CPAP, weight loss, or both for obstructive sleep apnea

BACKGROUNd: Obesity and obstructive sleep apnea tend to coexist and are associated with inflammation, insulin resistance, dyslipidemia, and high blood pressure, but their causal relation to these abnormalities is unclear. METHODS: We randomly assigned 181 patients with obesity, moderate-to-severe obstructive sleep apnea, and serum levels of C-reactive protein (CRP) greater than 1.0 mg per liter to receive treatment with continuous positive airway pressure (CPAP), a weight-loss intervention, or CPAP plus a weight-loss intervention for 24 weeks. We assessed the incremental effect of the combined interventions over each one alone on the CRP level (the primary end point), insulin sensitivity, lipid levels, and blood pressure. RESULTS: Among the 146 participants for whom there were follow-up data, those assigned to weight loss only and those assigned to the combined interventions had reductions in CRP levels, insulin resistance, and serum triglyceride levels. None of these changes were observed in the group receiving CPAP alone. Blood pressure was reduced in all three groups. No significant incremental effect on CRP levels was found for the combined interventions as compared with either weight loss or CPAP alone. Reductions in insulin resistance and serum triglyceride levels were greater in the combined-intervention group than in the group receiving CPAP only, but there were no significant differences in these values between the combined-intervention group and the weight-loss group. In per-protocol analyses, which included 90 participants who met prespecified criteria for adherence, the combined interventions resulted in a larger reduction in systolic blood pressure and mean arterial pressure than did either CPAP or weight loss alone. CONCLUSIONS: In adults with obesity and obstructive sleep apnea, CPAP combined with a weight-loss intervention did not reduce CRP levels more than either intervention alone. In secondary analyses, weight loss provided an incremental reduction in insulin resistance and serum triglyceride levels when combined with CPAP. In addition, adherence to a regimen of weight loss and CPAP may result in incremental reductions in blood pressure as compared with either intervention alone. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT0371293 .)

The Florey Adelaide Male Ageing Study (FAMAS): Design, procedures & participants

<p>Abstract</p> <p>Background</p> <p>The Florey Adelaide Male Ageing Study (FAMAS) examines the reproductive, physical and psychological health, and health service utilisation of the ageing male in Australia. We describe the rationale for the study, the methods used participant response rates, representativeness and attrition to date.</p> <p>Methods</p> <p>FAMAS is a longitudinal study involving approximately 1200 randomly selected men, aged 35–80 years and living in the north – west regions of Adelaide. Respondents were excluded at screening if they were considered incapable of participating because of immobility, language, or an inability to undertake the study procedures. Following a telephone call to randomly selected households, eligible participants were invited to attend a baseline clinic measuring a variety of biomedical and socio-demographic factors. Beginning in 2002, these clinics are scheduled to reoccur every five years. Follow-up questionnaires are completed annually. Participants are also invited to participate in sub-studies with selected collaborators.</p> <p>Results</p> <p>Of those eligible to participate, 45.1% ultimately attended a clinic. Non-responders were more likely to live alone, be current smokers, have a higheevalence of self-reported diabetes and stroke, and lower levels of hypercholesterolemia. Comparisons with the Census 2001 data showed that participants matched the population for most key demographics, although younger groups and never married men were under-represented and elderly participants were over-represented. To date, there has been an annual loss to follow-up of just over 1%.</p> <p>Conclusion</p> <p>FAMAS allows a detailed investigation into the effects of bio-psychosocial and behavioural factors on the health and ageing of a largely representative group of Australian men.</p

Role of Homer Proteins in the Maintenance of Sleep-Wake States

Sleep is an evolutionarily conserved process that is linked to diurnal cycles and normal daytime wakefulness. Healthy sleep and wakefulness are integral to a healthy lifestyle; this occurs when an organism is able to maintain long bouts of both sleep and wake. Homer proteins, which function as adaptors for group 1 metabotropic glutamate receptors, have been implicated in genetic studies of sleep in both Drosophila and mouse. Drosophila express a single Homer gene product that is upregulated during sleep. By contrast, vertebrates express Homer as both constitutive and immediate early gene (H1a) forms, and H1a is up-regulated during wakefulness. Genetic deletion of Homer in Drosophila results in fragmented sleep and in failure to sustain long bouts of sleep, even under increased sleep drive. However, deletion of Homer1a in mouse results in failure to sustain long bouts of wakefulness. Further evidence for the role of Homer1a in the maintenance of wake comes from the CREB alpha delta mutant mouse, which displays a reduced wake phenotype similar to the Homer1a knockout and fails to up-regulate Homer1a upon sleep loss. Homer1a is a gene whose expression is induced by CREB. Sustained behaviors of the sleep/wake cycle are created by molecular pathways that are distinct from those for arousal or short bouts, and implicate an evolutionarily-conserved role for Homer in sustaining these behaviors

Home-based transcranial direct current stimulation treatment for major depressive disorder: a fully remote phase 2 randomized sham-controlled trial

Transcranial direct current stimulation (tDCS) has been proposed as novel treatment in major depressive disorder (MDD). The present study is fully remote, multisite, double-blind, placebocontrolled, randomized superiority trial of 10-week home-based tDCS in MDD. Participants were 18 years or older, with MDD in current depressive episode of at least moderate severity as measured by Hamilton Depression Rating Scale (HDRS) (mean 19.07+2.73). 174 participants (120 women) were randomised to active (n=87) (mean age 37.09+11.14 years) or sham (n=87) (mean age 38.32+10.92 years) treatment. tDCS sessions were 5 sessions per week for 3 weeks then 3 sessions per week for 7 weeks in 10-week trial, followed by 10-week open label phase. Each session was 30 minutes, anode over left dorsolateral prefrontal cortex (DLPFC) and cathode over right DLPFC, active tDCS 2-mA, and sham tDCS 0-mA with brief ramp up and down to mimic active stimulation. In primary outcome, depressive symptoms showed significant improvement as measured by HDRS rating: active 9.41+6.25 point improvement (10-week mean 9.58+6.02) and sham 7.14+6.10 point improvement (10-week mean 11.66+5.96) (95% CI 0.51, 4.01, P = 0.012). There were no differences in discontinuation rates. In summary, 10-week home-based tDCS treatment with remotesupervision in MDD showed high efficacy, acceptability and safety

Abdominal adiposity and obstructive airway disease: testing insulin resistance and sleep disordered breathing mechanisms

Extent: 22p.Background: This study examined associations of abdominal adiposity with lung function, asthma symptoms and current doctor-diagnosed asthma and mediation by insulin resistance (IR) and sleep disordered breathing (SDB). Methods A random sample of 2500 households was drawn from the community of Whyalla, South Australia (The Whyalla Intergenerational Study of Health, WISH February 2008 - July 2009). Seven-hundred twenty-two randomly selected adults ([greater than or equal to]18 years) completed clinical protocols (32.2% response rate). Lung function was measured by spirometry. Post-bronchodilator FEV1/FVC was used to measure airway obstruction and reversibility of FEV1 was calculated. Current asthma was defined by self-reported doctor-diagnosis and evidence of currently active asthma. Symptom scores for asthma (CASS) and SDB were calculated. Intra-abdominal fat (IAF) was estimated using dual-energy x-ray absorptiometry (DXA). IR was calculated from fasting glucose and insulin concentrations. Results The prevalence of current doctor-diagnosed asthma was 19.9% (95% CI 16.7 - 23.5%). The ratio of observed to expected cases given the age and sex distribution of the population was 2.4 (95%CI 2.1, 2.9). IAF was not associated with current doctor-diagnosed asthma, FEV1/FVC or FEV1 reversibility in men or women but was positively associated with CASS independent of IR and SDB in women. A 1% increase in IAF was associated with decreases of 12mL and 20mL in FEV1 and FVC respectively in men, and 4mL and 7mL respectively in women. SDB mediated 12% and 26% of these associations respectively in men but had minimal effects in women. Conclusions In this population with an excess of doctor-diagnosed asthma, IAF was not a major factor in airway obstruction or doctor-diagnosed asthma, although women with higher IAF perceived more severe asthma symptoms which did not correlate with lower FEV1. Higher IAF was significantly associated with lower FEV1 and FVC and in men SDB mechanisms may contribute up to one quarter of this association.Matthew T Haren, Gary Misan, Tracey-Jayne Paterson, Richard E Ruffin, Janet F Grant, Jonathan D Buckley, Peter RC Howe, Jonathan Newbury, Anne W Taylor and Robyn A McDermot

Estimation of CT-derived abdominal visceral and subcutaneous adipose tissue depots from anthropometry in Europeans, South Asians and African Caribbeans

Background South Asians and African Caribbeans experience more cardiometabolic disease than Europeans. Risk factors include visceral (VAT) and subcutaneous abdominal (SAT) adipose tissue, which vary with ethnicity and are difficult to quantify using anthropometry. Objective We developed and cross-validated ethnicity and gender-specific equations using anthropometrics to predict VAT and SAT. Design 669 Europeans, 514 South Asians and 227 African Caribbeans (70±7 years) underwent anthropometric measurement and abdominal CT scanning. South Asian and African Caribbean participants were first-generation migrants living in London. Prediction equations were derived for CT-measured VAT and SAT using stepwise regression, then cross-validated by comparing actual and predicted means. Results South Asians had more and African Caribbeans less VAT than Europeans. For basic VAT prediction equations (age and waist circumference), model fit was better in men (R2 range 0.59-0.71) than women (range 0.35-0.59). Expanded equations (+ weight, height, hip and thigh circumference) improved fit for South Asian and African Caribbean women (R2 0.35 to 0.55, and 0.43 to 0.56 respectively). For basic SAT equations, R2 was 0.69-0.77, and for expanded equations it was 0.72-0.86. Cross-validation showed differences between actual and estimated VAT of <7%, and SAT of <8% in all groups, apart from VAT in South Asian women which disagreed by 16%. Conclusion We provide ethnicity- and gender-specific VAT and SAT prediction equations, derived from a large tri-ethnic sample. Model fit was reasonable for SAT and VAT in men, while basic VAT models should be used cautiously in South Asian and African Caribbean women. These equations will aid studies of mechanisms of cardiometabolic disease in later life, where imaging data are not available