nils-herrmann/clean_scirepeval huggingface dataset:
Screening and treatment of psychological distress in patients with metastatic colorectal cancer: study protocol of the TES trial

Psychological distress occurs frequently in patients with cancer. Psychological distress includes mild and severe forms of both anxious and depressive mood states. Literature indicates that effective management of psychological distress seems to require targeted selection of patients (T), followed by enhanced care (E), and the application of evidence based interventions. Besides, it is hypothesized that delivering care according to the stepped care (S) approach results in an affordable program. The aim of the current study is to evaluate the (cost)-effectiveness of the TES program compared to usual care in reducing psychological distress in patients with metastatic colorectal cancer (mCRC). This study is designed as a cluster randomized trial with 2 treatment arms: TES program for screening and treatment of psychological distress versus usual care. Sixteen hospitals participate in this study, recruiting patients with mCRC. Outcomes are evaluated at the beginning of chemotherapy and after 3, 10, 24, and 48 weeks. Primary outcome is the difference in treatment effect over time in psychological distress, assessed with the Hospital Anxiety and Depression Scale. Secondary outcomes include quality of life, patient evaluation of care, recognition and management of psychological distress, and societal costs. We created optimal conditions for an effective screening and treatment program for psychological distress in patients with mCRC. This involves targeted selection of patients, followed by enhanced and stepped care. Our approach will be thoroughly evaluated in this study. We expect that our results will contribute to the continuing debate on the (cost-) effectiveness of screening for and treatment of psychological distress in patients with cancer.
Statins promote potent systemic antioxidant effects through specific inflammatory pathways.

The pleiotropic actions of hydroxymethylglutaryl CoA reductase inhibitors (statins) include antiinflammatory and antioxidant actions. We recently reported that statins induce reductions in plasma protein levels of nitrotyrosine (NO2Tyr), a modification generated by nitric oxide-derived oxidants. Whether alternative oxidative pathways are suppressed in vivo after statin administration has not yet been reported.



As an extension of our prior study, hypercholesterolemic subjects with no known coronary artery disease were evaluated at baseline and after 12 weeks of atorvastatin therapy (10 mg/d). Plasma levels of protein-bound chlorotyrosine, NO2Tyr, dityrosine, and orthotyrosine, specific molecular fingerprints for distinct oxidative pathways upregulated in atheroma, were determined by mass spectrometry. In parallel, alterations in lipoproteins and C-reactive protein were determined. Statin therapy caused significant reductions in chlorotyrosine, NO2Tyr, and dityrosine (30%, 25%, and 32%, respectively; P<0.02 each) that were similar in magnitude to reductions in total cholesterol and apolipoprotein B-100 (25% and 29%, P<0.001 each). Nonsignificant decreases in orthotyrosine and C-reactive protein levels were observed (9% and 11%, respectively; P>0.10 each). Statin-induced reductions in oxidation markers were independent of decreases in lipids and lipoproteins.



Statins promote potent systemic antioxidant effects through suppression of distinct oxidation pathways. The major pathways inhibited include formation of myeloperoxidase-derived and nitric oxide-derived oxidants, species implicated in atherogenesis. The present results suggest potential mechanisms that may contribute to the beneficial actions of statins. They also have important implications for monitoring the antiinflammatory and antioxidant actions of these agents.
Minimal residual disease after intensive induction therapy in childhood acute lymphoblastic leukemia predicts outcome

We investigated the level of minimal residual disease (MRD) in 26 children with B-lineage acute lymphoblastic leukemia (ALL) after intensive induction therapy. A quantitative semi-nested polymerase chain reaction (PCR) detecting the clone-specific rearranged immunoglobulin heavy chain genes was developed to improve sensitivity and specificity of amplification. In all patients, one leukemic cell could be detected in a background of 105 normal blood mononuclear cells. All patients investigated were in complete remission at the end of induction therapy as evaluated by morphologic criteria. Nineteen patients (73%) had no detectable residual leukemic cells using the sensitive semi-nested PCR. Seven patients (27%) were PCR positive. Three had a low level (<2 × 10−5 leukemic cells per bone marrow cell), while four patients had a high level (>2 × 10−5) of detectable residual leukemic cells. All patients with low or undetectable levels of residual leukemia remained in complete remission at a median of 63 months from diagnosis (range 40–80 months), while all four patients with a high level of residual leukemia subsequently relapsed at a median of 21 months from diagnosis (range 13–37 months). The patient groups with undetectable or low, and high level of MRD did not differ significantly in other clinical or genetic features with prognostic significance. We conclude that the level of MRD at the end of the intensive induction therapy period is predictive of outcome in childhood B lineage ALL. If confirmed by large prospective studies, the level of MRD might be useful in stratifying patients into high and low risk categories.
Risk prediction by genetic risk scores for coronary heart disease is independent of self-reported family history

Genetic risk scores (GRSs) have been associated with coronary heart disease (CHD) in large studies. We asked whether expanding an established 27-variant GRS (GRS27) to a 50-variant GRS (GRS50) improved CHD prediction and whether GRSs are independent of self-reported family history of CHD.



The association between GRSs and incident CHD was assessed in Cox models adjusting for established risk factors in 23 595 participants of the Malmö Diet and Cancer study--a prospective, population-based study. During a median follow-up of 14.4 years, 2213 participants experienced a first CHD event. After adjustment for established risk factors, both GRS27 and GRS50 were associated with incident CHD [hazard ratio (HR) = 1.70 for high (top quintile) vs. low (bottom quintile) of GRS27; 95% confidence interval (CI): 1.48-1.94; Ptrend = 1.6 × 10(-15) and HR = 1.92 for GRS50; 95% CI: 1.67-2.20; Ptrend = 6.2 × 10(-22)]. Adding 23 single nucleotide polymorphisms (SNPs) to GRS27 improved risk prediction (P = 3 × 10(-6)). Further adjustment for self-reported family history did not appreciably change the risk estimates of either GRS27 (HR = 1.65; 95% CI: 1.45-1.89) or GRS50 (HR = 1.87; 95% CI: 1.63-2.14). The addition of GRS50 to established risk factors, including self-reported family history, improved discrimination (P < 0.0001) and reclassification (continuous net reclassification improvement index = 0.17, P < 0.0001). In young participants (below median age), those with high GRS50 had 2.4-fold greater risk (95% CI: 1.85-3.12) than those with low GRS50.



The addition of 23 SNPs to an existing GRS27 improved CHD risk prediction and was independent of self-reported family history. Coronary heart disease risk assessment by GRS could be particularly useful in young individuals.
A single-center, randomized, double-blind, active, and placebo-controlled study of KAI-1678, a novel PKC-epsilon inhibitor, in the treatment of acute postoperative orthopedic pain.

KAI-1678, a novel inhibitor of the interaction of the epsilon isoform of protein kinase C (εPKC) with its intracellular receptor, has demonstrated activity in countering hyperalgesia in several models of pain. In this controlled randomized trial, KAI-1678 was tested for analgesic activity in an orthopedic acute postoperative pain setting.



Following hip or knee replacement surgery, subjects were treated with KAI-1678, ketorolac, or saline. Subjects recorded their pain intensity on a visual analog scale and rated their quality of analgesia. The pain intensity differences between baseline and the evaluations were summed over the first 4 hours.



The analysis revealed that, while ketorolac displayed good analgesic activity, KAI-1678 was not significantly different than placebo. Analgesia quality ratings similarly did not show a difference between KAI-1678 and placebo in this pain model. A small excess of infusion site erythema was seen with KAI-1678, but otherwise the drug was safe and well tolerated.



We investigated the safety and efficacy of a novel inhibitor of εPKC and provide clinical evidence that inhibition of εPKC with KAI-1678 is not effective in the treatment of acute postoperative orthopedic pain.
Inhomogeneity in response to air pollution in European children (PEACE project).

The PEACE study is a multicentre panel study of the acute effects of particles with a 50% cut off aerodynamic diameter of 10 microns (PM10), black smoke (BS), sulphur dioxide (SO2), and nitrogen dioxide (NO2) on respiratory health of children with chronic respiratory symptoms. In the complete panels no consistent association between air pollution and respiratory health was found. The study evaluated whether potentially more sensitive subgroups in the panels did show effects of air pollution.



To evaluate heterogeneity in response to air pollution, effect estimates of air pollution on peak expiratory flow (PEF) and respiratory symptoms were calculated in subgroups based on presence of chronic respiratory symptoms, use of respiratory medication, atopy, sex, and baseline lung function.



The association between PEF and air pollution was positive in asthmatic children who used respiratory medication whereas the associations tended to be negative in children who did not use respiratory medication selected only on cough. No consistent association was found among asthmatic children who did not use medication. The association between daily prevalence of symptoms and concentrations of air pollution was not different between these subgroups.



None of the predefined potentially more sensitive subgroups showed a consistent association between air pollution, PEF, and respiratory symptoms.
Ofatumumab as single-agent CD20 immunotherapy in fludarabine-refractory chronic lymphocytic leukemia.

New treatments are needed for patients with fludarabine- and alemtuzumab-refractory (FA-ref) chronic lymphocytic leukemia (CLL) or patients with fludarabine-refractory CLL with bulky (> 5 cm) lymphadenopathy (BF-ref) who are less suitable for alemtuzumab treatment; these groups have poor outcomes with available salvage regimens. Ofatumumab (HuMax-CD20) is a human monoclonal antibody targeting a distinct small-loop epitope on the CD20 molecule. We conducted an international clinical study to evaluate the efficacy and safety of ofatumumab in patients with FA-ref and BF-ref CLL.



Patients received eight weekly infusions of ofatumumab followed by four monthly infusions during a 24-week period (dose 1 = 300 mg; doses 2 to 12 = 2,000 mg); response by an independent review committee (1996 National Cancer Institute Working Group criteria) was assessed every 4 weeks until week 24 and then every 3 months until month 24.



This planned interim analysis included 138 treated patients with FA-ref (n = 59) and BF-ref (n = 79) CLL. The overall response rates (primary end point) were 58% [corrected] and 47% in the FA-ref and BF-ref groups, respectively. Complete resolution of constitutional symptoms and improved performance status occurred in 57% and 48% of patients, respectively. Median progression-free survival and overall survival times were 5.7 and 13.7 months in the FA-ref group, respectively, and 5.9 and 15.4 months in the BF-ref group, respectively. The most common adverse events during treatment were infusion reactions and infections, which were primarily grade 1 or 2 events. Hematologic events during treatment included anemia and neutropenia.



Ofatumumab is an active, well-tolerated treatment providing clear clinical improvements for fludarabine-refractory patients with very poor-prognosis CLL.
Adiponectin is Not Associated With Blood Pressure in Normotensives and Untreated Hypertensives With Normal Kidney Function

The role of adiponectin in hypertension is still a matter of debate. Obtained conflicting results could be mostly explained with diversity of subjects included in different studies. Our aim was to analyze association of adiponectin with blood pressure (BP) in a group of normotensive and untreated hypertensive subjects. Participants (N=257) were selected from a random sample of 2487 subjects enrolled in an observational cross-sectional study. Subjects with diabetes and chronic kidney diseases were excluded. BP was measured using Omron M6 device following ESH/ESC guidelines. Adiponectin concentration was determined by ELISA. There were no differences in adiponectin values (mg/L) between hypertensives and normotensives (median 9.75; iqr: 7.44-17.88 vs 11.35; iqr: 7.43-12.63; P=0.17). On univariate linear regression adiponectin was not associated with systolic or diastolic BP (P>0.05). Furthermore, multivariate analysis did not show significant contribution of log-transformed adiponectin either to systolic (β=-0.040; P=0.43) or diastolic BP (β=0.066; P=0.33). In our group of normotensives and untreated hypertensives with normal kidney function adiponectin was not associated with BP even after adjustment for other risk factors. Our results and conclusions should not be extrapolated to subjects with other characteristics.
CT screening for lung cancer.

Recommendations against screening for lung cancer were based on the lack of a reduction in mortality of the screened group as compared with the control group in randomized control trials. These results were interpreted as showing that early detection of lung cancer as a result of screening did not decrease the mortality rate compared with detection after presentation of symptoms for the populations being screened. Evidence, however, shows that earlier-stage intervention leads to substantially higher rates of survival. Screening, therefore, is an effective means to prevent deaths from this otherwise fatal disease. This article discusses the evidence of both CT and chest radiograph screening.
Impact of dialysis modality on survival after kidney transplant failure.

An increasing number of patients are returning to dialysis after allograft loss (DAGL). These patients are at a higher mortality risk compared with incident ESRD patients. Among transplant-naïve patients, those treated with peritoneal dialysis (PD) enjoy an early survival advantage compared with those treated with hemodialysis (HD), but this advantage is not sustained over time. Whether a similar time-dependent survival advantage exists for PD-treated patients after allograft loss is unclear and may impact dialysis modality selection in these patients.



We identified 2110 adult patients who initiated dialysis after renal transplant failure between January 1991 and December 2005 from The Canadian Organ Replacement Register. Multivariable regression analysis was used to evaluate the impact of initial dialysis modality on early (2 years), late (after 2 years), and overall mortality using an intention-to-treat approach.



After adjustment, there was no difference in overall survival between HD- and PD-treated patients (hazard ratio((HD:PD)), 1.05; 95% confidence interval, 0.85 to 1.31), with similar results seen for both early and late survival. Superior survival was seen in more contemporary cohorts of patients returning to DAGL.



The use of PD compared with HD is associated with similar early and overall survival among patients initiating DAGL. Differences in both patient characteristics and predialysis management between patients returning to DAGL and transplant-naive incident dialysis patients may be responsible for the absence of an early survival advantage with the use of PD in DAGL patients.
Sympathetic nervous system activity and cardiovascular homeostasis during head-up tilt in patients with spinal cord injuries

The relationship between sympathetic nervous system activity and cardiovascular responses to head-up tilt in patients with spinal cord injuries and in able-bodied subjects was studied. Twenty-seven adults, nine in each of the three groups (tetraplegia, paraplegia, and able-bodied subjects) were tilted 70°, head up, for 12 minutes after 20 minutes supine rest. Differences between steady-state measurements of mean arterial pressure, stroke volume, and sympathetic nervous system activity were estimated in both positions. Sympathetic nervous system activity was reflected by the low-frequency peak of the blood pressure variability spectrum. From supine rest to head-up tilt, low-frequency power increased in able-bodies subjects (median, 0.42 mm Hg2, p=0.003), which was different (p=0.015) from patients with tetraplegia and paraplegia (−0.15 and −0.10 mm Hg2, respectively). Stroke volume and mean arterial pressure decreased in patients with tetraplegia (−40% and −9 mm Hg, respectively; p=0.008, both variables) more than in ablebodied subjects (−33%, 11 mm Hg, respectively) or patients with paraplegia (−24%, 8 mm Hg, respectively). Results indicated increased sympathetic nervous system activity during head-up tilt in able-bodied subjects, but not in patients with paraplegia or tetraplegia, whereas patients with tetraplegia, but not paraplegia, showed poorer cardiovascular homeostasis than able-bodied subjects. This suggests that patients with paraplegia maintained cardiovascular homeostasis during head-up tilt without increased sympathetic nervous system activity.
Induction of locomotor-like EMG activity in paraplegic persons by orthotic gait training

This is, to our knowledge, the first report demonstrating the effects of orthotic gait training on the activity of the spinal locomotor neural networks. Three subjects with complete spinal cord injury (SCI) performed 1-h training with reciprocating gait orthosis 5 days/week for 12 weeks. The results showed that after 3 (n=1) or 6 weeks (n=2) of training, EMG activities synchronized with locomotor rhythm appeared in the soleus muscle (SOL) in all subjects, although very little EMG activity accompanied the orthotic gait at the early training stage. Our results suggest that the induced modulation in the SOL EMG waveforms might be attributable to changes in the orthotic gait movement pattern, and/or changes in the interneuronal activities of the spinal locomotor neural networks, as a result of orthotic gait training.
Systematic literature review and validity evaluation of the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Functional Composite (MSFC) in patients with multiple sclerosis

There are a number of instruments that describe severity and progression of multiple sclerosis and they are increasingly used as endpoints to assess the effectiveness of therapeutic interventions. We examined to what extent the psychometric properties of two accepted instruments--EDSS and MSFC--meet methodological standards and the value they have in clinical trials.



We conducted a systematic literature search in relevant databases [MEDLINE (PubMed), ISI Web of Science, EMBASE, PsycINFO & PSYNDEX, CINAHL] yielding 3,860 results. Relevant full-text publications were identified using abstract and then full-text reviews, and the literature was reviewed.



For evaluation of psychometric properties (validity, reliability, sensitivity of change) of EDSS and MSFC, 120 relevant full-text publications were identified, 54 of them assessed the EDSS, 26 the MSFC and 40 included both instruments. The EDSS has some documented weaknesses in reliability and sensitivity to change. The main limitations of the MSFC are learning effects and the z-scores method used to calculate the total score. However, the methodological criterion of validity applies sufficiently for both instruments.For use in clinical studies, we found the EDSS to be preferred as a primary and secondary outcome measure in recent studies (50 EDSS, 9 MSFC).



Recognizing their strengths and weaknesses, both EDSS and MSFC are suitable to detect the effectiveness of clinical interventions and to monitor disease progression. Almost all publications identify the EDSS as the most widely used tool to measure disease outcomes in clinical trials. Despite some limitations, both instruments are accepted as endpoints and neither are discussed as surrogate parameters in identified publications. A great advantage of the EDSS is its international acceptance (e.g. by EMA) as a primary endpoint in clinical trials and its broad use in trials, enabling cross-study comparisons.
5α-Reductase Type 1 Modulates Insulin Sensitivity in Men

5α-Reductase (5αR) types 1 and 2 catalyze the A-ring reduction of steroids, including androgens and glucocorticoids. 5α-R inhibitors lower dihydrotestosterone in benign prostatic hyperplasia; finasteride inhibits 5αR2, and dutasteride inhibits both 5αR2 and 5αR1. In rodents, loss of 5αR1 promotes fatty liver.



Our objective was to test the hypothesis that inhibition of 5αR1 causes metabolic dysfunction in humans.



This double-blind randomized controlled parallel group study at a clinical research facility included 46 men (20-85 years) studied before and after intervention.



Oral dutasteride (0.5 mg daily; n = 16), finasteride (5 mg daily; n = 16), or control (tamsulosin; 0.4 mg daily; n = 14) was administered for 3 months.



Glucose disposal was measured during a stepwise hyperinsulinemic-euglycemic clamp. Data are mean (SEM).



Dutasteride and finasteride had similar effects on steroid profiles, with reduced urinary androgen and glucocorticoid metabolites and reduced circulating DHT but no change in plasma or salivary cortisol. Dutasteride, but not finasteride, reduced stimulation of glucose disposal by high-dose insulin (dutasteride by -5.7 [3.2] μmol/kg fat-free mass/min, versus finasteride +7.2 [3.0], and tamsulosin +7.0 [2.0]). Dutasteride also reduced suppression of nonesterified fatty acids by insulin and increased body fat (by 1.6% [0.6%]). Glucose production and glycerol turnover were unchanged. Consistent with metabolic effects of dutasteride being mediated in peripheral tissues, mRNA for 5αR1 but not 5αR2 was detected in human adipose tissue.



Dual inhibition of 5αRs, but not inhibition of 5αR2 alone, modulates insulin sensitivity in human peripheral tissues rather than liver. This may have important implications for patients prescribed dutasteride for prostatic disease.
Hematological recovery and peripheral blood progenitor cell mobilization after induction chemotherapy and GM-CSF plus G-CSF in breast cancer

In order to determine the effect of GM-CSF plus G-CSF in combination in breast cancer patients receiving an effective induction regimen, we compared hematological recovery and peripheral blood progenitor cell (PBPC) mobilization according to colony-stimulating factor (CSF) support. Forty-three breast cancer patients were treated by TNCF (THP-doxorubicin, vinorelbine, cyclophosphamide, fluorouracil, D1 to D4) with CSF support: 11 patients received GM-CSF (D5 to D14); 16 patients G-CSF (D5 to D14) and 16 patients GM-CSF (D5–D14) plus G-CSF (D10–D14). Between two subsequent cycles, progenitor cells were assessed daily, from D13 to D17. The WBC count was similar for patients receiving G-CSF alone or GM-CSF plus G-CSF, but significantly greater than that of patients receiving GM-CSF alone (P < 0.001). The GM-CSF plus G-CSF combination led to better PBPC mobilization, with significantly different kinetics (P < 0.001) and optimal mean values of CFU-GM, CD34+ cells and cells in cycle, at D15 compared to those obtained with G-CSF or GM-CSF alone. The significantly greater PBPC mobilization obtained with a CSF combination by D15 could be of value for PBPC collection and therapeutic reinjection after high-dose chemotherapies. Bone Marrow Transplantation (2000) 25, 705–710.