Effect of Surgically Assisted Rapid Maxillary Expansion on Upper Airway Volume: A Systematic Review

Accepted Manuscript The Effect of Surgically-Assisted Rapid Maxillary Expansion (SARME) on Upper Airway Volume: A Systematic Review Lloyd M. Buck, BDS, BSciDent(Hons), Postgraduate Student, Oyku Dalci, DDS, PhD, Senior Lecturer, M. Ali Darendeliler, BDS, PhD, Dip. Orth., Certif. Orth., Priv. Doc., MRACDS (Ortho), FICD, Professor and chair, Alexandra K. Papadopoulou, DDS, MSc, Dipl. Specialty Orthod, PhD, Senior Lecturer, Research Associate PII:

S0278-2391(15)01658-4

DOI:

10.1016/j.joms.2015.11.035

Reference:

YJOMS 57067

To appear in:

Journal of Oral and Maxillofacial Surgery

Received Date: 4 September 2015 Revised Date:

15 November 2015

Accepted Date: 30 November 2015

Please cite this article as: Buck LM, Dalci O, Darendeliler MA, Papadopoulou AK, The Effect of Surgically-Assisted Rapid Maxillary Expansion (SARME) on Upper Airway Volume: A Systematic Review, Journal of Oral and Maxillofacial Surgery (2016), doi: 10.1016/j.joms.2015.11.035. 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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The Effect of Surgically-Assisted Rapid Maxillary Expansion (SARME) on Upper Airway Volume: A Systematic Review

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Authors: Lloyd M. Buck BDS, BSciDent(Hons)1, Oyku Dalci DDS, PhD2 , M. Ali Darendeliler BDS, PhD, Dip. Orth., Certif. Orth., Priv. Doc., MRACDS (Ortho), FICD3, and Alexandra K. Papadopoulou DDS, MSc, Dipl. Specialty Orthod, PhD4.

1Postgraduate

Student, Discipline of Orthodontics, Faculty of Dentistry, University of Sydney. Sydney Dental Hospital, Sydney South West Area Health Service, Sydney, Australia.

Lecturer, Discipline of Orthodontics, Faculty of Dentistry, University of Sydney. Sydney Dental Hospital, Sydney South West Area Health Service, Sydney, Australia.

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2Senior

3Professor

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and chair, Discipline of Orthodontics, Faculty of Dentistry, University of Sydney. Sydney Dental Hospital, Sydney South West Area Health Service, Sydney, Australia.

4Senior Lecturer, Discipline of Orthodontics, Faculty of Dentistry, University of Sydney. Sydney Dental Hospital, Sydney South West Area Health Service, Sydney, Australia. Research Associate. Department of Oral Surgery and Implantology. Aristotle University of Thessaloniki, Thessaloniki, Greece.

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Address for Correspondence: Alexandra K. Papadopoulou, Discipline of Orthodontics, Faculty of Dentistry, University of Sydney, Sydney Dental Hospital, Level 2, 2 Chalmers St, Surry Hills, NSW 2010, Australia. Tel: +61 (2) 9351 8314 Fax: +61 (2) 9351 8336 E-mail: [email protected]

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The Effect of Surgically-Assisted Rapid Maxillary Expansion (SARME) on Upper Airway Volume: A

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Systematic Review

ABSTRACT

Purpose: Surgically-assisted rapid maxillary expansion (SARME) involves is required in non-growing

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patients when maturity or resistance precludes desired sutural separation by non-invasive techniques.

The aim of this review is to determine what volumetric changes occur in the upper airway spaces

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following SARME in adults. Methods: Systematic review was performed with data assessed for suitability of meta-analysis. The primary outcome measure of volumetric changes in an upper airway space was sought in non-growing subjects undergoing SARME. Electronic database searches were performed for published literature in Medline (via Ovid), PreMedline, Old Medline, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) spanning all available years to 1st August 2015. Unpublished literature was searched electronically through ClinicalTrials.gov and the National

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Research register. Additional hand searching of reference lists of relevant articles, grey searching and expert correspondence was conducted for any additional studies. Two authors independently screened search results, extracted data, and assessed the risk of bias of included studies. Results: Twenty-one

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studies were located by initial screening; 10 were then excluded after full-text review, leaving 11 studies eligible for inclusion in this systematic review having met all inclusion criteria. In total, 204

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treated patients were included in qualitative synthesis, mean ages 18-31 years. Ten studies evaluated nasal cavity volume, two evaluated palatal volume, and one oropharyngeal volume. Appliances used included tooth-borne hyrax and transpalatal distractor (TPD). Conclusions: SARME was found to

produce significant short term volume increase in the nasal cavity in non-growing patients, maintained for at least 63 months. Evidence weakly suggests there was no effect on oropharyngeal volume. However most studies were evaluated as having a high risk of bias. The effect of such volume changes on respiratory function still needs to be determined, thus SARME cannot yet be recommended for respiratory purposes.

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INTRODUCTION The concept of using surgical osteotomies to facilitate expansion of the maxilla was first described by

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Brown1 in 1938. This technique is performed in patients requiring correction of skeletal transverse

constriction where the stage of skeletal maturity, the degree of bony resistance or other factors like periodontal condition would jeopardize successful or predictable expansion by traditional orthopedic

means alone. After skeletal maturity has occurred, maxillary expansion is hindered by the increasing

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the mid-palatal and other circum-maxillary sutures4-6.

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rigidity of the bony structures2, 3 and the increasing degree of bony interdigitation and ossification of

SARME is based on the model of distraction osteogenesis, pioneered by Ilizarov7 in the 1950s, whereby bone growth is stimulated in a man-made osteotomy gap. The exact location and extent of osteotomy sites varies between techniques3,

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, however important considerations in the process

concern the surgical process, the latency period before expansion commences, the distraction rate,

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distraction frequency and consolidation time.

The resultant dimensional changes to the dental arch and skeletal structures have been extensively studies previously in 2-dimensions10. Skeletal modifications include the lateral separation of the

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maxillary halves, with lateral tipping in the frontal plane11, 12, an increase in nasal cavity width13, 14, and a corresponding increase in minimum cross-sectional area (MCA)14-17. More recently it has become

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possible to assess the upper airway in 3-dimensions with the advent of computed tomography and acoustic rhinometry (AR), developed by Hilberg18.

Better understanding of the impact of SARME on the upper airway, both dimensionally and functionally, will help to determine whether this treatment may be beneficial for adult patients with upper respiratory problems.

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The purpose of this study was to determine through systematic review from baseline values, the volumetric changes occurring in the upper airway spaces after surgically-assisted rapid maxillary

MATERIAL AND METHODS

Protocol and Registration

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expansion in non-growing subjects.

The study protocol was not registered. Due to the nature of this study as a systematic review, ethical

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approval was not required from the University of Sydney IRB.

Search Strategy

To address the research purpose, the investigators designed and implemented a systematic review of both published and unpublished literature. All stages were conducted according to the current Preferred

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Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist19. The international database of prospectively registered systematic reviews in health and social care (PROSPERO) and Cochrane register of systematic reviews was searched in November 2014 showing no existing or current review protocols assessing airway volumes and surgically assisted maxillary expansion.

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Electronic database searches were performed covering all available years up to August 2015 in Ovid Medline, PREMEDLINE, Old Medline, Embase, and Cochrane Central Register of Controlled Trials

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(CENTRAL). Limits were applied for English language and human subjects. Unpublished literature was searched electronically through ClinicalTrials.gov (www.clinicaltrials.gov) and the National Research register, ISRCTN (www.controlled-trials.com) using the terms “expansion”, “airway” and “volume”. Additional hand searching of reference lists of relevant articles, grey searching in Google Scholar and correspondence with experts in the field was conducted for location of any additional studies. The search strategy and search terms were developed in consultation with a senior health sciences librarian. Truncation symbols were utilized in order to retrieve all potential combinations of the search terms. Strategy and terms for Medline via Ovid are shown in Appendix A.

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Eligibility Criteria Evaluation of volumetric changes in any region of the upper airway were sought, with consideration

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made of all diagnostic apparatus used including acoustic rhinometry (AR), computed tomography (CT), cone-beam computed tomography (CBCT), in addition to any others. Studies had to report

quantified continuous data on the baseline and post-treatment measurements or data on the calculated

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change over the treatment period. Subjective or patient reported measures were not considered. The

effects were sought in non-growing human subjects such that the skeletal changes could be attributed to the treatment intervention, similarly studies involving other concomitant treatments that may

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influence results were excluded. Additionally subjects with syndromes, craniofacial anomalies or significant medical conditions were excluded to prevent any unusual treatment responses from altering results. Expansion appliances incorporating a jackscrew based active element were included, this included tooth-borne (hyrax) as well as bone-borne (TPD) style devices. Required study designs were Randomized Clinical Trials, Prospective or Retrospective Controlled Clinical Trials and Clinical trials

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of at least 8 subjects. Case Reports, Clinical trials of less than 8 subjects, review articles and opinion pieces were not considered. Although the ability to measure volumetric changes in the upper airway, especially with a high degree of accuracy, has been a recent facility, no publication date range was

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specified. No publication date limit was applied.

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Study Selection

Screening of retrieved articles, assessment of risk of bias, and extraction of data was conducted independently and in duplicate by 2 investigators (LB and AKP), any discrepancies in results were resolved by discussion before combination. Firstly, title & abstract screening was performed, followed by full-text assessment for second level evaluation. Any study where no abstract was available, or the information available was inconclusive in reaching a decision was assessed in full-text. During screening researchers were blinded to the articles author(s) and journal in order to minimize potential

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biases in the selection process of primary studies20. Where questions remained after full-text evaluation, efforts were made to contact relevant authors for clarification.

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Data Items and Collection

Data was retrieved using a customized data extraction form based on the Data Extraction Template for Cochrane Reviews, Appendix B. Both were first developed and piloted on a small random selection of

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studies. The primary outcome measure sought was the volumetric change measurements of the upper airway region considered; regions accepted included the nasal cavity, paranasal sinuses, oral cavity, and pharynx. The primary predictor variables recorded were subject age, gender and expansion

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appliance specifics. These included the appliance design, activation protocol and period, expansion amount and retention methods. The surgical technique including osteotomy type and location was also recorded. Timepoints were classified according to T1 (immediately prior to surgery), T2 (immediately following active expansion), T3 (immediately at completion of retention) and T4 (long-term follow up

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after retention).

Risk of Bias in Individual Studies

In a clinical trial, flaws in design, conduct, analyses and reporting can lead to either under or over-

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estimation of the true effect of the intervention21. All studies were assessed for risks of bias to highlight any inherent threats to the internal and external validity of their findings using 2 separate tools. First,

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the seven categories were considered per the Cochrane Risk of Bias Assessment Tool21: random

sequence generation, allocation concealment, blinding of participants and personnel, blinding of assessors (outcome assessment), incomplete outcome data, selective reporting of outcomes, and other potential bias sources. Judgments are expressed as either ‘Low risk’, ‘High risk’ or ‘Unclear risk’. Second, a customized tool was developed using elements from those of Lagravere et al.22 Nguyen et al.23 and Greenlee et al.24. This tool‘s maximum score was 25, studies were graded as being high (score > 20), moderate ( 20 ≤ score ≤ 12) or low (score < 12). The outcomes of bias assessment of the included studies will be used to determine the strength of the evidence located when drawing

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conclusions from the final data. The use of a checklist is recommended over scales25 or the combination into an single overall value21. This tool is considered the gold standard for assessing biases in randomized controlled trials (RCTs), it can also be used for other study designs like case

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series, however the estimation of bias provided will be higher.

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RESULTS

Study Selection and Characteristics

Database search yielded a total of 500 results, one additional study was located by hand searching. The

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details of database results are shown in Table 1. Removal of duplicates left 338 unique articles. After reviewing abstracts, 20 articles initially satisfied the inclusion criteria. After retrieval and review of these articles in full-text, 7 were found to not measure or report volume values for the airways26-32, and two appeared to use duplicate samples33, 34. Studies excluded at full-text review are shown in Table 2. Ultimately, 11 articles met all inclusion criteria for inclusion in this review; PRISMA flowchart is

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shown in Figure 1. These 11 studies comprised one retrospective clinical trial35, 8 prospective clinical trials14-16, 36-40, one controlled clinical trial41 and one RCT42. In total, 204 treated patients were included in qualitative synthesis. Collected data from included studies is summarized into tables. Table 3 shows participants, interventions, comparators, outcomes and study designs (PICO). Details of airway regions

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and calculation methods are shown in Table 4, measurements and outcome results are summarized in Table 5, the surgical techniques used in table 6, and expansion appliances and protocols are shown in

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Table 7. Quantitative analysis of data was not performed due to heterogeneities that existed between studies in patient baseline conditions, surgical techniques and expansion protocols.

Risk of Bias Within Studies: Selection bias was rated as high for most studies. The exception was Prado et al.42 who utilized block randomization to generate their sequence, and delivered it in opaque envelopes, proving to be the only allocation concealment noted across studies. There was no blinding of subjects seen in any study. This

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would be difficult to achieve due to the obvious and intrusive nature of an oral expansion device, as well as the need for patient compliance with activation revealing quite obviously the treated from a non-treated group; this is in addition to patients having received surgery which is a clear indicator of treatment. Location and visibility of the appliance also renders anonymity of differing appliance types

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impossible. Blinding of assessors was outlined by two studies, Nada et al.39 and Prado et al.42. The blinding of assessors was considered unlikely to be possible, as researchers were generally involved in

the patient treatment from screening and appliance placement to outcome assessment. Complete

outcome data reporting was found in all studies without selective reporting of results. No losses to

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follow up were disclosed or suspected.

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The primary outcome measure of airway volume change being a quantitative continuous variable, and not subjective, was not anticipated to be significantly affected by this lack of blinding. However, as a patient’s compliance with expander activation would directly affect the expansion amount, and this was anticipated to correlate with volume changes, the Hawthorne effect may have been present. Risk of bias assessments are shown through the Cochrane Risk of Bias Tool in Table 8, and by customized tool

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in Table 9.

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Results of Individual Studies:

Nasal Volume

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Seven studies investigated nasal cavity volume by acoustic rhinometry (AR), using hyrax (6)15, 16, 35, 36,

38, 41

and TPD (1)14. In hyrax, Zambon et al.16 found a minor but statistically insignificant increase in

total nasal volume following active expansion (p>0.05). During retention of 4 months there was again no changes reaching significance. There was significance in the differences between measures with and without decongestant (P<0.001). Babacan et al.36 recorded a gain of 14.09% in basal (p<0.05), and 17.86% in decongested (p<0.05) conditions after 6months retention without differences between these two groups (p>0.05). Insignificant changes were found by Baraldi et al.41 from T1-T3 in all areas of the

nose. No difference in volumes was detected between these time-points despite an increase in the nasal

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width and maxillomandibular transverse index following SARME. They found no correlation between the cephalometric and rhinometric measurements made. Mitsuda et al.38 demonstrated a significant increase in total volume after 6months retention both with and without decongestant; Without decongestant the right nasal cavity increased by 46.85% and left by 58.56% (p=-4.54), with

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decongestant was right 59.97% and left 64.94% (p=-4.54). The differences between decongested and non-decongested states were significantly different (right p=-3.892, left p=-3.916).

Wreidt et al.15 recorded positive changes in mean total nasal volume of 21.2%, or its components of:

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anterior gain 23.3%, middle gain 23.1% and a posterior gain of 19.7%, all at p<0.01. Seeberger et al.35 found all subjects demonstrated increases in all nasal cavity segments over a longer follow-up period of

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63months in decongested condition only. Volume increases were by 23.25% total, 25.31% anterior, 22.11% middle, 23.87% posteriorly and 30.36% at the isthmus. All were statistically significant at p<0.01.

Utilizing TPD appliance, Aras et al.14 showed statistically significant increase in total anterior nasal

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volume and total middle nasal volume. Increases by 6 months retention were 101% in total anterior (p=0.006), and 120% in total middle (p=0.005). Changes during retention proved statistically insignificant, indicating minimal relapse after appliance removal. By 12 months, increase from baseline

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was 62% in total anterior (p=0.045) and 114% in total middle volume (p=0.016).

Only two studies considered the nasal cavity by computed tomography. Deeb et al.37 observed great

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variation in volume changes between subjects with TPD by conventional CT, ranging from -1.5 to +12.8% from T1-T3. Fourteen patients had an increased in volume, while 2 had a small decrease. Overall the mean absolute change after 6months retention (T3) was a statistically insignificant 5.1% (p>0.05). They did not note any correlation between nasal volume change and the amount of transverse expansion at the appliance. At a long-term follow-up of 22 months using CBCT, Nada et al.39 found a

statistically significant increase in nasal cavity volume of 9.74% (p<0.001) in their hyrax group, and 12.95% (p<0.001) in TPD group. There was not a significant difference between these appliance results (p=0.35).

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Palatal Vault This was investigated by 2 studies15, 42. Prado et al.42 found after 4months retention palatal volume

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increased by 24.8 and 28.4% in each group (p<0.001), after an additional 6months of TPA in one group the increase was still 25.2% (p<0.001). After 6-12 months retention, when impressions were possible,

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Wreidt et al.15 found an 18.9% statistically significant increase (p<0.01).

Oropharynx

Only a single study assessed the oropharyngeal volume. Pereiro-Filho et al.40 assessed this after active

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expansion and again after 4months retention, changes at both were statistically insignificant.

DISCUSSION

The purpose of the present study was to determine from baseline values, any volumetric changes

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occurring in the upper airway spaces after surgically-assisted rapid maxillary expansion in nongrowing subjects. The results of this systematic review have shown that SARME produced significant short term volume increase in the nasal cavity, which were maintained for at least 63 months. Evidence

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relating to oropharyngeal volume was weak, but suggested there was no change.

Overall in the nasal cavity, six studies found statistically significant increases14, 15, 35, 36, 38, 39, while 3

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found changes that were not significant16, 37, 41. There was a positive change in group mean volumes of all airway regions measured in all studies following SARME; however, the great variability in individual response between patients did not result in all exhibiting statistically significant results. This is in accordance to findings of nasal volume increase produced by RME in growing subjects.36, 43-

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Volume increases in Aras et al.14 were significantly larger than other studies, they reasoned this was due to the fact their subjects had partial or near total nasal obstruction while others15, 16, 36, 38, 39 used

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only patients with no nasal disease. The effect of expansion of subjects with such small baseline values may therefore be more pronounced. By contrast, Deeb et al.37 recorded insignificant increases of much smaller magnitude when compared to other studies. Measurements in this CT study were taken from transverse skeletal landmarks rather than those by AR, which are effectively measuring soft tissue

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dimensions within the nasal cavity. Therefore, for an equivalent lateral increase in volume the inner soft tissue dimensions will display a higher percentage improvement in volume, compared to the larger skeletal dimensions.

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Wreidt et al.15 and Seeberger et al.35 both analyzed volumes in anterior, middle and posterior segments

of the nasal cavity by AR. Both showing evidence for a triangular expansion pattern in the transverse

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plane, with more expansion anteriorly that was also seen by Aras et al.14. Deeb et al.37 confirmed the same by CT, finding expansion ratios of 59, 26, and 15% for anterior, middle and posterior, respectively. The highest volume increase was in the lower anterior nasal cavity in the region of the nasal valve, a finding also shown by Wreidt et al.15 and Seeberger et al.35 and speculated by Mitsuda et al.38. This represents the region of greatest nasal airflow-resistance51. A number of authors attribute 15

. Failure to release the pterygo-

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improvements in nasal breathing to nasal valve enlargement3,

maxillary articulation at surgery was a common feature of these studies.

The degree of skeletal expansion generated using TPD has been claimed to be greater than other

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expanders52. Explanation for this may be the biomechanics of the force application relative to the centre of resistance of the maxillary halves, which is though to reside at the level of the pterygo-

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palatine fossa53. TPD will apply force higher than tooth-borne devices. However, other studies have found no difference in dental and skeletal indices between the two appliance types11. Nada et al.39

directly compared hyrax with TPD and although very slightly larger volume increase occurred in TPD, they found no significant difference. There was no compelling evidence to suggest a significant difference between the hyrax or TPD with regard to airway volume changes. Only one study involved multiple expander appliance designs, Baraldi et al41 who used Haas or banded hyrax but combined them precluding any assessment of a difference between such groups. Studies evaluating effects of

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RME on airway volume in growing subjects did not find any significant differences in outcome volume between bonded, banded or fan-type RME appliances.43, 50, 54-56

As only one study considered the oropharynx, broad conclusions cannot be drawn. Pereira-Filho et al.40

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did find small volume increases after expansion and 4months retention but not to significant levels.

There was however a statistically significant (p<0.05) increase in minimum cross-sectional area

(MCA) at T2 with its relocation more inferiorly, indicating some form of dimensional effects by SARME, but this did relapse somewhat by 4months. Similarly insignificant findings were reported on

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oropharyngeal volume by studies of RME in growing subjects.46, 48, 56, 57

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A degree of measurement error was present in all techniques. Acoustic rhinometry is said to involve errors of around 5-10%58. During AR, the use of nasal decongestant acts to remove the highly variable and dynamic changes in nasal mucosal engorgement from effecting volumetric readings. Of the seven studies employing AR to record nasal volume, three took both readings16, 36, 38, three recorded only with decongestant15, 35, 41, while Aras et al.14 only recorded basal conditions without decongestant.

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Other difficulties in standardizing nasal volume measurements with AR include factors like head posture of the subjects, ambient temperature and noise, rest time and operator experience to name a few. Overall, 5 of the 7 AR studies14, 16, 36, 38, 41 described some form of standardization guidelines to attempt to address this. Babacan et al.36 found both basal and decongested records comparable, while

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Mitsuda et al.38 and Zambon et al.16 noted significant differences. As all performed AR under standardized conditions, this indicates the nasal mucosal tissue play a noteworthy role in occupying

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nasal cavity space. Anterior nasal examination occurred in all as part of selection, and excluded those with obvious nasal obstruction or disease. However, Mitsuda et al.38 accepted subjects with turbinate

hypertrophy up to half the nasal lumen. Follow-up records were taken long enough post surgically to exclude inflammation relating to surgical release, thus other factors such as underlying allergic conditions like asthma or rhinitis may be suspected in these patients. In CT nasal cavity assessment, attempts to control ambient conditions or to administer decongestants are not seen. The accuracy of CT imaging of functional airway spaces like the oropharynx is questionable, as the position of the tongue and other muscles during breathing and swallowing can be highly dynamic and inconsistent. The

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accuracy between traditional CT and CBCT has been verified59. The comparability of volumetric measurements by AR and CT have also been shown by numerous authors, especially in the anterior nasal cavity45, 60-62. Terheyden63 found reasonable agreement between AR and CT in the anterior nose from nostrils to 6cm, with the mean error of AR found to be <0.01cm2 at the nasal valve and 0.02cm2

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at the nasal isthmus. As outlined in Table 4, the measurement techniques utilized between studies

differed, even in those of the same method. AR studies used slightly varied distances from the nares

into the nasal cavity, while radiographic studies based their volume calculations on differing computer

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software packages and a mixture or automatic and manual segmentation of airway boundaries.

Slight differences in the surgical technique existed mainly in the areas of midpalatal and

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pterygomaxillary separation. Anterior and lateral osteotomies running posteriorly from the midline below the nasal aperture, as well as mid-palatal separation without pterygomaxillary down-fracture was used by Aras et al.14 and Seeberger as described by Bell and Epker8. Baraldi et al.41, Mitsuda et al.38, Babacan et al.36 and Nada et al.39 made bilateral maxillary osteotomies extending from nasal lateral wall to pterygomaxillary suture including separation at the pterygoid plates and also separation of the

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midpalatal suture. A similar procedure was used by Pereiro-Filho et al.40 based on the work of Kraut9. In Prado et al.42, the mobilization method described by Betts et al.64 whereby bilateral osteotomies run from piriform rim to pterygomaxillary fissure parallel to the occlusal plane with a step present at the zygomatic buttress and including pterygoid plate release. Bone is removed at the buttress to allow for

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the expansion. Release of the nasal septum with midline palatal osteomoty The technique described by Glassman et al.65 was utilized by Deeb et al.37 and Zambon et al.16 by running osteotomy along the

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maxillary lateral walls from the piriform rim anteriorly, 5mm above the apices of teeth, and ending just anterior to the pterygoid fissure. Seperation of the pterygomaxillary articulation and midpalatal junction is not made. Wreidt et al.15 conducted bilateral para-median osteotomy of the palate, bilateral osteotomy of the zygomatico-alveolar crest to the anterior nasal aperture followed by anterior midline osteotomy with in-fracture of the maxillary segments to confirm mobilization. The inclusion of pterygomaxillary disjunction as part of surgery did not appear to increase the magnitude of volume change in the nasal cavity, variability was consistent with those who did not release the pterygoid plates.

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Initial healing times before expander activation varied across studies, a 4 day period was most common38, 41, 42, other studies used 3 days37, 5-7 days16, 7 days14, 35, 39, 40, and only 1-2 days in one study15. The distraction rate, or expansion protocol used following initial healing was most commonly

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2 quarter turns (0.5mm) per day41,38,16,35, 42. Others followed 3 quarter turns (0.75mm) per day40, 4 quarter turns (1mm) per day14,37, 39, and only one quarter turn (0.25mm) per day15, 36. Not all studies clearly described the amount of expander activation, which could be considered an important variable, especially to correlate with the observed volumetric changes. Across studies this was provided as either

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number of hyrax turns, number of days of turning, change in inter-molar and inter-canine widths, and by some this was not reported in any capacity. From those studies that did attempt to determine a

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relationship, there did not appear to be a correlation between the activation protocol or amount, and changes in airway volumes15, 16; however, this inability to find a correlation may also be a reflection of the small sample sizes used. A similar lack of correlation was found in RME studies in growing subjects that did record activation amount50, 66. This is a limitation of this review, hopefully future

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studies will accurately record activation quantity and test this relationship.

At the completion of active expansion it was most common for the appliance to be left in place for a fixed retention period to stabilize the changes and minimize relapse. Aras et al.14 fixed the TPD with a locking screw and retained it for 6.7±2.3 months. Deeb37 retained TPD for 3-6months followed by

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placement of an implant retained TPA at TPD removal. In hyrax appliances, Baraldi et al.41 and Mitsuda et al.38 kept the appliance for 4months followed by TPA placement, Wreidt et al.15 retained the

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hyrax also for 4months but followed with fixed orthodontic appliances and not TPA. As Prado et al.42 investigated different retention protocols, both groups kept the fixed expander in place for 4months, but only one group received TPA for a further 6months. Pereiro-Filho et al.40 and Zambon et al.16 stabilized the expander for 4months. The bonded expander was removed, cleaned and utilized as a removable retainer for 6months by Babacan et al.36. This illustrates the current lack of guideline or consensus for retention type and duration following SARME.

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Increases were found to be maintained over time. The nasal cavity, during retention, maintained its small insignificant increase in Zambon et al.16. Over the longer term, significant increases over baseline values were shown still by Aras et al.14 at 12 months following appliance removal. Increases were also present in Nada et al.39 at 22 months and Seeberger et al.35 at 63 months; however, these two studies

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included orthodontic fixed appliance treatment in some subjects during follow-up period. This was unlikely to increase nasal volume but may have provided some additional retentive effects. In palatal volume, Prado et al.42 found no significantly lower amount of relapse occurred from an additional

6months of TPA after 4months with passive hyrax after activation. This would indicate the changes

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generated are fairly stable.

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As growth changes are not expected to play a significant role in patients suitable to receive SARME, as they are normally skeletally mature, we can attribute reported changes to the treatment intervention. Zambon et al.16 did include subjects from 16 years old which may threaten to include some growth effects in their results; however, theirs was one of the few studies who did not detect notable increases.

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Of the articles located, study designs had a generally moderate risk of bias, with three using comparator groups36, 39, 42 and only a single with untreated control group41 to elucidate confounding factors. Of the 11 studies included in this review, there was only one RCT, one CCTs, and the remaining 9 were uncontrolled clinical trials of which one was retrospective. Risks of bias were perceived in a number of

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key methodological areas of the included studies with regards to adequate sequence generation and allocation concealment to treatment groups. Randomization is regarded as the only way to prevent both

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known an unknown confounders by ensuring groups share equal baseline characteristics21. Generally

non-randomized studies produce effect estimates that indicate more extreme benefits of the intervention than randomized trials. But, the extent, and even the direction, of this bias is difficult to predict21.There was a general failure to blind assessors of outcome measures to the subjects treatment. Blinding of patients to the presence of an expansion device is difficult, and given the objective nature of the outcome effect measures should not have influenced results significantly. Attrition bias and selective reporting, although rare, could also not be completely ruled out in the majority of studies.

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Attempts to minimize further bias being introduced in this systematic review were taken by the authors. Firstly all steps and methods were conducted under the PRISMA guidelines. All evaluation of database results and retrieved articles was performed independently and in duplicate by 2 reviewers, and any conflicting opinions were resolved by discussion to consensus. Data extraction and risk of bias

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assessment were also performed in duplicate to be impartial. Bias could not be completely avoided however. The search strategy used and databases searched were chosen under guidance of a senior

health sciences librarian, and were comprehensive but studies may have been missed due to location

bias by indexing within these databases. Publication bias exists in that, although unpublished works

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were searched, none were located, thus only published articles were included. Published studies are may be more likely to be reporting results of a positive nature. As a result of the biases present within

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the included studies and also the heterogeneity of the experimental methods used, extrapolation of the results presented to other patients and populations may be inaccurate. Although the results should be viewed with care, this review does represent the most up to date work on this topic.

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CONCLUSIONS

There is moderate quality evidence to suggest a significant increase in nasal cavity volume is produced by SARME in the short term, remaining to at least 63 months. Moderate quality evidence from a small

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number of studies also indicates significant increase in palatal volume is produced, remaining after

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retention. However, evidence is still weak to draw conclusions of the effect on oropharyngeal volume

How any increase in upper airway volume may impact functional respiratory parameters such as resistance to airflow, breathing mode or pathological conditions like OSA remains to be determined. Indication for SARME at this point remains to be based on orthodontic correction, and not primarily for airway changes.

Additional high-quality randomized controlled trials investigating the volumetric changes produced by SARME against untreated controls are required to better demonstrate the treatment effect, in

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conjunction with more standardized definitions of airway region boundaries to allow meaningful comparisons between studies.

ACKNOWLEDGEMENTS

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The authors would like to acknowledge the assistance of Lajos Bordas in the database searching

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References

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1. Brown JB: Elongation of the partially cleft palate. Am J Orthod Oral Surg 24:878, 1938 2. Basdra EK, Zöller JE, Komposch G: Surgically assisted rapid palatal expansion. J Clin Orthod 29:762, 1995 3. Koudstaal MJ, Poort LJ, Van der Wal KGH, Wolvius EB, Prahl-Andersen B, Schulten AJM: Surgically assisted rapid maxillary expansion (SARME): a review of the literature. Int J Oral Maxillofac Surg 34:709, 2005 4. Knaup B, Yildizhan F, Wehrbein H: Age-related changes in the midpalatal suture. J Orofac Orthop 65:467, 2004 5. Melsen B: Palatal growth studied on human autopsy material : A histologic microradiographic study. Am J Orthod 68:42, 1975 6. Persson M TB: Palatal suture closure in man from 15-35 years of age. Am J Orthod 72:42, 1977 7. Ilizarov GA: The principles of the Ilizarov method. Bull Hosp Jt Dis Orthop Inst 48:1, 1987 8. Bell W, Epker B: Surgical-orthodontic expansion of the maxilla. Am J Orthod 70:517, 1976 9. Kraut RA: Surgically assisted rapid maxillary expansion by opening the midpalatal suture. J Oral Maxillofac Surg 42:651, 1984 10. Lagravère MO, Major PW, Flores-Mir C: Dental and skeletal changes following surgically assisted rapid maxillary expansion. Int J Oral Maxillofac Surg 35:481, 2006 11. Koudstaal MJ, Wolvius EB, Schulten AJM, Hop WCJ, Van der Wal KGH: Stability, tipping and relapse of bone-borne versus tooth-borne surgically assisted rapid maxillary expansion; a prospective randomized patient trial. Int J Oral Maxillofac Surg 38:308, 2009 12. Byloff FK, Mossaz CF: Skeletal and dental changes following surgically assisted rapid palatal expansion. Eur J Orthod 26:403, 2004 13. Basciftci FA, Mutlu N, Karaman AI, Malkoc S, Küçükkolbasi H: Does the timing and method of rapid maxillary expansion have an effect on the changes in nasal dimensions? Angle Orthod 72:118, 2002 14. Aras A, Akay MC, Cukurova I, Gunbay T, Isiksal E, Aras I: Dimensional changes of the nasal cavity after transpalatal distraction using bone-borne distractor: an acoustic rhinometry and computed tomography evaluation. J Oral Maxillofac Surg 68:1487, 2010 15. Wriedt S, Kunkel M, Zentner A, Wahlmann UW: Surgically assisted rapid palatal expansion. An acoustic rhinometric, morphometric and sonographic investigation. J Orofac Orthop 62:107, 2001 16. Zambon CE, Ceccheti MM, Utumi ER, Pinna FR, Machado GG, Peres MP, Voegels RL: Orthodontic measurements and nasal respiratory function after surgically assisted rapid maxillary expansion: an acoustic rhinometry and rhinomanometry study. Int J Oral Maxillofac Surg 41:1120, 2012 17. Warren DW, Hershey G, Turvey TA, Hinton VA, Hairfield WM: The nasal airway following maxillary expansion. Am J Orthod Dentofacial Orthop 91:111, 1987 18. Hilberg O, Jackson AC, Swift DL, Pedersen OF: Acoustic rhinometry: evaluation of nasal cavity geometry by acoustic reflection. J Appl Physiol 66:295, 1989 19. Welch V, Petticrew M, Tugwell P, Moher D, O'Neill J, Waters E, White H: PRISMA-Equity 2012 extension: reporting guidelines for systematic reviews with a focus on health equity. Revista Panamericana de Salud Pública 34:60, 2013 20. Jørgensen AW, Hilden J, Gøtzsche PC: Cochrane reviews compared with industry supported meta-analyses and other meta-analyses of the same drugs: systematic review. Brit Med J 333:782, 2006 21. Higgins JPT, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, Savović J, Schulz KF, Weeks L, Sterne JAC: The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. Brit Med J 343, 2011 22. Lagravere MO, Major PW, Flores-Mir C: Long-term skeletal changes with rapid maxillary expansion: a systematic review. Angle Orthod 75:1046, 2005 23. Nguyen QV, Bezemer PD, Habets L, Prahl-Andersen B: A systematic review of the relationship between overjet size and traumatic dental injuries. Eur J Orthod 21:503, 1999 24. Greenlee GM, Huang GJ, Chen SS-H, Chen J, Koepsell T, Hujoel P: Stability of treatment for anterior open-bite malocclusion: a meta-analysis. Am J Orthod Dentofacial Orthop 139:154, 2011

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25. Viswanathan M, Ansari MT, Berkman ND, Chang S, Hartling L, McPheeters M, Santaguida PL, Shamliyan T, Singh K, Tsertsvadze A: Assessing the risk of bias of individual studies in systematic reviews of health care interventions. (ed., 2012, 26. Catunda IS, Vasconcelos BC, Caubi AF, do Amaral MF, Moreno EF, Melo AR: Evaluation of changes in nasal airway in patients having undergone surgically assisted maxillary expansion. J Craniofac Surg 24:1336, 2013 27. Kober C, Kannenberg S, Frank B, Al-Hakim G, Parvin A, Landes C, Sader R: Computerassisted pre- and postoperative evaluation of surgically assisted rapid maxillary expansion. Int J Comput Dent 14:233, 2011 28. Kurt G, Altug-Ataç AT, Atac MS, Karasu HA: Changes in nasopharyngeal airway following orthopedic and surgically assisted rapid maxillary expansion. J Craniofac Surg 21:312, 2010 29. Laudemann K, Santo G, Revilla C, Harth M, Kopp S, Sader RA, Landes CA: Assessment of surgically assisted rapid maxillary expansion regarding pterygomaxillary disjunction using thin volume-rendering technique: in variance analysis and in reliability, accuracy, and validity. Int J Oral Maxillofac Surg 69:2631, 2011 30. Reinbacher KE, Wallner J, Pau M, Feichtinger M, Karcher H, Quehenberger F, Zemann W: Surgically assisted rapid maxillary expansion: feasibility of not releasing the nasal septum. Int J Oral Maxillofac Surg 42:321, 2013 31. Seeberger R, Kater W, Schulte-Geers M, Thiele OC, Davids R, Hofele CH, Freier K: Surgically assisted rapid maxillary expansion. Effects on the nasal airways and nasal septum. HNO 58:806, 2010 32. Magnusson A, Bjerklin K, Nilsson P, Jönsson F, Marcusson A: Nasal cavity size, airway resistance, and subjective sensation after surgically assisted rapid maxillary expansion: A prospective longitudinal study. Am J Orthod Dentofacial Orthop 140:641, 2011 33. Tausche E, Deeb W, Hansen L, Hietschold V, Harzer W, Schneider M: CT analysis of nasal volume changes after surgically-assisted rapid maxillary expansion. J Orofac Orthop 70:306, 2009 34. Kunkel M, Ekert O, Wagner W: Changes in the nasal airway by transverse distraction of the maxilla. Mund Keifer Gesichts Chir 3:12, 1999 35. Seeberger R, Kater W, Davids R, Thiele OC: Long term effects of surgically assisted rapid maxillary expansion without performing osteotomy of the pterygoid plates. J Craniomaxillofac Surg 38:175, 2010 36. Babacan H, Sokucu O, Doruk C, Ay S: Rapid maxillary expansion and surgically assisted rapid maxillary expansion effects on nasal volume. Angle Orthod 76:66, 2006 37. Deeb W, Hansen L, Hotan T, Hietschold V, Harzer W, Tausche E: Changes in nasal volume after surgically assisted bone-borne rapid maxillary expansion. Am J Orthod Dentofacial Orthop 137:782, 2010 38. Mitsuda ST, Pereira MD, Passos AP, Hino CT, Ferreira LM: Effects of surgically assisted rapid maxillary expansion on nasal dimensions using acoustic rhinometry. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 109:191, 2010 39. Nada RM, van Loon B, Schols JG, Maal TJ, de Koning MJ, Mostafa YA, Kuijpers-Jagtman AM: Volumetric changes of the nose and nasal airway 2 years after tooth-borne and bone-borne surgically assisted rapid maxillary expansion. Eur J Oral Sci 121:450, 2013 40. Pereira-Filho VA, Monnazzi MS, Gabrielli MA, Spin-Neto R, Watanabe ER, Gimenez CM, Santos-Pinto A, Gabrielli MF: Volumetric upper airway assessment in patients with transverse maxillary deficiency after surgically assisted rapid maxillary expansion. Int J Oral Maxillofac Surg 43:581, 2014 41. Baraldi CE, Pretto SM, Puricelli E: Evaluation of surgically assisted maxillary expansion using acoustic rhinometry and postero-anterior cephalometry. Int J Oral Maxillofac Surg 36:305, 2007 42. Prado GP, Pereira MD, Bilo JP, Furtado F, Ferreira LM: Stability of surgically assisted rapid palatal expansion: a randomized trial. J Dent Res 92:49S, 2013 43. Sokucu O, Doruk C, Uysal OI: Comparison of the effects of RME and fan-type RME on nasal airway by using acoustic rhinometry. Angle Orthod 80:870, 2010 44. De Felippe NLO, Da Silveira AC, Viana G, Kusnoto B, Smith B, Evans CA: Relationship between rapid maxillary expansion and nasal cavity size and airway resistance: short- and long-term effects. Am J Orthod Dentofacial Orthop 134:370, 2008

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45. Doruk C, Sokucu O, Bicakci AA, Yilmaz U, Tas F: Comparison of nasal volume changes during rapid maxillary expansion using acoustic rhinometry and computed tomography. Eur J Orthod 29:251, 2007 46. Zeng J, Gao X: A prospective CBCT study of upper airway changes after rapid maxillary expansion. Int J Pediatr Otorhinolaryngol 77:1805, 2013 47. Cordasco G, Nucera R, Fastuca R, Matarese G, Lindauer SJ, Leone P, Manzo P, Martina R: Effects of orthopedic maxillary expansion on nasal cavity size in growing subjects: a low dose computer tomography clinical trial. Int J Pediatr Otorhinolaryngol 76:1547, 2012 48. Smith T, Ghoneima A, Stewart K, Liu S, Eckert G, Halum S, Kula K: Three-dimensional computed tomography analysis of airway volume changes after rapid maxillary expansion. Am J Orthod Dentofacial Orthop 141:618, 2012 49. Gorgulu S, Gokce SM, Olmez H, Sagdic D, Ors F: Nasal cavity volume changes after rapid maxillary expansion in adolescents evaluated with 3-dimensional simulation and modeling programs. Am J Orthod Dentofacial Orthop 140:633, 2011 50. Palaisa J, Ngan P, Martin C, Razmus T: Use of conventional tomography to evaluate changes in the nasal cavity with rapid palatal expansion. Am J Orthod Dentofacial Orthop 132:458, 2007 51. Proctor DF, Andersen IHP: The nose, upper airway physiology and the atmospheric environment. Elsevier Biomedical Press, 1982 52. Tausche E, Hansen L, Hietschold V, Lagravère MO, Harzer W: Three-dimensional evaluation of surgically assisted implant bone-borne rapid maxillary expansion: a pilot study. Am J Orthod Dentofacial Orthop 131:S92, 2007 53. Teuscher U: An appraisal of growth and reaction to extraoral anchorage simulation of orthodontic-orthopedic results. Am J Orthod 89:113, 1986 54. Kabalan O, Gordon J, Heo G, Lagravère MO: Nasal airway changes in bone-borne and toothborne rapid maxillary expansion treatments. Int Orthod 13:1, 2015 55. Motro M, Schauseil M, Ludwig B, Zorkun B, Mainusch S, Ateş M, Küçükkeleş N, Korbmacher-Steiner H: Rapid-maxillary-expansion induced rhinological effects: a retrospective multicenter study. Eur Arch Otorhinolaryngol 1, 2015 56. Pangrazio-Kulbersh V, Wine P, Haughey M, Pajtas B, Kaczynski R: Cone beam computed tomography evaluation of changes in the naso-maxillary complex associated with two types of maxillary expanders. Angle Orthod 82:448, 2012 57. Chang Y, Koenig LJ, Pruszynski JE, Bradley TG, Bosio JA, Liu D: Dimensional changes of upper airway after rapid maxillary expansion: a prospective cone-beam computed tomography study. Am J Orthod Dentofacial Orthop 143:462, 2013 58. Kunkel M, Hochban W: Acoustic rhinometry: a new diagnostic procedure—experimental and clinical experience. Int J Oral Maxillofac Surg 23:409, 1994 59. Liang X, Lambrichts I, Sun Y, Denis K, Hassan B, Li L, Pauwels R, Jacobs R: A comparative evaluation of cone beam computed tomography (CBCT) and multi-slice CT (MSCT). Part II: On 3D model accuracy. Eur J Radiol 75:270, 2010 60. Çakmak Ö, Coşkun M, Çelik H, Büyüklü F, Özlüoğlu LN: Value of acoustic rhinometry for measuring nasal valve area. Laryngoscope 113:295, 2003 61. Prasun D, Jura N, Tomi H, Pertti R, Markus R, Erkki L: Nasal airway volumetric measurement using segmented HRCT images and acoustic rhinometry. Am J Rhinol 13:97, 1999 62. Tarhan E, Coskun M, Cakmak O, Çelik H, Cankurtaran M: Acoustic rhinometry in humans: accuracy of nasal passage area estimates, and ability to quantify paranasal sinus volume and ostium size. J Appl Physiol 99:616, 2005 63. Terheyden H, Maune S, Mertens J, Hilberg O: Acoustic rhinometry: validation by threedimensionally reconstructed computer tomographic scans. J Appl Physiol 89:1013, 2000 64. Betts N, Vanarsdall R, Barber H, Higgins-Barber K, Fonseca R: Diagnosis and treatment of transverse maxillary deficiency. The International journal of adult orthodontics and orthognathic surgery 10:75, 1995 65. Glassman AS, Nahigian SJ, Medway JM, Aronowitz HI: Conservative surgical orthodontic adult rapid palatal expansion: Sixteen cases. Am J Orthod 86:207, 1984 66. Haralambidis A, Ari-Demirkaya A, Acar A, Kucukkeles N, Ates M, Ozkaya S: Morphologic changes of the nasal cavity induced by rapid maxillary expansion: a study on 3-dimensional computed tomography models. Am J Orthod Dentofacial Orthop 136:815, 2009

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Figure and Table Legend: Table 1 - Search Results by Database

Figure 1 - PRISMA Flowchart Table 3 - PICO of Included Studies Table 4 - Airway Region and Calculation of Included Studies

Table 6 - Surgical Techniques of Included Studies

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Table 5 - Measurement Techniques and Key Result Summary

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Table 2 - Studies Excluded at Full-text Review with Reasons

Table 7 - Expansion and Retention Protocols of Included Studies

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Table 8 - Risk of Bias Assessment by Cochrane Risk of Bias Tool

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Table 9 - Risk of Bias Assessment of Included Studies by Customized Tool

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Table 1: Search results by Database

Selected

284 194 11 11 0 -

11 11 0 1 0 0 0

% of 11 selected articles 100% 100% 0 9% 0 0 0

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Embase Ovid Medline Premedline CENTRAL Old Medline ClinicalTrials.gov National Research register

Results

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Database

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Table 2: Studies Excluded at Full-text Review with Reasons

PML ML Hand ML E, ML, CEN E, ML E E, ML E, ML

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Key to reason for exclusion of studies at FT: 1. Not assessing or measuring upper airway volume(s) 2. Duplicate sample or sample data used

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Reason 1 1 2 1,2 1 1 1 2 1

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Catunda et al.25 2013 Kober et al.26 2011 Kunkel et al.33 1999 Kurt et al.27 2010 Laudemann et al.28 2011 Reinbacher et al.29 2013 Seeberger & Hofele et al.30 2010 Tausche et al.32 2009 Magnusson et al.31 2011

Included after FT Review NO NO NO NO NO NO NO NO NO

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Database(s) Found

Study

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Table 3: Study Design, Participants, Intervention, Comparators and Outcome (PICO) of Included Studies

Turkey

Prospective Clinical Trial

Baraldi et al.43 2007

Brazil

Prospective Controlled Clinical Trial

13 (4m, 9f) mean age 25.13±6.93yrs

Deeb et al.39 2010

Germany

Prospective Clinical Trial

Mitsuda et al.40 2010

Brazil

Prospective Clinical Trial

Nada et al.41 2013

Netherlands

Prospective Cohort Study

16 (6m, 10f) mean age 28yr8m (range 17-36yrs) 27 (11m, 16f) mean age 28.03yrs (range 18-53yrs) Tooth-borne: 19 (5m, 14w) mean age 24.2 ± 7yrs Bone-borne: 13 (6m, 7w) mean age 31.9 ± 10 15 (6m, 9f) mean age 30.3 ±7.4yrs No Retention: 15 (8m, 7f) mean age 26.3±5.3yrs Retention: 15 (10m, 5f) mean age 25.3 ±5.0yrs 13 (5m, 8f) mean age 31.23 ± 6.11yrs 10 (5m, 5f) mean age 28.5yrs (range 16.9-43.6yrs) 27 (59.5%f) mean age 25.33yrs (range 17-44yrs)

Prospective Clinical Trial

Brazil

RCT

Seeberger et al.37 2010

Germany

Wreidt et al.16 2001

Germany

Retrospective Clinical Trial Prospective Clinical Trial

Zambon et al.17 2012

Brazil

Prospective Clinical Trial

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Brazil

Comparator No

RME: 10 (5b, 5g) mean age 12.3 ± 0.82yrs Untreated: 10 (4m, 6f) mean age 26.1±4.68yrs No

Inclusion Criteria Bilateral crossbite due to maxillary transverse deficiency w/ mouth or mixed breathing Skeletal maxillary constriction w/ bilateral posterior crossbite. No previous ENT surgery & adequate nasal cavity space

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Babacan et al.38 2006

Pereira-Filho et al.42 2013 Prado et al.44 2013

Participants 11 (5m, 6f) mean age 27.3yrs (range 19-41yrs) 10 (4m, 6f) mean age 18.7 ± 2.54yrs

Indication by Betts analysis, No Hx of previous maxillary expansion attempts, No extractions (except 8’s), No Hx nasal or palatal surgery Maxillary transverse constriction, no Hx of nasal disease

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Study design Prospective Clinical Trial

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Country Turkey

No

Bone-borne

Tooth-borne

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Study Aras et al.15 2010

Maxillary transverse deficiency >7mm, Bilateral posterior crossbite, no Hx of agenesis, nasal or Pa surgery or expansion Skeletal maturity Skeletal transverse maxillary deficiency >5mm, in addition to other skeletal discrepancy requiring orthognathic surgery No developments deformities

Intervention TPD

Outcome Nasal volume

RME

Nasal volume

RME

Nasal volume

TPD

Nasal volume

RME

Nasal volume

TPD

Nasal volume

RME

No

Transverse maxillary deficiency

RME

Oropharynx volume

No

Healthy adult pts, bilateral crossbite, Bilateral maxillary deficiency >5mm

RME

Nasal volume Palatal volume

No

Cross bite due to maxillary compression

RME

Nasal volume

No

Maxillary transverse deficit >5mm

RME

Palatal volume

No

Aged ≥16yrs, good periodontal condition, Permanent Mx molars & premolars, Maxillary constriction with orthodontic referral for surgical expansion

RME

Nasal volume

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Table 4: Airway Region and Calculation of Included Studies

Airway Region Nasal volume

Boundary Definition Vol1 = 0-22mm in from nares Vol2 = 22-54mm in from nares Not disclosed

Babacan et al.38 2006

Nasal volume

Baraldi et al.43 2007

Nasal volume

Deeb et al.39 2010

Nasal volume

Mitsuda et al.40 2010

Nasal volume

0-54mm in from nares

Nada et al.41 2013

Nasal volume

Pereira-Filho et al.42 2013

Oropharynx volume

Prado et al.44 2013

Palatal volume

Seeberger et al.37 2010

Nasal volume

Wreidt et al.16 2001

Nasal volume Palatal volume

Zambon et al.17 2012

Nasal volume

Coronal slices from soft-tissue nasion to posterior nasal spine Upper limit is plane from the posterior limit of the hard palate & parallel to Frankfort plane, with inferior limit plane from the most anterior and inferior point of the second cervical vertebra & also parallel to the Frankfort plane. Coronal plane at distal of upper first molars, vertically by an outline of the cervical margins of the teeth. Resulting outline was closed to produce a solid for volume calculation Anterior = 0-23mm in from nares Middle = 23-46mm in from nares Posterior = 46-70mm in from nares Not disclosed Coronal plane at distal of upper first molars, in the vertical dimension by the occlusal plane Not disclosed

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Software calculated area at 3 planes antero-posteriorly, area multiplied by distance between planes to calc volume AR – Computer calculated sum of areas over distance. Each recording taken 5 times & average used Manual segmentation in ITK-SNAP software with computed calculation Computer calculated using Dolphin Imaging 3D software (Dolphin Imaging and Management Solutions, Chatsworth, CA, USA)

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Vol1 = 0-22mm in from nares Vol2 = 22-54mm in from nares From anterior vicinity of the apertura piriformis to behind the choanae

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Calculation Method AR – Computer calculated sum of areas over distance. Each recording taken 5 times & average used AR – Computer calculated sum of areas over distance. Each recording taken 4 times & average used AR – Computer calculated sum of areas over distance.

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Study Aras et al.15 2010

Computer calculated using 3D software (Geomagic Qualify 12.0)

AR – Computer calculated sum of areas over distance.

AR – Computer calculated sum of areas over distance. The palatal vault was measured by filling the maxillary casts with ‘plastilin’ & determining its volume AR – Computer calculated sum of areas over distance.

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Table 4: Measurement Techniques, Time-points, Airway Regions & Key Result Summary of Included Studies

AR

Baraldi et al.43 2007

AR

Deeb et al.39 2010

CT

Mitsuda et al.40 2010

AR

Nada et al.41 2013

CBCT

CBCT

Prado et al.44 2013

Model scanning

AR

Wreidt et al.16 2001

AR

Effective (p=0.003, 0.026, 0.006) (p=0.013, 0.036, 0.045) (p=0.028, 0.005, 0.005) (p=0.131, 0.003, 0.016) Effective (p<0.05) Effective (p<0.05)

Nasal volume (ND) Volume1: R,L & Total

T1- Prior to surgery T2- n/a T3- After ~6m retention T1- Prior to surgery T2- n/a T3- After ~8m retention T1- Prior to surgery T2- n/a T3- After ~6m retention T1- Prior to surgery T2- n/a T3- After ~6m retention

Nasal volume (ND) Nasal volume (D)

T1-T3: 118%, 85%, 101% T1-T4: 65%, 58%, 62% T1-T3: 86%, 162%, 120% T1-T4: 82%, 151%, 114% T1-T3: 14.09% T1-T3: 17.86%

Nasal vol1 (D) Nasal vol2 (D)

T1-T3: 4.97% T1-T3: 8.61%

Not-effective (p>0.05) Not-effective (p>0.05)

Nasal volume

T1-T3: 5.1%

Not-effective (p>0.05)

T1-T3: 46.85% T1-T3: 59.97% T1-T3: 58.56% T1-T3: 64.94%

Effective (p=-4.37) Effective (p=-4.54) Effective (p=-4.54) Effective (p=-4.54)

T1-T4: 9.74% T1-T4: 12.95%

Effective (p<0.001) Effective (p<0.001)

T1-T2: 16.4% T2-T3: 6.8%

Not-effective (p>0.05) Not-effective (p>0.05)

T1-T3: 24.8%

Effective (p<0.001)

T1-T3: 28.4% T1-T4: 25.2% T1-T4: 23.25% T1-T4: 25.31% T1-T4: 22.11% T1-T4: 23.87% T1-T4: 30.36% T1-T3: 21.2% T1-T3:23.3% T1-T3: 23.1% T1-T3: 19.7%

Effective (p<0.001) Effective (p<0.001) Effective (p<0.01) Effective (p<0.01) Effective (p<0.01) Effective (p<0.01) Effective (p<0.01) Effective (p<0.01) Effective (p<0.01) Effective (p<0.01) Effective (p<0.01)

Volume2: R,L & Total

T1- Prior to surgery T2- n/a T3- n/a T4 - After pre-surgical orthodontics (~22m) T1- Prior to surgery T2- Immediately after active expansion T3- After ~6m (4m retention) Retention Group T1- Prior to surgery T2- n/a T3- After 4m hyrax retention T4- After further 6m no retention No retention Group T1- Prior to surgery T2- n/a T3- After 4m hyrax retention T4- After further 6m TPA retention T1- Prior to surgery T2- n/a T3- n/a T4 – After 63m

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Outcome

T1- Prior to surgery T2- n/a T3- After ~6m retention T4- 12m after expander removal

Nasal volume R (ND) Nasal volume R (D) Nasal volume L (ND) Nasal volume L (D) Nasal volume RME TPD Oropharynx volume

Palatal volume

EP

Pereira-Filho et al.42 2013

Approx Change (%)

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Babacan et al.38 2006

Region Measured

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Follow-up Time Points

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Measurement Technique

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Study

T1- Prior to surgery T2- n/a T3- Towards end of retention

Nasal volume Total (D) Nasal volume Anterior (D) Nasal volume Middle (D) Nasal volume Posterior (D) Nasal volume Isthmus (D) Nasal volume Total (D) Nasal volume Anterior (D) Nasal volume Middle (D) Nasal volume Posterior (D)

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Zambon et al.17 2012

AR

T1- Prior to surgery T2- n/a T3- At removal of hyrax ~6-12m T1- Prior to surgery T2- Imm after active expansion T3- After ~4m retention

Palatal volume

T1-T3: 18.9%

Effective (p<0.01)

Nasal volume (D)

T1-T2: 6.76% T1-T3: 9.18% T1-T2: 11.47% T1-T3: 10.38%

Not-effective (p>0.05) Not-effective (p>0.05)

Nasal volume (ND)

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Pa volume

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NOTE: (ND) denotes no-decongestant, (D) denotes the use of decongestant. Approximate percentage change was calculated by = (post-pre)/pre x 100

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Table 6: Surgical Techniques of Included Studies

Mitsuda et al.40 2010

Nada et al.41 2013

Pereira-Filho et al.42 2013 Prado et al.44 2013

Seeberger et al.37 2010

Wreidt et al.16 2001

Zambon et al.17 2012

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Activation at Surgery Yes

Initial Healing Period 7 days

Not disclosed

Not disclosed

Yes

4 days

Yes

3 days

Yes

4 days

Not disclosed

7 days

Not disclosed

7 days

Yes

4 days

Yes

7 days

Yes

1-2 days

Yes

5-7 days

SC

M AN U

Deeb et al.39 2010

TE D

Baraldi et al.43 2007

EP

Babacan et al.38 2006

Surgical Technique

Bilateral osteotomies from midline below the nasal aperture posteriorly without pterygomaxillary separation, also mid-palatal separation Bilateral osteotomies of lateral nasal wall to pterygomaxillary suture with pterygomaxillary separation, and mid-palatal separation Bilateral osteotomies of lateral nasal wall to pterygomaxillary suture with pterygomaxillary separation, and mid-palatal separation Bilateral osteotomies from midline below the nasal aperture posteriorly ending anterior to pterygomaxillary suture without pterygomaxillary separation. Nasal septum release but not midpalatal separation Bilateral osteotomies of lateral nasal wall to pterygomaxillary suture with pterygomaxillary separation, and mid-palatal separation Bilateral osteotomies of lateral nasal wall to pterygomaxillary suture with pterygomaxillary separation, and mid-palatal separation Bilateral osteotomies of lateral nasal wall to pterygomaxillary suture with pterygomaxillary separation, and mid-palatal separation Bilateral osteotomies of lateral nasal wall to pterygomaxillary suture with pterygomaxillary separation & step at zygomatic buttress, and mid-palatal separation Bilateral osteotomies from midline below the nasal aperture posteriorly without pterygomaxillary separation, also mid-palatal separation Bilateral para-median osteotomy of palate, bilateral lateral osteotomy from nasal aperture & anterior midline osteotomy with in-fracture of segments Bilateral osteotomies from midline below the nasal aperture posteriorly ending anterior to pterygomaxillary suture without pterygomaxillary separation. Nasal septum release but not midpalatal separation

AC C

Study Aras et al.15 2010

ACCEPTED MANUSCRIPT

Table 5: Expansion and Retention Protocols of Included Studies

Baraldi et al.43 2007

RME Hyrax or Haas

Deeb et al.39 2010

TPD (Dresden distractor)

Mitsuda et al.40 2010

Hyrax banded on U4s & U6s

Nada et al.41 2013

Hyrax banded on U4s & U6s TPD (Surgi-Tec) RME (banded on U4s & U6s)

Prado et al.44 2013

No Retention Group Hyrax RME (unspecified)

4 days healing period ¼ turn (0.2mm) twice per day until end point. No over expansion 4 days healing period ¼ turn (0.2mm) twice per day until end point. No over expansion 7 day healing period 2x ¼ turns per day (0.5mm/day)

EP

Pereira-Filho et al.42 2013

4 day healing period 2 activations (0.5mm) per day Overexpansion not stated 3 day healing period 4 activations per day until (0.25mm/each) with overexpansion of 0.5-1mm 4 day healing period 2x ¼ turns per day 7 day healing period 1mm activation per day 7 day healing period ¼ turn (0.25mm) every 8hrs (0.75mm per 24hrs) Slight overcorrection achieved

AC C

Retention Group Hyrax RME (unspecified) Seeberger et al.37 2010

Hyrax banded on U4s & U6s

Wreidt et al.16 2001

RME with 4 bands

Zambon et al.17 2012

Hyrax RME (banded on U4s & U6s)

RI PT

Hyrax full coverage bonded

Expansion Period Range 7-10days mean activation period 23.4 ± 1.57 days. “until the desired suture opening was achieved”

SC

Babacan et al.38 2006

Protocol 7 day healing period 1mm per day distraction rate ¼ turn per day until desired expansion achieved

Not specified

M AN U

Expander Design TPD (Surgi-Tec NV, Bruges, Belgium)

TE D

Study Aras et al.15 2010

1-2 days healing period ¼ turn per day. Overexpansion not stated 5-7day healing period ¼ turn morning & ¼ turn night End point not specified

Retention Blocking screw added to TPD, left for 6.7 ± 2.3months At endpoint screw tied off with 0.014” ligature wire, left for 1 week to minimize removal discomfort Appliance removed, cleaned and used as removal retainer for ~6m retention period RME mean retention period 6.19 ± 0.16 m Expander kept for 4m as retainer, then TPA

Mean activation period 8 ± 2 days. Average expansion 7.25mm

Appliance left in place for 3-6months after expansion complete

“until the planned expansion was achieved” Until Pa cusps of Mx teeth touched Bu cusps of Md teeth Mean activation period 14.4 ± 1.8 days Mean inter-molar expansion 6.93 ± 3.43mm

Appliance fixed with ligature wire and left in place 4m, then TPA Appliance fixed and left for 3m retention TPD blocked with screw for 3m retention Appliance stabilized and maintained for 4m retention

mean expansion of 4m retention group = 8.4 ± 1.46mm

Hyrax tied with wire for 4m retention

Mean expansion of 10m retention group = 8.95 ± 1.22mm

Hyrax tied with wire for 4m, then replaced with TPA 10m. Total 10m retention Not specified

Not specified

Activation between first molars 510.7mm n/a

Hyrax maintained for 6-12m retention

Hyrax ‘stabilized’ and maintained for 4m

ACCEPTED MANUSCRIPT

Table 6: Risk of Bias Assessment by Cochrane Risk of Bias Tool

Incomplete Outcome Data Addressed

Unclear Unclear Low Low Low Low Unclear Low Low Unclear Low

M AN U

TE D EP AC C

Low Low Low Low Low Low Low Low Unclear Low Low

Low Unclear Unclear Unclear Low Low High Low Unclear Unclear Unclear

RI PT

Outcome Assessment (Blinding)

High High High High High Low High Low High High High

SC

Allocation Concealment

High High High High High High High Low High High High

Other Sources of Bias

Random Sequence Generation

High High Unclear High High High High Low High High High

Free of Selective Reporting

Study Aras et al.15 2010 Babacan et al.38 2006 Baraldi et al.43 2007 Deeb et al.39 2010 Mitsuda et al.40 2010 Nada et al.41 2013 Pereira-Filho et al.42 2013 Prado et al.44 2013 Seeberger et al.37 2010 Wreidt et al.16 2001 Zambon et al.17 2012

ACCEPTED MANUSCRIPT

Table 7: Risk of Bias Assessment of Included Studies by Customized Tool

2 2 1 2 2 2 2 2 2 2 2 2

0 0 0 0 0 1 0 1 0 0 0 1

1 1 0 1 1 1 0 1 0 0 0 1

M AN U

TE D EP AC C

SC

2 2 2 2 2 2 2 2 2 2 2 2

Quality

Measurement Defined

0 0 0 1 1 0 0 1 1 0 1 1

TOTAL

Intervention Protocol Described

2 2 2 2 2 2 2 2 1 1 2 2

Reasonable Conclusion

Dropouts Mentioned

0 0 2 0 0 1 0 1 0 0 0 2

Conclusion

Presentation of Data

Follow-up Definition & Length

1 1 1 1 2 2 1 2 1 0 2 2

Confounders Analyzed

Controls Used

1 1 1 1 1 1 1 2 2 1 1 2

Appropriate Stats

Sample Size

2 2 2 2 2 2 2 2 2 2 2 2

Reliability/Error Testing

Selection Criteria

0 0 0 0 0 0 0 1 0 0 0 1

Assessor Blinding

Sample Described

TOTAL

Statistical Analysis

Randomization

Study Aras et al.15 2010 Babacan et al.38 2006 Baraldi et al.43 2007 Deeb et al.39 2010 Mitsuda et al.40 2010 Nada et al.41 2013 Pereira-Filho et al.42 2013 Prado et al.44 2013 Seeberger et al.37 2010 Wreidt et al.16 2001 Zambon et al.17 2012

Study Conduct

1 1 1 2 1 1 1 2 1 1 1 2

1 1 1 1 1 1 1 1 1 1 1 1

14 16 14 16 18 17 13 23 14 11 15 25

Moderate Moderate Moderate Moderate Moderate Moderate Moderate High Moderate Low Moderate

RI PT

Study Design

1 1 1 1 1 1 1 1 1 1 1 1

0 2 0 0 2 0 0 2 0 0 0 2

AC C

EP

TE D

M AN U

SC

RI PT

ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT

SC

SARME.mp (61) SARPE.mp (29) rapid maxillary expan$.mp (583) rapid palatal expan$.mp (298) maxillary expan$.mp (860) skeletal expan$.mp (42) palatal expan$.mp (2188) transverse expan$.mp (75) transpalatal distract$.mp (21) rapid maxillary disjunction.mp (0) rapid palatal disjunction.mp (1) 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 (2333) air$.mp (363985) volum$.mp (499056) 13 or 14 (826506) 12 and 15 (212)

AC C

EP

TE D

M AN U

1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16.

RI PT

Appendix A: Medline Search Strategy via Ovid

ACCEPTED MANUSCRIPT

Appendix B: Data Extraction Form

Study Name: Author & Year:

Control/Comparator Group (age, gender, ethnicity, etc): Methods of recruitment of participants: Inclusion Criteria: Exclusion Criteria:

Informed consent obtained? (Yes/No/Unclear)

Funding (if stated)

M AN U

Ethical approval (Yes/No/Unclear)

SC

Sample Group (age, gender, ethnicity, etc):

RI PT

Date form completed:

Statistical methods and their appropriateness (if relevant):

Principal health problem or diagnosis (if relevant): Other health problem/s (if relevant): Purpose of study (if stated):

TE D

Treatment received/receiving:

Volume Measurement Technique(s) used: Region that Volume Measured:

Definition/Boundaries of Measured Region(s): Other Measurements Taken:

EP

RME Technique Used:

Expansion Appliance Details: Activation Protocol:

AC C

Activation End-point:

Retention Protocol (method & timing): T2 Measurement Time-Point: T3 Measurement Time-Point: AR Specifics (measurement technique): CT Specifics (measurement & calculation technique): 3D Photographic/ Scanning Specifics (measurement & calculation technique): Error Assessment:

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