Adolescents with Obstructive Sleep Apnea Adhere Poorly to Positive Airway Pressure (PAP), but PAP Users Show Improved Attention and School Performance

Background: Obstructive Sleep Apnea (OSA) is associated with medical and neurobehavioral morbidity across the lifespan. Positive airway pressure (PAP) treatment has demonstrated efficacy in treating OSA and has been shown to improve daytime functioning in adults, but treatment adherence can be problematic. There are nearly no published studies examining functional outcomes such as academic functioning in adolescents treated with PAP. This study was conducted as an initial step towards determining whether PAP treatment improves daytime functioning among adolescents with OSA. Methods: Self-reported academic grades, self- and parent-reported academic quality of life, and objectively-measured attention were assessed before and after PAP was clinically initiated in a sample of 13 obese adolescents with OSA, as well as 15 untreated obese Controls without OSA. Based on adherence data, the treated group was divided into PAP Users (n = 6) and Non-Adherent participants (n = 7). Results: Though demographically similar, the three groups significantly differed in how their academic performance and attention scores changed from baseline to follow-up. Non-Adherent participants showed worsening functioning over time, while PAP Users showed stable or improved functioning, similar to controls. Conclusion: Although many adolescents prescribed PAP for OSA are non-adherent to the treatment, those who adhere t

Experimental and Human Evidence for Lipocalin-2 (Neutrophil Gelatinase-Associated Lipocalin [NGAL]) in the Development of Cardiac Hypertrophy and heart failure

Background-Cardiac hypertrophy increases the risk of developing heart failure and cardiovascular death. The neutrophil inflammatory protein, lipocalin-2 (LCN2/NGAL), is elevated in certain forms of cardiac hypertrophy and acute heart failure. However, a specific role for LCN2 in predisposition and etiology of hypertrophy and the relevant genetic determinants are unclear. Here, we defined the role of LCN2 in concentric cardiac hypertrophy in terms of pathophysiology, inflammatory expression networks, and genomic determinants. Methods and Results-We used 3 experimental models: a polygenic model of cardiac hypertrophy and heart failure, a model of intrauterine growth restriction and Lcn2-knockout mouse; cultured cardiomyocytes; and 2 human cohorts: 114 type 2 diabetes mellitus patients and 2064 healthy subjects of the YFS (Young Finns Study). In hypertrophic heart rats, cardiac and circulating Lcn2 was significantly overexpressed before, during, and after development of cardiac hypertrophy and heart failure. Lcn2 expression was increased in hypertrophic hearts in a model of intrauterine growth restriction, whereas Lcn2-knockout mice had smaller hearts. In cultured cardiomyocytes, Lcn2 activated molecular hypertrophic pathways and increased cell size, but reduced proliferation and cell numbers. Increased LCN2 was associated with cardiac hypertrophy and diastolic dysfunction in diabetes mellitus. In the YFS, LCN2 expression was associated with body mass index and cardiac mass and with levels of inflammatory markers. The single-nucleotide polymorphism, rs13297295, located near LCN2 defined a significant cis-eQTL for LCN2 expression. Conclusions-Direct effects of LCN2 on cardiomyocyte size and number and the consistent associations in experimental and human analyses reveal a central role for LCN2 in the ontogeny of cardiac hypertrophy and heart failure.Peer reviewe

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Cross-Group Comparisons on Descriptive Variables and Change Over Time in School Performance and Attention.

<p>Group data refer to percents for sex and race, and mean ± standard deviation for all others. Body Mass Index (BMI)  =  (mass in kg)/(height in m)². Age- and sex-adjusted BMI conversion made per US Centers for Disease Control and Prevention. Obstructive Index  =  OSA severity as indexed by the number of obstructive apneas + hypopneas per hour of sleep (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0016924#pone.0016924-Beebe3" target="_blank">[3]</a>). QOL  =  Quality of Life.</p

Change over time in sustained attention/vigilance and academic performance among adolescents who used PAP, those who were non-adherent to PAP treatment, and untreated controls.

<p>Error bars reflect the standard error of the mean. Higher scores denote better functioning. Self-reported academic grades are expressed according to the US 4-point convention (max  = 4.0; see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0016924#pone.0016924-Beebe3" target="_blank">[3]</a>). Vigilance is expressed as an age-adjusted z-score compared to published norms <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0016924#pone.0016924-Gordon1" target="_blank">[14]</a>. Academic quality of life is expressed on the 0–100 scale used by the Peds-QL, on which completely healthy individuals average around 80 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0016924#pone.0016924-Varni1" target="_blank">[13]</a>.</p

Contribution of behavior therapy to dietary treatment in cystic fibrosis: A randomized controlled study with 2-year follow-up

Behavioral intervention (BI) was compared to nutrition education (NE) to better understand the contribution of behavior therapy to nutrition management in children with cystic fibrosis (CF). Participants were 7 children between 6 and 12 years of age with weight for age percentiles ranging from the 3rd to the 27th. Families in each condition were seen for 7 sessions and provided the same nutrition information and calorie goals. The BI received training on child behavior management. Caloric intake across meals was evaluated via multiple baseline design. Results indicated that the BI had a greater increase in daily caloric intake (1,036 cal/day) and weight gain (1.42 kg) than the NE (408 cal/day, 0.78 kg). Improved caloric intake was maintained 2 years following treatment