use in chemoprevention. Yet, the MAP.3 design and implementation raise concerns regarding limited data maturity and not prospectively including key bone-related and other toxicities as study end points. Exemestane for prevention is juxtaposed against selective estrogen receptor modulators and the other aromatase inhibitors. Additional issues for prevention, including the influence of obesity, alternative dosing, and biomarker use in phase III trials, are addressed.



The recently completed MAP.3 trial of exemestane for breast cancer prevention offers a potential new standard for pharmaceutical risk reduction in high-risk postmenopausal women. In addition to describing key findings from the publication of MAP.3 and related trials, our review undertakes a detailed analysis of the strengths and weaknesses of MAP.3 as well as the implications for future prevention research.
Construct and criterion validity of the SF-12 health questionnaire in patients with acute myocardial infarction and unstable angina.

The aim of the study was to determine the construct and criterion validity of the 12-item short-form questionnaire (SF-12) in coronary patients with either acute myocardial infarction or unstable angina in Spain.



A total of 186 patients hospitalized with coronary heart disease have been studied. The construct validity has been analysed by means of the association between the SF-12v.1 and sociodemographic and clinical variables; and the criterion validity was tested by the correlations between 36-item short-form question (SF-36) and SF-12 summary scores. The equivalence between both health questionnaires was examined by means of the proportion of variance in the SF-36 physical and mental component summary (PCS-36 and MCS-36) scores explained by the 12 items adjusted by age and sex.



The validation result was as expected: female patients and those with poor education level, worse mental health, unstable angina, cardiovascular risk factor and co-morbidity obtained a lower score in the SF-12. The correlations between SF-36 and SF-12 summary scores were high. The equivalence between the SF-12 and SF-36 was good, because the models explained 87% of the variation in PCS-36 score and 93% of the variation in MCS-36.



The SF-12 is a valid tool in studies assessing health-related quality of life in coronary patients. The use of the SF-12 may be especially useful in patients where the clinical situation make difficult the application of the longer instrument.
Relations of the factors of the tripartite model of anxiety and depression to types of social anxiety.

Our primary goal was to examine the relations of the specific components of the tripartite model of anxiety and depression [Clark, L. A., Watson, D. (1991). Tripartite model of anxiety and depression: Psychometric evidence and taxonomic implications.  to two types of social anxiety (social interaction anxiety and performance anxiety) in 148 individuals with social phobia. In line with previous research, overall social anxiety was more closely related to the anhedonic depression (AD) or low positive affect factor of the tripartite model than to the physiological hyerarousal factor, controlling for general distress. However, as hypothesized, performance anxiety was more closely associated with the physiological hyerarousal factor, whereas social interaction anxiety was more closely associated with the AD or low positive affect factor. We also examined the convergent and discriminant validity of the Mood and Anxiety Symptom Questionnaire (MASQ; [Watson, D., Clark, L. A. (1991). The mood and anxiety symptom questionnaire. Unpublished manuscript, University of Iowa City]). Intercorrelations of the MASQ subscales were as expected, but correlations with measures of social anxiety, nonsocial anxiety, and depression provided only modest support for convergent and discriminant validity. Findings from this study provide a more detailed account of the specific components of the tripartite model that characterize the diversity of symptoms subsumed by social phobia.
Movement control exercise versus general exercise to reduce disability in patients with low back pain and movement control impairment. A randomised controlled trial

Non-specific low back pain (NSLBP) in subacute and chronic stages can be treated effectively with exercise therapy. Research guidelines recommend evaluating different treatments in defined subgroups of patients with NSLBP. A subgroup of patients with movement control impairment (MCI) improved significantly on patient specific function and disability in a previous case series after movement control exercises.



In a randomised controlled trial (RCT) we will compare the effectiveness of movement control and general exercise in patients with MCI. 106 participants aged 18 - 75 will be recruited in 5 outpatient hospital departments and 7 private practices.Patients randomly assigned to the movement control exercise group will be instructed to perform exercises according to their MCI. The general exercise group will follow an exercise protocol aimed at improving endurance and flexibility. Patients in both groups will receive 9 - 18 treatments and will be instructed to do additional exercises at home.The primary outcome is the level of disability assessed using the patient specific functional scale (PSFS) which links the perceived pain to functional situations and is measured before treatment and at 6 and 12 months follow-up. Secondary outcomes concern low back pain related disability (Roland Morris questionnaire, RMQ), graded chronic pain scale (GCPS), range of motion and tactile acuity.



To our knowledge this study will be the first to compare two exercise programs for a specific subgroup of patients with NSLBP and MCI. Results of this study will provide insight into the effectiveness of movement control exercise and contribute to our understanding of the mechanisms behind MCI and its relation to NSLBP.
Prognostic significance of angiogenic growth factor serum levels in patients with acute coronary syndromes.

In patients with acute coronary syndromes, compensatory processes are initiated, including angiogenesis and endothelial regeneration of ruptured or eroded plaques. Angiogenic growth factors like vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and basic fibroblast growth factor (bFGF) are upregulated during ischemia. However, it is unknown whether their serum levels are related to clinical outcome.



We measured VEGF, HGF, and bFGF levels in 1090 patients with acute coronary syndromes. Angiographic evaluation was performed at baseline as well as death, and nonfatal myocardial infarctions were recorded during 6-month follow-up. HGF and VEGF, but not bFGF, were significantly and independently associated with the patients' outcome. Patients with elevated VEGF serum levels suffered from adverse outcome (adjusted hazard ratio, 2.50 [1.52 to 4.82]; P=0.002). VEGF elevation was associated with evidence of ischemia and was a significant predictor of the effect of glycoprotein IIb/IIIa inhibition. In contrast, patients with high HGF levels had a significantly lower event rate compared with patients with low HGF levels (adjusted hazard ratio, 0.33 [0.21 to 0.51]; P<0.001). HGF levels did not correlate with evidence of ischemia and did not predict the effect of abciximab. Intriguingly, however, HGF levels significantly correlated with angiographically visible collateralization of the target vessel (22.4% versus 10.5%; P<0.001).



The angiogenic growth factors VEGF and HGF are independent predictors of the patients' prognosis in acute coronary syndromes. Whereas VEGF elevation correlated with the evidence of myocardial ischemia and indicated an adverse outcome, HGF elevation was independent of ischemia and associated with improved collateralization as well as a favorable prognosis.
Synbiotic therapy (Bifidobacterium longum/Synergy 1) initiates resolution of inflammation in patients with active ulcerative colitis: a randomised controlled pilot trial.

Ulcerative colitis (UC) is an acute and chronic inflammatory disease of the large bowel with unknown aetiology. The immune response against normal commensal microorganisms is believed to drive inflammatory processes associated with UC. Therefore, modulation of bacterial communities on the gut mucosa, through the use of probiotics and prebiotics, may be used to modify the disease state.



A synbiotic was developed for use in UC patients combining a probiotic, Bifidobacterium longum, isolated from healthy rectal epithelium, and a prebiotic (Synergy 1), a preferential inulin-oligofructose growth substrate for the probiotic strain. Treatment was employed in a double blinded randomised controlled trial using 18 patients with active UC for a period of one month. Clinical status was scored and rectal biopsies were collected before and after treatment, and transcription levels of epithelium related immune markers were measured.



Sigmoidoscopy scores (scale 0-6) were reduced in the test group (start 4.5 (1.4), end 3.1 (2.5)) compared with placebo (start 2.6 (2.1), end 3.2 (2.2)) (p=0.06). mRNA levels for human beta defensins 2, 3, and 4, which are strongly upregulated in active UC, were significantly reduced in the test group after treatment (p=0.016, 0.038, and 0.008, respectively). Tumour necrosis factor alpha and interleukin 1alpha, which are inflammatory cytokines that drive inflammation and induce defensin expression, were also significantly reduced after treatment (p=0.018 and 0.023, respectively). Biopsies in the test group had reduced inflammation and regeneration of epithelial tissue.



Short term synbiotic treatment of active UC resulted in improvement of the full clinical appearance of chronic inflammation in patients receiving this therapy.
Moderation of antidepressant response by the serotonin transporter gene.

There have been conflicting reports on whether the length polymorphism in the promoter of the serotonin transporter gene (5-HTTLPR) moderates the antidepressant effects of selective serotonin reuptake inhibitors (SSRIs). We hypothesised that the pharmacogenetic effect of 5-HTTLPR is modulated by gender, age and other variants in the serotonin transporter gene.



To test the hypothesis that the 5-HTTLPR differently influences response to escitalopram (an SSRI) compared with nortriptyline (a noradrenaline reuptake inhibitor).



The 5-HTTLPR and 13 additional markers across the serotonin transporter gene were genotyped in 795 adults with moderate-to-severe depression treated with escitalopram or nortriptyline in the Genome Based Therapeutic Drugs for Depression (GENDEP) project.



The 5-HTTLPR moderated the response to escitalopram, with long-allele carriers improving more than short-allele homozygotes. A significant three-way interaction between 5-HTTLPR, drug and gender indicated that the effect was concentrated in males treated with escitalopram. The single-nucleotide polymorphism rs2020933 also influenced outcome.



The effect of 5-HTTLPR on antidepressant response is SSRI specific conditional on gender and modulated by another polymorphism at the 5' end of the serotonin transporter gene.
Chimeric antigen receptor T cells for sustained remissions in leukemia.

Relapsed acute lymphoblastic leukemia (ALL) is difficult to treat despite the availability of aggressive therapies. Chimeric antigen receptor-modified T cells targeting CD19 may overcome many limitations of conventional therapies and induce remission in patients with refractory disease.



We infused autologous T cells transduced with a CD19-directed chimeric antigen receptor (CTL019) lentiviral vector in patients with relapsed or refractory ALL at doses of 0.76×10(6) to 20.6×10(6) CTL019 cells per kilogram of body weight. Patients were monitored for a response, toxic effects, and the expansion and persistence of circulating CTL019 T cells.



A total of 30 children and adults received CTL019. Complete remission was achieved in 27 patients (90%), including 2 patients with blinatumomab-refractory disease and 15 who had undergone stem-cell transplantation. CTL019 cells proliferated in vivo and were detectable in the blood, bone marrow, and cerebrospinal fluid of patients who had a response. Sustained remission was achieved with a 6-month event-free survival rate of 67% (95% confidence interval [CI], 51 to 88) and an overall survival rate of 78% (95% CI, 65 to 95). At 6 months, the probability that a patient would have persistence of CTL019 was 68% (95% CI, 50 to 92) and the probability that a patient would have relapse-free B-cell aplasia was 73% (95% CI, 57 to 94). All the patients had the cytokine-release syndrome. Severe cytokine-release syndrome, which developed in 27% of the patients, was associated with a higher disease burden before infusion and was effectively treated with the anti-interleukin-6 receptor antibody tocilizumab.



Chimeric antigen receptor-modified T-cell therapy against CD19 was effective in treating relapsed and refractory ALL. CTL019 was associated with a high remission rate, even among patients for whom stem-cell transplantation had failed, and durable remissions up to 24 months were observed. (Funded by Novartis and others; CART19 ClinicalTrials.gov numbers, NCT01626495 and NCT01029366.).
Phase II trial of infusional fluorouracil, irinotecan, and bevacizumab for metastatic colorectal cancer: efficacy and circulating angiogenic biomarkers associated with therapeutic resistance.

We investigated the efficacy of fluorouracil (FU), leucovorin, irinotecan, and bevacizumab (FOLFIRI + B) in a phase II trial in patients previously untreated for metastatic colorectal cancer (mCRC), and changes during treatment in plasma cytokines and angiogenic factors (CAFs) as potential markers of treatment response and therapeutic resistance.



We conducted a phase II, two-institution trial of FOLFIRI + B. Each 14-day cycle consisted of bevacizumab (5 mg/kg), irinotecan (180 mg/m(2)), bolus FU (400 mg/m(2)), and leucovorin (400 mg/m(2)) followed by a 46-hour infusion of FU (2,400 mg/m(2)). Levels of 37 CAFs were assessed using multiplex-bead assays and enzyme-linked immunosorbent assay at baseline, during treatment, and at the time of progressive disease (PD).



Forty-three patients were enrolled. Median progression-free survival (PFS), the primary end point of the study, was 12.8 months. Median overall survival was 31.3 months, with a response rate of 65%. Elevated interleukin-8 at baseline was associated with a shorter PFS (11 v 15.1 months, P = .03). Before the radiographic development of PD, several CAFs associated with angiogenesis and myeloid recruitment increased compared to baseline, including basic fibroblast growth factor (P = .046), hepatocyte growth factor (P = .046), placental growth factor (P < .001), stromal-derived factor-1 (P = .04), and macrophage chemoattractant protein-3 (P < .001).



Efficacy and tolerability of FOLFIRI + B appeared favorable to historical controls in this single arm study. Before radiographic progression, there was a shift in balance of CAFs, with a rise in alternate pro-angiogenic cytokines and myeloid recruitment factors in subsets of patients that may represent mechanisms of resistance.
Use of Non-Occupational Post-Exposure Prophylaxis does not Lead to an Increase in High Risk Sex Behaviors in Men Who have Sex with Men Participating in the EXPLORE Trial

Non-occupational post-exposure prophylaxis (nPEP) use is an HIV prevention strategy that has been recommended by the CDC to prevent HIV infection after a high risk sexual exposure since 1997. In a behavioral intervention trial of 4,295 MSM we assessed perceptions and use of nPEP over 4 years in six cities across the United States. Overall, 1.9% of MSM reported use of nPEP prior to enrollment, and 6.3% at least once during the trial. Awareness of nPEP was reported by 47.5%, with higher awareness in two sites with funded nPEP programs. Three seroconversions occurred in the 384 visits where nPEP courses were reported, with no effect of nPEP on risk of HIV acquisition in this cohort (hazard ratio = 0.91, 95% confidence interval [0.29, 2.86]). NPEP users were a riskier group: increased odds of nPEP use were observed in association with multiple partners and unprotected receptive and insertive anal sex with HIV infected partners and partners with unknown HIV status. NPEP use was also associated with use of illicit drugs (injection drugs, crack cocaine, hallucinogens, and amphetamines). Importantly, willingness to use nPEP after high risk sex was associated with lower odds of high risk sex. After an episode of nPEP use, nPEP users remained more likely to report high risk sex than those in this cohort who had not previously used nPEP. However, within the subset of people who had previously reported high risk sex, previous nPEP use was not associated with higher odds of high risk sex, thus allaying fears that availability of nPEP would lead to an increase in high risk sex.
Supraventricular tachyarrythmia prophylaxis after coronary artery surgery in chronic obstructive pulmonary disease patients (early amiodarone prophylaxis trial).

Supraventricular tachyarrhythmias (SVT) is common after coronary artery bypass grafting in chronic obstructive pulmonary disease (COPD). Preoperative FEV(1) is the major predetermining factor of mortality, morbidity and SVT.



Patients were divided into two groups according to their preoperative FEV(1) values. FEV(1) is <75% of predicted value in group 1 (no. 200), and >/=75% of predicted value in group 2 (no. 100). Group 1 is divided into two subgroups. SVT prophylaxis was not done in A subgroup (no. 100) whereas arrhythmia prophylaxis was done with amiodarone in all B subgroups (no. 100) in the early postoperative period.



Atrial fibrillation developed in 28 patients in group 1A, whereas it developed in 12 in group 1B (P=0.005). Atrial flutter developed in 10 patients in group 1A but in 3 patients in group 1B (P=0.045). Multifocal atrial tachycardia developed in 13 patients in group 1A and in 4 in group 1B (P=0.022). Multivariate analysis identified ejection fraction (P<0.002, odds ratio (OR) 0.93), inotropy requirement (P<0.001, OR 3.98) amiodarone (P<0.001, OR 0.18), and FEV(1)<75% of predicted value (P<0.048, OR 1.84) as predictor of SVT. There were statistically significant differences between A and B subgroups of group 1 for hospital (P<0.001) and intensive care unit (ICU) stay (P<0.001). There was also statistically significant difference between groups 1A and 2 comparison for ICU (P<0.001; 6.4+/-3.4 versus 1.4+/-0.6 days) and hospital stay (P<0.001; 17.6+/-8.2 versus 6.9+/-0.6 days).



Early prophylactic amiodarone not only significantly reduces SVT but also reduces SVT-related hospital and ICU stay. We strongly recommend prophylactic early use of amiodarone in COPD patients.
DNA analysis, chemoresistance testing and hormone receptor levels as prognostic factors in advanced ovarian carcinoma

Fifty patients with advanced (stage III or IV) ovarian carcinoma were followed-up until the date of their death or their fifth year of survival. Prognostic factors, including those currently in use, as well as ploidy and proliferation, chemoresistance testing and hormone receptor levels of the tumours were analysed for predictive value and independence from each other. In the univariate analysis, only stage, residual tumour, second-look status, chemoresistance, ploidy and proliferation were significantly correlated with survival. After being tested in a multivariate Cox regression model, however, only the results of chemoresistance testing at initiation of therapy, and second-look status at a later point, retained prognostic significance. Within the group of patients with a positive second-look, i.e., with the worst prognosis, the chemoresistance test was still able to discriminate between two subgroups with significantly different survival.
Pexelizumab, an anti-C5 complement antibody, as adjunctive therapy to primary percutaneous coronary intervention in acute myocardial infarction: the COMplement inhibition in Myocardial infarction treated with Angioplasty (COMMA) trial.

Complement, activated during myocardial ischemia and reperfusion, causes myocardial damage through multiple processes. The COMplement inhibition in Myocardial infarction treated with Angioplasty (COMMA) trial was performed to determine the effect of pexelizumab, a C5 complement inhibitor, on infarct size in patients with ST-segment-elevation myocardial infarction (MI) undergoing primary percutaneous coronary intervention.



In COMMA, 960 patients with MI (20% isolated inferior MI) were randomized to placebo, pexelizumab 2.0-mg/kg bolus, or pexelizumab 2.0-mg/kg bolus and 0.05-mg/kg per h infusion for 20 hours. Infarct size by creatine kinase-MB area under the curve, the primary outcome, did not differ significantly between groups (placebo median, 4393; bolus pexelizumab, 4526; bolus plus infusion pexelizumab, 4713 [ng/mL] x h; P=0.89 for bolus versus placebo; P=0.76 for bolus plus infusion versus placebo), nor did the composite of 90-day death, new or worsening heart failure, shock, or stroke (placebo, 11.1%; bolus, 10.7%; bolus plus infusion, 8.5%). The ninety-day mortality rate was significantly lower with pexelizumab bolus plus infusion (1.8% versus 5.9% with placebo; nominal P=0.014); the bolus-only group had an intermediate mortality rate (4.2%).



In patients with ST-elevation MI undergoing percutaneous coronary intervention, pexelizumab had no measurable effect on infarct size. However, the significant reduction in mortality suggests that pexelizumab may benefit patients through alternative novel mechanisms and provides impetus for additional investigation.