Performance comparison of peripheral arterial tonometry-based testing and polysomnography to diagnose obstructive sleep apnea in military personnel.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is increasingly common among military personnel, but diagnostic capabilities are challenged by limited capability for polysomnography (PSG). We sought to evaluate the diagnostic properties of peripheral arterial tonometry (PAT)-based home sleep apnea testing (HSAT) to accurately identify and classify OSA among active-duty military personnel. METHODS: This study was a retrospective review of all patients suspected of having OSA who completed an initial PAT-based HSAT followed by confirmatory PSG within 120 days. The diagnostic properties of a PAT-based, HSAT-derived apnea-hypopnea index (AHI) vs a PSG-derived AHI were assessed. RESULTS: Two hundred eight matched pairs of asynchronous studies were analyzed. The prevalence of OSA was 63.5%. PAT-based HSAT overdiagnosed 27.4% of patients with OSA and underdiagnosed 46.6% of patients with OSA. The majority (n = 116, 55.8%) of patients changed OSA severity classification (absent, mild, moderate, severe) after PSG. OSA severity classification concordance between PAT-based HSAT and PSG was observed in 53.4%, 40.5%, 28.6%, and 40.0% of patients with absent, mild, moderate, and severe OSA, respectively. Receiver operating characteristic curve analysis showed an area under the curve of 0.715 and a proposed PAT-based, HSAT-derived AHI cutoff score for OSA diagnosis of 9.0 events/h. This PAT-based, HSAT-derived AHI provided a 52% sensitivity, 83% specificity, 84% positive predictive value, and 50% negative predictive value. Bland-Altman plots showed an unacceptable degree of agreement between PAT-based, HSAT-derived AHI and AHI. CONCLUSIONS: There is significant discordance between PAT-based HSAT and PSG among active-duty military personnel evaluated for OSA. PAT-based HSAT may have limited utility for diagnosing OSA and grading severity in this unique patient population. CITATION: O'Reilly BM, Wang Q, Collen J, Matsangas P, Colombo CJ, Mysliwiec V. Performance comparison of peripheral arterial tonometry-based testing and polysomnography to diagnose obstructive sleep apnea in military personnel. J Clin Sleep Med. 2022;18(6):1523-1530.

5-Azacytidine Transiently Restores Dysregulated Erythroid Differentiation Gene Expression in TET2-Deficient Erythroleukemia Cells.

DNA methyltransferase inhibitors (DNMTI) like 5-Azacytidine (5-Aza) are the only disease-modifying drugs approved for the treatment of higher-risk myelodysplastic syndromes (MDS), however less than 50% of patients respond, and there are no predictors of response with clinical utility. Somatic mutations in the DNA methylation regulating gene tet-methylcytosine dioxygenase 2 (TET2) are associated with response to DNMTIs, however the mechanisms responsible for this association remain unknown. Using bisulfite padlock probes, mRNA sequencing, and hydroxymethylcytosine pull-down sequencing at several time points throughout 5-Aza treatment, we show that TET2 loss particularly influences DNA methylation (5mC) and hydroxymethylation (5hmC) patterns at erythroid gene enhancers and is associated with downregulation of erythroid gene expression in the human erythroleukemia cell line TF-1. 5-Aza disproportionately induces expression of these down-regulated genes in TET2KO cells and this effect is related to dynamic 5mC changes at erythroid gene enhancers after 5-Aza exposure. We identified differences in remethylation kinetics after 5-Aza exposure for several types of genomic regulatory elements, with distal enhancers exhibiting longer-lasting 5mC changes than other regions. This work highlights the role of 5mC and 5hmC dynamics at distal enhancers in regulating the expression of differentiation-associated gene signatures, and sheds light on how 5-Aza may be more effective in patients harboring TET2 mutations. IMPLICATIONS: TET2 loss in erythroleukemia cells induces hypermethylation and impaired expression of erythroid differentiation genes which can be specifically counteracted by 5-Azacytidine, providing a potential mechanism for the increased efficacy of 5-Aza in TET2-mutant patients with MDS. VISUAL OVERVIEW: http://mcr.aacrjournals.org/content/molcanres/19/3/451/F1.large.jpg.

Trauma associated sleep disorder: A parasomnia induced by trauma.

Nightmares and disruptive nocturnal behaviors that develop after traumatic experiences have long been recognized as having different clinical characteristics that overlap with other established parasomnia diagnoses. The inciting experience is typically in the setting of extreme traumatic stress coupled with periods of sleep disruption and/or deprivation. The limited number of laboratory documented cases and symptomatic overlap with rapid eye movement sleep behavior disorder (RBD) and posttraumatic stress disorder (PTSD) have contributed to difficulties in identifying what is a unique parasomnia. Trauma associated sleep disorder (TSD) incorporates the inciting traumatic experience and clinical features of trauma related nightmares and disruptive nocturnal behaviors as a novel parasomnia. The aims of this theoretical review are to 1) summarize the known cases and clinical findings supporting TSD, 2) differentiate TSD from clinical disorders with which it has overlapping features, 3) propose criteria for the diagnosis of TSD, and 4) present a hypothetical neurobiological model for the pathophysiology of TSD. Hyperarousal, as opposed to neurodegenerative changes in RBD, is a component of TSD that likely contributes to overriding atonia during REM sleep and the comorbid diagnosis of insomnia. Lastly, a way forward to further establish TSD as an accepted sleep disorder is proposed.

Adverse Effects of Cholinesterase Inhibitors in Dementia, According to the Pharmacovigilance Databases of the United-States and Canada.

This survey analyzes two national pharmacovigilance databases in order to determine the major adverse reactions observed with the use of cholinesterase inhibitors in dementia. We conducted a statistical analysis of the Food and Drug Administration Adverse Event Reporting System (FAERS) and the Canada Vigilance Adverse Reaction Database (CVARD) concerning the side effects of cholinesterase inhibitors. The statistics calculated for each adverse event were the frequency and the reporting odds ratios (ROR). A total of 9877 and 2247 reports were extracted from the FAERS and CVARD databases, respectively. A disproportionately higher frequency of reports of death as an adverse event for rivastigmine, compared to the other acetylcholinesterase inhibiting drugs, was observed in both the FAERS (ROR = 3.42; CI95% = 2.94-3.98; P<0.0001) and CVARD (ROR = 3.67; CI95% = 1.92-7.00; P = 0.001) databases. While cholinesterase inhibitors remain to be an important therapeutic tool against Alzheimer's disease, the disproportionate prevalence of fatal outcomes with rivastigmine compared with alternatives should be taken into consideration.

Adherence to positive airway pressure therapy in U.S. military personnel with sleep apnea improves sleepiness, sleep quality, and depressive symptoms.

OBJECTIVES: Obstructive sleep apnea (OSA) is frequently diagnosed in U.S. military personnel. OSA is associated with sleepiness, poor sleep quality, and service-related illnesses of insomnia, depression, post-traumatic stress disorder, and traumatic brain injury. METHODS: Observational study of active duty military personnel with OSA and adherence to positive airway pressure (PAP) assessed with smart chip technology. RESULTS: 58 men with mean age 36.2 ± 7.7 years, mean body mass index 31.4 ± 3.7 with mean apnea-hypopnea index (AHI) 19.1 ± 19.0 are reported. 23 (39.7%) participants were adherent to PAP, and 35 (60.3%) were nonadherent. No significant differences in baseline demographics, apnea-hypopnea index, service-related illnesses, or clinical instrument scores. Military personnel adherent to PAP had significantly improved sleepiness (p = 0.007), sleep quality (p = 0.013), depressive symptoms (p = 0.01), energy/fatigue (p = 0.027), and emotional well-being (p = 0.024). Participants with moderate-severe OSA were more likely to be in the adherent group when compared with participants diagnosed with mild OSA. CONCLUSIONS: Military personnel with OSA have low adherence to PAP. Adherence is associated with improved depressive symptoms, sleepiness, sleep quality, energy/fatigue, emotional well-being, and social functioning. Future research should focus on interventions to improve the management of OSA in military personnel.