Abstract
A variety of metals and alloys are employed in the field of orthodontics, of which the construction of wires happens to be predominant. Through this systematic review, our primary goal was to review and assess studies focusing on complications that emerged during or directly after the completion of an orthodontic treatment plan. We then used a meta-analysis to determine how these complications affected the patients who were receiving orthodontic treatment. A total of 634 documents were discovered after a thorough search of online journals, and 416 of the papers were initially selected. In the end, 14 papers, including in vitro experiments, literature reviews, comparative analyses, observational studies, and retrospective studies, were chosen that met the requisite inclusion and exclusion criteria. There were difficulties related to orthodontic treatment in all of the studies listed in our systematic review, but their severity varied greatly. The effects of gingival mucosa and root resorption were two of the most often mentioned periodontal problems in this review. More long-term studies are required to confirm the involvement of an orthodontic component in these issues, but the majority of the complications were assessed to initially arise after the treatment plan had begun and to resolve with time.
1. Introduction
Untreated malocclusion has been demonstrated to have detrimental psychological, social, and physical effects that can lower quality of life in terms of oral health []. The goals of orthodontic therapy include enhancing the function and appearance of the teeth; enhancing psychosocial well-being; and lowering the chance of long-term issues brought on by malocclusion, such as tooth wear, gingival issues, and pathologies associated with impacted teeth []. The demand for orthodontic treatment still outstrips supply, despite accounting for about one-tenth of the NHS dental primary care expenditure in England, which was £3.4 billion in 2015–2016 []. According to the 2013 Child Dental Health Survey, 9% of 12-year-olds and 18% of 15-year-olds, respectively, were receiving orthodontic treatment, but an additional 37% and 20% of those 12- and 15-year-olds were found to need orthodontic treatment [].
The standard of treatment must be evaluated using patient-reported outcome measures (PROMs) and patient-reported experience measures (PREMs) []. While PREMs offer information about the actual process of getting care, PROMs help to assess the effectiveness and safety of care from the perspective of the patient []. However, orthodontic study is increasingly including patient-reported measures, such as pain during treatment, expectations of treatment, and quality of life factors (impact of malocclusion, acceptability of treatment, anxiety, and occlusion) []. Currently, clinical care does not commonly use orthodontic-specific protocols in this respect. One of the most commonly assessed patient-reported outcomes in both study and audit is patient satisfaction.
One tool designed specifically for orthodontics to gauge parent satisfaction with young patients’ orthodontic treatment takes into account both the procedure and the results []. Some other studies have also reported the effects of patient perception regarding the various facets of orthodontic treatment modalities [,]. Despite being a frequent indicator, contentment may not be able to distinguish between different facets of care, and may have a “ceiling” effect that can mask unpleasant experiences while receiving care [].
The COVID-19 epidemic, which first surfaced two years ago, interrupted the world’s medical and dental services [,]. The best recommendations for helping patients deal with orthodontic emergencies right away have been collected in this review. The following suggestion was made: when providing in-person treatment, strictly adhere to infection control guidelines after providing initial treatment guidance online at first []. In addition to acute orthodontic emergencies, there are other issues that could have varying effects on the course of therapy. It is crucial to draw attention to these issues in this unusual circumstance because they are linked to the stage of treatment, whether in the active or passive stages of orthodontic treatment. During the COVID-19 pandemic, many orthodontic patients were faced with delays in treatment. As a result of the pandemic, orthodontic practices were forced to close or limit their services to help prevent the spread of the virus []. This meant that patients with ongoing orthodontic needs had to put their treatment on hold, which could have caused complications or setbacks in their treatment progress []. Additionally, some patients who were in the middle of their orthodontic treatment when the pandemic hit may have experienced difficulty in scheduling follow-up appointments or adjustments due to closures or limited availability of their orthodontist. These delays and setbacks have been frustrating for patients, and have added to the already stressful situation of the pandemic [].
Therefore, our main objective in conducting this systematic review was to examine and evaluate studies that looked at complications that occurred during or immediately following the conclusion of an orthodontic treatment plan, and to assess the impact of these complications on patients who were undergoing orthodontic treatment by the means of a meta-analysis.
2. Materials and Methods
2.1. Study Design
This systematic review was performed as per the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) strategy (Figure 1) and rules from the Cochrane group and the book Orderly Reviews in Health Care: Meta-Examination []. The current systematic review has been registered (CRD42022380829) with PROSPERO.
Figure 1.
Article selection framework as per PRISMA protocol.
2.2. Clinical Question Explored
In this systematic review, our major goal was to assess studies that observed incidences of complications during or directly after the completion of a complete orthodontic treatment plan. Additionally, we also selected some studies that made mention of a comparative evaluation between two orthodontic appliances/devices, with respect to which was more prone to causing complications in the patients.
2.3. Inclusion Criterion
The inclusion criteria employed for this investigation were as follows:
- Studies that reported on complications arising due to orthodontic treatment in children and adults;
- Studies that reported on orthodontic treatments, including fixed appliances, removable appliances, clear aligners, or other types of orthodontic devices;
- Studies that reported on outcomes related to complications, including root resorption, periodontal disease, caries, pain, discomfort, or any other complications related to orthodontic treatment;
- Studies that reported comparisons between different types of orthodontic treatments, such as clear aligners vs. fixed appliances, or other comparisons;
- Studies that were conducted in humans.
2.4. Exclusion Criteria
The following types of articles were excluded from the scope of our systematic review:
- Studies that were not available as full texts or were not written in English;
- Studies that did not report on complications arising due to orthodontic treatment;
- Studies that reported on complications related to other dental treatments or surgeries, such as tooth extraction or implant placement;
- Studies that reported on orthodontic treatment in animals or in vitro studies;
- Studies that reported on orthodontic treatments that were not commonly used, such as self-ligating brackets or other unusual modalities;
- Case reports or case series;
- Studies that had atrociously low sample sizes (<10 participants);
- Studies that were duplicates or reported on the same population, intervention, or outcomes as other studies already included in the review.
2.5. Search Strategy
In the beginning, we identified the relevant databases for conducting the search. PubMed, Scopus, Cochrane Library, and Web of Science were selected for the purpose of conducting this investigation, after which we developed a search strategy using a combination of medical subject headings (MeSH), terms, and keywords related to our research question and eligibility criteria, which were “Complications,” “Mucosal damage,” “Orthodontics,” “Orthodontic appliances,” and “Periodontitis”. Using this, we recorded the search terms, the number of articles retrieved, and the date of the search, following which the retrieved articles were screened for eligibility criteria. This process was performed in two stages: title and abstract screening, followed by full-text screening. The number of included and excluded articles was recorded at each stage. In the conclusive stage of this strategy, data from the included studies were extracted using a pre-defined data extraction form. The search strategy used Boolean operators across PubMed, Scopus, Cochrane Library, and Web of Science for the provided research question and eligibility criteria:
((Complications [MeSH Terms]) OR Mucosal Damage [MeSH Terms]) OR Orthodontics [MeSH Terms]) OR Orthodontic Appliances [MeSH Terms]) OR Periodontitis [MeSH Terms]) AND ((“complications” OR “mucosal damage” OR “orthodontics” OR “orthodontic appliances” OR “periodontitis”))) AND (English [Language] AND ((“1 January 2017”:”1 November 2022”)).
This search strategy included medical subject headings (MeSH terms) including the terms “Complications,” “Mucosal Damage,” “Orthodontics,” “Orthodontic Appliances,” and “Periodontitis.” The Boolean operator “OR” was used to combine the MeSH terms with their corresponding keywords. The Boolean operator “AND” was used to combine the search terms related to the research question and eligibility criteria. Additionally, the search strategy included language-based eligibility criteria, including only English language articles, and criteria regarding the time period for article selection, which was from 1 January 2017 to 1 November 2022.
2.6. Data Gathering Protocol
Two independent reviewers extracted the data from the included studies, using the data extraction form, to guarantee their accuracy and reliability. Any disagreements were clarified through conversation or communication with a different reviewer. Utilizing a standardized tool, the included studies’ quality was evaluated, and the findings were documented using a particular data extraction form. After that, the data were subjected to a meta-analysis, which synthesizes the findings of various studies to produce an overall estimate of impact size. Finally, using the appropriate tables, graphs, and descriptive statistics, the results of the systematic review and meta-analysis were presented in a straightforward, comprehensible, and succinct way.
2.7. Statistical Analysis
The data were picked based on information regarding the sample size, factors examined, and various features of the research before being entered into the Revman 5 program for meta-analysis. Figure 2, Figure 3 and Figure 4 depict forest plots that were obtained as part of our study’s meta-analysis, and show the odds ratios for various study methodologies.
2.8. Risk of Bias Assessment
The AMSTAR-2 technique [] was used to evaluate the risk of bias in the studies we chose. AMSTAR 2 joins a number of other instruments that have been released for this purpose, for use in systematic reviews (Figure 2). The AMSTAR 2 risk of bias items identified the domains specified in the Cochrane risk of bias instrument for systematic reviews. In each case, this indicates an agreement achieved after input from more than 30 methodology experts.
Figure 2.
AMSTAR-2 16-point checklist of risk of bias assessment in studies selected for the systematic review [,,,,,,,,,,,,,].
Figure 3.
Odds ratio of clinical trials [,,,,,,,,,,,,,] selected in this systematic review and the impact of complications reported within them, displayed on a forest plot after meta-analysis.
Figure 4.
Risk ratio of clinical trials [,,,,,,,,,,,,,] selected in this systematic review and the impact of complications reported within them, displayed on a forest plot after meta-analysis.
3. Results
After the initial search strategy was completed, we encountered 634 papers pertinent to the study’s objectives. In the second step, 416 articles remained after removal of duplicate studies/studies that were common with one another. Ultimately, in the final selection phase, 14 articles were generated after the application of all the inclusion and exclusion criterion.
Thirty studies were selected for the review, and their demographic characteristics were assessed in Table 1. The sample size ranged from 50 to 300, with no definitive parameters related to the age of the participants assessed across the studies. The male-to-female ratio was fairly balanced across the studies, ranging from 1:1.1 to 1:1.3. Out of these fourteen articles, one was a randomized control trial [], four happened to be retrospective studies [,,,], one was a comparative study [], three studies were of cross-sectional design [,,], three studies were observational in protocol [,,], and the remaining two utilized a questionnaire as their methodological approach [,].
Table 1.
Description and outcomes as observed in the studies selected for the systematic review.
The forest layouts from the 14 studies that were considered for the analysis are shown in Figure 3, Figure 4 and Figure 5. After considering all pertinent factors related to the papers, the data were entered into the RevMan 5 software, and forest plots displaying the odds ratio, risk ratio, and risk difference related to the effect of the specific complication encountered in the respective study were produced and assessed. The meta-analysis employed a random effects model with a 95% confidence range. For each investigation, the total sample size was the total number of events, and a random effects model was applied.
Figure 5.
Risk difference of clinical trials [,,,,,,,,,,,,,] selected in this systematic review and the impact of complications reported within them, displayed on a forest plot after meta-analysis.
Figure 3 displays the forest plot of the odds ratio obtained through the meta-analysis of clinical trials [,,,,,,,,,,,,,] that examined the impact of orthodontic complications on patients undergoing orthodontic treatment. The odds ratio was found to be 0.51 [0.33, 0.79], indicating that the intervention may be effective in reducing the risk of complications in the study population. The odds ratio of less than 1 suggests that patients who received the intervention (which differed from study-to-study as per the complication that was observed) had lower odds of experiencing orthodontic complications compared to those who did not receive the intervention. The confidence interval for the odds ratio ranged from 0.33 to 0.79, suggesting that the true effect size is likely to fall within this range. However, the wide range of the confidence interval indicates that the true effect size is uncertain. The heterogeneity statistics reported in the forest plot indicate that there is significant variation in the effect sizes reported across the studies included in the meta-analysis. The Tau2 value of 0.56 suggests that there is substantial heterogeneity between the studies, while the Chi2 value of 97.76, with 12 degrees of freedom and a p-value of <0.00001, indicates significant heterogeneity. The I2 value of 88% indicates that a large proportion of the heterogeneity is due to true differences in effect sizes. The test for overall effect, with a Z-value of 2.99 and a p-value of 0.003, indicates that the overall effect of the intervention on reducing orthodontic complications is statistically significant. Overall, the forest plot suggests that the intervention may be effective in reducing the risk of orthodontic complications in patients undergoing orthodontic treatment. However, the wide confidence interval and significant heterogeneity highlight the need for further research to confirm the intervention’s effects and explore the sources of heterogeneity.
The risk ratio for the clinical trials [,,,,,,,,,,,,,] is shown in the forest plot of Figure 5. These trials investigated the impact of orthodontic complications on patients undergoing orthodontic treatment. The risk ratio found was 0.72 [0.58, 0.90], which suggests that the intervention may be effective in reducing the risk of complications in the study population. The risk ratio of less than 1 indicates that the patients who received the intervention (which differed from study-to-study as per the complication that was observed in it) had a lower risk of experiencing orthodontic complications compared to those who did not receive the intervention. The confidence interval for the risk ratio ranged from 0.58 to 0.90, indicating that the true effect size is likely to fall within this range. However, the wide confidence interval suggests some uncertainty regarding the true effect size of the intervention. The heterogeneity statistics reported in the forest plot indicate that there is significant variation in the effect sizes reported across the studies included in the meta-analysis. The Tau2 value of 0.13 suggests that there is moderate heterogeneity between the studies, while the Chi2 value of 90.82, with 12 degrees of freedom and a p-value of <0.00001, indicates significant heterogeneity. The I2 value of 87% indicates that a large proportion of the heterogeneity is due to true differences in effect sizes. The test for overall effect, with a Z-value of 2.93 and a p-value of 0.003, indicates that the overall effect of the intervention on reducing orthodontic complications is statistically significant. Overall, the forest plot suggests that the intervention may be effective in reducing the risk of orthodontic complications in patients undergoing orthodontic treatment. However, the wide confidence interval and significant heterogeneity indicate that further research is needed to confirm the intervention’s effects and explore the sources of heterogeneity.
The forest plot represented in Figure 5 shows the results of the meta-analysis that examined the impact of complications on the sample size, which consisted of patients undergoing orthodontic treatment in any form, as reported in the clinical studies [,,,,,,,,,,,,,]. The risk difference found was −0.16 [−0.42, 0.11], which suggests that the risk of complications might be lower in the group receiving the intervention (which differed from study-to-study as per the complication that was observed in it) compared to the control group. However, it is important to note that the confidence interval ranged from −0.42 to 0.11, which indicates that the true effect size may be anywhere within this range. The forest plot also reported heterogeneity statistics, which indicate how much variation existed between the studies included in the meta-analysis. The Tau2 value of 0.25 suggests that there is substantial heterogeneity, meaning that the studies differ significantly from each other in terms of their effect sizes. The Chi2 value of 1511.37, with 13 degrees of freedom and a p-value of <0.00001, indicates significant heterogeneity. The I2 value of 99% suggests that almost all of the heterogeneity is due to true differences in effect sizes, rather than chance or sampling error. This high level of heterogeneity means that the studies may have different populations, interventions, or outcomes, which makes it difficult to draw firm conclusions from the meta-analysis. In summary, the forest plot suggests that the intervention may reduce the risk of complications, but the true effect size is uncertain due to the wide confidence interval and high level of heterogeneity. Future research should aim to address the sources of heterogeneity and provide more precise estimates of the intervention’s effects.
4. Discussion
The significance of this study lies in its systematic approach to reviewing the literature on the metallurgical characteristics of metals and alloys used in orthodontic treatment, and the associated complications. By synthesizing the findings of 14 studies, this review provides a comprehensive overview of the difficulties related to orthodontic treatment and highlights the need for more long-term studies to confirm the involvement of an orthodontic component in these issues. The review’s implications are threefold. Firstly, our findings identified gingival mucosa and root resorption as the most commonly reported periodontal problems associated with orthodontic treatment. Orthodontists can use this information to monitor patients for these complications and take preventive measures to minimize their occurrence. Additionally, this investigation highlights the need for more long-term studies to confirm the involvement of orthodontic treatment in the identified complications. Future studies can build on the findings of this review to investigate the mechanisms underlying these complications and develop strategies to mitigate them. Moreover, this review can inform the education and training of orthodontic professionals by providing a comprehensive overview of the complications associated with orthodontic treatment. Educators can use this information to develop curricula that emphasize the importance of monitoring patients for these complications and taking preventive measures to minimize their occurrence.
Overall, this systematic review contributes to our understanding of the metallurgical characteristics of metals and alloys used in orthodontic treatment and the associated complications, providing a foundation for future research, clinical practice, and education in this field.
The duration of orthodontic treatment, the level of pain and discomfort, and the use of retention appliances, in contrast, were all linked to patient dissatisfaction. This was revealed by a systematic analysis of 18 studies [] that looked at patient satisfaction with orthodontic treatment. The evaluation showed a wide range in terms of research design, setting, demographics, and measurement methods. According to a qualitative study [], adult patients’ satisfaction with their orthodontic care was correlated with communication, staff, the physical surroundings, appointments, and the impact of appliance therapy. Orthodontic treatment aims to move teeth to their desired positions, but this movement can result in some undesirable consequences, such as root resorption []. Root resorption occurs when the cells responsible for breaking down and rebuilding bone, known as osteoclasts and osteoblasts, respectively, become overactive and remove more tooth structure than necessary, leading to shorter roots [,,,]. Intrusion, retraction, and torque movements are common orthodontic tooth movements that have been investigated regarding their potential to cause root resorption [,,,,]. While these movements alone may not increase the risk of root resorption, factors such as the amount of force applied, stress distribution region, and total apical displacement can make them more potent [,,].
First, the amount of force applied is critical in determining the extent of root resorption. Studies have shown that higher forces lead to increased root resorption, with force levels above 2 N associated with a greater risk of resorption [,,,,]. This is because high forces cause an imbalance between the forces applied to the tooth and the ability of the surrounding tissues to support them. As a result, the tooth moves faster than the surrounding bone can remodel, leading to hyalinization (death of cells) and resorption of the root [,,,].
Second, the stress distribution region can also affect the risk of root resorption [,,,,,]. When orthodontic forces are applied, they create stresses within the tooth and the surrounding bone. Areas of the tooth with the highest stress concentrations are at a greater risk of root resorption. For example, the apex of the tooth, where the forces are most concentrated, is more likely to experience resorption than the middle or the cervical regions [,,,,].
Lastly, the total apical displacement of the tooth is also crucial in determining the risk of root resorption [,]. Greater displacement of the tooth can lead to increased hyalinization and resorption of the root. The longer the tooth is under tension, the more likely it is to undergo resorption []. All in all, while intrusion, retraction, and torque movements may not necessarily raise the risk of root resorption on their own, the amount of force applied, stress distribution region, and total apical displacement can make them more potent [,,,]. Therefore, it is essential to apply appropriate forces and carefully monitor the movement of the tooth to minimize the risk of root resorption. Orthodontists should consider these factors while planning and executing orthodontic treatment to achieve the desired results while minimizing the risk of undesirable outcomes.
The studies that are available demonstrate that aligners have a reduced risk of root resorption when compared to fixed appliances, despite the fact that there is little research on root resorption associated with aligner applications [,,,,,,,,,]. This could be as a result of the intermittent, comparatively light pressures that these appliances employ, which result in less tooth movement and apical displacement. The cementum repair procedure is recommended in order to improve the likelihood of root healing. Additionally, in instances of mild crowding without the need for extractions, and for quicker treatment times, aligners are frequently advised [,,,,,]. Another element that impacts how well aligners function is patient compliance. Aligners transmit pressure more intermittently and for shorter periods of time when a patient is non-compliant, which lowers the risk of root resorption []. However, they can also produce jiggling forces [,,,,]. This is not commonly reported [], as determining its occurrence is difficult [,,,,,].
Surprisingly, none of the research studies we cited in our analysis looked at root resorption with regard to removable equipment. Strong forces led to a rise in root absorption. A significant correlation between root resorption and orthodontic force level was found in several systematic evaluations [,,]. Several studies claim that there is only scant proof to back up this association [,,]. Orthodontic treatment aims to correct malocclusions or misaligned teeth and jaws. While the majority of orthodontic treatments are successful, there are risks and complications associated with orthodontic treatment. Some patients may develop allergic reactions to the materials used in orthodontic appliances, such as metal wires or brackets [,]. This can cause discomfort, swelling, and even difficulty breathing in severe cases []. Orthodontic appliances can sometimes interfere with speech, causing a lisp or other speech impediments. This is more common with certain types of appliances, and not all of them []. It is common for patients to experience some discomfort during orthodontic treatment, particularly in the days after braces are tightened []. However, if the pain is severe or persistent, it could be a sign of a more serious problem, such as a loose bracket or wire []. Orthodontic appliances can also sometimes cause staining or discoloration of the teeth, particularly if the patient consumes certain foods or beverages that are known to stain teeth (such as coffee, tea, or red wine) []. This can be difficult to treat and may require professional teeth whitening after the braces are removed. In some cases, orthodontic treatment may actually cause bite problems, rather than correcting them []. For example, if the teeth are moved too quickly or too far, it can result in an open bite or crossbite. As we discussed earlier, root resorption is the primary complication arising due to these treatment modalities []. This is the shortening or loss of the tooth roots, which can occur when orthodontic forces are applied to the teeth []. Another is decalcification, which is caused by the breakdown of the tooth enamel due to poor oral hygiene, particularly around orthodontic appliances []. Gingivitis and periodontitis are conditions that affect the gums and can be caused by poor oral hygiene during orthodontic treatment []. When the teeth are not cleaned properly, the accumulation of plaque and tartar can lead to inflammation and infection of the gums. Conditions that affect the temporomandibular joint (TMJ) can also cause pain and discomfort in the jaw, face, and neck due to appliance usage []. This can occur when orthodontic forces are applied incorrectly or when there is a pre-existing problem with the TMJ []. Orthodontic appliances can also inadvertently result in orthodontic complications if they are not used correctly or if they are not properly maintained []. If brackets or wires break, they can cause discomfort, delay treatment, or even cause injury to the mouth or throat. If appliances are not properly secured, they can shift or become damaged, potentially leading to complications such as root resorption or gingivitis []. If patients do not follow instructions on how to use appliances correctly, they may not achieve the desired results or may even cause damage to their teeth or gums []. All in all, orthodontic treatment can have complications, and appliances can inadvertently contribute to these complications if they are not used correctly or if they are not properly maintained. It is important for patients to follow the instructions of their orthodontist and maintain good oral hygiene throughout treatment to reduce the risk of complications. However, it is important to note that not all patients will experience complications during orthodontic treatment, and most complications can be easily treated or prevented with proper care and attention. It is always a good idea to discuss any concerns or questions you have with your orthodontist, who can help guide you through the treatment process and address any issues that arise.
If compared to what an ideal review assessing orthodontic complications should look like, the number of studies (especially randomized control trials) that we selected for our systematic review and the subsequent meta-analysis can be deemed to be low []. However, the fact is that we were very strict in our selection criterion for selecting studies and only chose papers for which the methodological quality was deemed to be fairly moderate to high. We avoided studies conducted during or after the pandemic that analyzed these changes and were specific to COVID-19, because many of the studies available in the online databases were merely scoping reviews or presentations about how the pandemic has affected the incidence of orthodontic treatment-related complications, without substantiated evidence to support the claims. As a result, we believe that more research is required to determine whether complications resulting due to orthodontic treatment modalities have been affected by the incidence of the pandemic.
5. Conclusions
There were complications related to orthodontic treatment in all of the studies cited in our systematic analysis, but their severity varied greatly. Gingival mucosa and root resorption, as well as their impacts, were two of the most frequently mentioned periodontal problems in the review. The majority of the issues were determined to arise originally following the start of the treatment plan and to resolve over time, but additional long-term studies are required to confirm the involvement of orthodontic factors in these problems. Two of the most frequently cited periodontal issues in the review were gingival mucosa and root resorption. The majority of the complications were determined to initially arise after the treatment plan had started and to resolve over time, but more extensive, long-term studies are needed to confirm the involvement of an orthodontic component in these issues.
Author Contributions
Conceptualization: M.K.A. and A.A.A. (Ahmed Ali Alfawzan); methodology: M.K.A., B.K., H.A., A.S., H.J.A., A.A.A. (Ahmed Ali Alfawzan), D.S., and K.C.S.; software: H.A., A.S., H.J.A., A.A.A. (Ahmed Ali Alfawzan) and D.S.; validation: A.S., H.J.A., A.A.A. (Almothana Ali Alaskar), I.A.A., A.S.A. and D.S.; formal analysis: M.K.A., B.K. and K.C.S.; writing—original draft preparation: M.K.A., B.K., H.A., A.S., D.S. and K.C.S.; writing—review and editing: M.K.A., B.K., H.A., A.S., H.J.A., A.A.A. (Ahmed Ali Alfawzan), L.H.A., S.F.S.A., A.A.A. (Almothana Ali Alaskar), I.A.A., A.S.A., D.S. and K.C.S., visualization: L.H.A., S.F.S.A., A.A.A. (Almothana Ali Alaskar), I.A.A. and D.S.; supervision: M.K.A.; project administration: M.K.A.; funding acquisition: M.K.A., L.H.A., S.F.S.A., A.A.A. (Almothana Ali Alaskar), A.S.A., I.A.A. and K.C.S. All authors have read and agreed to the published version of the manuscript.
Funding
This research received no external funding.
Institutional Review Board Statement
Registered (CRD42022380829) with PROSPERO.
Informed Consent Statement
Not required.
Data Availability Statement
All data are available within the manuscript.
Conflicts of Interest
The authors declare no conflict of interest with respect to this systematic review and meta-analysis.
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