Effect of simulated dawn on quality of sleep – a community-based trial

BACKGROUND: Morning light exposure administered as simulated dawn looks a promising method to treat Seasonal Affective Disorder, but it may moreover help with resetting the inaccurate organisation of body clock functions relative to sleep occurring in winter among people in general. Disturbances in sleep patterns are common and may compromise wellbeing even in the short term. Our hypothesis was that simulated dawn could improve the subjective quality of sleep during winter. METHODS: A community-based trial with 100 volunteer subjects provided with dawn simulators. Study period lasted for eight weeks, and subjects used the dawn simulators for two weeks at a time, each subject acting as his own control (ABAB-design). Main outcome measure was subjective quality of sleep recorded each morning with Groningen Sleep Quality Scale. RESULTS: 77 subjects completed the trial. Quality of sleep improved while subjects were using dawn simulator-devices (p = 0.001). The treatment became beneficial after six days' use of dawn simulator, but the effect did not last after the use was ceased. CONCLUSION: Dawn simulation may help to improve the subjective quality of sleep, but the benefits are modest. Further research is needed to verify these findings and to elucidate the mechanism by which dawn simulation acts on the sleep-wake pattern

Chronotype changes with age; seven-year follow-up from the Netherlands study of depression and anxiety cohort

Background: Chronotype reflects an individual's optimal daily timing of sleep, activity, and cognitive performance. Previous, cross-sectional, studies have suggested an age effect on chronotype with later chronotypes in adolescents and earlier chronotypes in children and elderly. Additionally, later chronotypes have been associated with more depressive symptoms. Few studies have been able to study longitudinal associations between chronotype and age, while adjusting for depressive symptoms. Methods: Chronotype was assessed twice with the Munich Chronotype Questionnaire 7 years apart in the Netherlands Study of Depression and Anxiety (T1: N = 1842, mean age (SD): 42.63 years (12.66)) and T2: N = 1829, mean age (SD) 50.67 (13.11)). The longitudinal association between change in age and change in chronotype was tested using a generalized estimated equation analysis adjusted for covariates (including level of depressive symptoms). Using age-bins of 5 years (age at T2), change in chronotype between T1 and T2 was analyzed with Linear Mixed Models. Results: We found a change towards an earlier chronotype with higher age (B (95% CI): -0.011 (-0.014-0.008), p < 0.001). For the age-bins, the difference in chronotype was significant for the 25-29 years age-bin. Limitations: The sample did not include individuals younger than 19 years or older than 68 years. Conclusions: In the whole sample chronotype changed towards becoming more morning-type over a period of 7 years, but this change was only significant for those aged 25-29 years. The study was performed in a large naturalistic cohort study with a wide age-range, including patients with a diagnosis of depressive and anxiety disorder and healthy controls.Stress and Psychopatholog

Psychometric testing of the Dutch evaluation of daily activity questionnaire in rheumatoid arthritis

Background: The Evaluation of Daily Activity Questionnaire (EDAQ) is a patient reported measure of activity limitations in Rheumatoid Arthritis (RA) and other musculoskeletal conditions, for which there is a Swedish (1) and an updated English version (2-4). The English version was translated into Dutch, and linguistically validated, with phrasing changes made following cognitive debriefing interviews with six Dutch people with RA. The Dutch EDAQ includes 138 items in 14 ‘domains’ (Eating/ Drinking; Personal Care; Dressing; Bathing; Cooking; Moving Indoors; House Cleaning; Laundry; Moving and Transfers; Moving Outdoors; Gardening/Household Maintenance; Caring; and Leisure/ Social Activities). Each domain is split into two sections: one (A) scores whether activities can be performed without aids, alternate methods or help; and another (B) which scores whether the activities can be performed with aids or alternate methods. All items are scored on a 0-3 scale (no difficulty to unable to do). Objectives: To test the reliability and validity of the Dutch version of the EDAQ in people with RA in the Netherlands. Methods: Participants from an out-patient Rheumatology clinic (Reinier de Graaf Hospital, Delft) completed postal questionnaires of demographic questions, the EDAQ, HAQ, SF36v2, RAQOL, a hand pain numeric rating scale (NRS) and a current condition severity scale. Three weeks later, the EDAQ was mailed again. Test-retest reliability of domain scores was evaluated using nonparametric correlations. Internal consistency was tested using Cronbach’s alpha. Validity of the 14 domains of the EDAQ against the other measures was assessed with non-parametric correlations. Results: 252 people participated: 155 women and 93 men; age = 65.16 (SD 13.45) years; RA duration =11.75 years (SD 9.93). 68 (27%) were employed; 20 had children <18y at home. Average pain score = 3 (IQR 1-6) and fatigue = 4 (IQR 2-7). 155 (62%) completed Test 2 and test-retest reliability of total domain scores was excellent for nine domains (rs= 0.81 -0.88) and moderate-substantial for five (rs=0.56-0.78). Internal consistency was high in all domains: Cronbach’s alpha= 0.79-0.92 for Section A. All domains of the EDAQ correlated significantly (p<0.001) with: HAQ rs= 0.51- 0.88; SF36v2 (Physical Function) rs= -0.55 to -0.87; SF36v2 Bodily Pain rs=0.44-0.67; SF36v2 (Vitality) rs= -0.35 to-0.62; RAQOL rs= 0.50-0.83; and hand pain rs=0.46-0.64. An exception was the ‘Caring’ domain as many did not have childcare responsibilities, and thus validity was lower compared to the above variables, although still significant (p<0.01; rs=0.16 to 0.31). Conclusions: The Dutch version of the EDAQ is a valid and reliable measure of daily activity in people with RA. It can be used in both clinical practice and research. References: (1) Nordenskiold et al (1998) Clin Rheumatol 17:6-16. (2) Hammond et al (2015) HQLO 12:143; (3) Hammond et al (2015) Rheumatology 54:1605-1615. (4) Hammond et al (2015) Br J Occ Ther 78:144-157. Acknowledgement: This research was funded by a EULAR Health Professionals Research Grant

Dried blood spot UHPLC-MS/MS analysis of oseltamivir and oseltamivircarboxylate—a validated assay for the clinic

The neuraminidase inhibitor oseltamivir (Tamiflu®) is currently the first-line therapy for patients with influenza virus infection. Common analysis of the prodrug and its active metabolite oseltamivircarboxylate is determined via extraction from plasma. Compared with these assays, dried blood spot (DBS) analysis provides several advantages, including a minimum sample volume required for the measurement of drugs in whole blood. Samples can easily be obtained via a simple, non-invasive finger or heel prick. Mainly, these characteristics make DBS an ideal tool for pediatrics and to measure multiple time points such as those needed in therapeutic drug monitoring or pharmacokinetic studies. Additionally, DBS sample preparation, stability, and storage are usually most convenient. In the present work, we developed and fully validated a DBS assay for the simultaneous determination of oseltamivir and oseltamivircarboxylate concentrations in human whole blood. We demonstrate the simplicity of DBS sample preparation, and a fast, accurate and reproducible analysis using ultra high-performance liquid chromatography coupled to a triple quadrupole mass spectrometer. A thorough validation on the basis of the most recent FDA guidelines for bioanalytical method validation showed that the method is selective, precise, and accurate (≤15% RSD), and sensitive over the relevant clinical range of 5–1,500 ng/mL for oseltamivir and 20–1,500 ng/mL for the oseltamivircarboxylate metabolite. As a proof of concept, oseltamivir and oseltamivircarboxylate levels were determined in DBS obtained from healthy volunteers who received a single oral dose of Tamiflu®