Zolpidem and Eszopiclone Pre-medication for PSG: Effects on Staging, Titration, and Adherence.

Introduction: The non-benzodiazepine sedative hypnotic (NBSH) eszopiclone improves polysomnography (PSG) quality and continuous positive airway pressure (CPAP) adherence. It is unclear whether zolpidem has the same effect and neither NBSH has been studied in populations with milder forms of obstructive sleep apnea. Materials and Methods: We performed a retrospective analysis on patients undergoing level I PSG at our institution. Patients are pre-medicated with NBSHs at the discretion of the sleep physician. We compared PSG/CPAP titration quality and subsequent CPAP adherence for patients receiving NBSHs or no pre-study medication. We adjusted for obstructive sleep apnea pre-test probability (PTP), arousal threshold, and other factors showing differences at baseline. Results: Data on 560 patients were analyzed. Mean age and body mass index were 42.2 ± 10.1 and 28.8 ± 4.5, respectively. Median apnea hypopnea index was 12.9 (6.4-25.3), 100 (18.0%) patients had normal studies, 97 (17.3%) were split, and 457 (81.6%) had a respiratory low-arousal threshold. After adjusting for differences at baseline, neither NBSH was associated with sleep efficiency, wake after sleep onset, or total sleep time on PSG. After adjustment, patients receiving eszopiclone had a higher apnea hypopnea index at the final CPAP pressure (ß = 14.2; 95% confidence intervals (CI) 7.2-21.2; p < 0.001) and were more likely to have an unacceptable titration (odds ratio (OR) = 6.6; 95% CI 2.0-21.0; p = 0.002). When only split-night studies were examined, there were no differences in any adherence variables across or between categories. Conclusions: In a population with predominantly mild obstructive sleep apnea, NBSHs did not improve PSG or CPAP titration quality and did not increase CPAP adherence. There was no difference in effect between eszopiclone and zolpidem.

A Rapid, Handheld Device to Assess Respiratory Resistance: Clinical and Normative Evidence.

INTRODUCTION: Following reports of respiratory symptoms among service members returning from deployment to South West Asia (SWA), an expert panel recommended pre-deployment spirometry be used to assess disease burden. Unfortunately, testing with spirometry is high cost and time-consuming. The airflow perturbation device (APD) is a handheld monitor that rapidly measures respiratory resistance (APD-Rr) and has promising but limited clinical data. Its speed and portability make it ideally suited for large volume pre-deployment screening. We conducted a pilot study to assess APD performance characteristics and develop normative values. MATERIALS AND METHODS: We prospectively enrolled subjects and derived reference equations for the APD from those without respiratory symptoms, pulmonary disease, or tobacco exposure. APD testing was conducted by medical technicians who received a 10-min in-service on its use. A subset of subjects performed spirometry and impulse oscillometry (iOS), administered by trained respiratory therapists. APD measures were compared with spirometry and iOS. RESULTS: The total study population included 199 subjects (55.8% males, body mass index 27.7 ± 6.0 kg/m2, age 49.9 ± 18.7 yr). Across the three APD trials, mean inspiratory (APD-Ri), expiratory (APD-Re), and average (APD-Ravg) resistances were 3.30 ± 1.0, 3.69 ± 1.2, and 3.50 ± 1.1 cm H2O/L/s. Reference equations were derived from 142 clinically normal volunteers. Height, weight, and body mass index were independently associated with APD-Ri, APD-Re, and APD-Ravg and were combined with age and gender in linear regression models. APD-Ri, APD-Re, and APD-Ravg were significantly inversely correlated with FEV1 (r = -0.39 to -0.42), FVC (r = -0.37 to -0.40), and FEF25-75 (r = -0.31 to -0.35) and positively correlated with R5 (r = 0.61-0.62), R20 (r = 0.50-0.52), X5 (r = -0.57 to -0.59), and FRES (r = 0.42-0.43). Bland-Altman plots showed that the APD-Rr closely approximates iOS when resistance is normal. CONCLUSION: Rapid testing was achieved with minimal training required, and reference equations were constructed. APD-Rr correlated moderately with iOS and weakly with spirometry. More testing is required to determine whether the APD has value for pre- and post-deployment respiratory assessment.

Using the STOPBANG questionnaire and other pre-test probability tools to predict OSA in younger, thinner patients referred to a sleep medicine clinic.

BACKGROUND: The STOPBANG questionnaire is used to predict the presence of obstructive sleep apnea (OSA). We sought to assess the performance of the STOPBANG questionnaire in younger, thinner patients referred to a sleep medicine clinic. METHODS: We applied the STOPBANG questionnaire to patients referred for level I polysomnography (PSG) at our sleep center. We calculated likelihood ratios and area under the receiver operator characteristic (AUROC) curve and performed sensitivity analyses. RESULTS: We performed our analysis on 338 patients referred for PSG. Only 17.2% (n = 58) were above age 50 years, and 30.5 and 6.8% had a BMI above 30 and 35 years, respectively. The mean apnea-hypopnea index (AHI) was 12.9 ± 16.4 and 63.9% had an AHI ≥5. The STOPBANG (threshold ≥3) identified 83.1% of patients as high risk for an AHI ≥5, and sensitivity, specificity, positive (PPV), and negative predictive values (NPV) were 83.8, 18.0, 64.4, and 38.0%, respectively. Positive and negative likelihood ratios were poor at 1.02-1.11 and 0.55-0.90, respectively, across AHI thresholds (AHI ≥5, AHI ≥15 and AHI ≥30), and AUROCs were 0.52 (AHI ≥5) and 0.56 (AHI ≥15). Sensitivity analyses adjusting for insomnia, combat deployment, traumatic brain injury, post-traumatic stress disorder, clinically significant OSA (ESS >10 and/or co-morbid disease), and obesity did not significantly alter STOPBANG performance. CONCLUSIONS: In a younger, thinner population with predominantly mild-to-moderate OSA, the STOPBANG Score does not accurately predict the presence of obstructive sleep apnea.

A mobile, web-based system can improve positive airway pressure adherence.

SleepMapper is a mobile, web-based system that allows patients to self-monitor their positive airway pressure therapy, and provides feedback and education in real time. In addition to the usual, comprehensive support provided at our clinic, we gave the SleepMapper to 30 patients initiating positive airway pressure. They were compared with patients initiating positive airway pressure at our clinic without SleepMapper (controls) to determine whether SleepMapper affected adherence. A total of 61 patients had polysomnographic and adherence data analysed, 30 were given SleepMapper and 31 received our standard of care. The two groups were well matched at baseline to include no significant differences in age, apnea-hypopnea index, percentage receiving split-night polysomnographs and starting pressures. Patients in the control group received significantly more non-benzodiazepine sedative hypnotics the night of their polysomnography and during positive airway pressure initiation. At 11 weeks, patients in the SleepMapper group had a greater percentage of nights with any use (78.0 ± 22.0 versus 55.5 ± 24.0%; P < 0.001) and >4 h positive airway pressure use (78.0 ± 22.0 versus 55.5 ± 24.0%; P = 0.02). There was a trend toward more patients in the SleepMapper group achieving >4 h of use for at least 70% of nights [9/30 (30%) versus 3/31 (9.7%); P = 0.06]. In multivariate linear regression, the SleepMapper remained significantly associated with percentage of nights >4 h positive airway pressure use (ß coefficient = 0.18; P = 0.02). Added to our usual, comprehensive programme to maximize positive airway pressure adherence in new users, the SleepMapper was independently associated with an 18% increase in nights >4 h of use.

Eszopiclone and Zolpidem Do Not Affect the Prevalence of the Low Arousal Threshold Phenotype.

STUDY OBJECTIVES: We sought to determine whether non benzodiazepine sedative hypnotics (NBSH) reduce the occurrence of the low arousal threshold (LAT) phenotype. METHODS: Consecutive patients with suspected obstructive sleep apnea (OSA) referred for polysomnography (PSG) had demographic and PSG data abstracted. LAT was estimated using PSG criteria. After adjusting for pretest probability (PTP) for OSA, we calculated the effect that premedication with NBSHs has on LAT prevalence. RESULTS: Five hundred seventy-nine patients with a mean age and body mass index of 42.2 ± 10.1 y and 28.9 ± 4.5 kg/m2, respectively, had data available for analysis. Most patients (444, or 80.9%) had a LAT, and administering a NBSH (zolpidem or eszopiclone) on the same night as the PSG did not change LAT prevalence (NBSH: 339 (83.3%) versus no drug: 100 (80.6%); p = 0.50). Adjusting for PTP, neither administration of eszopiclone (odds ratio 0.80 (95% confidence interval: 0.33-2.0); 0.69) nor zolpidem (odds ratio 1.65 (95% confidence interval: 0.8-3.5); p = 0.19) reduced the odds that a patient had a LAT. NBSHs did not change the mean SpO2 nadir, percentage hypopneas, or apnea-hypopnea index. There was no association between zolpidem or eszopiclone dosing and SpO2 nadir (zolpidem: ß = -0.69, p = 0.80; eszopiclone: ß = -1.53, p = 0.68), percentage hypopneas (zolpidem: ß = 2.2, p = 0.43; eszopiclone ß = -6.2, p = 0.46), or apnea-hypopnea index (zolpidem: ß = 3.1, p = 0.22; eszopiclone: ß = 2.6, p = 0.39). CONCLUSIONS: The LAT is common in our population and NBSH premedication does not alter its occurrence. Further studies are needed to determine how the LAT can be optimally managed to improve OSA treatment.

Molecular characterization of neuroendocrine prostate cancer and identification of new drug targets.

UNLABELLED: Neuroendocrine prostate cancer (NEPC) is an aggressive subtype of prostate cancer that most commonly evolves from preexisting prostate adenocarcinoma (PCA). Using Next Generation RNA-sequencing and oligonucleotide arrays, we profiled 7 NEPC, 30 PCA, and 5 benign prostate tissue (BEN), and validated findings on tumors from a large cohort of patients (37 NEPC, 169 PCA, 22 BEN) using IHC and FISH. We discovered significant overexpression and gene amplification of AURKA and MYCN in 40% of NEPC and 5% of PCA, respectively, and evidence that that they cooperate to induce a neuroendocrine phenotype in prostate cells. There was dramatic and enhanced sensitivity of NEPC (and MYCN overexpressing PCA) to Aurora kinase inhibitor therapy both in vitro and in vivo, with complete suppression of neuroendocrine marker expression following treatment. We propose that alterations in Aurora kinase A and N-myc are involved in the development of NEPC, and future clinical trials will help determine from the efficacy of Aurora kinase inhibitor therapy. SIGNIFICANCE: We report on the largest in-depth molecular analysis of NEPC and provide new insight into molecular events involved in the progression of prostate cancer.