nils-herrmann/clean_scirepeval huggingface dataset:
A phase II study of amrubicin and carboplatin for previously untreated patients with extensive-disease small cell lung cancer

Amrubicin is active in the treatment of extensive-disease small cell lung cancer (ED-SCLC), and carboplatin is an analogue of cisplatin with less non-hematological toxicity. The purpose of this study was to determine the efficacy and toxicity of amrubicin and carboplatin combination chemotherapy for previously untreated patients with ED-SCLC. Eligibility criteria were chemotherapy-naïve ED-SCLC patients, performance status 0–1, age ≤75, and adequate hematological, hepatic and renal function. Based on the phase I study, the patients received amrubicin 35 mg/m2 i.v. infusion on days 1, 2, and 3, and carboplatin AUC 5 i.v. infusion on day 1. Four cycles of chemotherapy were repeated every 3 weeks. Thirty-five patients were enrolled, and 34 patients were eligible and assessable for response, toxicity, and survival. Patients’ characteristics were as follows: male/female = 26/8; performance status 0/1 = 4/30; median age (range) = 64 (41–75); stage IV = 34. Evaluation of responses was 6 complete response, 21 partial response, and 7 stable disease (response rate 79.4 %, 95 % CI 63.6–88.5 %). Grade 3 and 4 leukopenia, neutropenia, and thrombocytopenia occurred in 59, 82, and 26 %, respectively. There were no treatment-related deaths or pneumonitis. Three patients experienced hypotension as an amrubicin infusion reaction. The median progression-free survival time was 6.5 months. The median overall survival time and 1-, 2-, and 3-year survival rates were 15.6 months, and 63, 28, and 7 %, respectively. Amrubicin and carboplatin were effective and tolerable as chemotherapy for previously untreated patients with ED-SCLC. Further investigation of amrubicin and carboplatin is warranted.
Effect of addition of single dose of oral montelukast to standard treatment in acute moderate to severe asthma in children between 5 and 15 years of age: a randomised, double-blind, placebo controlled trial.

To study the effect of the addition of a single dose of oral montelukast to standard therapy in acute moderate to severe asthma.



Double-blind randomised controlled trial.  Emergency room/outpatient paediatric services of a tertiary care hospital.



Children aged 5-15 years (without prior use of montelukast) with acute moderate to severe asthma exacerbation, as defined using Modified Pulmonary Index Score (MPIS) > or =9, were enrolled.



Children received montelukast (5-12 years: 5 mg and >12 years: 10 mg) or placebo orally in addition to the standard therapy. MPIS and forced expiratory volume in 1 second (FEV(1)) were recorded before administering study medication and thereafter, hourly for 4 hours.



The primary outcome was decrease in MPIS to less than 9 at the end of 4 hours.



117 children (60 in montelukast group and 57 in placebo group) were enrolled in the study. The number of children with decrease in MPIS to less than 9 at 4 hours was 33 (55%) in the montelukast group and 36 (63.2%) in the placebo group (p=0.37). There was significant improvement in MPIS and FEV(1) within both the groups from baseline to the end of 4 hours. No differences in side effects and hospitalisation rates were noticed between the two groups.



Single dose oral montelukast added to standard therapy of inhaled bronchodilators and systemic glucocorticoids did not provide additional clinical benefit in children with acute moderate to severe asthma.
Feasibility of T-cell-based adoptive immunotherapy in the first 12 patients with advanced urothelial urinary bladder cancer. Preliminary data on a new immunologic treatment based on the sentinel node concept.

Expected 2-yr survival for patients with urothelial urinary bladder cancer (UBC) with lymph node involvement (pN2) is 20%, regardless of standard neoadjuvant/adjuvant oncologic treatment. Tumor-reactive lymphocytes are present in sentinel nodes (SNs) draining human bladder cancer and display immunologic function on restimulation in vitro. Metinel nodes (MNs) drain secondarily from metastatic tumors and also possess tumor-reactive lymphocytes, which might be a source for adoptive T-cell immunotherapy.



To determine if MN detection and subsequent expansion of autologous T-helper cells with subsequent reinfusion was feasible and safe to perform in patients with metastatic UBC.



In an open trial, the first 12 included patients are described. Patients were prospectively selected from a single tertiary academic center and had metastatic UBC. All 12 patients were preoperatively staged as T2-T4b N1-2 and/or M0-M1 or MX.



MNs were excised in conjunction with intended cystectomy. T lymphocytes were extracted with enhancement and expansion of tumor specific T-helper cells, followed by reinfusion of expanded T cells.



All patients were preoperatively staged with transurethral resection of the bladder and routine computed tomography scan. Intended detection of MNs was performed intraoperatively with intended cystectomy. Harvested T cells were evaluated and cell cultures were established. Assessment of reinfusion of expanded, autologous, tumor-specific T-helper cells to six of the patients was performed, focusing on adverse effects.



In six patients, it was feasible to administer the treatment. Reinfusion of these T cells was performed without any major adverse effects. In six other patients, we encountered technical failures.



A novel adoptive immunotherapy based on T cells from tumor-draining lymph nodes is feasible in advanced UBC. Infusion of expanded, autologous, tumor-specific T-helper cells might be a future treatment option in metastasized UBC. Long-term overall survival remains to be determined.
Therapy effect of either paclitaxel or cyclophosphamide combination treatment in patients with epithelial ovarian cancer and relation to TP53 gene status.

Cell death after treatment with chemotherapy is exerted by activation of apoptosis, and the p53 protein has been shown to actively participate in this process. This recent focus on TP53 status as a possible determinant of cancer therapy response has raised the question of whether or not mutations in the TP53 gene have an influence on paclitaxel therapy. The TP53 status has been analysed at the DNA level in tumours from 45 ovarian cancer patients randomized to treatment with paclitaxel and cisplatin or cyclophosphamide and cisplatin. Therapy response was obtained for 38 patients with clinically evaluable disease after initial surgery. The positive response rate to the paclitaxel/cisplatin therapy was 85% vs 61% for the patients who received the cyclophosphamide/cisplatin regimen. A significant difference in relapse-free survival in favour of paclitaxel/cisplatin chemotherapy was found (P = 0.001). A total of 33 tumour samples (73%) had detectable sequence alterations in the TP53 gene. When relapse-free survival was estimated for all patients with TP53 alterations in their tumours, a significant better outcome for the paclitaxel/cisplatin group was found compared with the patient group receiving cyclophosphamide and cisplatin therapy (P = 0.002). We did not observe an association between TP53 tumour status and prognosis for patients who received paclitaxel/cisplatin combination treatment, indicating that the effect of this therapy is not influenced by this parameter.
Efficacy and safety of very early mobilisation within 24 h of stroke onset (AVERT): a randomised controlled trial

Early mobilisation after stroke is thought to contribute to the effects of stroke-unit care; however, the intervention is poorly defined and not underpinned by strong evidence. We aimed to compare the effectiveness of frequent, higher dose, very early mobilisation with usual care after stroke.



We did this parallel-group, single-blind, randomised controlled trial at 56 acute stroke units in five countries. Patients (aged ≥18 years) with ischaemic or haemorrhagic stroke, first or recurrent, who met physiological criteria were randomly assigned (1:1), via a web-based computer generated block randomisation procedure (block size of six), to receive usual stroke-unit care alone or very early mobilisation in addition to usual care. Treatment with recombinant tissue plasminogen activator was allowed. Randomisation was stratified by study site and stroke severity. Patients, outcome assessors, and investigators involved in trial and data management were masked to treatment allocation. The primary outcome was a favourable outcome 3 months after stroke, defined as a modified Rankin Scale score of 0-2. We did analysis on an intention-to-treat basis. 
Between July 18, 2006, and Oct 16, 2014, we randomly assigned 2104 patients to receive either very early mobilisation (n=1054) or usual care (n=1050); 2083 (99%) patients were included in the 3 month follow-up assessment. 965 (92%) patients were mobilised within 24 h in the very early mobilisation group compared with 623 (59%) patients in the usual care group. Fewer patients in the very early mobilisation group had a favourable outcome than those in the usual care group (n=480 [46%] vs n=525 [50%]; adjusted odds ratio [OR] 0·73, 95% CI 0·59-0·90; p=0·004). 88 (8%) patients died in the very early mobilisation group compared with 72 (7%) patients in the usual care group (OR 1·34, 95% CI 0·93-1·93, p=0·113). 201 (19%) patients in the very early mobilisation group and 208 (20%) of those in the usual care group had a non-fatal serious adverse event, with no reduction in immobility-related complications with very early mobilisation.



First mobilisation took place within 24 h for most patients in this trial. The higher dose, very early mobilisation protocol was associated with a reduction in the odds of a favourable outcome at 3 months. Early mobilisation after stroke is recommended in many clinical practice guidelines worldwide, and our findings should affect clinical practice by refining present guidelines; however, clinical recommendations should be informed by future analyses of dose-response associations.



National Health and Medical Research Council, Singapore Health, Chest Heart and Stroke Scotland, Northern Ireland Chest Heart and Stroke, UK Stroke Association, National Institute of Health Research.
Identification of very high risk octogenarians undergoing coronary artery bypass surgery: results of a multicenter study

Excellent late survival is expected after coronary artery bypass (CABG) in patients aged ≥80 years, but immediate postoperative mortality can be rather high. This study was planned to identify variables associated with very high operative risk in these fragile patients. This is a multicenter study including 2,246 patients aged ≥80 years who underwent isolated CABG at 68 Italian hospitals. The proportion of patients aged ≥80 years varied from 1.7 to 13.6 % (overall 5.6 %, p < 0.0001) in different institutions. The median logistic EuroSCORE varied from 6.2 to 31.7 % (overall median 11.3 %, p = <0.0001) in different institutions. Thirty-day mortality in patients aged ≥80 years correlated with that of patients aged <80 years (rho: 0.310, p = 0.027). The overall 30-day mortality rate was 6.5 %. Both logistic regression and CART showed that emergency procedure, low left ventricular ejection fraction, unstable hemodynamics, and use of nitrates infusion at arrival in the operating room were independent predictors of 30-day mortality. CART analysis showed that 30-day mortality among patients undergoing emergency CABG with unstable hemodynamic conditions was 32.60 % and it was 20.0 % in patients undergoing non-emergency operation with nitrates infusion at arrival in the operating room and left ventricular ejection fraction <30 %. The proportion and operative risk of patients aged ≥80 years and undergoing CABG significantly varied among institutions. Patients requiring emergency surgery, with unstable hemodynamic conditions, requiring nitrates infusion, and low ejection fraction have a prohibitive operative risk. This small proportion of patients may benefit from percutaneous coronary intervention in order to stabilize their preoperative conditions.
Ranitidine pharmacokinetics in continuous ambulatory peritoneal dialysis

Ranitidine kinetics in renal failure were evaluated in six patients undergoing continuous ambulatory peritoneal dialysis (CAPD). On separate occasions each patient received either 50 mg intravenously (i.v.) or 150 mg orally of ranitidine HCl. Following i.v. administration, the plasma concentration vs time curve was best described by a two compartment model with firstorder elimination. The mean ± SD distribution and elimination rate constants were 2.47±0.78 and 0.098±0.013 h, respectively. The area under the serum concentration vs time curve after the i.v. dose was 5979±2870 μg·h· 1−1, resulting in a mean volume of distribution of 76.81 and a total body clearance of 126 ml·min−1. Following oral administration the observed maximum plasma concentration was 904±483 μg·l−1 at 4.2±1.8 h, and the bioavailability was 69.7±35.6%. The peritoneal clerance of ranitidine was 3.2±0.7 and 2.6±0.6 ml·min−1 for the i.v. and oral groups, respectively. The amount of drug removed by dialysis was 561.2±336.2 μg for the i.v. and 1197.1±602.3 μg for the oral group. Four patients in the i.v. group had urine output during the study period with renal ranitidine clearance values of 9.9±9.9 ml· min−1. Two patients in the oral group had urine output and corresponding renal ranitidine clearance values of 5.1 and 20.1 ml·min−1. A dosage regimen for ranitidine is proposed based on ranitidine kinetics in patients undergoing CAPD.
Effects of open-label lisdexamfetamine dimesylate on self-reported quality of life in adults with ADHD.

To assess improvements in quality of life measurements during the open-label portion of a trial examining duration of efficacy of lisdexamfetamine dimesylate in a simulated adult workplace environment.



A 4-week, open-label, dose-optimization phase followed by a randomized, double-blind, multicenter, placebo-controlled, 2-way crossover phase to evaluate safety and efficacy of lisdexamfetamine dimesylate in the adult workplace environment was conducted. Clinical assessments included the ADHD Impact Module for Adults (AIM-A) to assess the effect of lisdexamfetamine dimesylate on perception of quality of life and the Clinical Global Impressions-Severity/Improvement to assess symptom severity at baseline and improvement over time. Safety assessments included physical examination, treatment-emergent adverse events, vital signs, and electrocardiogram measurements.



Questions 1 and 4 of the AIM-A suggest improvement from baseline in overall quality of life at week 4 with lisdexamfetamine dimesylate treatment. Post-hoc analysis revealed no significant differences attributable to either age or sex. Overall responses to questions 2 and 3, which related to overall life goals, did not change in a majority of participants during the 4-week open-label phase of this study. For all lisdexamfetamine dimesylate doses combined, treatment-emergent adverse events occurring in ≥ 5% of participants during the dose-optimization phase were decreased appetite (36.6%), dry mouth (30.3%), headache (19.7%), insomnia (18.3%), upper respiratory tract infection (9.9%), irritability (8.5%), nausea (7.7%), anxiety (5.6%), and feeling jittery (5.6%).



At the end of the dose-optimization phase, lisdexamfetamine dimesylate treatment suggested quality of life improvements in adults with ADHD, with a safety profile consistent with long-acting stimulant use.
The effect of walnut intake on factors related to prostate and vascular health in older men

Tocopherols may protect against prostate cancer and cardiovascular disease (CVD).



We assessed the effect of walnuts, which are rich in tocopherols, on markers of prostate and vascular health in men at risk for prostate cancer. We conducted an 8-week walnut supplement study to examine effects of walnuts on serum tocopherols and prostate specific antigen (PSA). Subjects (n = 21) consumed (in random order) their usual diet +/- a walnut supplement (75 g/d) that was isocalorically incorporated in their habitual diets. Prior to the supplement study, 5 fasted subjects participated in an acute timecourse experiment and had blood taken at baseline and 1, 2, 4, and 8 h after consuming walnuts (75 g).



During the timecourse experiment, triglycerides peaked at 4 h, and gamma-tocopherol (gamma-T) increased from 4 to 8 h. Triglyceride - normalized gamma-T was two-fold higher (P = 0.01) after 8 versus 4 h. In the supplement study, change from baseline was +0.83 +/- 0.52 micromol/L for gamma-T, -2.65 +/- 1.30 micromol/L for alpha-tocopherol (alpha-T) and -3.49 +/- 1.99 for the tocopherol ratio (alpha-T: gamma-T). A linear mixed model showed that, although PSA did not change, the ratio of free PSA:total PSA increased and approached significance (P = 0.07). The alpha-T: gamma-T ratio decreased significantly (P = 0.01), partly reflecting an increase in serum gamma-T, which approached significance (P = 0.08).



The significant decrease in the alpha-T: gamma-T ratio with an increase in serum gamma-T and a trend towards an increase in the ratio of free PSA:total PSA following the 8-week supplement study suggest that walnuts may improve biomarkers of prostate and vascular status.
Effect of online medical control on prehospital Code Stroke triage.

Prehospital Code Stroke triage has the potential to overwhelm stroke centres by falsely identifying patients as eligible for fibrinolysis. We sought to determine whether online medical control (whereby paramedics contact the medical control physician before a Code Stroke triage is assigned) reduced the proportion of false-positive Code Stroke patients.



Following the introduction of a protocol for prehospital Code Stroke triage in an urban centre, online medical control alternated with off-line medical control (whereby paramedics implement Code Stroke triage independently) over 4 discreet intervals. We reviewed data for patients triaged to 3 regional stroke centres to compare the proportion of false-positive Code Stroke patients during online versus off-line medical control. We predefined false positives as patients triaged as Code Stroke who had symptoms discovered on awakening, were last seen in their usual state of health greater than 2 hours before assessment or had a final diagnosis other than stroke.



The proportion of false positives was lower during online medical control (31% v. 42%, p = 0.003). This was explained by a lower proportion of patients whose symptoms were discovered on awakening (8% v. 14%, p < 0.001) and who were last seen in their usual state of health greater than 2 hours before assessment (22% v. 32%, p = 0.005). A final diagnosis of stroke was similar in the 2 groups (77% v. 79%, p = 0.39), as was the proportion of patients receiving fibrinolysis (35% v. 33%, p = 0.72). Eighteen percent of patients were denied Code Stroke triage during online control, most commonly because of the time of symptom onset.



Online medical control is associated with a reduced proportion of false-positive Code Stroke triage.
A phase III randomized study to evaluate the efficacy and safety of CT-P13 compared with reference infliximab in patients with active rheumatoid arthritis: 54-week results from the PLANETRA study

CT-P13 (Remsima®, Inflectra®) is a biosimilar of the infliximab reference product (RP; Remicade®). The aim of this study was to compare the 54-week efficacy, immunogenicity, safety, pharmacokinetics (PK) and pharmacodynamics (PD) of CT-P13 and RP in patients with active rheumatoid arthritis (RA).



In this multinational phase III double-blind study, patients with active RA and an inadequate response to methotrexate (MTX) were randomized (1:1) to receive CT-P13 (3 mg/kg) or RP (3 mg/kg) at weeks 0, 2, 6 and then every 8 weeks to week 54 in combination with MTX (12.5-25 mg/week). Efficacy endpoints included American College of Rheumatology (ACR)20, ACR50 and ACR70 response rates, Disease Activity Score in 28 joints (DAS28), Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), European League Against Rheumatism (EULAR) response rates, patient-reported outcomes and joint damage progression. Immunogenicity, safety and PK/PD outcomes were also assessed.



Of 606 randomized patients, 455 (CT-P13 233, RP 222) were treated up to week 54. At week 54, ACR20 response rate was highly similar between groups (CT-P13 74.7 %, RP 71.3 %). ACR50 and ACR70 response rates were also comparable between groups (CT-P13 43.6 % and 21.3 %, respectively; RP 43.1 % and 19.9 %, respectively). DAS28, SDAI and CDAI decreased from baseline to week 54 to a similar extent with CT-P13 and RP. Radiographic progression measured by Sharp scores as modified by van der Heijde was also comparable. With both treatments, patient assessments of pain, disease activity and physical ability, as well as mean scores on the Medical Outcomes Study Short Form Health Survey (SF-36), improved markedly at week 14 and remained stable thereafter up to week 54. The proportion of patients positive for antidrug antibodies at week 54 was similar between the two groups: 41.1 % and 36.0 % with CT-P13 and RP, respectively. CT-P13 was well tolerated and had a similar safety profile to RP. PK/PD results were also comparable between CT-P13 and RP.



CT-P13 and RP were comparable in terms of efficacy (including radiographic progression), immunogenicity and PK/PD up to week 54. The safety profile of CT-P13 was also similar to that of RP.
Treatment of child anxiety disorders via guided parent-delivered cognitive-behavioural therapy: randomised controlled trial.

Promising evidence has emerged of clinical gains using guided self-help cognitive-behavioural therapy (CBT) for child anxiety and by involving parents in treatment; however, the efficacy of guided parent-delivered CBT has not been systematically evaluated in UK primary and secondary settings.



To evaluate the efficacy of low-intensity guided parent-delivered CBT treatments for children with anxiety disorders.



A total of 194 children presenting with a current anxiety disorder, whose primary carer did not meet criteria for a current anxiety disorder, were randomly allocated to full guided parent-delivered CBT (four face-to-face and four telephone sessions) or brief guided parent-delivered CBT (two face-to-face and two telephone sessions), or a wait-list control group ( Presence and severity of child primary anxiety disorder (Anxiety Disorders Interview Schedule for DSM-IV, child/parent versions), improvement in child presentation of anxiety (Clinical Global Impression - Improvement scale), and change in child anxiety symptoms (Spence Children's Anxiety Scale, child/parent version and Child Anxiety Impact scale, parent version) were assessed at post-treatment and for those in the two active treatment groups, 6 months post-treatment.



Full guided parent-delivered CBT produced superior diagnostic outcomes compared with wait-list at post-treatment, whereas brief guided parent-delivered CBT did not: at post-treatment, 25 (50%) of those in the full guided CBT group had recovered from their primary diagnosis, compared with 16 (25%) of those on the wait-list (relative risk (RR) 1.85, 95% CI 1.14-2.99); and in the brief guided CBT group, 18 participants (39%) had recovered from their primary diagnosis post-treatment (RR = 1.56, 95% CI 0.89-2.74). Level of therapist training and experience was unrelated to child outcome.



Full guided parent-delivered CBT is an effective and inexpensive first-line treatment for child anxiety.