nils-herrmann/clean_scirepeval huggingface dataset:
CYP2C19*2 and other genetic variants affecting platelet response to clopidogrel in patients undergoing percutaneous coronary intervention.

Information regarding any possible additional effect of genetic variants other than CYP2C19*2 on platelet reactivity in patients undergoing percutaneous coronary intervention (PCI), while on dual antiplatelet therapy, is sparse.



Genotyping for CYP2C19*2, CYP2C19*17, CYP2C9*3, CYP2B6*5, ABCB1 and P2RY12 (c.-217+2739T>C) variants was performed in 146 consecutive PCI patients receiving clopidogrel. Platelet reactivity was assessed by the Verify Now P2Y12 point-of-care assay and high on-treatment platelet reactivity (HTPR) was defined as a Platelet Reactivity Unit (PRU)≥235.



We identified 65(44.5%) patients with HTPR and 38(26%) carriers of at least one CYP2C19*2 allele, which had higher platelet reactivity compared to non-carriers [least square (LS) mean difference 44.5, 95%CI 15.8-77.3, p=0.003]. In the entire study population, the presence of at least one CYP2C19*2 or P2RY12 allelic variant was independently associated with HTPR (OR=3.02, 95%CI 1.16-7.86, p=0.023 and OR=3.11, 95%CI 1.03-9.39, p=0.05 respectively). In CYP2C19*2 non-carriers, carriers of at least one CYP2B6*5 allelic variant had higher platelet reactivity compared to the remainders (LS mean difference 35.6, 95%CI 3.7-67.6, p=0.03) and the presence of at least one CYP2B6*5 or P2RY12 allelic variant was independently associated with HTPR (OR=3.26, 95%CI 1.08-9.86, p=0.04 and OR=4.27, 95%CI 1.11-16.4, p=0.04 respectively).



Apart from the CYP2C19*2, other genetic variants involved in clopidogrel metabolism and action like CYP2B6*5 and P2RY12 seem to have an important association with HTPR.
Detection of vein graft disease using high-resolution magnetic resonance angiography.

The application of previous magnetic resonance (MR) angiography techniques has enabled noninvasive differentiation between patent and occluded coronary artery bypass grafts. However, the detection of graft stenosis remains difficult. The purpose of our study was to determine the accuracy of high-resolution navigator-gated 3-dimensional (3-D) MR angiography in detecting vein graft disease. Methods and Results- MR angiography was performed in addition to coronary angiography with quantitative coronary analysis in 56 vein grafts from 38 patients (mean age 66.6+/-9.3 years), who presented with recurrent chest pain after bypass surgery. Eighteen grafts showed a luminal stenosis >/=50%, 11 grafts a stenosis >/=70%, and 6 grafts were occluded. All MR angiograms were evaluated independently by 2 blinded observers, who scored the presence of graft occlusion and graft stenosis >/=50% and >/=70% with a confidence level of 1 to 10. MR image quality was judged as insufficient in 6 grafts and these were excluded. Receiver-operator characteristic analysis revealed an area under the curve of 0.89 and 0.89 for identifying graft occlusion, 0.81 and 0.87 for stenosis >/=50%, and 0.82 and 0.79 for stenosis >/=70% for the 2 observers, respectively. Interobserver agreement in assessing graft occlusion and stenosis >/=50% and >/=70% was 94% (kappa=0.74, r=0.81), 72% (kappa=0.40, r=0.66), and 82% (kappa=0.53, r=0.72), respectively.



High-resolution navigator-gated 3-D MR angiography allows not only good differentiation between patent and occluded vein grafts but also the assessment of vein graft disease with a fair diagnostic accuracy. This approach offers perspective as a noninvasive diagnostic tool for patients who present with recurrent chest pain after vein graft surgery.
Effect of ramipril on the incidence of diabetes.

Previous studies have suggested that blockade of the renin-angiotensin system may prevent diabetes in people with cardiovascular disease or hypertension.



In a double-blind, randomized clinical trial with a 2-by-2 factorial design, we randomly assigned 5269 participants without cardiovascular disease but with impaired fasting glucose levels (after an 8-hour fast) or impaired glucose tolerance to receive ramipril (up to 15 mg per day) or placebo (and rosiglitazone or placebo) and followed them for a median of 3 years. We studied the effects of ramipril on the development of diabetes or death, whichever came first (the primary outcome), and on secondary outcomes, including regression to normoglycemia.



The incidence of the primary outcome did not differ significantly between the ramipril group (18.1%) and the placebo group (19.5%; hazard ratio for the ramipril group, 0.91; 95% confidence interval [CI], 0.81 to 1.03; P=0.15). Participants receiving ramipril were more likely to have regression to normoglycemia than those receiving placebo (hazard ratio, 1.16; 95% CI, 1.07 to 1.27; P=0.001). At the end of the study, the median fasting plasma glucose level was not significantly lower in the ramipril group (102.7 mg per deciliter [5.70 mmol per liter]) than in the placebo group (103.4 mg per deciliter [5.74 mmol per liter], P=0.07), though plasma glucose levels 2 hours after an oral glucose load were significantly lower in the ramipril group (135.1 mg per deciliter [7.50 mmol per liter] vs. 140.5 mg per deciliter [7.80 mmol per liter], P=0.01).



Among persons with impaired fasting glucose levels or impaired glucose tolerance, the use of ramipril for 3 years does not significantly reduce the incidence of diabetes or death but does significantly increase regression to normoglycemia.
The metabolic syndrome, inflammation, and risk of cognitive decline.

Several studies have reported an association between the metabolic syndrome and cardiovascular disease. Despite an increasing awareness that cardiovascular risk factors increase risk of cognitive decline and dementia, there are few data on the metabolic syndrome and cognition.



To determine if the metabolic syndrome is a risk factor for cognitive decline and if this association is modified by inflammation.



A 5-year prospective observational study conducted from 1997 to 2002 at community clinics at 2 sites.



A total of 2632 black and white elders (mean age, 74 years).



Association of the metabolic syndrome (measured using National Cholesterol Education Program guidelines) and high inflammation (defined as above median serum level of interleukin 6 and C-reactive protein) with change in cognition (Modified Mini-Mental State Examination [3MS]) at 3 and 5 years. Cognitive impairment was defined as at least a 5-point decline.



Compared with those without the metabolic syndrome (n = 1616), elders with the metabolic syndrome (n = 1016) were more likely to have cognitive impairment (26% vs 21%, multivariate adjusted relative risk [RR], 1.20; 95% confidence interval [CI], 1.02-1.41). There was a statistically significant interaction with inflammation and the metabolic syndrome (P = .03) on cognitive impairment. After stratifying for inflammation, those with the metabolic syndrome and high inflammation (n = 348) had an increased likelihood of cognitive impairment compared with those without the metabolic syndrome (multivariate adjusted RR, 1.66; 95% CI, 1.19-2.32). Those with the metabolic syndrome and low inflammation (n = 668) did not exhibit an increased likelihood of impairment (multivariate adjusted RR, 1.08; 95% CI, 0.89-1.30). Stratified multivariate random-effects models demonstrated that participants with the metabolic syndrome and high inflammation had greater 4-year decline on 3MS (P = .04) compared with those without the metabolic syndrome, whereas those with the metabolic syndrome and low inflammation did not (P = .44).



These findings support the hypothesis that the metabolic syndrome contributes to cognitive impairment in elders, but primarily in those with high level of inflammation.
Long-lasting immunogenicity and safety of a 2009 pandemic influenza A(H1N1) MF59-adjuvanted vaccine when co-administered with a 2009-2010 seasonal influenza vaccine in young patients with type 1 diabetes mellitus.

To evaluate the long-lasting immunogenicity and safety of a pandemic vaccine co-administered with a seasonal influenza vaccine in young subjects with Type 1 diabetes.



Eighty patients (mean age: 16.7 ± 5.5 years, disease duration: 10.2 ± 4.7 years) were randomly assigned to receive a single or a double dose (1 month apart) of MF59-adjuvanted influenza A(H1N1) vaccine, simultaneously with a single dose of a virosome-adjuvanted trivalent influenza vaccine for the 2009-2010 season.



One month after immunization, the rate of seroconversion to 2009 pandemic A(H1N1) was 92.5% with an overall 100% proportion of vaccinees with protective antibody titres (≥ 1:40). No significant differences were observed between vaccinees who received the one-dose or the two-dose schedule. Seasonal vaccine induced a significant increase of both seroprotection rates and antibody levels. Local adverse events at the injection site of pandemic and seasonal vaccines were reported by 66.3% and 50% of subjects, respectively. Solicited systemic adverse events, mainly mild in intensity, were reported by 26.7% of vaccinees. No subjects had an influenza-like illness during the 6-month follow-up.



One injection of 2009 pandemic influenza A(H1N1) MF59-adjuvanted vaccine is immunogenic and safe in young patients with Type 1 diabetes who are at increased risk of influenza morbidities. Pandemic vaccine can be safely co-administered with seasonal influenza vaccine.
Gender Analysis in the Outcomes of a Lifestyle Intervention Among Patients Who Had an Open Heart Surgery.

The aim of this study was to evaluate the gender-oriented differences in the outcomes of a lifestyle intervention trial (diet, smoking cessation, and exercise) among patients who had open heart surgery. A randomized, nonblind intervention study was performed on 500 patients who had open heart surgery. Immediately after hospital discharge, 250 patients were randomly allocated lifestyle intervention by receiving oral and written information in the form of a booklet with specific educational information for postoperative rehabilitation. The remaining 250 patients received the regular oral instructions. The applied lifestyle intervention proved to be beneficial only in men as far as quitting smoking (relative risk [RR]: 0.36, confidence interval [CI]: 0.16-0.80; P = .01) and returning to work (RR: 0.35, CI: 0.13-0.92; P = .03) are concerned. For both genders, no significant associations between dietary and physical activity recommendations were observed.



Lifestyle nursing intervention immediately after open heart surgery had a beneficial effect on men 1 year after the surgery but not on women. Thus, there is a need for gender-specific studies among women.
FDA Approval: Ibrutinib for Patients with Previously Treated Mantle Cell Lymphoma and Previously Treated Chronic Lymphocytic Leukemia.

On November 13, 2013, the FDA granted accelerated approval to ibrutinib (IMBRUVICA capsules; Pharmacyclics, Inc.) for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. On February 12, 2014, the FDA granted accelerated approval for the treatment of patients with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy. Ibrutinib is a first-in-class Bruton's tyrosine kinase (BTK) inhibitor that received all four expedited programs of the FDA: Fast-Track designation, Breakthrough Therapy designation, Priority Review, and Accelerated Approval. Both approvals were based on overall response rate (ORR) and duration of response (DOR) in single-arm clinical trials in patients with prior treatment. In MCL (N = 111), the complete and partial response rates were 17.1% and 48.6%, respectively, for an ORR of 65.8% [95% confidence interval (CI), 56.2%-74.5%]. The median DOR was 17.5 months (95% CI, 15.8-not reached). In CLL (N = 48), the ORR was 58.3% (95% CI, 43.2%-72.4%), and the DOR ranged from 5.6 to 24.2 months. The most common adverse reactions (≥ 30% in either trial) were thrombocytopenia, diarrhea, neutropenia, bruising, upper respiratory tract infection, anemia, fatigue, musculoskeletal pain, peripheral edema, and nausea.
A twin study of auditory processing indicates that dichotic listening ability is a strongly heritable trait

We administered tests commonly used in the diagnosis of auditory processing disorders (APDs) to twins recruited from the general population. We observed significant correlations in test scores between co-twins. Our analyses of test score correlations among 106 MZ and 33 DZ twin pairs indicate that dichotic listening ability is a highly heritable trait. Dichotic listening is the ability to identify and distinguish different stimuli presented simultaneously to each ear. Deficits in dichotic listening skills indicate a lesion or defect in interhemispheric information processing. Such defects or lesions can be prominent in elderly listeners, language-impaired children, stroke victims, and individuals with PAX6 mutations. Our data indicates that other auditory processing abilities are influenced by shared environment. These findings should help illuminate the etiology of APDs, and help to clarify the relationships between auditory processing abilities and learning/language disorders associated with APDs.
Naturally-Acquired Influenza-Specific CD4+ T-Cell Proliferative Responses Are Impaired in HIV-Infected African Adults

Seasonal influenza has been associated with greater morbidity and mortality in AIDS patients. Highly-active antiretroviral therapy (HAART) has led to some reduction in influenza-related complications but the nature of naturally-acquired T-cell immunity to influenza virus in an African setting, and how this changes with immune reconstitution following HAART is unknown. We measured influenza-specific CD4(+) T-cell immunity in unimmunized HIV-infected Malawian adults and then investigated immune reconstitution following HAART.



Peripheral blood mononuclear cells were isolated from HIV-infected and HIV-uninfected Malawian adults. CFSE proliferation and CD154 expression flow cytometry-based assays were used to measure influenza-specific CD4(+) T-cell immunity.



We found lower naturally-acquired proliferative influenza-specific CD4(+) T-cell responses in AIDS patients that was also present in asymptomatic HIV-infected adults with relatively high CD4 counts (>350 cells/µl). Influenza-specific CD4(+) T-cell immune reconstitution in HIV-infected patients on HAART for 12 months was poor despite a marked reduction in viral load and an increase in CD4 count. This poor immune reconstitution was characterised by a low influenza-specific proliferative CD4(+) T-cell response and reduced proportions of CD154-expressing influenza-specific CD4(+) T-cells in peripheral blood.



Our data suggest that asymptomatic HIV-infected adults may also be at risk of influenza-related complications and that HAART alone may not circumvent this risk in AIDS patients. This study highlights the need to identify possible interventions early in HIV infection to reduce the risk of influenza and to intensify influenza surveillance in these susceptible African populations.
Idiopathic intracranial hypertension in men.

To compare the characteristics of idiopathic intracranial hypertension (IIH) in men vs women in a multicenter study.



Medical records of all consecutive patients with definite IIH seen at three university hospitals were reviewed. Demographics, associated factors, and visual function at presentation and follow-up were collected. Patients were divided into two groups based on sex for statistical comparisons.



We included 721 consecutive patients, including 66 men (9%) and 655 women (91%). Men were more likely to have sleep apnea (24% vs 4%, p < 0.001) and were older (37 vs 28 years, p = 0.02). As their first symptom of IIH, men were less likely to report headache (55% vs 75%, p < 0.001) but more likely to report visual disturbances (35% vs 20%, p = 0.005). Men continued to have less headache (79% vs 89%, p = 0.01) at initial neuro-ophthalmologic assessment. Visual acuity and visual fields at presentation and last follow-up were significantly worse among men. The relative risk of severe visual loss for men compared with women was 2.1 (95% CI 1.4-3.3, p = 0.002) for at least one eye and 2.1 (95% CI 1.1-3.7, p = 0.03) for both eyes. Logistic regression supported sex as an independent risk factor for severe visual loss.



Men with idiopathic intracranial hypertension (IIH) are twice as likely as women to develop severe visual loss. Men and women have different symptom profiles, which could represent differences in symptom expression or symptom thresholds between the sexes. Men with IIH likely need to be followed more closely regarding visual function because they may not reliably experience or report other symptoms of increased intracranial pressure.
Impact of body habitus on quantitative and qualitative image quality in whole-body FDG-PET

Obtaining consistent high image quality is desirable for clinical positron emission tomography (PET). Body morphology may impact image quality. The purpose of this study was to define the average and the range of body sizes in patients undergoing tumor PET studies in our center and to determine how the body habitus affects the statistical and visual quality of PET images. Height, weight, body surface area (BSA), and body mass index (BMI) were determined in 101 male and 101 female patients (group 1) referred for clinical PET. The summed total counts from three consecutive transaxial slices on non-attenuation-corrected (NAC) 2D fluorine-18 fluorodeoxyglucose (FDG) PET images, which included the largest liver section and no lesions, were determined and compared with body morphology and injected doses (ID) in a representative group of 30 male and 30 female patients (group 2) spanning a range of body morphologies. The visual quality of images was also evaluated using a scoring system by three readers. The average height, weight, and BSA were greater in male than in female patients, but the average BMI was not different between them in group 1. The largest value of weight or BMI was more than four times the smallest value in female patients. The total true counts were best correlated with ID/weight (mCi/kg) in group 2 (r=0.929, P<0.0001). Intermediate to high total counts (930,000 or more) corresponded to ID/weight of 0.22 or higher. The average visual score was positively correlated with the total counts (ρ=0.63, P<0.0001) and with ID/weight (ρ=0.68, P<0.0001) on NAC images. The image quality in 22 (84.6%) of 26 patients with intermediate to high total counts was adequate to good, whereas that in 21 (61.8%) of 34 patients with lower total counts was suboptimal. A wide variety of body morphologies was observed in patients referred for clinical FDG-PET tumor studies in our center. The total counts and average image visual score were negatively correlated with weight. Counts in heavy patients were as low as one-fourth those in light patients. Adjusting injected FDG dose in each patient on the basis of body weight may be more appropriate to achieve consistent PET image quality than giving a fixed injected FDG dose.
Ideology and science in the individual psychotherapy of schizophrenia.

The efficacy of individual psychotherapy for acute schizophrenics has been the source of controversy for many decades. Discussion of the scientific issues, such as design, methodology, and assessment, has been clouded by strong ideological conflicts. The relative value of drugs and psychotherapy for schizophrenics has been the subject of tension and dispute between various psychiatric schools--psychoanalytic, interpersonal, biological, and behavioral. The Psychotherapy of Schizophrenia Project is discussed in terms of the mixture of scientific and ideological issues.
The effect of antipsychotics on the high-affinity state of D2 and D3 receptors: a positron emission tomography study With [11C]-(+)-PHNO.

Most antipsychotics are thought to have an effect on D(2) and D(3) receptors. The development of carbon 11-labeled (+)-4-propyl-9-hydroxynaphthoxazine ([(11)C]-(+)-PHNO), the first agonist radioligand with higher affinity for D(3) than D(2) receptors, allows one to differentiate the effects of antipsychotics on high-affinity vs low-affinity sites of the D(2) receptor and on D(3) vs D(2) receptor subtypes.



To examine the effects of antipsychotics (clozapine, risperidone, or olanzapine) on the high- vs high- + low-affinity sites of the D(2) and D(3) receptors by comparing the [(11)C]-(+)-PHNO and [(11)C]raclopride binding in the D(3) receptor-rich (globus pallidus and ventral striatum) and D(2) receptor-rich (caudate and putamen) regions.



Two sequential studies with different participants and appropriate controls were performed. The first compared the occupancy produced by 3 antipsychotics as measured with [(11)C]-(+)-PHNO and [(11)C]raclopride. The second was a double-blind, placebo-controlled experiment to compare the effect of pramipexole (a D(3) receptor-preferring agonist) vs placebo on the increased [(11)C]-(+)-PHNO signal observed in the globus pallidus of patients.



Positron Emission Tomography Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.



Twenty-three patients with schizophrenia and 23 healthy controls.



Antipsychotic occupancies as measured with [(11)C]-(+)-PHNO and [
The antipsychotic-treated patients showed high occupancies with both [(11)C]-(+)-PHNO and [(11)C]raclopride in the dorsal striatum, with [(11)C]raclopride occupancies about 20% higher. Most strikingly, patients did not show any occupancy with [(11)C]-(+)-PHNO in the globus pallidus as compared with normal controls or with their own scans using [(11)C]raclopride. This unblocked [(11)C]-(+)-PHNO signal was displaced by a single dose of pramipexole.



Antipsychotics block both the high- and low-affinity states of the D(2) receptors across the brain, but antipsychotic treatment does not block the [(11)C]-(+)-PHNO signal in the D(3) receptor-rich regions, despite the ongoing D(2) receptor blockade. This [(11)C]-(+)-PHNO signal in regions such as the globus pallidus seems increased despite antipsychotic treatment and is displaceable by a D(3) receptor-preferring agonist. The radiotracer [(11)C]-(+)-PHNO and the data open up new avenues for exploring the potential therapeutic significance of the D(3) receptor in schizophrenia.
Effect of enalapril on parasympathetic activity

To evaluate the effect of converting enzyme inhibition induced by enalapril on parasympathetic activity, we studied ten essential hypertensive patients, age range 38–58 years, WHO I–II. Parasympathetic evaluation was obtained by measuring the variation of heart period (VHP) during at least 1 minute of steady-state, regular respiration. VHP was derived from the difference between the mean of all maximum and the mean of all minimum heart periods. The higher the VHP, the higher the parasympathetic control of heart rate and vice versa. VHP was measured supine and with tilting (30°, 60°, 85°). Blood pressure was reduced after 1 month of enalapril treatment, while the heart rate did not change. VHP increased at the end of enalapril treatment compared with placebo: in the supine position it increased from 36±3.2 ms to 44±3.5 ms, p<0.01. VHP was also increased by enalapril at 30° (p<0.05) and 60° (p<0.05), while no difference was observed at 85° between placebo and enalapril. A positive correlation was found between supine enalapril changes of VHP and those of systolic and diastolic BP. In conclusion, enalapril seems to increase parasympathetic cardiovascular control in essential hypertensive patients. This result might explain the lack of increase in heart rate that would be expected as a result of the vasodilating effect of enalapril.