Challenges and limitations of clinical trials in the adolescent and young adult CNS cancer population: A systematic review.

Background: The adolescent and young adult (AYA) cancer population, aged 15-39, carries significant morbidity and mortality. Despite growing recognition of unique challenges with this age group, there has been little documentation of unmet needs in their care, trial participation, and quality of life, particularly in those with primary brain tumors. Methods: A systematic literature review of 4 databases was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. Studies included editorials, reviews, and practice guidelines on the challenges and limitations faced by the AYA population. Papers had to address CNS tumors. Results: Sixty-eight studies met the inclusion criteria. The challenges and limitations in clinical trials in the AYA population were synthesized into 11 categories: molecular heterogeneity, tumor biology, diagnostic delay, access to care, physician factors, patient factors, primary brain tumor (PBT) factors, accrual, limited trials, long term follow up, and trial design. The published papers' recommendations were categorized based on the target of the recommendation: providers, coordination of care, organizations, accrual, and trial design. The AYA cancer population was found to suffer from unique challenges and barriers to care and the construction of trials. Conclusions: The AYA CNS cancer population suffers from unique challenges and barriers to care and construction of trials that make it critical to acknowledge AYAs as a distinct patient population. In addition, AYAs with primary brain tumors are underrecognized and underreported in current literature. More studies in the AYA primary brain tumor patient population are needed to improve their care and participation in trials.

Dose-response relationship between positive airway pressure therapy and excessive daytime sleepiness: the HomePAP study.

STUDY OBJECTIVES: The clinical benefits of positive airway pressure (PAP) therapy for obstructive sleep apnea are assumed to require adherent PAP usage, defined by the Centers for Medicare & Medicaid Services as ≥ 4 hours of use ≥ 70% of nights. However, this definition is based on early data and does not necessarily capture improvements at subthreshold adherence. We explored dose-response relationships between PAP adherence measures and excessive daytime sleepiness from the HomePAP randomized controlled trial. METHODS: Participants aged ≥ 18 years with an apnea-hypopnea index ≥ 15 events/h and baseline sleepiness (Epworth Sleepiness Scale [ESS] ≥ 12) received PAP therapy. Data were collected at baseline, 1-month follow-up, and 3-months follow-up. Regression models and receiver operating characteristic curves evaluated PAP measures as predictors of ESS change and normalization (ESS < 10). RESULTS: In 119 participants (aged 49.4 ± 12.6 years, 66.4% male, 72.3% White), > 50% were PAP nonadherent per Centers for Medicare & Medicaid Services criteria at 3 months. The percentage of nights with PAP use ≥ 4 hours predicted ESS change (P = .023), but not when controlling for the apnea-hypopnea index. The percentage of nights with ≥ 4 hours and average PAP use provided the best discrimination for predicting ESS normalization; each 10% increase in PAP use ≥ 4 hours increased the odds of ESS normalization by 22% (P = .007); those using PAP ≥ 4 hours had a nearly 3-fold greater odds of ESS normalization (P = .025). PAP use for at least 4 hours and on 70% of nights provided the best balance between specificity (0.50) and sensitivity (0.73). CONCLUSIONS: Although subadherent PAP usage may still confer some benefit for patients with obstructive sleep apnea, adherence to current criteria confers the highest likelihood for ESS change and normalization. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Portable Monitoring for Diagnosis and Management of Sleep Apnea (HomePAP); URL: https://clinicaltrials.gov/ct2/show/NCT00642486; Identifier: NCT00642486. CITATION: Pascoe M, Bena J, Andrews ND, et al. Dose-response relationship between positive airway pressure therapy and excessive daytime sleepiness: the HomePAP study. J Clin Sleep Med. 2022;18(4):1027-1034.

Association of Hypoglossal Nerve Stimulation With Improvements in Long-term, Patient-Reported Outcomes and Comparison With Positive Airway Pressure for Patients With Obstructive Sleep Apnea.

Importance: Hypoglossal nerve stimulation (HNS) and positive airway pressure (PAP) have been shown to improve patient-reported outcomes (PROs) in obstructive sleep apnea (OSA). However, to our knowledge, there are no data that compare change in PROs between HNS and PAP or that indicate whether HNS improves comorbid insomnia or depression in the long term. Objectives: To determine whether HNS is associated with improvements in patient-reported sleepiness, insomnia, and depression in the long term and to compare the respective associations of HNS and PAP with improved PROs. Design, Setting, and Participants: This retrospective cohort study used data from patients treated at the Cleveland Clinic for OSA. Participants received either HNS (referred sample) from November 1, 2015, to September 31, 2018, or PAP (previous cohort) from January 1, 2010, to December 31, 2014, for OSA. Patients were matched 3:1 for PAP:HNS based on age, body mass index (BMI; calculated as weight in kilograms divided by height in meters squared), sex, and apnea hypopnea index (AHI). Data were collected at baseline and at prespecified follow-up points. Data were analyzed from March 26, 2020, to September 9, 2021. Exposures: Treatment with HNS vs PAP. Main Outcomes and Measures: Data collected included AHI and Epworth Sleepiness Scale (ESS), Functional Outcomes of Sleep Questionnaire (FOSQ), Insomnia Severity Index (ISI), and Patient Health Questionnaire-9 (PHQ-9; depression) scores. Results: Among 85 patients receiving HNS (mean [SD] age, 62.8 [9.5] years; 59 men [69.4%]; 77 White patients [90.6%]; mean [SD] BMI, 28.8 [3.1]), compared with 217 matched patients receiving PAP (mean [SD] age, 62.1 [9.9] years; 157 men [72.4%]; 173 White patients [81.2%]; mean [SD] BMI, 29.5 [3.1]) included in the analysis, significant improvements were seen in PHQ-9 scores for HNS vs PAP (least square means, -4.06 [95% CI, -5.34 to -2.79] vs -2.58 [95% CI, -3.35 to -1.82]; mean difference, -1.48 [95% CI, -2.78 to -0.19]) with comparable improvements in ESS, FOSQ, and ISI scores. Clinically meaningful differences were observed in 42 of 65 HNS group patients (64.6%) vs 118 PAP group patients (54.5%) for ESS scores, 29 of 49 HNS group patients (59.2%) vs 67 of 217 PAP group patients (30.9%) for FOSQ scores, 14 of 48 HNS group patients (29.2%) vs 53 of 217 PAP group patients (24.4%) for PHQ-9 scores, and 23 of 49 HNS group patients (46.9%) vs 79 of 217 PAP group patients (36.4%) for ISI scores. At the 1-year post-HNS assessment, meaningful improvements were seen in 17 of 28 patients (60.7%) for ESS scores, 11 of 20 patients (55.0%) for FOSQ scores, 7 of 23 patients (30.4%) for PHQ-9 scores, and 11 of 25 patients (44.0%) for ISI scores. Conclusions and Relevance: In this cohort study of patients with OSA, sustained improvements in PROs were observed 1 year after HNS and were comparable to those for PAP at 3 months. These findings suggest that HNS is a viable treatment for improving insomnia and depression in patients with OSA.

The Epworth Sleepiness Scale in epilepsy: Internal consistency and disease-related associations.

BACKGROUND: The Epworth Sleepiness Scale (ESS) is the most common instrument for measuring subjective sleep propensity in people with epilepsy but has not yet been validated in this population. STUDY OBJECTIVES: We aimed to systematically assess the validity, performance, and internal consistency of the ESS, as well as correlations between the ESS and disease-specific variables and patient-reported outcome measures in a cohort of adults with epilepsy (AWE). METHODS: Ninety-five AWE completed sleep and seizure diaries, in-laboratory polysomnography (PSG) and patient-reported outcome measures, including the ESS, Insomnia Severity Index (ISI), and the Beck Depression Inventory (BDI). Demographic information and data from 95 matched controls referred for PSG for suspected obstructive sleep apnea (OSA) was taken from the electronic medical record. Frequencies of high ESS item ratings (item score ≥2) were calculated for each group. Cronbach's α and factor analysis were performed to assess the internal consistency and validity of the ESS within cases and controls. Multivariable linear models were used to assess the association between ESS and predictors of interest, adjusting for demographic and disease-specific variables, including seizure type, frequency, and anti-seizure medication (ASM) therapy. RESULTS: While suspected OSA controls had significantly greater mean ESS total scores (9.9 vs 7.9, p = 0.004) and proportion with ESS >10 (42% vs 25%, p = 0.014), there were no significant differences in the severity of item responses, with the exception of "lying down to rest in the afternoon when circumstances permit," for which more controls rated as likely/very likely (79% vs 64%), p = 0.024). AWE with ESS >10 had higher mean standardized ASM dose (2.5 vs 1.7, p = 0.026). All ESS items were significantly correlated with the total score within each group. Cronbach's α was 0.75 for cases and 0.85 for controls, indicating good internal consistency of the ESS for both groups. After adjusting for demographic and sleep characteristics, higher ESS scores were associated with greater insomnia scores on the ISI (p = 0.024) and depressive symptoms on the BDI (p = 0.018). CONCLUSIONS: This study provides validity for the use of the ESS in adult populations with epilepsy.

Fluoroscopy-Guided Transfacet Lumbar Epidural Steroid Injection for Symptomatic Synovial Cyst Treatment: A Case Report.

We report the case of a patient with a right-sided L4 synovial cyst, which had been causing significant pain, who had a successful transfacet epidural steroid injection to rupture the cyst. Using fluoroscopy, the needle was advanced through the right L4 facet joint and the cyst was ruptured using saline. The needle was then advanced into the epidural space and a transfacet epidural steroid injection was done. The patient's symptoms resolved. Repeat magnetic resonance imaging (MRI) done 2 years later showed no recurrence of the cyst. We discuss the role of transfacet epidural steroid injection in synovial cysts treatment.

Feasibility of electronic sleep disorder screening in healthcare workers of a large healthcare system.

STUDY OBJECTIVES: Many healthcare workers live with sleep disorders and may be unaware of their condition. We aimed to ascertain sleep disorder symptoms including high-risk obstructive sleep apnea (hrOSA), significant insomnia, and excessive daytime sleepiness (EDS) by work shift in a sample of healthcare workers. We aim to inform the development of a mobile application for sleep disorder screening and electronically-delivered follow-up recommendations. METHODS: An initial survey, including the Epworth Sleepiness Scale (ESS) for EDS, Insomnia Severity Scale (ISI) for insomnia, and STOP questionnaire for hrOSA, was completed by healthcare workers at the Cleveland Clinic. A follow-up survey sent ∼3-6 months after screening assessed perceptions of the utility of screening and subsequent actions taken by those with abnormal scores. RESULTS: 871 of 2851 (30.7%) workers who participated had abnormal ESS scores, with a significantly greater portion of night shift workers with abnormal scores compared to day or evening shift workers (p < 0.001). 27.5% of all workers had moderate to severe insomnia symptoms, with higher percentages of moderate or severe scores in evening and night shift workers (p < 0.001). 36.9% of workers had hrOSA, and of those previously diagnosed with obstructive sleep apnea (OSA) and using positive airway pressure therapy, over 90% reported treatment adherence (≥4 h per night). At follow-up, 92% of 484 respondents believed that sleep screening was valuable, with most taking some action after receiving abnormal results and over a quarter seeking sleep center treatment. CONCLUSIONS: Many healthcare workers, especially shift workers, experience sleep disorder symptoms, and our findings suggest that electronic sleep disorder symptom screening is feasible.

Impact of Positive Airway Pressure on International Restless Legs Syndrome Score in Sleep Disordered Breathing.

STUDY OBJECTIVE: Studies have shown increased prevalence of restless legs syndrome (RLS) in sleep disordered breathing (SDB), however limited data have focused on the impact of SDB therapy on RLS. We hypothesize that positive airway pressure (PAP) will improve the International Restless Legs Syndrome (IRLS) score among SDB patients compared to patients without PAP. METHODS: Patients with AHI ≥ 5 who responded positively to a RLS qualifier question from January 2010 to May 2015 were included in this retrospective study. IRLS score was used to measure RLS symptom severity. Two-sample t-tests and one-way analysis of variance were used to compare changes in IRLS score and linear regression models were created to examine IRLS change with PAP use and PAP adherence (PAP usage ≥4 h nightly for ≥70% of nights), adjusting for potential confounders. RESULTS: In 434 patients (51.9 ± 13.4years, 50.5% female, 77.6% Caucasian; 325 PAP, 109 control), IRLS scores improved from baseline to follow-up, with the PAP group achieving significant improvement after adjustment for covariates (difference in IRLS: -1.8 (CI -3.6,0.00), p = 0.050). In self-reported PAP adherent patients, IRLS improvement was greater than controls (-5.3 ± 7.4 vs. -2.7 ± 7.6 respectively, p = 0.045), and comparable to non-adherent patients (-5.3 ± 7.4 vs. -3.0 ± 7.0, p = 0.091). CONCLUSIONS: Among SDB patients with a positive RLS qualifier, those who used PAP therapy achieved significantly greater improvement in IRLS scores than patients who did not use PAP, with more significant changes in the PAP adherent group. This is the first large clinical study to examine these relationships, providing a basis for future prospective interventional trials and informing clinicians of expected improvement in IRLS score in PAP treated SDB populations.

Effects of Pharmacotherapy Treatment on Patient-Reported Outcomes in a Narcolepsy and Idiopathic Hypersomnia Cohort.

STUDY OBJECTIVE: We aimed to evaluate the association between patient-reported outcomes (PROs) and treatment regimen/standardized dose (STD), a measure of drug burden, in patients with narcolepsy type 1 (NT1)/type 2 (NT2) and idiopathic hypersomnia (IH). METHODS: Patients age 18 years or older with NT1/NT2 and IH with baseline and ≥ 6-month follow-up during 2008-2010 were included. Changes in PROs (Epworth Sleepiness Scale [ESS], Fatigue Severity Scale [FSS], Patient Health Questionnaire 9 [PHQ-9], total sleep time [TST]) by diagnosis, treatment regimen (monotherapy versus polytherapy, sodium oxybate [SO] use), and STD were assessed by t tests and univariable/multivariable linear regressions, adjusting for patient characteristics. RESULTS: A total of 92 patients (26 [28.3%] NT1, 27 [29.3%] NT2, 39 [42.4%] IH) were included (age 43.8 ± 14.8 years; 66 [71.7%] female). Baseline PROs suggested excessive daytime sleepiness (ESS 14.2 ± 5.2 [74% patients > 10]), significant fatigue (FSS 47.5 ± 12.9), and mild depression (PHQ-9 9.0 [4.0, 14.0] [49.4% ≥ 10]). At follow-up, ESS and PHQ-9 improved significantly overall and within diagnostic, monotherapy/polytherapy, and SO use groups (all P < .01). FSS improved significantly overall (P = .016), but improvements were not significant for IH, monotherapy, polytherapy, and non-SO using groups. In multivariable models, PRO changes were not significantly different between groups, but baseline STD was associated with worsening PHQ-9 across PHQ-9 change models, and ESS worsened with increasing STD at follow-up (P = .056). CONCLUSIONS: Significant improvements in sleep-related PROs were seen with pharmacotherapy use, regardless of diagnosis or treatment type, highlighting the importance of individualized prescribing decisions for this population.

Effect of Positive Airway Pressure Therapy on Drowsy Driving in a Large Clinic-Based Obstructive Sleep Apnea Cohort.

STUDY OBJECTIVES: Drowsy driving related to obstructive sleep apnea (OSA) represents an important public health problem with limited data on the effect of positive airway pressure (PAP) therapy. We hypothesize that PAP therapy will reduce self-reported drowsy driving in a large clinic-based OSA cohort. METHODS: Drowsy driving (self-reported near-accidents/accidents) incidents from baseline to after PAP therapy (stratified by adherence) were compared in a cohort of 2,059 patients with OSA who initiated PAP therapy from January 1, 2010 to December 31, 2014. Multivariable logistic regression models evaluated the dependence of change in drowsy driving incidents on other factors, including change in Epworth Sleepiness Scale (ESS) and Patient Health Questionnaire-9 (PHQ9) scores. RESULTS: In the entire cohort (age 56.0 ± 13.1 years, 45.4% female, 76.0% white, average follow-up 124.4 ± 67.3 days), drowsy driving incidents reduced from 14.2 to 6.9% after PAP therapy (P < .001). In subgroups, drowsy driving incidents reduced from 14% to 5.3% (P < .001) in patients who self-reported adherence to PAP therapy and 14.1% to 5.3% (P < .001) in patients objectively adherent to PAP therapy. For each one-point improvement in Epworth Sleepiness Scale score, the odds of drowsy driving decreased by about 14% (odds ratio 0.86, 95% confidence interval 0.82 to 0.90). CONCLUSIONS: In this clinic-based cohort, drowsy driving improved after adherent PAP usage, with greater drowsy driving risk for those with greater sleep propensity. This highlights the importance of and need for routine drowsy driving assessments and careful clinical attention to PAP adherence and sleep propensity in this population. Our findings should be confirmed and may be used to provide support for initiatives to address the public health issue of drowsy driving.

Pregnancy and Contraception Experiences in Women With Narcolepsy: A Narcolepsy Network Survey.

STUDY OBJECTIVES: To explore knowledge and experiences of women with narcolepsy on pregnancy and contraception issues and their relationships with narcolepsy pharmacotherapy. METHODS: An 18-item survey was administered through the Narcolepsy Network website for 8 weeks during the fall of 2012. The survey ascertained demographic information; prescription narcolepsy medication use and discontinuation during pregnancy; physician counseling regarding pregnancy, contraception, and medication usage; and pregnancy history and outcomes. Frequencies of responses were analyzed and compared between pharmacotherapy groups. RESULTS: Surveys from 182 women (age 41.5 ± 15.2 years) with narcolepsy were analyzed. Most of the respondents (78.7%) who reported a history of pregnancy did not use pharmacotherapy during pregnancy. Most of them discontinued narcolepsy pharmacotherapy during pregnancy because of their own fear of harming the fetus (82.9%), and 58.5% noted advice of discontinuation from their narcolepsy physician as a factor in their decision. As an alternative to pharmacotherapy, 72.1% of women extended their sleep time, 32.6% discontinued working, and 27.9% discontinued driving. Similar pregnancy and fetal outcomes were reported between women using monotherapy, polytherapy, or no therapy during pregnancy, but some outcomes were worse than national averages. In general, women with narcolepsy were dissatisfied with the amount and type of counseling that they received regarding pregnancy and contraception. CONCLUSIONS: Improved health education counseling and symptom management options are needed for women with narcolepsy to improve pregnancy management and outcomes in this population.