Disturbed sleep in post-traumatic stress disorder: secondary symptom or core feature?

The hypothesis that rapid eye movement (REM) sleep disturbances are the hallmark of posttraumatic stress disorder (PTSD), proposed by Ross and colleagues in 1989, has stimulated a wealth of clinical, preclinical, and animal studies on the role of sleep in the pathophysiology of PTSD. The present review revisits this influential hypothesis in light of clinical and experimental findings that have since accumulated. Polysomnographic studies conducted in adults with PTSD have yielded mixed findings regarding REM sleep disturbances, and they generally suggest modest and nonspecific sleep disruptions. Prospective and treatment studies have provided more robust evidence for the relationship between sleep disturbances and psychiatric outcomes and symptoms. Experimental animal and human studies that have probed the relationship between REM sleep and fear responses, as well as studies focused more broadly on sleep-dependent affective and memory processes, also provide strong support for the hypothesis that sleep pl...

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Sleep Disturbances as the Hallmark of PTSD: Where Are We Now?

Sleep-specific mechanisms underlying posttraumatic stress disorder: Integrative review and neurobiological hypotheses

Temporal relations between sleep problems and both traumatic event exposure and PTSD: a critical review of the empirical literature.

The efficacy of nabilone, a synthetic cannabinoid, in the treatment of PTSD-associated nightmares: A preliminary randomized, double-blind, placebo-controlled cross-over design study.

Subjective reports of sleep disturbance indicate that 70–91% of patients with post-traumatic stress disorder (PTSD) have difficulty falling or staying asleep. Nightmares are reported by 19–71% of patients, depending on the severity of their PTSD and their exposure to physical aggression. Objective measures of sleep disturbance are inconsistent, with some studies that used these measures indicating poor sleep and others finding no differences compared with non-PTSD controls. Future research in this area may benefit from examining measures of instability in the microstructure of sleep. Additionally, recent findings suggest that sleep disordered breathing (SDB) and sleep movement disorders are more common in patients with PTSD than in the general population and that these disorders may contribute to the brief awakenings, insomnia and daytime fatigue in patients with PTSD. Overall, sleep problems have an impact on the development and symptom severity of PTSD and on the quality of life and functioning of patients. In terms of treatments, SSRIs are commonly used to treat PTSD, and evidence suggests that they have a small but significant positive effect on sleep disruption. Studies of serotonin-potentiating non-SSRIs suggest that nefazodone and trazodone lead to significant reductions in insomnia and nightmares, whereas cyproheptadine may exacerbate sleep problems in patients with PTSD. Prazosin, a centrally acting α1-adrenoceptor antagonist, has led to large reductions in nightmares and insomnia in small studies of patients with PTSD. Augmentation of SSRIs with olanzapine, an atypical antipsychotic, may be effective for treatment-resistant nightmares and insomnia, although adverse effects can be significant. Additional medications, including zolpidem, buspirone, gabapentin and mirtazapine, have been found to improve sleep in patients with PTSD. Large randomised, placebo-controlled trials are needed to confirm the above findings. In contrast, evidence suggests that benzodiazepines, TCAs and MAOIs are not useful for the treatment of PTSD-related sleep disorders, and their adverse effect profiles make further studies unlikely. Cognitive behavioural interventions for sleep disruption in patients with PTSD include strategies targeting insomnia and imagery rehearsal therapy (IRT) for nightmares. One large randomised controlled trial of group IRT demonstrated significant reductions in nightmares and insomnia. Similarly, uncontrolled studies combining IRT and insomnia strategies have demonstrated good outcomes. Uncontrolled studies of continuous positive airway pressure for SDB in patients with PTSD show that this treatment led to significant decreases in nightmares, insomnia and PTSD symptoms. Controlled studies are needed to confirm these promising findings.

Sleep disturbances in patients with post-traumatic stress disorder: epidemiology, impact and approaches to management

Although electrophysiological studies are commonly used in the management of patients with ventricular tachycardia (VT), the reproducibility of these studies during therapy has not been established in patients in whom VT is associated with conditions other than coronary artery disease. Therefore, we performed confirmation studies during drug therapy in 60 patients (mean age 48 +/- 18 years; 41 male) with sustained ventricular arrhythmias induced during initial study to assess the reproducibility of drug effect. The stimulation protocol used included the serial introduction of up to three premature ventricular stimuli during sinus rhythm and with ventricular pacing at two pacing rates. Rapid ventricular pacing techniques were also used. Antiarrhythmic drug efficacy was confirmed in 78% of patients. Sustained VT was induced at repeat electrophysiological study in 18% of patients during antiarrhythmic therapy that had been felt to be effective on the basis of a single drug study. We conclude that electrophysiological study results during antiarrhythmic therapy exhibit significant day-to-day variability. Sustained VT can be induced during antiarrhythmic therapy previously determined to be effective by electrophysiological techniques in many patients.

Reproducibility of electrophysiological testing during antiarrhythmic therapy for ventricular arrhythmias unrelated to coronary artery disease



Video capsule endoscopy (VCE) is an attractive method for diagnosing and objectively monitoring disease activity in celiac disease (CeD). Its use, facilitated by artificial intelligence-based tools, may allow computer-assisted interpretation of VCE studies, transforming a subjective test into a quantitative and reproducible measurement tool.



To evaluate and compare objective CeD severity assessment as determined with VCE by expert human readers and a machine learning algorithm (MLA).



Patients ≥ 18 years with histologically proven CeD underwent VCE. Examination frames were scored by three readers from one center and the MLA, using a 4-point ordinal scale for assessing the severity of CeD enteropathy. After scoring, curves representing CeD severity across the entire small intestine (SI) and individual tertiles (proximal, mid, and distal) were fitted for each reader and the MLA. All comparisons used Krippendorff’s alpha; values > 0.8 represent excellent to ‘almost perfect’ inter-reader agreement.



VCEs from 63 patients were scored. Readers demonstrated strong inter-reader agreement on celiac villous damage (alpha=0.924), and mean value reader curves showed similarly excellent agreement with MLA curves (alpha=0.935). Average reader and MLA curves were comparable for mean and maximum values for the first SI tertile (alphas=0.932 and 0.867, respectively) and the mean value over the entire SI (alpha=0.945).



A novel MLA demonstrated excellent agreement on whole SI imaging with three expert gastroenterologists. An ordinal scale permitted high inter-reader agreement, accurately and reliably replicated by the MLA. Interpreting VCEs using MLAs may allow automated diagnosis and disease burden assessment in CeD


Quantification of Celiac Disease Severity Using Video Capsule Endoscopy: A Comparison of Human Experts and Machine Learning Algorithms

The prevalence of mental health disorders is high among people with Cystic Fibrosis. The psychological symptoms in CF are associated with poor adherence, worse treatment outcomes, and greater health utilization/cost. Mental health and neurocognitive Adverse Events (AEs) have been reported with all available Cystic Fibrosis Transmembrane conductance Regulator (CFTR) modulators in small groups of patients. We report our experience with a dose reduction strategy in 10 of our patients on elexacaftor/tezacaftor/ivacaftor (7.9% of total number of patients) who self-reported developing intense anxiety, irritability, sleep disturbance and/or mental slowness after initiation of full dose treatment. Standard dose elexacaftor/tezacaftor/ivacaftor resulted in 14.3 points improvement in mean Percent Predicted Forced Expiratory Volume in 1 s (ppFEV1), and a mean difference in sweat chloride of −39.3 mmol/L. We initially discontinued and/or reduced therapy according to the AEs severity, with a subsequent planned dose escalation every 4–6 weeks guided by sustainability of clinical effectiveness, absence of AEs recurrence, and patients’ preferences. Clinical parameters including lung function and sweat chloride were monitored for up to 12 weeks to assess ongoing clinical response to the reduced dose regimen. Dose reduction resulted in resolution of self-reported mental/psychological AEs, without loss of clinical effectiveness (ppFEV1 was 80.7% on standard dose, and 83.4% at 12 weeks on reduced dose; sweat chloride was 33.4 and 34 mmol/L on standard and reduced dose, respectively). Furthermore, in a subgroup of patients who completed 24 weeks of the reduced dose regimen, repeat low dose Computed Tomography imaging showed a significant response when compared to pre-initiation of elexacaftor/tezacaftor/ivacaftor.

Individualized approach to elexacaftor/tezacaftor/ivacaftor dosing in cystic fibrosis, in response to self-reported anxiety and neurocognitive adverse events: A case series

Michael J Maher

Papers

Sleep disturbances in patients with post-traumatic stress disorder: epidemiology, impact and approaches to management

Reproducibility of electrophysiological testing during antiarrhythmic therapy for ventricular arrhythmias unrelated to coronary artery disease

Quantification of Celiac Disease Severity Using Video Capsule Endoscopy: A Comparison of Human Experts and Machine Learning Algorithms

Individualized approach to elexacaftor/tezacaftor/ivacaftor dosing in cystic fibrosis, in response to self-reported anxiety and neurocognitive adverse events: A case series