Preliminary evidence of psychological improvements and increased maternal-fetal attachment associated with a mindfulness sleep programme: secondary analysis of uncontrolled data in 11 pregnant women with insomnia disorder.

Treating insomnia during pregnancy improves sleep and depressed mood. However, given well-established links between poor sleep and a broad spectrum of adverse maternal outcomes, the benefits of insomnia care may reach beyond sleep and depression. The present study evaluated the preliminary efficacy of 'Perinatal Understanding of Mindful Awareness for Sleep' (PUMAS)-a mindfulness sleep programme tailored to pregnancy that combines behavioural sleep strategies and meditation-for enhancing everyday mindfulness and maternal-fetal attachment, as well as for alleviating anxiety, repetitive thinking, and sleep-related daytime impairment. We conducted a secondary analysis of a single-arm proof-of-concept trial of 11 pregnant women with fifth edition of the Diagnostic and Statistical Manual of Mental Disorders diagnosed insomnia disorder who completed PUMAS (six sessions), which was delivered in an individual format via telemedicine video. Pre- and post-treatment outcomes included the Cognitive and Affective Mindfulness Scale-Revised (CAMS-R), Maternal-Fetal Attachment Scale (MFAS), Generalised Anxiety Disorder seven-item survey (GAD-7), Perseverative Thinking Questionnaire (PTQ), Daytime Insomnia Symptoms Response Scale (DISRS), and the Patient-Reported Outcomes Measurement Information System Sleep-Related Impairment Scale (PROMIS-SRI). Symptom changes were evaluated with paired-samples t tests. Results showed PUMAS patients reported large increases in CAMS-R (Cohen's dz = 1.81) and medium-large increases in MFAS scores (Cohen's dz = 0.73). Moreover, PUMAS patients reported large reductions in scores on the GAD-7 (Cohen's dz = 1.09), PTQ (Cohen's dz = 1.26), DISRS (Cohen's dz = 1.38), and PROMIS-SRI (Cohen's dz = 1.53). Preliminary evidence suggests that a mindfulness-based perinatal sleep programme may benefit several domains of maternal wellbeing beyond sleep and depression. PUMAS substantially enhanced patient ratings of everyday mindfulness and maternal-fetal attachment, while reporting alleviations in anxiety, perseverative thinking, insomnia-focused rumination, and sleep-related daytime impairment.

The Combination of Aroxybutynin and Atomoxetine in the Treatment of Obstructive Sleep Apnea (MARIPOSA): A Randomized Controlled Trial.

Rationale: Obstructive sleep apnea (OSA) is a common sleep disorder for which the principal treatment option, continuous positive airway pressure, is often poorly tolerated. There is currently no approved pharmacotherapy for OSA. However, recent studies have demonstrated improvement in OSA with combined antimuscarinic and noradrenergic drugs. Objectives: The aim of this study was to evaluate the efficacy and safety of AD109, a combination of the novel antimuscarinic agent aroxybutynin and the norepinephrine reuptake inhibitor atomoxetine, in the treatment of OSA. Methods: Phase II randomized, double-blind, placebo-controlled, parallel-group, 4-week trial comparing AD109 2.5/75 mg, AD109 5/75 mg, atomoxetine 75 mg alone, and placebo (www.clinicaltrials.gov identifier NCT05071612). Measurements and Main Results: Of 211 randomized patients, 181 were included in the prespecified efficacy analyses. Sleep was assessed by two baseline and two treatment polysomnograms. Apnea-hypopnea index with a 4% desaturation criterion (primary outcome) was reduced from a median (IQR) of 20.5 (12.3-27.2) to 10.8 (5.6-18.5) in the AD109 2.5/75 mg arm (-47.1%), from 19.4 (13.7-26.4) to 9.5 (6.1-19.3) in the AD109 5/75 mg arm (-42.9%; both P < 0.0001 vs. placebo), and from 19.0 (11.8-28.8) to 11.8 (5.5-21.5) with atomoxetine alone (-38.8%; P < 0.01 vs. placebo). Apnea-hypopnea index with a 4% desaturation criterion decreased from 20.1 (11.9-25.9) to 16.3 (11.1-28.9) in the placebo arm. Subjectively, there was improvement in fatigue with AD109 2.5/75 mg (P < 0.05 vs. placebo and atomoxetine). Atomoxetine taken alone decreased total sleep time (P < 0.05 vs. AD109 and placebo). The most common adverse events were dry mouth, insomnia, and urinary hesitancy. Conclusions: AD109 showed clinically meaningful improvement in OSA, suggesting that further development of the compound is warranted. Clinical trial registered with www.clinicaltrials.gov (NCT05071612).

Improved resilience following digital cognitive behavioral therapy for insomnia protects against insomnia and depression one year later.

BACKGROUND: While the negative consequences of insomnia are well-documented, a strengths-based understanding of how sleep can increase health promotion is still emerging and much-needed. Correlational evidence has connected sleep and insomnia to resilience; however, this relationship has not yet been experimentally tested. This study examined resilience as a mediator of treatment outcomes in a randomized clinical trial with insomnia patients. METHODS: Participants were randomized to either digital cognitive behavioral therapy for insomnia (dCBT-I; n = 358) or sleep education control (n = 300), and assessed at pre-treatment, post-treatment, and 1-year follow-up. A structural equation modeling framework was utilized to test resilience as a mediator of insomnia and depression. Risk for insomnia and depression was also tested in the model, operationalized as a latent factor with sleep reactivity, stress, and rumination as indicators (aligned with the 3-P model). Sensitivity analyses tested the impact of change in resilience on the insomnia relapse and incident depression at 1-year follow-up. RESULTS: dCBT-I resulted in greater improvements in resilience compared to the sleep education control. Furthermore, improved resilience following dCBT-I lowered latent risk, which was further associated with reduced insomnia and depression at 1-year follow-up. Sensitivity analyses indicated that each point improvement in resilience following treatment reduced the odds of insomnia relapse and incident depression 1 year later by 76% and 65%, respectively. CONCLUSIONS: Improved resilience is likely a contributing mechanism to treatment gains following insomnia therapy, which may then reduce longer-term risk for insomnia relapse and depression.

The sleep response to stress: how sleep reactivity can help us prevent insomnia and promote resilience to trauma.

Sleep reactivity is a predisposition to sleep disturbance during environmental perturbations, pharmacological challenges, or stressful life events. Consequently, individuals with highly reactive sleep systems are prone to insomnia disorder after a stressor, engendering risk of psychopathology and potentially impeding recovery from traumatic stress. Thus, there is tremendous value in ameliorating sleep reactivity to foster a sleep system that is robust to stress exposure, ultimately preventing insomnia and its downstream consequences. We reviewed prospective evidence for sleep reactivity as a predisposition to insomnia since our last review on the topic in 2017. We also reviewed studies investigating pre-trauma sleep reactivity as a predictor of adverse post-traumatic sequelae, and clinical trials that reported the effect of behavioural treatments for insomnia on mitigating sleep reactivity. Most studies measured sleep reactivity via self-report using the Ford Insomnia Response to Stress Test (FIRST), demonstrating high scores on this scale reliably indicate a sleep system with a lower capacity to tolerate stress. Nascent evidence suggests elevated sleep reactivity prior to trauma increases the risk of negative posttraumatic outcomes, namely acute stress disorder, depression, and post-traumatic stress disorder. Lastly, sleep reactivity appears most responsive to behavioural insomnia interventions when delivered early during the acute phase of insomnia. Overall, the literature strongly supports sleep reactivity as a premorbid vulnerability to incident acute insomnia disorder when faced with an array of biopsychosocial stressors. The FIRST identifies individuals at risk of insomnia a priori, thereby guiding early interventions toward this vulnerable population to prevent insomnia and promote resilience to adversity.

Pre-pandemic sleep reactivity prospectively predicts distress during the COVID-19 pandemic: The protective effect of insomnia treatment.

The COVID-19 pandemic is a rare stressor that has precipitated an accompanying mental health crisis. Prospective studies traversing the pandemic's onset can elucidate how pre-existing disease vulnerabilities augured risk for later stress-related morbidity. We examined how pre-pandemic sleep reactivity predicted maladaptive stress reactions and depressive symptoms in response to, and during, the pandemic. This study is a secondary analysis of a randomised controlled trial from 2016 to 2017 comparing digital cognitive behavioural therapy for insomnia (dCBT-I) against sleep education (N = 208). Thus, we also assessed whether dCBT-I moderated the association between pre-pandemic sleep reactivity and pandemic-related distress. Pre-pandemic sleep reactivity was measured at baseline using the Ford Insomnia Response to Stress Test. In April 2020, participants were recontacted to report pandemic-related distress (stress reactions and depression). Controlling for the treatment condition and the degree of COVID-19 impact, higher pre-pandemic sleep reactivity predicted more stress reactions (ß = 0.13, ± 0.07 SE, p = 0.045) and depression (ß = 0.22, ± 0.07 SE, p = 0.001) during the pandemic. Further, the odds of reporting clinically significant stress reactions and depression during the pandemic were over twice as high in those with high pre-pandemic sleep reactivity. Notably, receiving dCBT-I in 2016-2017 mitigated the relationship between pre-pandemic sleep reactivity and later stress reactions (but not depression). Pre-pandemic sleep reactivity predicted psychological distress 3-4 years later during the COVID-19 pandemic, and dCBT-I attenuated its association with stress reactions, specifically. Sleep reactivity may inform prevention and treatment efforts by identifying individuals at risk of impairment following stressful events.

SLeep Education for Everyone Program (SLEEP) Results in Sustained Improvements in Sleep Outcomes at Six Months.

OBJECTIVE: Community-delivered sleep education interventions have been demonstrated to be effective in improving sleep outcomes, but whether these benefits persist once the program ends is not well characterized. This study sought to determine whether the previously reported positive effects attributed to the SLeep Education for Elders Program (SLEEP) were maintained six months after program completion. METHOD: Nineteen participants were surveyed three times: at baseline, program completion (six weeks), and the six-month post-program timepoint. Sleep outcomes for quality, duration, insomnia symptoms, sleep hygiene behaviors, and excessive daytime sleepiness were assessed using validated surveys, including the Pittsburgh Sleep Quality Index (from which duration was also extracted), the Insomnia Severity Index, the Sleep Hygiene Index, and the Epworth Sleepiness Scale. RESULTS: Longitudinal models adjusted for baseline sleep problems revealed the benefits achieved immediately after the program were retained at six months for sleep quality (estimate: -2.0 (95%CI: -2.7, -1.3)), sleep duration (estimate: 0.9 (95%CI: 0.6, 1.2)), insomnia symptoms (estimate: -3.5 95%CI: (-4.6, -2.3)), and sleep hygiene behaviors (estimate: -2.6 (-4.3, -0.9)). CONCLUSIONS: These results suggest that a community-delivered sleep education intervention can produce sustained benefits for participants and should be considered as a tool to address uncomplicated sleep issues.

[68 Ga]Ga-FAPI-46 PET for non-invasive detection of pulmonary fibrosis disease activity.

PURPOSE: The lack of effective molecular biomarkers to monitor idiopathic pulmonary fibrosis (IPF) activity or treatment response remains an unmet clinical need. Herein, we determined the utility of fibroblast activation protein inhibitor for positron emission tomography (FAPI PET) imaging in a mouse model of pulmonary fibrosis. METHODS: Pulmonary fibrosis was induced by intratracheal administration of bleomycin (1 U/kg) while intratracheal saline was administered to control mice. Subgroups from each cohort (n = 3-5) underwent dynamic 1 h PET/CT after intravenously injecting FAPI-46 radiolabeled with gallium-68 ([68 Ga]Ga-FAPI-46) at 7 days and 14 days following disease induction. Animals were sacrificed following imaging for ex vivo gamma counting and histologic correlation. [68 Ga]Ga-FAPI-46 uptake was quantified and reported as percent injected activity per cc (%IA/cc) or percent injected activity (%IA). Lung CT density in Hounsfield units (HU) was also correlated with histologic examinations of lung fibrosis. RESULTS: CT only detected differences in the fibrotic response at 14 days post-bleomycin administration. [68 Ga]Ga-FAPI-46 lung uptake was significantly higher in the bleomycin group than in control subjects at 7 days and 14 days. Significantly (P = 0.0012) increased [68 Ga]Ga-FAPI-46 lung uptake in the bleomycin groups at 14 days (1.01 ± 0.12%IA/cc) vs. 7 days (0.33 ± 0.09%IA/cc) at 60 min post-injection of the tracer was observed. These findings were consistent with an increase in both fibrinogenesis and FAP expression as seen in histology. CONCLUSION: CT was unable to assess disease activity in a murine model of IPF. Conversely, FAPI PET detected both the presence and activity of lung fibrogenesis, making it a promising tool for assessing early disease activity and evaluating the efficacy of therapeutic interventions in lung fibrosis patients.

The Relationship of Neuroticism with Sleep Quality: The Mediating Role of Emotional, Cognitive and Metacognitive Factors.

BACKGROUND: Poor sleep quality is associated with a broad range of psychopathology and is a common problem among college students. This study aimed to investigate the mediating role of metacognitive beliefs related to sleep, emotion regulation and a negative cognitive style related to anxiety (looming cognitive style) in the relation between neuroticism and reported sleep quality. PARTICIPANTS: Participants were 343 undergraduates from three universities in Tehran (56.3% females, Mean age = 22.01 ± 2.74 years). METHOD: Data were gathered with a questionnaire packet that included the Pittsburgh Sleep Quality Index (PSQI), Metacognitions Questionnaire-Insomnia (MCQ-I), Emotion Regulation Questionnaire (ERQ), Looming Maladaptive Style Questionnaire (LMSQ) and Neuroticism subscale of NEO-PI-R. RESULTS: Structural equation modeling analyses supported a proposed model (R2 = 37%) which proposed that neuroticism both directly and indirectly linked to reported sleep quality through metacognitions related to sleep, cognitive reappraisal and looming cognitive style (χ2 = 1194.87, p < .001; CFI = 0.93, NFI = 0.90, RMSEA = 0.065, GFI = 0.92, SRMR = 0.069, IFI = 0.93). CONCLUSIONS: The results provide evidence for the impact of neuroticism on reported sleep quality through metacognitive, cognitive and emotional factors. The result suggest that special attention should be paid to these factors in the treatment and psychopathology of sleep quality.

Self-efficacy in Insomnia Symptom Management after Digital CBT-I Mediates Insomnia Severity during the COVID-19 Pandemic.

STUDY OBJECTIVES: Digital cognitive behavioral therapy for insomnia (dCBT-I) can reduce acute insomnia and depressive symptoms and prevent symptom recurrence. The current study evaluated self-efficacy in managing insomnia symptoms as a potential mediator of the relationship between prior dCBT-I and subsequent insomnia and depressive symptoms assessed during the coronavirus 2019 (COVID-19) pandemic. METHOD: Participants were 208 adults who completed a randomized controlled trial of dCBT-I versus sleep education in 2016-2017 and also completed self-report assessments of insomnia, depression, and self-efficacy in managing insomnia symptoms. Data were collected in May 2020, five weeks into state-wide COVID-19 stay-at-home orders. Regression and mediation analyses were used to evaluate the extent to which self-efficacy accounted for the relationship between treatment condition and improvement in insomnia and depressive symptoms from pre-treatment to COVID-19 follow-up. RESULTS: Prior dCBT-I predicted greater self-efficacy in managing insomnia symptoms. Self-efficacy accounted for 49% and 67% of the protective effect of dCBT-I against COVID-era insomnia and depressive symptoms, respectively. CONCLUSIONS: This study affirms the importance of self-efficacy as a key intervention outcome and potential mechanism by which dCBT-I predicts future sleep and mental health. Future studies that evaluate the role of self-efficacy in treatment effectiveness and resilience can provide additional clues about how to optimize dCBT-I for maximum benefit to public health.

Examining Patient Feedback and the Role of Cognitive Arousal in Treatment Non-response to Digital Cognitive-behavioral Therapy for Insomnia during Pregnancy.

OBJECTIVE: Insomnia affects over half of pregnant and postpartum women. Early evidence indicates that cognitive-behavioral therapy for insomnia (CBTI) improves maternal sleep and mood. However, standard CBTI may be less efficacious in perinatal women than the broader insomnia population. This study sought to identify patient characteristics in a perinatal sample associated with poor response to CBTI, and characterize patient feedback to identify areas of insomnia therapy to tailor for the perinatal experience. PARTICIPANTS: Secondary analysis of 46 pregnant women with insomnia symptoms who were treated with digital CBTI in a randomized controlled trial. METHODS: We assessed insomnia, cognitive arousal, and depression before and after prenatal treatment, then 6 weeks postpartum. Patients provided feedback on digital CBTI. RESULTS: Residual cognitive arousal after treatment was the most robust factor associated with treatment non-response. Critically, CBTI responders and non-responders differed on no other sociodemographic or pretreatment metrics. After childbirth, short sleep (<6 hrs/night) was associated with maternal reports of poor infant sleep quality. Patient feedback indicated that most patients preferred online treatment to in-person treatment. Although women described digital CBTI as convenient and helpful, many patients indicated that insomnia therapy would be improved if it addressed sleep challenges unique to pregnancy and postpartum. Patients requested education on maternal and infant sleep, flexibility in behavioral sleep strategies, and guidance to manage infant sleep. CONCLUSIONS: Modifying insomnia therapy to better alleviate refractory cognitive arousal and address the changing needs of women as they progress through pregnancy and early parenting may increase efficacy for perinatal insomnia.Name: Insomnia and Rumination in Late Pregnancy and the Risk for Postpartum DepressionURL: clinicaltrials.govRegistration: NCT03596879.

Mother-to-Infant Bonding is Associated with Maternal Insomnia, Snoring, Cognitive Arousal, and Infant Sleep Problems and Colic.

OBJECTIVE: Emerging evidence links maternal and infant sleep problems to impairments in the mother-to-infant bond, but the independence and directionality of these associations remain unclear. The present study characterized concurrent and prospective effects of maternal sleep disturbances and poor infant sleep on the mother-infant relationship. As common sequalae of problematic sleep, nocturnal cognitive hyperarousal and daytime sleepiness were investigated as facilitating mechanisms. PARTICIPANTS: Sixty-seven pregnant women enrolled in a prospective study on maternal sleep. METHODS: Sociodemographic information and clinical symptoms were measured prenatally then weekly across the first two postpartum months. Women reported insomnia symptoms, sleep duration, snoring, daytime sleepiness, nocturnal cognitive arousal (broadly focused and perinatal-specific), perseverative thinking, depression, infant colic, infant sleep quality, and mother-infant relationship quality. Mixed effects models were conducted to test hypotheses. RESULTS: Prenatal snoring and weak maternal-fetal attachment augured poorer postpartum bonding. Poor infant sleep was associated with increased odds for maternal insomnia and short sleep. Impairments in the mother-to-infant bond were linked to maternal insomnia, nocturnal perinatal-focused rumination, daytime sleepiness, depression, and poor infant sleep. Postnatal insomnia predicted future decreases in mother-infant relationship quality, and nocturnal cognitive hyperarousal partially mediated this association. CONCLUSIONS: Both maternal and infant sleep problems were associated with poorer mother-to-infant bonding, independent of the effects of maternal depression and infant colic. Perseverative thinking at night, particularly on infant-related concerns, was linked to impaired bonding, rejection and anger, and infant-focused anxiety. Improving maternal and infant sleep, and reducing maternal cognitive arousal, may improve the maternal-to-infant bond.

Relationship between sleep efficacy endpoints and measures of functional status and health-related quality of life in participants with narcolepsy or obstructive sleep apnea treated for excessive daytime sleepiness.

This study examined the correlation between improvements in excessive daytime sleepiness in participants with obstructive sleep apnea or narcolepsy and changes in functional status, work productivity and health-related quality of life. Data from two 12-week randomized controlled trials of solriamfetol were analyzed. Participants completed the Epworth Sleepiness Scale, 10-item Functional Outcomes of Sleep Questionnaire, Work Productivity and Activity Impairment questionnaire and 36-Item Short Form Health Survey and performed the Maintenance of Wakefulness Test at baseline and weeks 4, 8 and 12. Patient Global Impression of Change was assessed at weeks 4, 8 and 12. Pearson correlations were calculated for change in scores from baseline to week 12. For both studies, changes in the 10-item Functional Outcomes of Sleep Questionnaire were highly correlated (absolute value >0.5) with changes in Epworth Sleepiness Scale scores; changes in multiple domain scores of the 36-Item Short Form Health Survey and Work Productivity and Activity Impairment questionnaire were moderately correlated (0.3-0.5) with changes in Epworth Sleepiness Scale scores in both studies and highly correlated for participants with narcolepsy. Changes in Maintenance of Wakefulness Test scores correlated moderately with changes in Epworth Sleepiness Scale scores in both studies. At week 12, Patient Global Impression of Change ratings correlated highly with Epworth Sleepiness Scale and 10-item Functional Outcomes of Sleep Questionnaire scores for both disorders. Other correlations were low. Self-reported assessments of sleepiness and global improvement appear to be more strongly correlated with measures of functioning and health-related quality of life than objectively assessed sleepiness.

Production of diverse PET probes with limited resources: 24 18F-labeled compounds prepared with a single radiosynthesizer.

New radiolabeled probes for positron-emission tomography (PET) are providing an ever-increasing ability to answer diverse research and clinical questions and to facilitate the discovery, development, and clinical use of drugs in patient care. Despite the high equipment and facility costs to produce PET probes, many radiopharmacies and radiochemistry laboratories use a dedicated radiosynthesizer to produce each probe, even if the equipment is idle much of the time, to avoid the challenges of reconfiguring the system fluidics to switch from one probe to another. To meet growing demand, more cost-efficient approaches are being developed, such as radiosynthesizers based on disposable "cassettes," that do not require reconfiguration to switch among probes. However, most cassette-based systems make sacrifices in synthesis complexity or tolerated reaction conditions, and some do not support custom programming, thereby limiting their generality. In contrast, the design of the ELIXYS FLEX/CHEM cassette-based synthesizer supports higher temperatures and pressures than other systems while also facilitating flexible synthesis development. In this paper, the syntheses of 24 known PET probes are adapted to this system to explore the possibility of using a single radiosynthesizer and hot cell for production of a diverse array of compounds with wide-ranging synthesis requirements, alongside synthesis development efforts. Most probes were produced with yields and synthesis times comparable to literature reports, and because hardware modification was unnecessary, it was convenient to frequently switch among probes based on demand. Although our facility supplies probes for preclinical imaging, the same workflow would be applicable in a clinical setting.

Efficacy of digital CBT for insomnia to reduce depression across demographic groups: a randomized trial.

BACKGROUND: Insomnia and depression are highly comorbid and mutually exacerbate clinical trajectories and outcomes. Cognitive behavioral therapy for insomnia (CBT-I) effectively reduces both insomnia and depression severity, and can be delivered digitally. This could substantially increase the accessibility to CBT-I, which could reduce the health disparities related to insomnia; however, the efficacy of digital CBT-I (dCBT-I) across a range of demographic groups has not yet been adequately examined. This randomized placebo-controlled trial examined the efficacy of dCBT-I in reducing both insomnia and depression across a wide range of demographic groups. METHODS: Of 1358 individuals with insomnia randomized, a final sample of 358 were retained in the dCBT-I condition and 300 in the online sleep education condition. Severity of insomnia and depression was examined as a dependent variable. Race, socioeconomic status (SES; household income and education), gender, and age were also tested as independent moderators of treatment effects. RESULTS: The dCBT-I condition yielded greater reductions in both insomnia and depression severity than sleep education, with significantly higher rates of remission following treatment. Demographic variables (i.e. income, race, sex, age, education) were not significant moderators of the treatment effects, suggesting that dCBT-I is comparably efficacious across a wide range of demographic groups. Furthermore, while differences in attrition were found based on SES, attrition did not differ between white and black participants. CONCLUSIONS: Results provide evidence that the wide dissemination of dCBT-I may effectively target both insomnia and comorbid depression across a wide spectrum of the population.

The Mediating Effect of Sleep Disturbance on the Relationship Between Nonmalignant Chronic Pain and Suicide Death.

IMPORTANCE: Few studies have examined the relationship between nonmalignant chronic pain (NMCP) and suicide death, and even fewer have specifically explored what role sleep disturbance might play in the association between NMCP and suicide death. OBJECTIVE: To assess whether sleep disturbance mediates the relationship between NMCP and suicide death. DESIGN: This case-control study included 2,674 individuals who died by suicide between 2000 and 2013 (cases) and 267,400 matched individuals (controls). SETTING: Eight Mental Health Research Network (MHRN)-affiliated healthcare systems. PARTICIPANTS: All cases and matched controls were health plan members for at least 10 months during the year prior to the index date. MAIN OUTCOMES AND MEASURES: Sociodemographic data and diagnosis codes for NMCP and sleep disorders were extracted from the MHRN's Virtual Data Warehouse. Suicide mortality was identified using International Statistical Classification of Diseases and Related Health Problems (ICD)-10 codes from official government mortality records matched to health system records. RESULTS: After accounting for covariates, there was a significant relationship between NMCP and sleep disturbance; those who were diagnosed with NMCP were more likely to develop subsequent sleep disturbance. Similarly, sleep disturbance was significantly associated with suicide death. Finally, a significant indirect effect of NMCP on suicide death, through sleep disturbance, and a nonsignificant direct effect of NMCP on suicide death provide support for a fully mediated model. CONCLUSIONS AND RELEVANCE: There is a need for clinicians to screen for both sleep disturbance and suicidal ideation in NMCP patients and for health systems to implement more widespread behavioral treatments that address comorbid sleep problems and NMCP.

Validation of the German version of the Ford Insomnia Response to Stress Test.

The purpose of this study was to assess the psychometric properties of a German version of the Ford Insomnia Response to Stress Test with groups with and without sleep problems. Three studies were analysed. Data set 1 was based on an initial screening for a sleep training program (n = 393), data set 2 was based on a study to test the test-retest reliability of the Ford Insomnia Response to Stress Test (n = 284) and data set 3 was based on a study to examine the influence of competitive sport on sleep (n = 37). Data sets 1 and 2 were used to test internal consistency, factor structure, convergent validity, discriminant validity and test-retest reliability of the Ford Insomnia Response to Stress Test. Content validity was tested using data set 3. Cronbach's alpha of the Ford Insomnia Response to Stress Test was good (α = 0.80) and test-retest reliability was satisfactory (r = 0.72). Overall, the one-factor model showed the best fit. Furthermore, significant positive correlations between the Ford Insomnia Response to Stress Test and impaired sleep quality, depression and stress reactivity were in line with the expectations regarding the convergent validity. Subjects with sleep problems had significantly higher scores in the Ford Insomnia Response to Stress Test than subjects without sleep problems (P < 0.01). Competitive athletes with higher scores in the Ford Insomnia Response to Stress Test had significantly lower sleep quality (P = 0.01), demonstrating that vulnerability for stress-induced sleep disturbances accompanies poorer sleep quality in stressful episodes. The findings show that the German version of the Ford Insomnia Response to Stress Test is a reliable and valid questionnaire to assess the vulnerability to stress-induced sleep disturbances.

The impact of stress on sleep: Pathogenic sleep reactivity as a vulnerability to insomnia and circadian disorders.

Sleep reactivity is the trait-like degree to which stress exposure disrupts sleep, resulting in difficulty falling and staying asleep. Individuals with highly reactive sleep systems experience drastic deterioration of sleep when stressed, whereas those with low sleep reactivity proceed largely unperturbed during stress. Research shows that genetics, familial history of insomnia, female gender and environmental stress influence how the sleep system responds to stress. Further work has identified neurobiological underpinnings for sleep reactivity involving disrupted cortical networks and dysregulation in the autonomic nervous system and hypothalamic-pituitary-adrenal axis. Sleep reactivity is most pathologically and clinically pertinent when in excess, such that high sleep reactivity predicts risk for future insomnia disorder, with early evidence suggesting high sleep reactivity corresponds to severe insomnia phenotypes (sleep onset insomnia and short sleep insomnia). High sleep reactivity is also linked to risk of shift-work disorder, depression and anxiety. Importantly, stress-related worry and rumination may exploit sensitive sleep systems, thereby augmenting the pathogenicity of sleep reactivity. With the development of cost-effective assessment of sleep reactivity, we can now identify individuals at risk of future insomnia, shift-work disorder and mental illness, thus identifying a target population for preventive intervention. Given that insomniacs with high sleep reactivity tend to present with severe insomnia phenotypes, patient sleep reactivity may inform triaging to different levels of treatment. Future research on sleep reactivity is needed to clarify its neurobiology, characterize its long-term prospective associations with insomnia and shift-work disorder phenotypes, and establish its prognostic value for mental illness and other non-sleep disorders.

Assessing Stress-Induced Sleep Reactivity in College Students: The European Portuguese Version of the Ford Insomnia Response to Stress Test (FIRST).

OBJECTIVE AND BACKGROUND: Over the past few years, the comprehensive models of insomnia have exhibited impressive developments. However, there is scarce knowledge on predisposing or vulnerability factors for insomnia. One of the most promising constructs to aid in filling this gap is stress-induced sleep reactivity assessed through self-report. Our aim was to study the psychometric properties of the European Portuguese version of the Ford Insomnia Response to Stress Test (FIRST). PARTICIPANTS: We recruited a large sample of students attending medical school (N = 699). METHODS: Several analyses were carried out such as internal consistency, construct validity, and discriminant groups' analysis. RESULTS: It was observed that FIRST-PT shows good internal consistency (Cronbach´s alpha = .81) and validity indicators. Interestingly, and contrary to what was observed in the previously published studies on psychometric properties of the FIRST, it was observed that a two-factor solution (Factor I = rumination, Factor II = worry) was the most adequate one to explain the correlation matrix, accounting for approximately 44% of the total variance. CONCLUSIONS: The FIRST-PT proved to be a useful and reliable tool to measure stress-induced sleep reactivity. However, these results should be replicated in other groups, particularly clinical samples, in order to verify the stability of its factorial dimension.

Characterization of Condensed Tannins from Purple Prairie Clover (Dalea purpurea Vent.) Conserved as either Freeze-Dried Forage, Sun-Cured Hay or Silage.

Conservation methods have been shown to affect forage nutrient composition and value, but little information is available about the effect of forage conservation on plant condensed tannins (CT). The objective of this study was to assess the effects of conservation method on the concentration, chemical composition and biological activity of CT. Whole-plant purple prairie clover (PPC, Dalea purpurea Vent.) was harvested at full flower and conserved as freeze-dried forage (FD), hay (HAY) or silage (SIL). Concentration of CT in conserved PPC was determined by the butanol-HCl-acetone method. Structural composition, protein-precipitation capacity and anti-bacterial activity of CT isolated from conserved forage were determined by in situ thiolytic degradation followed by HPLC-MS analysis, a protein precipitation assay using bovine serum albumin and ribulose 1,5-disphosphate carboxylase as model proteins and by an Escherichia coli (E. coli) growth test, respectively. Conservation method had no effect on concentration of total CT, but ensiling decreased (p < 0.001) extractable CT and increased (p < 0.001) protein- and fiber-bound CT. In contrast, hay-making only increased (p < 0.01) protein-bound CT. Regardless of conservation method, epigallocatechin (EGC), catechin (C) and epicatechin (EC) were the major flavan-3-ol units, and gallocatechin (GC) was absent from both terminal and extension units of PPC CT. The SIL CT had the lowest (p < 0.001) EGC, but the highest (p < 0.01) EC in the extension units. Similarly, SIL CT exhibited a lower (p < 0.001) mean degree of polymerization (mDP), but higher (p < 0.001) procyanidins (PC) than FD or HAY CT. The protein-precipitating capacity of CT in conserved PPC ranked (p < 0.001) as FD > HAY > SIL. E. coli growth n M9 medium was inhibited by 25-100 µg/mL of CT isolated from FD, HAY and SIL (p < 0.05), but preservation method had no effect on the ability of CT to inhibit bacterial growth. The results demonstrated that ensiling decreased the extractability and protein-precipitating capacity of CT by increasing the proportions of PC. Purple prairie clover conserved as hay retained more biologically active CT than if it was conserved as silage.

Association Between Stress-Related Sleep Reactivity and Metacognitive Beliefs About Sleep in Insomnia Disorder: Preliminary Results.

To evaluate the relation between stress-related sleep reactivity and metacognitive beliefs about sleep in subjects with insomnia disorder (93) and in a group of healthy controls (30) a set of variables, including Ford Insomnia Response to Stress Test (FIRST) and Metacognition Questionnaire-Insomnia (MCQ-I), have been used. Internal consistency of the Italian version of FIRST was studied. Univariate correlation, regression analysis, and principal component analysis were also performed. The Italian version of FIRST showed good internal consistency and discriminant validity. Sleep reactivity was higher in women (p < .05) and correlates positively in both genders with metacognitive beliefs about sleep (p < .01) in insomnia. In insomnia, metacognitive beliefs may play a key role in modulating sleep reactivity. Therapeutic strategies acting selectively on metacognition to reduce stress-related sleep reactivity in insomnia may be useful.