nils-herrmann/clean_scirepeval huggingface dataset:
Dabigatran attenuates thrombin generation to a lesser extent than warfarin: could this explain their differential effects on intracranial hemorrhage and myocardial infarction?

Compared with warfarin, dabigatran is associated with less intracranial hemorrhage, but an increased risk of myocardial infarction. To explore these phenomena, we compared their effects on thrombin generation. Thrombin generation in plasma from 10 patients taking therapeutic doses of warfarin (mean INR 2.6) was compared with that in plasma containing 250 ng/mL dabigatran. Although lag times were similar when thrombin generation was induced by recalcification or with a range of tissue factor concentrations, there was a greater reduction in peak thrombin generation and endogenous thrombin potential in plasma from warfarin-treated patients than in dabigatran-containing plasma. Similar results were obtained when thrombin generation was determined in plasma samples from 18 warfarin or 36 dabigatran treated patients entered into the RE-LY trial. Warfarin suppresses thrombin generation more efficiently than dabigatran. Greater suppression of normal hemostatic mechanisms in the brain and pathological thrombosis at sites of atherosclerotic plaque disruption may explain the higher rate of intracranial bleeding and lower rate of myocardial infarction with warfarin compared with dabigatran.
Laparoscopic liver surgery: 8 years of multicenter Spanish register.

To present the data of laparoscopy in liver surgery and to assess the real indications and outcomes of this kind of approach.



From February 2000 to March 2008, a prospective study was performed on 182 patients from 15 Spanish surgical centres.



A total of 308 lesions was collected. The mean age was 57 years old, and 61.5% were female. Among patients with cystic lesions we found: 45 simple cysts, 19 policystic diseases, 12 hydatidic cysts and 2 cystoadenomas. Among solid lesions (n = 104), we found 34 patients with benign pathology (12 focal nodular hyperplasia, 10 adenomas, 7 haemangyomas and 5 other lesions) and 70 with malignant pathology (38 metastases, 29 hepatocellular carcinomas, 2 cholangiocarcinomas and 1 lymphoma). The global rate of conversion was 8.8%. The global morbidity rate was 14.8%, and 5 of them required re-intervention.



Nowadays there are strong criteria for patients being submitted to laparoscopy procedures based both on type and location features. The postoperative morbidity rate is low, also for hepatocellular carcinoma in cirrhotic liver. In case of malignant pathology, we think the use of ultrasonography is mandatory to obtain a free margin, which implies a long-term survival rate.
Family history and symptom levels during treatment for bipolar I affective disorder

Studies of family history and lithium response in patients with bipolar affective disorder have produced mixed results, but the majority have shown relationships between the presence of affective disorder among relatives and positive responses to lithium in probands. The analysis presented here sought to confirm and to further characterize such relationships.



Subjects described here participated in a long-term, prospective follow-up; had a history of Research Diagnostic Criteria manic disorder or schizoaffective disorder, manic type; and took lithium for periods of 26 weeks or longer. The majority participated in a family study in which first-degree relatives were directly interviewed. Morbidity during lithium and during anticonvulsant trials was quantified in alternative ways, as were the risks among first-degree relatives for bipolar I and nonbipolar affective disorders.



Familial loading for bipolar affective disorder was not associated with better outcomes during lithium treatment. Rather, the presence of major depressive disorder (MDD) among relatives was associated with slower improvement during acute treatment and with higher symptom levels during continuing treatment. Findings for morbidity during anticonvulsant treatment were similar. The patients who experienced symptom persistence with lithium did so as well during periods of anticonvulsant treatment and during periods without thymoleptics.



A family history of MDD may have an enduring and negative prognostic significance that manifests across treatment conditions. Though difficult to reconcile with several earlier studies, these findings invite replication and further exploration.
Novel sequence variations in the brain-derived neurotrophic factor gene and association with major depression and antidepressant treatment response.

Variations in the brain-derived neurotrophic factor gene (BDNF) have been associated with psychiatric disorders. Deep sequencing of the BDNF gene may identify new variations and bring further insight into psychiatric genetics.



To better characterize sequence variability in the BDNF gene by resequencing a genomic DNA region of 22 kilobases that contained all BDNF exons and their flanking regions.



Case-control study.



University of California, Los Angeles, and University of Miami.



Two hundred sixty-four controls and 272 Mexican Americans with major depressive disorder (MDD) from Los Angeles who were assessed by the same bilingual clinical research team.



Identification of novel genetic polymorphisms in the BDNF gene and assessment of their frequencies and associations with MDD or antidepressant response.



We identified 83 novel single-nucleotide polymorphisms (SNPs): 30 in untranslated regions, 4 in coding sequences, 37 in introns, and 12 in upstream regions; 3 of 4 rare novel coding SNPs were nonsynonymous. Association analyses of patients with MDD and controls showed that 6 SNPs were associated with MDD (rs12273539, rs11030103, rs6265, rs28722151, rs41282918, and rs11030101) and 2 haplotypes in different blocks (one including Val66, another near exon VIIIh) were significantly associated with MDD. One recently reported 5' untranslated region SNP, rs61888800, was associated with antidepressant response after adjusting for age, sex, medication, and baseline score on the 21-item Hamilton Depression Rating Scale.



Our data support the concept that extensive resequencing of key candidate genes can lead to the discovery of substantial numbers of new variants. Further studies using larger independent samples are needed to confirm the association of the rs61888800 SNP with antidepressant response.
Healthier options for public schoolchildren program improves weight and blood pressure in 6- to 13-year-olds.

Childhood obesity and related health consequences continue to be major clinical and public health issues in the United States. Schools provide an opportunity to implement obesity prevention strategies to large and diverse pediatric audiences. Healthier Options for Public Schoolchildren was a quasiexperimental elementary school-based obesity prevention intervention targeting ethnically diverse 6- to 13-year-olds (kindergarten through sixth grade). Over 2 school years (August 2004 to June 2006), five elementary schools (four intervention, one control, N=2,494, 48% Hispanic) in Osceola County, FL, participated in the study. Intervention components included integrated and replicable nutrition, physical activity, and lifestyle educational curricula matched to state curricula standards; modified school meals, including nutrient-dense items, created by registered dietitians; and parent and staff educational components. Demographic, anthropometric, and blood pressure data were collected at baseline and at three time points over 2 years. Repeated measures analysis showed significantly decreased diastolic blood pressure in girls in the intervention group compared to controls (P<0.05). Systolic blood pressure decreased significantly for girls in the intervention group compared to controls during Year 1 (fall 2004 to fall 2005) (P<0.05); while not statistically significant the second year, the trend continued through Year 2. Overall weight z scores and body mass index z scores decreased significantly for girls in the intervention group compared to controls (P<0.05 and P<0.01, respectively). School-based prevention interventions, including nutrition and physical activity components, show promise in improving health, particularly among girls. If healthy weight and blood pressure can be maintained from an early age, cardiovascular disease in early adulthood may be prevented.
Psychodynamic Motivation and Training program (PMT) for the secondary prevention in patients with stable coronary heart disease: study protocol for a randomized controlled trial of feasibility and effects

Nonpharmacological secondary prevention of coronary heart disease is considered a safe and effective measure to substantially reduce mortality. Despite the effectiveness of lifestyle changes, the compliance rate of patients is very low mainly due to psychosocial barriers. Psychotherapeutic approaches that address how persons think about themselves and their behaviors appear to have a significant potential for improving health behavior.



Against this background, our study aims to examine the feasibility and effects of a Psychodynamic Motivation and Training program (PMT) as compared to one session of advice in exercise training (EX) and treatment as usual (TAU). For that purpose, 90 patients with stable coronary heart disease and a physically inactive lifestyle will be randomly assigned to the three groups (each with n = 30). The primary outcome is the change in the individual anaerobic threshold as determined by spiroergometry from baseline to six month follow-up. Secondary endpoints include change in endothelial function, biomarkers of inflammation and oxidative stress, quality of life, symptoms of fatigue, illness perception and feasibility of the treatment approach. We hypothesize that physical fitness will improve more in PMT than in EX and TAU, with PMT and EX more than TAU, and that the effects will be more pronounced for participants with current mental or psychosocial distress.



The results of the study will help to determine the effectiveness of a psychodynamic lifestyle change approach and to identify measures for designing specifically tailored interventions to improve compliance with cardiovascular prevention.
Effect of Vitamin D Supplementation on Glycemic Control in Patients With Type 2 Diabetes (SUNNY Trial): A Randomized Placebo-Controlled Trial.

Low vitamin D status has been associated with impaired glycemic control in patients with type 2 diabetes. The purpose of our study was to evaluate the effect of vitamin D supplementation on glycemic control in patients with type 2 diabetes.



This randomized, double-blind, placebo-controlled trial was conducted in 275 adult patients with type 2 diabetes without insulin treatment. Patients were randomly assigned to receive either vitamin D3 (50,000 IU/month) or placebo for 6 months. To assess the primary outcome of the study, change in HbA(1c), we performed a linear regression analysis.



Mean baseline serum 25-hydroxyvitamin D [25(OH)D] increased from 60.6 ± 23.3 to 101.4 ± 27.6 nmol/L and 59.1 ± 23.2 to 59.8 ± 23.2 nmol/L in the vitamin D and placebo group, respectively. Mean baseline HbA(1c) was 6.8 ± 0.5% (51 ± 6 mmol/mol) in both groups. After 6 months, no effect was seen on HbA(1c) (mean difference: β = 0.4 [95% CI -0.6 to 1.5]; P = 0.42) and other indicators of glycemic control (HOMA of insulin resistance, fasting insulin, and glucose) in the entire study population. Subgroup analysis in patients with a serum 25(OH)D <50 nmol/L or an HbA(1c) level >7% (53 mmol/mol) did not differ the results.



In a well-controlled group of patients with type 2 diabetes, intermittent high-dose vitamin D supplementation did not improve glycemic control.
Adherence to adalimumab therapy in Crohn's disease: a French multicenter experience.

We evaluated adherence to adalimumab therapy in Crohn's disease (CD).



This was an observational multicenter study conducted in four French university hospitals between April 4, 2008 and January 1, 2010. Patients were systematically asked, at each clinical visit, whether or not they delayed or missed an injection of adalimumab over the past 3 months. Patients were also asked about the reasons for their nonadherence.



Of the 108 patients analyzed, 33 (30.6%) delayed the administration of at least one injection and 16 (14.8%) missed at least one injection over the past 3 months. The main reasons for overall nonadherence were: forgetfulness (24.6%), infection (24.6%), and travel (20%). Other reasons for nonadherence were intentional nonadherence (10.8%), pharmaceutical supply issues (9.2%), side effects (7.7%), pregnancy (1.5%), and CD-related hospitalization (1.5%). Adalimumab regimen of 40 mg every other week was a positive predictor for injection delays (P = 0.02, odds ratio [OR] = 3.76, 95% confidence interval [CI], 1.28-11.05), whereas having at least one relapse in the past 12 months was associated with fewer delays (P = 0.02, OR = 0.37, 95% CI, 0.15-0.87). [correction made here after initial online publication]. Disease duration over 90 months negatively predicted failure to inject adalimumab (P = 0.009, OR = 0.17, 95% CI, 0.05-0.64).



The overall nonadherence rate for adalimumab use was 45.4%. Most of the reasons for nonadherent behaviors could be avoided. An adalimumab regimen of 40 mg every other week was negatively related to adalimumab adherence; both the occurrence of at least one relapse in the past 12 months and disease duration over 90 months were positively related to adherence.
Lung cancer detectability by test, histology, stage, and gender: estimates from the NLST and the PLCO trials.

Implementing optimal lung cancer screening programs requires knowledge of the natural history and detectability of lung cancer. This information can be derived from the results of clinical trials with the aid of microsimulation models.



Data from the Surveillance, Epidemiology, and End Results (SEER) program and individual-level data from the National Lung Screening Trial (NLST) and the Prostate, Lung, Colon, and Ovarian Cancer Screening trial (PLCO) were used to investigate the sensitivity (by histology and stage) of CT and chest radiography (CXR) and the mean preclinical sojourn time (MPST) of lung cancer (by gender, histology, and stage). The MISCAN-Lung model was used to reproduce the lung cancer incidence by method of detection (clinically or screen-detected), gender, histology, and stage in both trials and SEER, by calibrating CT and CXR sensitivity and natural history parameters.



CT sensitivity ranges from 8.83% to 99.35% and CXR sensitivity from 2.51% to 97.31%, depending on histology and stage. CT sensitivity for stage IA is more than 3-fold higher compared with CXR, for all histologies. The total MPST estimates for lung cancer progressing through preclinical stages IA to IV range from 3.09 to 5.32 years for men and 3.35 to 6.01 years for women. The largest difference in total MPST between genders was estimated for adenocarcinoma.



We estimate longer MPSTs for lung cancer compared with previous research, suggesting a greater window of opportunity for lung cancer screening.



This study provides detailed insights into the natural history of lung cancer and CT screening effectiveness.
Effects of enalapril, candesartan or both on neurohumoral activation and LV volumes and function in patients with heart failure not treated with a beta-blocker.

The long-term effects of the angiotensin-receptor blocker candesartan, the angiotensin-converting enzyme inhibitor enalapril or their combination have been incompletely studied in a large cohort of patients with heart failure not treated with beta-blockers. The objective of this study was to investigate the changes in neurohormones and LV volumes and ejection fraction in patients treated with enalapril, candesartan, or enalapril plus candesartan without concomitant beta-blocker therapy.



Three hundred and ninety-two patients from the RESOLVD pilot study not treated with a beta-blocker at baseline or at any time during the trial were analyzed. Norepinephrine, endothelin-1, big endothelin-1, angiotensin-II, aldosterone, N-terminal proANP, BNP, and radionuclide angiography were measured before and after 43 weeks of treatment with candesartan alone (n = 162), or enalapril alone (n = 45), or candesartan plus enalapril (n = 185). Endpoints were assessed at baseline and after 43 weeks of therapy.



LV end-diastolic and end-systolic volumes increased significantly at 43 weeks in all groups except for patients treated with enalapril plus candesartan. BNP decreased at 43 weeks only in patients receiving dual angiotensin-II suppression (-6.1 +/- 37.8 pmol/l). Angiotensin-II levels were significantly increased in patients treated with candesartan (+23.6 +/- 47.1 pg/ml; p<0.05).



We conclude that angiotensin-II modulation, with enalapril and candesartan, without concomitant utilization of beta-blocker lead to a decrease in BNP and an attenuation of the increase in LV end-diastolic and end-systolic volumes without a reversal of this process in the long term.
Similar antiviral efficacy and tolerability between efavirenz and lopinavir/ritonavir, administered with abacavir/lamivudine (Kivexa), in antiretroviral-naïve patients: a 48-week, multicentre, randomized study (Lake Study).

Although efavirenz and lopinavir/ritonavir(r) are both recommended antiretroviral agents in antiretroviral-naïve HIV-infected patients, there are few randomized comparisons of their efficacy and tolerability.



A multicenter and randomized study was performed including 126 antiretroviral-naïve patients, randomly assigned to efavirenz+Kivexa (n=63) or lopinavir/r+Kivexa (n=63). Efficacy endpoints were the percentage of patients with HIV-RNA < or =50 copies/mL at week 48 and CD4 recovery. Safety was assessed by comparing toxicity and discontinuations. Statistical analyses were performed on an intention-to-treat (ITT) basis (Missing=Failure).



At week 48, 56.7% of patients in the efavirenz and 63.2% in the lopinavir/r groups showed HIV-1 RNA <50 copies/mL (P=0.770) (intention-to-treat analysis; Missing=Failure). Only 1 (1.53%) patient from each group experienced virological failure. CD4 values increased in both groups (298 cells in the efavirenz group, P=0.001; 249 cells in the lopinavir/r group, P=0.002; P=0.126 between groups). HDL-cholesterol only increased in the efavirenz group (from 39+/-12 mg/dL to 49+/-11; P=0.001). Discontinuations were more frequent in the lopinavir/r group (36.5% versus 28.5%; P=0.193), but more patients with efavirenz interrupted due to toxicity (11.1% versus 6.3%); most of them were attributed to hypersensitivity reaction.



Similar virological efficacy was observed for efavirenz and lopinavir/r, when administered with Kivexa in antiretroviral-naïve patients, while immunological improvement was slightly superior for efavirenz. The higher rate of discontinuation due to toxicity in the efavirenz group was related to a higher incidence of hypersensitivity reaction. Nowadays, the use of the new formulation of lopinavir/r and the HLA-B*5701 genotype test before starting abacavir should improve the safety profiles of these regimens.
Neural synchronization deficits linked to cortical hyper-excitability and auditory hypersensitivity in fragile X syndrome

Studies in the fmr1 KO mouse demonstrate hyper-excitability and increased high-frequency neuronal activity in sensory cortex. These abnormalities may contribute to prominent and distressing sensory hypersensitivities in patients with fragile X syndrome (FXS). The current study investigated functional properties of auditory cortex using a sensory entrainment task in FXS.



EEG recordings were obtained from 17 adolescents and adults with FXS and 17 age- and sex-matched healthy controls. Participants heard an auditory chirp stimulus generated using a 1000-Hz tone that was amplitude modulated by a sinusoid linearly increasing in frequency from 0-100 Hz over 2 s.



Single trial time-frequency analyses revealed decreased gamma band phase-locking to the chirp stimulus in FXS, which was strongly coupled with broadband increases in gamma power. Abnormalities in gamma phase-locking and power were also associated with theta-gamma amplitude-amplitude coupling during the pre-stimulus period and with parent reports of heightened sensory sensitivities and social communication deficits.



This represents the first demonstration of neural entrainment alterations in FXS patients and suggests that fast-spiking interneurons regulating synchronous high-frequency neural activity have reduced functionality. This reduced ability to synchronize high-frequency neural activity was related to the total power of background gamma band activity. These observations extend findings from fmr1 KO models of FXS, characterize a core pathophysiological aspect of FXS, and may provide a translational biomarker strategy for evaluating promising therapeutics.
18F-FDG PET/CT lung 'focalities' without coregistered CT findings: an interpretative clinical dilemma.

The aim of the study was to assess the prevalence of focal fluorine-18 fluorodeoxyglucose (18F-FDG) activity in the lungs using 18F-FDG PET/computed tomography (CT) without matching CT findings.



A total of 10,500 consecutive 18F-FDG PET/CT records over 4 years were reviewed for focal incongruence between PET and CT, potentially indicating an artifact 18F-FDG (2.2 MBq/kg) was injected through a butterfly needle, followed by a 10 ml saline flush. Non-contrast-enhanced low-dose CT (140 kV and 40-80 mA) was coregistrated with PET.



Sixteen patients (12 men and four women; mean age 63 years, range 44-83) had focal pulmonary areas of high 18F-FDG activity [mean maximum standardized uptake value (SUV max) 15.8; range 3.5-81.0], typically peripheral, with a mean maximum diameter of 1.3 cm (range 0.5-2.2 cm) on PET. 18F-FDG focality was singular in 14 patients, whereas two patients had two foci each. None had corresponding CT abnormalities. Identification of these 'focalities' during the acquisition phase led to late respiratory gated thoracic PET acquisitions in eight patients at 2 h with no significant changes in the location or size of the 'focalities'. Five PET/CTs repeated at 48 h did not confirm the 'focalities'. Five had negative follow-up contrast-enhanced CT. 18F-FDG-positive 'focalities' at PET/CT without anatomical correlation findings were considered as 'artefactual accumulation' of the tracer.



In the absence of morphological abnormality, focal pulmonary 18F-FDG activity is very rare (1.5 cases/1000 PET scans) but potentially very 'dangerous'. Artefact identification during acquisition can lead to late respiratory gated images for more confident interpretation, avoiding erroneous reports or further imaging procedures.