nils-herrmann/clean_scirepeval huggingface dataset:
Multinational, observational study of procalcitonin in ICU patients with pneumonia requiring mechanical ventilation: a multicenter observational study

The intent of this study was to determine whether serum procalcitonin (PCT) levels are associated with prognosis, measured as organ dysfunctions and 28-day mortality, in patients with severe pneumonia.



This was a multicenter, observational study of critically ill adult patients with pneumonia requiring mechanical ventilation conducted in 10 academic hospitals in Canada, the United States, and Central Europe. PCT was measured daily for 14 days using an immuno-luminometric assay.



We included 175 patients, 57 with community acquired pneumonia (CAP), 61 with ventilator associated pneumonia (VAP) and 57 with hospital acquired pneumonia (HAP). Initial PCT levels were higher in CAP than VAP patients (median (interquartile range: IQR); 2.4 (0.95 to 15.8) vs. 0.7 (0.3 to 2.15), ng/ml, P < 0.001) but not significantly different to HAP (2.2 (0.4 to 8.0) ng/ml). The 28-day ICU mortality rate for all patients was 18.3% with a median ICU length of stay of 16 days (range 1 to 142 days). PCT levels were higher in non-survivors than in survivors. Initial and maximum PCT levels correlated with maximum Sequential Organ Failure Assessment (SOFA) score r2 = 0.50 (95% CI: 0.38 to 0.61) and r² = 0.57 (0.46 to 0.66), respectively. Receiver operating curve (ROC) analysis on discrimination of 28-day mortality showed areas under the curve (AUC) of 0.74, 0.70, and 0.69 for maximum PCT, initial PCT, and Acute Physiology and Chronic Health Evaluation (APACHE) II score, respectively. The optimal cut-off to predict mortality for initial PCT was 1.1 ng/ml (odds ratio: OD 7.0 (95% CI 2.6 to 25.2)) and that for maximum PCT was 7.8 ng/ml (odds ratio 5.7 (95% CI 2.5 to 13.1)).



PCT is associated with the severity of illness in patients with severe pneumonia and appears to be a prognostic marker of morbidity and mortality comparable to the APACHE II score.
Treatment with daclatasvir and sofosbuvir for 24 weeks without ribavirin in cirrhotic patients who failed first-generation protease inhibitors

Treatment of patients with chronic hepatitis C who failed the triple therapy with first generation of protease inhibitors is not still defined. The combined use of sofosbuvir (SOF) and daclatasvir (DCV) seems to be promising due to higher genetic barrier, good tolerance and effectiveness. We described the treatment with this drug combination in a real-life cohort of 20 cirrhotic patients with genotype 1 who failed the triple therapy. 18 of them (90%) with Child–Pugh A, 11 (55%) with genotype 1a, 17 (85%) with more than 1 and 8 (40%) with more than 2 previous failed treatment; all patients had at baseline NS3 resistance-associated variants related to triple therapy failure. RBV was not administered due to anemia in previous treatments. The sustained virological response was 100%. Treatment with SOF + DCV without RBV for 24 weeks is safe and effective in cirrhotic patients who failed triple therapy with the first generation of protease inhibitors.
Simulation of a network manufacturing process

A GPSS model was developed to simulate the flow of parts through the stages of a network manufacturing process. The general network consists of M sequential stages, with a variable number of machines per stage. Parts can be processed on any of the Ni machines at stage i, and different types of parts may be mixed within a single machine. The simulator is used to evaluate scheduling policies proposed for each stage of the process. Scheduling policies to be considered are first in-first out (FIFO), last in-first out (LIFO), minimum process time, maximum process time, random, and priority.
Genomic alterations in breast cancer patients from Northeast India using 10K SNP arrays

North-east India has always been a ‘hotspot’ for population geneticists because of its unique, strategic geographic location and the presence of linguistically, culturally and demographically diverse populations practicing various tobacco habits. This region reports a high incidence of breast cancer in females with a history of extensive exposure to tobacco. Therefore, this population is constantly exposed to a high level of genotoxic stress. Accumulation of multiple and discrete genetic events during tobacco exposure can combine to drive breast cancer pathogenesis. Direct analysis of the tumor genome can reveal the genomic events accumulated during tumor progression. Hence, we investigated genomic alterations in breast cancer patients with tobacco exposure.
Intravenous administration of auto serum-expanded autologous mesenchymal stem cells in stroke.

Transplantation of human mesenchymal stem cells has been shown to reduce infarct size and improve functional outcome in animal models of stroke. Here, we report a study designed to assess feasibility and safety of transplantation of autologous human mesenchymal stem cells expanded in autologous human serum in stroke patients. We report an unblinded study on 12 patients with ischaemic grey matter, white matter and mixed lesions, in contrast to a prior study on autologous mesenchymal stem cells expanded in foetal calf serum that focused on grey matter lesions. Cells cultured in human serum expanded more rapidly than in foetal calf serum, reducing cell preparation time and risk of transmissible disorders such as bovine spongiform encephalomyelitis. Autologous mesenchymal stem cells were delivered intravenously 36-133 days post-stroke. All patients had magnetic resonance angiography to identify vascular lesions, and magnetic resonance imaging prior to cell infusion and at intervals up to 1 year after. Magnetic resonance perfusion-imaging and 3D-tractography were carried out in some patients. Neurological status was scored using the National Institutes of Health Stroke Scale and modified Rankin scores. We did not observe any central nervous system tumours, abnormal cell growths or neurological deterioration, and there was no evidence for venous thromboembolism, systemic malignancy or systemic infection in any of the patients following stem cell infusion. The median daily rate of National Institutes of Health Stroke Scale change was 0.36 during the first week post-infusion, compared with a median daily rate of change of 0.04 from the first day of testing to immediately before infusion. Daily rates of change in National Institutes of Health Stroke Scale scores during longer post-infusion intervals that more closely matched the interval between initial scoring and cell infusion also showed an increase following cell infusion. Mean lesion volume as assessed by magnetic resonance imaging was reduced by >20% at 1 week post-cell infusion. While we would emphasize that the current study was unblinded, did not assess overall function or relative functional importance of different types of deficits, and does not exclude placebo effects or a contribution of recovery as a result of the natural history of stroke, our observations provide evidence supporting the feasibility and safety of delivery of a relatively large dose of autologous mesenchymal human stem cells, cultured in autologous human serum, into human subjects with stroke and support the need for additional blinded, placebo-controlled studies on autologous mesenchymal human stem cell infusion in stroke.
Effects of different forms of hazelnuts on blood lipids and α-tocopherol concentrations in mildly hypercholesterolemic individuals

Diets high in nuts reduce cholesterol, probably due to their favorable lipid profile and other bioactive substances. However, the physical form of the nut may be important as the cell wall of intact nuts may limit the hypocholesterolemic effect of nuts by reducing lipid bioavailability. Therefore, we investigated the effects on blood lipids of incorporating three different forms of hazelnuts (ground, sliced and whole) into the usual diet.In a randomized crossover study with three phases, 48 mildly hypercholesterolemic participants were asked to consume 30 g of ground, sliced or whole hazelnuts for 4 weeks. Body weight, plasma total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triacylglycerol (TAG), apolipoprotein (apo) A1, apo B100 and α-tocopherol were measured at baseline and at the end of each dietary phase.There were no significant differences in any outcome variable between the different forms of nuts (all P⩾0.159). However, compared with baseline, mean values at the end of each hazelnut intervention were significantly higher for HDL-C (P=0.023) and α-tocopherol (P=0.005), and significantly lower for TC (P<0.001), LDL-C (P<0.001), TC:HDL-C ratio (P<0.001), apo B100 (P=0.002) and apo B100:apo A1 ratio (P<0.001), with no significant difference in body weight (P=0.813).Conclusions: The ingestion of three different forms of hazelnuts equally improved the lipoprotein profile and α-tocopherol concentrations in mildly hypercholesterolemic individuals. Hazelnuts can therefore be incorporated into the usual diet as a means of reducing cardiovascular disease risk.
Adductor tenotomy as a treatment for groin pain in professional soccer players.

Chronic, exercise-related groin pain is a debilitating condition. Nonoperative treatment has limited efficacy, but surgical intervention on the adductor-abdomino complex may be used to alleviate symptoms and allow return to play (RTP). The purpose of this study was to report the outcome of adductor tenotomy and hernioplasty for professional soccer players with groin pain. Between 2000 and 2006, a total of 155 professional and recreational soccer players with recalcitrant groin pain (with or without lower abdominal pain) and resistance to conservative treatment were included in this retrospective analysis. Ninety-six patients were treated with adductor tenotomy and 59 patients were treated with combined adductor tenotomy and hernioplasty. No difference in pre- or postoperative parameters was detected between groups, apart from abdominal wall muscle defects revealed during ultrasound for patients in the combined group. The RTP time and subjective and objective outcome measures were compared. A combined score was developed to evaluate outcomes that consisted of overall satisfaction (50%), RTP time (15%), and Tegner scores (35%). Mean RTP was 11 weeks (range, 4-36 weeks). Postoperative Tegner score remained 8.2 (same as the preinjury Tegner score). Subjective outcome was rated 4.3 of 5. The combined score indicated 80% of good or excellent results for both groups. Surgical intervention allows RTP at the same level in professional soccer players following failure of nonoperative treatments. Athletes with adductor syndrome and accompanying sportsman's hernia may benefit from adductor tenotomy alone.
Population Pharmacokinetic Modelling of Irosustat in Postmenopausal Women with Oestrogen-Receptor Positive Breast Cancer Incorporating Non-Linear Red Blood Cell Uptake

Irosustat is the ‘first-in-class’ irreversible potent steroid sulphatase inhibitor with lack of oestrogenic activity. The objective of this work was to develop a population model characterizing simultaneously the pharmacokinetic profiles of irosustat in plasma and whole blood. This clinical study was an open label, multicentre, phase I multiple cohort dose escalation trial conducted in 35 postmenopausal women with oestrogen-receptor positive breast cancer. Patients received 1, 5, 20, 40, or 80 mg oral doses. Irosustat was administered as a single oral dose to each patient followed by an observation period of 7 days. On day 8 each patient received once daily oral administration until day 34. Concentrations of irosustat in both blood and plasma were obtained and pharmacokinetic analyses were performed with NONMEM 7.2. Irosustat showed non-linear disposition characteristics modelled as maximum binding capacity into the red blood cells. Plasma concentration corresponding to half of the maximum capacity was 32.79 ng/mL. The value of the blood to plasma concentration ratio in linear conditions was 419, indicating very high affinity for the red blood cells. Apparent plasma and blood clearances were estimated in 1199.52 and 3.90 L/day, respectively. Pharmacokinetics of irosustat showed low-moderate inter-subject variability, and neither the demographics (e.g., age, or weight) nor the phenotypes for CYP2C9, CYP2C19, and CYP3A5 enzymes showed statistically significant effects. Relative bioavailability was decreased as the administered dose was augmented. The model predicted a 47% decrease in relative bioavailability in the 40 mg with respect to the 1 mg dose.
[Type of treatment and short-term outcome in elderly patients with acute myocardial infarction admitted to hospitals with a primary coronary angioplasty facility. The TRIANA (TRatamiento del Infarto Agudo de miocardio eN Ancianos) Registry].

The nature and outcome of treatment for acute myocardial infarction in elderly patients admitted to Spanish hospitals with primary angioplasty facilities are not well documented.



Prospective analysis of registry data on patients > or =75 years old with ST-segment-elevation acute myocardial infarction admitted between April and July 2002 to Spanish hospitals with an active primary angioplasty program.



We followed up 410 consecutive patients for 1 month. Their mean age was 80 (4.3) years and 46% were female. The median delay between symptom onset and arrival at hospital was 190 minutes. Around 42% of patients received no reperfusion therapy, 35% were treated by thrombolysis, and 22% by primary angioplasty. Patients who underwent reperfusion therapy were younger, were more frequently male, had a shorter delay from symptom onset to hospital arrival, and had a better initial hemodynamic status (Killip Class). However, they were more likely to have extensive anterior infarctions. Overall, 30-day mortality was 24.9%. Independent predictors of death were age, systolic blood pressure, and Killip class >1, but not use of thrombolysis or primary angioplasty.



Over 42% of elderly patients with myocardial infarction admitted to Spanish hospitals with angioplasty facilities did not receive reperfusion therapy. Thrombolysis was the most frequently used reperfusion therapy. However, neither thrombolysis nor primary angioplasty improved 30-day mortality.
Comparative effectiveness of social problem-solving therapy and reminiscence therapy as treatments for depression in older adults.

Compared the effects of 2 psychotherapies based on divergent conceptualizations of depression in later life. Seventy-five older adults diagnosed with major depressive disorder were assigned randomly to problem-solving therapy (PST), reminiscence therapy (RT), or a waiting-list control (WLC) condition. Participants in PST and RT were provided with 12 weekly sessions of group treatment. Dependent measures, taken at baseline, posttreatment, and 3-month follow-up, included self-report and observer-based assessments of depressive symptomatology. At posttreatment, both the PST and the RT conditions produced significant reductions in depressive symptoms, compared with the WLC group, and PST participants experienced significantly less depression than RT subjects. Moreover, a significantly greater proportion of participants in PST versus RT demonstrated sufficient positive change to warrant classification of their depression as improved or in remission at the posttreatment and follow-up evaluations.
Attenuated adrenocortical and blood pressure responses to psychological stress in ad libitum and abstinent smokers

Chronic smoking may alter physiological systems involved in the stress response. This study was designed to examine the effects of ad libitum smoking and abstinence on adrenocortical and cardiovascular responses to acute psychological stress in dependent cigarette smokers. We evaluated differences among abstinent smokers, smokers who continued to smoke at their normal rate, and nonsmokers in salivary cortisol concentrations, systolic and diastolic blood pressure (BP), heart rate (HR), and mood reports. Measurements were obtained during rest and in response to acute psychological stress (public speaking) in one session (stress session) and during continuous rest in a control session. Thirty-eight smokers (21 women) and 32 nonsmokers (18 women) participated. Smokers were assigned to either abstain from smoking the night prior to and the day of each session, or to continue smoking at their normal rate before each session. All groups showed significant stress-induced changes in BP and HR. Smokers, regardless of their assigned condition, showed attenuated systolic BP responses to the public-speaking stressor when compared to nonsmokers. While resting cortisol levels were greater among smokers than nonsmokers, no cortisol response to the acute stressor was demonstrated in either ad libitum or abstinent smokers. These results indicate that chronic smoking diminishes adrenocortical and cardiovascular responses to stress, and that short-term abstinence does not correct these alterations.
Controlled trial of an audit facilitator in diagnosis and treatment of childhood asthma in general practice.

To test whether an audit facilitator could alter the pattern of diagnosis and treatment of childhood asthma.



Randomised stratified controlled trial.



12 general practices in Tayside.



3373 children aged 1-15 inclusive who had symptoms suggestive of asthma or possible asthma drawn from a systematic review of 10,725 general practice case records.



Children were targeted for a clinical review by their general practitioner or practice nurses.



Asthma related consultations, prescriptions, hospital attendances, and health service costs 12 months before and after study.



Compared with controls (n = 1563) the intervention group (n = 1585) had more practice initiated consultations for asthma (relative risk 2.18 (95% confidence interval 1.74 to 2.73)), new diagnoses of asthma (2.83 (2.26 to 3.54)), and past diagnoses reaffirmed (1.30 (1.08 to 1.58)), and they were more frequently prescribed inhaled cromoglycate (1.52 (1.02 to 2.25)). Hospital inpatient day rates fell from 152 to 122 in the intervention group and rose from 69 to 117 in the control group between the year before and the year after study. Total primary care costs rose from 30,118 pounds to 37,243 pounds in the intervention group and fell from 29,131 pounds to 27,990 pounds in the control group. Hospital care cost fell in the intervention group from 25,406 pounds to 20,727 pounds and rose in the control group from 12,699 pounds to 19,650 pounds.



An audit facilitator can favourably influence the pattern of diagnosis and treatment of childhood asthma in general practice. This may have an impact on health service costs.
Subcutaneous Abatacept vErsus Intravenous Abatacept: A Phase IIIb Noninferiority Study in Patients With an Inadequate Response to Methotrexate

To compare the efficacy and safety of subcutaneous (SC) and intravenous (IV) abatacept.



In this phase IIIb double-blind, double-dummy, 6-month study, patients with rheumatoid arthritis (RA) and inadequate responses to methotrexate were randomized to receive 125 mg SC abatacept on days 1 and 8 and weekly thereafter (plus an IV loading dose [∼10 mg/kg] on day 1) or IV abatacept (∼10 mg/kg) on days 1, 15, and 29 and every 4 weeks thereafter. The primary end point for determining the noninferiority of SC abatacept to IV abatacept was the proportion of patients in each group meeting the American College of Rheumatology 20% improvement criteria (achieving an ACR20 response) at month 6. Other efficacy end points, immunogenicity, and safety were also assessed.



Of 1,457 patients, 693 of 736 (94.2%) treated with SC abatacept and 676 of 721 (93.8%) treated with IV abatacept completed 6 months. At month 6, 76.0% (95% confidence interval 72.9, 79.2) of SC abatacept-treated patients versus 75.8% (95% confidence interval 72.6, 79.0) of IV abatacept-treated patients achieved an ACR20 response (estimated difference between groups 0.3% [95% confidence interval -4.2, 4.8]), confirming noninferiority of SC abatacept to IV abatacept. Onset and magnitude of ACR responses and disease activity and physical function improvements were comparable between the SC and IV abatacept-treated groups. The proportions of adverse events (AEs) and serious AEs over 6 months were 67.0% and 4.2%, respectively, in the SC abatacept-treated group and 65.2% and 4.9%, respectively, in the IV abatacept-treated group, with comparable frequencies of serious infections, malignancies, and autoimmune events between groups. SC injection site reactions (mostly mild) occurred in 19 SC abatacept (IV placebo)-treated patients (2.6%) and 18 IV abatacept (SC placebo)-treated patients (2.5%). Abatacept-induced antibodies occurred in 1.1% of SC abatacept-treated patients and 2.3% of IV abatacept-treated patients.



SC abatacept provides efficacy and safety comparable with that of IV abatacept, with low immunogenicity and high retention rates, consistent with the established IV abatacept profile. Rates of injection site reactions were low. SC abatacept will provide additional treatment options, such as an alternative route of administration, for patients with RA.
Polymorphism of the DQA1 promoter region (QAP) and DRB1, QAP, DQA1, DQB1 haplotypes in systemic lupus erythematosus

We have investigated the DNA polymorphism for the DQA1 promoter region (QAP) and HLA-class II DRB1, DQA1, and DQB1 genes in 178 central European patients with Systemic lupus erythematosus (SLE) using polymerase chain reaction and Dig-ddUTP labeled oligonucleotides. Increased frequencies of DRB1*02 and *03 are confirmed by DNA typing. In addition, the frequencies of DQA1*0501, *0102 and DQB1*0201, *0602 alleles are increased in the patients as compared to controls. The strongest association to SLE is found with DRB1*03 and DQB1*0201 alleles (p<10−7, p corr. <10−5 and p<10−6, p corr. <10−4, respectively). By investigating the DQA1 promoter region in the SLE patients we have detected nine different QAP variants. Increased frequencies of QAP1.2 and QAP4.1 are observed in patients as compared to controls (p <0.05, p corr. = n. s.). Analysis of linkage disquilibria demonstrates a very strong association between QAP variants and DQA1, DRB1 alleles.  QAP variants are completely associated with DQA1 and DRB1 alleles, whereas others can combine with different DQA1 and DRB1 alleles. 02-positive patients and controls carry QAP1.2, and all DRB1*03-positive patients and controls carry QAP4.1. Conversely, the QAP1.2 variant appears only in DRB1*02 haplotypes, while the QAP4.1 variant can be observed in DRB1*03, *11, and *1303 haplotypes. Based on the strong linkage disequilibria between DRB1-DQA1-DQB1 genes and between DRB1-QAP-DQA1, we have deduced the four-point haplotypes for DRB1-QAP-DQA1-DQB1 in patients and controls. Two haplotypes DRB1*02-QAP1.2-DQA1*0102-DQB1*0602-and DRB1*03-QAP4.1-DQA1*0501-DQB1*0201 are significantly increased in patient as compared to controls (p<0.01, p corr. = n.s., RR = 1.8 and p <10−7, p corr. <10−5, RR = 3.1, respectively). The analysis of relative risks attributed to the various alleles of QAP, DQA1, and DQB1 as well as the investigation of the deduced DRB1-QAP-DQA1-DQB1 haplotypes leads to the conclusion that QAP4.1 and DQA1*0501 on the DR3 haplotypes are probably not involved in SLE susceptibility. There is no evidence for the involvement of DQ2 α/β dimers coded in transposition. Thus, susceptibility to SLE is on the DR3 haplotype most probably localized at DRB1 or telomeric of DRB1, while for the DR2 haplotype such orientation cannot be given.