Epidemiology and direct medical costs of osteoporotic fractures in men and women in Switzerland

The aim of this study was to estimate the hospitalization incidence and the total number of hospital days related to all fractures and osteoporotic fractures in the year 2000 in Switzerland and to compare these with data from other frequent disorders in men and women. The official administrative and medical statistics database of the Swiss Federal Office of Statistics (SFOS) from the year 2000 was used. It covered 81.2% of all registered patient admissions and was considered to be representative of the entire population. We included the ICD-10 codes of 84 diagnoses that were compatible with an underlying osteoporosis and applied the best matching age-specific osteoporosis attribution rates published for the ICD-9 diagnosis codes to the individual ICD-10 codes. To preserve comparability with previously published data from 1992, we grouped the data related to the ICD-10 fracture codes into seven diagnosis pools (fractures of the axial skeleton, fractures of the proximal upper limbs, fractures of the distal upper limbs, fractures of the proximal lower limbs, fractures of the distal lower limbs, multiple fractures, and osteoporosis) and analyzed them separately for women and men by age group. Incidences of hospitalization due to fractures were calculated, and the direct medical costs related to hospitalization were estimated. In addition, we compared the results with those from chronic pulmonary obstructive disease (COPD), stroke, acute myocardial infarction, heart failure, diabetes and breast carcinoma from the same database. In Switzerland during 2000, 62,535 hospitalizations for fractures (35,586 women and 26,949 men) were registered. Fifty-one percent of all fractures in women and 24% in men were considered as osteoporotic. The overall incidences of hospitalization due to fractures were 969 and 768 per 100,000 in women and men, respectively. The hospitalization incidences for fractures of the proximal lower limbs and the axial skeleton increased exponentially after the age of 65 years. The direct medical cost of hospitalization of patients with osteoporosis and/or related fractures was 357 million CHF. Hip fractures accounted for approximately half of these costs in women and men. Among other common diseases in women and men, osteoporosis ranked number 1 in women and number 2 (behind COPD) in men. When compared with data from 1992, the average length of stay had shortened by 8.4 days for women and 4.7 days for men, leading to a decrease of almost 40% in direct medical costs related to acute hospitalizations. This apparent decrease in cost might result from a shift into the ambulatory cost segment, for which the assessment and management tools need to be developed. We conclude that, in 2000, osteoporosis continued to be a heavy burden on the Swiss healthcare system. Lack of awareness of the disease and its consequences prevents widespread use of drugs with anti-fracture efficacy. This limits their potential to reduce costs.

Optimized Demineralization Technique for the Measurement of Stable Isotope Ratios of Nonexchangeable H in Soil Organic Matter

To make use of the isotope ratio of nonexchangeable hydrogen (δ2Hn (nonexchangeable)) of bulk soil organic matter (SOM), the mineral matrix (containing structural water of clay minerals) must be separated from SOM and samples need to be analyzed after H isotope equilibration. We present a novel technique for demineralization of soil samples with HF and dilute HCl and recovery of the SOM fraction solubilized in the HF demineralization solution via solid-phase extraction. Compared with existing techniques, organic C (Corg) and organic N (Norg) recovery of demineralized SOM concentrates was significantly increased (Corg recovery using existing techniques vs new demineralization method: 58% vs 78%; Norg recovery: 60% vs 78%). Chemicals used for the demineralization treatment did not affect δ2Hn values as revealed by spiking with deuterated water. The new demineralization method minimized organic matter losses and thus artificial H isotope fractionation, opening up the opportunity to use δ2Hn analyses of SOM as a new tool in paleoclimatology or geospatial forensics.

Bone-Conditioned Medium Inhibits Osteogenic and Adipogenic Differentiation of Mesenchymal Cells In Vitro

BACKGROUND AND PURPOSE Autografts are used for bone reconstruction in regenerative medicine including oral and maxillofacial surgery. Bone grafts release paracrine signals that can reach mesenchymal cells at defect sites. The impact of the paracrine signals on osteogenic, adipogenic, and chondrogenic differentiation of mesenchymal cells has remained unclear. MATERIAL AND METHODS Osteogenesis, adipogenesis, and chondrogenesis were studied with murine ST2 osteoblast progenitors, 3T3-L1 preadipocytes, and ATDC5 prechondrogenic cells, respectively. Primary periodontal fibroblasts from the gingiva, from the periodontal ligament, and from bone were also included in the analysis. Cells were exposed to bone-conditioned medium (BCM) that was prepared from porcine cortical bone chips. RESULTS BCM inhibited osteogenic and adipogenic differentiation of ST2 and 3T3-L1 cells, respectively, as shown by histological staining and gene expression. No substantial changes in the expression of chondrogenic genes were observed in ATDC5 cells. Primary periodontal fibroblasts also showed a robust decrease in alkaline phosphatase and peroxisome proliferator-activated receptor gamma (PPARγ) expression when exposed to BCM. BCM also increased collagen type 10 expression. Pharmacologic blocking of transforming growth factor (TGF)-β receptor type I kinase with SB431542 and the smad-3 inhibitor SIS3 at least partially reversed the effect of BCM on PPARγ and collagen type 10 expression. In support of BCM having TGF-β activity, the respective target genes were increasingly expressed in periodontal fibroblasts. CONCLUSIONS The present work is a pioneer study on the paracrine activity of bone grafts. The findings suggest that cortical bone chips release soluble signals that can modulate differentiation of mesenchymal cells in vitro at least partially involving TGF-β signaling.

Relative Energy Balance, CKD, and Risk of Cardiovascular and All-Cause Mortality.

BACKGROUND Mortality risk for people with chronic kidney disease is substantially greater than that for the general population, increasing to a 7-fold greater risk for those on dialysis therapy. Higher body mass index, generally due to higher energy intake, appears protective for people on dialysis therapy, but the relationship between energy intake and survival in those with reduced kidney function is unknown. STUDY DESIGN Prospective cohort study with a median follow-up of 14.5 (IQR, 11.2-15.2) years. SETTING & PARTICIPANTS Blue Mountains Area, west of Sydney, Australia. Participants in the general community enrolled in the Blue Mountains Eye Study (n=2,664) who underwent a detailed interview, food frequency questionnaire, and physical examination including body weight, height, blood pressure, and laboratory tests. PREDICTORS Relative energy intake, food components (carbohydrates, total sugars, fat, protein, and water), and estimated glomerular filtration rate (eGFR). Relative energy intake was dichotomized at 100%, and eGFR, at 60mL/min/1.73m(2). OUTCOMES All-cause and cardiovascular mortality. MEASUREMENTS All-cause and cardiovascular mortality using unadjusted and adjusted Cox proportional regression models. RESULTS 949 people died during follow-up, 318 of cardiovascular events. In people with eGFR<60mL/min/1.73m(2) (n=852), there was an increased risk of all-cause mortality (HR, 1.48; P=0.03), but no increased risk of cardiovascular mortality (HR, 1.59; P=0.1) among those with higher relative energy intake compared with those with lower relative energy intake. Increasing intake of carbohydrates (HR per 100g/d, 1.50; P=0.04) and total sugars (HR per 100g/d, 1.62; P=0.03) was associated significantly with increased risk of cardiovascular mortality. LIMITATIONS Under-reporting of energy intake, baseline laboratory and food intake values only, white population. CONCLUSIONS Increasing relative energy intake was associated with increased all-cause mortality in patients with eGFR<60mL/min/1.73m(2). This effect may be mediated by increasing total sugars intake on subsequent cardiovascular events.

Brain metabolite composition during early human brain development as measured by quantitative in vivo 1H magnetic resonance spectroscopy

Biochemical maturation of the brain can be studied noninvasively by (1)H magnetic resonance spectroscopy (MRS) in human infants. Detailed time courses of cerebral tissue contents are known for the most abundant metabolites only, and whether or not premature birth affects biochemical maturation of the brain is disputed. Hence, the last trimester of gestation was observed in infants born prematurely, and their cerebral metabolite contents at birth and at expected term were compared with those of fullterm infants. Successful quantitative short-TE (1)H MRS was performed in three cerebral locations in 21 infants in 28 sessions (gestational age 32-43 weeks). The spectra were analyzed with linear combination model fitting, considerably extending the range of observable metabolites to include acetate, alanine, aspartate, cholines, creatines, gamma-aminobutyrate, glucose, glutamine, glutamate, glutathione, glycine, lactate, myo-inositol, macromolecular contributions, N-acetylaspartate, N-acetylaspartylglutamate, o-phosphoethanolamine, scyllo-inositol, taurine, and threonine. Significant effects of age and location were found for many metabolites, including the previously observed neuronal maturation reflected by an increase in N-acetylaspartate. Absolute brain metabolite content in premature infants at term was not considerably different from that in fullterm infants, indicating that prematurity did not affect biochemical brain maturation substantially in the studied population, which did not include infants of extremely low birthweight.

Active surveillance for rheumatic heart disease in endemic regions: a systematic review and meta-analysis of prevalence among children and adolescents

BACKGROUND Rheumatic heart disease accounts for up to 250 000 premature deaths every year worldwide and can be regarded as a physical manifestation of poverty and social inequality. We aimed to estimate the prevalence of rheumatic heart disease in endemic countries as assessed by different screening modalities and as a function of age. METHODS We searched Medline, Embase, the Latin American and Caribbean System on Health Sciences Information, African Journals Online, and the Cochrane Database of Systematic Reviews for population-based studies published between Jan 1, 1993, and June 30, 2014, that reported on prevalence of rheumatic heart disease among children and adolescents (≥5 years to <18 years). We assessed prevalence of clinically silent and clinically manifest rheumatic heart disease in random effects meta-analyses according to screening modality and geographical region. We assessed the association between social inequality and rheumatic heart disease with the Gini coefficient. We used Poisson regression to analyse the effect of age on prevalence of rheumatic heart disease and estimated the incidence of rheumatic heart disease from prevalence data. FINDINGS We included 37 populations in the systematic review and meta-analysis. The pooled prevalence of rheumatic heart disease detected by cardiac auscultation was 2·9 per 1000 people (95% CI 1·7-5·0) and by echocardiography it was 12·9 per 1000 people (8·9-18·6), with substantial heterogeneity between individual reports for both screening modalities (I(2)=99·0% and 94·9%, respectively). We noted an association between social inequality expressed by the Gini coefficient and prevalence of rheumatic heart disease (p=0·0002). The prevalence of clinically silent rheumatic heart disease (21·1 per 1000 people, 95% CI 14·1-31·4) was about seven to eight times higher than that of clinically manifest disease (2·7 per 1000 people, 1·6-4·4). Prevalence progressively increased with advancing age, from 4·7 per 1000 people (95% CI 0·0-11·2) at age 5 years to 21·0 per 1000 people (6·8-35·1) at 16 years. The estimated incidence was 1·6 per 1000 people (0·8-2·3) and remained constant across age categories (range 2·5, 95% CI 1·3-3·7 in 5-year-old children to 1·7, 0·0-5·1 in 15-year-old adolescents). We noted no sex-related differences in prevalence (p=0·829). INTERPRETATION We found a high prevalence of rheumatic heart disease in endemic countries. Although a reduction in social inequalities represents the cornerstone of community-based prevention, the importance of early detection of silent rheumatic heart disease remains to be further assessed. FUNDING UBS Optimus Foundation.

Toward Cove-Edged Low Band Gap Graphene Nanoribbons

Graphene nanoribbons (GNRs), defined as nanometer-wide strips of graphene, have attracted increasing attention as promising candidates for next-generation semiconductors. Here, we demonstrate a bottom-up strategy toward novel low band gap GNRs (E-g = 1.70 eV) with a well-defined cove-type periphery both in solution and on a solid substrate surface with chrysene as the key monomer. Corresponding cyclized chrysene-based oligornerS consisting of the dimer and tetramer are obtained via an Ullmann Coupling followed by oxidative intramolecular cyclodehydrogenation in solution, and much higher GNR homologues via on-surface synthesis. These oligomers adopt nonplanar structures due to the isteric repulsion between the two C-H bonds at the inner cove position. Characterizations by single crystal X-ray analysis, UV-vis absorption spectroscopy, NMR spectroscopy, and scanning tunneling microscopy (STM) are described. The interpretation is assisted by density functional theory (DFT) calculations.

Multiple causes of the Younger Dryas cold period

The Younger Dryas cooling event disrupted the overall warming trend in the North Atlantic region during the last deglaciation. Climate change during the Younger Dryas was abrupt and thus provides insights into the sensitivity of the climate system to perturbations. The sudden Younger Dryas cooling has traditionally been attributed to a shutdown of the Atlantic Meridional Overturning Circulation by meltwater discharges. However, alternative explanations such as strong negative radiative forcing14 and a shift in atmospheric circulation have also been offered. Here we investigate the importance of these different forcings in coupled climate model experiments constrained by data assimilation. We find that the Younger Dryas climate signal as registered in proxy evidence is best simulated using a combination of processes: a weakened Atlantic Meridional Overturning Circulation, moderate negative radiative forcing and an altered atmospheric circulation. We conclude that none of the individual mechanisms alone provide a plausible explanation for the Younger Dryas cold period. We suggest that the triggers for abrupt climate changes such as the Younger Dryas are more complex than suggested so far, and that studies on the response of the climate system to perturbations should account for this complexity.

Latent profiles of work motivation in adolescents in relation to work expectations, goal engagement, and changes in work experiences

Motivation plays a key role in successful entry into working life. Based on a cross-sectional and a one-year longitudinal study, we used a person-centered approach to explore work-related motivation (i.e., autonomous goals, positive affect, and occupational self-efficacy) among 577 students in 8th grade (Study 1) and 949 adolescents in vocational training (Study 2). Based on latent profile analysis, in both studies we identified four groups that were characterized by different levels of overall motivation and one group characterized by low positive affect and mean levels in autonomous goals and self-efficacy. Profiles characterized by high levels of motivation showed the highest levels of positive work expectations and goal engagement and the lowest levels of negative work expectations in Study 1 and the highest levels of person-job fit, work engagement, and job satisfaction in Study 2. Moreover, latent difference score analysis showed that motivational profiles predicted changes in person-job fit and work engagement across one year but not in job satisfaction. The results imply that career counselors should be aware of characteristic motivational patterns of clients that may require specific counseling approaches.