TBS (Trabecular Bone Score) is More Sensitive Than BMD to Diabetes-Related Fracture Risk

Background:Type 2 diabetes (T2D) is associated with increased fracture risk but paradoxically greater BMD. TBS (trabecular bone score), a novel grey-level texture measurement extracted from DXA images, correlates with 3D parameters of bone micro-architecture. We evaluated the ability of lumbar spine (LS) TBS to account for the increased fracture risk in diabetes. Methods:29,407 women ≥50 years at the time of baseline hip and spine DXA were identified from a database containing all clinical BMD results for the Province of Manitoba, Canada. 2,356 of the women satisfied a well-validated definition for diabetes, the vast majority of whom (>90%) would have T2D. LS L14 TBS was derived for each spine DXA examination blinded to clinical parameters and outcomes. Health service records were assessed for incident non-traumatic major osteoporotic fracture codes (mean follow-up 4.7 years). Results:In linear regression adjusted for FRAX risk factors (age,BMI, glucocorticoids, prior major fracture, rheumatoid arthritis, COPD as a smoking proxy, alcohol abuse) and osteoporosis therapy, diabetes was associated with higher BMD for LS, femoral neck and total hip but lower LS TBS (all p<0.001). Similar results were seen after excluding obese subjects withBMI>30. In logistic regression (Figure), the adjusted odds ratio (OR) for a skeletal measurement in the lowest vs highest tertile was less than 1 for all BMD measurements but increased for LS TBS (adjusted OR 2.61, 95%CI 2.30-2.97). Major osteoporotic fractures were identified in 175 (7.4%) with and 1,493 (5.5%) without diabetes (p < 0.001). LS TBS predicted fractures in those with diabetes (adjusted HR 1.27, 95%CI 1.10-1.46) and without diabetes (HR 1.31, 95%CI 1.24-1.38). LS TBS was an independent predictor of fracture (p<0.05) when further adjusted for BMD (LS, femoral neck or total hip). The explanatory effect of diabetes in the fracture prediction model was greatly reduced when LS TBS was added to the model (indicating that TBS captured a large portion of the diabetes-associated risk), but was paradoxically increased from adding any of the BMD measurements. Conclusions:Lumbar spine TBS is sensitive to skeletal deterioration in postmenopausal women with diabetes, whereas BMD is paradoxically greater. LS TBS predicts osteoporotic fractures in those with diabetes, and captures a large portion of the diabetes-associated fracture risk. Combining LS TBS with BMD incrementally improves fracture prediction.

Predictors of substance use reduction in an epidemiological first-episode psychosis cohort.

AIM: To assess the predictors of a significant decrease or cessation of substance use (SU) in a treated epidemiological cohort of first-episode psychosis (FEP) patients. METHOD: Participants were FEP patients of the Early Psychosis Prevention and Intervention Centre in Australia. Patients' medical files were reviewed using a standardized file audit. Data on 432 patients with FEP and baseline co-morbid substance use disorder (SUD) were available for analysis. Predictors of reduction/cessation of SU at follow up were examined using logistic regression analyses. RESULTS: In univariate analyses, a reduction/cessation of SU was predicted by baseline measures reflecting higher education, employment, accommodation with others, cannabis use disorder (CUD) only (rather than poly-SUDs), better global functioning and better premorbid social and occupational functioning, later age at onset of psychosis, and a diagnosis of non-affective psychosis. In multivariate analysis, CUD alone and better premorbid social and occupational functioning remained significant predictors. CONCLUSIONS: Addressing SUDs and social and occupational goals in people with FEP may offer opportunities to prevent SUDs becoming more severe or entrenched. Further longitudinal research on recovery from SU and FEP is needed to disentangle directions of influence and identify key targets for intervention.

Determinants of science-based cooperation: evidence in a sample of small and micro firms

We study the determining factors of cience-based cooperation in the case of small and micro firms. In this research, we propose an analytical framework based on the resource-based view of the firm and we identify a set of organisational characteristics, which we classify as internal, external and structural factors. Each factor can be linked to at least one reason, from the firm¿s point of view, to cooperate with universities and public research centres. Each reason can, in turn, be used as an indicator of a firm¿s organisational needs or organisational capacities. In order to validate the theoretical model, we estimate a logistic regression that models the propensity to participate in science-based cooperation activities within a sample of 285 small and micro firms located in Barcelona. The results show the key role played by the absorptive capacity of new and small companies.

Alcohol consumption and binge drinking in young adult childhood cancer survivors.

BACKGROUND: This study compared frequency of alcohol consumption and binge drinking between young adult childhood cancer survivors and the general population in Switzerland, and assessed its socio-demographic and clinical determinants. PROCEDURE: Childhood cancer survivors aged <16 years when diagnosed 1976-2003, who had survived >5 years and were currently aged 20-40 years received a postal questionnaire. Reported frequency of alcohol use and of binge drinking were compared to the Swiss Health Survey, a representative general population survey. Determinants of frequent alcohol consumption and binge drinking were assessed in a multivariable logistic regression. RESULTS: Of 1,697 eligible survivors, 1,447 could be contacted and 1,049 (73%) responded. Survivors reported more often than controls to consume alcohol frequently (OR = 1.7; 95%CI = 1.3-2.1) and to engage in binge drinking (OR = 2.9; 95%CI = 2.3-3.8). Peak frequency of binge drinking in males occurred at age 24-26 years in survivors, compared to age 18-20 in the general population. Socio-demographic factors (male gender, high educational attainment, French and Italian speaking, and migration background from Northern European countries) were most strongly associated with alcohol consumption patterns among both survivors and controls. CONCLUSIONS: The high frequency of alcohol consumption found in this study is a matter of concern. Our data suggest that survivors should be better informed on the health effects of alcohol consumption during routine follow-up, and that such counseling should be included in clinical guidelines. Future research should study motives of alcohol consumption among survivors to allow development of targeted health interventions for this vulnerable group.

Dynamic Capabilities and Firm Performance

Firms operating in a changing environment have a need for structures and practices that provide flexibility and enable rapid response to changes. Given the challenges they face in attempts to keep up with market needs, they have to continuously improve their processes and products, and develop new products to match market requirements. Success in changing markets depends on the firm's ability to convert knowledge into innovations, and consequently their internal structures and capabilities have an important role in innovation activities. According 10 the dynamic capability view of the firm, firms thus need dynamic capabilities in (he form ofassets, processes and structures that enable strategic flexibility and support entrepreneurial opportunity sensing and exploitation. Dynamic capabilities are also needed in conditions of rapid change in the operating environment, and in activities such as new product development and expansion to new markets. Despite the growing interest in these issues and the theoretical developments in the field of strategy research, there are still only very few empirical studies, and large-scale empirical studies in particular, that provide evidence that firms'dynamic capabilities are reflected in performance differences. This thesis represents an attempt to advance the research by providing empirical evidence of thelinkages between the firm's dynamic capabilities and performance in intenationalization and innovation activities. The aim is thus to increase knowledge and enhance understanding of the organizational factors that explain interfirm performance differences. The study is in two parts. The first part is the introduction and the second part comprises five research publications covering the theoretical foundations of the dynamic capability view and subsequent empirical analyses. Quantitative research methodology is used throughout. The thesis contributes to the literature in several ways. While a lot of prior research on dynamic capabilities is conceptual in nature, or conducted through case studies, this thesis introduces empirical measures for assessing the different aspects, and uses large-scale sampling to investigate the relationships between them and performance indicators. The dynamic capability view is further developed by integrating theoretical frameworks and research traditions from several disciplines. The results of the study provide support for the basic tenets of the dynamic capability view. The empirical findings demonstrate that the firm's ability to renew its knowledge base and other intangible assets, its proactive, entrepreneurial behavior, and the structures and practices that support operational flexibility arepositively related to performance indicators.

Stratification of the severity of critically ill patients with classification trees

Background: Development of three classification trees (CT) based on the CART (Classification and Regression Trees), CHAID (Chi-Square Automatic Interaction Detection) and C4.5 methodologies for the calculation of probability of hospital mortality; the comparison of the results with the APACHE II, SAPS II and MPM II-24 scores, and with a model based on multiple logistic regression (LR). Methods: Retrospective study of 2864 patients. Random partition (70:30) into a Development Set (DS) n = 1808 and Validation Set (VS) n = 808. Their properties of discrimination are compared with the ROC curve (AUC CI 95%), Percent of correct classification (PCC CI 95%); and the calibration with the Calibration Curve and the Standardized Mortality Ratio (SMR CI 95%). Results: CTs are produced with a different selection of variables and decision rules: CART (5 variables and 8 decision rules), CHAID (7 variables and 15 rules) and C4.5 (6 variables and 10 rules). The common variables were: inotropic therapy, Glasgow, age, (A-a)O2 gradient and antecedent of chronic illness. In VS: all the models achieved acceptable discrimination with AUC above 0.7. CT: CART (0.75(0.71-0.81)), CHAID (0.76(0.72-0.79)) and C4.5 (0.76(0.73-0.80)). PCC: CART (72(69- 75)), CHAID (72(69-75)) and C4.5 (76(73-79)). Calibration (SMR) better in the CT: CART (1.04(0.95-1.31)), CHAID (1.06(0.97-1.15) and C4.5 (1.08(0.98-1.16)). Conclusion: With different methodologies of CTs, trees are generated with different selection of variables and decision rules. The CTs are easy to interpret, and they stratify the risk of hospital mortality. The CTs should be taken into account for the classification of the prognosis of critically ill patients.

Additive effects of HLA alleles and innate immune genes determine viral outcome in HCV infection.

BACKGROUND: Chronic HCV infection is a leading cause of liver-related morbidity globally. The innate and adaptive immune responses are thought to be important in determining viral outcomes. Polymorphisms associated with the IFNL3 (IL28B) gene are strongly associated with spontaneous clearance and treatment outcomes. OBJECTIVE: This study investigates the importance of HLA genes in the context of genetic variation associated with the innate immune genes IFNL3 and KIR2DS3. DESIGN: We assess the collective influence of HLA and innate immune genes on viral outcomes in an Irish cohort of women (n=319) who had been infected from a single source as well as a more heterogeneous cohort (Swiss Cohort, n=461). In the Irish cohort, a number of HLA alleles are associated with different outcomes, and the impact of IFNL3-linked polymorphisms is profound. RESULTS: Logistic regression was performed on data from the Irish cohort, and indicates that the HLA-A*03 (OR 0.36 (0.15 to 0.89), p=0.027) -B*27 (OR 0.12 (0.03 to 0.45), p=<0.001), -DRB1*01:01 (OR 0.2 (0.07 to 0.61), p=0.005), -DRB1*04:01 (OR 0.31 (0.12 to 0.85, p=0.02) and the CC IFNL3 rs12979860 genotypes (OR 0.1 (0.04 to 0.23), p<0.001) are significantly associated with viral clearance. Furthermore, DQB1*02:01 (OR 4.2 (2.04 to 8.66), p=0.008), KIR2DS3 (OR 4.36 (1.62 to 11.74), p=0.004) and the rs12979860 IFNL3 'T' allele are associated with chronic infection. This study finds no interactive effect between IFNL3 and these Class I and II alleles in relation to viral clearance. There is a clear additive effect, however. Data from the Swiss cohort also confirms independent and additive effects of HLA Class I, II and IFNL3 genes in their prediction of viral outcome. CONCLUSIONS: This data supports a critical role for the adaptive immune response in the control of HCV in concert with the innate immune response.

Decoding auditory EEG responses in healthy and clinical populations: A comparative study.

BACKGROUND: Analyses of brain responses to external stimuli are typically based on the means computed across conditions. However in many cognitive and clinical applications, taking into account their variability across trials has turned out to be statistically more sensitive than comparing their means. NEW METHOD: In this study we present a novel implementation of a single-trial topographic analysis (STTA) for discriminating auditory evoked potentials at predefined time-windows. This analysis has been previously introduced for extracting spatio-temporal features at the level of the whole neural response. Adapting the STTA on specific time windows is an essential step for comparing its performance to other time-window based algorithms. RESULTS: We analyzed responses to standard vs. deviant sounds and showed that the new implementation of the STTA gives above-chance decoding results in all subjects (in comparison to 7 out of 11 with the original method). In comatose patients, the improvement of the decoding performance was even more pronounced than in healthy controls and doubled the number of significant results. COMPARISON WITH EXISTING METHOD(S): We compared the results obtained with the new STTA to those based on a logistic regression in healthy controls and patients. We showed that the first of these two comparisons provided a better performance of the logistic regression; however only the new STTA provided significant results in comatose patients at group level. CONCLUSIONS: Our results provide quantitative evidence that a systematic investigation of the accuracy of established methods in normal and clinical population is an essential step for optimizing decoding performance.

Association study of lipoprotein(a) genetic markers, traditional risk factors, and coronary heart disease in HIV-1-infected patients.

Objectives: General population studies have shown associations between copy number variation (CNV) of the LPA gene Kringle-IV type-2 (KIV-2) coding region, single-nucleotide polymorphism (SNP) rs6415084 in LPA and coronary heart disease (CHD). Because risk factors for HIV-infected patients may differ from the general population, we aimed to assess whether these potential associations also occur in HIV-infected patients. Methods: A unicenter, retrospective, case-control (1:3) study. Eighteen HIV-patients with confirmed diagnosis of acute myocardial infarction (AMI) were adjusted for age, gender, and time since HIV diagnosis to 54 HIV-patients without CHD. After gDNA extraction from frozen blood, both CNV and SNP genotyping were performed using real-time quantitative PCR. All genetic and non-genetic variables for AMI were assessed in a logistic regression analysis. Results: Our results did not confirm any association in terms of lipoprotein(a) LPA structural genetic variants when comparing KIV-2 CNV (p = 0.67) and SNP genotypes (p = 0.44) between AMI cases and controls. However, traditional risk factors such as diabetes mellitus, hypertension, and CD4(+) T cell count showed association (p < 0.05) with CHD. Conclusion: Although significant associations of AMI with diabetes, hypertension and CD4(+) T cell count in HIV-patients were found, this study could not confirm the feasibility neither of KIV-2 CNV nor rs6415084 in LPA as genetic markers of CHD in HIV-infected patients.Highlights:● Individuals with HIV infection are at higher risk of coronary heart disease (CHD) than the non-infected population.● Our results showed no evidence of LPA structural genetic variants associated with CHD in HIV-1-infected patients.● Associations were found between diabetes mellitus, arterial hypertension, CD4(+) T cell count, and CHD.● The clinical usefulness of these biomarkers to predict CHD in HIV-1-infected population remains unproven.● Further studies are needed to assess the contribution of common genetic variations to CHD in HIV-infected individuals.

Transactional sex and HIV risks - evidence from a cross-sectional national survey among young people in Uganda.

BACKGROUND: Transactional sex is associated with the HIV epidemic among young people in Uganda. Few quantitative studies based on nationally representative survey data explored the relationship between sexual behaviors, HIV infection, and transactional sex. OBJECTIVE: This study aimed to determine the associations between risky sexual behaviors, participation in transactional sex, and HIV sero-status among men and women aged 15-24 in Uganda. DESIGN: The study uses data from the Uganda AIDS Indicator Survey, a cross-sectional national HIV serological study conducted in 2011. We analyzed data on 1,516 men and 2,824 women aged 15-24 who had been sexually active in the 12 months preceding the survey. Private, face-to-face interviews were also conducted to record the sociodemographics, sexual history, and experiences of sexual coercion. Logistic regression analysis was performed to measure associations between sexual behaviors and transactional sex, and associations between HIV sero-status and transactional sex. RESULTS: Among young people who had been sexually active in the 12 months prior to the survey, 5.2% of young men reported paying for sex while 3.7% of young women reported receiving gifts, favors, or money for sex. Lower educational attainment (ORadjusted 3.25, CI 1.10-9.60) and experience of sexual coercion (ORadjusted 2.83, CI 1.07-7.47) were significantly associated with paying for sex among men. Multiple concurrent sexual relationships were significantly associated with paying for sex among young men (ORadjusted 5.60, CI 2.08-14.95) and receiving something for sex among young women (ORadjusted 8.04, CI 2.55-25.37). Paying for sex among young men and having three to five lifetime sexual partners among young women were associated with increased odds of testing positive for HIV. CONCLUSIONS: Transactional sex is associated with sexual coercion and HIV risk behaviors such as multiple concurrent sexual partnerships among young people in Uganda. In addition, transactional sex appears to place young men at increased risk for HIV in Uganda. Both sexes appear equally vulnerable to risks associated with transactional sex, and therefore should be targeted in intervention programs. In addition, strengthening universal education policy and improving school retention programs may be beneficial in reducing risky sexual behaviors and transactional sex.

Medication incidents in primary care medicine: protocol of a study by the Swiss Federal Sentinel Reporting System.

BACKGROUND/RATIONALE: Patient safety is a major concern in healthcare systems worldwide. Although most safety research has been conducted in the inpatient setting, evidence indicates that medical errors and adverse events are a threat to patients in the primary care setting as well. Since information about the frequency and outcomes of safety incidents in primary care is required, the goals of this study are to describe the type, frequency, seasonal and regional distribution of medication incidents in primary care in Switzerland and to elucidate possible risk factors for medication incidents. Label="METHODS AND ANALYSIS" ="METHODS"/> <AbstractText STUDY DESIGN AND SETTING: We will conduct a prospective surveillance study to identify cases of medication incidents among primary care patients in Switzerland over the course of the year 2015. PARTICIPANTS: Patients undergoing drug treatment by 167 general practitioners or paediatricians reporting to the Swiss Federal Sentinel Reporting System. INCLUSION CRITERIA: Any erroneous event, as defined by the physician, related to the medication process and interfering with normal treatment course. EXCLUSION CRITERIA: Lack of treatment effect, adverse drug reactions or drug-drug or drug-disease interactions without detectable treatment error. PRIMARY OUTCOME: Medication incidents. RISK FACTORS: Age, gender, polymedication, morbidity, care dependency, hospitalisation. STATISTICAL ANALYSIS: Descriptive statistics to assess type, frequency, seasonal and regional distribution of medication incidents and logistic regression to assess their association with potential risk factors. Estimated sample size: 500 medication incidents. LIMITATIONS: We will take into account under-reporting and selective reporting among others as potential sources of bias or imprecision when interpreting the results. ETHICS AND DISSEMINATION: No formal request was necessary because of fully anonymised data. The results will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT0229537.

Natural history of growth hormone deficiency in a pediatric cohort.

BACKGROUND/AIMS: Controversies still exist regarding the evaluation of growth hormone deficiency (GHD) in childhood at the end of growth. The aim of this study was to describe the natural history of GHD in a pediatric cohort. METHODS: This is a retrospective study of a cohort of pediatric patients with GHD. Cases of acquired GHD were excluded. Univariate logistic regression was used to identify predictors of GHD persisting into adulthood. RESULTS: Among 63 identified patients, 47 (75%) had partial GHD at diagnosis, while 16 (25%) had complete GHD, including 5 with multiple pituitary hormone deficiencies. At final height, 50 patients underwent repeat stimulation testing; 28 (56%) recovered and 22 (44%) remained growth hormone (GH) deficient. Predictors of persisting GHD were: complete GHD at diagnosis (OR 10.1, 95% CI 2.4-42.1), pituitary stalk defect or ectopic pituitary gland on magnetic resonance imaging (OR 6.5, 95% CI 1.1-37.1), greater height gain during GH treatment (OR 1.8, 95% CI 1.0-3.3), and IGF-1 level <-2 standard deviation scores (SDS) following treatment cessation (OR 19.3, 95% CI 3.6-103.1). In the multivariate analysis, only IGF-1 level <-2 SDS (OR 13.3, 95% CI 2.3-77.3) and complete GHD (OR 6.3, 95% CI 1.2-32.8) were associated with the outcome. CONCLUSION: At final height, 56% of adolescents with GHD had recovered. Complete GHD at diagnosis, low IGF-1 levels following retesting, and pituitary malformation were strong predictors of persistence of GHD. © 2015 S. Karger AG, Basel.

Systematic analysis of factors associated with progression and regression of ulcerative colitis in 918 patients.

BACKGROUND: Studies that systematically assess change in ulcerative colitis (UC) extent over time in adult patients are scarce. AIM: To assess changes in disease extent over time and to evaluate clinical parameters associated with this change. METHODS: Data from the Swiss IBD cohort study were analysed. We used logistic regression modelling to identify factors associated with a change in disease extent. RESULTS: A total of 918 UC patients (45.3% females) were included. At diagnosis, UC patients presented with the following disease extent: proctitis [199 patients (21.7%)], left-sided colitis [338 patients (36.8%)] and extensive colitis/pancolitis [381 (41.5%)]. During a median disease duration of 9 [4-16] years, progression and regression was documented in 145 patients (15.8%) and 149 patients (16.2%) respectively. In addition, 624 patients (68.0%) had a stable disease extent. The following factors were identified to be associated with disease progression: treatment with systemic glucocorticoids [odds ratio (OR) 1.704, P = 0.025] and calcineurin inhibitors (OR: 2.716, P = 0.005). No specific factors were found to be associated with disease regression. CONCLUSIONS: Over a median disease duration of 9 [4-16] years, about two-thirds of UC patients maintained the initial disease extent; the remaining one-third had experienced either progression or regression of the disease extent.

Endometrial cancer and oral contraceptives : an individual participant meta-analysis of 27 276 women with endometrial cancer from 36 epidemiological studies.

BACKGROUND: Oral contraceptives are known to reduce the incidence rate of endometrial cancer, but it is uncertain how long this effect lasts after use ceases, or whether it is modified by other factors. METHODS: Individual participant datasets were sought from principal investigators and provided centrally for 27 276 women with endometrial cancer (cases) and 115 743 without endometrial cancer (controls) from 36 epidemiological studies. The relative risks (RRs) of endometrial cancer associated with oral contraceptive use were estimated using logistic regression, stratified by study, age, parity, body-mass index, smoking, and use of menopausal hormone therapy. FINDINGS: The median age of cases was 63 years (IQR 57-68) and the median year of cancer diagnosis was 2001 (IQR 1994-2005). 9459 (35%) of 27 276 cases and 45 625 (39%) of 115 743 controls had ever used oral contraceptives, for median durations of 3·0 years (IQR 1-7) and 4·4 years (IQR 2-9), respectively. The longer that women had used oral contraceptives, the greater the reduction in risk of endometrial cancer; every 5 years of use was associated with a risk ratio of 0·76 (95% CI 0·73-0·78; p<0·0001). This reduction in risk persisted for more than 30 years after oral contraceptive use had ceased, with no apparent decrease between the RRs for use during the 1960s, 1970s, and 1980s, despite higher oestrogen doses in pills used in the early years. However, the reduction in risk associated with ever having used oral contraceptives differed by tumour type, being stronger for carcinomas (RR 0·69, 95% CI 0·66-0·71) than sarcomas (0·83, 0·67-1·04; case-case comparison: p=0·02). In high-income countries, 10 years use of oral contraceptives was estimated to reduce the absolute risk of endometrial cancer arising before age 75 years from 2·3 to 1·3 per 100 women. INTERPRETATION: Use of oral contraceptives confers long-term protection against endometrial cancer. These results suggest that, in developed countries, about 400 000 cases of endometrial cancer before the age of 75 years have been prevented over the past 50 years (1965-2014) by oral contraceptives, including 200 000 in the past decade (2005-14). FUNDING: Medical Research Council, Cancer Research UK.

Physical Activity and Snus: Is There a Link?

The study aimed at assessing the link between physical activity (PA), sports activity and snus use among young men in Switzerland. Data from the Cohort Study on Substance Use Risk Factors (C-SURF) were used to measure PA with the International Physical Activity Questionnaire and sports activity with a single item. Multivariate logistic regression analysis was conducted to measure the association between snus use, PA and sports activity. Similar models were run for smoking and snuff use. Snus use increased in a dose-response association with PA (high level: OR = 1.72; 95% CI 1.16-2.55) and with individuals exercising once a week or more often (OR = 1.65; 95% CI 1.26-2.16; p < 0.001) or almost every day (OR = 2.27; 95% CI 1.72-3.01; p < 0.001) in separate models. Entered simultaneously, only sports and exercise maintained a basically unchanged significant dose-response relationship, whereas PA became non-significant. A non-significant dose-response relation was found for cigarette smoking and snuff use, indicating that the association with sport is specific to snus and not to tobacco use in general or smokeless tobacco in particular. This study showed that the association between snus use and sports is not specific to Nordic countries.