Examining patient and professional perspectives in the UK for gene therapy in haemophilia.

INTRODUCTION: With the development of gene therapy for people with haemophilia (PWH), it is important to understand how people impacted by haemophilia (PIH) and clinicians prioritise haemophilia treatment attributes to support informed treatment decisions. OBJECTIVE: To examine the treatment attribute preferences of PIH and clinical experts in the United Kingdom (UK) and to develop a profile of gene therapy characteristics fit for use in future discrete choice experiments (DCEs). METHODS: Semi-structured interviews were conducted with PIH (n = 14) and clinical experts (n = 6) who ranked pre-defined treatment attributes by importance. Framework analysis was conducted to identify key themes and treatment attributes; points were allocated based on the rankings. Synthesis of results by a multidisciplinary group informed development of a profile of gene therapy characteristics for use in future research. RESULTS: Key themes identified by PIH and clinical experts included patient relevant features and the importance of 'informed decision making'. The six top-ranked treatment attributes were 'effect on factor level' (79 points), 'uncertainty regarding long-term risks' (57 points), 'impact on daily life' (41 points), 'frequency of monitoring' (33 points), 'impact on ability to participate in physical activity' (29 points), and 'uncertainty regarding long-term benefits' (28 points). The final treatment characteristics were categorised as therapeutic option, treatment effectiveness, safety concerns, impact on self-management and quality of life (role limitations). CONCLUSION: We identified several gene therapy characteristics important to PIH and clinicians in the UK. These characteristics will be used in a future DCE to further investigate patient preferences for gene therapy.

Emotions and lung cancer screening: Prioritising a humanistic approach to care.

Low-dose computed tomography lung cancer screening has mortality benefits. Yet, uptake has been low. To inform strategies to better deliver and promote screening, in 2018, we interviewed 27 long-term smokers immediately following lung cancer screening in Australia, prior to receiving scan results. Existing lung screening studies employ the Health Belief Model. Reflecting growing acknowledgement of the centrality of emotions to screening uptake, we draw on psychological and sociological theories on emotions to thematically and abductively analyse the emotional dimensions of lung cancer screening, with implications for screening promotion and delivery. As smokers, interviewees described feeling stigmatised, with female participants internalising and male participants resisting stigma. Guilt and fear related to lung cancer were described as screening motivators. The screening itself elicited mild positive emotions. Notably, interviewees expressed gratitude for the care implicitly shown through lung screening to smokers. More than individual risk assessment, findings suggest lung screening campaigns should prioritise emotions. Peer workers have been found to increase cancer screening uptake in marginalised communities, however the risk to confidentiality-especially for female smokers-limits its feasibility in lung cancer screening. Instead, we suggest involving peer consultants in developing targeted screening strategies that foreground emotions. Furthermore, findings suggest prioritising humanistic care in lung screening delivery. Such an approach may be especially important for smokers from low socioeconomic backgrounds, who perceive lung cancer screening and smoking as sources of stigma and face a higher risk of dying from lung cancer and lower engagement with screening.

Polysomnographic Predictors of Treatment Response to Cognitive Behavioral Therapy for Insomnia in Participants With Co-morbid Insomnia and Sleep Apnea: Secondary Analysis of a Randomized Controlled Trial.

OBJECTIVE: Co-morbid insomnia and sleep apnea (COMISA) is a common and debilitating condition that is more difficult to treat compared to insomnia or sleep apnea-alone. Emerging evidence suggests that cognitive behavioral therapy for insomnia (CBTi) is effective in patients with COMISA, however, those with more severe sleep apnea and evidence of greater objective sleep disturbance may be less responsive to CBTi. Polysomnographic sleep study data has been used to predict treatment response to CBTi in patients with insomnia-alone, but not in patients with COMISA. We used randomized controlled trial data to investigate polysomnographic predictors of insomnia improvement following CBTi, versus control in participants with COMISA. METHODS: One hundred and forty five participants with insomnia (ICSD-3) and sleep apnea [apnea-hypopnea index (AHI) ≥ 15] were randomized to CBTi (n = 72) or no-treatment control (n = 73). Mixed models were used to investigate the effect of pre-treatment AHI, sleep duration, and other traditional (AASM sleep macrostructure), and novel [quantitative electroencephalography (qEEG)] polysomnographic predictors of between-group changes in Insomnia Severity Index (ISI) scores from pre-treatment to post-treatment. RESULTS: Compared to control, CBTi was associated with greater ISI improvement among participants with; higher AHI (interaction p = 0.011), less wake after sleep onset (interaction p = 0.045), and less N3 sleep (interaction p = 0.005). No quantitative electroencephalographic, or other traditional polysomnographic variables predicted between-group ISI change (all p > 0.09). DISCUSSION: Among participants with COMISA, higher OSA severity predicted a greater treatment-response to CBTi, versus control. People with COMISA should be treated with CBTi, which is effective even in the presence of severe OSA and objective sleep disturbance.

Effect of depression, anxiety, and stress symptoms on response to cognitive behavioral therapy for insomnia in patients with comorbid insomnia and sleep apnea: a randomized controlled trial.

STUDY OBJECTIVES: Patients with comorbid insomnia and sleep apnea (COMISA) report increased severity of depression, anxiety, and stress symptoms compared to patients with either insomnia or sleep apnea alone. Although cognitive behavioral therapy for insomnia (CBTi) is an effective treatment for COMISA, previous research suggests a reduced response to CBTi by patients with insomnia and depression, anxiety, and stress symptoms. Therefore, we used randomized controlled trial data to investigate the impact of depression, anxiety, and stress symptoms before treatment on changes in insomnia after CBTi vs control in patients with COMISA. METHODS: 145 patients with COMISA (insomnia as defined by the International Classification of Sleep Disorders, third edition and apnea-hypopnea index ≥ 15 events/h) were randomized to CBTi (n = 72) or no-treatment control (n = 73). One-week sleep diaries and standardized questionnaire measures of insomnia, sleepiness, fatigue, depression, anxiety, and stress were completed pretreatment and posttreatment. Mixed models were used to examine interactions between depression, anxiety, and stress symptoms before treatment, intervention-group (CBTi, control), and time (pretreatment, posttreatment) on insomnia symptoms. RESULTS: Approximately half of this COMISA sample reported at least mild symptoms of depression (57%), anxiety (53%), and stress (48%) before treatment. Patients reporting greater depression, anxiety, and stress symptoms before treatment also reported increased severity of insomnia, daytime fatigue, and sleepiness. Improvements in questionnaire and diary-measured insomnia symptoms improved during CBTi and were not moderated by severity of depression, anxiety, or stress symptoms before treatment (all interaction P ≥ .11). CONCLUSIONS: We found no evidence that symptoms of depression, anxiety, or stress impair the effectiveness of CBTi in improving insomnia symptoms in patients with COMISA. Patients with COMISA and comorbid symptoms of depression, anxiety, and stress should be referred for CBTi to treat insomnia and improve subsequent management of their obstructive sleep apnea. CLINICAL TRIAL REGISTRATION: Registry: Australian New Zealand Clinical Trials Registry; Name: Treating comorbid insomnia with obstructive sleep apnea (COMISA) study: A new treatment strategy for patients with combined insomnia and sleep apnea; URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=365184; Identifier: ACTRN12613001178730.

Cognitive behavioural therapy for insomnia reduces sleep apnoea severity: a randomised controlled trial.

Insomnia and obstructive sleep apnoea (OSA) frequently co-occur and may be causally related through sleep fragmentation and/or hyperarousal mechanisms. Previous studies suggest that OSA treatment can improve insomnia severity. However, the effect of insomnia treatment on OSA severity has not been investigated. We performed a randomised controlled trial to investigate the effect of cognitive behavioural therapy for insomnia (CBTi) on OSA severity, controlling for potential sleep-stage and posture effects. 145 patients with comorbid insomnia (International Classification of Sleep Disorders, 3rd Edn) and untreated OSA (apnoea-hypopnoea index (AHI) ≥15 events·h-1 sleep) were randomised to a four-session CBTi programme or to a no-treatment control. Overnight sleep studies were completed pre- and post-treatment to measure AHI, arousal index and sleep architecture, to investigate the effect of intervention group, time, sleep stage (N1-3 or REM) and posture (supine or nonsupine) on OSA severity. The CBTi group showed a 7.5 event·h-1 greater AHI difference (mean (95% CI) decrease 5.5 (1.3-9.7) events·h-1, Cohen's d=0.2, from 36.4 events·h-1 pre-treatment) across sleep-stages and postures, compared to control (mean increase 2.0 (-2.0-6.1) events·h-1, d=0.01, from 37.5 events·h-1 at pre-treatment; interaction p=0.012). Compared to control, the CBTi group also had a greater reduction in total number (mean difference 5.6 (0.6-10.6) greater overall reduction; p=0.029) and duration of nocturnal awakenings (mean difference 21.1 (2.0-40.3) min greater reduction; p=0.031) but showed no difference in the arousal index, or sleep architecture. CBTi consolidates sleep periods and promotes a 15% decrease in OSA severity in patients with comorbid insomnia and OSA. This suggests that insomnia disorder may exacerbate OSA and provides further support for treating insomnia in the presence of comorbid OSA.

The effect of cognitive and behavioral therapy for insomnia on week-to-week changes in sleepiness and sleep parameters in patients with comorbid insomnia and sleep apnea: a randomized controlled trial.

STUDY OBJECTIVES: While cognitive and behavioral therapy for insomnia (CBTi) is an effective treatment in patients with comorbid moderate and severe obstructive sleep apnea (OSA), there is concern that the bedtime restriction component of CBTi might dangerously exacerbate daytime sleepiness in such patients. We examined randomized controlled trial data to investigate the effect of OSA severity, and pretreatment daytime sleepiness on week-to-week changes in daytime sleepiness and sleep parameters during CBTi and no-treatment control. METHODS: One hundred and forty-five patients with untreated physician-diagnosed OSA (apnea-hypopnea index ≥15) and psychologist-diagnosed insomnia (ICSD-3) were randomized to a 4-week CBTi program (n = 72) or no-treatment control (n = 73). The Epworth sleepiness scale (ESS) and sleep diaries were completed during pretreatment, weekly CBTi sessions, and posttreatment. Effects of OSA severity, pretreatment daytime sleepiness, and intervention group on weekly changes in daytime sleepiness and sleep parameters were investigated. RESULTS: The CBTi group reported a 15% increase in ESS scores following the first week of bedtime restriction (M change = 1.3 points, 95% CI = 0.1-2.5, p = 0.031, Cohen's d = 0.27) which immediately returned to pretreatment levels for all subsequent weeks, while sleep parameters gradually improved throughout CBTi. There were no differences in changes in daytime sleepiness during treatment between CBTi and control groups or OSA-severity groups. Higher pretreatment ESS scores were associated with a greater ESS reduction during CBTi. CONCLUSIONS: CBTi appears to be a safe and effective treatment in the presence of comorbid moderate and severe OSA. Nevertheless, patients living with comorbid insomnia and sleep apnea and treated with CBTi should be monitored closely for increased daytime sleepiness during the initial weeks of bedtime restriction therapy. CLINICAL TRIAL REGISTRATION: Treating comorbid insomnia with obstructive sleep apnoea (COMISA) study: A new treatment strategy for patients with combined insomnia and sleep apnoea, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id = 365184 Australian New Zealand Clinical Trials Registry: ACTRN12613001178730. Universal Trial Number: U1111-1149-4230.

Cognitive and behavioral therapy for insomnia increases the use of continuous positive airway pressure therapy in obstructive sleep apnea participants with comorbid insomnia: a randomized clinical trial.

STUDY OBJECTIVES: Insomnia and obstructive sleep apnea (OSA) commonly co-occur which makes OSA difficult to treat with continuous positive airway pressure (CPAP). We conducted a randomized controlled trial in participants with OSA and co-occurring insomnia to test the hypothesis that initial treatment with cognitive and behavioral therapy for insomnia (CBT-i), versus treatment as usual (TAU) would improve insomnia symptoms and increase subsequent acceptance and use of CPAP. METHODS: One hundred and forty-five participants with OSA (apnea-hypopnea index ≥ 15) and comorbid insomnia were randomized to either four sessions of CBT-i, or TAU, before commencing CPAP therapy until 6 months post-randomization. Primary between-group outcomes included objective average CPAP adherence and changes in objective sleep efficiency by 6 months. Secondary between-group outcomes included rates of immediate CPAP acceptance/rejection, and changes in; sleep parameters, insomnia severity, and daytime impairments by 6 months. RESULTS: Compared to TAU, participants in the CBT-i group had 61 min greater average nightly adherence to CPAP (95% confidence interval [CI] = 9 to 113; p = 0.023, d = 0.38) and higher initial CPAP treatment acceptance (99% vs. 89%; p = 0.034). The CBT-i group showed greater improvement of global insomnia severity, and dysfunctional sleep-related cognitions by 6 months (both: p < 0.001), and greater improvement in sleep impairment measures immediately following CBT-i. There were no between-group differences in sleep outcomes, or daytime impairments by 6 months. CONCLUSIONS: In OSA participants with comorbid insomnia, CBT-i prior to initiating CPAP treatment improves CPAP use and insomnia symptoms compared to commencing CPAP without CBT-i. OSA patients should be evaluated for co-occurring insomnia and considered for CBT-i before commencing CPAP therapy. CLINICAL TRIAL: Treating comorbid insomnia with obstructive sleep apnea (COMSIA) study: A new treatment strategy for patients with combined insomnia and sleep apnea, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=365184 Australian New Zealand Clinical Trials Registry: ACTRN12613001178730. Universal Trial Number: U1111-1149-4230.