Treatment of allergic rhinitis using mobile technology with real‐world data: The MASK observational pilot study

Background

Large observational implementation studies are needed to triangulate the findings from randomized control trials as they reflect “real‐world” everyday practice. In a pilot study, we attempted to provide additional and complementary insights on the real‐life treatment of allergic rhinitis (AR) using mobile technology.

Methods

A mobile phone app (Allergy Diary, freely available in Google Play and Apple App stores) collects the data of daily visual analog scales (VAS) for (i) overall allergic symptoms, (ii) nasal, ocular, and asthma symptoms, (iii) work, as well as (iv) medication use using a treatment scroll list including all medications (prescribed and over the counter (OTC)) for rhinitis customized for 15 countries.

Results

A total of 2871 users filled in 17 091 days of VAS in 2015 and 2016. Medications were reported for 9634 days. The assessment of days appeared to be more informative than the course of the treatment as, in real life, patients do not necessarily use treatment on a daily basis; rather, they appear to increase treatment use with the loss of symptom control. The Allergy Diary allowed differentiation between treatments within or between classes (intranasal corticosteroid use containing medications and oral H1‐antihistamines). The control of days differed between no [best control], single, or multiple treatments (worst control).

Conclusions

This study confirms the usefulness of the Allergy Diary in accessing and assessing everyday use and practice in AR. This pilot observational study uses a very simple assessment (VAS) on a mobile phone, shows novel findings, and generates new hypotheses.

     

Sleep and sleep ecology in the first 3 years: a web-based study

This study was designed to provide data on sleep patterns during the first 3 years, based on a large US–Canada Internet sample, to assess the prevalence of parental interventions and related factors of infant sleep ecology and to evaluate the links between sleep ecology and sleep. Five thousand six parents completed a web-based online questionnaire about their children, aged from birth to 36 months. The questionnaire included items pertaining to sleep patterns, sleep environment, sleep-related parental interventions, sleep position, and demographic information. The results reflected clear sleep-related developmental changes including a decrease in daytime sleep and total sleep time, as well as consolidation of sleep during the night, which was manifested in a decrease in night wakings and nocturnal wakefulness. Sleep ecology and parental behaviors significantly explained a portion of the variance in the child's sleep patterns. Parental interventions that encourage independence and self-soothing were associated with extended and more consolidated sleep, especially in comparison to more active interactions that were associated with shorter and more fragmented sleep. These findings provide parents and professionals reference data for assessing sleep in young children. Furthermore, the results provide information on specific ecological factors that are associated with increased risk for sleep problems.     

2B‐Alert App: A mobile application for real‐time individualized prediction of alertness

Knowing how an individual responds to sleep deprivation is a requirement for developing personalized fatigue management strategies. Here we describe and validate the 2B‐Alert App, the first mobile application that progressively learns an individual’s trait‐like response to sleep deprivation in real time, to generate increasingly more accurate individualized predictions of alertness. We incorporated a Bayesian learning algorithm within the validated Unified Model of Performance to automatically and gradually adapt the model parameters to an individual after each psychomotor vigilance test. We implemented the resulting model and the psychomotor vigilance test as a smartphone application (2B‐Alert App), and prospectively validated its performance in a 62‐hr total sleep deprivation study in which 21 participants used the app to perform psychomotor vigilance tests every 3 hr and obtain real‐time individualized predictions after each test. The temporal profiles of reaction times on the app‐conducted psychomotor vigilance tests were well correlated with and as sensitive as those obtained with a previously characterized psychomotor vigilance test device. The app progressively learned each individual’s trait‐like response to sleep deprivation throughout the study, yielding increasingly more accurate predictions of alertness for the last 24 hr of total sleep deprivation as the number of psychomotor vigilance tests increased. After only 12 psychomotor vigilance tests, the accuracy of the model predictions was comparable to the peak accuracy obtained using all psychomotor vigilance tests. With the ability to make real‐time individualized predictions of the effects of sleep deprivation on future alertness, the 2B‐Alert App can be used to tailor personalized fatigue management strategies, facilitating self‐management of alertness and safety in operational and non‐operational settings.     

Poor sleep quality associates with self‐reported psychiatric and cardiometabolic symptoms independently of sleep timing patterns in a large sample of rural and urban workers

Poor sleep associates with mental and cardiometabolic pathological outcomes. The participation of sleep timing features in the pathways by which this relationship occurs is not clear. This study aims to evaluate the interrelationship between sleep quality and self‐reported psychiatric/cardiometabolic symptoms, considering mediation and moderation effects of sleep timing patterns, and urban versus rural work environment, respectively; and to verify the association between sleep quality and polymorphisms of AANAT, RORA and TIMELESS genes. An epidemiological survey was performed in a rural area in southern Brazil. Eight‐hundred and twenty‐nine subjects were evaluated for sleep quality using the Pittsburgh Sleep Quality Index, and sleep timing patterns using the Munich Chronotype Questionnaire. Work characteristics and psychiatric/cardiometabolic symptoms were assessed using a structured self‐report questionnaire. Three polymorphisms of AANAT, RORA and TIMELESS (rs3760138, rs782931 and rs774045, respectively) were genotyped in blood samples. We found statistically significant associations of poor sleep quality with self‐reported psychiatric symptoms (B = 0.382; 95% CI 0.289–0.476; adjusted p‐value <.001), and with self‐reported cardiometabolic symptoms (B = 0.079; 95% CI 0.013–0.151; adjusted p‐value = .048). The genetic analysis showed that RORA GA/AA genotype was associated to poor sleep quality (B = 0.146, 95% CI 0.054–0.239; adjusted p‐value = .004). No moderated mediation effects were observed in the conditional analysis. TIMELESS polymorphism was not included in the analysis due to the low frequency of risk genotypes. These results yield new insights regarding the interrelationship between sleep characteristics and psychiatric/cardiometabolic self‐reported symptoms, taking into account genes related to the biological clocks and melatonin pathways.     

Insomnia as a mediating therapeutic target for depressive symptoms: A sub‐analysis of participant data from two large randomized controlled trials of a digital sleep intervention

Insomnia predicts the onset of depression, commonly co‐presents with depression and often persists following depression remission. However, these conditions can be challenging to treat concurrently using depression‐specific therapies. Cognitive behavioural therapy for insomnia may be an appropriate treatment to improve both insomnia and depressive symptoms. We examined the effects of a fully‐automated digital cognitive behavioural therapy intervention for insomnia (Sleepio) on insomnia and depressive symptoms, and the mediating role of sleep improvement on depressive symptoms in participants from two randomized controlled trials of digital cognitive behavioural therapy for insomnia. We also explored potential moderators of intervention effects. All participants met criteria for probable insomnia disorder and had clinically significant depressive symptomatology (PHQ‐9 ≥ 10; n = 3,352). Individuals allocated to treatment in both trials were provided access to digital cognitive behavioural therapy. Digital cognitive behavioural therapy significantly improved insomnia (p < .001; g = 0.76) and depressive symptoms (p < .001; g = 0.48) at post‐intervention (weeks 8–10), and increased the odds (OR = 2.9; 95% CI = 2.34, 3.65) of clinically significant improvement in depressive symptoms (PHQ‐9 < 10). Improvements in insomnia symptoms at mid‐intervention mediated 87% of the effects on depressive symptoms at post‐intervention. No variables moderated effectiveness outcomes, suggesting generalizability of these findings. Our results suggest that effects of digital cognitive behavioural therapy for insomnia extend to depressive symptoms in those with clinically significant depressive symptomatology. Insomnia may, therefore, be an important therapeutic target to assist management of depressive symptoms.     

The two‐process model of sleep regulation: a reappraisal

In the last three decades the two‐process model of sleep regulation has served as a major conceptual framework in sleep research. It has been applied widely in studies on fatigue and performance and to dissect individual differences in sleep regulation. The model posits that a homeostatic process (Process S) interacts with a process controlled by the circadian pacemaker (Process C), with time‐courses derived from physiological and behavioural variables. The model simulates successfully the timing and intensity of sleep in diverse experimental protocols. Electrophysiological recordings from the suprachiasmatic nuclei (SCN) suggest that S and C interact continuously. Oscillators outside the SCN that are linked to energy metabolism are evident in SCN‐lesioned arrhythmic animals subjected to restricted feeding or methamphetamine administration, as well as in human subjects during internal desynchronization. In intact animals these peripheral oscillators may dissociate from the central pacemaker rhythm. A sleep/fast and wake/feed phase segregate antagonistic anabolic and catabolic metabolic processes in peripheral tissues. A deficiency of Process S was proposed to account for both depressive sleep disturbances and the antidepressant effect of sleep deprivation. The model supported the development of novel non‐pharmacological treatment paradigms in psychiatry, based on manipulating circadian phase, sleep and light exposure. In conclusion, the model remains conceptually useful for promoting the integration of sleep and circadian rhythm research. Sleep appears to have not only a short‐term, use‐dependent function; it also serves to enforce rest and fasting, thereby supporting the optimization of metabolic processes at the appropriate phase of the 24‐h cycle.     

Mental health problems in adolescents with delayed sleep phase: results from a large population‐based study in Norway

The aim of the current study was to compare mental health problems, resilience and family characteristics in adolescents with and without delayed sleep phase (DSP) in a population‐based sample. Data were taken from the youth@hordaland‐survey, a large population‐based study in Hordaland County in Norway conducted in 2012. In all, 9338 adolescents aged 16–19 years (53.5% girls) provided self‐reported data on a wide range of instruments assessing mental health symptoms, including depression, anxiety, obsessive–compulsive behaviours, attention deficit hyperactive disorder (ADHD) symptoms, perfectionism, resilience and sleep. Measures of socioeconomic status were also included. Three hundred and six adolescents (prevalence 3.3%) were classified as having DSP [according to the International Classification of Sleep Disorders‐2 (ICSD‐2)] criteria. Adolescents with DSP reported higher levels of depression, anxiety and ADHD symptoms. Adolescents with DSP also exhibited significantly lower levels of resilience. The Cohen's d effect sizes ranged from small [obsessive–compulsive disorder (OCD): d = 0.15] to moderate (inattention: d = 0.71). In the fully adjusted model, the significant predictors of DSP included inattention [odds ratio (OR): 2.11], lack of personal structure (OR: 2.07), low (OR: 1.85) and high (OR: 1.91) paternal education, parents not living together (OR: 1.81), hyperactivity/inattention (OR: 1.71) and poorer family economy (OR: 1.59). In conclusion, the high symptom load across a range of mental health measures suggests that a broad and thorough clinical approach is warranted when adolescents present with DSP.     

Self‐reported sleep quality is more closely associated with mental and physical health than chronotype and sleep duration in young adults: A multi‐instrument analysis

Sleep and circadian rhythms are considered to be important determinants of mental and physical health. Epidemiological studies have established the contribution of self‐reported sleep duration, sleep quality and chronotype to health outcomes. Mental health and sleep problems are more common in women and men are more likely to be evening types. Few studies have compared the relative strength of these contributions and few studies have assessed these contributions separately in men and women. Furthermore, sleep and circadian characteristics are typically assessed with a limited number of instruments and a narrow range of variables is considered, leaving the understanding of the relative contribution of different predictors somewhat fractionary. We compared sleep quality, sleep duration and chronotype as predictors for self‐reported mental and physical health and psychological characteristics in 410 men and 261 women aged 18 to 30. To ascertain that results were not dependent on the use of specific instruments we used a multitude of validated instruments including the Morningness‐Eveningness‐Questionnaire, Munich‐ChronoType‐Questionnaire, Pittsburgh‐Sleep‐Quality‐Index, British‐Sleep‐Survey, Karolinska‐Sleep‐Diary, Insomnia‐Severity‐Index, SF‐36‐Health Survey, General‐Health‐Questionnaire, Dutch‐Eating‐Behaviour‐Questionnaire, Big‐Five‐Inventory, Behaviour‐Inhibition‐System‐Behaviour‐Activation‐System, and the Positive‐Affect‐Negative‐Affect‐Schedule. Relative contributions of predictors were quantified as local effect sizes derived from multiple regression models. Across all questionnaires, sleep quality was the strongest independent predictor of health and in particular mental health and more so in women than in men. The effect of sleep duration and social jetlag was inconspicuous. A greater insight into the independent contributions of sleep quality and chronotype may aid the understanding of sleep‐health interactions in women and men.     

An approach to understanding sleep and depressed mood in adolescents: person‐centred sleep classification

Depressive mood in youth has been associated with distinct sleep dimensions, such as timing, duration and quality. To identify discrete sleep phenotypes, we applied person‐centred analysis (latent class mixture models) based on self‐reported sleep patterns and quality, and examined associations between phenotypes and mood in high‐school seniors. Students (n = 1451; mean age = 18.4 ± 0.3 years; 648 M) completed a survey near the end of high‐school. Indicators used for classification included school night bed‐ and rise‐times, differences between non‐school night and school night bed‐ and rise‐times, sleep‐onset latency, number of awakenings, naps, and sleep quality and disturbance. Mood was measured using the total score on the Center for Epidemiologic Studies‐Depression Scale. One‐way anova tested differences between phenotype for mood. Fit indexes were split between 3‐, 4‐ and 5‐phenotype solutions. For all solutions, between phenotype differences were shown for all indicators: bedtime showed the largest difference; thus, classes were labelled from earliest to latest bedtime as ‘A’ (n = 751), ‘B’ (n = 428) and ‘C’ (n = 272) in the 3‐class solution. Class B showed the lowest sleep disturbances and remained stable, whereas classes C and A each split in the 4‐ and 5‐class solutions, respectively. Associations with mood were consistent, albeit small, with class B showing the lowest scores. Person‐centred analysis identified sleep phenotypes that differed in mood, such that those with the fewest depressive symptoms had moderate sleep timing, shorter sleep‐onset latencies and fewer arousals. Sleep characteristics in these groups may add to our understanding of how sleep and depressed mood associate in teens.     

Maternal postpartum stress and toddler developmental delays: Results from a multisite study of racially diverse families

Maternal psychosocial stress during pregnancy can adversely influence child development, but few studies have investigated psychosocial stress during the postpartum period and its association with risk of toddler developmental delays. Moreover, given the expanding diversity of the U.S. population, and well-documented health and stress disparities for racial and ethnic minorities, research examining the effect of postpartum stress on risk of developmental delays in diverse populations is of critical importance. In this study, data from the Community Child Health Network provided the opportunity to test maternal postpartum stress as a predictor of toddler risk of developmental delay in a sample of African American, Latina and non-Hispanic White women and their toddlers (N = 1537) recruited in urban, suburban, and rural communities. Postpartum maternal stress over 1 year was operationalized as perceived stress, life events, and negative impact of life events. Regression results revealed higher risk of developmental delays in toddlers whose mothers experienced more negative life events, greater negative impact of events, and higher perceived stress over the year. Prenatal stress, pregnancy/birth complications, and postpartum depression did not explain these associations. Maternal postpartum stress may contribute to increased risk for developmental delays and is an important target for psychosocial intervention.     

Development and application of a one‐step real‐time RT‐PCR using a minor‐groove‐binding probe for the detection of a novel bunyavirus in clinical specimens

A highly sensitive one‐step real‐time RT‐PCR method using a minor‐groove‐binding (MGB) probe was developed for detection and quantitation of severe febrile with thrombocytopenia syndrome virus (SFTSV). The assay could discriminate SFTSV infection from other related viral diseases in human with a minimum detection limit of 10 viral RNA copies/µl and was 1,000 times more sensitive than the conventional PCR. Strong linear correlations (r² > 0.99) between the C_t values and viral RNA standards over a linear range were obtained. The coefficients of variation of intra‐ and inter‐assay reproducibility were both less than 2%. The RT‐PCR was also shown to be highly specific, as no positive signals were detected for other related viruses. Evaluation of this assay with serum samples from laboratory confirmed cases and healthy donors showed 100% clinical diagnostic sensitivity and over 99% specificity. Clinical application with samples from 287 patients admitted to the hospital with suspected SFTSV infection showed that 15% were infected by SFTSV. This assay was rapid, requiring just over 2 hr, including the nucleic acid extraction step. J. Med. Virol. 85:370–377, 2013. © 2012 Wiley Periodicals, Inc.     

Parenting Coordination: Applying Clinical Thinking to the Management and Resolution of Post‐Divorce Conflict

There is a small but significant number of parents who remain stuck in a high level of conflict with each other after the legal conclusion of their divorce. Exposure to chronically high levels of parental conflict is a strong risk factor negatively affecting both children's short‐ and long‐term adjustment. Parenting coordination is a nonadversarial, child‐focused dispute‐resolution process designed to help divorced parents contain their conflict to protect children from its negative effect. Parenting coordination is a hybrid role combining different skills and conflict‐resolution approaches. In high‐conflict divorce, each parent's internalization of relationship patterns constructed from past experiences contributes to the intractable nature of the interparent conflict. A case presentation illustrates how this clinical perspective enhances the parenting coordinator's ability to work with parents to manage and contain their parenting conflicts with each other.     

Hypoxia‐induced changes in recovery sleep,core body temperature,urinary 6‐sulphatoxymelatonin and free cortisol after a simulated long‐duration flight

Fatigue and sleep disorders often occur after long‐haul flights, even when no time zones are crossed. In this controlled study, we assessed the effects of two levels of hypoxia (at 8000 ft and 12 000 ft) on recovery sleep. Core body temperature (CBT), a circadian marker, urinary 6‐sulphatoxymelatonin and free cortisol were studied in 20 young healthy male volunteers exposed for 8 h (08:00–16:00 hours) in a hypobaric chamber to a simulated cabin altitude of 8000 ft and, 4 weeks later, 12 000 ft. Each subject served as his own control. Sleep was recorded by polysomnography for three consecutive nights for each exposure. CBT was monitored by telemetry during the three 24‐h cycles (control, hypoxic exposure and recovery). Free urinary cortisol and 6‐sulphatoxymelatonin levels were assayed twice daily between 08:00 and 20:00 hours (day) and between 20:00 and 08:00 hours (night). We showed significant changes in circadian patterns of CBT at both altitudes, suggesting a phase delay, and changes in recovery sleep but only at 12 000 ft. We observed an increase in sleep onset latency which correlated positively with the increase in CBT levels during the first recovery night and a decrease in the duration of stage N₂ (formerly S₂), which correlated negatively with the mid‐range crossing time, a reliable phase marker of CBT rhythm. This study shows clearly the impact of hypobaric hypoxia on circadian time structure during air flights leading to a phase delay of CBT, independent of jet lag and consequences on sleep during recovery.