SYSTEMATIC REVIEW

Year : 2015  |  Volume : 6  |  Issue : 4  |  Page : 134-140

Implications and applications of systematic reviews for evidence-based dentistry and comparative effectiveness research: A sample study on antibiotics for oro-facial cellulitis treatment

Quyen Bach¹, Vandan Kasar¹, Francesco Chiappelli^2
1 Student, Division of Oral Biology and Medicine, Section of Oral Biology, UCLA School of Dentistry, Los Angeles, California, USA
² Student, Division of Oral Biology and Medicine, Section of Oral Biology; Evidence-Based Decision Practice-Based Research Network, UCLA School of Dentistry, Los Angeles, California, USA

Correspondence Address:
Francesco Chiappelli
School of Dentistry, Division of Oral Biology and Medicine, UCLA Center for the Health Sciences 63-090, 10833 Le Conte Avenue, Los Angeles - 90095-1668, California
USA

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/2155-8213.170639

Introduction: Comparative effectiveness and efficacy research for analysis and practice (CEERAP) was performed to assess the effects of penicillin-based versus erythromycin-based antibiotic treatments in patients with skin and soft tissue infections (SSTIs) including cellulitis, impetigo, and erysipelas. Because SSTIs, especially orofacial cellulitis, are volatile infectious diseases of a life-threatening nature, research on the most efficacious remedies is necessary. Methods: The stringent bibliome yielded three systematic reviews, which were examined for quality of research synthesis protocol and clinical relevance. Results: The sample size of three, rendered the statistical analyses and cumulative meta-analysis problematic. Conclusion: The systematic review outlined here should aid in increasing clinical awareness, improving patient health literacy, and promoting consensus of the best evidence base (BEB) to mitigate the threat of sepsis and potential death caused by cellulitis infections.

Keywords: Best evidence base (BEB), comparative effectiveness and efficacy research for analysis and practice (CEERAP), erythromycin, evidence-based dentistry (EBD), orofacial cellulitis, penicillin, skin and soft tissue infections (SSTIs), systematic review

Introduction

• Antibiotic treatments administered orally in males and females of all ages 2 weeks after completion of the antibiotic regime.
• Patients were diagnosed with either cellulitis or similar SSTIs, erysipelas and impetigo.
• The clinical outcome of interest was the elimination of threat to health from sepsis caused by cellulitis, as measured by the reduced presence of laboratory markers of inflammation and infection.
• The clinical outcome was measured 2 weeks after antibiotic treatment and in a hospital-dentistry setting.

1. Preparing the topic.
   • Topic refinement.
   • Developing an analytic framework.
   • Search, bibliome, and publication bias.
2. Study eligibility and relevance.
   • Identify study eligibility criteria.
   • Search for relevant studies.
   • Select evidence for inclusion.
3. Extracting data from studies.
   • Grade strength of evidence: Expansion of the Grading of Recommendations Assessment, Development, and Evaluation (EX-GRADE), Revised Assessment for Multiple Systematic Reviews (R-AMSTAR), Risk of Bias, Appraisal of Guidelines and Research and Evaluation, Europe (AGREE).
4. Analyzing and synthesizing studies.
   • Quantitative consensus.
   • Qualitative consensus.
5. Reporting the systematic review.

1. Preparing the topic.
   
   This step sets the stage for the entire systematic review and consists of three main components: Topic refinement, analytic frameworks as well as search, bibliome, and publication bias. After developing a topic based on its appropriateness, importance, and feasibility, the topic can be refined to a PICOTS question. Modeling these components graphically in an analytical framework can present the information in such a way that helps to visually link factors such as interventions and stakeholder investment to final outcomes, and everything in between [Figure 1]. ^[6] When later searching and refining the bibliome, that is, in the process of eliminating irrelevant evidence after examining all the available literature on a topic, an issue becomes apparent: A degree of publication bias exists. It is important to keep this bias in mind as the process continues, as it is an inevitable issue that may have an effect on the outcome. ^[7]

   Figure 1: Schematic representation of the systematic review process. The systematic review protocol involves 5 essential steps, each delineated by its own set of subprocesses and criteria Click here to view

2. Study eligibility and relevance in pursuance of the bibliome.
   
   The PICOTS question derived in the previous step will enable the formulation of key questions, literature search, inclusion and exclusion criteria, and data extraction. When determining the eligibility criteria, one effectively controls how wide or narrow the scope of a systematic review will be. The criteria for study eligibility may include such factors as study design, studies in foreign languages, gray literature, and year of publication. After defining the eligibility criteria, the next step is to search for relevant studies, i.e., randomized controlled trials (RCTs) that are within the inclusion and exclusion criteria. To perform this literature search, a set of keywords or Medical Subject Headings (MeSH) words should be utilized with search engines that produce curated results such as PubMed and MEDLINE databases [Figure 2]. The overarching goal of selecting studies for eligibility and relevance is to reduce bias and increase the applicability of study results to the issue at hand.

   Figure 2: Framework of literature search. This figure shows the process by which the 3 resulting systematic reviews were chosen for qualitative analysis Click here to view

3. Extracting data from studies.
   
   After selecting relevant studies, one must proceed to grade the strength of evidence extracted from these studies by using assessment tools. Grading often and ideally provides the researcher with a quantifiable value, which can subsequently function as an indicator of quality and/or completeness. Evaluating the strength of evidence is crucial to allow the use of papers from authors with a variety of perspectives, and to reach a consensus of the best available evidence base. Among the wide array of grading systems presently at the disposal of evidence-based dentistry researchers, the most recommended ones grade the strength of evidence based on the risk of bias, consistency, directness, and precision. ^[7] Many practical guidelines have been developed by our group, which include but are not limited to the following: EX-GRADE, ^[8] R-AMSTAR, ^[9] Risk of Bias, ^[7] and AGREE. ^[10] The steps of each assessment tool are described in further detail below.
   1. EX-GRADE is an expansion of the Grading of Recommendations Assessment, Development, and Evaluation. This assessment is based on eight questions each worth 4 points, which assesses the report based on the evidence provided and the strength of the recommendation made in the report. ^[8] The four domains in this assessment include:
      • Study design.
      • Study quality.
      • Consistency.
      • Directness.
   2. R-AMSTAR or Revised Assessment for Multiple Systematic Reviews provides an 11-item checklist to validate the content and methodological quality of the systematic reviews. This assessment quantifies systematic review quality with a score out of maximum 44, with 44 indicating the lowest possible risk of bias. ^[9] The R-AMSTAR considers 11 criteria:
      • A priori design.
      • Duplicate study selection and data extraction.
      • Comprehensive literature search.
      • Status of publication.
      • Inclusion and exclusion criteria.
      • Relevant characteristics of the population (age, sex, and socioeconomic data).
      • Scientific quality of the included studies.
      • Utilization of included studies in the formation of conclusions.
      • Statistical methods of combining data or conclusions.
      • Likelihood of publication bias.
      • Conflicts of interest.
   3. A risk of bias tool was created (Cochrane Risk of Bias), which covered six specific domains ^*:
      • Sequence generation.
      • Allocation concealment.
      • Blinding of participants and researchers.
      • Incomplete outcome data.
      • Selective outcome reporting.
      • Other sources of bias.
      
      ^* Within each domain, assessments of one or more of the following criteria were evaluated:
      • Selection bias.
      • Performance bias.
      • Detection bias.
      • Attrition bias.
      • Reporting bias.
      • Other research protocol-related biases. ^[7],[11]
   4. AGREE stands for Appraisal of Guidelines and Research and Evaluation, Europe ^* The AGREE grading tool utilizes a system of 23 criteria points, which are evaluated from points 1-4. The six main domains for this instrument are:
      • Scope and purpose.
      • Stakeholder involvement.
      • Rigor of development.
      • Clarity and presentation.
      • Applicability.
      • Editorial independence.
   ^*AGREE was revised to the AGREE II, which was expanded to include a 7-point scoring system instead of 4, and some of the criteria were improved upon to make better the power and sensitivity of the tool. ^[10]
4. Analyzing and synthesizing studies.
   
   When the researcher has finished compiling evidence, he or she can analyze the results in two distinct ways: Quantitative or qualitative consensus. A meta-analysis is a statistical analysis designed to compare and combine results from different studies to identify patterns among the results, sources of disagreement among those results, or other interesting relationships that may come to light in the context of multiple studies. ^[12] In brief, meta-analysis provides valuable information to better understand alternative intervention efficacy, consistency of study effects, and statistical heterogeneity. ^[12] The key to quantitative consensus is reaching a quantifiable conclusion, which can provide valuable results after applying statistical analysis methods. By contrast, qualitative consensus can be used when obtaining a quantitative conclusion is not possible such as in situations of research designs with insufficient data and small sample sizes. The qualitative consensus method utilizes open-ended interview questions, contextual evidence, and consensus among the research group by taking in multiple opinions.


Two qualitative consensus methods generally used include the Delphi process and the RAND expert panel:
• The RAND expert panel is a multidisciplinary consensus panel, which combines both scientific evidence and clinical experience in order to create the best clinical procedure. The process begins by a thorough systematic review of the literature for the clinical procedure in question. A set of indications are created for that procedure and independently rated by nine expert panelists. The scores are discussed in a group in a face-to-face fashion, and rerated until a consensus is reached on the clinical procedure that is brought to a clinical setting. ^[13]
• The Delphi process is another communication method, which utilizes a panel of experts. In this technique, the panelists are kept anonymous, even from one another, as they respond to multiple rounds of questionnaires. A moderator disseminates the responses in a statistical form. The overall goal of this method is to reach an expert consensus while minimizing the potential issues arising from group dynamics from a face-to-face discussion, as seen in the RAND expert panel. ^[8]
5. Reporting the systematic review.
   
   The final step in performing an effective systematic review is reporting the findings. When reporting a comparative effectiveness review, a standard template should be used to ensure high clarity. The template should include an abstract, introduction, methods, results, and discussion. If a review is not reported accurately, readers may come across issues when evaluating the strength of evidence.

Results

• Interventions for cellulitis and erysipelas.
• Systemic antibiotics for symptomatic apical periodontitis and acute apical abscess in adults.
• Interventions for impetigo. ^{[2],[15],[16]}

Discussion

Figure 3: Dissemination and Utilization of Research Results [Moura et al. 2013] The following mechanisms and protocols were discussed in relation to their potential to improve dissemination and utilization of the best available evidence Click here to view

• A RAND expert panel, which will define and promote the necessity to have timely and cost-effective clinical interventions. ^[8]
• Health care institutions should have a committee in place that reviews the RAND expert panels clinical consensus and decides if it is financially feasible to enact the new procedure.
• Improvement in the use of laboratory test results and patient communication via training with model of care used in medical schools. ^[17]
• Improvement of patient literacy regarding pre- and postoperative procedures.
• Training of clinicians to determine consensus using BEB.

• Media: If a change or clinical intervention is significant to the extent that more patients would benefit from being aware of it, the media should be alerted to disseminate the information via advertisements, news articles, or social health magazines.
• Surveys assessing the following outcome measures can be implemented:
  1. Patient satisfaction.
  2. Health literacy.
  3. Incentive or motivation to.
     Go forth with treatment.
     Adhere to treatment specifications by the prescribing doctor.
     Complete the treatment.
     Incentive and motivation values could be determined and defined systematically by Weiner's attribution theory of motivation. ^[18]

Conclusion

References

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