nils-herrmann/clean_scirepeval huggingface dataset:
Double-blind placebo-controlled randomised trial of vitamin E and pentoxifylline in patients with chronic arm lymphoedema and fibrosis after surgery and radiotherapy for breast cancer.

Treatment-induced arm lymphoedema is a common and distressing complication of curative surgery and radiotherapy for early breast cancer. A number of studies testing alpha-tocopherol (vitamin E) and pentoxifylline suggest evidence of clinical regression of superficial radiation-induced fibrosis but there is only very limited evidence from randomised trials. Arm lymphoedema after lymphatic radiotherapy and surgery has been used in the present study as a clinical system for testing these drugs in a double-blind placebo-controlled randomised phase II trial.



Sixty-eight eligible research volunteers with a minimum 20% increase in arm volume at a median 15.5 years (range 2-41) after axillary/supraclavicular radiotherapy (plus axillary surgery in 51/68 (75%) cases) were randomised to active drugs or placebo. All volunteers were given dl-alpha tocopheryl acetate 500 mg twice a day orally plus pentoxifylline 400 mg twice a day orally, or corresponding placebos, for 6 months. The primary endpoint was volume of the ipsilateral limb measured opto-electronically using a perometer and expressed as a percentage of the contralateral limb volume.



At 12 months post-randomisation, there was no significant difference between treatment and control groups in terms of arm volume. Absolute change in arm volume at 12 months was 2.5% (95% CI -0.40 to 5.3) in the treatment group compared to 1.2% (95% CI -2.8 to 5.1) in the placebo group. The difference in mean volume change between randomisation groups at 12 months was not statistically significant (P = 0.6), -1.3% (95% CI -6.1 to 3.5), nor was there a significant difference in response at 6 months (P = 0.7), where mean change in arm volume from baseline in the treatment and placebo groups was -2.3% (95% CI -7.9 to 3.4) and -1.1% (95% CI -3.9 to 1.7), respectively. There were no significant differences between randomised groups in terms of secondary endpoints, including tissue induration (fibrosis) in the irradiated breast or chest wall, pectoral fold or supraclavicular fossa, change in photographic breast/chest wall appearance or patient self-assessment of function and Quality of Life at either 6 or 12 months.



The study fails to demonstrate efficacy of dl-alpha tocopheryl acetate plus pentoxifylline in patients with arm lymphoedema following axillary surgery and lymphatic radiotherapy, nor does it suggest any benefits of these drugs in radiation-induced induration (fibrosis) in the breast, chest wall, pectoral fold, axilla or supraclavicular fossa.
The development and first validation of the Manchester Early Morning Symptoms Index (MEMSI) for patients with COPD.

Early morning symptoms (EMS) in people with COPD are associated with poor health, impaired activities and increased exacerbation risk. We describe the development and preliminary validation of the Manchester Early Morning Symptom Index (MEMSI) to quantify EMS in COPD.



Focus groups and cognitive debriefing with patients with COPD were used to develop the potential item list, followed by a cross-sectional study to finalise the items for inclusion. In addition to test-retest reliability, comparisons with the St George's Respiratory Questionnaire-C (SGRQ-C), modified Medical Research Council Dyspnoea Scale, Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-F) and Hospital Anxiety and Depression Scale (HADS) evaluated construct validity. Hierarchical methods informed item deletion and Rasch analysis was applied to assess scale unidimensionality.



23 items were identified from the focus groups and debriefings. The cross-sectional study involved 203 patients with COPD (mean age 64.7 SD 7.5 years, male 63%, Global Initiative for Chronic Obstructive Lung Disease (GOLD): 1:14% 2:41% 3:25% 4: 7%). 13 items were removed during item reduction. MEMSI contains 10 items, demonstrates good overall fit to the Rasch model (χ(2) p=0.26) and item score distribution; excellent reliability (Person Separation Index: 0.91) and good test-retest repeatability (r=0.82). It correlates with the SGRQ-C (r=0.73), FACIT-F (r=-0.65) and HADS (r=0.53-0.54) indicating good construct validity.



MEMSI is a reliable and valid unidimensional measure of EMS for patients with COPD. It is simple to use and score supporting its suitability for research and clinical use. Work is underway to determine the minimal clinical important difference and cross-cultural validity.
Clopidogrel improves systemic endothelial nitric oxide bioavailability in patients with coronary artery disease: evidence for antioxidant and antiinflammatory effects.

Platelet stimulation and activation are known not only as prerequisite of clot formation but are increasingly recognized as important contributors to inflammation and vascular injury. The present study in patients with symptomatic coronary disease investigated whether platelet adenosine diphosphate receptor blockade by clopidogrel exerts beneficial effects on endothelial nitric oxide bioavailability, oxidative stress, and/or inflammatory status.



One hundred three consecutive patients with symptomatic coronary disease and long-term aspirin therapy were studied. Endothelium-dependent and -independent vasodilation was determined measuring forearm blood flow (FBF)-responses to acetylcholine with and without N(G)-monomethyl-L-arginin (L-NMMA) and sodium nitroprusside, by using venous occlusion plethysmography. Patients were randomized to receive additional treatment with clopidogrel or placebo. Vascular function tests were repeated after 5 weeks and showed significant improvement of acetylcholine-induced vasodilatation and L-NMMA responses in the clopidogrel-added group (max. FBF from 9.8+/-0.3 to 14.7+/-0.4; L-NMMA-response from 3.7+/-0.1 to 6.8+/-0.3 mL/100 mL/min). In contrast, no significant changes were observed in the placebo group. Sodium nitroprusside-induced vasodilation was not changed in either group. Urinary excretion of 8-iso-prostaglandin F2alpha and plasma levels of hsCRP, sCD40L, and RANTES were reduced in patients on additional treatment with clopidogrel, but not in patients on placebo.



Clopidogrel improves endothelial nitric oxide bioavailability and diminishes biomarkers of oxidant stress and inflammation in patients with symptomatic coronary artery disease, suggesting that beyond inhibition of platelet aggregation, adenosine phosphate receptor blockade may also have promising vasoprotective effects.
Phase III placebo-controlled, double-blind, randomized trial of pegfilgrastim to reduce the risk of febrile neutropenia in breast cancer patients receiving docetaxel/cyclophosphamide chemotherapy

Pegfilgrastim is a pegylated form of filgrastim, a recombinant protein of granulocyte colony-stimulating factor, that is used to reduce the risk of febrile neutropenia (FN). Here, we report the results of a phase III trial of pegfilgrastim in breast cancer patients receiving docetaxel and cyclophosphamide (TC) chemotherapy. We conducted a double-blind, placebo-controlled, randomized trial to determine the efficacy of pegfilgrastim in reducing the risk of FN in early-stage breast cancer patients. A total of 351 women (177 in the pegfilgrastim group and 174 in the placebo group) between 20 and 69 years of age with stage I–III invasive breast carcinoma who were to receive TC chemotherapy (docetaxel 75 mg/m2 and cyclophosphamide 600 mg/m2 every 3 weeks) as either neoadjuvant or adjuvant therapy were enrolled; 346 of these patients were treated with either pegfilgrastim (n = 173) or placebo (n = 173). The incidence of FN was significantly lower in the pegfilgrastim group than in the placebo group (1.2 vs. 68.8 %, respectively; P < 0.001). In addition, patients in the pegfilgrastim group required less hospitalization and antibiotics for FN. Most adverse events were consistent with those expected for breast cancer subjects receiving TC chemotherapy. Pegfilgrastim is safe and significantly reduces the incidence of FN in breast cancer patients.
Evaluation of CYP2D6 and efficacy of tamoxifen and raloxifene in women treated for breast cancer chemoprevention: results from the NSABP P1 and P2 clinical trials.

Controversy exists regarding the association between CYP2D6 enzyme activity and tamoxifen effectiveness in the adjuvant treatment of invasive breast cancer; however, this association in the primary prevention of breast cancer is unknown.



We conducted a nested case-control study in the context of the NSABP P1 and P2 prevention trials to determine the impact of CYP2D6 genotype, CYP2D6 inhibitor use, and metabolizer status (CYP2D6 genotype combined with CYP2D6 inhibitor use), on breast cancer events. Women who developed breast cancer (both noninvasive and invasive) while on 5 years of selective estrogen receptor modulators therapy (cases) were matched to controls free of breast cancer. Comprehensive CYP2D6 genotyping was conducted for alleles associated with absent (*3, *4, *5, and *6), reduced (*10, *17, and *41), and increased (*1XN and *2XN) enzyme activity. Information regarding the use of CYP2D6 inhibitors was recorded.



A total of 591 cases were matched to 1,126 controls and DNA was genotyped in more than 97%. In patients treated with tamoxifen, there was no association of CYP2D6 genotype [OR (extensive/poor metabolizer): 0.90; 95% CI: 0.46-1.74, P = 0.74), use of a potent CYP2D6 inhibitor (OR 0.92; 95% CI: 0.575-1.486), or CYP2D6 metabolizer status (OR 1.03; 95% CI: 0.669-1.607) with breast cancer occurrence. Likewise, there was no association between any CYP2D6 metabolism parameter with breast cancer events in raloxifene-treated patients.



In the NSABP P1 and P2 clinical trials, alterations in CYP2D6 metabolism are not associated with either tamoxifen or raloxifene efficacy.
Cyclosporine and mycophenolate mofetil prophylaxis with fludarabine and melphalan conditioning for unrelated donor transplantation: a prospective study of 22 patients with hematologic malignancies

In an attempt to decrease toxicity in high-risk patients undergoing unrelated donor hematopoietic stem cell transplantation (URD HSCT), we tested a combination of cyclosporine (CSP) and mycophenolate mofetil (MMF) as graft-versus-host disease (GVHD) prophylaxis with the reduced-intensity conditioning regimen fludarabine/melphalan (Flu/Mel). A total of 22 adult patients with advanced myeloid (n=15) and lymphoid (n=7) malignancies were treated. All patients received Flu 25 mg/m2 for 5 days and Mel 140 mg/m2, with CSP 3 mg/kg daily and MMF 15 mg/kg three times a day. The median age was 49 years (range 18–66). Durable engraftment was seen in all but one patient with myelofibrosis. The 1-year nonrelapse mortality was 32%, 27% from GVHD. The cumulative incidence of acute GVHD grade 2–4 and 3–4 was 63 and 41%, respectively. With a median follow-up of 18 months, the disease-free survival (DFS) and overall survival (OS) are 55 and 59%, respectively. For patients with AML and MDS (n=14), the DFS and OS is 71%. For patients undergoing a second transplant (n=14), the DFS and OS is 57%. In conclusion, this regimen is associated with acceptable toxicity but high rates of GVHD in high-risk patients undergoing URD HSCT. Encouraging disease control for patients with advanced myeloid malignancies was observed.
The Effects of Low Doses of Δ-9 Tetrahydrocannabinol on Reinforcement Processing in the Risky Decision-Making of Young Healthy Adults

Research suggests that risky decision-making is sensitive to neuromodulatory influences acting upon corticolimbic circuitry. However, while other evidence attests to effects of Δ-9 tetrahydrocannabinol (THC) on the activity of reward pathways, relatively little is known about the possible involvement of cannabinoid activity in risky choice. In this experiment, we examined the effects of a single sublingual 5 mg dose of THC on a test of risky decision-making (requiring choices between simultaneously presented gambles differing in their magnitude of gains, magnitude of losses and the probability with which these outcomes were delivered). Tests of non-normative decision-making involving risk-aversion when deciding between gains and risk-seeking choices when deciding between losses were also included. In all, 15 healthy adults were administered 5 mg THC and placebo in a double-blind, placebo-controlled, within-subject, cross-over design. THC had three principal effects relative to placebo: (i) THC reduced choice of gambles with variable gains and losses, but increased choice of gambles with zero-expected value; (ii) THC reduced participants' attention towards losses when the probability of winning was low (and the probability of losing was high); and (iii) THC speeded participants' responses to gambles with large compared to small potential gains. These results suggest that THC mediates specific motivational processes and the processing of reinforcement cues during risky choice, perhaps reflecting altered CB1 receptor or catecholamine activity within corticolimbic pathways.
Reduced-intensity conditioning for myeloma: lower nonrelapse mortality but higher relapse rates compared with myeloablative conditioning.

Despite the widespread adoption of reduced-intensity conditioning (RIC) for myeloma, there are few data comparing outcomes with RIC with myeloablative conditioning (MAC). We report the outcomes of patients undergoing allogeneic transplantations for myeloma and reported to the EBMT. A minimum data set was available on 320 RIC and 196 MAC allografts performed between 1998 and 2002. The RIC patients were older (51 vs 45 years) with more progressive disease (28% vs 21%) and more had received a prior transplant (76% vs 11%). In addition, there was a longer time to transplantation and an increased use of peripheral blood and T-cell depletion. For RIC and MAC, respectively, the nonrelapse mortality (NRM) at 2 years was 24% and 37% (P = .002); overall survival, 38.1% and 50.8% (not significant [ns]); and progression-free survival (PFS), 18.9% and 34.5% (P = .001). On multivariate analysis, RIC was associated with a reduction in NRM (HR, 0.5), but this was offset by an increase in relapse risk (HR, 2.0), and the conditioning intensity did not impact on overall survival or retain significance for PFS. These data suggest that there is a continuing need to investigate dose intensity in the conditioning for myeloma allografts.
Physiological effects of nonthyroidal illness syndrome in patients after cardiac surgery.

In a prospective randomized placebo-controlled study, we assessed potential physiological effects of nonthyroidal illness syndrome (NTIS) in acute illness. Coronary artery bypass graft surgery was employed as a prospective model of acute illness and NTIS. Triiodothyronine (T(3)) or placebo was infused for 24 h after surgery, with a T(3) dose selected to maintain postoperative serum T(3) concentrations at preoperative levels. Patients were evaluated before coronary artery bypass graft and during the postoperative period. Cardiovascular function was monitored with Swan-Ganz catheter measurements and ECG. Urinary nitrogen excretion and L-[1-(13)C]leucine flux were used to evaluate protein metabolism. Serum measurements of relevant hormones, iron, and total iron-binding capacity were used to assess effects on sex steroid, growth hormone axis, and iron responses to illness. Cardiovascular function was not affected by T(3) infusion, except for a transient higher cardiac index in the T(3) group 6 h after surgery (3.04 +/- 0.12 for T(3) and 2.53 +/- 0.08 for placebo, P = 0.0016). Protein metabolism was not affected; changes in urinary nitrogen excretion and L-[1-(13)C]leucine flux were equivalent in the two groups (P = 0.35 and P = 0.95, respectively). No differences were observed in changes in testosterone, estrogens, growth hormone, insulin-like growth hormone I, iron, or total iron-binding capacity between T(3) and placebo groups. We conclude that, in the early stages of major illness, the decrease in circulating T(3) concentrations in NTIS has only a minimal transient physiological impact on cardiac function and plays no significant role in protecting against protein catabolism or modulating other endocrine responses or iron responses to illness.
Long-term outcomes and prognostic factors in patients treated with intraoperatively planned prostate brachytherapy.

Evaluate outcomes and prognostic factors in men with localized prostate cancer.



A total of 3760 patients have undergone prostate seed implantation at our institution. This review is of our initial 304 consecutive patients treated before January 30, 2001. A total of 124 patients were treated with (125)I implant monotherapy and 180 with (103)Pd implant combined with 45-Gy external beam radiation therapy.



The median followup was 10.3 years. A 10-year biochemical control for low risk (LR) was 98% , intermediate risk (IR) 94%, high risk (HR) 78%, and HR with one HR factor 88% (p < 0.001); cause-specific survival was 99%, 98%, and 84% for LR, IR, and HR, respectively (p < 0.001); No significant difference in outcome was seen for LR and IR patients (p > 0.3). On multivariate analysis, only pretreatment PSA, Gleason score, and T-stage were significant for biochemical control. Most biochemical failures occurred within 5 years (93%).



With a minimum followup of 10 years, results are excellent and do not differ for LR or IR prostate cancer patients. HR patients are a very heterogeneous group, and excellent results can still be achieved for HR patients with only one HR feature.
Prevalence and clinical outcome of polyvascular atherosclerotic disease in patients undergoing coronary intervention.

The goal of this study was to evaluate the prevalence and outcomes of polyvascular disease (polyVD; defined as lower extremity artery disease, carotid artery disease, renal artery disease, or abdominal aortic aneurysm) in patients undergoing percutaneous coronary intervention (PCI).



The subjects were 1,597 patients who underwent PCI and who were prospectively enrolled in the study. The carotid, renal and peripheral arteries and abdominal aorta were simultaneously evaluated using duplex ultrasound and ankle-brachial index to evaluate the presence of polyVD. The primary endpoint was major adverse cardiovascular events (MACE: cardiovascular death, myocardial infarction [MI], and stroke). PolyVD was found in 446 of 1,597 patients (27.9%). MACE were significantly higher in the polyVD group compared to those with coronary artery disease (CAD) alone (n=1,151; 12.1% vs. 3.8%, P<0.0001). The incidence of cardiovascular death and stroke were significantly higher in the polyVD group (7.9% vs. 1.6%, P<0.0001; 3.6% vs. 1.2%, P=0.006, respectively). The incidence of MI was similar in the 2 groups (3.7% vs. 1.3%, P=0.08). The adjusted hazard ratios for MACE in patients with 1, 2, and 3 arterial beds (compared with CAD alone) increased from 1.64 to 1.74 to 10.62 (P<0.0001).



There was a high incidence of MACE in patients with polyVD undergoing PCI and this incidence increased with the number of arterial beds.
Cyclophosphamide induces differentiation of Th17 cells in cancer patients.

Low doses of the alkylating agent cyclophosphamide (CTX) mediate antiangiogenic and immunostimulatory effects, leading to potent tumoricidal activity in association with various immunotherapeutic strategies. Here, we show in rodents and cancer patients that CTX markedly promotes the differentiation of CD4(+) T helper 17 (Th17) cells that can be recovered in both blood and tumor beds. However, CTX does not convert regulatory T cells into Th17 cells. Because Th17 are potent inducers of tissue inflammation and autoimmunity, these results suggest impact on the clinical management of various types of malignancies treated with alkylating agents and a potential need to optimize CTX-based immunotherapy in patients.
Unmet care demands as perceived by stroke patients: deficits in health care?

To describe unmet care demands as perceived by stroke patients and to identify sociodemographic and health characteristics associated with these unmet demands to investigate the appropriateness of health care.



Sample of patients who participated in a multicentre study (23 hospitals) on quality of care in The Netherlands.



Non-institutionalised patients who had been admitted to hospital because of stroke. Patients were interviewed six months (n = 382) and five years (n = 224) after stroke.



Six months after stroke data were collected on: (a) sociodemographic characteristics in terms of age, sex, living arrangement, educational level, and regional level of urbanisation; (b) health characteristics in terms of cognitive function, disability, emotional distress, and general health perception; (c) utilisation of professional care; and (d) unmet care demands as perceived by patients. Data on utilisation of care and unmet demands were also collected five years after stroke. Data were collected from June 1991 until December 1996.



The percentage of unmet care demands was highest at six months after stroke (n = 120, 31%). Multiple logistic regression analyses showed that disabled patients were more likely to be unmet demanders for therapy, (I)ADL care and aids (range odds ratio (OR) = 3.5 to 7.9) than to be no demanders, whereas emotionally distressed patients were more likely to be unmet demanders for psychosocial support (OR = 3.8). When comparing unmet demanders with care users only for (instrumental) activities of daily living (I)ADL care differences were found: men (OR = 3.8), disabled patients (OR = 3.0), and emotionally distressed patients (OR = 6.5) were more likely to be users.



Patients who perceived an unmet care demand do appear genuinely to have an unmet care need as supported by assessment of their health status: (a) types of unmet care demands correspond with types of health problems and (b) unmet demanders were in general unhealthier than no demanders and more comparable with care users for health characteristics.



To improve an equitable distribution of healthcare services, guidelines for indicating and allocating health care have to be developed and should be based on scientific evidence and consensus meetings including professionals' and patients' perspectives.
Early and repetitive stimulation of the arm can substantially improve the long-term outcome after stroke: a 5-year follow-up study of a randomized trial.

Several studies have investigated the effect of therapeutic interventions for the arm in the acute phase after stroke, with follow-ups at a maximum of 12 months. The aim of this study was to examine the effect of repetitive sensorimotor training of the arm at 5 years after stroke.



One hundred consecutive stroke patients were randomly allocated either to an experimental group that received daily additional sensorimotor stimulation of the arm or to a control group. The intervention period was 6 weeks. Assessments of the patients were made before, midway, and after intervention, and at 6 and 12 months after stroke. In this study, 62 patients were reassessed at 5 years after stroke. The Brunnström-Fugl-Meyer (BFM) test, Action Research Arm (ARA) test, and Barthel index (BI) were used as the primary outcome measures.



At the 5-year follow-up, there was a statistically significant difference for both the BFM and ARA tests in favor of the experimental group. The mean differences in improvement between the groups from the initial evaluation to the 5-year assessment corresponded to 17 points on the BFM and 17.4 on the ARA. No effect was found for the BI. The treatment was most effective in patients with a severe initial motor deficit.



Adding a specific intervention for the arm during the acute phase after a stroke resulted in a clinically meaningful and long-lasting effect on motor function. The effect can be attributed to early, repetitive, and targeted stimulation.