Optimization of the Antibacterial Spectrum and the Developability Profile of the Novel-Class Natural Product Corramycin.

Corramycin 1 is a novel zwitterionic antibacterial peptide isolated from a culture of the myxobacterium Corallococcus coralloides. Though Corramycin displayed a narrow spectrum and modest MICs against sensitive bacteria, its ADMET and physchem profile as well as its high tolerability in mice along with an outstanding in vivo efficacy in an Escherichia coli septicemia mouse model were promising and prompted us to embark on an optimization program aiming at enlarging the spectrum and at increasing the antibacterial activities by modulating membrane permeability. Scanning the peptidic moiety by the Ala-scan strategy followed by key stabilization and introduction of groups such as a primary amine or siderophore allowed us to enlarge the spectrum and increase the overall developability profile. The optimized Corramycin 28 showed an improved mouse IV PK and a broader spectrum with high potency against key Gram-negative bacteria that translated into excellent efficacy in several in vivo mouse infection models.

Targeted Hypoglossal Nerve Stimulation for Patients With Obstructive Sleep Apnea: A Randomized Clinical Trial.

Importance: Evidence is lacking from randomized clinical trials of hypoglossal nerve stimulation in obstructive sleep apnea (OSA). Objective: To evaluate the safety and effectiveness of targeted hypoglossal nerve stimulation (THN) of the proximal hypoglossal nerve in patients with OSA. Design, Setting, and Participants: This randomized clinical trial (THN3) was conducted at 20 centers and included 138 patients with moderate to severe OSA with an apnea-hypopnea index (AHI) of 20 to 65 events per hour and body mass index (calculated as weight in kilograms divided by height in meters squared) of 35 or less. The trial was conducted from May 2015 through June 2018. Data were analyzed from January 2022 through January 2023. Intervention: Implant with THN system; randomized 2:1 to activation at month 1 (treatment) or month 4 (control). All received 11 months of THN with follow-up at months 12 and 15, respectively. Main Outcomes and Measures: Primary effectiveness end points comprised AHI and oxygen desaturation index (ODI) responder rates (RRs). Treatment responses at months 4 and 12/15 were defined as a 50% or greater reduction in AHI to 20 or less per hour and an ODI decrease of 25% or greater. Coprimary end points comprised (1) month 4 AHI and ODI RR in the treatment greater than the control group and (2) month 12/15 AHI and ODI RR in the entire cohort exceeding 50%. Secondary end points included sleep apnea severity (AHI and ODI) and patient-reported outcomes (Epworth Sleepiness Scale, Functional Outcomes of Sleep Questionnaire, and EQ-5D visual analog scale). Results: Among 138 participants, the mean (SD) age was 56 (9) years, and 19 (13.8%) were women. Month 4 THN RRs were substantially greater in those in the treatment vs control group (AHI, 52.3% vs 19.6%; ODI, 62.5% vs 41.3%, respectively) with treatment-control standardized mean differences of 0.725 (95% CI, 0.360-1.163) and 0.434 (95% CI, 0.070-0.843) for AHI and ODI RRs, respectively. Months 12/15 RRs were 42.5% and 60.4% for AHI and ODI, respectively. Improvements in AHI, ODI, Epworth Sleepiness Scale, Functional Outcomes of Sleep Questionnaire, and EQ-5D visual analog scale scores were all clinically meaningful (medium to large effect size). Two serious adverse events and 100 nonserious related adverse events were observed from the implant procedure or study protocol. Conclusions and Relevance: This randomized clinical trial found that THN demonstrated improvements in sleep apnea, sleepiness, and quality of life in patients with OSAs over an extended AHI and body mass index range without prior knowledge of pharyngeal collapse pattern. Clinically meaningful improvements in AHI and patient-reported responses compared favorably with those of distal hypoglossal nerve stimulation trials, although clinically meaningful differences were not definitive for ODI. Trial Registration: ClinicalTrials.gov Identifier: NCT02263859.

The Value of Oxygen Desaturation Index for Diagnosing Obstructive Sleep Apnea: A Systematic Review.

OBJECTIVES: Intermittent hypoxemia is a risk factor for developing complications in obstructive sleep apnea (OSA) patients. The objective of this systematic review was to identify articles evaluating the accuracy of the oxygen desaturation index (ODI) as compared with the apnea-hypopnea index (AHI) and then provide possible values to use as a cutoff for diagnosing adult OSA. STUDY DESIGN: Systematic Review of Literature. METHODS: PubMed, the Cochrane Library, and SCOPUS databases were searched through November 2019. RESULTS: Eight studies (1,924 patients) met criteria (age range: 28-70.9 years, body mass index range: 21.9-37 kg/m2 , and AHI range: 0.5-62 events/hour). Five studies compared ODI and AHI simultaneously, and three had a week to months between assessments. Sensitivities ranged from 32% to 98.5%, whereas specificities ranged from 47.7% to 98%. Significant heterogeneity was present; however, for studies reporting data for a 4% ODI ≥ 15 events/hour, the specificity for diagnosing OSA ranged from 75% to 98%, and only one study reported the positive predictive value, which was 97%. Direct ODI and AHI comparisons were not made because of different hypopnea scoring, different oxygen desaturation categories, and different criteria for grading OSA severity. CONCLUSION: Significant heterogeneity exists in studies comparing ODI and AHI. Based on currently published studies, consideration should be given for diagnosing adult OSA with a 4% ODI of ≥ 15 events/hour and for recommending further evaluation for diagnosing OSA with a 4% ODI ≥ 10 events/hour. Screening with oximetry may be indicated for the detection of OSA in select patients. Further study is needed before a definitive recommendation can be made. Laryngoscope, 131:440-447, 2021.

SAR439859, a Novel Selective Estrogen Receptor Degrader (SERD), Demonstrates Effective and Broad Antitumor Activity in Wild-Type and Mutant ER-Positive Breast Cancer Models.

Primary treatment for estrogen receptor-positive (ER+) breast cancer is endocrine therapy. However, substantial evidence indicates a continued role for ER signaling in tumor progression. Selective estrogen receptor degraders (SERD), such as fulvestrant, induce effective ER signaling inhibition, although clinical studies with fulvestrant report insufficient blockade of ER signaling, possibly due to suboptimal pharmaceutical properties. Furthermore, activating mutations in the ER have emerged as a resistance mechanism to current endocrine therapies. New oral SERDs with improved drug properties are under clinical investigation, but the biological profile that could translate to improved therapeutic benefit remains unclear. Here, we describe the discovery of SAR439859, a novel, orally bioavailable SERD with potent antagonist and degradation activities against both wild-type and mutant Y537S ER. Driven by its fluoropropyl pyrrolidinyl side chain, SAR439859 has demonstrated broader and superior ER antagonist and degrader activities across a large panel of ER+ cells, compared with other SERDs characterized by a cinnamic acid side chain, including improved inhibition of ER signaling and tumor cell growth. Similarly, in vivo treatment with SAR439859 demonstrated significant tumor regression in ER+ breast cancer models, including MCF7-ESR1 wild-type and mutant-Y537S mouse tumors, and HCI013, a patient-derived tamoxifen-resistant xenograft tumor. These findings indicate that SAR439859 may provide therapeutic benefit to patients with ER+ breast cancer, including those who have resistance to endocrine therapy with both wild-type and mutant ER.

Discovery of 6-(2,4-Dichlorophenyl)-5-[4-[(3S)-1-(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-8,9-dihydro-7H-benzo[7]annulene-2-carboxylic acid (SAR439859), a Potent and Selective Estrogen Receptor Degrader (SERD) for the Treatment of Estrogen-Receptor-Positive Breast Cancer.

More than 75% of breast cancers are estrogen receptor alpha (ERα) positive (ER+), and resistance to current hormone therapies occurs in one-third of ER+ patients. Tumor resistance is still ERα-dependent, but mutations usually confer constitutive activation to the hormone receptor, rendering ERα modulator drugs such as tamoxifen and aromatase inhibitors ineffective. Fulvestrant is a potent selective estrogen receptor degrader (SERD), which degrades the ERα receptor in drug-resistant tumors and has been approved for the treatment of hormone-receptor-positive metastatic breast cancer following antiestrogen therapy. However, fulvestrant shows poor pharmacokinetic properties in human, low solubility, weak permeation, and high metabolism, limiting its administration to inconvenient intramuscular injections. This Drug Annotation describes the identification and optimization of a new series of potent orally available SERDs, which led to the discovery of 6-(2,4-dichlorophenyl)-5-[4-[(3S)-1-(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-8,9-dihydro-7H-benzo[7]annulene-2-carboxylic acid (43d), showing promising antitumor activity in breast cancer mice xenograft models and whose properties warranted clinical evaluation.

Updated Concepts on Treatment Outcomes for Obstructive Sleep Apnea.

Obstructive sleep apnea is a highly prevalent and poorly understood condition that not only leads to significant individual patient health damage, but carries a large societal cost secondary to excessive healthcare utilization, motor-vehicle accidents, and work absenteeism. While a significant fund of knowledge about its damaging effects on the cardiovascular system and neural pathways has been gathered over the past few decades, the translation to direct patient care still presents numerous challenges. With the exception of clear issues such as socially unacceptable snoring and breathing irregularities, the exact cause and effect relationship between airway narrowing, hypoxemia, and sleep fragmentation with subjective sleep-related complaints and neurocognitive symptoms is less clear. Besides better-defined clinical diagnostic criteria, the need for clear serum, saliva, or urine biomarkers to assess the physiologic burden of disease remains a work in progress, as are well-defined long-term clinically relevant outcomes of interest. Here, readers will be guided to a critical evaluation on the current main metrics of sleep study, suggested steps on diagnostic and treatment goals, and introduced to the concept of a continuum of disease.

Dexmedetomidine versus propofol during drug-induced sleep endoscopy and sedation: a systematic review.

BACKGROUND: The purpose of the present study is to review the international literature, using a systematic review, for studies comparing propofol and dexmedetomidine for drug-induced sleep endoscopy (DISE) or sedation in which there is a description of the effect of the agents on the upper airway and associated variables (e.g., vital signs, sedation scores). METHODS: This is a systematic review through October 4, 2016. PubMed/MEDLINE and four additional databases were accessed for this study. RESULTS: Two hundred twenty studies were screened, 79 were downloaded, and 10 met criteria. The majority of the studies identified dexmedetomidine as the preferred pharmacologic agent for DISE due to an overall safer and more stable profile based upon hemodynamic stability. However, propofol provided greater airway obstruction with oxygen desaturations. With either agent, the degree of obstruction in the upper airway lacks some degree of validity as to whether the obstructions accurately represent natural sleep or are simply a drug-induced effect. CONCLUSION: Dexmedetomidine and propofol have their advantages and disadvantages during DISE. Generally, dexmedetomidine was preferred and seemed to provide a more stable profile based upon cardiopulmonary status. However, propofol has a quicker onset, has a shorter half-life, and can demonstrate larger degrees of obstruction, which might more accurately reflect what happens during REM sleep. Additional research is recommended.

Genial tubercle advancement and genioplasty for obstructive sleep apnea: A systematic review and meta-analysis.

OBJECTIVE: To perform a systematic review and meta-analysis for studies evaluating genioplasty alone, genial tubercle advancement (GTA) alone, and GTA with hyoid surgery (GTA-HS) to treat obstructive sleep apnea (OSA). DATA SOURCES: Ten databases. REVIEW METHODS: Three authors searched through November 15, 2015. RESULTS: 1,207 studies were screened; 69 were downloaded; and 13 studies met inclusion criteria. A total of 111 patients were included, with 27 standard genioplasty, 10 modified genioplasty, 24 GTA, and 50 GTA-HS patients. For standard genioplasty, the apnea-hypopnea index (AHI) reduced from a mean ± standard deviation (M ± SD) of 18.8 ± 3.8 (95% confidence interval [CI] 17.6, 20.0) to 10.8 ± 4.0 (95% CI 9.5, 12.1) events/hour (relative reduction 43.8%), P value = 0.0001. Genioplasty improved lowest oxygen saturation (LSAT) from 82.3 ± 7.3% (95% CI 80.0, 84.7) to 86.8 ± 5.2% (95% CI 85.1, 88.5), P value = 0.0032. For modified genioplasty AHI increased by 37.3%. For GTA, the AHI reduced from an M ± SD of 37.6 ± 24.2 (95% CI 27.9, 47.3) to 20.4 ± 15.1 (95% CI 14.4, 26.4) events/hour (relative reduction 45.7%), P value = 0.0049. GTA improved LSAT from 83.1 ± 8.3% (95% CI 79.8, 86.4) to 85.5 ± 6.8% (95% CI 82.8, 88.2), P value = 0.2789. For GTA-HS, the AHI reduced from an M ± SD of 34.5 ± 22.1 (95% CI 28.4, 40.6) to 15.3 ± 17.6 (95% CI 10.4, 20.2) events/hour (relative reduction 55.7%), P value < 0.0001; GTA-HS improved LSAT from 80.1 ± 16.6% (95% CI 75.5, 84.7) to 88.3 ± 6.9% (95% CI 86.4, 90.2), P value = 0.0017. CONCLUSION: Standard genioplasty, GTA and GTA-HS can improve OSA outcomes such as AHI and LSAT. Given the low number of studies, these procedures remain as an area for additional OSA research. Laryngoscope, 127:984-992, 2017.

Rapid maxillary expansion for pediatric obstructive sleep apnea: A systematic review and meta-analysis.

OBJECTIVES/HYPOTHESIS: To perform a systematic review with meta-analysis for sleep study outcomes in children who have undergone rapid maxillary expansion (RME) as treatment for obstructive sleep apnea (OSA). DATA SOURCES: PubMed/MEDLINE and eight additional databases. REVIEW METHODS: Three authors independently and systematically reviewed the international literature through February 21, 2016. RESULTS: Seventeen studies reported outcomes for 314 children (7.6 ± 2.0 years old) with high-arched and/or narrow hard palates (transverse maxillary deficiency) and OSA. Data were analyzed based on follow-up duration: ≤3 years (314 patients) and >3 years (52 patients). For ≤3-year follow-up, the pre- and post-RME apnea-hypopnea index (AHI) decreased from a mean ± standard deviation (M ± SD) of 8.9 ± 7.0/hr to 2.7 ± 3.3/hr (70% reduction). The cure rate (AHI <1/hr) for 90 patients for whom it could be calculated was 25.6%. Random effects modeling for AHI standardized mean difference (SMD) is -1.54 (large effect). Lowest oxygen saturation (LSAT) improved from 87.0 ± 9.1% to 96.0 ± 2.7%. Random effects modeling for LSAT SMD is 1.74 (large effect). AHI improved more in children with previous adenotonsillectomy or small tonsils (73-95% reduction) than in children with large tonsils (61% reduction). For >3-year follow-up (range = 6.5-12 years), the AHI was reduced from an M ± SD of 7.1 ± 5.7/hr to 1.5 ± 1.8/hr (79% reduction). CONCLUSIONS: Improvement in AHI and lowest oxygen saturation has consistently been seen in children undergoing RME, especially in the short term (<3-year follow-up). Randomized trials and more studies reporting long-term data (≥3-year follow-up) would help determine the effect of growth and spontaneous resolution of OSA. Laryngoscope, 2016 Laryngoscope, 127:1712-1719, 2017.

Predictors of Nasal Obstruction: Quantification and Assessment Using Multiple Grading Scales.

UNLABELLED: Objective. To evaluate the association between nasal obstruction and (1) demographic factors, (2) medical history, (3) physical tests, and (4) nasal exam findings. Study Design. CASE SERIES: Methods. Chart review at a tertiary medical center. Results. Two hundred-forty consecutive patients (52.1 ± 17.5 years old, with a Nasal Obstruction Symptom Evaluation (NOSE) score of 32.0 ± 24.1) were included. Demographic factors and inferior turbinate sizes were not associated with NOSE score or Nasal Obstruction Visual Analog Scale (NO-VAS). A significant association was found between higher NOSE score on univariate analysis and positive history of nasal trauma (p = 0.0136), allergic rhinitis (p < 0.0001), use of nasal steroids (p = 0.0108), higher grade of external nasal deformity (p = 0.0149), higher internal nasal septal deviation grade (p = 0.0024), and narrow internal nasal valve angle (p < 0.0001). Multivariate analysis identified the following as independent predictors of high NOSE score: NO-VAS: ≥50 (Odds Ratio (OR) = 17.6 (95% CI 5.83-61.6), p < 0.0001), external nasal deformity: grades 2-4 (OR = 4.63 (95% CI 1.14-19.9), p = 0.0339), and allergic rhinitis: yes (OR = 5.5 (95% CI 1.77-18.7), p = 0.0041). Conclusion. Allergic rhinitis, NO-VAS score ≥ 50, and external nasal deformity (grades 2-4) were statistically significant independent predictors of high NOSE scores on multivariate analysis. Inferior turbinate size was not associated with NOSE scores or NO-VAS.

Mini Tracheostomy for Obstructive Sleep Apnea: An Evidence Based Proposal.

Objective. To search for articles evaluating the use of tracheostomies (either permanent stomas or tracheostomy tubes) in adult obstructive sleep apnea (OSA) patients and to evaluate the potential for the use of mini tracheostomies as treatment for OSA. Study Design. Systematic review. Methods. Nine databases were searched from inception through July 21, 2015. Results. The overall tracheostomy search yielded 516 articles, of which eighteen studies provided polysomnographic data. No study was identified (empty review) for the use of mini tracheostomies for treating OSA. The mini tracheostomy search yielded ninety-five articles which describe findings for either mini tracheostomy kits (inner cannula diameter of 4 mm) or the performance of mini tracheotomies. Six articles described the use of mini tracheostomies as a temporary procedure to relieve acute upper airway obstruction and none described the use for OSA. For tracheostomy stomal sites, suturing the skin directly to the tracheal rings with defatting can minimize stomal site collapse. The smallest tracheostomy stomal size that can successfully treat OSA has not been described. Conclusion. Mini tracheostomies as small as 4 mm have been successfully used in the short term to relieve upper airway obstruction. Given that polysomnography data are lacking, additional research is needed.

Maxillary expansion and maxillomandibular expansion for adult OSA: A systematic review and meta-analysis.

OBJECTIVE: This study sought to systematically review the international literature for articles evaluating maxillary expansion and maxillomandibular expansion as treatments for obstructive sleep apnea (OSA) in adults and to perform a meta-analysis. DATA SOURCES: Nine databases (including MEDLINE/PubMed). REVIEW METHODS: Searches were performed through January 8, 2016. The PRISMA statement was followed. RESULTS: Eight adult studies (39 patients) reported polysomnography and/or sleepiness outcomes. Six studies reported outcomes for maxillary expansion (36 patients), and the apnea-hypopnea index (AHI) decreased from a mean (M) ± standard deviation (SD) of 24.3 ± 27.5 [95% CI 15.3, 33.3] to 9.9 ± 13.7 [95% CI 5.4, 14.4] events/hr (relative reduction: 59.3%). Maxillary expansion improved lowest oxygen saturation (LSAT) from a M ± SD of 84.3 ± 8.1% [95% CI 81.7, 87.0] to 86.9 ± 5.6% [95% CI 85.1, 88.7]. Maxillomandibular expansion was reported in two studies (3 patients) and AHI decreased from a M ± SD of 47.53 ± 29.81 [95% CI -26.5 to 121.5] to 10.7 ± 3.2 [95% CI 2.8, 18.6] events/hr (relative reduction: 77.5%). Maxillomandibular expansion improved LSAT from a M ± SD of 76.7 ± 14.5% [95% CI 40.7, 112.7] to 89.3 ± 3.1 [95% CI 81.6, 97]. CONCLUSION: The current literature demonstrates that maxillary expansion can improve and maxillomandibular expansion can possibly improve AHI and LSAT in adults; however, given the paucity of studies, these remain open for additional research efforts.

Nasal Septal Deviations: A Systematic Review of Classification Systems.

Objective. To systematically review the international literature for internal nasal septal deviation classification systems and summarize them for clinical and research purposes. Data Sources. Four databases (including PubMed/MEDLINE) were systematically searched through December 16, 2015. Methods. Systematic review, adhering to PRISMA. Results. After removal of duplicates, this study screened 952 articles for relevance. A final comprehensive review of 50 articles identified that 15 of these articles met the eligibility criteria. The classification systems defined in these articles included C-shaped, S-shaped, reverse C-shaped, and reverse S-shaped descriptions of the septal deviation in both the cephalocaudal and anteroposterior dimensions. Additional studies reported use of computed tomography and categorized deviation based on predefined locations. Three studies graded the severity of septal deviations based on the amount of deflection. The systems defined in the literature also included an evaluation of nasal septal spurs and perforations. Conclusion. This systematic review ascertained that the majority of the currently published classification systems for internal nasal septal deviations can be summarized by C-shaped or reverse C-shaped, as well as S-shaped or reverse S-shaped deviations in the anteroposterior and cephalocaudal dimensions. For imaging studies, predefined points have been defined along the septum. Common terminology can facilitate future research.

Tonsillectomy for adult obstructive sleep apnea: A systematic review and meta-analysis.

OBJECTIVES/HYPOTHESIS: To determine if sleepiness and sleep study variables (e.g., Apnea-Hypopnea Index [AHI] and lowest oxygen saturation) improve following isolated tonsillectomy for adult obstructive sleep apnea (OSA). STUDY DESIGN: Systematic review and meta-analysis. METHODS: Nine databases (PubMed/MEDLINE included) were searched through November 24, 2015. RESULTS: Seventeen studies (n = 216 patients, 34.4 ± 10.0 years and body mass index: 29.0 ± 6.1 kg/m(2) ) met criteria. Tonsils sizes were hypertrophied, large, enlarged, extremely enlarged, or grades 2 to 4. Apnea-Hypopnea Index decreased by 65.2% (from 40.5 ± 28.9/hour to 14.1 ± 17.1/hour) (n = 203). The AHI mean difference (MD) was -30.2 per hour (95% confidence interval [CI] -39.3, -21.1) (P value < 0.00001). The AHI SMD was -1.37 (-1.65, -1.09) (large effect). Lowest oxygen saturation improved from 77.7 ± 11.9% to 85.5 ± 8.2% (n = 186). Lowest oxygen saturation MD was 8.5% (95% CI 5.2, 11.8) (P value < 0.00001). The Epworth Sleepiness Scale decreased from 11.6 ± 3.7 to 6.1 ± 3.9 (P value < 0.00001) (n = 125). Individual patient outcomes (n = 54) demonstrated an 85.2% success rate (AHI < 20/hour and ≥ 50% reduction) and a 57.4% cure rate. Individual patient data meta-analysis showed preoperative AHI < 30 per hour to be a significant predictor of surgical success (P value < 0.001) and cure (P value = 0.043); among patients with preoperative AHI < 30 per hour, tonsillectomy success rate was 100% (25 of 25) and cure rate was 84% (21 of 25) with a mean postoperative AHI of 2.4 ± 2.1 per hour; this compares to tonsillectomy success rate of 72.4% (21 of 29), cure rate of 10 of 29 (34.4%), and mean postoperative AHI of 14.3 ± 13.9 per hour for patients with preoperative AHI ≥ 30 per hour. CONCLUSION: Isolated tonsillectomy can be successful as treatment for adult OSA, especially among patients with large tonsils and mild to moderate OSA (AHI < 30/hour). Laryngoscope, 2016 Laryngoscope, 126:2176-2186, 2016.

Inferior Turbinate Size and CPAP Titration Based Treatment Pressures: No Association Found among Patients Who Have Not Had Nasal Surgery.

Objective. To evaluate the effect of turbinate sizes on the titrated continuous positive airway pressure (CPAP) therapeutic treatment pressures for patients with obstructive sleep apnea (OSA) who have not had nasal surgery. Study Design. Retrospective case series. Methods. A chart review was performed for 250 consecutive patients. Results. 45 patients met inclusion criteria. The mean ± standard deviation (M ± SD) for age was 54.6 ± 22.4 years and for body mass index was 28.5 ± 5.9 kg/m(2). The Spearman's rank correlation coefficient (r s ) between CPAP therapeutic treatment pressures and several variables were calculated and were weakly correlated (age r s = 0.29, nasal obstruction r s = -0.30), moderately correlated (body mass index r s = 0.42 and lowest oxygen saturation r s = -0.47), or strongly correlated (apnea-hypopnea index r s = 0.60 and oxygen desaturation index (r s = 0.62)). No statistical significance was found with one-way analysis of variance (ANOVA) between CPAP therapeutic treatment pressures and inferior turbinate size (right turbinates p value = 0.2012, left turbinate p value = 0.3064), nasal septal deviation (p value = 0.4979), or mask type (p value = 0.5136). Conclusion. In this study, CPAP titration based therapeutic treatment pressures were not found to be associated with inferior turbinate sizes; however, the CPAP therapeutic treatment pressures were strongly correlated with apnea-hypopnea index and oxygen desaturation index.

Five-Minute Awake Snoring Test for Determining CPAP Pressures (Five-Minute CPAP Test): A Pilot Study.

Objective. To develop a quick, simple, bedside test for determining continuous positive airway pressures (CPAP) for obstructive sleep apnea (OSA) patients. Study Design. Prospective case series at a tertiary medical center. Methods. The Five-Minute Awake Snoring Test for Determining CPAP (Five-Minute CPAP Test) was developed and tested. Patients wear a soft-gel nasal triangle mask while holding a tongue depressor with the wide section (1.75 cm) between the teeth. Fixed pressure nasal CPAP is applied while the patient simulates snoring at 4 centimeters of water pressure. The pressure is incrementally titrated up and then down to determine the lowest pressure at which the patient cannot snore (Quiet Pressure). Results. Overall, thirty-eight patients participated. All could simulate snoring. Correlation coefficients were statistically significant between Quiet Pressures and body mass index (r s = 0.60 [strong positive relationship], p = 0.0088), apnea-hypopnea index (r s = 0.49 [moderate positive relationship], p = 0.039), lowest oxygen saturation (r s = -0.47 [moderate negative relationship], p = 0.048), and oxygen desaturation index (r s = 0.62 [strong positive relationship], p = 0.0057). Conclusion. This pilot study introduces a new concept, which is the final product of over one year of exploration, development, and testing. Five-Minute CPAP Test is a quick, inexpensive, and safe bedside test based on supine awake simulated snoring with nasal CPAP.

Hyoid surgery alone for obstructive sleep apnea: A systematic review and meta-analysis.

OBJECTIVES/HYPOTHESIS: The primary objective was to determine if sleep study variables (e.g., apnea-hypopnea index [AHI] and lowest oxygen saturation) and quantitative sleepiness data improve following isolated hyoid surgery for obstructive sleep apnea (OSA). STUDY DESIGN: Systematic review and meta-analysis. METHODS: Nine databases, including PubMed, were searched through September 5, 2015. RESULTS: Four hundred ninety-eight studies were screened, 64 were reviewed, and nine studies met inclusion criteria. A total of 101 patients were identified who underwent hyoid surgery alone for treatment of OSA. Subanalyses were performed for: 1) type of surgery, 2) primary versus secondary hyoid surgery, 3) positional versus nonpositional OSA, 4) age, and 5) body mass index. In patients undergoing isolated hyoid surgery, the AHI decreased from a mean ± standard deviation of 37.3 ± 21.1 (95% confidence interval [CI]: 33.1, 41.5) to 23.0 ± 18.6 (95% CI: 19.3, 26.7) events/hour, which correspond to a 38.3% reduction (P < .0001). AHI reduced by 38.3% for hyoid myotomy with suspension, by 50.7% for hyothyroidopexy, and by 7.1% for hyoid expansion. The Epworth Sleepiness Scale decreased by 3.2 points from 10.3 ± 4.9 (95% CI: 8.8, 11.8) to 7.1 ± 4.2 (95% CI: 5.8, 8.4; P = .0027). CONCLUSIONS: Isolated hyoid surgery has reduced OSA severity and improved sleepiness in adults. Hyothyroidopexy provided a 50.7% reduction in AHI, followed by hyoid myotomy with suspension (38.3% reduction in AHI) and hyoid expansion (7.1% reduction in AHI). The current literature lacks high-quality evidence with regard to hyoid surgery, and additional studies are needed to further elucidate the effect of hyoid surgery in OSA. LEVEL OF EVIDENCE: NA Laryngoscope, 126:1702-1708, 2016.

Supraglottoplasty for laryngomalacia with obstructive sleep apnea: A systematic review and meta-analysis.

OBJECTIVES/HYPOTHESIS: To determine if apnea-hypopnea index (AHI) and lowest oxygen saturation (LSAT) improve following isolated supraglottoplasty for laryngomalacia with obstructive sleep apnea (OSA) in children. STUDY DESIGN: Systematic review and meta-analysis. METHODS: Nine databases, including PubMed/MEDLINE, were searched through September 30, 2015. RESULTS: A total of 517 studies were screened; 57 were reviewed; and 13 met criteria. One hundred thirty-eight patients were included (age range: 1 month-12.6 years). Sixty-four patients had sleep exclusive laryngomalacia, and in these patients: 1) AHI decreased from a mean (M) ± standard deviation (SD) of 14.0 ± 16.5 (95% confidence interval [CI] 10.0, 18.0) to 3.3 ± 4.0 (95% CI 2.4, 4.4) events/hour (relative reduction: 76.4% [95% CI 53.6, 106.4]); 2) LSAT improved from a M ± SD of 84.8 ± 8.4% (95% CI 82.8, 86.8) to 87.6 ± 4.4% (95% CI 86.6, 88.8); 3) standardized mean differences (SMD) demonstrated a small effect for LSAT and a large effect for AHI; and 4) cure (AHI < 1 event/hour) was 10.5% (19 patients with individual data). Seventy-four patients had congenital laryngomalacia, and in these patients: 1) AHI decreased from a M ± SD of 20.4 ± 23.9 (95% CI 12.8, 28.0) to 4.0 ± 4.5 (95% CI 2.6, 5.4) events/hour (relative reduction: 80.4% [95% CI 46.6, 107.4]); 2) LSAT improved from a M ± SD of 74.5 ± 11.9% (95% CI 70.9, 78.1) to 88.4 ± 6.6% (95% CI 86.4, 90.4); 3) SMD demonstrated a large effect for both AHI and LSAT; and 4) cure was 26.5% (38 patients with individual data). CONCLUSION: Supraglottoplasty has improved AHI and LSAT in children with OSA and either sleep exclusive laryngomalacia or congenital laryngomalacia; however, the majority of them are not cured. Laryngoscope, 126:1246-1255, 2016.