Serum 25-hydroxyvitamin D level and kidney function decline in a Swiss general adult population.

Molecular evidence suggests that levels of vitamin D are associated with kidney function loss. Still, population-based studies are limited and few have considered the potential confounding effect of baseline kidney function. This study evaluated the association of serum 25-hydroxyvitamin D with change in eGFR, rapid eGFR decline, and incidence of CKD and albuminuria. Baseline (2003-2006) and 5.5-year follow-up data from a Swiss adult general population were used to evaluate the association of serum 25-hydroxyvitamin D with change in eGFR, rapid eGFR decline (annual loss >3 ml/min per 1.73 m(2)), and incidence of CKD and albuminuria. Serum 25-hydroxyvitamin D was measured at baseline using liquid chromatography-tandem mass spectrometry. eGFR and albuminuria were collected at baseline and follow-up. Multivariate linear and logistic regression models were used considering potential confounding factors. Among the 4280 people included in the analysis, the mean±SD annual eGFR change was -0.57±1.78 ml/min per 1.73 m(2), and 287 (6.7%) participants presented rapid eGFR decline. Before adjustment for baseline eGFR, baseline 25-hydroxyvitamin D level was associated with both mean annual eGFR change and risk of rapid eGFR decline, independently of baseline albuminuria. Once adjusted for baseline eGFR, associations were no longer significant. For every 10 ng/ml higher baseline 25-hydroxyvitamin D, the adjusted mean annual eGFR change was -0.005 ml/min per 1.73 m(2) (95% confidence interval, -0.063 to 0.053; P=0.87) and the risk of rapid eGFR decline was null (odds ratio, 0.93; 95% confidence interval, 0.79 to 1.08; P=0.33). Baseline 25-hydroxyvitamin D level was not associated with incidence of CKD or albuminuria. The association of 25-hydroxyvitamin D with eGFR decline is confounded by baseline eGFR. Sufficient 25-hydroxyvitamin D levels do not seem to protect from eGFR decline independently from baseline eGFR.

Impacts of Globalization Processes on the Swiss National Business Elite Community : A Diachronic Analysis of Swiss Large Corporations (1980-2010)

This paper investigates the impacts of globalization processes on the Swiss business elite community during the 1980-2010 period. Switzerland has been characterized in the 20th century by its extraordinary stability and by the strong cohesion of its elite community. To study recent changes, we focus on Switzerland's 110 largest firms' by adopting a diachronic perspective based on three elite cohorts (1980, 2000, and 2010). An analysis of interlocking directorates allows us to describe the decline of the Swiss corporate network. The second analysis focuses on top managers' profiles in terms of education, nationality as well as participation in national community networks that used to reinforce the cultural cohesion of the Swiss elite community, especially the militia army. Our results highlight a slow but profound transformation of top management profiles, characterized by a decline of traditional national elements of legitimacy and the emergence of new "global" elements. The diachronic and combined analysis brings into light the strong cultural changes experienced by the national business elite community.

Chronological order of appearance of extraintestinal manifestations relative to the time of IBD diagnosis in the Swiss Inflammatory Bowel Disease Cohort

BACKGROUND: Data evaluating the chronological order of appearance of extraintestinal manifestations (EIMs) relative to the time of inflammatory bowel disease (IBD) diagnosis is currently lacking. We aimed to assess the type, frequency, and chronological order of appearance of EIMs in patients with IBD. METHODS: Data from the Swiss Inflammatory Bowel Disease Cohort Study were analyzed. RESULTS: The data on 1249 patients were analyzed (49.8% female, median age: 40 [interquartile range, 30-51 yr], 735 [58.8%] with Crohn's disease, 483 [38.7%] with ulcerative colitis, and 31 [2.5%] with indeterminate colitis). A total of 366 patients presented with EIMs (29.3%). Of those, 63.4% presented with 1, 26.5% with 2, 4.9% with 3, 2.5% with 4, and 2.7% with 5 EIMs during their lifetime. Patients presented with the following diseases as first EIMs: peripheral arthritis 70.0%, aphthous stomatitis 21.6%, axial arthropathy/ankylosing spondylitis 16.4%, uveitis 13.7%, erythema nodosum 12.6%, primary sclerosing cholangitis 6.6%, pyoderma gangrenosum 4.9%, and psoriasis 2.7%. In 25.8% of cases, patients presented with their first EIM before IBD was diagnosed (median time 5 mo before IBD diagnosis: range, 0-25 mo), and in 74.2% of cases, the first EIM manifested itself after IBD diagnosis (median: 92 mo; range, 29-183 mo). CONCLUSIONS: In one quarter of patients with IBD, EIMs appeared before the time of IBD diagnosis. Occurrence of EIMs should prompt physicians to look for potential underlying IBD.

Cadmium body burden of the Swiss population.

Urinary cadmium (Cd) excretion was measured within a representative Swiss collective. With a median of 0.23 µg/24 h (n = 1409) and the 95th percentile at 0.81 µg/24 h, no increased health risk for the general non-exposed population was identified. The independent variables Age, BMI and Smoking habit had a significant effect on urinary Cd excretion. No association was found with the region of residence and sex. A subsample comparison between 24-h and spot urines of the same subjects (n = 90) did not reveal an evident concentration difference for both creatinine-adjusted sample types. Dependencies on age and gender were observed for creatinine, which consequently impacts on the creatinine normalisation of urine samples.

Serum Vitamin D Concentrations Are Not Associated with Insulin Resistance in Swiss Adults.

BACKGROUND: Low vitamin D status has been associated with an increased risk of developing type 2 diabetes and insulin resistance (IR), although this has been recently questioned. OBJECTIVE: We examined the association between serum vitamin D metabolites and incident IR. METHODS: This was a prospective, population-based study derived from the CoLaus (Cohorte Lausannoise) study including 3856 participants (aged 51.2 ± 10.4 y; 2217 women) free from diabetes or IR at baseline. IR was defined as a homeostasis model assessment (HOMA) index >2.6. Fasting plasma insulin and glucose were measured at baseline and at follow-up to calculate the HOMA index. The association of vitamin D metabolites with incident IR was analyzed by logistic regression, and the results were expressed for each independent variable as ORs and 95% CIs. RESULTS: During the 5.5-y follow-up, 649 (16.9%) incident cases of IR were identified. Participants who developed IR had lower baseline serum concentrations of 25-hydroxyvitamin D3 [25(OH)D3 (25-hydroxycholecalciferol); 45.9 ± 22.8 vs. 49.9 ± 22.6 nmol/L; P < 0.001], total 25(OH)D3 (25(OH)D3 + epi-25-hydroxyvitamin D3 [3-epi-25(OH)D3]; 49.1 ± 24.3 vs. 53.3 ± 24.1 nmol/L; P < 0.001), and 3-epi-25(OH)D3 (4.2 ± 2.9 vs. 4.3 ± 2.5 nmol/L; P = 0.01) but a higher 3-epi- to total 25(OH)D3 ratio (0.09 ± 0.05 vs. 0.08 ± 0.04; P = 0.007). Multivariable analysis adjusting for month of sampling, age, and sex showed an inverse association between 25(OH)D3 and the likelihood of developing IR [ORs (95% CIs): 0.86 (0.68, 1.09), 0.60 (0.46, 0.78), and 0.57 (0.43, 0.75) for the second, third, and fourth quartiles compared with the first 25(OH)D3 quartile; P-trend < 0.001]. Similar associations were found between total 25(OH)D3 and incident IR. There was no significant association between 3-epi-25(OH)D3 and IR, yet a positive association was observed between the 3-epi- to total 25(OH)D3 ratio and incident IR. Further adjustment for body mass index, sedentary status, and smoking attenuated the association between 25(OH)D3, total 25(OH)D3, and the 3-epi- to total 25(OH)D3 ratio and the likelihood of developing IR. CONCLUSION: In the CoLaus study in healthy adults, the risk of incident IR is not associated with serum concentrations of 25(OH)D3 and total 25(OH)D3.

Transient detectable viremia and the risk of viral rebound in patients from the Swiss HIV Cohort Study.

BACKGROUND: Temporary increases in plasma HIV RNA ('blips') are common in HIV patients on combination antiretroviral therapy (cART). Blips above 500 copies/mL have been associated with subsequent viral rebound. It is not clear if this relationship still holds when measurements are made using newer more sensitive assays. METHODS: We selected antiretroviral-naive patients that then recorded one or more episodes of viral suppression on cART with HIV RNA measurements made using more sensitive assays (lower limit of detection below 50 copies/ml). We estimated the association in these episodes between blip magnitude and the time to viral rebound. RESULTS: Four thousand ninety-four patients recorded a first episode of viral suppression on cART using more sensitive assays; 1672 patients recorded at least one subsequent suppression episode. Most suppression episodes (87 %) were recorded with TaqMan version 1 or 2 assays. Of the 2035 blips recorded, 84 %, 12 % and 4 % were of low (50-199 copies/mL), medium (200-499 copies/mL) and high (500-999 copies/mL) magnitude respectively. The risk of viral rebound increased as blip magnitude increased with hazard ratios of 1.20 (95 % CI 0.89-1.61), 1.42 (95 % CI 0.96-2.19) and 1.93 (95 % CI 1.24-3.01) for low, medium and high magnitude blips respectively; an increase of hazard ratio 1.09 (95 % CI 1.03 to 1.15) per 100 copies/mL of HIV RNA. CONCLUSIONS: With the more sensitive assays now commonly used for monitoring patients, blips above 200 copies/mL are increasingly likely to lead to viral rebound and should prompt a discussion about adherence.

High hepatic and extrahepatic mortality and low treatment uptake in HCV-coinfected persons in the Swiss HIV cohort study between 2001 and 2013.

BACKGROUND & AIMS: The landscape of HCV treatments is changing dramatically. At the beginning of this new era, we highlight the challenges for HCV therapy by assessing the long-term epidemiological trends in treatment uptake, efficacy and mortality among HIV/HCV-coinfected people since the availability of HCV therapy. METHODS: We included all SHCS participants with detectable HCV RNA between 2001 and 2013. To identify predictors for treatment uptake uni- and multivariable Poisson regression models were applied. We further used survival analyses with Kaplan-Meier curves and Cox regression with drop-out as competing risk. RESULTS: Of 12,401 participants 2107 (17%) were HCV RNA positive. Of those, 636 (30%) started treatment with an incidence of 5.8/100 person years (PY) (95% CI 5.3-6.2). Sustained virological response (SVR) with pegylated interferon/ribavirin was achieved in 50% of treated patients, representing 15% of all participants with replicating HCV-infection. 344 of 2107 (16%) HCV RNA positive persons died, 59% from extrahepatic causes. Mortality/100 PY was 2.9 (95% CI 2.6-3.2) in untreated patients, 1.3 (1.0-1.8) in those treated with failure, and 0.6 (0.4-1.0) in patients with SVR. In 2013, 869/2107 (41%) participants remained HCV RNA positive. CONCLUSIONS: Over the last 13years HCV treatment uptake was low and by the end of 2013, a large number of persons remain to be treated. Mortality was high, particularly in untreated patients, and mainly due to non-liver-related causes. Accordingly, in HIV/HCV-coinfected patients, integrative care including the diagnosis and therapy of somatic and psychiatric disorders is important to achieve mortality rates similar to HIV-monoinfected patients.

Heritability of ambulatory and office blood pressure in the Swiss population.

BACKGROUND: Blood pressure (BP) is known to aggregate in families. Yet, heritability estimates are population-specific and no Swiss data have been published so far. We estimated the heritability of ambulatory and office BP in a Swiss population-based sample. METHODS: The Swiss Kidney Project on Genes in Hypertension is a population-based family study focusing on BP genetics. Office and ambulatory BP were measured in 1009 individuals from 271 nuclear families. Heritability was estimated for SBP, DBP, and pulse pressure using a maximum likelihood method implanted in the Statistical Analysis in Genetic Epidemiology software. RESULTS: The 518 women and 491 men included in this analysis had a mean (±SD) age of 48.3 (±17.4) and 47.3 (±17.7) years, and a mean BMI of 23.8 (±4.2) and 25.9 (±4.1) kg/m, respectively. Narrow-sense heritability estimates (±standard error) for ambulatory SBP, DBP, and pulse pressure were 0.37 ± 0.07, 0.26 ± 0.07, and 0.29 ± 0.07 for 24-h BP; 0.39 ± 0.07, 0.28 ± 0.07, and 0.27 ± 0.07 for day BP; and 0.25 ± 0.07, 0.20 ± 0.07, and 0.30 ± 0.07 for night BP, respectively (all P < 0.001). Heritability estimates for office SBP, DBP, and pulse pressure were 0.21 ± 0.08, 0.25 ± 0.08, and 0.18 ± 0.07 (all P < 0.01). CONCLUSIONS: We found significant heritability estimates for both ambulatory and office BP in this Swiss population-based study. Our findings justify the ongoing search for the genetic determinants of BP.

Call for uniform neuropsychological assessment after aneurysmal subarachnoid hemorrhage: Swiss recommendations.

BACKGROUND: In a high proportion of patients with favorable outcome after aneurysmal subarachnoid hemorrhage (aSAH), neuropsychological deficits, depression, anxiety, and fatigue are responsible for the inability to return to their regular premorbid life and pursue their professional careers. These problems often remain unrecognized, as no recommendations concerning a standardized comprehensive assessment have yet found entry into clinical routines. METHODS: To establish a nationwide standard concerning a comprehensive assessment after aSAH, representatives of all neuropsychological and neurosurgical departments of those eight Swiss centers treating acute aSAH have agreed on a common protocol. In addition, a battery of questionnaires and neuropsychological tests was selected, optimally suited to the deficits found most prevalent in aSAH patients that was available in different languages and standardized. RESULTS: We propose a baseline inpatient neuropsychological screening using the Montreal Cognitive Assessment (MoCA) between days 14 and 28 after aSAH. In an outpatient setting at 3 and 12 months after bleeding, we recommend a neuropsychological examination, testing all relevant domains including attention, speed of information processing, executive functions, verbal and visual learning/memory, language, visuo-perceptual abilities, and premorbid intelligence. In addition, a detailed assessment capturing anxiety, depression, fatigue, symptoms of frontal lobe affection, and quality of life should be performed. CONCLUSIONS: This standardized neuropsychological assessment will lead to a more comprehensive assessment of the patient, facilitate the detection and subsequent treatment of previously unrecognized but relevant impairments, and help to determine the incidence, characteristics, modifiable risk factors, and the clinical course of these impairments after aSAH.

Swiss medical centres vary significantly when it comes to outcomes of neonates with a very low gestational age.

AIM: This study quantified the impact of perinatal predictors and medical centre on the outcome of very low-gestational-age neonates (VLGANs) born at <32 completed weeks in Switzerland. METHODS: Using prospectively collected data from a 10-year cohort of VLGANs, we developed logistic regression models for three different time points: delivery, NICU admission and seven days of age. The data predicted survival to discharge without severe neonatal morbidity, such as major brain injury, moderate or severe bronchopulmonary dysplasia, retinopathy of prematurity (≥stage three) or necrotising enterocolitis (≥stage three). RESULTS: From 2002 to 2011, 6892 VLGANs were identified: 5854 (85%) of the live-born infants survived and 84% of the survivors did not have severe neonatal complications. Predictors for adverse outcome at delivery and on NICU admission were low gestational age, low birthweight, male sex, multiple birth, birth defects and lack of antenatal corticosteroids. Proven sepsis was an additional risk factor on day seven of life. The medical centre remained a statistically significant factor at all three time points after adjusting for perinatal predictors. CONCLUSION: After adjusting for perinatal factors, the survival of Swiss VLGANs without severe neonatal morbidity was strongly influenced by the medical centre that treated them.

Patients' characteristics associated with the decision of "do not attempt cardiopulmonary resuscitation" order in a Swiss hospital

Présentation En accord avec la loi suisse, seul le patient peut décider de la notification, dans son dossier, d'un ordre de «non réanimation » (DNACPR) en cas d'arrêt cardio-respiratoire. L'équipe médicale peut exceptionnellement prendre une telle décision, si elle juge qu'une réanimation n'a aucune chance d'aboutir. Les mécanismes menant à ce processus de décision n'ont pas encore été complètement investigués, en particulier en Suisse. Enjeu Notre étude vise à déterminer la prévalence de l'ordre de «non réanimation» après l'admission, l'auteur de cette décision, ainsi que son association avec certaines caractéristiques propres aux patients : le sexe, l'âge, la situation familiale, la nationalité, la religion, le nombre et le type de comorbidités. Nous cherchons ainsi à mieux définir quels sont les facteurs importants dans ce processus décisionnel complexe où le jugement médical, ainsi que l'information apportée aux patients sont primordiaux. Contexte de recherche Nous avons effectué une étude observationnelle sur une durée de 6 semaines, en analysant les formulaires d'admission de 194 patients hospitalisés dans le service de médecine interne du CHUV, dans les 72 heures après leur admission. Résultats L'étude montre que plus de la moitié des 194 dossiers de patients analysés ont un ordre de « non réanimation » (DNACPR) (53%). 27% de ces décisions ont été prises par les patients eux-mêmes, 12% par leur représentant thérapeutique/famille et 61% par les équipes médicales. Nous trouvons une association statistiquement significative entre l'ordre DNACPR et l'âge, avec un âge moyen de 80.7 +-10.8 ans dans le groupe « non réanimation » versus 67.5 +- 15.1 ans dans le groupe « réanimation », entre l'ordre DNACPR et une pathologie oncologique, quel que soit le stade de cette dernière, ainsi qu'entre l'ordre DNACPR et la religion protestante. Une analyse de sous-groupe montre que l'âge, ainsi que la pathologie oncologique sont statistiquement significatifs lors de l'analyse des décisions prises par les équipes médicales. La religion protestante est, quant à elle, significative lors de l'analyse des décisions prises par le patient ou son représentant. Perspectives Contrairement aux publications passées, cette étude montre une prédominance de l'ordre de «non réanimation » (DNACPR) à l'admission dans un service de médecine interne, principalement sur décision médicale. La plupart des patients ont été jugés incapables de discernement sur la question ou n'ont tout simplement pas été impliqués dans le processus décisionnel. Une réflexion doit avoir lieu afin de prendre des mesures de sensibilisation auprès des équipes médicales et d'approfondir la formation médicale et éthique sur le sujet de la détermination de l'attitude de réanimation. D'autres études qualitatives permettraient de mieux comprendre les motivations ayant mené à ces nombreuses décisions médicales, ainsi que les critères importants pour les patients.

Assessing the Paradox Between Transmitted and Acquired HIV Type 1 Drug Resistance Mutations in the Swiss HIV Cohort Study From 1998 to 2012.

BACKGROUND: Transmitted human immunodeficiency virus type 1 (HIV) drug resistance (TDR) mutations are transmitted from nonresponding patients (defined as patients with no initial response to treatment and those with an initial response for whom treatment later failed) or from patients who are naive to treatment. Although the prevalence of drug resistance in patients who are not responding to treatment has declined in developed countries, the prevalence of TDR mutations has not. Mechanisms causing this paradox are poorly explored. METHODS: We included recently infected, treatment-naive patients with genotypic resistance tests performed ≤1 year after infection and before 2013. Potential risk factors for TDR mutations were analyzed using logistic regression. The association between the prevalence of TDR mutations and population viral load (PVL) among treated patients during 1997-2011 was estimated with Poisson regression for all TDR mutations and individually for the most frequent resistance mutations against each drug class (ie, M184V/L90M/K103N). RESULTS: We included 2421 recently infected, treatment-naive patients and 5399 patients with no response to treatment. The prevalence of TDR mutations fluctuated considerably over time. Two opposing developments could explain these fluctuations: generally continuous increases in the prevalence of TDR mutations (odds ratio, 1.13; P = .010), punctuated by sharp decreases in the prevalence when new drug classes were introduced. Overall, the prevalence of TDR mutations increased with decreasing PVL (rate ratio [RR], 0.91 per 1000 decrease in PVL; P = .033). Additionally, we observed that the transmitted high-fitness-cost mutation M184V was positively associated with the PVL of nonresponding patients carrying M184V (RR, 1.50 per 100 increase in PVL; P < .001). Such association was absent for K103N (RR, 1.00 per 100 increase in PVL; P = .99) and negative for L90M (RR, 0.75 per 100 increase in PVL; P = .022). CONCLUSIONS: Transmission of antiretroviral drug resistance is temporarily reduced by the introduction of new drug classes and driven by nonresponding and treatment-naive patients. These findings suggest a continuous need for new drugs, early detection/treatment of HIV-1 infection.

Ribavirin Concentrations Do Not Predict Sustained Virological Response in HIV/HCV-Coinfected Patients Treated with Ribavirin and Pegylated Interferon in the Swiss HIV Cohort Study.

BACKGROUND: Ribavirin (RBV) is an essential component of most current hepatitis C (HCV) treatment regimens and still standard of care in the combination with pegylated interferon (pegIFN) to treat chronic HCV in resource limited settings. Study results in HIV/HCV-coinfected patients are contradicting as to whether RBV concentration correlates with sustained virological response (SVR). METHODS: We included 262 HCV treatment naïve HIV/HCV-coinfected Swiss HIV Cohort Study (SHCS) participants treated with RBV and pegIFN between 01.01.2001-01.01.2010, 134 with HCV genotype (GT) 1/4, and 128 with GT 2/3 infections. RBV levels were measured retrospectively in stored plasma samples obtained between HCV treatment week 4 and end of therapy. Uni- and multivariable logistic regression analyses were used to evaluate the association between RBV concentration and SVR in GT 1/4 and GT 2/3 infections. The analyses were repeated stratified by treatment phase (week 4-12, 13-24, >24) and IL28B genotype (CC versus CT/TT). RESULTS: SVR rates were 35.1% in GT 1/4 and 70.3% in GT 2/3 infections. Overall, median RBV concentration was 2.0 mg/L in GT 1/4, and 1.9 mg/L in GT 2/3, and did not change significantly across treatment phases. Patients with SVR had similar RBV concentrations compared to patients without SVR in both HCV genotype groups. SVR was not associated with RBV levels ≥2.0 mg/L (GT 1/4, OR 1.19 [0.5-2.86]; GT 2/3, 1.94 [0.78-4.80]) and ≥2.5 mg/L (GT 1/4, 1.56 [0.64-3.84]; GT 2/3 2.72 [0.85-8.73]), regardless of treatment phase, and IL28B genotype. CONCLUSION: In HIV/HCV-coinfected patients treated with pegIFN/RBV, therapeutic drug monitoring of RBV concentrations does not enhance the chance of HCV cure, regardless of HCV genotype, treatment phase and IL28B genotype.