nils-herrmann/clean_scirepeval huggingface dataset:
Relationship between preventability of death after coronary artery bypass graft surgery and all-cause risk-adjusted mortality rates.

The goal of this study was to determine the relationship between all-cause, risk-adjusted, in-hospital mortality after coronary artery bypass graft surgery and the proportion of preventable in-hospital deaths as a measure of quality of care at an institution level.



We conducted a retrospective analysis of 347 randomly selected in-hospital deaths after isolated coronary artery bypass graft surgery at 9 institutions in Ontario over the period of 1998 to 2003. Nurse-abstracted chart summaries were reviewed by 2 experienced cardiac surgeons who were blinded to patient, surgeon, and hospital and used a standardized implicit tool to identify preventable death. A third reviewer reassessed all cases in which the first 2 reviewers disagreed. Rates of preventable deaths were estimated for each hospital and compared with all-cause mortality rates. A structured adverse event audit completed by each surgeon-reviewer was used to identify quality improvement opportunities for the preventable deaths. A total of 111 of 347 deaths (32%) were judged preventable despite a low risk-adjusted mortality range (1.3% to 3.1%) across hospitals. No significant correlation was found between all-cause, risk-adjusted in-hospital mortality rates and the proportion of preventable deaths at the hospital level (Spearman coefficient, -0.42; P=0.26). A large proportion of preventable deaths were related to problems in the operating room (86%) and intensive care unit (61%). Many deaths were associated with deviations in perioperative care (32% based on concurrence of 2 reviewers, and another 42% in cases in which 1 reviewer reached that opinion).



Approximately one third of in-hospital coronary artery bypass graft deaths were judged preventable by surgeon reviewers. All-cause risk-adjusted mortality rates are convenient measures of institutional quality of care but were not correlated with preventable mortality in our jurisdiction. Providers should conduct detailed adverse event audits to drive meaningful improvements in quality.
Determining appropriate timing of adaptive radiation therapy for nasopharyngeal carcinoma during intensity-modulated radiation therapy

To determine appropriate timing of an adaptive radiation therapy (ART) replan by evaluating anatomic and dosimetric changes of target volumes and organs at risk (OARs) during intensity-modulated radiation therapy (IMRT) for nasopharyngeal carcinoma (NPC).



Nineteen NPC patients were recruited. Each patient had repeat computed tomography (CT) scans after each five fractions and at treatment completion. Automatic re-contouring the targets and OARs by using deformable registration algorithm was conducted through CT-CT fusion. Anatomic changes were assessed by comparing the initial CT and repeated CT. Hybrid plans with re-contouring were generated and the dose-volume histograms (DVH) of the hybrid plan and the original plan were compared.



Progressive volume reductions in gross target volume for primary disease (GTVnx), gross target volume for involved lymph nodes (GTVnd), and parotids were observed over time. Comparing with the original plan, each hybrid plan had no significant difference in homogeneity index (HI) for all the targets. Some parameters for planning target volumes for primary disease and high-risk clinical target volume (PTVnx and PTV1, respectively) improved significantly, notably starting from the 10th fraction. These parameters included mean dose (Dmean), dose to 95% of the volume (D95), percentage of the volume receiving 95% of the prescription dose (V95), and conformity index (CI) for PTVnx, and Dmean, D95, and CI for PTV1. The dosimetric parameters for PTVnd remained the same in general except for D95 and V95 which had significant improvement at specific time points; whereas for PTV2, similar trend of dosimetric changes was also observed. Dose to some OARs increased significantly at some time points.



There were significant anatomic and dosimetric changes in the targets and OARs. The target dose coverage in the hybrid plans did not get worse, but overdose occurred in some critical structures. Significant dosimetric changes should be considered as a trigger point at which ART replanning is indicated. D95/V95/CI for PTV2, Dmax for the brain stem, spinal cord, right eyeball and left lens, and Dmean/V30 for the parotids and glottis were taken into account for predicting the need for ART. Two replans at the 5th and 15th fractions were suggested.
The efficacy and biobehavioural basis of baclofen in the treatment of alcoholic liver disease (BacALD): study protocol for a randomised controlled trial.

Effective treatments for alcohol use disorders in those with significant liver disease are critically lacking. The primary aim of the current study is to explore the effectiveness and biobehavioural basis of low and high dose baclofen in improving treatment outcomes for alcohol dependence in people with alcoholic liver disease (The BacALD study).



This double-blind, placebo-controlled study will randomize 180 participants to a 12-week regime of either baclofen (30 mg/day baclofen, 75 mg/day baclofen) or placebo. Participants must meet the ICD-10 criteria for alcohol dependence in addition to alcoholic liver disease (ALD) defined as the presence of symptoms and/or signs referable to liver disease or its complications with or without cirrhosis. Primary outcome measures will include total abstinence duration, and time to lapse and relapse. Furthermore, 60 of the ALD patients enrolled in the trial will also participate in a pharmacokinetic and cue-reactivity component, along with an additional 30 healthy volunteers matched for age and gender randomised to a 1 week regime of either 30 mg/day baclofen or 75 mg/day baclofen. At week 1, plasma levels of baclofen and β-p-chlorophenol-γ-hydroxybutric acid will be measured at 0, 1 and 4 h following baclofen administration and psychophysiological responses to alcohol-associated stimuli will be assessed in a cue reactivity paradigm. Recruitment commenced in late March 2013.



This trial will demonstrate the efficacy and safety of two doses of baclofen in patients with alcoholic liver disease and will explore the biobehavioural mechanisms of the treatment effect.
Understanding and Fixing Multiple Language Interoperability Issues: The C/Fortran Case

We performed an empirical study to understand interoperability issues in C and Fortran programs. C/Fortran interoperability is very common and is representative of general language interoperability issues, such as how interfaces between languages are defined and how data types are shared. Fortran presents an additional challenge, since several ad hoc approaches to C/Fortran interoperability were in use long before a standard mechanism was defined. We explored 20 applications, automatically analyzing over 12 million lines of code. We found that only 3% of interoperability instances follow the ISO standard to describe interfaces; the rest follow a combination of compiler-dependent ad hoc approaches. Several parameters in cross-language functions did not have standards-compliant interoperable types, and about one-fourth of the parameters that were passed by reference could be passed by value. We propose that automated refactoring tools may provide a viable way to migrate programs to use the new interoperability features. We present two refactorings to transform code for this purpose and one refactoring to evolve code thereafter; all of these are instances of multiple language refactorings.
Investigation and management of iron deficiency anaemia in general practice: a cluster randomised controlled trial of a simple management prompt.

Iron deficiency anaemia (IDA) remains the most common cause of anaemia and is frequently secondary to occult gastrointestinal blood loss requiring further investigation. The study was designed to prospectively assess the adequacy of investigation of IDA and to establish whether a simple computerised prompt would increase the completeness of investigation of patients presenting to their general practitioners.



All men aged >20 and women aged >50 newly found to have a probable IDA (n=431) in primary care were randomised according to general practice (n=89) to one of two computer generated prompts, by the haematology laboratories in two large district general hospitals. Data were collected 12 months after the index date. The primary outcome measure was the adequacy of investigation of the cause of anaemia. Multiple logistic regression was used to analyse each binary outcome.



Two hundred and three (47%) of 431 patients presenting to their general practitioner with an IDA were adequately managed and 140/357 (39%) of patients who were otherwise fit for investigation had no tests at all. Twenty one (17%) of 125 patients who did have adequate investigation at the time of presentation were found to have colorectal cancer. Only 30% of patients had a confirmed diagnosis within 12 months. The prompt did not affect the level of investigation (odds ratio 0.88, 95% confidence interval (CI) 0.60 to 1.29, p=0.52). The initial prescribing of oral iron was improved (odds ratio 2.19, 95% CI 1.27 to 3.77, p=0.005), but not the documented prescribing of a full therapeutic course or the use of follow up blood counts.



The investigation and management of IDA presenting in general practice remains inadequate and is not improved by a simple management prompt.
Evaluation of an AIDS education programme for young adults.

To evaluate the impact of an AIDS education programme designed for young adults.



A randomised trial with a pre-post test design.



Participants were drawn from six youth training centres in the city of Nottingham, England.



All trainees aged 16-19 years attending the six centres were included in the sample and centres were randomly allocated to experimental (n = 173) and control (n = 164) groups. The response rate to both questionnaires was high (71%).



Data on sexual behaviour, knowledge, and attitudes towards HIV/AIDS were obtained by confidential questionnaire. Two thirds of the sample were sexually active. There were no differences between groups at pre-test and no differences by sex. The experimental group had a significantly higher level of knowledge than the control group post-test. Significantly more experimental than control trainees knew post-test that HIV could be transmitted via anal sex and through broken skin. In addition, twice as many experimental (53%) as control trainees (25%; p < 0.001) were aware that a cure for AIDS was unlikely in the near future. There were no observed effects on sexual behaviour, intentions, or attitudes.



The Streetwize UK educational programme had a significant impact on young adults' knowledge of HIV/AIDS transmission and prevention in the short term. If community based AIDS education is to do more than merely inform, however, resources must be made available for peer led interventions and skills training.
Uptake of an innovation in surgery: observations from the cluster-randomized Quality Initiative in Rectal Cancer trial.

Theory suggests the uptake of a medical innovation is influenced by how potential adopters perceive innovation characteristics and by characteristics of potential adopters. Innovation adoption is slow among the first 20% of individuals in a target group and then accelerates. The Quality Initiative in Rectal Cancer (QIRC) trial assessed if rectal cancer surgery outcomes could be improved through surgeon participation in the QIRC strategy. We tested if traditional uptake of innovation concepts applied to surgeons in the experimental arm of the trial.



The QIRC strategy included workshops, access to opinion leaders, intraoperative demonstrations, postoperative questionnaires, and audit and feedback. For intraoperative demonstrations, a participating surgeon invited an outside surgeon to demonstrate optimal rectal surgery techniques. We used surgeon timing in a demonstration to differentiate early and late adopters of the QIRC strategy. Surgeons completed surveys on perceptions of the strategy and personal characteristics.



Nineteen of 56 surgeons (34%) requested an operative demonstration on their first case of rectal surgery. Early and late adopters had similar perceptions of the QIRC strategy and similar characteristics. Late adopters were less likely than early adopters to perceive an advantage for the surgical techniques promoted by the trial (p = 0.023).



Most traditional diffusion of innovation concepts did not apply to surgeons in the QIRC trial, with the exception of the importance of perceptions of comparative advantage.
Efficacy and safety of CH-1504, a metabolically stable antifolate, in patients with active rheumatoid arthritis: results of a phase II multicenter randomized study.

To investigate the potential efficacy, safety, and tolerability of daily use of CH-1504 in patients with active rheumatoid arthritis (RA). US National Institutes of Health database no. NCT00658047.



In our phase II randomized double-blind double-dummy study, patients naive to methotrexate (MTX; n = 201) and having moderate to severe RA received either CH-1504 (0.25 mg, 0.5 mg, or 1.0 mg once-daily oral doses) or MTX (titrated to 20.0 mg once-weekly oral doses). All received weekly 10-mg folate supplementation. Efficacy and safety were assessed at 2, 4, 8, and 12 weeks, with a treatment-free followup at 16 weeks. Safety and tolerability were assessed. Primary efficacy endpoint was proportion of patients achieving ACR20 response at Week 12. Secondary endpoints included difference from baseline in the 28-joint Disease Activity Score (DAS28) and individual components of the American College of Rheumatology (ACR) composite index.



Demographic characteristics were similar in all treatment groups: mean age 54.3 ± 11.4 years, female sex 87%, mean baseline DAS28 6.6 ± 0.9. At Week 12, CH-1504 demonstrated comparable efficacy compared to MTX as measured by ACR20, DAS28, and ACR composite core-set measures, including tender and swollen joints. No dose-response relationship was observed. Adverse events across treatment groups were mild. Liver enzyme levels increased from baseline to Week 16 in the MTX group, with qualitatively lesser increases in the CH-1504 groups. Two patients in the MTX group withdrew because of gastrointestinal-related adverse events. CH-1504 appeared safe and well tolerated at all dose levels.



CH-1504 has comparable efficacy to MTX and is safe and well tolerated. Metabolically stable antifolates are a promising therapeutic option that warrants further study.
Phase II study of vinflunine in patients with metastatic renal cell carcinoma

An open-label, multicentre, non-comparative phase II trial to determine the response rate of intravenous vinflunine as first line chemotherapy in patients with metastatic renal cell carcinoma (RCC).  Patients with metastatic RCC were treated with vinflunine 350 mg/m2 (n = 11) or 320 mg/m2 (n = 22) administered intravenously every 21 days.  Out of 33 patients included in this study, one partial response was observed in the group treated at 350 mg/m2 and none in the group receiving 320 mg/m2 resulting in a response rate in this population of 9.1% (95% CI: 0.2–41.3). Median progression free survival was 5.6 months (95% CI: 2.8–14.4) for patients treated at 350 mg/m2, and 3.3 months (95% CI: 1.6–6.4) for those treated at 320 mg/m2.The median survival time was 10.4 months (95% CI: 6.8–12.4) for the whole study population. The principal toxicities were grade 3/4 neutropaenia —90.9% at 350 mg/m2 and 68.1% at 320 mg/m2, febrile neutropaenia was recorded in 3 patients (27.3%) at 350 mg/m2 and in 5 patients (22.7%) at 320 mg/m2. One episode of thromboembolic event was reported in 1 patient at each dose level.  Vinflunine given intravenously once every 3 weeks has not shown any clinically relevant activity in the management of patients with metastatic renal cell carcinoma; tolerance of the treatment was better at a dose of 320 mg/m2 than at 350 mg/m2.
Effect of intermittent fasting and refeeding on insulin action in healthy men.

Insulin resistance is currently a major health problem. This may be because of a marked decrease in daily physical activity during recent decades combined with constant food abundance. This lifestyle collides with our genome, which was most likely selected in the late Paleolithic era (50,000-10,000 BC) by criteria that favored survival in an environment characterized by fluctuations between periods of feast and famine. The theory of thrifty genes states that these fluctuations are required for optimal metabolic function. We mimicked the fluctuations in eight healthy young men [25.0 +/- 0.1 yr (mean +/- SE); body mass index: 25.7 +/- 0.4 kg/m(2)] by subjecting them to intermittent fasting every second day for 20 h for 15 days. Euglycemic hyperinsulinemic (40 mU.min(-1).m(-2)) clamps were performed before and after the intervention period. Subjects maintained body weight (86.4 +/- 2.3 kg; coefficient of variation: 0.8 +/- 0.1%). Plasma free fatty acid and beta-hydroxybutyrate concentrations were 347 +/- 18 and 0.06 +/- 0.02 mM, respectively, after overnight fast but increased (P < 0.05) to 423 +/- 86 and 0.10 +/- 0.04 mM after 20-h fasting, confirming that the subjects were fasting. Insulin-mediated whole body glucose uptake rates increased from 6.3 +/- 0.6 to 7.3 +/- 0.3 mg.kg(-1).min(-1) (P = 0.03), and insulin-induced inhibition of adipose tissue lipolysis was more prominent after than before the intervention (P = 0.05). After the 20-h fasting periods, plasma adiponectin was increased compared with the basal levels before and after the intervention (5,922 +/- 991 vs. 3,860 +/- 784 ng/ml, P = 0.02). This experiment is the first in humans to show that intermittent fasting increases insulin-mediated glucose uptake rates, and the findings are compatible with the thrifty gene concept.
Detection of child mental health disorders by general practitioners.

Few children with mental disorders access specialist services. Although previous studies suggest that general practitioner (GP) recognition is limited, parents may not be presenting these problems.



To compare GP recognition of disorders with child mental health data and to examine factors affecting recognition, in particular whether recognition is enhanced if the parent expresses concern during the consultation.



A two-phase design involving an initial community survey of children between the ages of 5 and 11 years. In the second phase, primary care attenders who were regarded by their GP as having a mental health disorder were compared with those who were not.



Five general practices in Croydon, outer London.



For 186 children attending primary care, GP recognition of disorders was compared with the results of a child mental health questionnaire completed by parents. Accuracy and predictors of GP recognition were examined.



Seventy-four per cent of children meeting criteria for caseness were not recognised by GPs as having a mental health disorder. The expression of parental concern in the consultation about a mental health problem increased the sensitivity of recognition from 26% to 88%. Expression of concern also increased GP recognition of non-cases; this reflected GP identification of other mental health and learning problems. Only a third of parents who had concerns expressed these during the consultation.



GPs are responsive to concern and take parental views into account. As well as detecting disorders, GPs are also sensitive to other psychosocial and educational problems that may present in primary care. There is a need for parental education about child mental health disorders.
A single anti-microRNA antisense oligodeoxyribonucleotide (AMO) targeting multiple microRNAs offers an improved approach for microRNA interference

Anti-miRNA antisense inhibitors (AMOs) have demonstrated their utility in miRNA research and potential in miRNA therapy. Here we report a modified AMO approach in which multiple antisense units are engineered into a single unit that is able to simultaneously silence multiple-target miRNAs, the multiple-target AMO or MTg-AMO. We validated the technique with two separate MTg-AMOs: anti-miR-21/anti-miR-155/anti-miR-17-5p and anti-miR-1/anti-miR-133. We first verified the ability of the MTg-AMOs to antagonize the repressive actions of their target miRNAs using luciferase reporter activity assays and to specifically knock down the levels of their target miRNAs using real-time RT-PCR methods. We then used the MTg-AMO approach to identify several tumor suppressors-TGFBI, APC and BCL2L11 as the target genes for oncogenic miR-21, miR-155 and miR-17-5p, respectively, and two cardiac ion channel genes HCN2 (encoding a subunit of cardiac pacemaker channel) and CACNA1C (encoding the alpha-subunit of cardiac L-type Ca(2+) channel) for the muscle-specific miR-1 and miR-133. We further demonstrated that the MTg-AMO targeting miR-21, miR-155 and miR-17-5p produced a greater inhibitory effect on cancer cell growth, compared with the regular single-target AMOs. Moreover, while using the regular single-target AMOs excluded HCN2 as a target gene for either miR-1 or miR-133, the MTg-AMO approach is able to reveal HCN2 as the target for both miR-1 and miR-133. Our findings suggest the MTg-AMO as an improved approach for miRNA target finding and for studying function of miRNAs. This approach may find its broad application for exploring biological processes involving multiple miRNAs and multiple genes.
A three-stage genome-wide association study identifies a susceptibility locus for late radiotherapy toxicity at 2q24.1

There is increasing evidence supporting the role of genetic variants in the development of radiation-induced toxicity. However, previous candidate gene association studies failed to elucidate the common genetic variation underlying this phenotype, which could emerge years after the completion of treatment. We performed a genome-wide association study on a Spanish cohort of 741 individuals with prostate cancer treated with external beam radiotherapy (EBRT). The replication cohorts consisted of 633 cases from the UK and 368 cases from North America. One locus comprising TANC1 (lowest unadjusted P value for overall late toxicity = 6.85 × 10−9, odds ratio (OR) = 6.61, 95% confidence interval (CI) = 2.23–19.63) was replicated in the second stage (lowest unadjusted P value for overall late toxicity = 2.08 × 10−4, OR = 6.17, 95% CI = 2.25–16.95; Pcombined = 4.16 × 10−10). The inclusion of the third cohort gave unadjusted Pcombined = 4.64 × 10−11. These results, together with the role of TANC1 in regenerating damaged muscle, suggest that the TANC1 locus influences the development of late radiation-induced damage.