Positive and negative impacts of elexacaftor/tezacaftor/ivacaftor: Healthcare providers' observations across US centers.

BACKGROUND: Elexacaftor/tezacaftor/ivacaftor (ETI) has been associated with unprecedented clinical improvements, transforming the management of cystic fibrosis (CF). However, side effects with implications for safety and well-being have been reported, including neuropsychiatric changes. This study aimed to better characterize the emerging positive and negative impacts of ETI. METHODS: The Cystic Fibrosis Foundation's Mental Health Advisory Committee distributed a 26-item survey to US CF care teams to assess clinician observations of patient-reported experiences with ETI. Survey responses measured the prevalence of these effects in five domains: (1) positive physical and psychological effects, (2) sleep difficulties, (3) cognitive difficulties, (4) worsening mental health, and (5) concerns about the future and finances. RESULTS: Seventy-five healthcare providers responded from a pediatric, adult, and combined centers. Positive physical effects of ETI and increased optimism were reported in the upper quartiles (50%-100%) and rated as having a significant impact on daily functioning. Sleep and cognitive difficulties were reported in 1%-24%, with slight impacts on functioning, and psychological symptoms (e.g., increased stress, depression, anxiety) and new psychiatric medications were reported in 1%-24%, with moderate impacts. Concerns about the future were reported in 1%-24%, with minimal impacts. CONCLUSION: Across US centers, providers most often observed positive physical effects of ETI. However, a variety of negative side effects were also reported, including sleep disruptions and worsening psychological functioning, which should be systematically monitored by CF teams. These national-level data are a first step in evaluating the prevalence and consequences of these side effects and can directly inform future studies.

Pilot RCT of a telehealth intervention to reduce symptoms of depression and anxiety in adults with cystic fibrosis.

BACKGROUND: Adults with cystic fibrosis (awCF) have higher levels of depression and anxiety than community samples. The Coping and Learning to Manage Stress with CF (CALM) intervention was developed for awCF reporting elevated symptoms of depression or anxiety. METHODS: In this pilot study, awCF were randomly assigned to either six telehealth sessions (CALM; n = 15) or treatment-as-usual (TAU; n = 16). Primary outcomes were depression and anxiety. Secondary outcomes were coping self-efficacy and health-related quality of life (HrQOL). Tertiary outcomes were feasibility, acceptability, and satisfaction. Assessments were completed at baseline, post-intervention, and 3-month follow-up. Group differences were examined via independent samples t-tests. Effect size (ES) was calculated via Cohen's d to provide a measure of the magnitude of the treatment effect. RESULTS: At post-intervention, the CALM group had a lower mean score than the TAU group for depression (medium ES) and anxiety (large ES). The CALM group had higher (i.e., better) mean scores than the TAU group for coping (large ES) and HrQOL domains of Social Functioning (large ES) and Vitality (large ES). Most treatment gains were not sustained at 3-month follow-up. CALM was feasible, requiring <12 min. for setup and scheduling, and allowed seamless participation when hospitalized. Mean scores for acceptability and satisfaction indicated that most participants either agreed or strongly agreed that CALM was acceptable and satisfactory. CONCLUSIONS: CALM shows promise as an intervention to reduce symptoms of depression and anxiety and improve coping and HrQOL. Next steps are to add a booster session and examine CALM via a multi-site RCT.

Impact of daytime sleepiness and insomnia on simple and complex cognitive task performances.

OBJECTIVE: To examine the individual and combined effects of daytime sleepiness and insomnia disorder (ID) on measures of cognitive functioning. DESIGN AND SETTING: This study was conducted at a medical center using a cross-sectional research design. PARTICIPANTS: 35 persons with ID (Mage = 40.6 years; 25 women) and 54 normal sleepers (NS; Mage = 31.5 years; 38 women). METHODS AND MEASURES: Participants underwent two nights of home-based polysomnography (PSG) followed by daytime testing with a four-trial Multiple Sleep Latency Test (MSLT). Before each MSLT nap, they completed a computer-administered battery of reaction time tasks. Measures of response latencies and response accuracy were tabulated and used as dependent measures. The ID and NS groups were each subdivided into "alert" (eg, MSLT mean latency > 8 min) and "sleepy" (eg, MSLT mean latency ≤ 8 min) subgroups to identify hyperaroused persons with ID and allow for their comparisons with the other participant subgroups. RESULTS: Multivariate analyses of variance showed a significant main effect for level of daytime sleepiness (F [1, 84] = 8.52, p = 0.0045) on simpler performance tasks and a significant main effect for presence vs. absence of ID (F [1,84] = 6.62, p = 0.012) on complex tasks. A lack of significant participant type x MSLT alertness level interactions in study analyses suggested those ID participants with presumed hyperaousal were not relatively more impaired than the other participant subgroups. CONCLUSIONS: Daytime performance deficits on simple tasks seem most dependent on individuals' levels of daytime sleepiness, whereas performance deficits on more complex tasks appears related to the presence of ID. Therefore, it seems best to use complex performance measures both to document cognitive deficits among those with ID and to determine if insomnia treatments reduce such impairments. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02290405.

Neurocognitive performance in insomnia disorder: The impact of hyperarousal and short sleep duration.

Given the recent evidence on the association between hyperarousal in insomnia disorder and neurocognitive deficits, we aimed to examine the effect of short sleep duration on neurocognitive reaction time tests in insomnia disorder sufferers. We recruited subjects with insomnia disorder (n = 35, mean age = 40.6 years) who scored ≥29 on a Hyperarousal Scale, and a group of controls (n = 54, mean age = 31.5 years) who had no sleep disorders and scored <26 on the Hyperarousal Scale. Participants completed two in-home polysomnograms and four daytime trials of neurocognitive tests, including simple reaction time, choice reaction time, big circle-little circle, rapid visual information processing, attention switching task, and spatial working memory tests. Total sleep time divided study cohorts into subgroups of short (total sleep time <6 hr) and normal (total sleep time ≥6 hr) sleepers. ANCOVA showed a significant interaction between participant type (insomnia disorder versus controls) and sleep duration (short versus normal) for spatial working memory-latency (p = 0.020) and spatial working memory-errors (p = 0.025). The short-sleeping insomnia disorder group had longer spatial working memory-latencies and more spatial working memory-errors than did normal-sleeping controls. Regardless of sleep duration, those with insomnia disorder had more attentional deficits with longer attention switching task-latency (p = 0.011) and more attention switching task-incorrect trials (p = 0.015) than the control group. Normal-sleepers only had longer attention switching task-latency than short-sleepers (p = 0.004). A phenotype of insomnia disorder with hyperarousal and short sleep duration is associated with daytime cognitive deficits in complex attentional and spatial working memory tasks.

Insomnia, Short Sleep Duration, and High Blood Pressure: Recent Evidence and Future Directions for the Prevention and Management of Hypertension.

PURPOSE OF REVIEW: To summarize research from the past 2 years on the association between insomnia, short sleep duration, and hypertension and provide a critical analysis of the evidence and suggestions for future directions in this field. RECENT FINDINGS: Evidence indicates that the association between insomnia and elevated blood pressure (BP) or stage 1 and 2 hypertension is stronger in those with chronic insomnia, as compared to those with isolated insomnia symptoms, and primarily found in those with the insomnia with objective short sleep duration phenotype. There is a key gap in ambulatory BP monitoring across the sleep-wake cycle as well as in randomized clinical trials testing the effectiveness of pharmacological or cognitive-behavioral insomnia therapies in lowering BP. Insomnia is a strong candidate to join the list of risk factors for hypertension along with obstructive sleep apnea. In the meantime, chronic insomnia should become part of the routine assessment of patients with elevated BP and should be a source for referral, diagnostic evaluation, and treatment, rather than regarded as a symptom of the underlying medical disorder.

Insomnia Patients With Objective Short Sleep Duration Have a Blunted Response to Cognitive Behavioral Therapy for Insomnia.

Study Objectives: This study examined whether individuals with insomnia and objective short sleep duration <6 h, a subgroup with greater risks of adverse health outcomes, differ in their response to cognitive-behavioral therapy for insomnia (CBT-I) when compared to individuals with insomnia and normal sleep duration ≥6 h. Methods: Secondary analyses of a randomized, clinical trial with 60 adult participants (n = 31 women) from a single academic medical center. Outpatient treatment lasted 8 weeks, with a final follow-up conducted at 6 months. Mixed-effects models controlling for age, sex, CBT-I treatment group assignment, and treatment provider examined sleep parameters gathered via actigraphy, sleep diaries, and an Insomnia Symptom Questionnaire (ISQ) across the treatment and follow-up period. Results: Six months post-CBT-I treatment, individuals with insomnia and normal sleep duration ≥6 h fared significantly better on clinical improvement milestones than did those with insomnia and short sleep duration <6 h. Specifically, individuals with insomnia and normal sleep duration had significantly higher insomnia remission (ISQ < 36.5; χ2[1, N = 60] = 44.72, p < .0001), more normative sleep efficiency (SE) on actigraphy (SE > 80%; χ2[1, N = 60] = 21, p < .0001), normal levels of middle of the night wake after sleep onset (MWASO) <31 minutes (χ2[1, N = 60] = 37.85, p < .0001), and a >50% decline in MWASO (χ2[1, N = 60] = 60, p < .0001) compared to individuals with insomnia and short sleep duration. Additionally, those with insomnia and normal sleep duration had more success decreasing their total wake time (TWT) at the 6-month follow-up compared to those with insomnia and short sleep duration (χ2[2, N = 60] = 44.1, p < .0001). Receiver-operating characteristic curve analysis found that using a 6-h cutoff with actigraphy provided a 95.7% sensitivity and 91.9% specificity for determining insomnia remission, with the area under the curve = 0.986. Conclusions: Findings suggest that individuals with insomnia and objective short sleep duration <6 h are significantly less responsive to CBT-I than those with insomnia and normal sleep duration ≥6 h. Using an actigraphy TST cutoff of 6 hours to classify sleep duration groups was highly accurate and provided good discriminant value for determining insomnia remission.

Meta-cognitive skills training enhances computerized cognitive remediation outcomes among individuals with first-episode psychosis.

AIM: Meta-cognitive skills training (MST) is a frequent component of cognitive remediation programmes for individuals with psychosis. However, no study has investigated whether incorporating such activities produces increased clinical benefits compared with computerized cognitive remediation alone. METHODS: Individuals with first-episode psychosis who completed computerized cognitive remediation with concurrent meta-cognitive skills training (CCR + MST) were compared with a historical control group who received computerized cognitive remediation alone (CCR) and did not differ from the CCR + MST group with regard to pre-intervention cognition, diagnosis, age, duration of psychotic illness or sex. Participants completed assessments of cognition and real-world functioning before and after 6 months of treatment. RESULTS: Individual receiving CCR + MST experience greater gains in cognition and real-world functioning than individuals who received CCR. CONCLUSIONS: MST may be an important component within cognitive remediation programmes for first-episode psychosis.

Objective but Not Subjective Short Sleep Duration Associated with Increased Risk for Hypertension in Individuals with Insomnia.

STUDY OBJECTIVES: To examine the relationship between hypertension prevalence in individuals with insomnia who have short total sleep duration < 6 h or sleep duration ≥ 6 h, using both objective and subjective measures of total sleep duration. METHODS: Using a cross-sectional, observational design, 255 adult volunteers (n = 165 women; 64.7%) meeting current diagnostic criteria for insomnia disorder (MAge = 46.2 y, SDAge = 13.7 y) participated in this study at two large university medical centers. Two nights of polysomnography, 2 w of sleep diaries, questionnaires focused on sleep, medical, psychological, and health history, including presence/absence of hypertension were collected. Logistic regressions assessed the odds ratios of hypertension among persons with insomnia with short sleep duration < 6 h compared to persons with insomnia with a sleep duration ≥ 6 h, measured both objectively and subjectively. RESULTS: Consistent with previous studies using objective total sleep duration, individuals with insomnia and short sleep duration < 6 h were associated with a 3.59 increased risk of reporting hypertension as a current medical problem as compared to individuals with insomnia with sleep duration ≥ 6 h. Increased risk for hypertension was independent of major confounding factors frequently associated with insomnia or hypertension. No significant risk was observed using subjectively determined total sleep time groups. Receiver operating characteristic curve analysis found that the best balance of sensitivity and specificity using subjective total sleep time was at a 6-h cutoff, but the area under the receiver operating characteristic curve showed low accuracy and did not have good discriminant value. CONCLUSIONS: Objectively measured short sleep duration increased the odds of reporting hypertension more than threefold after adjusting for potential confounders; this relationship was not significant for subjectively measured sleep duration. This research supports emerging evidence that insomnia with objective short sleep duration is associated with an increased risk of comorbid hypertension.