Prospective study of insulin-like growth factor-I, insulin-like growth factor-binding protein 3, genetic variants in the IGF1 and IGFBP3 genes and risk of coronary artery disease.

Although experimental studies have suggested that insulin-like growth factor I (IGF-I) and its binding protein IGFBP-3 might have a role in the aetiology of coronary artery disease (CAD), the relevance of circulating IGFs and their binding proteins in the development of CAD in human populations is unclear. We conducted a nested case-control study, with a mean follow-up of six years, within the EPIC-Norfolk cohort to assess the association between circulating levels of IGF-I and IGFBP-3 and risk of CAD in up to 1,013 cases and 2,055 controls matched for age, sex and study enrolment date. After adjustment for cardiovascular risk factors, we found no association between circulating levels of IGF-I or IGFBP-3 and risk of CAD (odds ratio: 0.98 (95% Cl 0.90-1.06) per 1 SD increase in circulating IGF-I; odds ratio: 1.02 (95% Cl 0.94-1.12) for IGFBP-3). We examined associations between tagging single nucleotide polymorphisms (tSNPs) at the IGF1 and IGFBP3 loci and circulating IGF-I and IGFBP-3 levels in up to 1,133 cases and 2,223 controls and identified three tSNPs (rs1520220, rs3730204, rs2132571) that showed independent association with either circulating IGF-I or IGFBP-3 levels. In an assessment of 31 SNPs spanning the IGF1 or IGFBP3 loci, none were associated with risk of CAD in a meta-analysis that included EPIC-Norfolk and eight additional studies comprising up to 9,319 cases and 19,964 controls. Our results indicate that IGF-I and IGFBP-3 are unlikely to be importantly involved in the aetiology of CAD in human populations.

Hemodynamic and humoral effects of the new renin inhibitor enalkiren in normal humans.

The effect of the renin inhibitor enalkiren (Abbott-64662) was evaluated in eight normal volunteer subjects on a standardized sodium diet (100 mmol/day) by measurement of various components of the renin-angiotensin system and drug levels in plasma. On day 1, vehicle and doses of 0.001, 0.003, and 0.01 mg/kg i.v. were administered within 2 minutes at 90-minute intervals. On day 2, vehicle and doses of 0.01, 0.03, and 0.1 mg/kg i.v. were given. With the higher doses, blood pressure tended to decrease slightly with no change in heart rate. Plasma renin activity and plasma angiotensin-(1-8)octapeptide (angiotensin II) fell markedly in a dose-dependent manner. Inhibition of plasma renin activity was maximal 5 minutes after administration of the drug and persisted 90 minutes after the doses of 0.03 and 0.1 mg/kg. Not surprisingly, there was a close correlation between plasma renin activity and plasma angiotensin II levels (r = 0.81, n = 28, p less than 0.001). In contrast, active and total renin measured directly by monoclonal antibodies rose in dose-related fashion in response to renin inhibition. Pharmacokinetic parameters were calculated using the plasma drug concentrations obtained up to 6 hours after the 0.1 mg/kg dose. By means of a two-compartment model, plasma mean half-life of the drug was estimated at 1.60 +/- 0.43 hours.

Telementoring during endovascular treatment of abdominal aortic aneurysms: a prospective study.

PURPOSE: To explore the use of telementoring for distant teaching and training in endovascular aortic aneurysm repair (EVAR). METHODS: According to a prospectively designed study protocol, 48 patients underwent EVAR: the first 12 patients (group A) were treated at a secondary care center by an experienced interventionist, who was training the local team; a further 12 patients (group B) were operated by the local team at their secondary center with telementoring by the experienced operator from an adjacent suite; and the last 24 patients (group C) were operated by the local team with remote telementoring support from the experienced interventionist at a tertiary care center. Telementoring was performed using 3 video sources; images were transmitted using 4 ISDN lines. EVAR was performed using intravascular ultrasound and simultaneous fluoroscopy to obtain road mapping of the abdominal aorta and its branches, as well as for identifying the origins of the renal arteries, assessing the aortic neck, and monitoring the attachment of the stent-graft proximally and distally. RESULTS: Average duration of telementoring was 2.1 hours during the first 12 patients (group B) and 1.2 hours for the remaining 24 patients (group C). There was no difference in procedural duration (127+/-59 minutes in group A, 120+/-4 minutes in group B, and 119+/-39 minutes in group C; p=0.94) or the mean time spent in the ICU (26+/-15 hours in group A, 22+/-2 hours in group B, and 22+/-11 hours for group C; p=0.95). The length of hospital stay (11+/-4 days in group A, 9+/-4 days in group B, and 7+/-1 days in group C; p=0.002) was significantly different only for group C versus A (p=0.002). Only 1 (8.3%) patient (in group A: EVAR performed by the experienced operator) required conversion to open surgery because of iliac artery rupture. This was the only conversion (and the only death) in the entire study group (1/12 in group A versus 0/36 in groups B + C, p=0.31). CONCLUSIONS: Telementoring for EVAR is feasible and shows promising results. It may serve as a model for development of similar projects for teaching other invasive procedures in cardiovascular medicine.

Association of socioeconomic status with sleep disturbances in the Swiss population-based CoLaus study.

OBJECTIVE: To examine the association of socioeconomic status (SES) with subjective and objective sleep disturbances and the role of socio-demographic, behavioural and psychological factors in explaining this association. METHODS: Analyses are based on 3391 participants (53% female, aged 40-81 years) of the follow-up of the CoLaus study (2009-2012), a population-based sample of the city of Lausanne, Switzerland. All participants completed a sleep questionnaire and a sub-sample (N = 1569) underwent polysomnography. RESULTS: Compared with men with a high SES, men with a low SES were more likely to suffer from poor sleep quality [prevalence ratio (PR) for occupational position = 1.68, 95% Confidence Interval (CI): 1.30-2.17], and to have long sleep latency (PR = 4.90, 95%CI: 2.14-11.17), insomnia (PR = 1.47, 95% CI: 1.12-1.93) and short sleep duration (PR = 3.03, 95% CI: 1.78-5.18). The same pattern was observed among women (PR = 1.29 for sleep quality, 2.34 for sleep latency, 2.01 for daytime sleepiness, 3.16 for sleep duration, 95%CIs ranging from 1.00 to 7.51). Use of sleep medications was not patterned by SES. SES differences in sleep disturbances were only marginally attenuated by adjustment for other socio-demographic, behavioural and psychological factors. Results from polysomnography confirmed poorer sleep patterns among participants with low SES (p <0.05 for sleep efficiency/stage shifts), but no SES differences were found for sleep duration. CONCLUSIONS: In this population-based sample, low SES was strongly associated with sleep disturbances, independently of socio-demographic, behavioural, and psychological factors. Further research should establish the extent to which social differences in sleep contribute to socioeconomic differences in health outcomes.

Preoperative nutritional screening by the specialist instead of the nutritional risk score might prevent excess nutrition: a multivariate analysis of nutritional risk factors.

BACKGROUND: The aim of the current study was to assess whether widely used nutritional parameters are correlated with the nutritional risk score (NRS-2002) to identify postoperative morbidity and to evaluate the role of nutritionists in nutritional assessment. METHODS: A randomized trial on preoperative nutritional interventions (NCT00512213) provided the study cohort of 152 patients at nutritional risk (NRS-2002 ≥3) with a comprehensive phenotyping including diverse nutritional parameters (n=17), elaborated by nutritional specialists, and potential demographic and surgical (n=5) confounders. Risk factors for overall, severe (Dindo-Clavien 3-5) and infectious complications were identified by univariate analysis; parameters with P<0.20 were then entered in a multiple logistic regression model. RESULTS: Final analysis included 140 patients with complete datasets. Of these, 61 patients (43.6%) were overweight, and 72 patients (51.4%) experienced at least one complication of any degree of severity. Univariate analysis identified a correlation between few (≤3) active co-morbidities (OR=4.94; 95% CI: 1.47-16.56, p=0.01) and overall complications. Patients screened as being malnourished by nutritional specialists presented less overall complications compared to the not malnourished (OR=0.47; 95% CI: 0.22-0.97, p=0.043). Severe postoperative complications occurred more often in patients with low lean body mass (OR=1.06; 95% CI: 1-1.12, p=0.028). Few (≤3) active co-morbidities (OR=8.8; 95% CI: 1.12-68.99, p=0.008) were related with postoperative infections. Patients screened as being malnourished by nutritional specialists presented less infectious complications (OR=0.28; 95% CI: 0.1-0.78), p=0.014) as compared to the not malnourished. Multivariate analysis identified few co-morbidities (OR=6.33; 95% CI: 1.75-22.84, p=0.005), low weight loss (OR=1.08; 95% CI: 1.02-1.14, p=0.006) and low hemoglobin concentration (OR=2.84; 95% CI: 1.22-6.59, p=0.021) as independent risk factors for overall postoperative complications. Compliance with nutritional supplements (OR=0.37; 95% CI: 0.14-0.97, p=0.041) and supplementation of malnourished patients as assessed by nutritional specialists (OR=0.24; 95% CI: 0.08-0.69, p=0.009) were independently associated with decreased infectious complications. CONCLUSIONS: Nutritional support based upon NRS-2002 screening might result in overnutrition, with potentially deleterious clinical consequences. We emphasize the importance of detailed assessment of the nutritional status by a dedicated specialist before deciding on early nutritional intervention for patients with an initial NRS-2002 score of ≥3.

Prospective motion correction of 3D echo-planar imaging data for functional MRI using optical tracking.

We evaluated the performance of an optical camera based prospective motion correction (PMC) system in improving the quality of 3D echo-planar imaging functional MRI data. An optical camera and external marker were used to dynamically track the head movement of subjects during fMRI scanning. PMC was performed by using the motion information to dynamically update the sequence's RF excitation and gradient waveforms such that the field-of-view was realigned to match the subject's head movement. Task-free fMRI experiments on five healthy volunteers followed a 2×2×3 factorial design with the following factors: PMC on or off; 3.0mm or 1.5mm isotropic resolution; and no, slow, or fast head movements. Visual and motor fMRI experiments were additionally performed on one of the volunteers at 1.5mm resolution comparing PMC on vs PMC off for no and slow head movements. Metrics were developed to quantify the amount of motion as it occurred relative to k-space data acquisition. The motion quantification metric collapsed the very rich camera tracking data into one scalar value for each image volume that was strongly predictive of motion-induced artifacts. The PMC system did not introduce extraneous artifacts for the no motion conditions and improved the time series temporal signal-to-noise by 30% to 40% for all combinations of low/high resolution and slow/fast head movement relative to the standard acquisition with no prospective correction. The numbers of activated voxels (p<0.001, uncorrected) in both task-based experiments were comparable for the no motion cases and increased by 78% and 330%, respectively, for PMC on versus PMC off in the slow motion cases. The PMC system is a robust solution to decrease the motion sensitivity of multi-shot 3D EPI sequences and thereby overcome one of the main roadblocks to their widespread use in fMRI studies.

Copy number variations and cognitive phenotypes in unselected populations

IMPORTANCE: The association of copy number variations (CNVs), differing numbers of copies of genetic sequence at locations in the genome, with phenotypes such as intellectual disability has been almost exclusively evaluated using clinically ascertained cohorts. The contribution of these genetic variants to cognitive phenotypes in the general population remains unclear. OBJECTIVE: To investigate the clinical features conferred by CNVs associated with known syndromes in adult carriers without clinical preselection and to assess the genome-wide consequences of rare CNVs (frequency ≤0.05%; size ≥250 kilobase pairs [kb]) on carriers' educational attainment and intellectual disability prevalence in the general population. DESIGN, SETTING, AND PARTICIPANTS: The population biobank of Estonia contains 52,000 participants enrolled from 2002 through 2010. General practitioners examined participants and filled out a questionnaire of health- and lifestyle-related questions, as well as reported diagnoses. Copy number variant analysis was conducted on a random sample of 7877 individuals and genotype-phenotype associations with education and disease traits were evaluated. Our results were replicated on a high-functioning group of 993 Estonians and 3 geographically distinct populations in the United Kingdom, the United States, and Italy. MAIN OUTCOMES AND MEASURES: Phenotypes of genomic disorders in the general population, prevalence of autosomal CNVs, and association of these variants with educational attainment (from less than primary school through scientific degree) and prevalence of intellectual disability. RESULTS: Of the 7877 in the Estonian cohort, we identified 56 carriers of CNVs associated with known syndromes. Their phenotypes, including cognitive and psychiatric problems, epilepsy, neuropathies, obesity, and congenital malformations are similar to those described for carriers of identical rearrangements ascertained in clinical cohorts. A genome-wide evaluation of rare autosomal CNVs (frequency, ≤0.05%; ≥250 kb) identified 831 carriers (10.5%) of the screened general population. Eleven of 216 (5.1%) carriers of a deletion of at least 250 kb (odds ratio [OR], 3.16; 95% CI, 1.51-5.98; P = 1.5e-03) and 6 of 102 (5.9%) carriers of a duplication of at least 1 Mb (OR, 3.67; 95% CI, 1.29-8.54; P = .008) had an intellectual disability compared with 114 of 6819 (1.7%) in the Estonian cohort. The mean education attainment was 3.81 (P = 1.06e-04) among 248 (≥250 kb) deletion carriers and 3.69 (P = 5.024e-05) among 115 duplication carriers (≥1 Mb). Of the deletion carriers, 33.5% did not graduate from high school (OR, 1.48; 95% CI, 1.12-1.95; P = .005) and 39.1% of duplication carriers did not graduate high school (OR, 1.89; 95% CI, 1.27-2.8; P = 1.6e-03). Evidence for an association between rare CNVs and lower educational attainment was supported by analyses of cohorts of adults from Italy and the United States and adolescents from the United Kingdom. CONCLUSIONS AND RELEVANCE: Known pathogenic CNVs in unselected, but assumed to be healthy, adult populations may be associated with unrecognized clinical sequelae. Additionally, individually rare but collectively common intermediate-size CNVs may be negatively associated with educational attainment. Replication of these findings in additional population groups is warranted given the potential implications of this observation for genomics research, clinical care, and public health.

Adjusting fracture probability by trabecular bone score.

The aim of the present study was to determine the impact of trabecular bone score on the probability of fracture above that provided by the clinical risk factors utilized in FRAX. We performed a retrospective cohort study of 33,352 women aged 40-99 years from the province of Manitoba, Canada, with baseline measurements of lumbar spine trabecular bone score (TBS) and FRAX risk variables. The analysis was cohort-specific rather than based on the Canadian version of FRAX. The associations between trabecular bone score, the FRAX risk factors and the risk of fracture or death were examined using an extension of the Poisson regression model and used to calculate 10-year probabilities of fracture with and without TBS and to derive an algorithm to adjust fracture probability to take account of the independent contribution of TBS to fracture and mortality risk. During a mean follow-up of 4.7 years, 1754 women died and 1639 sustained one or more major osteoporotic fractures excluding hip fracture and 306 women sustained one or more hip fracture. When fully adjusted for FRAX risk variables, TBS remained a statistically significant predictor of major osteoporotic fractures excluding hip fracture (HR/SD 1.18, 95 % CI 1.12-1.24), death (HR/SD 1.20, 95 % CI 1.14-1.26) and hip fracture (HR/SD 1.23, 95 % CI 1.09-1.38). Models adjusting major osteoporotic fracture and hip fracture probability were derived, accounting for age and trabecular bone score with death considered as a competing event. Lumbar spine texture analysis using TBS is a risk factor for osteoporotic fracture and a risk factor for death. The predictive ability of TBS is independent of FRAX clinical risk factors and femoral neck BMD. Adjustment of fracture probability to take account of the independent contribution of TBS to fracture and mortality risk requires validation in independent cohorts.

The Classification of Vitreous Seeds in Retinoblastoma and Response to Intravitreal Melphalan.

PURPOSE: To evaluate the clinical characteristics of the 3 classifications of vitreous seeds in retinoblastoma-dust (class 1), spheres (class 2), and clouds (class 3)-and their responses to intravitreal melphalan. DESIGN: Retrospective, bi-institutional cohort study. PARTICIPANTS: A total of 87 patient eyes received 475 intravitreal injections of melphalan (median dose, 30 μg) given weekly, a median of 5 times (range, 1-12 times). METHODS: At presentation, the vitreous seeds were classified into 3 groups: dust, spheres, and clouds. Indirect ophthalmoscopy, fundus photography, ultrasonography, and ultrasonic biomicroscopy were used to evaluate clinical response to weekly intravitreal melphalan injections and time to regression of vitreous seeds. Kaplan-Meier estimates of time to regression and ocular survival, patient survival, and event-free survival (EFS) were calculated and then compared using the Mantel-Cox test of curve. MAIN OUTCOME MEASURES: Time to regression of vitreous seeds, patient survival, ocular survival, and EFS. RESULTS: The difference in time to regression was significantly different for the 3 seed classes (P < 0.0001): the median time to regression was 0.6, 1.7, and 7.7 months for dust, spheres, and clouds, respectively. Eyes with dust received significantly fewer injections and a lower median and cumulative dose of melphalan, whereas eyes with clouds received significantly more injections and a higher median and cumulative dose of melphalan. Overall, the 2-year Kaplan-Meier estimates for ocular survival, patient survival, and EFS (related to target seeds) were 90.4% (95% confidence interval [CI], 79.7-95.6), 100%, and 98.5% (95% CI, 90-99.7), respectively. CONCLUSIONS: The regression and response of vitreous seeds to intravitreal melphalan are different for each seed classification. The vitreous seed classification can be predictive of time to regression, number, median dose, and cumulative dose of intravitreal melphalan injections required.

Trends in self-reported prevalence and management of hypertension, hypercholesterolemia and diabetes in Swiss adults between 1992 and 2007

PURPOSE: to assess the trends of prevalence of self-reported cardiovascular risk factors (CV RFs: hypertension, hypercholesterolemia, diabetes) and their management for the period of 1992 to 2007 in Switzerland. METHODS: four health interview surveys conducted between 1992 and 2007 in representative samples of the Swiss population (63,782 subjects overall). Self-reported CV RFs prevalence, treatment and control levels were computed after weighting. Weights were calculated by raking ratio such that the marginal distribution of the weighted totals conforms to the marginal distribution of the target population. Multivariate analysis was conducted using logistic regression. RESULTS: prevalence of all CV RFs increased between 1992 and 2007. Also, the prevalence of self-reported treatment among subjects with CV RFs increased, as confirmed by multivariate analysis: OR for hypolipidemic treatment relative to 1992: 0.64 [0.52-0.78]; 1.39 [1.18-1.65] and 2.00 [1.69-2.36] for 1997, 2002 and 2007, respectively. Still, in 2007, circa 40% of hypertensive, 60% of hypercholesterolemic and 50% of diabetic subjects weren't treated. On the other hand, there is an increase of the prevalence of controlled RFs as reported by treated subjects. This was confirmed by multivariate analysis 12.1 [12.0 - 12.2]; 4.16 [4.1 - 4.23] and 2.85 [2.79 - 2.90] for hypertension, hypercholesterolemia and diabetes, respectively, in 2007, relative to 1992. CONCLUSION: the prevalence of self-reported hypertension, hypercholesterolemia and diabetes increased between 1992 and 2007 in the Swiss population. Despite a good control of treated subjects, still a significant percentage of subjects with CV RFs are not treated.

La Calypso: nos offres en soins

Après ses premiers 8 mois de fonctionnement, présentation de La Calypso, unité de soins spécifique de prise en charge pour des sevrages Haut Seuil

André Roumieux : une vie d'infirmier en psychiatrie (1951-1986)

Il nous a retracé l'évolution de la profession d'infirmier en psychiatrie pendant les 35 années de sa carrière à Ville-Evrard. Evolutions portées aussi bien par des personnages, le Dr Sivadon par exemple, que par les événements politiques de la scène française, Mai 68 et ses conséquences. Les maîtres-mots sont: ouverture des portes vers la cité, respect de la dignité humaine et liberté des malades. Mais aussi, silence, parole, et écriture des infirmiers, et particulièrement la sienne.