- Email: [email protected]
Mandibular advancement for adult obstructive sleep apnea: A systematic review and meta-analysis
Accepted Manuscript Mandibular Advancement for Adult Obstructive Sleep Apnea: A Systematic Review and Meta-Analysis Michael W. Noller, BS, Christian Guilleminault, MD, Christopher Gouveia, MD, Douglas Mack, B.S, Charles Vivian, B.S, Jose Abdullatif, MD, Stefano Mangili, MD, Stanley Yung Liu, MD, DDS, Soroush Zaghi, MD, Macario Camacho, MD PII:
S1010-5182(17)30345-1
DOI:
10.1016/j.jcms.2017.10.006
Reference:
YJCMS 2807
To appear in:
Journal of Cranio-Maxillo-Facial Surgery
Received Date: 5 August 2017 Revised Date:
28 September 2017
Accepted Date: 5 October 2017
Please cite this article as: Noller MW, Guilleminault C, Gouveia C, Mack D, Vivian C, Abdullatif J, Mangili S, Liu SY, Zaghi S, Camacho M, Mandibular Advancement for Adult Obstructive Sleep Apnea: A Systematic Review and Meta-Analysis, Journal of Cranio-Maxillofacial Surgery (2017), doi: 10.1016/ j.jcms.2017.10.006. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Mandibular Advancement for Adult Obstructive Sleep Apnea: A Systematic Review and Meta-Analysis
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Michael W. Noller, Christian Guilleminault, Christopher Gouveia, Douglas Mack, Charles Vivian, Jose Abdullatif, Stefano Mangili, Stanley Yung Liu, Soroush Zaghi, Macario Camacho
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Christian Guilleminault, MD Stanford Hospital and Clinics Department of Psychiatry Sleep Medicine Division 450 Broadway Redwood city, CA 94063
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Michael W. Noller, BS School of Medicine Uniformed Services University of the Health Sciences Bethesda, Maryland, USA 20814 Phone: 970-581-6850 Fax: 808-433-9033 Email: [email protected]
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*Corresponding Author
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Christopher J. Gouveia, MD Department of Otolaryngology-Head and Neck Surgery Division of Sleep Surgery Stanford Hospital and Clinics Stanford, CA, USA 95304
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Douglas Mack, B.S. School of Medicine Uniformed Services University of the Health Sciences Bethesda, Maryland, USA 20814 Charles Vivian, B.S. School of Medicine Uniformed Services University of the Health Sciences Bethesda, Maryland, USA 20814 Jose Abdullatif, MD Instituto Ferrero de Neurología y Sueño División de Cirugía de Sueño Junín 1120, Buenos Aires, Argentina
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Stefano Mangili, MD Istituti Ospedalieri Bresciani, S.Anna Hospital Department of Surgery ENT, Head and Neck surgery Brescia, Lombardy, Italy, 25100
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public, commercial, or not-for-profit sectors.
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Conflicts of Interest: There are no conflicts of interest between this research and any
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of the authors herein listed.
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Disclaimer: The views expressed in this manuscript are those of the authors and do not
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reflect the official policy or position of the Department of the Army, Department of
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Defense, or the US Government
Stanley Yung Liu, MD, DDS Department of Otolaryngology-Head and Neck Surgery Division of Sleep Surgery Stanford Hospital and Clinics Stanford, CA, USA 95304
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Soroush Zaghi, MD UCLA Medical Center, Santa Monica Santa Monica, CA, 90404
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Macario Camacho, MD Tripler Army Medical Center Division of Otolaryngology, Sleep Surgery and Sleep Medicine 1 Jarrett White Rd Tripler AMC, HI 96859
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------------------------------------------------------------------Institution where the work was primarily performed: Tripler Army Medical Center, Honolulu, HI, USA
Short running title: Mandibular Advancement for Adult OSA
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This manuscript has not been presented at a meeting.
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Funding: This research did not receive any specific grant from funding agencies in the
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Abstract Objectives:
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Patients with mandibular insufficiency can be predisposed to obstructive sleep apnea (OSA). The objective of this study was to systematically review the international literature for mandibular advancement surgeries (MAS) as treatment for adult OSA, and then to perform a meta-analysis.
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Methods:
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Four authors searched five databases from the inception of each database through April 5, 2017. The PRISMA statement was followed.
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Results:
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972 studies were screened, 84 were downloaded, and 11 (57 patients) met criteria. In patients with mandibular insufficiency, MAS reduced apnea-hypopnea index (AHI) (50 patients) from 45.9±24.7 to 6.2±10.4 events/hr (87% decrease). The lowest oxygen saturation (LSAT) (55 patients) increased from 71.9±14.6% to 89.0±11.0% The AHI mean difference was -34.8 events/hr [95% CI -43.9, -25.8]. The AHI standardized mean difference was -1.8 [95% CI -2.5, -1.2] (indicating a large magnitude of effect). Surgical cure was seen in 75% of those with >16mm of mandibular advancement vs. 35% of those with <16mm of advancement [Odds Ratio 5.5; 95% CI 1.06-28.4; Chi Square p = 0.035].
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Conclusions:
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The current literature supports isolated mandibular advancement as an efficacious treatment modality for adult OSA in select patients with mandibular insufficiency.
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Keywords: Mandibular Advancement; Sleep Apnea Syndromes; Systematic Review; Meta-Analysis
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Introduction
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Obstructive Sleep Apnea (OSA) remains an ongoing concern for the medical and surgical communities due to its effects on sleep quality, and its associations with
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increased cardiovascular mortality (Somers et al. 2008). Of the many causes of OSA,
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the small or retrognathic mandible is an anatomical predisposition that is well
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documented to contribute to OSA severity. One of the leading treatments that has
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emerged for retrognathia is mandibular distraction osteogenesis (MDO), a surgical
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procedure that induces histogenesis by progressively advancing divided segments of
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the mandibular body (Natu et al. 2014). Additionally, mandibular advancement (MA)
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with placement of plates and screws has been used as well. Collectively, we will refer
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to MDO and MA as mandibular advancement surgeries (MAS).
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The use of MAS for the treatment of OSA in congenital retrognathia has become increasingly common, and previous systematic reviews have been performed that
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address its success in children (Breik et al. 2016, Tsui et al. 2016). However, published
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results are relatively sparse for the procedure’s benefit in acquired retrognathia of
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adulthood, and a meta-analysis of those published results has yet to be done to quantify
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the procedure’s benefit.
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The objective of this study was to systematically review all international
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publications reporting polysomnography data for MAS as an isolated treatment for OSA
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in adult patients, and then perform a meta-analysis with the available data. The study
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inclusion criteria were as follows using the PICOS acronym: (1) Patients: any adult
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patient (≥18 years old) with obstructive sleep apnea; (2) Intervention: mandibular
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distraction osteogenesis or mandibular advancement surgeries; (3) Comparison:
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polysomnography data pre-surgical and post-surgical; (4) Outcomes: oxygen
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desaturation index (ODI), apnea-hyponea index (AHI), respiratory disturbance index
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(RDI), Lowest oxygen saturation (LSAT), mean oxygen saturation (MSAT), sleepiness,
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quality of life; (5) Study design: any study design from case reports through
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randomized controlled-trials.
Methods
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Protocol
The Tripler Army Medical Center approved this study via the protocol TAMC
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16N14 (systematic review and meta-analysis).
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Study eligibility criteria
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Studies were included without any limitations based on language or the year of publication. Articles were excluded if, in addition to MAS, surgical procedures known to
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affect obstructive sleep apnea (e.g. maxillary advancement, genioplasty, palate surgery
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etc) were also performed. Concomitant TMJ arthroplasty was not considered a reason
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for exclusion.
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Information Sources
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The databases that were searched included Google Scholar, The Cochrane
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Library, Embase, Cumulative Index to Nursing and Allied Health (CINAHL) and
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PubMed/MEDLINE. The searches were initiated in October 15, 2015 and were
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completed April 5, 2017. The databases were each individually searched from the
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initiation of each database.
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Search Strategy
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An example of a search strategy, which we used in PubMed/MEDLINE as
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follows: surgery AND (“mandibular distraction” OR “distraction osteogenesis" OR
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"mandibular advancement”) AND (“hypersomnia sleep apnea syndrome” OR OSA OR
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“sleep apnea” OR “sleep apnoea”).
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Study Selection and Data Collection
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Four authors (M.C., J.A., S.M. and M.N.) independently searched the
international literature for relevant studies to include in this review. Titles and abstracts
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were reviewed first, and the studies that were potentially relevant were each
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downloaded in full text form. Once the manuscripts were downloaded, they were
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independently reviewed by at least two co-authors for inclusion. Data was extracted
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from the manuscripts and documented in a table. If a study did not report all the data
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necessary for inclusion in the meta-analysis, or if there was an unresolvable
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discrepancy in the data, then the authors were contacted at least twice based on the
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contact information from the manuscript.
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Data Items
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If a study provided both AHI and obstructive apnea-hypopnea index (OAHI),
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OAHI was used preferentially as we are evaluating the effect of surgery on obstructive
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sleep apnea and not central sleep apnea. If multiple follow-up polysomnography
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measurements were provided by a study, then the data from the most recent
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polysomnogram was used (so long as no additional surgeries were performed).
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Summary measures:
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Summary measures included the weighted mean differences (MD) and the standardized mean differences (SMD). The associated 95% confidence intervals [95%
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CI] were also calculated based on the data. The magnitudes of effect for SMD were
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assigned using Cohen’s guidelines as small = 0.2, medium = 0.5, and large = 0.8
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(Cohen 1988).
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Heterogeneity and Risk of Bias
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For the meta-analysis, Review Manager Software (REVMAN) version 5.3
(Copenhagen: The Nordic Cochrane Centre: The Cochrane Collaboration, 2014) was
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used for data analysis. REVMAN was used to calculate the Cochrane Q statistic (Q
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statistic), and based on previously published studies a value ≤0.10 was deemed
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statistically significant (Lau et al. 1997). Another measure of heterogeneity
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(inconsistency) was calculated by REVMAN as well (I2 statistic), and values were
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defined as follows: 25% (low), 50% (moderate) and 75% (high) levels of inconsistency
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(Higgins et al. 2003).
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Sensitivity analysis
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After performing the meta-analysis and calculating the Q statistic and I2 statistic,
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if there was heterogeneity, then a sensitivity analysis was performed in order to identify
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which study or studies were responsible.
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Results
The search strategy yielded 972 studies, of which 84 were potentially relevant
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and were downloaded in their full versions. Studies were excluded for absent pre- and
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post-surgical polysomnography, for inadequate separation of results from pediatric
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patients, or for the inclusion of additional surgeries besides MDO. In total, 11 articles
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met inclusion and exclusion criteria (Paoli et al. 2001, Li et al. 2002, Harada et al. 2003,
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Wang et al. 2003, Woodson et al. 2003, Zhou et al. 2005, Hamada et al. 2007, Liang et
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al. 2007, Feiyun et al. 2010, Manikandhan et al. 2014, Yadav et al. 2014). Figure 1
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demonstrates the exclusions at each stage. Included studies were evaluated using The National Institute for Health and
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Clinical Excellence (NICE) quality assessment tool (Methods for Development of NICE
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Public Health Guidance. London). The results can be seen in Table 1.
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Meta-analysis of the eleven studies included demonstrated a reduced AHI (50
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patients) from a Mean ± SD of 45.89±23.73 to 6.15±10.44 events per hour (86.60%
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decrease). The LSAT (55 patients) increased from a mean ± SD of 71.93±14.63 to
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88.95±10.95 (See Table II).
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A subanalysis using random effects modeling was performed on the four studies
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with AHI/RDI data in which it could be combined (29 patients), and there was an
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AHI/RDI mean difference (MD) of -34.80 events per hour [95% CI -43.86, -25.75],
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overall effect (Z) = 7.53, P value <0.00001, Q statistic P value = 0.54 (no heterogeneity
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present), I2 = 0% (no inconsistency). The AHI standardized mean difference (SMD) was
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-1.83 [95% CI -2.48, -1.17] (large magnitude of effect), overall effect Z = 5.49, P value <
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0.00001, Q statistic P value 0.97 (no heterogeneity present), I2 = 0% (no inconsistency)
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(See Figure 2).
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Random effects subanalysis of the five studies with LSAT data (36 patients)
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demonstrated an LSAT mean difference (MD) of 12.80% [95% CI 4.86, 20.73], overall
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effect Z = 3.16, P value = 0.002, Q statistic P value = 0.01 (heterogeneity present), I2 =
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70% (inconsistency present). After removing the study by Li et al. 2002 in a Sensitivity
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Analysis, MD contained no heterogeneity (Q statistic P value = 0.76) and no
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inconsistency (I2 = 0%). The LSAT SMD was 1.15 [95% CI 0.63, 1.67] (large magnitude
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of effect), overall effect Z = 4.35, P value < 0.0001, Q statistic P value 0.77 (no
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heterogeneity present), I2 = 0% (no inconsistency) (See Figure 3). Among the individual patient data available, patient differences between pre- and
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post-operative mandibular advancement are summarized in Table 3. There were
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significantly decreased AHI, RDI and LSAT on PSG in MAS post-operative patients (p <
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0.001). Over half of patients receiving mandibular advancement were cured of their
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disease by AHI criteria (AHI <5 events per hour), and 80% were cured by RDI criteria
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(RDI <5 events per hour). Surgery was successful in nearly all patients (defined as 50%
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reduction in AHI/RDI and a postoperative AHI/RDI<20). Additionally, among the
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individual patient data, there were, on regression analysis, significantly increased odds
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of surgical cure were found among patients with >16mm of mandibular advancement vs.
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<16mm of advancement [Odds Ratio 5.5; 95% CI 1.06-28.4; Chi Square p = 0.035]
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(See Figure 4). The 16 mm cutoff demonstrates that surgical cure was seen in 75% of
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those with >16mm of mandibular advancement vs. 35% of those with <16mm of
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advancement
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Discussion
The major finding from this study is that OSA has been shown to improve
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significantly after mandibular advancement or mandibular distraction osteogenesis in
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adult patients with mandibular insufficiency. This significant improvement is
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demonstrated by the dramatic reduction in the apnea-hypopnea index from 46 to 6
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events per hour (87% decrease) and also the dramatic increase in the lowest oxygen
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saturation from 72% to 89%. To our knowledge, this meta-analysis is the first to
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systematically review the literature and provide a summary. Given that there was no
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heterogeneity (Q-statistic) and no inconsistency (I2), the currently published studies are
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consistent in their findings of improved OSA outcomes.
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Although there is no previous meta-analysis on the topic that we could find, there have been other skeletal surgery meta-analyses for adult OSA, such as that for
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genioplasty/genioglossus advancement, maxillary expansion/maxillomandibular
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expansion and maxillomandibular advancement (Abdullatif et al. 2016, Zaghi et al. 2016,
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Song et al. 2017). Based on improvement in apnea-hypopnea index, previously the
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most successful of skeletal surgeries for adult OSA was maxillomandibular
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advancement (MMA), and prior reviews have documented that AHI reduced from 57.2
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to 9.5 events/hr (83% reduction) (Zaghi et al. 2016). The finding of an 87% reduction in
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the apnea-hypopnea index for a mandibular advancement alone was quite surprising
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given that an MMA, which involves moving the maxilla as well, had an 83% reduction.
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However, these are different population groups, as many patients who undergo MMA
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don’t necessarily have significant micrognathia or retrognathia. Rather an MMA gains a
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great deal of its benefit from maxillary advancement, counter-clockwise rotation, and
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resultant lateral pharyngeal wall stability (Liu et al. 2016). In some patients undergoing
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MMA surgery as treatment for OSA, the maxillomandibular complex is moved as an
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entire unit, keeping the occlusion the same. However, in patients with micrognathia or
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retrognathia, and the only surgery is mandibular advancement – therefore, by definition,
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because only the mandible is moving forward – the dental occlusion will change.
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The findings of this meta-analysis are logical, given that a small mandible or retrodisplaced mandible will cause the tongue to be posteriorly displaced, and therefore
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will be crowding the upper airway. Therefore, moving the mandible anteriorly will move
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the tongue anteriorly, which will also open the upper airway. It has been shown that
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tongue-lip adhesion and mandibular advancement surgeries have improved obstructive
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sleep apnea in children as demonstrated by two studies evaluating surgery in children
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with Pierre-Robin sequence (Tsui et al. 2016, Camacho et al. 2017). Although no
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previous meta-analysis on adults has been performed, there have been eleven studies
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in the international literature confirming that mandibular advancement alone can
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improve OSA.
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There are limitations to this study. The current literature is limited to case reports and small case series. However, it would be difficult to perform randomized trials for
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patients with significant mandibular insufficiency given that the advancement of the
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mandible is a targeted and patient-specific surgery which has been demonstrated to
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improve function, occlusion, and OSA outcomes. Given that the medical and surgical
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literature can be biased against negative findings, it is possible that studies
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demonstrating a worsening of OSA or no difference in OSA may have either not been
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submitted for publication or were rejected from publication.
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Conclusions
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The current international literature has demonstrated a significant improvement in
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adult obstructive sleep apnea after isolated mandibular advancement or mandibular
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distraction osteogenesis in patients with mandibular insufficiency.
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Liu, S. Y., L. K. Huon, T. Iwasaki, A. Yoon, R. Riley, N. Powell, C. Torre and R. Capasso (2016). "Efficacy of Maxillomandibular Advancement Examined with Drug-Induced Sleep Endoscopy and Computational Fluid Dynamics Airflow Modeling." Otolaryngol Head Neck Surg 154(1): 189-195.
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Zhou, L., X. Wang, C. Liang, B. Yi and Z. L. Li (2005). "[Orthognathic surgery and distraction osteogenesis for treatment of obstructive sleep apnea hypopnea syndrome]." Zhongguo Yi Xue Ke Xue Yuan Xue Bao 27(3): 357-362
409 Study Site
Outcomes Analyzed
Evidence level
1
2
3
2014 Yadav, PCS
India
V
No
Yes
No
2014, Manikandhan, PCS
India
V
No
Yes
Yes
2010, Feiyun, PCS
China
III
No
Yes
No
2007, Hamada, RCR
Japan
NA
NA
NA
2007, Liang, RCS
China
AHI. LSAT AHI. LSAT RDI. LSAT AHI. LSAT LSAT
IV
No
Yes
2005, Zhou, RCS
China
IV
No
Yes
China
2003, Woodson, RCR
USA
RDI
NA
2003, Harada, RCR
Japan
AI. LSAT
NA
2002, Li, PCS
USA
V
2001, Paoli, RCR
France
RDI. LSAT AHI. LSAT
NA
6
7
8
Yes
Yes
No
Yes
Yes
No
Yes
No
Yes
Yes
No
Yes
No
Yes
No
NA
NA
NA
NA
NA
Yes
Yes
No
No
Yes
No
Yes
Yes
No
No
Yes
No
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
No
Yes
Yes
No
Yes
Yes
Yes
No
NA
NA
NA
NA
NA
NA
NA
NA
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Table 1: General characteristics and quality criteria of included studies. AHI = Apnea/Hypopnea Index; RDI = Respiratory Disturbance Index; AI = Apnea Index; LSAT = Lowest Oxygen Saturation. NA = Not Applicable; PCS = Prospective Case Series; RCR = Retrospective Case Report. *Quality Assessment of cases series studies checklist from National Institute for Health and Clinical Excellence (NICE): 1) Case series collected in more than one center, i.e. multi-center study? 2) Is the hypothesis/aim/objective of the study clearly described? 3) Are the inclusion and exclusion criteria (case definition) clearly reported? 4) Is there a clear definition of the outcomes reported? 5) Were data collected prospectively? 6) Is there an explicit statement that patients were recruited consecutively? 7) Are the main findings of the study clearly described? 8) Are outcomes stratified? (e.g., by abnormal results, disease stage, patient characteristics)?
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410 411 412 413 414 415 416 417 418 419 420 421 422 423 424 425 426 427 428 429 430 431 432 433
NA
5
NA
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AHI. LSAT AHI LSAT
4
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Year, Study Authors, Design
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434 435 436 437 438 439 Age
Pre-Op AHI/RDI
Post-Op AHI/RDI
AHI/RDI percent Change
Pre-Op LSAT
Post-Op LSAT
Yadav 2014
8
25.5±8.8
38.13±22.12
5.36±6.23
-85.94%
67.84±18.75
86.69±7.96
Manikandhan 2014
13
23.3±6.3
44.86±22.31
12.88±13.75
-71.29%
68.38±14.71
80.98±12.88
16
27 (18-43)
47.3*
2.1*
-95.56%
75.4
98.2
1
31.3
41.4
4.8
-88.41%
77
87
Liang 2007
7
35±13.2
NR
NR
Zhou 2005
4
24.5±7.33
61.43±33.28
3.3±1.5
Wang 2003
1
36
96.2
5.8
Woodson 2003
1
48
38*
2*x
Harada 2003
1
31
29.9+
5.8+
77
87
Li 2002
4
54.5±10.1
39.73±20.33*
4.9±4.87*
-87.67%
84.5±3.32
87.5±3.32
Paoli 2001
1
44
23.4
11.9
-49.15%
56
83
Total
57
29.7±12.8
45.89±23.73
6.15±10.44
-86.60%
71.93±14.63
88.95±10.95
-
74.14±9.48
89.43±6.48
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Feiyun 2010 Hamada 2007
-94.63%
62.75±16.62
85.5±4.51
-93.97%
NR
NR
-94.74%
NR
NR
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-80.60%+
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Table 2: Polysomnographic Data Pre- and Post-Mandibular Advancement Surgery. AHI=Apnea/hypopnea Index; RDI=Respiratory Disturbance Index; LSAT=Lowest oxygen saturation. N = Number; NR=Not Reported. *=RDI; +=Apnea Index; x=PSG performed with CPAP in place at 4cm H2O
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440 441 442 443 444 445 446 447 448 449 450 451 452 453 454 455 456 457 458 459 460 461 462 463 464 465 466 467
N
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Study Authors Year
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468 469 470 471 472 473 Post-MA NA NA NA
P Value NA NA NA
29 20/29 27/29 5 40 57
45.7 (25.0) 69.0 93.1 39.4 (17.6) 70.1 (14.6) NA
8.7 (10.4) 6.9 6.9 4.9 (4.9) 85.2 (9.0) 16.1 (6.3)
p < 0.001 p < 0.001 p < 0.001 p < 0.001 p < 0.001 NA
15/29 4/5
NA NA
51.7 80
NA NA
26/29 5/5
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Pre-MA 30.2 (11.5) 72.7 20.1 (5.9)
NA NA
89.7 100
NA NA
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Table 3: Individual differences between pre- and post-operative mandibular advancement patients. MA=Mandibular Advancement; BMI=Body Mass Index; AHI=Apnea/hypopnea Index; RDI=Respiratory Disturbance Index; LSAT=Lowest oxygen saturation; NA=Not Applicable.
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474 475 476 477 478 479 480 481 482 483 484 485 486 487 488 489 490 491 492 493 494 495 496 497
No. of Patients 57 32/44 11
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Characteristic Age, mean (SD), y Male, % Preop BMI, mean (SD) Polysomnography AHI, mean (SD), events/h AHI > 30 events/h, % AHI > 20 events/h, % RDI, mean (SD), des/h LSAT, mean (SD) Mandibular Advancement, mean (SD), mm Surgical Cure, % AHI surgical cure RDI surgical cure Surgical Success, % AHI surgical success RDI surgical success
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Figure 1: Flow diagram demonstrating literature search, study inclusion and exclusion.
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Figure 2: Mean Difference in AHI/RDI Pre- and Post-Mandibular Advancement Surgery, with 95% confidence Intervals (Top); Standardized Mean Difference in AHI/RDI pre- and post-Mandibular Advancement Surgery, with 95% confidence interval (Bottom).
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Figure 3: Mean Difference in LSAT Pre- and Post-Mandibular Advancement Surgery, with 95% confidence Intervals (Top); Standardized Mean Difference in LSAT pre- and post-Mandibular Advancement Surgery, with 95% confidence interval (Bottom).
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Figure 4: Surgical Cure by Mandibular Advancement >16mm (Yes/No). Surgical Cure set as an AHI<5 events per hour.
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S1010-5182(17)30345-1
DOI:
10.1016/j.jcms.2017.10.006
Reference:
YJCMS 2807
To appear in:
Journal of Cranio-Maxillo-Facial Surgery
Received Date: 5 August 2017 Revised Date:
28 September 2017
Accepted Date: 5 October 2017
Please cite this article as: Noller MW, Guilleminault C, Gouveia C, Mack D, Vivian C, Abdullatif J, Mangili S, Liu SY, Zaghi S, Camacho M, Mandibular Advancement for Adult Obstructive Sleep Apnea: A Systematic Review and Meta-Analysis, Journal of Cranio-Maxillofacial Surgery (2017), doi: 10.1016/ j.jcms.2017.10.006. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Mandibular Advancement for Adult Obstructive Sleep Apnea: A Systematic Review and Meta-Analysis
4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46
Michael W. Noller, Christian Guilleminault, Christopher Gouveia, Douglas Mack, Charles Vivian, Jose Abdullatif, Stefano Mangili, Stanley Yung Liu, Soroush Zaghi, Macario Camacho
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Christian Guilleminault, MD Stanford Hospital and Clinics Department of Psychiatry Sleep Medicine Division 450 Broadway Redwood city, CA 94063
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Michael W. Noller, BS School of Medicine Uniformed Services University of the Health Sciences Bethesda, Maryland, USA 20814 Phone: 970-581-6850 Fax: 808-433-9033 Email: [email protected]
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*Corresponding Author
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Christopher J. Gouveia, MD Department of Otolaryngology-Head and Neck Surgery Division of Sleep Surgery Stanford Hospital and Clinics Stanford, CA, USA 95304
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Douglas Mack, B.S. School of Medicine Uniformed Services University of the Health Sciences Bethesda, Maryland, USA 20814 Charles Vivian, B.S. School of Medicine Uniformed Services University of the Health Sciences Bethesda, Maryland, USA 20814 Jose Abdullatif, MD Instituto Ferrero de Neurología y Sueño División de Cirugía de Sueño Junín 1120, Buenos Aires, Argentina
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Stefano Mangili, MD Istituti Ospedalieri Bresciani, S.Anna Hospital Department of Surgery ENT, Head and Neck surgery Brescia, Lombardy, Italy, 25100
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public, commercial, or not-for-profit sectors.
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Conflicts of Interest: There are no conflicts of interest between this research and any
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of the authors herein listed.
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Disclaimer: The views expressed in this manuscript are those of the authors and do not
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reflect the official policy or position of the Department of the Army, Department of
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Defense, or the US Government
Stanley Yung Liu, MD, DDS Department of Otolaryngology-Head and Neck Surgery Division of Sleep Surgery Stanford Hospital and Clinics Stanford, CA, USA 95304
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Soroush Zaghi, MD UCLA Medical Center, Santa Monica Santa Monica, CA, 90404
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Macario Camacho, MD Tripler Army Medical Center Division of Otolaryngology, Sleep Surgery and Sleep Medicine 1 Jarrett White Rd Tripler AMC, HI 96859
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------------------------------------------------------------------Institution where the work was primarily performed: Tripler Army Medical Center, Honolulu, HI, USA
Short running title: Mandibular Advancement for Adult OSA
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This manuscript has not been presented at a meeting.
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Funding: This research did not receive any specific grant from funding agencies in the
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Abstract Objectives:
88 89 90 91
Patients with mandibular insufficiency can be predisposed to obstructive sleep apnea (OSA). The objective of this study was to systematically review the international literature for mandibular advancement surgeries (MAS) as treatment for adult OSA, and then to perform a meta-analysis.
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Methods:
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Four authors searched five databases from the inception of each database through April 5, 2017. The PRISMA statement was followed.
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Results:
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972 studies were screened, 84 were downloaded, and 11 (57 patients) met criteria. In patients with mandibular insufficiency, MAS reduced apnea-hypopnea index (AHI) (50 patients) from 45.9±24.7 to 6.2±10.4 events/hr (87% decrease). The lowest oxygen saturation (LSAT) (55 patients) increased from 71.9±14.6% to 89.0±11.0% The AHI mean difference was -34.8 events/hr [95% CI -43.9, -25.8]. The AHI standardized mean difference was -1.8 [95% CI -2.5, -1.2] (indicating a large magnitude of effect). Surgical cure was seen in 75% of those with >16mm of mandibular advancement vs. 35% of those with <16mm of advancement [Odds Ratio 5.5; 95% CI 1.06-28.4; Chi Square p = 0.035].
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Conclusions:
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The current literature supports isolated mandibular advancement as an efficacious treatment modality for adult OSA in select patients with mandibular insufficiency.
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Keywords: Mandibular Advancement; Sleep Apnea Syndromes; Systematic Review; Meta-Analysis
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Introduction
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Obstructive Sleep Apnea (OSA) remains an ongoing concern for the medical and surgical communities due to its effects on sleep quality, and its associations with
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increased cardiovascular mortality (Somers et al. 2008). Of the many causes of OSA,
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the small or retrognathic mandible is an anatomical predisposition that is well
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documented to contribute to OSA severity. One of the leading treatments that has
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emerged for retrognathia is mandibular distraction osteogenesis (MDO), a surgical
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procedure that induces histogenesis by progressively advancing divided segments of
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the mandibular body (Natu et al. 2014). Additionally, mandibular advancement (MA)
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with placement of plates and screws has been used as well. Collectively, we will refer
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to MDO and MA as mandibular advancement surgeries (MAS).
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The use of MAS for the treatment of OSA in congenital retrognathia has become increasingly common, and previous systematic reviews have been performed that
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address its success in children (Breik et al. 2016, Tsui et al. 2016). However, published
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results are relatively sparse for the procedure’s benefit in acquired retrognathia of
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adulthood, and a meta-analysis of those published results has yet to be done to quantify
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the procedure’s benefit.
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The objective of this study was to systematically review all international
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publications reporting polysomnography data for MAS as an isolated treatment for OSA
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in adult patients, and then perform a meta-analysis with the available data. The study
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inclusion criteria were as follows using the PICOS acronym: (1) Patients: any adult
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patient (≥18 years old) with obstructive sleep apnea; (2) Intervention: mandibular
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distraction osteogenesis or mandibular advancement surgeries; (3) Comparison:
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polysomnography data pre-surgical and post-surgical; (4) Outcomes: oxygen
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desaturation index (ODI), apnea-hyponea index (AHI), respiratory disturbance index
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(RDI), Lowest oxygen saturation (LSAT), mean oxygen saturation (MSAT), sleepiness,
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quality of life; (5) Study design: any study design from case reports through
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randomized controlled-trials.
Methods
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Protocol
The Tripler Army Medical Center approved this study via the protocol TAMC
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16N14 (systematic review and meta-analysis).
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Study eligibility criteria
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Studies were included without any limitations based on language or the year of publication. Articles were excluded if, in addition to MAS, surgical procedures known to
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affect obstructive sleep apnea (e.g. maxillary advancement, genioplasty, palate surgery
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etc) were also performed. Concomitant TMJ arthroplasty was not considered a reason
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for exclusion.
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Information Sources
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The databases that were searched included Google Scholar, The Cochrane
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Library, Embase, Cumulative Index to Nursing and Allied Health (CINAHL) and
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PubMed/MEDLINE. The searches were initiated in October 15, 2015 and were
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completed April 5, 2017. The databases were each individually searched from the
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initiation of each database.
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Search Strategy
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An example of a search strategy, which we used in PubMed/MEDLINE as
171
follows: surgery AND (“mandibular distraction” OR “distraction osteogenesis" OR
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"mandibular advancement”) AND (“hypersomnia sleep apnea syndrome” OR OSA OR
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“sleep apnea” OR “sleep apnoea”).
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Study Selection and Data Collection
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Four authors (M.C., J.A., S.M. and M.N.) independently searched the
international literature for relevant studies to include in this review. Titles and abstracts
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were reviewed first, and the studies that were potentially relevant were each
178
downloaded in full text form. Once the manuscripts were downloaded, they were
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independently reviewed by at least two co-authors for inclusion. Data was extracted
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from the manuscripts and documented in a table. If a study did not report all the data
181
necessary for inclusion in the meta-analysis, or if there was an unresolvable
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discrepancy in the data, then the authors were contacted at least twice based on the
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contact information from the manuscript.
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Data Items
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If a study provided both AHI and obstructive apnea-hypopnea index (OAHI),
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OAHI was used preferentially as we are evaluating the effect of surgery on obstructive
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sleep apnea and not central sleep apnea. If multiple follow-up polysomnography
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measurements were provided by a study, then the data from the most recent
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polysomnogram was used (so long as no additional surgeries were performed).
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Summary measures:
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Summary measures included the weighted mean differences (MD) and the standardized mean differences (SMD). The associated 95% confidence intervals [95%
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CI] were also calculated based on the data. The magnitudes of effect for SMD were
194
assigned using Cohen’s guidelines as small = 0.2, medium = 0.5, and large = 0.8
195
(Cohen 1988).
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Heterogeneity and Risk of Bias
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For the meta-analysis, Review Manager Software (REVMAN) version 5.3
(Copenhagen: The Nordic Cochrane Centre: The Cochrane Collaboration, 2014) was
199
used for data analysis. REVMAN was used to calculate the Cochrane Q statistic (Q
200
statistic), and based on previously published studies a value ≤0.10 was deemed
201
statistically significant (Lau et al. 1997). Another measure of heterogeneity
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(inconsistency) was calculated by REVMAN as well (I2 statistic), and values were
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defined as follows: 25% (low), 50% (moderate) and 75% (high) levels of inconsistency
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(Higgins et al. 2003).
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Sensitivity analysis
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After performing the meta-analysis and calculating the Q statistic and I2 statistic,
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if there was heterogeneity, then a sensitivity analysis was performed in order to identify
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which study or studies were responsible.
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Results
The search strategy yielded 972 studies, of which 84 were potentially relevant
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and were downloaded in their full versions. Studies were excluded for absent pre- and
213
post-surgical polysomnography, for inadequate separation of results from pediatric
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patients, or for the inclusion of additional surgeries besides MDO. In total, 11 articles
215
met inclusion and exclusion criteria (Paoli et al. 2001, Li et al. 2002, Harada et al. 2003,
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Wang et al. 2003, Woodson et al. 2003, Zhou et al. 2005, Hamada et al. 2007, Liang et
217
al. 2007, Feiyun et al. 2010, Manikandhan et al. 2014, Yadav et al. 2014). Figure 1
218
demonstrates the exclusions at each stage. Included studies were evaluated using The National Institute for Health and
220
Clinical Excellence (NICE) quality assessment tool (Methods for Development of NICE
221
Public Health Guidance. London). The results can be seen in Table 1.
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Meta-analysis of the eleven studies included demonstrated a reduced AHI (50
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patients) from a Mean ± SD of 45.89±23.73 to 6.15±10.44 events per hour (86.60%
224
decrease). The LSAT (55 patients) increased from a mean ± SD of 71.93±14.63 to
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88.95±10.95 (See Table II).
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A subanalysis using random effects modeling was performed on the four studies
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with AHI/RDI data in which it could be combined (29 patients), and there was an
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AHI/RDI mean difference (MD) of -34.80 events per hour [95% CI -43.86, -25.75],
229
overall effect (Z) = 7.53, P value <0.00001, Q statistic P value = 0.54 (no heterogeneity
230
present), I2 = 0% (no inconsistency). The AHI standardized mean difference (SMD) was
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-1.83 [95% CI -2.48, -1.17] (large magnitude of effect), overall effect Z = 5.49, P value <
232
0.00001, Q statistic P value 0.97 (no heterogeneity present), I2 = 0% (no inconsistency)
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(See Figure 2).
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Random effects subanalysis of the five studies with LSAT data (36 patients)
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demonstrated an LSAT mean difference (MD) of 12.80% [95% CI 4.86, 20.73], overall
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effect Z = 3.16, P value = 0.002, Q statistic P value = 0.01 (heterogeneity present), I2 =
237
70% (inconsistency present). After removing the study by Li et al. 2002 in a Sensitivity
238
Analysis, MD contained no heterogeneity (Q statistic P value = 0.76) and no
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239
inconsistency (I2 = 0%). The LSAT SMD was 1.15 [95% CI 0.63, 1.67] (large magnitude
240
of effect), overall effect Z = 4.35, P value < 0.0001, Q statistic P value 0.77 (no
241
heterogeneity present), I2 = 0% (no inconsistency) (See Figure 3). Among the individual patient data available, patient differences between pre- and
243
post-operative mandibular advancement are summarized in Table 3. There were
244
significantly decreased AHI, RDI and LSAT on PSG in MAS post-operative patients (p <
245
0.001). Over half of patients receiving mandibular advancement were cured of their
246
disease by AHI criteria (AHI <5 events per hour), and 80% were cured by RDI criteria
247
(RDI <5 events per hour). Surgery was successful in nearly all patients (defined as 50%
248
reduction in AHI/RDI and a postoperative AHI/RDI<20). Additionally, among the
249
individual patient data, there were, on regression analysis, significantly increased odds
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of surgical cure were found among patients with >16mm of mandibular advancement vs.
251
<16mm of advancement [Odds Ratio 5.5; 95% CI 1.06-28.4; Chi Square p = 0.035]
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(See Figure 4). The 16 mm cutoff demonstrates that surgical cure was seen in 75% of
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those with >16mm of mandibular advancement vs. 35% of those with <16mm of
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advancement
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Discussion
The major finding from this study is that OSA has been shown to improve
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significantly after mandibular advancement or mandibular distraction osteogenesis in
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adult patients with mandibular insufficiency. This significant improvement is
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demonstrated by the dramatic reduction in the apnea-hypopnea index from 46 to 6
262
events per hour (87% decrease) and also the dramatic increase in the lowest oxygen
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saturation from 72% to 89%. To our knowledge, this meta-analysis is the first to
264
systematically review the literature and provide a summary. Given that there was no
265
heterogeneity (Q-statistic) and no inconsistency (I2), the currently published studies are
266
consistent in their findings of improved OSA outcomes.
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Although there is no previous meta-analysis on the topic that we could find, there have been other skeletal surgery meta-analyses for adult OSA, such as that for
269
genioplasty/genioglossus advancement, maxillary expansion/maxillomandibular
270
expansion and maxillomandibular advancement (Abdullatif et al. 2016, Zaghi et al. 2016,
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Song et al. 2017). Based on improvement in apnea-hypopnea index, previously the
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most successful of skeletal surgeries for adult OSA was maxillomandibular
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advancement (MMA), and prior reviews have documented that AHI reduced from 57.2
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to 9.5 events/hr (83% reduction) (Zaghi et al. 2016). The finding of an 87% reduction in
275
the apnea-hypopnea index for a mandibular advancement alone was quite surprising
276
given that an MMA, which involves moving the maxilla as well, had an 83% reduction.
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However, these are different population groups, as many patients who undergo MMA
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don’t necessarily have significant micrognathia or retrognathia. Rather an MMA gains a
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great deal of its benefit from maxillary advancement, counter-clockwise rotation, and
280
resultant lateral pharyngeal wall stability (Liu et al. 2016). In some patients undergoing
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MMA surgery as treatment for OSA, the maxillomandibular complex is moved as an
282
entire unit, keeping the occlusion the same. However, in patients with micrognathia or
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retrognathia, and the only surgery is mandibular advancement – therefore, by definition,
284
because only the mandible is moving forward – the dental occlusion will change.
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The findings of this meta-analysis are logical, given that a small mandible or retrodisplaced mandible will cause the tongue to be posteriorly displaced, and therefore
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will be crowding the upper airway. Therefore, moving the mandible anteriorly will move
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the tongue anteriorly, which will also open the upper airway. It has been shown that
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tongue-lip adhesion and mandibular advancement surgeries have improved obstructive
290
sleep apnea in children as demonstrated by two studies evaluating surgery in children
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with Pierre-Robin sequence (Tsui et al. 2016, Camacho et al. 2017). Although no
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previous meta-analysis on adults has been performed, there have been eleven studies
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in the international literature confirming that mandibular advancement alone can
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improve OSA.
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There are limitations to this study. The current literature is limited to case reports and small case series. However, it would be difficult to perform randomized trials for
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patients with significant mandibular insufficiency given that the advancement of the
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mandible is a targeted and patient-specific surgery which has been demonstrated to
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improve function, occlusion, and OSA outcomes. Given that the medical and surgical
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literature can be biased against negative findings, it is possible that studies
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demonstrating a worsening of OSA or no difference in OSA may have either not been
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submitted for publication or were rejected from publication.
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Conclusions
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The current international literature has demonstrated a significant improvement in
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adult obstructive sleep apnea after isolated mandibular advancement or mandibular
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distraction osteogenesis in patients with mandibular insufficiency.
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References Abdullatif, J., V. Certal, S. Zaghi, S. A. Song, E. T. Chang, M. B. Gillespie and M. Camacho (2016). "Maxillary expansion and maxillomandibular expansion for adult OSA: A systematic review and metaanalysis." J Craniomaxillofac Surg 44(5): 574-578.
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Breik, O., D. Tivey, K. Umapathysivam and P. Anderson (2016). "Mandibular distraction osteogenesis for the management of upper airway obstruction in children with micrognathia: a systematic review." Int J Oral Maxillofac Surg 45(6): 769-782.
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Camacho, M., M. W. Noller, S. Zaghi, L. K. Reckley, C. Fernandez-Salvador, E. Ho, B. Dunn and D. K. Chan (2017). "Tongue-lip adhesion and tongue repositioning for obstructive sleep apnoea in Pierre Robin sequence: A systematic review and meta-analysis." J Laryngol Otol: 1-6. Cohen, J. (1988). Statistical power analysis for the behavioral sciences. Hillsdale, N.J., L. Erlbaum Associates.
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Feiyun, P., L. Wei, C. Jun, X. Xin, S. Zhuojin and Y. Fengguo (2010). "Simultaneous correction of bilateral temporomandibular joint ankylosis with mandibular micrognathia using internal distraction osteogenesis and 3-dimensional craniomaxillofacial models." J Oral Maxillofac Surg 68(3): 571-577. Hamada, T., T. Ono, R. Otsuka, E. Honda, K. Harada, T. Kurabayashi and K. Ohyama (2007). "Mandibular distraction osteogenesis in a skeletal Class II patient with obstructive sleep apnea." Am J Orthod Dentofacial Orthop 131(3): 415-425.
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Harada, K., M. Higashinakagawa and K. Omura (2003). "Mandibular lengthening by distraction osteogenesis for treatment of obstructive sleep apnea syndrome: a case report." Cranio 21(1): 61-67. Higgins, J. P., S. G. Thompson, J. J. Deeks and D. G. Altman (2003). "Measuring inconsistency in metaanalyses." Bmj 327(7414): 557-560.
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310 311 312 313 314 315 316 317 318 319 320 321 322 323 324 325 326 327 328 329 330 331 332 333 334 335 336 337 338 339 340 341 342 343 344 345 346 347 348 349 350 351 352 353 354 355
Lau, J., J. P. Ioannidis and C. H. Schmid (1997). "Quantitative synthesis in systematic reviews." Ann Intern Med 127(9): 820-826. Li, K. K., N. B. Powell, R. W. Riley and C. Guilleminault (2002). "Distraction osteogenesis in adult obstructive sleep apnea surgery: a preliminary report." J Oral Maxillofac Surg 60(1): 6-10. Liang, C., X. Wang, B. Yi, Z. L. Li and X. X. Wang (2007). "[Clinical study of simultaneous correction of unilateral temporomandibular joint ankylosis and mandibular micrognathia with internal distraction osteogenesis]." Beijing Da Xue Xue Bao 39(1): 33-36.
ACCEPTED MANUSCRIPT
Liu, S. Y., L. K. Huon, T. Iwasaki, A. Yoon, R. Riley, N. Powell, C. Torre and R. Capasso (2016). "Efficacy of Maxillomandibular Advancement Examined with Drug-Induced Sleep Endoscopy and Computational Fluid Dynamics Airflow Modeling." Otolaryngol Head Neck Surg 154(1): 189-195.
RI PT
Manikandhan, R., G. Lakshminarayana, P. Sneha, P. Ananthnarayanan, J. Naveen and H. F. Sailer (2014). "Impact of mandibular distraction osteogenesis on the oropharyngeal airway in adult patients with obstructive sleep apnea secondary to retroglossal airway obstruction." J Maxillofac Oral Surg 13(2): 9298. Methods for Development of NICE Public Health Guidance. London, U. N. I. f. H. a. C. E.
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Natu, S. S., I. Ali, S. Alam, K. Y. Giri, A. Agarwal and V. A. Kulkarni (2014). "The biology of distraction osteogenesis for correction of mandibular and craniomaxillofacial defects: A review." Dent Res J (Isfahan) 11(1): 16-26.
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Paoli, J. R., F. Lauwers, L. Lacassagne and M. Tiberge (2001). "Treatment of obstructive sleep apnea syndrome by mandibular elongation using osseous distraction followed by a Le Fort I advancement osteotomy: case report." J Oral Maxillofac Surg 59(2): 216-219.
TE D
Somers, V. K., D. P. White, R. Amin, W. T. Abraham, F. Costa, A. Culebras, S. Daniels, J. S. Floras, C. E. Hunt, L. J. Olson, T. G. Pickering, R. Russell, M. Woo and T. Young (2008). "Sleep apnea and cardiovascular disease: an American Heart Association/american College Of Cardiology Foundation Scientific Statement from the American Heart Association Council for High Blood Pressure Research Professional Education Committee, Council on Clinical Cardiology, Stroke Council, and Council On Cardiovascular Nursing. In collaboration with the National Heart, Lung, and Blood Institute National Center on Sleep Disorders Research (National Institutes of Health)." Circulation 118(10): 1080-1111. Song, S. A., E. T. Chang, V. Certal, M. Del Do, S. Zaghi, S. Y. Liu, R. Capasso and M. Camacho (2017). "Genial tubercle advancement and genioplasty for obstructive sleep apnea: A systematic review and meta-analysis." Laryngoscope 127(4): 984-992.
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Tsui, W. K., Y. Yang, L. K. Cheung and Y. Y. Leung (2016). "Distraction osteogenesis as a treatment of obstructive sleep apnea syndrome: A systematic review." Medicine (Baltimore) 95(36): e4674. Wang, X., X. X. Wang, C. Liang, B. Yi, Y. Lin and Z. L. Li (2003). "Distraction osteogenesis in correction of micrognathia accompanying obstructive sleep apnea syndrome." Plast Reconstr Surg 112(6): 1549-1557; discussion 1558-1549.
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356 357 358 359 360 361 362 363 364 365 366 367 368 369 370 371 372 373 374 375 376 377 378 379 380 381 382 383 384 385 386 387 388 389 390 391 392 393 394 395 396 397 398 399 400 401 402 403
Woodson, B. T., P. R. Hanson, M. B. Melugin and A. A. Gama (2003). "Sequential upper airway changes during mandibular distraction for obstructive sleep apnea." Otolaryngol Head Neck Surg 128(1): 142-144. Yadav, R., O. Bhutia, G. Shukla and A. Roychoudhury (2014). "Distraction osteogenesis for management of obstructive sleep apnoea in temporomandibular joint ankylosis patients before the release of joint." J Craniomaxillofac Surg 42(5): 588-594. Zaghi, S., J. E. Holty, V. Certal, J. Abdullatif, C. Guilleminault, N. B. Powell, R. W. Riley and M. Camacho (2016). "Maxillomandibular Advancement for Treatment of Obstructive Sleep Apnea: A Meta-analysis." JAMA Otolaryngol Head Neck Surg 142(1): 58-66.
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Zhou, L., X. Wang, C. Liang, B. Yi and Z. L. Li (2005). "[Orthognathic surgery and distraction osteogenesis for treatment of obstructive sleep apnea hypopnea syndrome]." Zhongguo Yi Xue Ke Xue Yuan Xue Bao 27(3): 357-362
409 Study Site
Outcomes Analyzed
Evidence level
1
2
3
2014 Yadav, PCS
India
V
No
Yes
No
2014, Manikandhan, PCS
India
V
No
Yes
Yes
2010, Feiyun, PCS
China
III
No
Yes
No
2007, Hamada, RCR
Japan
NA
NA
NA
2007, Liang, RCS
China
AHI. LSAT AHI. LSAT RDI. LSAT AHI. LSAT LSAT
IV
No
Yes
2005, Zhou, RCS
China
IV
No
Yes
China
2003, Woodson, RCR
USA
RDI
NA
2003, Harada, RCR
Japan
AI. LSAT
NA
2002, Li, PCS
USA
V
2001, Paoli, RCR
France
RDI. LSAT AHI. LSAT
NA
6
7
8
Yes
Yes
No
Yes
Yes
No
Yes
No
Yes
Yes
No
Yes
No
Yes
No
NA
NA
NA
NA
NA
Yes
Yes
No
No
Yes
No
Yes
Yes
No
No
Yes
No
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
No
Yes
Yes
No
Yes
Yes
Yes
No
NA
NA
NA
NA
NA
NA
NA
NA
EP
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Table 1: General characteristics and quality criteria of included studies. AHI = Apnea/Hypopnea Index; RDI = Respiratory Disturbance Index; AI = Apnea Index; LSAT = Lowest Oxygen Saturation. NA = Not Applicable; PCS = Prospective Case Series; RCR = Retrospective Case Report. *Quality Assessment of cases series studies checklist from National Institute for Health and Clinical Excellence (NICE): 1) Case series collected in more than one center, i.e. multi-center study? 2) Is the hypothesis/aim/objective of the study clearly described? 3) Are the inclusion and exclusion criteria (case definition) clearly reported? 4) Is there a clear definition of the outcomes reported? 5) Were data collected prospectively? 6) Is there an explicit statement that patients were recruited consecutively? 7) Are the main findings of the study clearly described? 8) Are outcomes stratified? (e.g., by abnormal results, disease stage, patient characteristics)?
AC C
410 411 412 413 414 415 416 417 418 419 420 421 422 423 424 425 426 427 428 429 430 431 432 433
NA
5
NA
M AN U
2003, Wang, RCR
AHI. LSAT AHI LSAT
4
SC
Year, Study Authors, Design
RI PT
408
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434 435 436 437 438 439 Age
Pre-Op AHI/RDI
Post-Op AHI/RDI
AHI/RDI percent Change
Pre-Op LSAT
Post-Op LSAT
Yadav 2014
8
25.5±8.8
38.13±22.12
5.36±6.23
-85.94%
67.84±18.75
86.69±7.96
Manikandhan 2014
13
23.3±6.3
44.86±22.31
12.88±13.75
-71.29%
68.38±14.71
80.98±12.88
16
27 (18-43)
47.3*
2.1*
-95.56%
75.4
98.2
1
31.3
41.4
4.8
-88.41%
77
87
Liang 2007
7
35±13.2
NR
NR
Zhou 2005
4
24.5±7.33
61.43±33.28
3.3±1.5
Wang 2003
1
36
96.2
5.8
Woodson 2003
1
48
38*
2*x
Harada 2003
1
31
29.9+
5.8+
77
87
Li 2002
4
54.5±10.1
39.73±20.33*
4.9±4.87*
-87.67%
84.5±3.32
87.5±3.32
Paoli 2001
1
44
23.4
11.9
-49.15%
56
83
Total
57
29.7±12.8
45.89±23.73
6.15±10.44
-86.60%
71.93±14.63
88.95±10.95
-
74.14±9.48
89.43±6.48
SC
Feiyun 2010 Hamada 2007
-94.63%
62.75±16.62
85.5±4.51
-93.97%
NR
NR
-94.74%
NR
NR
M AN U
-80.60%+
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Table 2: Polysomnographic Data Pre- and Post-Mandibular Advancement Surgery. AHI=Apnea/hypopnea Index; RDI=Respiratory Disturbance Index; LSAT=Lowest oxygen saturation. N = Number; NR=Not Reported. *=RDI; +=Apnea Index; x=PSG performed with CPAP in place at 4cm H2O
AC C
440 441 442 443 444 445 446 447 448 449 450 451 452 453 454 455 456 457 458 459 460 461 462 463 464 465 466 467
N
RI PT
Study Authors Year
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468 469 470 471 472 473 Post-MA NA NA NA
P Value NA NA NA
29 20/29 27/29 5 40 57
45.7 (25.0) 69.0 93.1 39.4 (17.6) 70.1 (14.6) NA
8.7 (10.4) 6.9 6.9 4.9 (4.9) 85.2 (9.0) 16.1 (6.3)
p < 0.001 p < 0.001 p < 0.001 p < 0.001 p < 0.001 NA
15/29 4/5
NA NA
51.7 80
NA NA
26/29 5/5
SC
RI PT
Pre-MA 30.2 (11.5) 72.7 20.1 (5.9)
NA NA
89.7 100
NA NA
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Table 3: Individual differences between pre- and post-operative mandibular advancement patients. MA=Mandibular Advancement; BMI=Body Mass Index; AHI=Apnea/hypopnea Index; RDI=Respiratory Disturbance Index; LSAT=Lowest oxygen saturation; NA=Not Applicable.
AC C
474 475 476 477 478 479 480 481 482 483 484 485 486 487 488 489 490 491 492 493 494 495 496 497
No. of Patients 57 32/44 11
M AN U
Characteristic Age, mean (SD), y Male, % Preop BMI, mean (SD) Polysomnography AHI, mean (SD), events/h AHI > 30 events/h, % AHI > 20 events/h, % RDI, mean (SD), des/h LSAT, mean (SD) Mandibular Advancement, mean (SD), mm Surgical Cure, % AHI surgical cure RDI surgical cure Surgical Success, % AHI surgical success RDI surgical success
EP
TE D
M AN U
Figure 1: Flow diagram demonstrating literature search, study inclusion and exclusion.
AC C
498 499 500 501 502 503 504 505 506 507 508 509 510 511 512 513 514 515 516 517 518 519 520 521 522 523 524
SC
RI PT
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EP
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M AN U
SC
Figure 2: Mean Difference in AHI/RDI Pre- and Post-Mandibular Advancement Surgery, with 95% confidence Intervals (Top); Standardized Mean Difference in AHI/RDI pre- and post-Mandibular Advancement Surgery, with 95% confidence interval (Bottom).
AC C
525 526 527 528 529 530 531 532 533 534 535 536 537 538 539 540 541 542 543 544 545 546 547 548 549 550 551 552 553 554 555
RI PT
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EP
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M AN U
Figure 3: Mean Difference in LSAT Pre- and Post-Mandibular Advancement Surgery, with 95% confidence Intervals (Top); Standardized Mean Difference in LSAT pre- and post-Mandibular Advancement Surgery, with 95% confidence interval (Bottom).
AC C
556 557 558 559 560 561 562 563 564 565 566 567 568 569 570 571 572 573 574 575 576 577 578 579 580 581 582 583 584 585 586 587 588 589
SC
RI PT
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Figure 4: Surgical Cure by Mandibular Advancement >16mm (Yes/No). Surgical Cure set as an AHI<5 events per hour.
AC C
591 592 593 594 595 596 597 598 599 600 601 602 603 604 605 606 607 608 609 610 611
TE D
M AN U
SC
RI PT
590