A new EEG biomarker of neurobehavioural impairment and sleepiness in sleep apnea patients and controls during extended wakefulness

ObjectiveTo explore the use of detrended fluctuation analysis (DFA) scaling exponent of the awake electroencephalogram (EEG) as a new alternative biomarker of neurobehavioural impairment and sleepiness in obstructive sleep apnea (OSA).MethodsEight patients with moderate–severe OSA and nine non-OSA controls underwent a 40-h extended wakefulness challenge with resting awake EEG, neurobehavioural performance (driving simulator and psychomotor vigilance task) and subjective sleepiness recorded every 2-h. The DFA scaling exponent and power spectra of the EEG were calculated at each time point and their correlation with sleepiness and performance were quantified.ResultsDFA scaling exponent and power spectra biomarkers significantly correlated with simultaneously tested performance and self-rated sleepiness across the testing period in OSA patients and controls. Baseline (8am) DFA scaling exponent but not power spectra were markers of impaired simulated driving after 24-h extended wakefulness in OSA (r = 0.738, p = 0.037). OSA patients had a higher scaling exponent and delta power during wakefulness than controls.ConclusionsThe DFA scaling exponent of the awake EEG performed as well as conventional power spectra as a marker of impaired performance and sleepiness resulting from sleep loss.SignificanceDFA may potentially identify patients at risk of neurobehavioural impairment and assess treatment effectiveness.     

ApoA-I Induction as a Potential Cardioprotective Strategy: Rationale for the SUSTAIN and ASSURE Studies

Background  

Considerable interest has focused on the development of therapies that target the functionality of high-density lipoproteins (HDL). Upregulation of endogenous synthesis of the major protein on HDL particles, apolipoprotein A-I (apoA-I), represents a novel approach to generation of new HDL particles. The Study of Quantitative Serial Trends in Lipids with Apolipoprotein A-I Stimulation (SUSTAIN, NCT01423188) study aims to evaluate the lipid efficacy, safety and tolerability of an apoA-I inducer (RVX-208). The ApoA-I Synthesis Stimulation and Intravascular Ultrasound for Coronary Atheroma Regression Evaluation (ASSURE, NCT01067820) study aims to evaluate the effect of RVX-208 on plaque burden.     

Nutritional intake and oxidative stress in chronic heart failure

Background and aimsPatients with chronic heart failure (CHF) are known to be at risk of malnutrition, and cardiac cachexia is an adverse prognostic indicator. The aim of this study was to determine the dietary adequacy of CHF patients compared with Dietary Reference Values, to compare the nutritional intake and status of CHF patients to a healthy comparison group, and finally to determine whether nutritional intake and status depended on New York Heart Association (NYHA) functional class.Methods and ResultsPatients with CHF (n = 39) and a comparison group of 27 healthy participants, who did not have CHF, were asked to complete a four-day food diary, and energy and nutrient intakes were calculated. F_2α-isoprostanes were measured in urine as an indicator of oxidative stress and antioxidants were measured in serum or plasma. Overall 73% of the CHF patients were consuming less than recommended energy intakes, and more than 50% of these patients were also consuming less than recommended vitamin D, selenium and zinc intakes. Nutrient intake (energy, vitamin B6, D, E, iron, folate and riboflavin) was lower in CHF patients than in the comparison group, with vitamin B6 and folate intake and antioxidant status decreasing, and isoprostane status increasing as NYHA functional class increased.ConclusionThe majority of CHF patients do not meet dietary reference values for energy and a range of nutrients, and nutrient intake is lower in CHF patients than in healthy individuals. Dietary inadequacy tends to be increased in those with more severe disease.     

Characteristics of AZD9708, a novel, selective β2-adrenoceptor agonist with rapid onset and long duration of action

Here we describe the pre-clinical pharmacological profile of AZD9708, a novel long-acting β₂-adrenoceptor agonist that has potential as a once-daily therapy for asthma and chronic obstructive pulmonary disease (COPD).AZD9708 is a potent and selective agonist at the human β₂-adrenoceptor, with selectivity over human β₁- and β₃-adrenoceptors of >500 and >24 fold, respectively. AZD9708 relaxes carbachol-induced contraction of human bronchial rings with a time to 90% of maximal relaxation of 13–20 min, similar to that seen with formoterol and quicker than salmeterol. In anesthetized guinea pigs, AZD9708 provides significant protection against histamine-induced airway constriction at 24 h after intratracheal and nebulized doses. This is longer than with intratracheal salmeterol, which is bronchoprotective for approximately 8 h, and formoterol, which is bronchoprotective for 8 and 12 h following nebulized and intratracheal dosing, respectively.AZD9708 also shows the potential for a greater therapeutic margin than widely used β₂-adrenoceptor agonists such as formoterol. At a defined efficacy dose that provides 80% bronchoprotection (ED₈₀), formoterol leads to a decrease in blood potassium levels in guinea pigs, whilst AZD9708 is not associated with significant reductions in potassium levels at doses up to 7 times the ED₈₀. [¹⁴C]AZD9708 is associated with extensive protein binding in both human (mean 1.0% free) and rat (mean 2.6% free) plasma.This pharmacological profile indicates the potential of AZD9708 to become an important addition to the range of bronchodilators available for the treatment of patients with obstructive airways disease.     

Development of a robotic walker for individuals with cerebral palsy

Abstract

Objective: This study describes the first use of a robotic walker in youth and young adults with cerebral palsy (CP) Gross Motor Function Classification (GMFCS) IV.

Methods: Semi-structured interviews were conducted before and after each robotic walker trial. Interviews were recorded, then transcribed and subjected to thematic analysis.

Results: Five participants (4 male, 13–22?years of age) with quadriplegia secondary to CP were recruited. Four individuals with mixed tone quadriplegia GMFCS IV were able to independently walk with the device. One individual with significant dyskinesia was unable to utilize the device. The assessment team included two physiotherapists, an occupational therapist, a physiatrist and three engineers. Major themes related to physical and social impacts were identified. Some physical advantages include the ability to walk hands-free and promotion of physical fitness. Examples of physical barriers include limited harness design and large device size. Social advantages include increased independence and peer engagement. Finally, a social disadvantage identified was limited use on uneven terrains.

Discussion: Suggestions for modifications for identified challenges and disadvantages include decreasing the size of the robotic walker, more harness designs, decreasing the force required to take an initial step, adding a joy stick for user control and creating a more versatile base that can be used on different terrains such as ice or baseball fields.

Conclusion: Robotics holds great hope for individuals with CP where mobility options are limited. Physical and social advantages are evident. Recommendations for future improvement and studies of use in exercise and participation are provided.

• IMPLICATIONS FOR REHABILITATION

• As youth and young adults with cerebral palsy age, options for mobilization can become limited with challenges in placing them in a walking device due to size and numerous other physical limitations.

• A robotic walker with a built-in mechanical lift is available for individuals with cerebral palsy.

• This study was able to gather important information and recommendations to tailor a new robotic walker prototype specifically for individuals with cerebral palsy.