nils-herrmann/clean_scirepeval huggingface dataset:
Intensive insulin therapy protects the endothelium of critically ill patients.

The vascular endothelium controls vasomotor tone and microvascular flow and regulates trafficking of nutrients and biologically active molecules. When endothelial activation is excessive, compromised microcirculation and subsequent cellular hypoxia contribute to the risk of organ failure. We hypothesized that strict blood glucose control with insulin during critical illness protects the endothelium, mediating prevention of organ failure and death. In this preplanned subanalysis of a large, randomized controlled study, intensive insulin therapy lowered circulating levels of ICAM-1 and tended to reduce E-selectin levels in patients with prolonged critical illness, which reflects reduced endothelial activation. This effect was not brought about by altered levels of endothelial stimuli, such as cytokines or VEGF, or by upregulation of eNOS. In contrast, prevention of hyperglycemia by intensive insulin therapy suppressed iNOS gene expression in postmortem liver and skeletal muscle, possibly in part via reduced NF-kappaB activation, and lowered the elevated circulating NO levels in both survivors and nonsurvivors. These effects on the endothelium statistically explained a significant part of the improved patient outcome with intensive insulin therapy. In conclusion, maintaining normoglycemia with intensive insulin therapy during critical illness protects the endothelium, likely in part via inhibition of excessive iNOS-induced NO release, and thereby contributes to prevention of organ failure and death.
Does asymmetric basal ganglia or thalamic activation aid in seizure foci lateralization on ictal SPECT studies?

Basal ganglia or thalamic activation has been reported in ictal SPECT studies of patients with intractable epilepsy. We hypothesized that lateralization of activation of these subcortical structures may aid in the lateralization of seizure foci in patients in whom the cortical focus is subtle or equivocal.



This was a retrospective analysis of 72 ictal (99m)Tc-ethylcysteinate dimer SPECT studies in 43 patients with intractable epilepsy in whom seizure laterality could be eventually determined. All patients underwent video-electroencephalography (EEG) monitoring, MRI, and one or more ictal SPECT scans as well as an interictal SPECT scan. Intracranial electrode EEG monitoring and surgery were performed as clinically indicated. Ictal and interictal studies were coregistered with patients' MRI scans using automated software, and ictal minus interictal subtraction images were obtained. The presence of asymmetric basal ganglia or thalamic activation was determined by 2 experienced observers who were unaware of clinical information. The final seizure focus was determined by surgical cure in 37 patients. In patients in whom surgery was not indicated or initial surgery was performed at another institution (n = 6), a consistent focus detected by intracranial electrode monitoring or repeated stereotypical seizures all originating from the same site on video-surface EEG monitoring was considered to indicate the final seizure focus.



Thirty-five patients had neocortical seizures and 8 had mesial temporal lobe seizures. Asymmetric basal ganglia activation was seen in 22 (30.6%) studies. This activation was ipsilateral to the final determined seizure focus in 17 of 22 of these studies (77.3%) and contralateral in 5 of 22 (21.7%). Asymmetric thalamic activation was seen in 15 studies (20.8%), of which 12 of 15 (80%) were ipsilateral to the final seizure focus, whereas 3 of 15 (20%) were contralateral. In 3 of 5 studies with contralateral basal ganglia activation and 1 of 3 studies with contralateral thalamic activation, the SPECT study as a whole was found to be falsely localizing. In another 2 cases of contralateral subcortical activation, the SPECT study as a whole was considered nonlocalizing. Worse outcome was not observed in patients with false ictal SPECT subcortical lateralization; however, the presence of asymmetric subcortical uptake, regardless of relationship to seizure focus, was associated with decreased incidence of seizures at 1 y after surgery.



Although asymmetric basal ganglia or thalamic activation is common, it is rarely the sole indicator of seizure localization. However, it may be a useful confirmatory sign in subtle cases of cortical localization. In cases of false ictal SPECT subcortical lateralization, the basal ganglia appear to follow cortical activation pattern. Furthermore, there appears to be a correlation between lateralizing uptake in subcortical structures on ictal SPECT and postsurgical outcome in intractable epilepsy patients.
Adefovir Dipivoxil Alone or in Combination with Ongoing Lamivudine in Patients with Decompensated Liver Disease and Lamivudine-resistant Hepatitis B Virus

The purpose of this prospective study was to evaluate the efficacy and safety of adefovir dipivoxil with or without ongoing lamivudine in decompensated lamivudine-resistant chronic hepatitis B patients. Forty-six hepatitis B e antigen (HBeAg)-positive patients with decompensated liver function and lamivudine-resistant hepatitis B virus (HBV) were assigned to adefovir dipivoxil monotherapy (n=18) or combination therapy with ongoing lamivudine (n=28) according to their own preference. After 24 weeks of treatment, 83% of monotherapy and 86% of combination therapy showed serum HBV DNA below detection limit (<0.5 pg/mL). Alanine aminotransferase (ALT) normalized in 78% and 82% respectively. Median Child-Pugh-Turcotte (CPT) score or Model for End-Stage Liver Disease (MELD) score reduced significantly by 3 or 5 point in monotherapy and 2 or 2 point in combination therapy respectively. There were no significant differences in rate of undetectable serum HBV DNA, median change of ALT and median reduction of CPT or MELD scores between the two groups. In conclusion, both adefovir dipivoxil monotherapy and combination therapy with ongoing lamivudine result in comparable virologic, biochemical, and clinical improvements in HBeAg-positive patients with decompensated liver function and lamivudine-resistant HBV. Combination with lamivudine showed no additional benefit over monotherapy during 24 weeks of treatment in these patients.
Bioequivalence of oral and intravenous carbamazepine formulations in adult patients with epilepsy

To evaluate the safety, tolerability, and comparative pharmacokinetics (PK) of intravenous and oral carbamazepine.



In this phase 1, open-label study, adult patients with epilepsy on a stable oral carbamazepine dosage (400-2,000 mg/day) were converted to intravenous carbamazepine (administered at 70% of the oral dosage). A 28-day outpatient period preceded an up to 10-day inpatient period and a 30-day follow-up period. Intravenous carbamazepine was administered over 15 or 30 min every 6 h on days 1-7; some patients in the 15-min group were eligible to receive four 2- to 5-min (rapid) infusions on day 8. Patients underwent blood sampling to determine the area under the concentration-time curve (AUC) for carbamazepine and metabolite carbamazepine-10,11-epoxide following oral (day 0) and intravenous carbamazepine administration (days 1, 7, and 8). Bioequivalence was evaluated in patients with normal renal function (creatinine clearance >80 ml/min). Safety assessments were conducted through day 38.



Ninety-eight patients enrolled and 77 completed the PK component. The mean daily oral and intravenous carbamazepine dosage for 64 PK-evaluable patients with normal renal function was 962.5 and 675.1 mg (70% of oral dosage), respectively. Steady-state minimum concentration (C(min)) and overall exposure (AUC0-24) for intravenous carbamazepine infused over 30, 15, or 2-5 min were similar to oral carbamazepine. The 90% confidence intervals (CIs) for the ratios of the adjusted means for AUC0-24, maximum concentration (Cmax), and C(min) were within the 80%-125% bioequivalence range for 30-min intravenous infusions versus oral administration, but exceeded the upper limit for Cmax for the 15-min and rapid infusions. All intravenous carbamazepine infusions were well tolerated.



Intravenous carbamazepine infusions (70% of oral daily dose) of 30-, 15-, and 2- to 5-min duration, given every 6 h, maintained patients' plasma carbamazepine concentrations. Intravenous carbamazepine 30-min infusions were bioequivalent to oral carbamazepine in patients with normal renal function; rapid infusions were well-tolerated in this study.
Cognitive dysfunction follows left heart catheterisation but is not related to microembolic count.

Left heart catheterisation with coronary angiography (CA) may lead to cognitive dysfunction, as a result of neurological injury. The aim was to assess the incidence of cognitive dysfunction in elderly patients three months after CA and investigate any association between cognitive dysfunction and microembolic count during CA.



This was a prospective observational study with a control cohort. Cognitive testing was undertaken at baseline and at 3 months using a battery of 8 neuropsychological tests. Subjects comprised 51 CA patients, aged ≥ 50 years, with normal baseline cognition, and 31 community control participants. Microemboli were measured by Transcranial Doppler throughout the procedure. All patients underwent trans-femoral CA with aortography and ventriculography. Cognitive dysfunction was defined in an individual when their reliable change index score was less than -1.96 on 2 or more tests and/or their combined z score was less than -1.96. Microembolic count was assessed by off-line manual counting and automatic software was also used to count and differentiate gaseous from solid microemboli.



Cognitive dysfunction was identified in 15.7% of patients at 3 months. Microemboli were detected in all patients, predominantly during aortography and ventriculography. The median total embolic count was 365 (IQR 192, 574), the majority being gaseous (84%). There was no multivariable association between cognitive dysfunction at 3 months and microembolic count.



This study demonstrated that cognitive dysfunction following CA is not associated with microembolic load. Cognitive dysfunction occurs in 15.7% of patients at 3 months. This is reassuring for the proceduralist and suggests that other perioperative elements are involved.
Comprehensive ICF core set for obstructive pulmonary diseases: validation of the activities and participation component through the patient's perspective.

This study aimed to validate the Activities and Participation component of the Comprehensive International Classification of Functioning, Disability and Health (ICF) Core Set for Obstructive Pulmonary Diseases (OPD) from the patient's perspective.



A cross-sectional qualitative study was conducted with a convenience sample of outpatients with Chronic Obstructive Pulmonary Disease (COPD). Individual interviews were performed and analysed according to the meaning condensation procedure.



Fifty-one participants (70.6% male) with a mean age of 69.5 ± 10.8 years old were included. Twenty-one of the 24 categories contained in the Activities and Participation component of the Comprehensive ICF Core Set for OPD were identified by the participants. Additionally, seven second-level categories that are not covered by the Core Set were reported: complex interpersonal interactions, informal social relationships, family relationships, conversation, maintaining a body position, eating and preparing meals.



The activities and participation component of the ICF Core Set for OPD was largely supported by the patient's perspective. The categories included in the ICF Core Set that were not confirmed by the participants and the additional categories that were raised need to be further investigated in order to develop an instrument according to the patient's perspective. This will promote a more patient-centred assessments and rehabilitation interventions.  Activities and Participation component of the Comprehensive ICF Core Set for OPD is largely supported by the perspective of patients with COPD and therefore could be used in the assessment of patients' individual and social life. The information collected through the Activities and Participation component of the Comprehensive ICF Core Set for OPD could be used to plan and assess rehabilitation interventions for patients with COPD.
A randomised evaluation of CollAborative care and active surveillance for Screen-Positive EldeRs with sub-threshold depression (CASPER): study protocol for a randomized controlled trial

Depression accounts for the greatest burden of disease among all mental health problems, and is expected to become the second-highest amongst all general health problems by 2020. By the age of 75, 1 in 7 older people meet formal diagnostic criteria for depression. Efforts to ameliorate the burden of illness and personal suffering associated with depression in older people have focussed on those with more severe depressive syndromes. Less attention has been paid to those with mild disorders/sub-threshold depressive syndromes but these patients also suffer impairments in their quality of life and level of functioning.



The CASPER study has been designed to assemble an epidemiological cohort of people over 75 years of age (the CASPER cohort), from which we will identify those eligible to participate in a trial of collaborative care for sub-threshold depression (the CASPER trial).We aim to undertake a pragmatic randomised controlled multi-centre trial evaluating the effectiveness and cost-effectiveness of collaborative care; a low intensity psychological intervention in addition to usual general practitioner care versus usual general practitioner care alone. General practitioners from practices based in the North of England will be asked to identify potentially eligible patients over the age of 75 years. Patients will be sent a letter inviting them to participate in the study.We aim to recruit approximately 540 participants for the CASPER trial. A diagnostic interview will be carried out to ascertain trial eligibility with the major depressive episode module of the Mini International Neuropsychiatric Interview (M.I.N.I.), eligible participants randomised to either the intervention or usual care. The primary outcome will be measured with the Patient Health Questionnaire-9 (PHQ-9) and additional quality of life measures will be collected. Data will be collected at baseline, 4 and 12 months for both trial and cohort participants.
Effects of a whey protein supplementation on intrahepatocellular lipids in obese female patients.

High protein diets have been shown to improve hepatic steatosis in rodent models and in high-fat fed humans. We therefore evaluated the effects of a protein supplementation on intrahepatocellular lipids (IHCL), and fasting plasma triglycerides in obese non diabetic women.



Eleven obese women received a 60 g/day whey protein supplement (WPS) for 4-weeks, while otherwise nourished on a spontaneous diet, IHCL concentrations, visceral body fat, total liver volume (MR), fasting total-triglyceride and cholesterol concentrations, glucose tolerance (standard 75 g OGTT), insulin sensitivity (HOMA IS index), creatinine clearance, blood pressure and body composition (bio-impedance analysis) were assessed before and after 4-week WPS.



IHCL were positively correlated with visceral fat and total liver volume at inclusion. WPS decreased significantly IHCL by 20.8 ± 7.7%, fasting total TG by 15 ± 6.9%, and total cholesterol by 7.3 ± 2.7%. WPS slightly increased fat free mass from 54.8 ± 2.2 kg to 56.7 ± 2.5 kg, p = 0.005). Visceral fat, total liver volume, glucose tolerance, creatinine clearance and insulin sensitivity were not changed.



WPS improves hepatic steatosis and plasma lipid profiles in obese non diabetic patients, without adverse effects on glucose tolerance or creatinine clearance.
Re: Projecting individualized absolute invasive breast cancer risk in African American women.

In their " Discussion, " Gail et al. (1) seem to be saying that a problem with a model's concordance statistic (or area under a receiver operating curve [AUC]) is that it is inherently retrospective, implying that one should therefore not place much stock in it. The concordance statistic from the Gail model is retrospective in the same sense that the Gail model's parameter estimates (which produce the estimated risks) are retrospective; that is, all of these measures derive from existing data on risk factors and outcomes. As is the case with the model's parameter estimates, if the model is applied to a sample or population similar in key respects to that from which it has been derived, we can reasonably expect that the AUC will be generalizable. The key issue about the AUC is not, then, that it is retrospective or at least any more retrospective than parameter estimates. The authors next state that " … if a model includes age only and predicts that every woman in the age range 60-64 years has a 1.7% risk of breast cancer … then the AUC will be 0.50. Some would mistakenly construe this to mean that the model does not perform any better than a coin fl ip in predicting who will or will not get breast cancer. In fact, if one predicted that none of these women would be diagnosed with invasive breast cancer in the next fi ve years, one would predict correctly for 100 – 1.7 = 98.3% of the women. " This latter statement is true, but one does not need to rely on such a statistical model as support for a prediction that no women will get breast cancer during a period of 5 years. One simply needs general population incidence rates to see that only a small minority of women will develop disease over a period of 5 years. In recent years, the Gail model has been promoted as a decision-making aid for women with respect to chemo-prevention of breast cancer. If the goal in providing risk estimates is to help women with such dichotomous decision making about prophylaxis, or even with entrance (or not) into a clinical trial, one cannot imply that a model is doing a good job by giving everyone the same risk estimate. A model that gives each person the same risk estimate has zero discriminatory ability — no individual …
Markers of endothelial and platelet activation are associated with high on-aspirin platelet reactivity in patients with stable coronary artery disease.

Aspirin inhibits the cyclooxygenase-1 (COX-1) mediated thromboxane A2 synthesis. Despite COX-1 inhibition, in patients with coronary artery disease (CAD), platelets can be activated through other mechanisms, like activation by thrombin.



At baseline in this cross-sectional substudy of the ASCET trial, 1001 stable CAD patients, all on single aspirin treatment, were classified by the PFA100® method, as having high on-aspirin residual platelet reactivity (RPR) or not. Markers of hypercoagulability, endothelial and platelet activation as related to RPR, were evaluated to explore the potential mechanisms behind high on-aspirin RPR.



Altogether, 25.9% (n=259) of the patients were found to have high on-aspirin RPR. S-thromboxane B(2) levels were very low and did not differ between patients having high on-aspirin RPR or not. Patients with high on-aspirin RPR had significantly higher levels of von Willebrand Factor (vWF) (124 vs 100%, p<0.001, platelet count (236 vs 224 × 10(9)/l, p=0.008), total TFPI (68.4 vs 65.5 ng/ml, p=0.005) and ß-thromboglobulin (ß-TG) (33.3 vs 31.3 IU/ml, p=0.041) compared to patients with low on-aspirin RPR. No significant differences between the groups were observed in levels of endogenous thrombin generation (ETP), pro-thrombin fragment 1+2 (F1+2), D-dimer, soluble TF (sTF) or P-selectin (all p>0.05).



The high on-aspirin RPR as defined by PFA100® seems not to be due to increased thrombin activity as evaluated with ETP, sTF, F1+2 or D-dimer. The elevated levels of platelet count, ß-TG, TFPI and especially vWF might be explained by increased endothelial and platelet activation in these patients.
Validation and comparative evaluation of the osteoporosis self-assessment tool (OST) in a Caucasian population from Belgium.

Risk indices have been developed to identify women at risk of low bone mineral density (BMD) who should undergo BMD testing.



To compare the performance of four risk indices in White ambulatory women in Belgium.



Epidemiological cross-sectional study.



Records were analysed for 4035 postmenopausal White women without Paget's disease or advanced osteoarthritis, seen at an out-patient osteoporosis centre between January 1996 and September 1999. Osteoporosis risk index scores were compared to bone density T-scores. The ability of each risk index to identify women with low BMD (T-score < -2.0) or osteoporosis (T < -2.5) was evaluated.



Using an Osteoporosis Self-Assessment Tool (OST) score <2 to recommend DXA referral, sensitivity ranged from 85% at the lumbar spine to 97% at the total hip to detect BMD T-scores of <or= -2.5, and specificity ranged from 34% at the total hip to 37% at the femoral neck and lumbar spine. The negative predictive value was high at all skeletal sites (89-99%), demonstrating the usefulness of the OST to identify patients who have normal BMD and should not receive DXA testing. All risk indices performed similarly, although the OST had somewhat better sensitivity and somewhat lower specificity than the other indices at the cut-offs evaluated. Among the 11-12% of women who were classified as highest risk using OST or the Osteoporosis Index of Risk (OSIRIS), 81-85% had low bone mass and 68-74% had osteoporosis.



The performance of these risk indices among women in Belgium was similar to that reported earlier for other samples in Asian countries, the US, and the Netherlands. The OST and other risk indices are effective and efficient tools to help target high-risk women for DXA testing.
Genome-wide association study and admixture mapping identify different asthma-associated loci in Latinos: the Genes-environments & Admixture in Latino Americans study.

Asthma is a complex disease with both genetic and environmental causes. Genome-wide association studies of asthma have mostly involved European populations, and replication of positive associations has been inconsistent.



We sought to identify asthma-associated genes in a large Latino population with genome-wide association analysis and admixture mapping.



Latino children with asthma (n = 1893) and healthy control subjects (n = 1881) were recruited from 5 sites in the United States: Puerto Rico, New York, Chicago, Houston, and the San Francisco Bay Area. Subjects were genotyped on an Affymetrix World Array IV chip. We performed genome-wide association and admixture mapping to identify asthma-associated loci.



We identified a significant association between ancestry and asthma at 6p21 (lowest P value: rs2523924, P < 5 × 10(-6)). This association replicates in a meta-analysis of the EVE Asthma Consortium (P = .01). Fine mapping of the region in this study and the EVE Asthma Consortium suggests an association between PSORS1C1 and asthma. We confirmed the strong allelic association between SNPs in the 17q21 region and asthma in Latinos (IKZF3, lowest P value: rs90792, odds ratio, 0.67; 95% CI, 0.61-0.75; P = 6 × 10(-13)) and replicated associations in several genes that had previously been associated with asthma in genome-wide association studies.



Admixture mapping and genome-wide association are complementary techniques that provide evidence for multiple asthma-associated loci in Latinos. Admixture mapping identifies a novel locus on 6p21 that replicates in a meta-analysis of several Latino populations, whereas genome-wide association confirms the previously identified locus on 17q21.