nils-herrmann/clean_scirepeval huggingface dataset:
Hospitalizations, nursing home admissions, and deaths attributable to diabetes.

To estimate all-cause hospitalizations, nursing home admissions, and deaths attributable to diabetes using a new methodology based on longitudinal data for a representative sample of older U.S. adults.



A simulation model, based on data from the National Health and Nutrition Examination Survey (NHANES) I Epidemiologic Followup Study, was used to represent the natural history of diabetes and control for a variety of baseline risk factors. The model was applied to 6,265 NHANES III adults aged 45-74 years. The prevalence of risk factors in NHANES III, fielded in 1988-1994, better represents today's adults.



For all NHANES III adults aged 45-74 years, a diagnosis of diabetes accounted for 8.6% of hospitalizations, 12.3% of nursing home admissions, and 10.3% of deaths in 1988-1994. For people with diabetes, diabetes alone was responsible for 43.4% of hospitalizations, 52.1% of nursing home admissions, and 47% of deaths. Adjusting for related cardiovascular conditions, which may provide more accurate estimates of attributable risks for people with diabetes, increased these estimates to 51.4, 57.1, and 56.8%, respectively.



Risks of institutionalization and death attributable to diabetes are large. Efforts to translate recent trials of primary prevention into practice and continued efforts to prevent complications of diabetes could have a substantial impact on hospitalizations, nursing home admissions, and deaths and their societal costs.
Epigenetic changes in Alzheimer's disease: Decrements in DNA methylation

DNA methylation is a vital component of the epigenetic machinery that orchestrates changes in multiple genes and helps regulate gene expression in all known vertebrates. We evaluated immunoreactivity for two markers of DNA methylation and eight methylation maintenance factors in entorhinal cortex layer II, a region exhibiting substantial Alzheimer's disease (AD) pathology in which expression changes have been reported for a wide variety of genes. We show, for the first time, neuronal immunoreactivity for all 10 of the epigenetic markers and factors, with highly significant decrements in AD cases. These decrements were particularly marked in PHF1/PS396 immunoreactive, neurofibrillary tangle-bearing neurons. In addition, two of the DNA methylation maintenance factors, DNMT1 and MBD2, have been reported also to interact with ribosomal RNAs and ribosome synthesis. Consistent with these findings, DNMT1 and MBD2, as well as p66α, exhibited punctate cytoplasmic immunoreactivity that co-localized with the ribosome markers RPL26 and 5.8s rRNA in ND neurons. By contrast, AD neurons generally lacked such staining, and there was a qualitative decrease in RPL26 and 5.8s rRNA immunoreactivity. Collectively, these findings suggest epigenetic dysfunction in AD-vulnerable neurons.
Decision-making in elderly patients with severe aortic stenosis: why are so many denied surgery?

To analyse decision-making in elderly patients with severe, symptomatic aortic stenosis (AS).



In the Euro Heart Survey on valvular heart disease, 216 patients aged > or =75 had severe AS (valve area < or =0.6 cm(2)/m(2) body surface area or mean gradient > or =50 mmHg) and angina or New York Heart Association class III or IV. Patient characteristics were analysed according to the decision to operate or not. A decision not to operate was taken in 72 patients (33%). In multivariable analysis, left ventricular (LV) ejection fraction [OR = 2.27, 95% CI (1.32-3.97) for ejection fraction 30-50, OR = 5.15, 95% CI (1.73-15.35) for ejection fraction < or =30 vs. >50%, P = 0.003] and age [OR = 1.84, 95% CI (1.18-2.89) for 80-85 years, OR=3.38, 95% CI (1.38-8.27) for > or =85 vs. 75-80 years, P = 0.008] were significantly associated with the decision not to operate; however, the Charlson comorbidity index was not [OR = 1.72, 95% CI (0.83-3.50), P = 0.14 for index > or =2 vs. <2]. Neurological dysfunction was the only comorbidity significantly linked with the decision not to operate.



Surgery was denied in 33% of elderly patients with severe, symptomatic AS. Older age and LV dysfunction were the most striking characteristics of patients who were denied surgery, whereas comorbidity played a less important role.
Relative Effectiveness of Letrozole Compared With Tamoxifen for Patients With Lobular Carcinoma in the BIG 1-98 Trial.

To evaluate the relative effectiveness of letrozole compared with tamoxifen for patients with invasive ductal or lobular carcinoma.



Patients diagnosed with early-stage invasive ductal carcinoma (IDC) or classic invasive lobular carcinoma (ILC) who were randomly assigned onto the Breast International Group (BIG) 1-98 trial and who had centrally reviewed pathology data were included (N = 2,923). HER2-negative IDC and ILC were additionally classified as hormone receptor-positive with high (luminal B [LB] -like) or low (luminal A [LA] -like) proliferative activity by Ki-67 labeling index. Survival analyses were performed with weighted Cox models that used inverse probability of censoring weighted modeling.



The median follow-up time was 8.1 years. In multivariable models for disease-free survival (DFS), significant interactions between treatment and histology (ILC or IDC; P = .006) and treatment and subgroup (LB like or LA like; P = .01) were observed. In the ILC subset, there was a 66% reduction in the hazard of a DFS event with letrozole for LB (hazard ratio [HR], 0.34; 95% CI, 0.21 to 0.55) and a 50% reduction for LA subtypes (HR, 0.50; 95% CI, 0.32 to 0.78). In the IDC subset, there was a significant 35% reduction in the hazard of a DFS event with letrozole for the LB subtype (HR, 0.65; 95% CI, 0.53 to 0.79), but no difference between treatments was noted for IDC and the LA subtype (HR, 0.95; 95% CI, 0.76 to 1.20).



The magnitude of benefit of adjuvant letrozole is greater for patients diagnosed with lobular carcinoma versus ductal carcinoma.
Association of Small Dense LDL Serum Levels and Circulating Monocyte Subsets in Stable Coronary Artery Disease

Atherosclerosis is considered to be an inflammatory disease in which monocytes and monocyte-derived macrophages play a key role. Circulating monocytes can be divided into three distinct subtypes, namely in classical monocytes (CM; CD14++CD16-), intermediate monocytes (IM; CD14++CD16+) and non-classical monocytes (NCM; CD14+CD16++). Low density lipoprotein particles are heterogeneous in size and density, with small, dense LDL (sdLDL) crucially implicated in atherogenesis. The aim of this study was to examine whether monocyte subsets are associated with sdLDL serum levels.



We included 90 patients with angiographically documented stable coronary artery disease and determined monocyte subtypes by flow cytometry. sdLDL was measured by an electrophoresis method on polyacrylamide gel.



Patients with sdLDL levels in the highest tertile (sdLDL≥4mg/dL;T3) showed the highest levels of pro-inflammatory NCM (15.2±7% vs. 11.4±6% and 10.9±4%, respectively; p<0.01) when compared with patients in the middle (sdLDL=2-3mg/dL;T2) and lowest tertile (sdLDL=0-1mg/dL;T1). Furthermore, patients in the highest sdLDL tertile showed lower CM levels than patients in the middle and lowest tertile (79.2±8% vs. 83.9±7% and 82.7±5%; p<0.01 for T3 vs. T2+T1). Levels of IM were not related to sdLDL levels (5.6±4% vs. 4.6±3% vs. 6.4±3% for T3, T2 and T1, respectively). In contrast to monocyte subset distribution, levels of circulating pro- and anti-inflammatory markers were not associated with sdLDL levels.



The atherogenic lipoprotein fraction sdLDL is associated with an increase of NCM and a decrease of CM. This could be a new link between lipid metabolism dysregulation, innate immunity and atherosclerosis.
Brain morphometry using diffusion-weighted magnetic resonance imaging: application to schizophrenia.

Loss of cortical gray matter is accompanied by a commensurate increase in the sulcal and intraventricular cerebrospinal fluid volume. On diffusion-weighted magnetic resonance imaging, this would be reflected as a higher apparent diffusion coefficient in affected brain regions. On the basis of the above premise, we suggest that the apparent diffusion coefficient may be used as a surrogate marker for the assessment of regional brain volume deficits. We demonstrate this approach by voxelwise analysis of registered apparent diffusion coefficient images from a group of 15 patients with schizophrenia and 15 age-matched healthy controls. We found widespread regional apparent diffusion coefficient increases in patients. Affected areas included the bilateral insular cortex, hippocampus, temporal lobe, and occipital areas. These results largely concur with previous findings of cortical volume deficits in schizophrenia.
Prolonged running, not fluoxetine treatment, increases neurogenesis, but does not alter neuropathology, in the 3xTg mouse model of Alzheimer's disease.

Reductions in adult neurogenesis have been documented in the original 3xTg mouse model of Alzheimer's disease (AD), notably occurring at the same age when spatial memory deficits and amyloid plaque pathology appeared. As this suggested reduced neurogenesis was associated with behavioral deficits, we tested whether activity and pharmacological stimulation could prevent memory deficits and modify neurogenesis and/or neuropathology in the 3xTg model backcrossed to the C57Bl/6 strain. We chronically administered the antidepressant fluoxetine to one group of mice, allowed access to a running wheel in another, and combined both treatments in a third cohort. All treatments lasted for 11 months. The female 3xTg mice failed to exhibit any deficits in spatial learning and memory as measured in the Morris water maze, indicating that when backcrossed to the C57Bl/6 strain, the 3xTg mice lost the behavioral phenotype that was present in the original 3xTg mouse maintained on a hybrid background. Despite this, the backcrossed 3xTg mice expressed prominent intraneuronal amyloid beta (Aβ) levels in the cortex and amygdala, with lower levels in the CA1 area of the hippocampus. In the combined cohort, fluoxetine treatment interfered with exercise and reduced the total distance run. The extent of Aβ neuropathology, the tau accumulations, or BDNF levels, were not altered by prolonged exercise. Thus, neuropathology was present but not paralleled by spatial memory deficits in the backcrossed 3xTg mouse model of AD. Prolonged exercise for 11 months did improve the long-term survival of newborn neurons generated during middle-age, whereas fluoxetine had no effect. We further review and discuss the relevant literature in this respect.
Effect of risedronate on hip structural geometry: a 1-year, double-blind trial in chemotherapy-induced postmenopausal women.

Chemotherapy-induced menopause is associated with bone loss. The effect on structural geometry is unknown. Our objective was to determine if oral bisphosphonate therapy could maintain or improve femoral geometry in breast cancer patients with chemotherapy-induced menopause.



This preplanned 1 year interim, secondary analysis of the Risedronate's Effect on Bone loss in Breast CAncer Study (REBBeCA Study) examined hip structure analysis (HSA), i.e. changes in the bone cross-sectional area (bone CSA), section modulus (SM: measure of bending strength), cortical thickness (CT) and buckling ratio (BR: index of cortical bone stability), in a double-blind trial of 87 newly postmenopausal, nonmetastatic breast cancer patients, randomized to risedronate, 35 mg once weekly (RIS) versus placebo (PBO).



After 12 months, intertrochanteric parameters demonstrated percentage improvement (RIS vs. PBO) from baseline in bone CSA (mean+/-SD: 4.25+/-6.29 vs. 0.60+/-5.99%), SM (3.97+/-6.40 vs. 0.80+/-7.08%), and CT [5.20+/-6.98 vs. 1.13+/-6.87% (all p-values <0.05 except SM p=0,0643)]. Similar improvements were observed at the femoral shaft [bone CSA: 2.24+/-5.74 vs. -0.78+/-5.73%; SM: 1.62+/-6.23 vs. -1.39+/-7.06%; CT: 3.79+/-7.84 vs. -0.17+/-7.90% (all p-values <0.05, RIS vs. PBO, except SM p= p =0.0568)]. At both sites, the BR had significant decreases consistent with improved strength.



We conclude that RIS improves measures of hip structural geometry in women with breast cancer following chemotherapy.
Treatment of traumagenic beliefs among sexually abused girls and their mothers: an evaluation study.

The objective of this study was to evaluate and compare the efficacy of two short-term individual therapy interventions for sexually abused girls and their nonoffending female caretakers. Thirty-two girls, ages 8 to 13, and their caretakers from primarily low-income, African-American families were randomly assigned to a theoretically based, structured experimental treatment program or to a relatively unstructured comparison intervention. Measures of child outcome were completed before and after the treatment program by each parent and child, and by a clinician blind to treatment condition. Pre- and postmeasures of maternal outcome were completed by the caretaker and a clinician not involved in the treatment. Both treatment programs yielded decreases in children's posttraumatic stress disorder symptoms and traumagenic beliefs reflecting self-blame and powerlessness, and increases in children's overall psychosocial functioning. The experimental intervention was more effective than the comparison program in increasing abuse-related caretaker support of the child and in decreasing caretaker self-blame and expectations of undue negative impact of the abuse on the child. Clinical implications of these findings include the development of interventions targeting sexually abused children's traumagenic beliefs and nonoffending parents' support of their victimized children.
Biphasic anti-osteoclastic action of intravenous alendronate therapy in multiple myeloma bone disease

Multiple myeloma is a malignancy of plasma cells with osteolytic bone destruction. Bisphosphonates inhibit osteoclast activity and are widely used for the treatment of myeloma bone disease. We analyzed the changes in urinary cross-linked N-telopeptides of collagen (u-NTx) and urinary calcium (u-Ca) after bisphosphonate alendronate therapy in ten patients with myeloma bone disease. In all patients, the levels of u-Ca and u-NTx decreased within a week. After the maximum decrease of u-NTx, u-NTx started increasing in half of the patients. However, this further increase in u-NTx decreased again without any additional therapy. Disease severity and pretreatment u-NTx concentrations did not differ between patients with and without the rebound. Patients who did not have rebound had decreased bone marrow monocytes and decreased serum concentrations of interleukin 18, which is produced by monocytes. Our results suggest that impaired activity of monocytes, which are possible osteoclast precursors, is related to reduced bone destruction in multiple myeloma.
Epidemiology of diabetes mellitus in German general practitioners' consultation--results of the SESAM 2-study.

The treatment of chronic diseases is of eminent importance in primary care, and type 2-diabetes mellitus is one of the most common dysfunctions. Its world-wide prevalence has been increasing from year to year. Thus, to estimate the prevalence and incidence of diabetes mellitus, we performed the SESAM (Sächsiche epidemiologische Studie in der Allgemeinmedizin) 2-study in cooperation with general practitioners (GPs) from the German state of Saxony; 270 of the 2510 (10.8%) solicited physicians participated. Cross-sectional data were collected from 1 October 1999 until 30 September 2000, from randomly selected patients previously known to the practitioner. From a total of 8877 consultations with 270 GPs, diabetes was prevalent in 14% (n = 1241) of the patients and the incidence was 0.3% (27 of 8877 cases). The consultation prevalence was estimated at 14.3% (n = 1268; CI 13.6-15%). Of the diabetic patients, 3.5% (n = 44) suffered from type 1-diabetes, while type 2-diabetes was found in 66.9% (n = 848) of the cases. "Other diabetes" was determined in 19.2% (n = 244), and "not further specified diabetes", in 10.4% (n = 132) of the cases. Related to the German population in general, the prevalence ranged from 7.9 to 9.2%. The estimated consultation prevalence is about four times higher than that in other European countries. These data are of importance in illustrating the epidemiology of diabetes in the population and the direct repercussions for GPs. They also point out the significance of diabetes as a major challenge to the German health care system.
Evaluation and management of heterotopic ossification in patients with spinal cord injury

Sixty-three patients with paralysis secondary to spinal cord injury (SCI) were screened for heterotopic ossification (HO) by bone scintigraphy 27±14 (mean±SD) days after SCI. There were four female and 59 male patients, 36 had paraplegia and 27 tetraplegia. The age of patients was 28±9 years. Bone scintigraphy was obtained with a 3-phase test using 99m-technetium labeled diphosphonate, and the positive third phase was used as a criterion for diagnosis of HO. Bone scintigraphy was negative for HO in 27 patients (14 tetraplegic and 13 paraplegic) and positive in 36 patients (13 tetraplegic and 23 paraplegic). The patients with positive HO were treated with etidronate, first with an intravenous dose of 300 mg/day for 3 days, and then with an oral dose of 20 mg/kg/day for 6 months. The follow-up of patients consisted of clinical and radiographic evaluations every 2 – 4 months. The extent of HO was classified radiographically. In the treated group of patients who completed the entire course of etidronate therapy one patient developed HO, the remaining 28 (97%) patients had no radiographic evidence of HO during the follow-up of 10.6±4.5 months after initiation of therapy. Our data indicate that: (a) early HO can be detected in the asymptomatic patients using bone scintigraphy on the average of 4 weeks (27±14 days) after SCI and (b) the therapy with etidronate might be effective in the prevention of HO in majority of patients when the treatment is initiated in an early stage of heterotopic bone formation.
Pharmacokinetics of phenylacetate administered as a 30-min infusion in children with refractory cancer

Phenylacetate (PAA), a deaminated metabolite of phenylalanine, suppresses tumor growth and induces differentiation in preclinical tumor models. We performed a pharmacokinetic study, as part of a phase I trial, of PAA in children with refractory cancer. PAA was administered as a 30-min i.v. infusion at a dose of 1.8 or 2.5 g/m2. Serial plasma samples were collected for up to 24 h after the end of the infusion in 27 children. The concentrations of PAA and its inactive metabolite, phenylacetylglutamine (PAG), were measured using a reverse-phase high-performance liquid chromatography assay with ultraviolet detection. PAA and PAG concentrations were best described by a two-compartment model (one compartment for each compound) with capacity-limited conversion of PAA to PAG. The half-life of PAA was 55±18 min at the 1.8 g/m2 dose and 77±22 min at the 2.5 g/m2 dose. The half-life of PAG was 112±53 min at the 1.8 g/m2 dose and 135±75 min at the 2.5 g/m2 dose. The clearance of PAA was 66±33 ml/min per m2 at the 1.8 g/m2 dose and 60±24 ml/min per m2 at the 2.5 g/m2 dose. The Michaelis-Menten constants describing the conversion of PAA to PAG in the model (Vm and Km) were (means±SD) 18.4±13.8 mg/m2 per min and 152±155 μg/ml, respectively. The volumes of distribution for PAA and PAG (Vd-PAA and Vd-PAG) were 7.9±3.4 l/m2 and 34.4±16.1 l/m2, respectively. The first-order elimination rate constant for PAG (ke-PAG) was 0.0091±0.0039 min−1. The capacity-limited conversion of PAA to PAG has important implications for the dosing of PAA, and the pharmacokinetic model described here may be useful for individualizing the infusion rate of the drug in future clinical trials.
Combination of methotrexate and sulphasalazine in patients with rheumatoid arthritis: pharmacokinetic analysis and relationship to clinical response.

1. The influence of sulphasalazine (SASP) on the pharmacokinetics of low dose methotrexate (MTX) and the relation between pharmacokinetic variables and clinical response was studied in 15 patients with active rheumatoid arthritis despite > 6 months of SASP treatment. 2. SASP was stopped for 2 weeks. Thereafter a single oral dose of 7.5 mg MTX was administered after a standard breakfast. Blood was sampled initially every 30 min, thereafter hourly during 8 h. Urine was sampled every hour. Then 2000 mg SASP daily + 7.5 mg MTX weekly was given. After 4 weeks the same procedure was repeated supplemented with concomitant administration of 1000 mg SASP. Clinical measurements included Ritchie articular index, number of swollen joints, ESR and the disease activity score. Pharmacokinetic analysis was performed using a two-compartment model with first order absorption and lag time. Results are given as mean (s.d.). Paired t-test or signed rank test were applied in the statistical analysis. 3. Pharmacokinetics of MTX without vs with SASP, means +/- s.d. were follows: AUC: 673 +/- 179 vs 628 +/- 210 (95% confidence interval [CI] of the difference was -71 to 159) ng ml-1, MRT: 5.2 +/- 1.3 vs 5.2 +/- 1.1 (95% CI -0.4 to 0.4) h, t1/2,z: 4.3 +/- 1.1 vs 4.2 +/- 1.1 (95% CI -0.3 to 0.5) h, V/F: 59.3 +/- 29.3 vs 65.5 +/- 25.3 (95% -23.8 to 11.4) 1, CL/F: 12.3 +/- 5.0 vs 13.5 +/- 4.8 (95% CI -4.5 to 2.3) 1 h-1. CLR/F: 6.2 +/- 1.3 vs 6.3 +/- 2.1 (95% CI -1.3 to 1.1) l h-1. All P values were > or = 0.3. 4. A weak correlation existed between the change of ESR and the MRT, the t1/2,z and the V/F (Spearman correlation coefficients of 0.43, 0.50 and 0.50 respectively, 0.05 < P < 0.1). 5. There is no significant influence of chronic SASP administration on the pharmacokinetics of MTX or vice versa. Of the clinical variables, only the ESR correlated consistently with some pharmacokinetic variables on MTX.
Three-dimensional and two-dimensional quantitative coronary angiography, and their prediction of reduced fractional flow reserve.

We investigated whether three-dimensional (3D) and two-dimensional quantitative coronary angiography (2D-QCA) measurements differed in their accuracy in predicting reduced fractional flow reserve (FFR), and how this varied with stenosis severity and the FFR cut-off used.



Three-dimensional and 2D-QCA were compared in their measurements of minimum luminal area (MLA), percentage area stenosis, lesion length, minimum luminal diameter (MLD) and percentage diameter stenosis, and in their prediction of functionally significant FFR. In total, 63 target lesions were interrogated in 63 patients undergoing elective percutaneous coronary intervention. Of all measurements of lesion severity obtained by 3D-QCA, MLA best correlated with FFR (R = 0.63, P < 0.001), and was the most accurate predictor of FFR < 0.75 (C statistic 0.86, P < 0.001). Of 2D-QCA measurements, MLD correlated best with FFR (R = 0.58, P < 0.001), and best predicted FFR < 0.75 (C statistic 0.80, P < 0.001). Overall, 3D-QCA showed a non-significant trend towards more accurate prediction of FFR than 2D-QCA, especially in intermediate lesions. The relationship between FFR and apparent stenosis severity was found to be curvilinear. Both 3D- and 2D-QCA were less accurate in intermediate lesions, and in predicting FFR ≤ 0.80 than in predicting FFR <0.75.



The accuracy of QCA in predicting functionally significant FFR is limited and is dependent on FFR cut-off used and lesion severity. Where FFR is not available or contraindicated, 3D-QCA may assist in the evaluation of coronary lesions of intermediate severity.