Sleep Quality in Neuromyelitis Optica Spectrum Disorder: A Systematic Review.

Background: This review summarizes the literature on sleep quality in neuromyelitis optica spectrum disorder (NMOSD) and discusses these findings in the context of current knowledge of sleep physiology. Methods: A literature search was performed using Ovid MEDLINE, Embase, and Scopus from inception to September 3, 2020. All included studies reported at least 1 measure of sleep quality in individuals with NMOSD. Pittsburgh Sleep Quality Index (PSQI) scores of individuals from 4 studies were compared with those from a data set of controls. Results: Thirteen studies (1041 individuals with NMOSD) were included in the review. Disturbed sleep was demonstrated across subjective metrics based on patient surveys and objective metrics such as polysomnography. An estimated 70% of individuals with NMOSD can be classified as poor sleepers. Standardized mean difference between PSQI scores of 183 individuals with NMOSD and those of 9284 controls was 0.72 (95% CI, 0.57-0.86; P < .001). Decreased sleep quality was significantly associated with decreased quality of life and increased anxiety, depression, and disability status. Sleep disturbances in NMOSD were similar in severity to those in multiple sclerosis. Conclusions: Sleep disturbances are a major contributor to NMOSD disease burden and may arise from the disruption of sleep circuitry, in addition to physical and psychological complications. Multiple processes involved in sleep regulation may be affected, such as, but not limited to, neural circadian circuit disruption, direct effects of inflammation, aminergic projecting system abnormalities, glymphatic system impairment, and development of sleep disorders such as restless legs syndrome/sleep apnea. A better understanding of these mechanisms is necessary for developing effective therapies for NMOSD-associated sleep disturbances.

Lesional psychiatric neurosurgery: meta-analysis of clinical outcomes using a transdiagnostic approach.

BACKGROUND: Four ablative neurosurgical procedures are used in the treatment of refractory psychiatric illness. The long-term effects of these procedures on psychiatric symptoms across disorders has never been synthesised and meta-analysed. METHODS: A preregistered systematic review was performed on studies reporting clinical results following ablative psychiatric neurosurgery. Four possible outcome measures were extracted for each study: depression, obsessive-compulsive symptoms, anxiety and clinical global impression. Effect sizes were calculated using Hedge's g. Equipercentile linking was used to convert symptom scores to a common metric. The main outcome measures were the magnitude of improvement in depression, obsessive compulsive symptoms, anxiety and clinical global impression. The secondary outcome was a subgroup analysis comparing the magnitude of symptom changes between the four procedures. RESULTS: Of 943 articles, 43 studies reporting data from 1414 unique patients, were included for pooled effects estimates with a random-effects meta-analysis. Results showed that there was a large effect size for improvements in depression (g=1.27; p<0.0001), obsessive-compulsive symptoms (g=2.25; p<0.0001) and anxiety (g=1.76; p<0.0001). The pooled clinical global impression improvement score was 2.36 (p<0.0001). On subgroup analysis, there was only a significant degree of heterogeneity in effect sizes between procedure types for anxiety symptoms, with capsulotomy resulting in a greater reduction in anxiety than cingulotomy. CONCLUSIONS: Contemporary ablative neurosurgical procedures were significantly associated with improvements in depression, obsessive-compulsive symptoms, anxiety and clinical global impression. PROSPERO REGISTRATION NUMBER: CRD42020164784.

A potential paradigm shift in opioid crisis management: The role of pharmacogenomics.

Pharmacogenetic investigations into the opioid crisis suggest genetic variation could be a significant cause of opioid-related morbidity and mortality. Variability in opioid system genes, including single nucleotide polymorphisms, manifest after pharmacogenetic testing, as previously invisible risk factors for addiction and overdose. Pharmacodynamic genes regulate opioid-sensitive brain networks and neural reward circuitry. Pharmacokinetic genes expressed in drug metabolic pathways regulate blood levels of active vs. inactive opioid metabolites. Elucidating the complex interplay of genetic variations in pharmacokinetic and pharmacodynamic pathways will shed new light on the addictive and toxic properties of opioids. This narrative review serves to promote understanding of key genetic mechanisms affecting the metabolism and actions of opioids, and to explore causes of the recent surge in opioid-related mortality associated with COVID-19. Personalised treatment plans centred around an individual's genetic makeup could make opioid-based pain management and opioid use disorder (OUD) treatments safer and more effective at both the individual and system levels.

Predicting Lung Function Following Lobectomy: A New Method to Adjust for Inherent Selection Bias.

BACKGROUND: Predictions that overestimate post-lobectomy lung function are more likely than underestimates to lead to lobectomy. Studies of post-lobectomy lung function have included only surgical patients, so overestimates are overrepresented. This selection bias has led to incorrect estimates of prediction bias, which has led to inaccurate threshold values for determining lobectomy eligibility. OBJECTIVE: The objective of this study was to demonstrate and adjust for this selection bias in order to arrive at correct estimates of prediction bias, the 95% limits of agreement, and adjusted threshold values for determining when exercise testing is warranted. METHODS: We conducted a retrospective study of patients evaluated for lobectomy. We used multiple imputations to determine postoperative results for patients who did not have surgery because their predicted postoperative values were low. We combined these results with surgical patients to adjust for selection bias. We used the Bland-Altman method and the bivariate normal distribution to determine threshold values for surgical eligibility. RESULTS: Lobectomy evaluation was performed in 114 patients; 79 had lobectomy while 35 were ineligible based on predicted values. Prediction bias using the Bland-Altman method changed significantly after controlling for selection bias. To achieve a postoperative FEV1 > 30% and DLCO ≥30%, a predicted FEV1 > 46% and DLCO ≥53% were required. Compared to current guidelines, using these thresholds would change management in 17% of cases. CONCLUSION: The impact of selection bias on estimates of prediction accuracy was significant but can be corrected. Threshold values for determining surgical eligibility should be reassessed.