nils-herrmann/clean_scirepeval huggingface dataset:
Clinical significance of treatment effects with aripiprazole versus placebo in a study of manic or mixed episodes associated with pediatric bipolar I disorder.

Published studies in adult and pediatric bipolar disorder have used different definitions of treatment response. This analysis aimed to compare different definitions of response in a large sample of children and adolescents.



Anexploratory analysis of a 4-week, multicenter, placebo-controlled study assessed patients (n=296; ages, 10-17 years) with an acute manic/mixed episode associated with BIPOLAR I disorder who were randomized to aripiprazole (10 or 30 mg/day) or placebo. The primary efficacy endpoint was mean change from baseline to week 4 in young mania rating scale (YMRS) total score.  clinical global impressions-bipolar disorder (CGI-BP) Overall and mania scales, child global assessment scale (CGAS), and parent and subject general behavior inventory. Response was compared across seven operational definitions. Cohen's κ and Spearman's correlation tested relationships between various response definitions or changes in outcome measures and clinically meaningful improvement (defined as a CGI-BP overall improvement score of 1 or 2).



Response rates varied depending upon the operational definition, but were highest for 95% reliable change (statistical method used to determine individual change from previous assessment) and ≥33% reduction in YMRS total score. Response rate definitions with the highest validity in terms of predicting clinically meaningful improvement were: ≥50% reduction on YMRS (κ=0.64), a composite definition of response (YMRS <12.5, children's depression rating scale-revised (CDRS-R) ≤40, and CGAS ≥51; κ=0.59), and 95% reliable change on the CGAS or 33% reduction on YMRS (κ=0.56). Parent ratings of symptoms were generally better at detecting symptom improvement than were subject ratings (κ=∼0.4-0.5 vs. ∼0.2 when compared with CGI-BP overall improvement score).



Clinically meaningful definitions of response in acute treatment of a manic/mixed episode in pediatric subjects include a 50% change in YMRS and a composite measure of response. Parent-reported measures of symptom improvement appear reliable for assessing symptom change.
Enoxaparin dosing and associated risk of in-hospital bleeding and death in patients with non ST-segment elevation acute coronary syndromes.

The efficacy of enoxaparin sodium in non-ST-segment elevation acute coronary syndromes is well established; however, concerns remain regarding bleeding risk. The extent to which bleeding risk is attributable to excess dosing of enoxaparin is unclear.



Using data from the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines) National Quality Improvement Initiative, we determined the frequency of administration of excess (>10 mg above the recommended dose), lower-than-recommended (>10 mg below the recommended dose), and recommended doses of enoxaparin. We also determined unadjusted and adjusted risks of in-hospital major bleeding and death associated with excess and lower-than-recommended doses of enoxaparin.



Of 10 687 patients, 2002 (18.7%) received an excess dose and 3116 (29.2%) received a lower-than-recommended dose of enoxaparin. Patients receiving excess doses were older (median age, 78 vs 66 years), smaller (median body mass index [calculated as weight in kilograms divided by height in meters squared], 26.2 vs 27.8), and more likely to be female (59.5% vs 38.2%) than patients receiving recommended doses (P < .001 for all). After adjustment for baseline characteristics, an excess dose was significantly associated with major bleeding (odds ratio, 1.43; 95% confidence interval [CI], 1.18-1.75) and death (odds ratio, 1.35; 95% CI, 1.03-1.77) compared with a recommended dose. A lower-than-recommended dose was not associated with major bleeding (odds ratio, 1.01; 95% CI, 0.84-1.21), but there was a trend toward higher mortality (odds ratio, 1.25; 95% CI, 0.93-1.68).



Almost half the patients treated with enoxaparin did not receive a recommended dose and had worse outcomes, especially those receiving an excess dose. Improved adherence to the recommended dose could substantially improve the safety profile of enoxaparin.
Risk of colorectal cancer seven years after flexible sigmoidoscopy screening: randomised controlled trial

To determine the risk of colorectal cancer after screening with flexible sigmoidoscopy.



Randomised controlled trial.



Population based screening in two areas in Norway-city of Oslo and Telemark county (urban and mixed urban and rural populations).



55 736 men and women aged 55-64 years.



Once only flexible sigmoidoscopy screening with or without a single round of faecal occult blood testing (n=13 823) compared with no screening (n=41 913).



Planned end points were cumulative incidence and mortality of colorectal cancer after 5, 10, and 15 years. This first report from the study presents cumulative incidence after 7 years of follow-up and hazard ratio for mortality after 6 years.



No difference was found in the 7 year cumulative incidence of colorectal cancer between the screening and control groups (134.5 v 131.9 cases per 100 000 person years). In intention to screen analysis, a trend towards reduced colorectal cancer mortality was found (hazard ratio 0.73, 95% confidence interval 0.47 to 1.13, P=0.16). For attenders compared with controls, a statistically significant reduction in mortality was apparent for both total colorectal cancer (hazard ratio 0.41, 0.21 to 0.82, P=0.011) and rectosigmoidal cancer (0.24, 0.08 to 0.76, P=0.016).



A reduction in incidence of colorectal cancer with flexible sigmoidoscopy screening could not be shown after 7 years' follow-up. Mortality from colorectal cancer was not significantly reduced in the screening group but seemed to be lower for attenders, with a reduction of 59% for any location of colorectal cancer and 76% for rectosigmoidal cancer in per protocol analysis, an analysis prone to selection bias.
Survival benefit in a randomized clinical trial of faecal occult blood screening for colorectal cancer.

Early detection of colorectal cancer could reduce cancer-specific mortality. The aim of this trial was to evaluate the effect of faecal occult blood test (FOBT) screening on colorectal cancer mortality in a Swedish population.



All 68,308 citizens in Göteborg born between 1918 and 1931 were randomized to a screening or a control group at the age of 60-64 years. All were screened two to three times with rehydrated Hemoccult-II. Compliance was 70.0 per cent (23,916 individuals). Those with a positive test result were offered sigmoidoscopy and a double-contrast enema. The primary endpoint was death from colorectal cancer.



After a mean of 9 years from the last screening, there was a significant reduction in colorectal cancer mortality in the screening group compared with the control group. The overall risk ratio of death from colorectal cancer was 0.84 (95 per cent confidence interval 0.71 to 0.99). The groups did not differ in incidence of colorectal cancer or in overall mortality.



FOBT screening significantly reduces colorectal cancer mortality.
Internal consistency and validity of the Stroke Impact Scale 2.0 (SIS 2.0) and SIS-16 in an Australian sample

The impact of stroke is multidimensional however standard stroke measures do not discriminate well when stroke patients are less physically impaired. The Stroke Impact Scale 2.0 (SIS 2.0) is a multidimensional measure of the impact of stroke but its' psychometric properties require further testing. The SIS-16 is a measure of physical functioning designed to be more sensitive to differences in physical functioning than current stroke outcome measures but there is only preliminary information detailing its' reliability and validity. The current study examined the internal consistency and validity of the SIS 2.0 and SIS-16 in an Australian sample of stroke patients.  The SIS 2.0, SIS-16, World Health Organization Bref-Scale (WHOQOL-BREF) and Zung's Self-Rating Depression Scale (SDS) were completed by 74 stroke patients in rural Victoria, Australia.  The item convergent validity index indicated good item convergence of the SIS-16 and SIS 2.0 domains. The item discriminant validity index had only adequate divergence for most SIS 2.0 domains. Internal consistencies of the SIS-16 and SIS 2.0 domains were acceptable (α = 0.87–0.95). Correlations between the SIS-16 and SIS 2.0 and the WHOQOL-BREF and SDS supported the convergent and discriminant validity of the SIS-16 and all the dimensions of the SIS 2.0 except 'Participation' which lacked discriminant validity.  The SIS 2.0 and SIS-16 had good psychometric properties with support for the internal consistency and validity of both measures.
Circulating atrial natriuretic peptide genetic association study identifies a novel gene cluster associated with stroke in whites.

The goal of this study was to identify genetic determinants of plasma N-terminal proatrial natriuretic peptide (NT-proANP) in the general community by performing a large-scale genetic association study and to assess its functional significance in in vitro cell studies and on disease susceptibility.



Genotyping was performed across 16 000 genes in 893 randomly selected individuals, with replication in 891 subjects from the community. Plasma NT-proANP1-98 concentrations were determined using a radioimmunoassay. Thirty-three genome-wide significant single-nucleotide polymorphisms were identified in the MTHFR-CLCN6-NPPA-NPPB locus and were all replicated. To assess the significance, in vitro functional genomic studies and clinical outcomes for carriers of a single-nucleotide polymorphism rs5063 (V32M) located in NPPA that represented the most significant variation in this genetic locus were assessed. The rs5063 variant allozyme in transfected HEK293 cells was decreased to 55±8% of wild-type protein (P=0.01) as assessed by quantitative western blots. Carriers of rs5063 had lower NT-proANP levels (1427 versus 2291 pmol/L; P<0.001) and higher diastolic blood pressures (75 versus 73 mm Hg; P=0.009) and were at an increased risk of stroke when compared with wild-type subjects independent of age, sex, diabetes mellitus, hypertension, atrial fibrillation, and cholesterol levels (hazard ratio, 1.6; P=0.004).



This is the first large-scale genetic association study of circulating NT-proANP levels performed with replication and functional assessment that identified genetic variants in the MTHFR-CLCN6-NPPA-NPPB cluster to be significantly associated with NT-proANP levels. The clinical significance of this variation is related to lower NT-proANP levels, higher blood pressures, and an increased risk of stroke in the general community.
Endoscopic band ligation versus propranolol for the primary prophylaxis of variceal bleeding in cirrhotic patients with high risk esophageal varices.

Gastroesophageal variceal bleeding is a common complication of portal hypertension. Current guidelines recommend thorn-blockers for primary prophylaxis. However, evidence suggests that endoscopic variceal ligation (EVL) reduce bleeding episodes.



To compare endoscopic EVL with propranolol (PPL) for primary prophylaxis of variceal bleeding.



We conducted a randomized controlled trial. Over a 9-year period, 75 patients with cirrhosis and high-risk esophageal varices (HREV) were recruited and allocated to EVL (n=39) or PPL (n=36). Primary outcome was variceal bleeding. Secondary outcomes were survival, source of bleeding and serious adverse events. Analyses were made by intention-to-treat.



Baseline characteristics were similar. Medium follow-up was 1647+/-1096 days. complete follow-up was achieved in 85% of patients. Variceal bleeding occurred in 12% of EVL and in 25% of PPL group (p=0.17). The actuarial risks of bleeding after 2 years were similar in both groups. Overall mortality was 51% in EVL and 33% in PPL group (p=0.17). Patients in the EVL group showed a lower rate of esophageal variceal bleeding (5.1% v/s 25%, p=0.027) and a higher rate of subcardial variceal bleeding compared with PPL group (7.7% v/s 0%, p=0.027). Serious adverse events related to EVL occurred in 2 patients, including 1 death.



The present study supports that PPL should be considered the first choice in primary prophylaxis of variceal bleeding offering similar effects and lower severe adverse events compared with EVL.
Accuracy of colposcopy in the diagnostic setting compared with the screening setting.

To estimate the accuracy of colposcopy to identify cervical precancer in screening and diagnostic settings.



As part of a larger clinical trial to evaluate the diagnostic accuracy of optical spectroscopy, we recruited 1,850 patients into a diagnostic or a screening group depending on their history of abnormal findings on Papanicolaou tests. Colposcopic examinations were performed and biopsies specimens obtained from abnormal and normal colposcopic sites for all patients. The criterion standard of test accuracy was the histologic report of biopsies. We calculated sensitivities, specificities, likelihood ratios, receiver operating characteristic curves, and areas under the receiver operating characteristic curves.



The prevalence of high-grade squamous intraepithelial lesions (HSIL) or cancer was 29.0% for the diagnostic group and 2.2% for the screening group. Using a disease threshold of HSIL, colposcopy had a sensitivity of 0.983 and a specificity of 0.451 in the diagnostic group when the test threshold was low-grade squamous intraepithelial lesions (LSIL), and a sensitivity of 0.714 and a specificity of 0.813 when the test threshold was HSIL. Using the same HSIL disease threshold, in the screening group, colposcopy had a sensitivity of 0.286 and a specificity of 0.877 when the test threshold was LSIL, and a sensitivity of 0.191 and a specificity of 0.961 when the threshold was HSIL. The colposcopy area under the receiver operating characteristic curve was 0.821 (95% confidence interval 0.79-0.85) in the diagnostic setting compared with 0.587 (95% confidence interval 0.56-0.62) in the screening setting. Changing the disease threshold to LSIL demonstrated similar patterns in the tradeoff of sensitivity and specificity and measure of accuracy.



Colposcopy performs well in the diagnostic setting and poorly in the screening setting. Colposcopy should not be used to screen for cervical intraepithelial neoplasia.
Different functional outcomes in patients with delirium and subsyndromal delirium one month after hospital discharge.

Subsyndromal delirium has an increasing relevance in the medical literature. There are only three studies in hospitalized elderly patients. Our goal is to demonstrate the importance of this syndrome in a population with more complexity and cognitive impairment than in previous studies.



Prospective multicentre study in three tertiary hospitals. The health outcomes recorded in the follow-up at 1 month were the persistence of delirium, hospital readmission, discharge destination, death, Barthel index and the Delirium Rating Scale Revised 98. To assess the impact of delirium in the Barthel index at 30 days, we adjusted univariate and multivariate linear regression models.



85 patients were enrolled; 75.3% of the patients had at least 1 positive item in the Confusion Assessment Method; 45 patients (53%) were diagnosed with delirium and 19 (22.3%) with subsyndromal delirium (SSD). The 30-day risk of death was associated with lower levels of albumin (p = 0.021) and the Cumulative Illness Rating Scale in Geriatrics (CIRS-G; p = 0.003). Adjusting for CIRS-G and the initial Barthel index, the diagnosis of delirium appears to be related to a lower Barthel index at 30 days (p = 0.019), showing a significant linear gradient (p < 0.005).



SSD could help get more accurate diagnoses as well as improve patient management.
Recurrence after hepatic resection in colorectal 
cancer liver metastasis
-Review article-


The outcomes and management of colorectal liver metastasis have undergone many changes. The incidence of recurrence after liver resection for hepatic metastasis remains very high. Liver resection, which provides the only curative treatment, is believed to have improved the long-term outcome of these patients. However, the management and outcomes of patients with colorectal liver metastasis have greatly improved in the last decade, suggesting that the current use of aggressive multimodality treatments, including surgical resection combined with modern chemotherapeutic regimens, effectively prolong the life expectancy of these patients.
Bedside end-tidal CO2 tension as a screening tool to exclude pulmonary embolism.

End tidal carbon dioxide tension (P(ET,CO(2))) is a surrogate for dead space ventilation which may be useful in the evaluation of pulmonary embolism (PE). We aimed to define the optimal P(ET,CO(2)) level to exclude PE in patients evaluated for possible thromboembolism. 298 patients were enrolled over 6 months at a single academic centre. P(ET,CO(2)) was measured within 24 h of contrast-enhanced helical computed tomography, lower extremity duplex or ventilation/perfusion scan. Performance characteristics were measured by comparing test results with clinical diagnosis of PE. PE was diagnosed in 39 (13%) patients. Mean P( ET,CO(2)) in healthy volunteers did not differ from P( ET,CO(2)) in patients without PE (36.3+/-2.8 versus 35.5+/-6.8 mmHg). P(ET,CO(2 )) in patients with PE was 30.5+/-5.5 mmHg (p<0.001 versus patients without PE). A P(ET,CO(2)) of >or=36 mmHg had optimal sensitivity and specificity (87.2 and 53.0%, respectively) with a negative predictive value of 96.6% (95% CI 92.3-98.5). This increased to 97.6% (95% CI 93.2-99.) when combined with Wells score <4. A P(ET,CO(2)) of >or=36 mmHg may reliably exclude PE. Accuracy is augmented by combination with Wells score. P( ET,CO(2)) should be prospectively compared to D-dimer in accuracy and simplicity to exclude PE.
Measurement of novel biomarkers of neuronal injury and cerebral oxygenation after routine vaginal delivery versus cesarean section in term infants.

It remains unclear if mode of delivery can have any impact on the neonatal brain. Our aim was to determine in term newborns any differences based on mode of delivery in either neuronal injury biomarkers, phosphorylated axonal neurofilament heavy chain (pNF-H) and ubiquitin C-terminal hydrolase (UCHL1), or brain oxygenation values, regional cerebral tissue oxygen saturation (CrSO2) and cerebral fractional tissue oxygen extraction (CFOE).



An Institutional Review Board approved prospective observational pilot study of well newborns. Serum pNF-H and UCHL1 levels were measured on the day following delivery. CrSO2 values along with CFOE values were also measured using near-infrared spectroscopy (NIRS) and pulse oximetry.



There were 22 subjects, 15 born vaginally and seven born by cesarean section. No difference was found in mean pNF-H (107.9±54.3 pg/mL vs. 120.2±43.3 pg/mL, P=0.66) or mean UCHL1 (4.0±3.5 pg/mL vs. 3.0±2.2 pg/mL, P=0.68). No difference was found in mean CrSO2 (80.8±5.3% vs. 80.8±5.6%, P=0.99) or mean CFOE (0.17±0.06 vs. 0.15±0.08, P=0.51).



We found no difference in neuronal injury markers between term neonates born vaginally compared to those born by cesarean section. From a neurologic standpoint, this supports current obstetric practice guidelines that emphasize vaginal birth as the preferred delivery method whenever possible.
Infusion of 7.2% NaCl/6% hydroxyethyl starch 200/0.5 in on-pump coronary artery bypass surgery patients: a randomized, single-blind pilot study.

NaCl 7.2%/6% hydroxyethyl starch (HES) 200/0.5 (HSH) has shown its beneficial effects in cardiac surgery and immunomodulatory values in experiment and human studies. However, there is concern regarding detrimental renal effects of chloride and HES in the intensive care setting.



The objective of this study was to evaluate the influence of HSH on kidney integrity and the level of inflammatory mediators in on-pump coronary artery bypass surgery patients.



This was a single-center, prospective, randomized, single-blind pilot study.



This work was performed at a tertiary cardiothoracic referral center during the period from February to August 2012.



Forty patients scheduled for on-pump coronary artery bypass surgery were included.



PATIENTS were randomized to receive once either 7.2% NaCl/6% HES 200/0.5 (HSH group, n = 20) or placebo (0.9% NaCl; control group, n = 20) at a dose of 4 mL·kg for 30 min after anesthesia induction.



The primary end point was the incidence of acute kidney injury (AKI) defined according to the Kidney Disease: Improving Global Outcomes. Secondary end points were peak serum cystatin C, peak urine neutrophil gelatinase-associated lipocalin, plasma levels of interleukin 6 (IL-6), IL-10, intercellular adhesion molecule 1, and endothelial-leukocyte adhesion molecule (E-selectin).



The incidence of AKI within 48 h was similar between the groups (HSH: four patients [20%]; control: six patients [30%]). There was a significantly lower peak value for serum cystatin C in the HSH group (0.83 [0.73-0.89] mg·L) compared with the control group (1.02 [0.88-1.15] mg·L; P = 0.001). PATIENTS in both groups had similar peak postoperative urine neutrophil gelatinase-associated lipocalin concentrations. NaCl 7.2%/6% hydroxyethyl starch 200/0.5 significantly reduces levels of IL-6 and IL-10 at 4 h after cardiopulmonary bypass and intercellular adhesion molecule 1 and E-selectin at 4 h after cardiopulmonary bypass and on postoperative day 1 (P < 0.05 for all).



NaCl 7.2%/6% hydroxyethyl starch 200/0.5 does not lead to the increase in AKI incidence when used for the volume therapy in on-pump coronary artery bypass surgery patients. NaCl 7.2%/6% hydroxyethyl starch 200/0.5 usage enhanced neither tubular injury nor alteration of glomerular filtration. In addition, HSH can reduce the level of the inflammatory mediators after surgery.
Can learning potential in schizophrenia be assessed with the standard CVLT-II? An exploratory study.

This study examined the potential of using the regular administration of a common neuropsychological test, the CVLT-II, to assess learning potential in schizophrenia. Based on List A trial 1 performance and the learning slope, a schizophrenia sample was divided into three learning potential groups (non-learners, learners and high-achievers) that differed in the use of learning strategies. High-achievers utilized more semantic clustering than learners and non-learners, and non-learners were less consistent in words recalled than the other two groups. This standard administration approach is a promising, time-saving alternative to the modified tests of learning potential used so far.