Increased mean diffusivity of the caudal motor SNc identifies patients with REM sleep behaviour disorder and Parkinson's disease.

Idiopathic rapid eye movement sleep behaviour disorder (iRBD)-a Parkinson's disease (PD) prodrome-might exhibit neural changes similar to those in PD. Substantia nigra pars compacta (SNc) degeneration underlies motor symptoms of PD. In iRBD and early PD (ePD), we measured diffusion MRI (dMRI) in the caudal motor SNc, which overlaps the nigrosome-1-the earliest-degenerating dopaminergic neurons in PD-and in the striatum. Nineteen iRBD, 26 ePD (1.7 ± 0.03 years), and 46 age-matched healthy controls (HCs) were scanned at Western University, and 47 iRBD, 115 ePD (0.9 ± 0.01 years), and 56 HCs were scanned through the Parkinson's Progression Markers Initiative, using 3T MRI. We segmented the SNc and striatum into subregions using automated probabilistic tractography to the cortex. We measured mean diffusivity (MD) and fractional anisotropy (FA) along white-matter bundles and subregional surfaces. We performed group-level and classification analyses. Increased caudal motor SNc surface MD was the only iRBD-HCs and ePD-HCs difference replicating across datasets (padj < 0.05). No iRBD-ePD differences emerged. Caudal motor SNc surface MD classified patient groups from HCs at the single-subject level with good-to-excellent balanced accuracy in an independent sample (0.91 iRBD and 0.86 iRBD and ePD combined), compared to fair performance for total SNc surface MD (0.72 iRBD and ePD). Caudal motor SNc surface MD correlated significantly with MDS-UPDRS-III scores in ePD patients. Using dMRI and automated segmentation, we detected changes suggesting altered microstructural integrity in iRBD and ePD in the nigrostriatal subregion known to degenerate first in PD. Surface MD of the caudal motor SNc presents a potential measure for inclusion in neuroimaging biomarkers of iRBD and PD.

Subregional analysis of striatum iron in Parkinson's disease and rapid eye movement sleep behaviour disorder.

The loss of dopamine in the striatum underlies motor symptoms of Parkinson's disease (PD). Rapid eye movement sleep behaviour disorder (RBD) is considered prodromal PD and has shown similar neural changes in the striatum. Alterations in brain iron suggest neurodegeneration; however, the literature on striatal iron has been inconsistent in PD and scant in RBD. Toward clarifying pathophysiological changes in PD and RBD, and uncovering possible biomarkers, we imaged 26 early-stage PD patients, 16 RBD patients, and 39 age-matched healthy controls with 3 T MRI. We compared mean susceptibility using quantitative susceptibility mapping (QSM) in the standard striatum (caudate, putamen, and nucleus accumbens) and tractography-parcellated striatum. Diffusion MRI permitted parcellation of the striatum into seven subregions based on the cortical areas of maximal connectivity from the Tziortzi atlas. No significant differences in mean susceptibility were found in the standard striatum anatomy. For the parcellated striatum, the caudal motor subregion, the most affected region in PD, showed lower iron levels compared to healthy controls. Receiver operating characteristic curves using mean susceptibility in the caudal motor striatum showed a good diagnostic accuracy of 0.80 when classifying early-stage PD from healthy controls. This study highlights that tractography-based parcellation of the striatum could enhance sensitivity to changes in iron levels, which have not been consistent in the PD literature. The decreased caudal motor striatum iron was sufficiently sensitive to PD, but not RBD. QSM in the striatum could contribute to development of a multivariate or multimodal biomarker of early-stage PD, but further work in larger datasets is needed to confirm its utility in prodromal groups.

Treatment for patients with sleep apnea on opioids for chronic pain: results of the OpSafe trial.

STUDY OBJECTIVES: Approximately 20% of North Americans are afflicted with chronic pain with 3% being opioid users. The objective was to determine whether patients on opioids for chronic pain with newly diagnosed sleep apnea attended sleep clinic review and followed treatment recommendations. METHODS: The study was a post hoc analysis from a multicenter perspective cohort study. Inclusion criteria included adults taking opioid medications for chronic pain for >3 months. Demographic data and daily opioid dose were collected. Sleep apnea was diagnosed via level 1 polysomnography. Patients who attended sleep clinic review were grouped based on the types of treatment they received. RESULTS: A total of 204 patients completed polysomnography and 58.8% were diagnosed to have sleep apnea (apnea-hypopnea index ≥5 events/h). Of those with sleep apnea, 58% were recommended to have an evaluation by a sleep physician. Body mass index and age were 29.5 ± 6 kg/m² and 56 ± 12 years, respectively. Of those with newly diagnosed sleep apnea, 25% received treatment, with the majority being treated with positive airway pressure therapy, whereas the rest received positional therapy and opioids/sedative reduction. The adherence rate of positive airway pressure therapy was 55% at 1 year. Over 50% of participants on opioids for chronic pain with newly diagnosed sleep apnea declined attendance for sleep clinic review or treatment. CONCLUSIONS: There was a high refusal rate to attend clinic for treatment. Adherence to positive airway pressure therapy was low at 55%. This sheds light on the high rate of treatment nonadherence and the need for further research. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Opioid Safety Program in Pain Clinics (Op-Safe); URL: https://www.clinicaltrials.gov/ct2/show/NCT02513836; Identifier: NCT02513836.

Development of Learning Curves for Bronchoscopy: Results of a Multicenter Study of Pulmonary Trainees.

BACKGROUND: There are currently no reference standards for the development of competence in bronchoscopy. RESEARCH QUESTION: The aims of this study were to (1) develop learning curves for bronchoscopy skill development and (2) estimate the number of bronchoscopies required to achieve competence. STUDY DESIGN AND METHODS: Trainees from seven North American academic centers were enrolled at the beginning of their pulmonology training. Performance during clinical bronchoscopies was assessed by supervising physicians using the Ontario Bronchoscopy Assessment Tool (OBAT). Group-level learning curves were modeled using a quantile regression growth model, where the dependent variable was the mean OBAT score and the independent variable was the number of bronchoscopies performed at the time the OBAT was completed. RESULTS: A total of 591 OBAT assessments were collected from 31 trainees. The estimated regression quantiles illustrate significantly different learning curves based on trainees' performance percentiles. When competence was defined as the mean OBAT score for all bronchoscopies rated as being completed without need for supervision, the mean OBAT score associated with competence was 4.54 (95% CI, 4.47-4.58). Using this metric, the number of bronchoscopies required to achieve this score varied from seven to 10 for the 90th percentile of trainees and from 109 to 126 for the lowest 10th percentile of trainees. When competence was defined as the mean OBAT score for the first independent bronchoscopy, the mean was 4.40 (95% CI, 4.20-4.60). On the basis of this metric, the number of bronchoscopies required varied from one to 11 for the 90th percentile of trainees and from 83 to 129 for the lowest 10th percentile of trainees. INTERPRETATION: We were able to generate learning curves for bronchoscopy across a range of trainees and centers. Furthermore, we established the average number of bronchoscopies required for the attainment of competence. This information can be used for purposes of curriculum planning and allows a trainee's progress to be compared with an established norm.

SIESTA - Home sleep study with BresoDx for obstructive sleep apnea: a randomized controlled trial.

STUDY OBJECTIVES: The objectives of this study were to evaluate (1) the accuracy of the clinical diagnosis of obstructive sleep apnea (OSA) informed by the home sleep study with a Type 4 portable monitor BresoDx® versus Type 1 polysomnography (PSG); and (2) agreement of the apnea-hypopnea index (AHI) compared between BresoDx and PSG. MATERIAL AND METHODS: This was a randomized, parallel, multicentre, single-blind, pragmatic controlled trial enrolling adults referred to three Ontario sleep clinics for suspected OSA. Participants were randomized to BresoDx followed by PSG (one-night apart) or PSG followed by BresoDx sleep testing sequence arms. The primary outcomes included the accuracy of clinical diagnosis and OSA severity measured by AHI between tests. RESULTS: In sum, 233 participants completed both sleep studies and 206 completed physician consultation visits. The agreement between clinical diagnosis informed by PSG versus BresoDx was fair (Cohen's kappa coefficient = 0.28). The sensitivity of BresoDx-informed clinical diagnosis against PSG was between 0.86 and 0.89, and the specificity between 0.38 and 0.44. For AHI cut-off of ≥5 events/hour the sensitivity, specificity and positive and negative predictive values were 0.85, 0.48, 0.81 and 0.54. CONCLUSIONS: Home sleep apnea testing with BresoDx can be used in a referral population with a high pretest probability of OSA similar to other Type IV devices. This study complements the existing body of evidence suggesting that home testing with portable devices plays a valuable role for diagnosing of OSA in a variety of settings. SIESTA TRIAL REGISTRATION: www.clinicaltrials.gov (Identifier: NCT02003729).