Comparisons of serum vitamin d levels, status, and determinants in populations with and without chronic kidney disease not requiring renal dialysis: a 24-hour urine collection population-based study.

OBJECTIVE: Vitamin D deficiency is frequent in the general population and might be even more prevalent among populations with kidney failure. We compared serum vitamin D levels, vitamin D insufficiency/deficiency status, and vitamin D level determinants in populations without chronic kidney disease (CKD) and with CKD not requiring renal dialysis. DESIGN AND METHODS: This was a cross-sectional, multicenter, population-based study conducted from 2010 to 2011. Participants were from 10 centers that represent the geographical and cultural diversity of the Swiss adult population (≥15 years old). INTERVENTION: CKD was defined using estimated glomerular filtration rate and 24-hour albuminuria. Serum vitamin D was measured by liquid chromatography-tandem mass spectrometry. Statistical procedures adapted for survey data were used. MAIN OUTCOME MEASURE: We compared 25-hydroxy-vitamin D (25(OH)D) levels and the prevalence of vitamin D insufficiency/deficiency (serum 25(OH)D < 30 ng/mL) in participants with and without CKD. We tested the interaction of CKD status with 6 a priori defined attributes (age, sex, body mass index, walking activity, serum albumin-corrected calcium, and altitude) on serum vitamin D level or insufficiency/deficiency status taking into account potential confounders. RESULTS: Overall, 11.8% (135 of 1,145) participants had CKD. The 25(OH)D adjusted means (95% confidence interval [CI]) were 23.1 (22.6-23.7) and 23.5 (21.7-25.3) ng/mL in participants without and with CKD, respectively (P = .70). Vitamin D insufficiency or deficiency was frequent among participants without and with CKD (75.3% [95% CI 69.3-81.5] and 69.1 [95% CI 53.9-86.1], P = .054). CKD status did not interact with major determinants of vitamin D, including age, sex, BMI, walking minutes, serum albumin-corrected calcium, or altitude for its effect on vitamin D status or levels. CONCLUSION: Vitamin D concentration and insufficiency/deficiency status are similar in people with or without CKD not requiring renal dialysis.

Population pharmacokinetic analysis and pharmacogenetics of raltegravir in HIV-positive and healthy individuals.

The objectives of this study were to characterize raltegravir (RAL) population pharmacokinetics in HIV-positive (HIV(+)) and healthy individuals, identify influential factors, and search for new candidate genes involved in UDP glucuronosyltransferase (UGT)-mediated glucuronidation. The pharmacokinetic analysis was performed with NONMEM. Genetic association analysis was performed with PLINK using the relative bioavailability as the phenotype. Simulations were performed to compare once- and twice-daily regimens. A 2-compartment model with first-order absorption adequately described the data. Atazanavir, gender, and bilirubin levels influenced RAL relative bioavailability, which was 30% lower in HIV(+) than in healthy individuals. UGT1A9*3 was the only genetic variant possibly influencing RAL pharmacokinetics. The majority of RAL pharmacokinetic variability remains unexplained by genetic and nongenetic factors. Owing to the very large variability, trough drug levels might be very low under the standard dosing regimen, raising the question of a potential relevance of therapeutic drug monitoring of RAL in some situations.

Vitamin D levels and associated factors: a population-based study in Switzerland.

QUESTIONS UNDER STUDY: To update the prevalence of vitamin D insufficiency and to identify factors associated with vitamin D status in the Swiss adult population. METHODS: Data from the 2010-2011 Swiss Study on Salt intake, a population-based study in the Swiss population, was used. Vitamin D concentration in serum was measured by liquid chromatography- tandem mass spectrometry. Major factors that influence vitamin D levels were taken into account. Survey statistical procedures were used to estimate means and prevalences of vitamin D levels and status. Monthly-specific tertiles of vitamin D and ordinal logistic regression were used to determine the associations of covariates of interest with vitamin D status. RESULTS: The prevalences of vitamin D insufficiency (serum 25-hydroxyvitamin D: 20-29.9 ng/ml) and deficiency (<20 ng/ml) were the highest in the January-March period; 26.4% (95%CI: 21.6-31.7) and 61.6% (95%CI: 56.0-67.0), respectively. In the same period, more than 9 of ten men were vitamin D insufficient or deficient. Each unit increase of Body Mass Index was associated with an 8% decreased likelihood of being in a higher vitamin D tertiles. Oral contraceptive, altitude, urinary excretion of calcium, use of vitamin D supplement or treatment, high wine consumption, physical activity were associated with vitamin D tertiles. Compared to the French-speaking region, the Italian-speaking region was independently associated with a higher likelihood of being in higher vitamin D tertiles (OR: 1.66, 95%CI: 1.14-2.43). CONCLUSIONS: Low levels of vitamin D are common among Swiss adults, in particular during winter months and outside the Italian-speaking region.

Population pharmacokinetics of ganciclovir in solid-organ transplant recipients receiving oral valganciclovir.

Valganciclovir (VGC) is an oral prodrug of ganciclovir (GCV) recently introduced for prophylaxis and treatment of cytomegalovirus infection. Optimal concentration exposure for effective and safe VGC therapy would require either reproducible VGC absorption and GCV disposition or dosage adjustment based on therapeutic drug monitoring (TDM). We examined GCV population pharmacokinetics in solid organ transplant recipients receiving oral VGC, including the influence of clinical factors, the magnitude of variability, and its impact on efficacy and tolerability. Nonlinear mixed effect model (NONMEM) analysis was performed on plasma samples from 65 transplant recipients under VGC prophylaxis or treatment. A two-compartment model with first-order absorption appropriately described the data. Systemic clearance was markedly influenced by the glomerular filtration rate (GFR), patient gender, and graft type (clearance/GFR = 1.7 in kidney, 0.9 in heart, and 1.2 in lung and liver recipients) with interpatient and interoccasion variabilities of 26 and 12%, respectively. Body weight and sex influenced central volume of distribution (V(1) = 0.34 liter/kg in males and 0.27 liter/kg in females [20% interpatient variability]). No significant drug interaction was detected. The good prophylactic efficacy and tolerability of VGC precluded the demonstration of any relationship with GCV concentrations. In conclusion, this analysis highlights the importance of thorough adjustment of VGC dosage to renal function and body weight. Considering the good predictability and reproducibility of the GCV profile after treatment with oral VGC, routine TDM does not appear to be clinically indicated in solid-organ transplant recipients. However, GCV plasma measurement may still be helpful in specific clinical situations.

La réhabilitation psychosociale a l'aube du XXIème siècle. I: Principes, population cible et pathologie en cause

The relatively recent development of the psychosocial rehabilitation has its origins mainly in the progress of modern psychopharmacology, the assertion of the rights of the patients and the result of the studies showing that the evolution of persons suffering from severe and persistent mental illnesses can prove to be positive in many cases. In spite of the heterogeneity of the experiences and of the theoretical references, the core principles of the psychosocial rehabilitation imposed themselves. These principles can be classified according to three levels, that of relational ethics, that of the method of intervention and that of the institutional device. A recent study showed that 2.4@1000 of the general adult population of the Canton of Vaud live in sociotherapeutic and rehabilitation accommodations. In this sample, there is a important percentage of relatively young persons (55.3% are under 40). In institutional accommodation there is a majority of patients suffering from major personality disorders and addiction (40.6%), followed by psychotic disorders (37.2%), persistent mood disorders (12.3%), neurotic disorders (6.6%) and psycho-organic disorders (3.3%). In home based rehabilitation, the ratio of patients with psychotic disorders is more important (53.1%). This difference would indicate that people with schizophrenia would have a better social outcome than personality disorders with addiction

Hyperhomocysteinemia is independently associated with albuminuria in the population-based CoLaus study.

Increased serum levels of homocysteine and uric acid have each been associated with cardiovascular risk. We analyzed whether homocysteine and uric acid were associated with glomerular filtration rate (GFR) and albuminuria independently of each other. We also investigated the association of MTHFR polymorphisms related to homocysteine with albuminuria to get further insight into causality. This was a cross-sectional population-based study in Caucasians (n = 5913). Hyperhomocysteinemia was defined as total serum homocysteine ≥ 15 μmol/L. Albuminuria was defined as urinary albumin-to-creatinine ratio > 30 mg/g. Uric acid was associated positively with homocysteine (r = 0.246 in men and r = 0.287 in women, P < 0.001). The prevalence of albuminuria increased across increasing homocysteine categories (from 6.4% to 17.3% in subjects with normal GFR and from 3.5% to 14.5% in those with reduced GFR, P for trend < 0.005). Hyperhomocysteinemia (OR = 2.22, 95% confidence interval: 1.60-3.08, P < 0.001) and elevated serum uric acid (OR = 1.27, 1.08-1.50, per 100 μmol/L, P = 0.004) were significantly associated with albuminuria, independently of hypertension and type 2 diabetes. The 2-fold higher risk of albuminuria associated with hyperhomocysteinemia was similar to the risk associated with hypertension or diabetes. MTHFR alleles related to higher homocysteine were associated with increased risk of albuminuria. In the general adult population, elevated serum homocysteine and uric acid were associated with albuminuria independently of each other and of renal function.

Serum calcium levels are associated with novel cardiometabolic risk factors in the population-based CoLaus study.

BACKGROUND: Associations of serum calcium levels with the metabolic syndrome and other novel cardio-metabolic risk factors not classically included in the metabolic syndrome, such as those involved in oxidative stress, are largely unexplored. We analyzed the association of albumin-corrected serum calcium levels with conventional and non-conventional cardio-metabolic risk factors in a general adult population. METHODOLOGY/PRINCIPAL FINDINGS: The CoLaus study is a population-based study including Caucasians from Lausanne, Switzerland. The metabolic syndrome was defined using the Adult Treatment Panel III criteria. Non-conventional cardio-metabolic risk factors considered included: fat mass, leptin, LDL particle size, apolipoprotein B, fasting insulin, adiponectin, ultrasensitive CRP, serum uric acid, homocysteine, and gamma-glutamyltransferase. We used adjusted standardized multivariable regression to compare the association of each cardio-metabolic risk factor with albumin-corrected serum calcium. We assessed associations of albumin-corrected serum calcium with the cumulative number of non-conventional cardio-metabolic risk factors. We analyzed 4,231 subjects aged 35 to 75 years. Corrected serum calcium increased with both the number of the metabolic syndrome components and the number of non-conventional cardio-metabolic risk factors, independently of the metabolic syndrome and BMI. Among conventional and non-conventional cardio-metabolic risk factors, the strongest positive associations were found for factors related to oxidative stress (uric acid, homocysteine and gamma-glutamyltransferase). Adiponectin had the strongest negative association with corrected serum calcium. CONCLUSIONS/SIGNIFICANCE: Serum calcium was associated with the metabolic syndrome and with non-conventional cardio-metabolic risk factors independently of the metabolic syndrome. Associations with uric acid, homocysteine and gamma-glutamyltransferase were the strongest. These novel findings suggest that serum calcium levels may be associated with cardiovascular risk via oxidative stress.

Cricotracheal resection for adult and pediatric subglottic stenoses: Similarities and differences

Since the mid-1970s thoracic surgeons have used cricotracheal resection (CTR) in the adult population. Similar positive results have from then on been reported by different investigators using this technique. In contrast, otolaryngologists have typically used an anterior midline approach to the larynx and trachea for their laryngotracheal reconstructions (LTRs), both in adults and children. The fear of injury to the recurrent laryngeal nerve (RLN), the risk of a dehiscence of the anastomosis, and the interference with normal growth of the larynx in the pediatric age group were the main reasons put forward for not using a CTR for the cure of subglottic stenosis. In this article, we describe the similarities and differences in CTRs performed for adult and pediatric cases. The high rate (>90%) of success for severe pediatric SGS using CTR compares most favorably with LTR, which is still used in most otolaryngology departments. The reasons lie in the full resection of the stenosis and the restoration of a steady cartilaginous framework of the larynx and trachea with full mucosal lining on both sides of the anastomosis. Furthermore, CTR can be associated with a Rethi procedure for the cure of combined posterior glottic and subglottic stenoses. Good results from series of two different centers suggest that CTR will become the treatment of choice for pediatric severe SGS, as is presently the case in the adult population.

Forgoing dental care for economic reasons in Switzerland: a six-year cross-sectional population-based study

BACKGROUND: While oral health is part of general health and well-being, oral health disparities nevertheless persist. Potential mechanisms include socioeconomic factors that may influence access to dental care in the absence of universal dental care insurance coverage. We investigated the evolution, prevalence and determinants (including socioeconomic) of forgoing of dental care for economic reasons in a Swiss region, over the course of six years. METHODS: Repeated population-based surveys (2007-2012) of a representative sample of the adult population of the Canton of Geneva, Switzerland. Forgone dental care, socioeconomic and insurance status, marital status, and presence of dependent children were assessed using standardized methods. RESULTS: A total of 4313 subjects were included, 10.6% (457/4313) of whom reported having forgone dental care for economic reasons in the previous 12 months. The crude percentage varied from 2.4% in the wealthiest group (monthly income ≥ 13,000 CHF, 1 CHF ≈ 1$) to 23.5% among participants with the lowest income (<3,000 CHF). Since 2007/8, forgoing dental care remained stable overall, but in subjects with a monthly income of <3,000 CHF, the adjusted percentage increased from 16.3% in 2007/8 to 20.6% in 2012 (P trend = 0.002). Forgoing dental care for economic reasons was independently associated with lower income, younger age, female gender, current smoking, having dependent children, divorced status and not living with a partner, not having a supplementary health insurance, and receipt of a health insurance premium cost-subsidy. CONCLUSIONS: In a Swiss region without universal dental care insurance coverage, prevalence of forgoing dental care for economic reasons was high and highly dependent on income. Efforts should be made to prevent high-risk populations from forgoing dental care.

Short-term effects of particulate matters on pulse pressure in two general population studies.

OBJECTIVES: To explore the association of short-term exposure to particulate matter with aerodynamic diameters less than 10 μm (PM10) with pulse pressure, SBP, and DBP taking outdoor temperature into account in two large population-based studies in Switzerland. METHODS: We used data from the Bus Santé study including 5605 adults in Geneva and the CoLaus study including 6183 adults in Lausanne. PM10 and meteorological data were measured from fixed monitoring stations. We analyzed the association of short-term exposure to PM10 (on the day of examination visit and up to 7 days before) with pulse pressure, SBP, and DBP by linear regression, controlling for potential confounders and effect modifiers. RESULTS: Average PM10 levels were 22.4 μg/m in Geneva and 31.7 μg/m in Lausanne. In adjusted models, for each 10 μg/m increase in 7-day PM10 average, pulse pressure and SBP increased by 0.583 (95% confidence interval, 0.296-0.870) mmHg and 0.490 (0.056-0.925) mmHg in Geneva, and 0.183 (0.017-0.348) mmHg and 0.036 (0.042-0.561) mmHg in Lausanne, respectively. Stronger associations of pulse pressure and SBP with PM10 were observed when outdoor temperature was above 5°C. CONCLUSION: Positive associations of pulse pressure and SBP with short-term exposure to PM10 were found and replicated in the Swiss adult population. Our results suggest that even low levels of air pollution may substantially impact cardiovascular risk in the general population.

5C.09: Heritability of renal function parameters and electrolyte levels in the Swiss population

OBJECTIVE: Electrolytes handling by the kidney is essential for volume and blood pressure (BP) homeostasis but their distribution and heritability are not well described. We estimated the heritability of kidney function as well as of serum and urine concentrations, renal clearances and fractional excretions for sodium, chloride, potassium, calcium, phosphate and magnesium in a Swiss population-based study. DESIGN AND METHOD: Nuclear families were randomly selected from the general population in Switzerland. We estimated glomerular filtration rate (eGFR) using the CKD-EPI and MDRD equations. Urine was collected separately during day and night over 24-hour. We used the ASSOC program (S.A.G.E.) to estimate narrow sense heritability, including as covariates in the model: age, sex, body mass index and study center. RESULTS: The 1128 participants (537 men and 591 women from 273 families), had mean (sd) age of 47.4(17.5) years, body mass index of 25.0 (4.5) kg/m2 and CKD-EPI of 98.0(18.5) mL/min/1.73 m2. Heritability estimates (SE) were 46.0% (0.06), 48.0% (0.06) and 18.0% (0.06) for CKD-EPI, MDRD and 24-hour creatinine clearance (P < 0.05), respectively. Heritability [SE] of serum concentration was highest for calcium (37%[0.06]) and lowest for sodium (13%[0.05]). Heritabilities [SE] of 24-h urine concentrations and excretions, and of fractional excretions were highest for calcium (51%[0.06], 44%[0.06] and 51%[0.06], respectively) and lowest for potassium (11%[0.05], 10%[0.05] and 16%[0.06], respectively). All results were statistically different from zero.(Figure is included in full-text article.) CONCLUSIONS: : Serum and urine levels, urinary excretions and renal handling of electrolytes, particularly calcium, are heritable in the general adult population. Identifying genetic variants involved in electrolytes homeostasis may provide useful insight into the pathophysiological mechanisms involved in common chronic diseases such as kidney diseases, hypertension and diabetes.

Les infections pneumococciques: état des lieux et perspectives en matière de vaccination de l'adulte [Pneumococcal infections: Appraisal and perspectives in terms of adult vaccination].

Pneumococcal diseases are the first cause of bacterial infections in adult and in the aged adult. While its considerable morbi-mortality is potentially preventable through vaccination, the interest of anti-pneumococcal vaccination in these populations is still debated. Effectiveness appraisal of current anti-pneumococcal vaccines and the perspectives in terms of preventive strategies against Streptococcus pneumoniae infections in the adult population are presented.

The natural history of type II odontoid fractures in the elderly population. A retrospective study over a 14 years period.

Odontoid fractures are the most common cervical fractures in the adult population. They represent 9 to 18 % of all cervical fractures and the type II is the most common. The incidence of neurologic deficits (ND) in odontoid fractures varies between 3 to 25%. A recent study showed that patients with ND had a mortality rate increased by 4.72 times and a complication rate higher of 1.18 times. The most common complication in patients with ND was respiratory distress8. Surprisingly, although type II odontoid fractures are frequent cervical fractures, their natural history has been poorly described. Surgery for odontoid fractures is well described. However, there are so far guidelines based on class II and class III evidence only regarding indications for surgery and regarding surgical techniques. The class II guidelines recommend to consider surgical stabilization and fusion for type II odontoid in patients over 50 years of age. The class III recommendations are to first manage non-displaced odontoid type II fracture with external immobilization and that translation of 5mm or more is associated with a high rate of non- union with the conservative treatment and should be treated surgically.

Epidemiology and prevention of cardiovascular disease in the Seychelles Islands (Indian Ocean)

This article presents selected findings and lessons from a cardiovascular research and prevention program initiated in 1989 in the Republic of Seychelles, a country in demographic and epidemiological transition. Rapid and sustained aging of the population (e.g., two-fold increase of people aged 30-39 from 1979 to 1995) implies, over the next few decades, further dramatic increase of the burden of chronic diseases, particularly cardiovascular disease (CVD). Epidemiological surveillance shows high age-specific rates of CVD (particularly stroke), high prevalence of peripheral atherosclerosis (plaques in carotid and femoral arteries), high prevalence of classical modifiable risk factors in the adult population (particularly hypertension), and substantial proportions of children with overweight. Stagnant life expectancy in men and an increase in women have been observed over the last two decades; this occurred despite largely improved health services and reduced infant mortality rates, and may reflect the large CVD burden found in middle-aged men (less so in middle-aged women). A national program of prevention of CVD has been initiated since 1991, which includes a mix of interventions to reduce risk factors in the general population and in high-risk individuals. Substantial research to back the prevention program indeed shows, at the moment, epidemiological patterns in Seychelles similar to those observed in Western countries (e.g., an association between peripheral atherosclerosis [as a proxy of CVD] and low density lipoprotein-cholesterol, smoking, diabetes, and [inversely] walking). This clearly supports the view that promotion of healthy lifestyles and control of conventional risk factors should be the main targets for CVD prevention and control.

Trends in self-reported prevalence and management of hypertension, hypercholesterolemia and diabetes in Swiss adults, 1997-2007.

Switzerland has a low mortality rate from cardiovascular diseases, but little is known regarding prevalence and management of cardiovascular risk factors (CV RFs: hypertension, hypercholesterolemia and diabetes) in the general population. In this study, we assessed 10-year trends in self-reported prevalence and management of cardiovascular risk factors in Switzerland. data from three national health interview surveys conducted between 1997 and 2007 in representative samples of the Swiss adult population (49,261 subjects overall). Self-reported CV RFs prevalence, treatment and control levels were computed. The sample was weighted to match the sex - and age distribution, geographical location and nationality of the entire adult population of Switzerland. self-reported prevalence of hypertension, hypercholesterolemia and diabetes increased from 22.1%, 11.9% and 3.3% in 1997 to 24.1%, 17.4% and 4.8% in 2007, respectively. Prevalence of self-reported treatment among subjects with CV RFs also increased from 52.1%, 18.5% and 50.0% in 1997 to 60.4%, 38.8% and 53.3% in 2007 for hypertension, hypercholesterolemia and diabetes, respectively. Self-reported control levels increased from 56.4%, 52.9% and 50.0% in 1997 to 80.6%, 75.1% and 53.3% in 2007 for hypertension, hypercholesterolemia and diabetes, respectively. Finally, screening during the last 12 months increased from 84.5%, 86.5% and 87.4% in 1997 to 94.0%, 94.6% and 94.1% in 2007 for hypertension, hypercholesterolemia and diabetes, respectively. in Switzerland, the prevalences of self-reported hypertension, hypercholesterolemia and diabetes have increased between 1997 and 2007. Management and screening have improved, but further improvements can still be achieved as over one third of subjects with reported CV RFs are not treated.