nils-herrmann/clean_scirepeval huggingface dataset:
Trial of the route of early nutritional support in critically ill adults.

From the Clinical Trials Unit, Intensive Care National Audit and Research Centre (S.E.H., F.P., D.A.H., K.M.R.), the Departments of Nutrition and Dietetics (D.E.B.) and Adult Critical Care (D.E.B., R.B.), Guy’s and St. Thomas’ NHS Foundation Trust, the Department of Intensive Care, Imperial College Healthcare NHS Trust (E.S., R.L.), the Division of Asthma, Allergy and Lung Biology, King’s College London (R.B.), National Institute for Health Research Biomedical Research Centre, University College London Hospitals NHS Foundation Trust and University College London (G.B., M.G.M.), and the Department of Surgery and Cancer, Imperial College London (R.L.) — all in London. Address reprint requests to Dr. Rowan at the Intensive Care National Audit and Research Centre, Napier House, 24 High Holborn, London WC1V 6AZ, United Kingdom, or at kathy.rowan@icnarc.org.
[Characterization of and costs associated to the profile of patients with type 2 diabetes treated with metformin who are added a second oral antidiabetic drug: a population study].

To determine compliance, metabolic control, complications and healthcare costs of patients treated with metformin started a second antidiabetic drug in patients with type 2 diabetes (T2DM).



Design multicenter observational retrospective. Patients were evaluated ≥30 years (age), treated with metformin and started a second antidiabetic treatment during 2008-2009. There were 4 patient groups (metformin and another antidiabetic): a) dipeptidyl peptidase-4 inhibitors (IDPP4), b) sulfonylureas, c) glitazones and d) insulin.



comorbidity, metabolic control, compliance and complications. Patients were followed for 2 years. The cost model differed direct health costs (primary care / specialist) and indirect (labor productivity).



logistic regression models and ANCOVA, p<0.05.



2067 patients were included (mean age: 66.6 years male: 53.1%). 25.1% started a second treatment with IDPP4; 42.9% sulfonylureas, 14.0% glitazones and 18.0% insulin. At 2 years follow-up, patients treated with IDPP4 showed greater adherence vs. 70.3%. 59.9%, 60.3% and 58.4; better control of 64.3% vs. DM2. 62.6%, 62.8% and 50.5% and a decrease of 13.9% compared to hypoglycaemia 40.4%, 37.6% and 58.9% respectively (p<0.001). The average / unit total costs was €2,321 vs. €2,475, €2,724 and €3,164, respectively, p<0.001. Rates of cardiovascular events and renal failure were 3.7%, 6.4%, 7.6% and 10.2% respectively.



Sulfonylureas were the most commonly used drugs. Patients treated with IDPP4 had higher compliance and control of diabetes, with lower rates of hypoglycaemia and healthcare costs.
Reduction in serum clusterin is a potential therapeutic biomarker in patients with castration-resistant prostate cancer treated with custirsen

Elevated levels of clusterin (CLU), a stress-induced and secreted cytoprotective chaperone, are associated with advanced tumor stage, metastasis, treatment resistance, and adverse outcome in several cancers. Custirsen, a second-generation antisense oligonucleotide, inhibits CLU production in tumor cells and reduces serum CLU levels. A Phase 2 study evaluated custirsen in combination with second-line chemotherapy in men with metastatic castration-resistant prostate cancer (mCRPC) who had progressed while on or within 6 months of first-line docetaxel-based chemotherapy. Exploratory analyses evaluated serum CLU levels during custirsen treatment and correlative clinical effects on prostate-specific antigen (PSA) response, overall survival, and any relationship between serum CLU and PSA. Men with mCRPC were treated with mitoxantrone/prednisone/custirsen (MPC, n = 22) or docetaxel retreatment/prednisone/custirsen (DPC plus DPC-Assigned, n = 45) in an open-label, multicenter study. Subject-specific profiles of PSA and serum CLU levels during treatment were characterized using statistical modeling to compute subject-specific summary measures; these measures were analyzed for relationship to survival using proportional hazard regression. Estimated individual serum CLU response profiles were scored as below or at/above the median level for the population through 100 days postrandomization. Median survival was longer for subjects scoring below the median serum CLU level compared with subjects at/above the median level, respectively (MPC: 15.1 months vs. 6.2 months; DPC-Pooled: 17.0 months vs. 12.1 months). Lowered serum CLU levels during custirsen treatment when in combination with either chemotherapy regimen were predictive of longer survival in mCRPC. These results support further evaluation of serum CLU as a therapeutic biomarker.
Clinical and pharmacokinetic study evaluating the effect of food on the disposition of 9-nitrocamptothecin and its 9-aminocamptothecin metabolite in patients with solid tumors

9-Nitrocamptothecin (9NC) is an orally administered camptothecin analogue that has completed phase III trials for pancreatic cancer. In biological matrices, camptothecin analogues exist in equilibrium between the active-lactone (LAC) and inactive-hydroxy acid (HA) forms. 9NC has been administered on an empty stomach; however, it is unclear if food alters the absorption and disposition of 9NC and its 9-aminocamptothecin (9AC) active-metabolite. Thus, we evaluated the disposition of 9NC and 9AC after administration of 9NC under fasting conditions and after a standard meal.  Patients were randomized to receive 9NC as a single oral dose at 1.5 mg/m2 with 8 ounces (oz) of an acidic beverage under fasting conditions, or after a meal consisting of two eggs, 8 oz of orange juice, buttered toast, 8 oz of milk, and 4 oz of hash brown potatoes. Following a 72 h washout period, 9NC was administered with the alternative condition (i.e., with food or fasting). 9NC was then continued for 5 days of every week. Serial blood samples were obtained prior to and from 0.25 to 24 h after administration of 9NC. The total (sum of LAC + HA) of 9NC and 9AC were measured by an LC-MS/MS assay. Area under the plasma concentration versus time curve (AUC) for 9NC and 9AC total were calculated. After the pharmacokinetic section of the study, patients received 9NC 1.5 mg/m2 orally under fasting conditions daily for 5 days per week for 8 weeks.  Sixteen patients with median (range) age 62 (47–83) years, diagnoses of colorectal (six patients), lung (two patients), and other (eight patients) malignancies, received 83 [median (range) 4 (2–9)] weeks of therapy. Patients with toxicities greater than grade 2: were diarrhea (1), nausea (2), vomiting (2), fatigue (2), anemia (3), neutropenia (3), and febrile neutropenia (2). Three patients (lung, unknown primary, and colon) had stable disease for eight weeks. The mean±SD of 9NC AUCfood and 9NC AUCfast (n=9) were 330±182 and 558±379 ng/ml·h, respectively (P<0.05). The mean±SD of 9AC AUCfood and 9AC AUCfast (n=9) were 244±60 and 256±101 ng/ml·h, respectively (P>0.05). The mean ± SD ratio of 9NC AUCfood to AUCfasting in individual patients (n=9) was 0.67±0.22. The mean ± SD ratio of 9AC AUCfood to AUCfasting in individual patients (n=9) was 1.14±0.61.  Co-administration of 9NC with food reduces the oral absorption of 9NC; however, there was no difference in the exposure of 9AC. The is high interpatient variability in the effect of food on the absorption of 9NC and the interpatient variability in the effect of food on the disposition of 9AC is even greater when compared to 9NC.
Effects of chronic carotid baroreceptor activation on arterial stiffness in severe heart failure

Heart failure with reduced ejection fraction (HFrEF) is characterized by activation of the sympathetic nervous system and increased arterial stiffness, leading to an impaired ventricular-vascular coupling. Baroreflex activation therapy (BAT) has been shown to reduce muscle sympathetic nerve activity (MSNA) and improve clinical status of patients with HFrEF. The purpose of this investigation was to determine the effects of BAT on arterial stiffness in HFrEF. MSNA, clinical variables, and parameters of central blood pressure (BP) and arterial stiffness were collected in 18 NYHA Class III HFrEF patients, nine receiving BAT and nine continuing with optimal medical management alone. Patients were followed for 3 months, with measurements at that time compared to baseline evaluation. Baseline characteristics of the groups were well matched. At 3 months, BAT did not improve central BP and arterial stiffness despite a significant amelioration of MSNA, NYHA class, Minnesota living with heart failure questionnaire score, number of heart failure medications and six-minute walking distance. The control group exhibited no significant changes in all the measured variables. Despite significant reductions in MSNA and clinical improvement, BAT does not appear to chronically modify arterial stiffness within this HFrEF cohort. Additional study is required to determine if this result applies to the HFrEF population as a whole.
Dopaminergic Influences on Emotional Decision Making in Euthymic Bipolar Patients

We recently reported that the D2/D3 agonist pramipexole may have pro-cognitive effects in euthymic patients with bipolar disorder (BPD); however, the emergence of impulse-control disorders has been documented in Parkinson’s disease (PD) after pramipexole treatment. Performance on reward-based tasks is altered in healthy subjects after a single dose of pramipexole, but its potential to induce abnormalities in BPD patients is unknown. We assessed reward-dependent decision making in euthymic BPD patients pre- and post 8 weeks of treatment with pramipexole or placebo by using the Iowa Gambling Task (IGT). The IGT requires subjects to choose among four card decks (two risky and two conservative) and is designed to promote learning to make advantageous (conservative) choices over time. Thirty-four BPD patients completed both assessments (18 placebo and 16 pramipexole). Baseline performance did not differ by treatment group (F=0.63; p=0.64); however, at week 8, BPD patients on pramipexole demonstrated a significantly greater tendency to make increasingly high-risk, high-reward choices across the five blocks, whereas the placebo group’s pattern was similar to that reported in healthy individuals (treatment × time × block interaction, p<0.05). Analyses of choice strategy using the expectancy valence model revealed that after 8 weeks on pramipexole, BPD patients attended more readily to feedback related to gains than to losses, which could explain the impaired learning. There were no significant changes in mood symptoms over the 8 weeks, and no increased propensity toward manic-like behaviors were reported. Our results suggest that the enhancement of dopaminergic activity influences risk-associated decision-making performance in euthymic BPD. The clinical implications remain unknown.
The nosology of psychotic disorders: a comparison among competing classification systems.

This study examined the concordance and predictive validity of two empirical and two operational classification systems of psychotic disorders. Latent class analysis (LCA) was applied to 16 index episode and to their corresponding 16 lifetime symptom ratings of 660 psychotic inpatients, who were also diagnosed according to DSM-IV and ICD-10 criteria. The resulting classes or diagnoses were validated against clinical (premorbid adjustment, treatment response, and course) and etiologic (morbidity risk of schizophrenia and major mood disorders) variables. LCA of index episode and lifetime ratings showed that five classes of psychotic disorders provided the best fit to the data: schizophrenia, psychosis, schizomania/schizobipolar, schizodepression, and mixed psychosis (cycloid psychosis for index episode ratings and atypical schizophrenia for lifetime ratings). The concordance between the empirical and operational classification systems was poor. Irrespective of the classification method used, the most powerful validators were the clinical ones, whereas the etiologic validators played a negligible role in validating the classes or diagnoses. Overall, DSM-IV and ICD-10 classifications had more clinical validity than empirical classifications, mainly because of circularity in operational definitions regarding treatment response and course of the disorders. With the exception of the category of schizophrenia, which showed some nosological stability across the four classification systems, the number and type of categories of psychosis were highly dependent upon the set of classification procedures. These results make clear the problems inherent in drawing well-defined boundaries between psychotic disorders.
A phase I/II study of 4 monthly courses of high-dose cyclophosphamide and thiotepa for metastatic breast cancer patients

This pilot phase I/II study intended to determine the maximum tolerated dose of cyclophosphamide and thiotepa administered on four consecutive courses with peripheral blood progenitor cell and granulocyte-colony stimulating factor support, as first-line therapy for hormone-refractory metastatic breast cancer patients. Twenty-eight patients were entered in the study. After two courses of epirubicin (120 mg m−2) and cyclophosphamide (2 g m−2) followed by granulocyte-colony stimulating factor injection and leukaphereses, patients received four cycles of cyclophosphamide and thiotepa. Each cycle was followed by peripheral blood progenitor cell and granulocyte-colony stimulating factor supports, then repeated every 28 to 35 days. Six escalating dose levels of cyclophosphamide and thiotepa were planned, beginning at cyclophosphamide 1.5 g m−2 and thiotepa 200 mg m−2. At least three patients were enrolled for each dose level. Eighteen patients completed the study. The maximum tolerated dose was 3000 mg m−2 cyclophosphamide and 400 mg m−2 thiotepa per course. Haematological toxicity was manageable on an outpatient basis and did not increase significantly with dose escalation. Dose-limiting toxicity was chemotherapy-induced immuno-suppression, which resulted in one toxic death and two life-threatening infections. Median times to treatment failure and survival were 11 and 26 months, respectively. Three patients were alive, free of disease 30 months after completion of the study. Such therapy allows for high-dose intensity and high cumulative doses on a short period of time with manageable toxicity.
Anti-HBV DNA vaccination does not prevent relapse after discontinuation of analogues in the treatment of chronic hepatitis B: a randomised trial--ANRS HB02 VAC-ADN.

The antiviral efficacy of nucleos(t)ide analogues whose main limitation is relapse after discontinuation requires long-term therapy. To overcome the risk of relapse and virological breakthrough during long-term therapy, we performed a phase I/II, open, prospective, multicentre trial using a HBV envelope-expressing DNA vaccine.



70 patients treated effectively with nucleos(t)ide analogues for a median of 3 years (HBV DNA <12 IU/mL for at least 12 months) were randomised into two groups: one received five intramuscular injections of vaccine (weeks 0, 8, 16, 40 and 44) and one did not receive the vaccine. Analogues were stopped after an additional 48 weeks of treatment in patients who maintained HBV DNA <12 IU/mL with no clinical progression and monthly HBV DNA for 6 months. The primary endpoint was defined as viral reactivation at week 72 (HBV DNA >120 IU/mL) or impossibility of stopping treatment at week 48.



Reactivation occurred in 97% of each group after a median 28 days without liver failure but with an HBV DNA <2000 IU/mL in 33%; 99% of adverse reactions were mild to moderate. Immune responses were evaluated by enzyme-linked immunosorbent spot and proliferation assays: there was no difference in the percentage of patients with interferon-γ secreting cells and a specific T-cell proliferation to HBcAg but not to HBsAg after reactivation in each group.



Although it is fairly well tolerated, the HBV DNA vaccine does not decrease the risk of relapse in HBV-treated patients or the rate of virological breakthrough, and does not restore the anti-HBV immune response despite effective viral suppression by analogues.
Manual lymphatic drainage versus exercise in the early postoperative period for breast cancer.

To compare the effect of active exercise and manual lymphatic drainage (MLD) on postoperative wound healing complications, shoulder range of motion (ROM) and upper limb (UL) perimetry in women undergoing radical mastectomy for breast cancer.



Controlled non-randomized clinical trial with 89 women undergoing breast cancer surgery with axillary lymph node dissection (Brazilian Registry of Clinical Trials: 906). Women were matched for staging, age and body mass index, with 46 women allocated to the exercise group and 43 in the MLD group, receiving 2 weekly sessions during one month. Assessments were performed in the preoperative and 60 d after surgery, including inspection, palpation, goniometry and perimetry.



No significant difference existed between groups relative to individual and clinical surgical characteristics. The incidence of seroma, number of punctures performed, dehiscence and infection was similar in both groups. A comparison of shoulder ROM and UL perimetry between groups, obtained in the preoperative and postoperative period, did not show any significant difference.



The performance of active exercise or MLD did not demonstrate difference in wound healing complications, shoulder ROM and UL perimetry at 60 d after surgery, suggesting that these techniques may be employed, according to the complaints or symptoms of each woman and physical therapist experience.
XbaI polymorphism of the estrogen receptor alpha gene influences the effect of raloxifene on the endothelial function.

Cardiovascular disease is the leading cause of death in postmenopausal women and estrogen deficiency may be an important factor in its development. The selective estrogen receptor modulator, raloxifene, exerts a part of its actions through the estrogen receptor alpha (ESR1) activation. We explored if polymorphisms of the ESR1 modify the effects of 6 months raloxifene treatment on endothelial function.



A total of 53 postmenopausal women, mean age 59.7+/-6.2, finished the prospective clinical trial. The PvuII, XbaI, and P325P polymorphisms of the ESR1 gene were analyzed. In all subjects endothelium-dependent flow mediated dilatation (FMD) and cell adhesion molecules (CAM) ICAM-1, VCAM-1 and E-selectin were measured before and after 6 months of raloxifene treatment.



There was no difference in FMD between the ESR1 genotypes, at baseline. After raloxifene treatment, the FMD was significantly greater in subjects with XX genotype of XbaI polymorphism compared to xx (p=0.03) and borderline greater when compared to Xx genotype (p=0.053). The FMD increased significantly with raloxifene treatment in women with Xx genotype of XbaI and Pp genotype of PvuII polymorphisms (p=0.027 and p=0.034, respectively). The P325P polymorphism did not influence the FMD after raloxifene. None of the ESR1 gene polymorphisms had any impact on the levels of CAM before or after the treatment. When analysing the whole group, a significant decrease in E-selectin (p<0.001) and a small increase in ICAM-1 levels (p=0.029) was observed with raloxifene treatment, but no influence on VCAM-1 levels or FMD overall was seen.



Our data suggest that XbaI and possibly PvuII polymorphisms of the ESR1 gene influence the impact of raloxifene treatment on endothelial function. This effect could be of pharmacogenomic and clinical importance.
Toward semantic search via SMT solver

Searching for code is a common task among programmers, with the ultimate goal of reuse. While the process of searching for code -- issuing a query and selecting a relevant match -- is straightforward, several costs must be balanced, including the costs of specifying the query, examining the results to find desired code, and not finding a relevant result. For syntactic searches the query cost is quite low, but the results are often irrelevant, so the examination cost is high and matches may be missed. Semantic searches may return more relevant results, but current techniques that involve writing complex specifications or executing code against test cases are costly to the developer. We propose an approach for semantic search in which developers specify lightweight specifications and an SMT solver identifies matching programs from a repository. A program repository is automatically encoded offline so the search is efficient. Programs are encoded at various abstraction levels to enable partial matches when no, or few, exact matches exist. We instantiate this approach on a subset of the Yahoo! Pipes mashup language. Preliminary results show promise for the feasibility of the approach.
Empowerment and satisfaction in a multinational study of routine clinical practice.

Decision-making between mental health clinicians and patients is under-researched. We tested whether mental health patients are more satisfied with a decision made (i) using their preferred decision-making style and (ii) with a clinician with the same decision-making style preference.



As part of the CEDAR Study (ISRCTN75841675), a convenience sample of 445 patients with severe mental illness from six European countries were assessed for desired clinical decision-making style (rated by patients and paired clinicians), decision-specific experienced style and satisfaction.



Patients who experienced more involvement in decision-making than they desired rated higher satisfaction (OR=2.47, P=0.005, 95% CI 1.32-4.63). Decisions made with clinicians whose decision-making style preference was for more active involvement than the patient preference were rated with higher satisfaction (OR=3.17, P=0.003, 95% CI 1.48-6.82).



More active involvement in decision-making than the patient stated as desired was associated with higher satisfaction. A clinical orientation towards empowering, rather than shared, decision-making may maximise satisfaction.
Cardiac effects of antiretroviral therapy in HIV-negative infants born to HIV-positive mothers: NHLBI CHAART-1 (National Heart, Lung, and Blood Institute Cardiovascular Status of HAART Therapy in HIV-Exposed Infants and Children cohort study).

The aim of this study was to investigate the possible effects of antiretroviral therapy (ART) in utero on cardiac development and function in human immunodeficiency virus (HIV)-negative children.



ART reduces vertical HIV transmission. Long-term cardiotoxicity after in utero exposure to ART is unknown in children but has occurred in young animals.



Using a prospective multisite cohort study design, echocardiograms taken between birth and 24 months were compared in 2 groups of HIV-negative infants of HIV-positive mothers: 136 infants exposed to ART (ART+) and 216 unexposed infants (ART-).



Mean left ventricular (LV) mass z-scores were consistently lower in ART+ girls than in ART- girls: differences in mean z-scores were -0.46 at birth (p = 0.005), -1.02 at 6 months (p < 0.001), -0.74 at 12 months (p < 0.001), and -0.79 at 24 months (p < 0.001). Corresponding differences in z-scores for boys were smaller: 0.13 at 1 month (p = 0.42), -0.44 at 6 months (p = 0.01), -0.15 at 12 months (p = 0.37), and -0.21 at 24 months (p = 0.21). Septal wall thickness and LV dimension were smaller than expected in ART+ infants, but LV contractility was consistently about 1 SD higher at all ages (p < 0.001). In ART+ infants, LV fractional shortening was higher than in ART- infants; girls showed a greater difference.



Fetal exposure to ART is associated with reduced LV mass, LV dimension, and septal wall thickness z-scores and increased LV fractional shortening and contractility up to age 2 years. These effects are more pronounced in girls than in boys. Fetal ART exposure may impair myocardial growth while improving depressed LV function.