Clinical, polysomnographic and genome-wide association analyses of narcolepsy with cataplexy: a European Narcolepsy Network study.

The aim of this study was to describe the clinical and PSG characteristics of narcolepsy with cataplexy and their genetic predisposition by using the retrospective patient database of the European Narcolepsy Network (EU-NN). We have analysed retrospective data of 1099 patients with narcolepsy diagnosed according to International Classification of Sleep Disorders-2. Demographic and clinical characteristics, polysomnography and multiple sleep latency test data, hypocretin-1 levels, and genome-wide genotypes were available. We found a significantly lower age at sleepiness onset (men versus women: 23.74 ± 12.43 versus 21.49 ± 11.83, P = 0.003) and longer diagnostic delay in women (men versus women: 13.82 ± 13.79 versus 15.62 ± 14.94, P = 0.044). The mean diagnostic delay was 14.63 ± 14.31 years, and longer delay was associated with higher body mass index. The best predictors of short diagnostic delay were young age at diagnosis, cataplexy as the first symptom and higher frequency of cataplexy attacks. The mean multiple sleep latency negatively correlated with Epworth Sleepiness Scale (ESS) and with the number of sleep-onset rapid eye movement periods (SOREMPs), but none of the polysomnographic variables was associated with subjective or objective measures of sleepiness. Variant rs2859998 in UBXN2B gene showed a strong association (P = 1.28E-07) with the age at onset of excessive daytime sleepiness, and rs12425451 near the transcription factor TEAD4 (P = 1.97E-07) with the age at onset of cataplexy. Altogether, our results indicate that the diagnostic delay remains extremely long, age and gender substantially affect symptoms, and that a genetic predisposition affects the age at onset of symptoms.

Readmission from orthopedic surgical site infections: an integrative review

Abstract OBJECTIVE Characterizing readmissions from orthopedic surgical site infections. METHOD An integrative review of literature in the LILACS, IBECS, MEDLINE, Cochrane, SciELO and PUBMED databases, using the descriptors Patient readmission, Wound infection, Cross infection, Orthopedic procedures, Orthopedics. RESULTS 78 studies were identified and 10 publications were selected. Surgical site infections are the most common cause of unplanned orthopedic readmissions, representing long periods of hospitalization, new surgical procedures and high costs, and greater possibility of subsequent hospitalizations. Most significant predictors have indicated average length of hospitalization, need for intensive care, emergency status at admission, risk of death, age > 65 years, males and higher body mass index. CONCLUSION Readmission rates have increasingly become measures of quality and concerns about costs. New studies could involve issues related to indirect costs, specifically social and psychological costs.

The control of hypertension in men and women: a comparative analysis

Abstract OBJECTIVE To compare men and women who have hypertension with reference to the following: high blood pressure, biosocial variables, habits and life styles, mental disorders, and social support networks. METHOD 290 hypertensive patients (women, 62.1%) were evaluated. The assessments involved the following: measuring blood pressure with an automatic measuring device, evaluating social status through the Social Support Scale, and the use of a Self-Report Questionnaire (SRQ-20) to identify common mental disorders. A value of p<0.05 was considered statistically significant. RESULTS Women were found to be different to men (p<0.05) in the following areas having: better control of their blood pressure (64.4% vs 52.7%), less salary incomes, less diabetes, higher total cholesterol, higher body mass index and wider abdominal circumferences. They also had lower systolic blood pressure, lower levels of alcohol consumption and a greater prevalence for mental disorders. The social support assessment revealed that hypertensive women received less help with preparing meals but had more company from people which allowed them to engage in enjoyable activities. CONCLUSION Women had more control over their blood pressure than men, despite the presence of negative biopsychosocial factors that may have influenced their adherence to the treatments.

Is thinness more prevalent than obesity in Portuguese adolescents?

There is little information regarding the prevalence of thinness in European adolescents. This was assessed in a convenience sample of children and adolescents from the Lisbon area (Portugal). Cross-sectional study including 2494 boys and 2519 girls aged 10-18 years. Body mass index (BMI), waist and hip were measured using standardized methods; thinness was defined using international criteria. Body fat was assessed by bioelectrical impedance. In girls, prevalence of thinness, overweight and obesity were 5.6%, 19.7% and 4.7%, respectively, whereas the corresponding numbers in boys were 3.9%, 17.4% and 5.3%. Prevalence of thinness increased whereas obesity decreased with age: from 1.5% to 7.6% for thinness and from 9.2% to 3.8% for obesity in girls aged 10 and 18, respectively. In boys, the corresponding trends were from 0% to 7.3% for thinness and from 10.6% to 3% for obesity. After adjusting for age, differences were found between BMI groups for weight, body fat percentage, fat mass, lean mass, waist and hip, while no differences regarding height were found between thin and normal weight participants. The prevalence of thinness is more frequent than obesity after age 14 in girls and 16 years in boys. Thinness is associated with a decreased body weight and body fat, whereas no consistent effect on height was noted.

Prevalence of normal weight obesity in the general population

Background and Aims: normal weight obesity (NWO) has been defined as an excessive body fat (BF) associated with a normal body mass index (BMI). Little is known regarding its prevalence in the general population or which cut-offs for BF should be used. Methods: convenience sample of 1,523 Portuguese adults. BF was measured by validated hand-held bioimpedance. NWO was defined as a BMI<25 kg/m2 and a %BF mass>30%, along other published criteria. Results: prevalence of NWO was 10.1% in women and 3.2% in men. In women, prevalence of NWO increased considerably with age, and virtually all women aged over 55 with a BMI<25 kg/m2 were actually considered as NWO. Using gender specific cut-offs for BF (29.1% in men and 37.2% in women) led to moderately lower of NWO in women. Using gender- and age-specific cut-points for %BF considerably decreased the prevalence of NWO in women (0.5 to 2.5% depending on the criterion) but not in men (1.9 to 3.4%). Conclusions: gender- and age- specific or at least gender-specific, instead of single cut-offs for %BF, should be used to characterize and study NWO.

Chirurgie bariatrique en 2013: principes, avantages et inconvénients des interventions a disposition [Bariatric surgery in 2013: principles, advantages and disadvantages of the available procedures].

For severe obesity (BMI > 35 kg/m2), bariatric surgery is not only the best, but often the only means of obtaining sufficient and durable weight loss. This article aims to review the available bariatric procedures. Gastric bypass remains the reference when it comes to the risk/benefit ratio. Gastric banding is declining rapidly due to the high prevalence of long-term complications. Primary malabsorptive procedures remain largely unpopular because of their potential nutritional complications. Sleeve gastrectomy, although it is not reversible as it includes a significant gastric resection, increases currently in popularity because of its apparent simplicity and the fact that early results regarding weight loss mimic those obtained with gastric bypass.

Nocturnal hypoglycaemias in type 1 diabetic patients: what can we learn with continuous glucose monitoring?

AIM: In type 1 diabetic patients (T1DM), nocturnal hypoglycaemias (NH) are a serious complication of T1DM treatment; self-monitoring of blood glucose (SMBG) is recommended to detect them. However, the majority of NH remains undetected on an occasional SMBG done during the night. An alternative strategy is the Continuous glucose monitoring (CGMS), which retrospectively shows the glycaemic profile. The aims of this retrospective study were to evaluate the true incidence of NH in T1DM, the best SMBG time to predict NH, the relationship between morning hyperglycaemia and NH (Somogyi phenomenon) and the utility of CGMS to reduce NH. METHODS: Eighty-eight T1DM who underwent a CGMS exam were included. Indications for CGMS evaluation, hypoglycaemias and correlation with morning hyperglycaemias were recorded. The efficiency of CGMS to reduce the suspected NH was evaluated after 6-9 months. RESULTS: The prevalence of NH was 67% (32% of them unsuspected). A measured hypoglycaemia at bedtime (22-24 h) had a sensitivity of 37% to detect NH (OR=2.37, P=0.001), while a single measure < or =4 mmol/l at 3-hour had a sensitivity of 43% (OR=4.60, P<0.001). NH were not associated with morning hyperglycaemias but with morning hypoglycaemias (OR=3.95, P<0.001). After 6-9 months, suspicions of NH decreased from 60 to 14% (P<0.001). CONCLUSION: NH were highly prevalent and often undetected. SMBG at bedtime, which detected hypoglycaemia had sensitivity almost equal to that of 3-hour and should be preferred because it is easier to perform. Somogyi phenomenon was not observed. CGMS is useful to reduce the risk of NH in 75% of patients.

High prevalence of major cardiovascular risk factors in first-degree relatives of individuals with familial premature coronary artery disease--the GENECARD project.

BACKGROUND: Hypertension, hypercholesterolemia, obesity and smoking are highly prevalent among patients with familial premature coronary artery disease (FP-CAD). Whether these risk factors equally affect other family members remains unknown. METHODS: We examined 222 FP-CAD patients, 158 unaffected sibs, 197 offspring and 94 spouses in 108 FP-CAD families (> or = 2 sibs having survived CAD diagnosed before age 51 (M)/56 (F)), and compared them to population controls. RESULTS: Unaffected sibs had a higher prevalence of hypertension (49% versus 24%, p<0.001), hypercholesterolemia (47% versus 34%, p=0.002), abdominal obesity (35% versus 24%, p=0.006) and smoking (39% versus 24%, p=0.001) than population controls. Offspring had a higher prevalence of hypertension (females), hypercholesterolemia and abdominal obesity than population controls. No difference was observed between spouses and controls. Compared to unaffected sibs, FP-CAD affected sibs had a similar risk factor profile, except for smoking, which was more prevalent (76% versus 39%, p=0.008). CONCLUSIONS: Hypertension, obesity and hypercholesterolemia are highly prevalent among first-degree relatives, but not spouses, of patients with FP-CAD. These persons deserve special medical attention due to their familial/genetic susceptibility to atherogenic metabolic abnormalities. In these families, smoking may be the trigger for FP-CAD.

Low compliance with dietary recommendations for food intake among adults.

BACKGROUND & AIMS: To assess the adherence to the national dietary recommendations and to identify factors contributing to dietary compliance in Switzerland. METHODS: Population-based cross-sectional study in Lausanne, Switzerland (CoLaus study), 2009-2012. Dietary intake was assessed using a validated food frequency questionnaire. Participants were dichotomized according to whether they followed the national recommendations for fruits, vegetables, meat, fish and dairy products. RESULTS: Data from 4371 participants (54% women, mean age ± SD: 57.6 ± 10.5 years) were analyzed. Compliance with the recommendations was low: only 39.4%, 7.1%, 61.3%, 66.4%, and 8.4% complied with the Swiss recommendations for fruit (≥2/day), vegetables (≥3/day), meat (≤5/week), fish (≥1/week) and dairy products (≥3/day), respectively. In multivariate analyses, gender, age, smoking status, Swiss-born status, education, being on a diet and body mass index were associated with dietary compliance, while no difference was found between women before and after menopause. Factors specifically associated with fruits, vegetables, meat, fish or dairy products recommendations were identified. CONCLUSION: The low degree of compliance with dietary recommendations calls for a continued effort to increase the population awareness of the importance of a healthy and balanced diet, especially for vegetables and dairy products. This study identified determinants that should guide this effort.

Roux-en-Y gastric bypass vs gastric banding for morbid obesity: a case-matched study of 442 patients.

HYPOTHESIS: Gastric banding (GB) and Roux-en-Y gastric bypass (RYGBP) are used in the treatment of morbidly obese patients. We hypothesized that RYGBP provides superior results. DESIGN: Matched-pair study in patients with a body mass index (BMI) less than 50. SETTING: University hospital and regional community hospital with a common bariatric surgeon. PATIENTS: Four hundred forty-two patients were matched according to sex, age, and BMI. INTERVENTIONS: Laparoscopic GB or RYGBP. MAIN OUTCOME MEASURES: Operative morbidity, weight loss, residual BMI, quality of life, food tolerance, lipid profile, and long-term morbidity. RESULTS: Follow-up was 92.3% at the end of the study period (6 years postoperatively). Early morbidity was higher after RYGBP than after GB (17.2% vs 5.4%; P<.001), but major morbidity was similar. Weight loss was quicker, maximal weight loss was greater, and weight loss remained significantly better after RYGBP until the sixth postoperative year. At 6 years, there were more failures (BMI>35 or reversal of the procedure/conversion) after GB (48.3% vs 12.3%; P<.001). There were more long-term complications (41.6% vs 19%; P.001) and more reoperations (26.7% vs 12.7%; P<.001) after GB. Comorbidities improved more after RYGBP. CONCLUSIONS: Roux-en-Y gastric bypass is associated with better weight loss, resulting in a better correction of some comorbidities than GB, at the price of a higher early complication rate. This difference, however, is largely compensated by the much higher long-term complication and reoperation rates seen after GB.

Impact and cost of a 2-week community-based screening and awareness program for diabetes and cardiovascular risk factors in a Swiss canton.

BACKGROUND: Community-based diabetes screening programs can help sensitize the population and identify new cases. However, the impact of such programs is rarely assessed in high-income countries, where concurrent health information and screening opportunities are common place. INTERVENTION AND METHODS: A 2-week screening and awareness campaign was organized as part of a new diabetes program in the canton of Vaud (population of 697,000) in Switzerland. Screening was performed without appointment in 190 out of 244 pharmacies in the canton at the subsidized cost of 10 Swiss Francs per participant. Screening included questions on risk behaviors, measurement of body mass index, blood pressure, blood cholesterol, random blood glucose (RBG), and A1c if RBG was >/=7.0 mmol/L. A mass media campaign promoting physical activity and a healthy diet was channeled through several media, eg, 165 spots on radio, billboards in 250 public places, flyers in 360 public transport vehicles, and a dozen articles in several newspapers. A telephone survey in a representative sample of the population of the canton was performed after the campaign to evaluate the program. RESULTS: A total of 4222 participants (0.76% of all persons aged >/=18 years) underwent the screening program (median age: 53 years, 63% females). Among participants not treated for diabetes, 3.7% had RBG >/= 7.8 mmol/L and 1.8% had both RBG >/= 7.0 mmol/L and A1c >/= 6.5. Untreated blood pressure >/=140/90 mmHg and/or untreated cholesterol >/=5.2 mmol/L were found in 50.5% of participants. One or several treated or untreated modifiable risk factors were found in 78% of participants. The telephone survey showed that 53% of all adults in the canton were sensitized by the campaign. Excluding fees paid by the participants, the program incurred a cost of CHF 330,600. CONCLUSION: A community-based screening program had low efficiency for detecting new cases of diabetes, but it identified large numbers of persons with elevated other cardiovascular risk factors. Our findings suggest the convenience of A1c for mass screening of diabetes, the usefulness of extending diabetes screening to other cardiovascular risk factors, and the importance of a robust background communication campaign.

A new highly penetrant form of obesity due to deletions on chromosome 16p11.2.

Obesity has become a major worldwide challenge to public health, owing to an interaction between the Western 'obesogenic' environment and a strong genetic contribution. Recent extensive genome-wide association studies (GWASs) have identified numerous single nucleotide polymorphisms associated with obesity, but these loci together account for only a small fraction of the known heritable component. Thus, the 'common disease, common variant' hypothesis is increasingly coming under challenge. Here we report a highly penetrant form of obesity, initially observed in 31 subjects who were heterozygous for deletions of at least 593 kilobases at 16p11.2 and whose ascertainment included cognitive deficits. Nineteen similar deletions were identified from GWAS data in 16,053 individuals from eight European cohorts. These deletions were absent from healthy non-obese controls and accounted for 0.7% of our morbid obesity cases (body mass index (BMI) >or= 40 kg m(-2) or BMI standard deviation score >or= 4; P = 6.4 x 10(-8), odds ratio 43.0), demonstrating the potential importance in common disease of rare variants with strong effects. This highlights a promising strategy for identifying missing heritability in obesity and other complex traits: cohorts with extreme phenotypes are likely to be enriched for rare variants, thereby improving power for their discovery. Subsequent analysis of the loci so identified may well reveal additional rare variants that further contribute to the missing heritability, as recently reported for SIM1 (ref. 3). The most productive approach may therefore be to combine the 'power of the extreme' in small, well-phenotyped cohorts, with targeted follow-up in case-control and population cohorts.

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition.

Elevated endocannabinoid plasma levels are associated with coronary circulatory dysfunction in obesity.

AIMS: Aim of this study was to evaluate a possible association between endocannabinoid (EC) plasma levels, such as anandamide (AEA) and 2-arachidonoylglycerol (2-AG), and coronary circulatory function in obesity. METHODS AND RESULTS: Myocardial blood flow (MBF) responses to cold pressor test (CPT) and during pharmacological vasodilation with dipyridamole were measured with (13)N-ammonia PET/CT. Study participants (n = 77) were divided into three groups based on their body mass index (BMI, kg/m(2)): control group 20 ≤ BMI <25 (n = 21); overweight group, 25 ≤ BMI <30 (n = 26); and obese group, BMI ≥ 30 (n = 30). Anandamide plasma levels, but not 2-AG plasma levels, were significantly elevated in obesity as compared with controls, respectively [0.68 (0.53, 0.78) vs. 0.56 (0.47, 0.66) ng/mL, P = 0.020, and 2.2 (1.21, 4.59) vs. 2.0 (0.80, 5.90) ng/mL, P = 0.806)]. The endothelium-related change in MBF during CPT from rest (ΔMBF) progressively declined in overweight and obese when compared with control group [0.21 (0.10, 0.27) and 0.09 (-0.01, 0.15) vs. 0.26 (0.23, 0.39) mL/g/min; P = 0.010 and P = 0.0001, respectively). Compared with controls, hyperaemic MBFs were significantly lower in overweight and obese individuals [2.39 (1.97, 2.62) vs. 1.98 (1.69, 2.26) and 2.10 (1.76, 2.36); P = 0.007 and P = 0.042, respectively)]. In obese individuals, AEA and 2-AG plasma levels were inversely correlated with ΔMBF to CPT (r = -0.37, P = 0.046 and r = -0.48, P = 0.008) and hyperaemic MBFs (r = -0.38, P = 0.052 and r = -0.45, P = 0.017), respectively. CONCLUSIONS: Increased EC plasma levels of AEA and 2-AG are associated with coronary circulatory dysfunction in obese individuals. This observation might suggest increases in EC plasma levels as a novel endogenous cardiovascular risk factor in obesity, but needing further investigations.

Adiponectin isoform distribution in serum and in follicular fluid of women undergoing treatment by ICSI.

Adiponectin is an adipokine, present in the circulation in comparatively high concentrations and different molecular weight isoforms. For the first time, the distribution of these isoforms in serum and follicular fluid (FF) and their usefulness as biological markers for infertility investigations was studied. In vitro study. University based hospital. Fifty-four women undergoing intracytoplasmic sperm injection (ICSI). Oocytes were retrieved, fertilized in vitro using ICSI, and the resulting embryos transferred. Serum was collected immediately prior to oocyte retrieval. Adiponectin isoforms (high molecular weight (HMW), medium and low molecular weight) were determined in serum and FF. Total adiponectin and the different isoform levels were compared with leptin and ovarian steroid concentrations. Adiponectin isoforms in serum and FF. Adiponectin isoform distribution differed between serum and FF; the HMW fraction made up half of all adiponectin in the serum but only 23.3% in the FF. Total and HMW adiponectin in both serum and FF correlated negatively with the body mass index and the concentration of leptin. No correlations were observed for total adiponectin or its isoforms with estradiol, progesterone, anti-Mullerian hormone, inhibin B, or the total follicle stimulating hormone (FSH) dose administered during the ovarian stimulation phase. This study shows for the first time that adiponectin isoform distribution varies between the serum and FF compartments in gonadotropin stimulated patients. A trend towards higher HMW adiponectin serum levels in successful ICSI cycles compared to implantation failures was observed; studies with larger patient groups are required to confirm this observation.