Glick, M., Carrasco-Labra, A., & Urquhart, O. (2023) Statistics for Dental Clinicians (1st ed.). Wiley.

Statistics for Dental Clinicians helps dental practitioners to understand and interpret the scientific literature and apply the concepts to their clinical practice. Written using clear, accessible language, the book breaks down complex statistical and study design principles and demonstrates how statistics can inform clinical practice.

Chapters cover the basic building blocks of statistics, including clinical study designs, descriptive and inferential statistical concepts, and interpretation of study results, including differentiating between clinical and statistical significance. An extensive glossary of statistical terms, as well as graphs, figures, tables, and illustrations are included throughout to improve reader comprehension. Select readings accompany each chapter.

With comprehensive coverage of a broad topic, written using accessible language and shining light on statistical complexity often found in writings related to clinical topics, Statistics for Dental Clinicians is an essential guide for any dental practitioner wishing to improve their understanding of the biomedical literature.

ISBN: 978-1-119-81016-2

Preamble xi

1 What is statistics and why do we need it? 1

2 Understanding and interpreting measures of association 8

3 Understanding and interpreting a standard deviation and normal distribution 17

4 Understanding and interpreting standard error 24

5 Understanding and interpreting hypothesis testing and p-values 30

6 Understanding and interpreting a confidence interval 38

7 Understanding and interpreting power analysis and sample size 45

8 Understanding and interpreting a survival analysis 54

9 Understanding and interpreting a probabilistic-based diagnosis 61

10 Understanding and interpreting a correlation 69

11 Understanding and interpreting a regression analysis 76

12 Understanding and interpreting confounding and effect modification 86

13 Understanding and interpreting bias 98

14 Understanding and interpreting patient-reported outcomes 106

15 Understanding and interpreting a cross-sectional study 113

16 Understanding and interpreting a case-control study 120

17 Understanding and interpreting a cohort study 126

18 Understanding and interpreting a randomized controlled trial 133

19 Understanding and interpreting meta-analyses 145

20 Understanding and interpreting statistical and clinical significance 155

Appendix 1 Formulas and equations 160

Appendix 2 Z-table 183

Appendix 3 T-table 185

Glossary 189

Index 210



Verdugo-Paiva F, Urquhart O, Matanhire-Zihanzu CN, Martins-Pfeifer CC, Booth E, Booth HA, Aljarahi H, Button J, Pinto-Grunfeld C, Villanueva J, Kohler IV, Glick M, Carrasco-Labra A. Barriers to and facilitators for creating, disseminating, implementing, monitoring and evaluating oral health policies in the WHO African region: A scoping review. Community Dent Oral Epidemiol. 2024 Jun 3. doi: 10.1111/cdoe.12984. Epub ahead of print. PMID: 38828735.

Objective: To advance oral health policies (OHPs) in the World Health Organization (WHO) African region, barriers to and facilitators for creating, disseminating, implementing, monitoring and evaluating OHPs in the region were examined.

Methods: Global Health, Embase, PubMed, Public Affairs Information Service Index, ABI/Inform, Web of Science, Academic Search Complete, Scopus, Dissertations Global, Google Scholar, WHO’s Institutional Repository for Information Sharing (IRIS), the WHO Noncommunicable Diseases Document Repository and the Regional African Index Medicus and African Journals Online were searched. Technical officers at the WHO Regional Office for Africa were contacted. Research studies and policy documents reporting barriers to and facilitators for OHP in the 47 Member States in the WHO African region published between January 2002 and March 2024 in English, French or Portuguese were included. Frequencies were used to summarize quantitative data, and descriptive content analysis was used to code and classify barrier and facilitator statements.

Results: Eighty-eight reports, including 55 research articles and 33 policy documents, were included. The vast majority of the research articles and policy documents were country-specific, but they were lacking for most countries. Frequently mentioned barriers across policy at all stages included financial constraints, a limited and poorly organized workforce, deprioritization of oral health, the absence of health information systems, inadequate integration of oral health services within the overarching health system and limited oral health literacy. Facilitators included a renewed commitment to establishing national OHPs, recognition of a need to diversify the oral health workforce, and an increased understanding of the influence of social determinants of health among oral health care providers.

Conclusions: Most countries lack a country-specific body of evidence to assist policymakers in anticipating barriers to and facilitators for OHPs. The barriers and facilitators relevant to disparate subnational, national, and regional conditions and circumstances must be considered to advance the creation, dissemination, implementation, monitoring and evaluation of OHPs in the WHO African region.

DOI | PubMed

Urquhart O, Matanhire-Zihanzu CN, Kulkarni R, Parrado EA, Aljarahi H, Bhosale AS, Braimoh O, Button J, Chifamba T, Emmanuel AT, Gatarayiha A, Kohler IV, Martins-Pfeifer CC, Ojukwu BT, Robbins M, Sofola O, Taiwo OO, Uti O, Makino Y, Glick M, Carrasco-Labra A. Oral Health Policy and Research Capacity: Perspectives From Dental Schools in Africa. Int Dent J. 2024 Apr 26:S0020-6539(24)00045-5. doi: 10.1016/j.identj.2024.01.020. Epub ahead of print. PMID: 38677971.

Introduction and aims: The prioritisation of oral health in all health policies in the WHO African region is gaining momentum. Dental schools in this region are key stakeholders in informing the development and subsequent downstream implementation and monitoring of these policies. The objectives of our study are to determine how dental schools contribute to oral health policies (OHPs) in this region, to identify the barriers to and facilitators for engaging with other local stakeholders, and to understand their capacity to respond to population and public health needs.

Methods: We developed a needs assessment survey, including quantitative and qualitative questions. The survey was developed electronically in Qualtrics and distributed by email in February 2023 to the deans or other designees at dental schools in the WHO African region. Data were analysed in SAS version 9.4 and ATLAS.ti.

Results: The capacity for dental schools to respond to population and public health needs varied. Most schools have postgraduate programs to train the next generation of researchers. However, these programs have limitations that may hinder the students from achieving the necessary skills and training. A majority (75%) of respondents were aware of the existence of national OHPs and encountered a myriad of challenges when engaging with them, including a lack of coordination with other stakeholders, resources, and oral health professionals, and the low priority given to oral health. Their strengths as technical experts and researchers was a common facilitator for engaging with OHPs.

Conclusion: Dental schools in the region face common challenges and facilitators in engaging in the OHP process. There were several school-specific research and training capacities that enabled them to respond to population and public health needs. Overall, shared challenges and facilitators can inform stakeholder dialogues at a national and subnational level and help develop tailored solutions for enhancing the oral health policy pipeline.

Keywords: Barrier; Facilitator; Oral health; Policy; Research; WHO African region.

DOI | PubMed

Fisher JMatanhire-Zihanzu CBuse KA new approach to oral health can lead to healthier societies doi:10.1136/bmj.q925

New definitions of oral health provide an opportunity to change mindsets and promote innovation to tackle high levels of unmet needs, but this will only be realised with a radical change in practice, argue Julian Fisher and colleagues.


Fisher, J., Splieth, C., Matanhire-Zihanzu, C., Glick, M. Advancing the concept of global oral health to strengthen actions for planetary health and One Health. Int J Equity Health 23, 71 (2024).

Advancing the concept of global oral health can help tackle the triple planetary crises of climate change, nature and biodiversity loss, and pollution and waste. A model for oral and planetary health places more explicit focus on understanding the state of the Earth’s systems, changing environment in relation to planetary health boundaries and their impact on human well-being. This can facilitate a planet-centric critical thinking for equity in global oral health that contributes to UN 2030 Agenda for Sustainable Development.


Alajlan N, Carrasco-Labra A, Karabucak B, Lee SM. Systemic Corticosteroid Uses in Endodontics- Part 2: Enhancing the Success of Local Anesthesia. J Endod. 2024 Mar 13:S0099-2399(24)00161-4. doi: 10.1016/j.joen.2024.03.002. Epub ahead of print. PMID: 38490300.

Introduction: Chronic inflammation in irreversible pulpitis leads to heightened sensitivity of nociceptive receptors, resulting in persistent hyperalgesia. This poses significant challenges in achieving effective anesthesia for patients with irreversible pulpitis. Various anesthetic techniques and pharmacological approaches have been employed to enhance the success of local anesthesia. Recently, the preemptive use of anti-inflammatory agents, specifically corticosteroids, has gained attention and shown promising results in randomized controlled trials. This systemic review and meta-analysis aimed to evaluate the impact of systemically administered corticosteroids on enhancing anesthetic success in patients undergoing endodontic treatment.

Methods: A comprehensive search was conducted across multiple databases including PubMed, Cochrane Library, Embase, Scopus, Dentistry & Oral Science, and ProQuest. Additionally, the references of primary studies and related systematic reviews were manually searched for additional relevant publications. The primary outcome assessed was the success of anesthesia, and the effect measure was Risk Ratio (RR) using the random-effects inverse variance method. Statistical significance was set at p < .05. The certainty of the evidence was evaluated using the GRADE approach.

Results: Twelve studies involving 917 participants were analyzed to determine the frequency of successful anesthesia. The corticosteroid group demonstrated a significantly higher number of patients achieving successful anesthesia (RR = 1.66; 95% CI, 1.34 to 2.06;p< .00001). However, heterogeneity within the pooled data analysis was observed (I2= 57%,p=0.007).

Conclusions: Moderate certainty evidence indicates that preemptive use of systemic corticosteroids enhances the success of local anesthesia, specifically inferior alveolar nerve block (IANB), in cases of irreversible pulpitis.

Keywords: Dexamethasone; corticosteroids; endodontics; inferior alveolar nerve block; local anesthesia; pulpitis.

DOI | PubMed

Alajlan N, Carrasco-Labra A, Karabucak B, Lee SM. Systemic Corticosteroid Uses in Endodontics- Part 1: Managing Postoperative Pain. J Endod. 2024 Mar 13:S0099-2399(24)00163-8. doi: 10.1016/j.joen.2024.03.004. Epub ahead of print. PMID: 38490301.

Introduction: This study aimed to systematically search and review all available literature regarding systemic (oral or locally injected) corticosteroids in endodontics to assess their effect on postoperative pain.

Methods: A search was conducted using PubMed, Cochrane Library, Embase, Scopus, Dentistry & Oral Science, and ProQuest. Randomized controlled trials enrolling participants undergoing endodontic treatment and assessing the presence of pain and pain scores at 6, 12, and 24 hours postoperatively were included. We synthesize the effect measures using risk ratios, standardized mean differences, and their corresponding 95% confidence intervals. Meta-analysis was performed using the random-effects inverse variance method. The level of significance was set at p < .05. The certainty of the evidence was evaluated using GRADE approach.

Results: A total of 2,303 participants from 29 trials were included. Patients who received corticosteroids were significantly less likely to report pain at 6 hours (RR= 2.5; 95% CI, 1.74 to 3.61; p < .00001), 12 hours (RR= 2.10; 95% CI, 1.53 to 2.90; p < .00001) and 24 hours (RR= 1.77; 95% CI, 1.38 to 2.28; p < .00001) postoperatively. Furthermore, they reported lower pain intensity at 6 hours (SMD= – 0.82; 95% CI, -1.17 to -0.48; p < .00001), 12 hours (SMD= – 0.63; 95% CI, -0.75 to -0.51; p < .00001) and 24 hours (SMD= – 0.68; 95% CI, – 0.90 to -0.46; p < .00001) postoperatively.

Conclusion: Moderate certainty evidence indicates that the use of systemic corticosteroids likely results in a moderate to large reduction in postoperative endodontic pain.

Keywords: Corticosteroids; endodontics; postoperative pain; systematic review.

DOI | PubMed

Glick M. Embracing the need for a whole health home. J Am Dent Assoc. 2024.

Carrasco-Labra A, Polk DE, Urquhart O, Aghaloo T, Claytor JW Jr, Dhar V, Dionne RA, Espinoza L, Gordon SM, Hersh EV, Law AS, Li BS, Schwartz PJ, Suda KJ, Turturro MA, Wright ML, Dawson T, Miroshnychenko A, Pahlke S, Pilcher L, Shirey M, Tampi M, Moore PA. Evidence-based clinical practice guideline for the pharmacologic management of acute dental pain in adolescents, adults, and older adults: A report from the American Dental Association Science and Research Institute, the University of Pittsburgh, and the University of Pennsylvania. J Am Dent Assoc. 2024 Feb;155(2):102-117.e9.  PMID: 38325969.

Background: A panel convened by the American Dental Association Science and Research Institute, the University of Pittsburgh, and the University of Pennsylvania conducted systematic reviews and meta-analyses and formulated evidence-based recommendations for the pharmacologic management of acute dental pain after simple and surgical tooth extraction(s) and for the temporary management (ie, definitive dental treatment not immediately available) of toothache associated with pulp and periapical diseases in adolescents, adults, and older adults.

Types of Studies Reviewed : The panel conducted 4 systematic reviews to determine the effect of opioid and nonopioid analgesics, local anesthetics, corticosteroids, and topical anesthetics on acute dental pain. The panel used the Grading of Recommendations, Assessment, Development and Evaluation approach to assess the certainty of the evidence and the Grading of Recommendations, Assessment, Development and Evaluation Evidence-to-Decision Framework to formulate recommendations.

Results : The panel formulated recommendations and good practice statements using the best available evidence. There is a beneficial net balance favoring the use of nonopioid medications compared with opioid medications. In particular, nonsteroidal anti-inflammatory drugs alone or in combination with acetaminophen likely provide superior pain relief with a more favorable safety profile than opioids.

Conclusions and Practical Implications : Nonopioid medications are first-line therapy for managing acute dental pain after tooth extraction(s) and the temporary management of toothache. The use of opioids should be reserved for clinical situations when the first-line therapy is insufficient to reduce pain or there is contraindication of nonsteroidal anti-inflammatory drugs. Clinicians should avoid the routine use of just-in-case prescribing of opioids and should exert extreme caution when prescribing opioids to adolescents and young adults.

Key Words : Clinical practice guideline; acute dental pain; tooth extractions; toothache; analgesics; opioids

Abbreviation Key : CPG, Clinical practice guidelines; FDA, US Food and Drug Administration; GRADE, Grading of Recommendations, Assessment, Development and Evaluation; MME, Morphine milligram equivalents; NSAID, Nonsteroidal anti-inflammatory drug; RCT, Randomized controlled trial;


Carrasco-Labra A, Verdugo-Paiva F, Matanhire-Zihanzu C, Booth E, Kohler IV, Urquhart O, Glick M. Barriers to and facilitators for the creation, dissemination, implementation, monitoring, and evaluation of oral health policies in the WHO Africa region: A scoping review protocol [version 2; peer review: 1 approved, 1 approved with reservations]F1000Research 2024, 12:1160.

Background: Evidence-informed oral health policies (OHP) can be instrumental in ending the neglect of oral health globally. When appropriately developed and implemented, OHP can improve the efficiency of healthcare systems and the quality of health outcomes. However, more than half of the countries in the World Health Organization (WHO) African region did not have an oral health policy or even the existence of a policy in need of additional and more national-specific OHP as part of non-communicable diseases and universal health coverage agendas. The objective of this protocol’s study is to determine the barriers to and facilitators for the creation, dissemination, implementation, monitoring, and evaluation of OHP in the WHO Africa region.

Methods: We will conduct a systematic search in Global Health, Embase, PubMed, PAIS, ABI/Inform, Web of Science, Academic Search Complete, Scopus, databases that index gray literature, and the WHO policy repositories. We will include qualitative, quantitative, or mixed-methods research studies and OHP documents published since January 1, 2002, which address stakeholders’ perceptions and experiences regarding barriers to and facilitators for the creation, dissemination, implementation, monitoring, and evaluation of OHP in countries part of the WHO African region. We will produce descriptive statistics (frequencies and proportions) for quantitative data and conduct descriptive content analysis for qualitative data.

Discussion: To effectively establish evidence-based OHP in the WHO African region, it is crucial to recognize existing challenges and opportunities for progress. The findings of this review will be relevant for Chief Dental Officers at ministries of health, administrators of dental schools, or academic institutions in the WHO African region and will inform a stakeholder dialogue meeting in Kenya in November of 2023.



Busse J WCasassus RCarrasco-Labra A, Durham JMock DZakrzewska J M et al. Management of chronic pain associated with temporomandibular disorders: a clinical practice guideline doi:10.1136/bmj-2023-076227

Clinical question : What is the comparative effectiveness of available therapies for chronic pain associated with temporomandibular disorders (TMD)?

Current practice : TMD are the second most common musculoskeletal chronic pain disorder after low back pain, affecting 6-9% of adults globally. TMD are associated with pain affecting the jaw and associated structures and may present with headaches, earache, clicking, popping, or crackling sounds in the temporomandibular joint, and impaired mandibular function. Current clinical practice guidelines are largely consensus-based and provide inconsistent recommendations.

Recommendations : For patients living with chronic pain (≥3 months) associated with TMD, and compared with placebo or sham procedures, the guideline panel issued: (1) strong recommendations in favour of cognitive behavioural therapy (CBT) with or without biofeedback or relaxation therapy, therapist-assisted mobilisation, manual trigger point therapy, supervised postural exercise, supervised jaw exercise and stretching with or without manual trigger point therapy, and usual care (such as home exercises, stretching, reassurance, and education); (2) conditional recommendations in favour of manipulation, supervised jaw exercise with mobilisation, CBT with non-steroidal anti-inflammatory drugs (NSAIDS), manipulation with postural exercise, and acupuncture; (3) conditional recommendations against reversible occlusal splints (alone or in combination with other interventions), arthrocentesis (alone or in combination with other interventions), cartilage supplement with or without hyaluronic acid injection, low level laser therapy (alone or in combination with other interventions), transcutaneous electrical nerve stimulation, gabapentin, botulinum toxin injection, hyaluronic acid injection, relaxation therapy, trigger point injection, acetaminophen (with or without muscle relaxants or NSAIDS), topical capsaicin, biofeedback, corticosteroid injection (with or without NSAIDS), benzodiazepines, and β blockers; and (4) strong recommendations against irreversible oral splints, discectomy, and NSAIDS with opioids.

How this guideline was created : An international guideline development panel including patients, clinicians with content expertise, and methodologists produced these recommendations in adherence with standards for trustworthy guidelines using the GRADE approach. The MAGIC Evidence Ecosystem Foundation (MAGIC) provided methodological support. The panel approached the formulation of recommendations from the perspective of patients, rather than a population or health system perspective.

The evidence : Recommendations are informed by a linked systematic review and network meta-analysis summarising the current body of evidence for benefits and harms of conservative, pharmacologic, and invasive interventions for chronic pain secondary to TMD.

Understanding the recommendation : These recommendations apply to patients living with chronic pain (≥3 months duration) associated with TMD as a group of conditions, and do not apply to the management of acute TMD pain. When considering management options, clinicians and patients should first consider strongly recommended interventions, then those conditionally recommended in favour, then conditionally against. In doing so, shared decision making is essential to ensure patients make choices that reflect their values and preference, availability of interventions, and what they may have already tried. Further research is warranted and may alter recommendations in the future.


Verdugo-Paiva F, Bonfill Cosp X, Alonso-Coello P, Ávila-Oliver C, Glick M, Carrasco-Labra A. How oral health care organizations formulate actionable statements to inform practice and policy: A protocol for a systematic survey [version 1; peer review: awaiting peer review]F1000Research 2023, 12:1261

Background: Oral diseases are a major global public health problem that impacts the quality of life of those affected. While widespread consensus exists on the importance of high-quality, evidence-informed guidelines to inform practice and public health decisions in medicine, appropriate methodologies and standards are not commonly adhered to among producers of oral health guidelines. This systematic survey aims to identify organizations developing evidence-informed guidelines and policy documents in oral health globally, and describe the methods and processes used.

Methods: We will conduct manual searches on the websites of guideline developers, Ministries of Health, and scientific societies. Additionally, we will systematically search electronic databases to identify published guidelines and collect the name of the responsible entity. We will include organizations that regularly develop guidelines on any oral health topic and that explicitly declare the inclusion of research evidence in its development process. Subsequently, we will use a standardized form to extract data about the characteristics of the organization, the characteristics of their guideline or policy documents, and their formal recommendation development processes. These data will be extracted from various sources, such as the organization’s official website, the methods section of each guideline, or methodological handbooks. We will use descriptive statistics to analyze the extracted data.

Discussion: This systematic survey will synthesize key characteristics and methodologies used by organizations developing evidence-informed guidelines. This study will provide the basis for future development of a sustainable and connected collaborative network for evidence-informed guidelines and policy documents in oral health globally. The results will be disseminated through peer-reviewed publications, conference presentations, and targeted dissemination of findings with the identified organizations. Our systematic survey represents a necessary first step toward improving the field of oral health policies and guidelines.

Keywords: Guidelines; guidance; Recommendations; GRADE; Practice statements; Policy; Evidence-to-decision framework; Evidence-Based Dentistry, Oral Health policy


Glick M, Urquhart O, Bhosale AS, Carrasco-Labra A, Edelson JT. A unified voice to drive global improvements in oral health. BMC Global and Public Health 2023;1(1):19.

Approximately, 3.47 billion individuals worldwide are affected by oral disorders, with untreated dental caries being the most prevalent issue, impacting 2.30 billion people. Addressing this complex health problem requires a collective and unified approach from the oral health community. However, stakeholders often focus on their own interests, leading to information silos and a lack of diverse perspectives. To foster collaboration, tackle critical topics, and promote effective communication, the Global Oral Health Forum was organized as a 2-day meeting. The forum aimed to dismantle existing silos and cultivate a unified message to drive global improvements in oral health. By bridging gaps between stakeholders and encouraging dialogue, the forum sought to transcend individual interests and foster a holistic approach. The meeting provided a space for diverse viewpoints, concerns, and expertise to converge, facilitating meaningful discussions and overcoming the limitations of an echo chamber. The inclusive environment aimed to integrate different perspectives, generate innovative ideas, and pave the way for impactful changes in oral health worldwide. The outcome of the Global Oral Health Forum I includes suggested action points that emphasize collaboration, knowledge sharing, and policy development. These recommendations aim to promote preventive strategies, improve access to oral healthcare, enhance oral health education, and foster interdisciplinary research and innovation. By implementing these actions, the global oral health community can work together to address the challenges posed by oral disorders and improve oral health outcomes for billions of individuals worldwide.


Zaror C, Seiffert A, Deana NF, Espinoza-Espinoza G, Atala-Acevedo C, Diaz R, Carrasco-Labra A. Emergency and sequalae management of traumatic dental injuries: a systematic survey of clinical practice guidelines. BMC Oral Health. 2023 Sep 30;23(1):704.

Background: The prevalence and consequences of traumatic dental injuries (TDI) make them a public health problem. Trustworthy TDI clinical practice guidelines (CPGs) assist clinicians in determining a diagnosis and guide them to the most appropriate therapy. The aim of this systematic survey was to identify and evaluate the quality of CPGs for the diagnosis, emergency management, and follow-up of TDIs.

Materials and methods: A systematic search was carried out in MEDLINE, EMBASE, Epistemonikos, Trip database, CPG websites, and dental societies to identify documents providing recommendations for the emergency and sequelae management of TDIs. Reviewers assessed the included guidelines independently and in duplicate, using the AGREE II instrument. ANOVA or Student’s t-tests were used to determine the attributes of CPGs associated with the total score in AGREE II.

Results: Ten CPGs published between 2010 and 2020 were included, mostly from Europe (n = 6). The overall agreement between reviewers was very good (0.94; 95%CI 0.91-0.97). The mean scores (the higher the score, the better the domain assessment) per domain were as follows: Scope and purpose 78.0 ± 18.9%; stakeholder involvement 46.9 ± 29.6%; rigour of development 41.8 ± 26.7%; clarity of presentation 75.8 ± 17.6%; applicability 15.3 ± 18.8%; and editorial independence 41.7 ± 41.7%. The overall mean rate was 4 ± 1.3 out of a maximum score of 7. Two guidelines were recommended by the reviewers for use in practice and rated as high quality. CPGs developed by government organizations showed a significantly higher overall score.

Conclusions: The overall quality of CPGs on TDI was suboptimal. CPG developers should synthesize the evidence and formulate recommendations using high-quality methodologies and standards in a structured, transparent, and explicit way.

Keywords: AGREE II; Clinical practice guidelines; Systematic review; Traumatic dental injuries.

DOI | PubMed

Carrasco-Labra A, Urquhart O, Glick M. A practitioner’s guide to developing critical appraisal skills: How to interpret the magnitude of clinical study results. J Am Dent Assoc. 2023 Sep;154(9):836-841.

Background: In the oral health literature, researchers sometimes report measures of association that are inappropriate for their study design. Clinicians using evidence to inform their practice should be able to interpret clinical study results on the basis of the types of measures of association, independent of what the researchers of a study reported.

Types of studies reviewed: The authors summarized which measures of association can be derived from experimental and observational studies and how to interpret them in the context of different study designs. They also suggested how inferences can be made on the basis of particular designs.

Results: Measures of association derived from randomized controlled trials and cohort studies differ from those of case-control and cross-sectional studies. These differences can be attributed to the temporality between exposures and outcomes inherent in the respective study designs. Different measures of association reported from the same study may lead to different clinical decisions. Furthermore, the same measure of association with the same effect estimate derived from different study designs may contribute to different clinical decisions.

Conclusions and practical implications: Measures of association should be interpreted in the context of a particular study design. Study designs and specific measures of association should be considered when drawing conclusions from clinical studies. Clinicians using the literature to inform practice should be cognizant of measures of association reported for a particular study design and whether the authors have interpreted the measure of association correctly in the context of their chosen study design.

Keywords: Measure of association; absolute risk difference; contingency table; odds ratio; relative risk; relative risk difference; study design.

DOI | PubMed

Carrasco-Labra A, Polk DE, Urquhart O, Aghaloo T, Claytor JW Jr, Dhar V, Dionne RA, Espinoza L, Gordon SM, Hersh EV, Law AS, Li BS, Schwartz PJ, Suda KJ, Turturro MA, Wright ML, Dawson T, Miroshnychenko A, Pahlke S, Pilcher L, Shirey M, Tampi M, Moore PA. Evidence-based clinical practice guideline for the pharmacologic management of acute dental pain in children: A report from the American Dental Association Science and Research Institute, the University of Pittsburgh School of Dental Medicine, and the Center for Integrative Global Oral Health at the University of Pennsylvania. J Am Dent Assoc. 2023 Sep;154(9):814-825.e2.

Background: A guideline panel convened by the American Dental Association Council on Scientific Affairs, American Dental Association Science and Research Institute, University of Pittsburgh School of Dental Medicine, and Center for Integrative Global Oral Health at the University of Pennsylvania conducted a systematic review and meta-analyses and formulated evidence-based recommendations for the pharmacologic management of acute dental pain after 1 or more simple and surgical tooth extractions and the temporary management of toothache (that is, when definitive dental treatment not immediately available) associated with pulp and furcation or periapical diseases in children (< 12 years).

Types of studies reviewed: The authors conducted a systematic review to determine the effect of analgesics and corticosteroids in managing acute dental pain. They used the Grading of Recommendations Assessment, Development and Evaluation approach to assess the certainty of the evidence and the Grading of Recommendations Assessment, Development and Evaluation Evidence to Decision framework to formulate recommendations.

Results: The panel formulated 7 recommendations and 5 good practice statements across conditions. There is a small beneficial net balance favoring the use of nonsteroidal anti-inflammatory drugs alone or in combination with acetaminophen compared with not providing analgesic therapy. There is no available evidence regarding the effect of corticosteroids on acute pain after surgical tooth extractions in children.

Conclusions and practical implications: Nonopioid medications, specifically nonsteroidal anti-inflammatory drugs like ibuprofen and naproxen alone or in combination with acetaminophen, are recommended for managing acute dental pain after 1 or more tooth extractions (that is, simple and surgical) and the temporary management of toothache in children (conditional recommendation, very low certainty). According to the US Food and Drug Administration, the use of codeine and tramadol in children for managing acute pain is contraindicated.

Keywords: Clinical practice guideline; acute dental pain; analgesics; corticosteroids; opioids; pediatric dentistry; tooth extractions; toothache.

DOI | PubMed

Listl S, Baltussen R, Carrasco-Labra A, Carrer FC, Lavis JN. Evidence-Informed Oral Health Policy Making: Opportunities and Challenges. Journal of Dental Research. 2023;0(0).

Despite a clear need for improvement in oral health systems, progress in oral health systems transformation has been slow. Substantial gaps persist in leveraging evidence and stakeholder values for collective problem solving. To truly enable evidence-informed oral health policy making, substantial “know-how” and “know-do” gaps still need to be overcome. However, there is a unique opportunity for the oral health community to learn and evolve from previous successes and failures in evidence-informed health policy making. As stated by the Global Commission on Evidence to Address Societal Challenges, COVID-19 has created a once-in-a-generation focus on evidence, which has fast-tracked collaboration among decision makers, researchers, and evidence intermediaries. In addition, this has led to a growing recognition of the need to formalize and strengthen evidence-support systems. This article provides an overview of recent advancements in evidence-informed health policy making, including normative goals and a health systems taxonomy, the role of evidence-support and evidence-implementation systems to improve context-specific decision-making processes, the evolution of learning health systems, and the important role of citizen deliberations. The article also highlights opportunities for evidence-informed policy making to drive change in oral health systems. All in all, strengthening capacities for evidence-informed health policy making is critical to enable and enact improvements in oral health systems.

Keywords: Citizen science; decision making; evidence-based dentistry; stakeholder participation.

DOI | PubMed

Dhar V, Pilcher L, Fontana M, González-Cabezas C, Keels MA, Mascarenhas AK, Nascimento M, Platt JA, Sabino GJ, Slayton R, Tinanoff N, Young DA, Zero DT, Pahlke S, Urquhart O, O’Brien KK, Carrasco-Labra A. Evidence-based clinical practice guideline on restorative treatments for caries lesions: A report from the American Dental Association. J Am Dent Assoc. 2023 Jul;154(7):551-566.e51.

Background: An expert panel convened by the American Dental Association (ADA) Council on Scientific Affairs together with the ADA Science and Research Institute’s program for Clinical and Translational Research conducted a systematic review and developed recommendations for the treatment of moderate and advanced cavitated caries lesions in patients with vital, nonendodontically treated primary and permanent teeth.

Types of studies reviewed: The authors searched for systematic reviews comparing carious tissue removal (CTR) approaches in Ovid MEDLINE, Embase, Cochrane Database of Systematic Reviews, and Trip Medical Database. The authors also conducted a systematic search for randomized controlled trials comparing direct restorative materials in Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials,, and the World Health Organization International Clinical Trials Registry Platform. The authors used the Grading of Recommendations Assessment, Development, and Evaluation approach to assess the certainty of the evidence and formulate recommendations.

Results: The panel formulated 16 recommendations and good practice statements: 4 on CTR approaches specific to lesion depth and 12 on direct restorative materials specific to tooth location and surfaces involved. The panel conditionally recommended for the use of conservative CTR approaches, especially for advanced lesions. Although the panel conditionally recommended for the use of all direct restorative materials, they prioritized some materials over the use of others for certain clinical scenarios.

Practical implications: The evidence suggests that more conservative CTR approaches may decrease the risk of adverse effects. All included direct restorative materials may be effective in treating moderate and advanced caries lesions on vital, nonendodontically treated primary and permanent teeth.

Keywords: American Dental Association; Evidence-based dentistry; caries; clinical practice guideline; direct restorative materials; general dentistry; pediatric dentistry.

DOI | PubMed

Abt E, Weyant RJ, Frantsve-Hawley J, Carrasco-Labra A. The potential harm of not following clinical practice guideline recommendations. J Am Dent Assoc. 2023 Aug;154(8):760-765.

Background: Clinical practice guidelines (CPGs) provide recommendations for clinicians on the basis of best evidence. CPGs are often not followed because of numerous barriers, including lack of awareness, inability to understand recommendations, and problems with implementation.

Case description: A case report is presented in which treatment of a patient’s incipient caries lesions may not have followed a CPG available to practitioners, recommending conservative nonrestorative medical interventions. The resulting treatment led to pain and the need for endodontic therapy and full-coverage restoration.

Practical implications: This case represents possible mismanagement leading to undue pain and additional costs that could have been avoided by being aware of, and following, the recommendations from CPGs.

Keywords: Clinical practice guidelines; evidence-based dentistry; operative dentistry.

DOI | PubMed

Wang Y, Devji T, Carrasco-Labra A, Qasim A, Hao Q, Kum E, Devasenapathy N, King MT, Terluin B, Terwee CB, Walsh M, Furukawa TA, Tsujimoto Y, Guyatt GH. An extension minimal important difference credibility item addressing construct proximity is a reliable alternative to the correlation item. J Clin Epidemiol. 2023 May;157:46-52.

Objectives: Minimal important difference (MID), the smallest change or difference that patients perceive as important, aids interpretation of change in patient-reported outcome measure (PROM) scores. A credibility instrument that assesses the methodological rigor of an anchor-based MID includes one core item addressing the correlation between the PROM and the anchor. However, the majority of MID studies in literature fail to report the correlation. To address this issue, we extended the anchor-based MID credibility instrument by adding an item addressing construct proximity as an alternative to the correlation item.

Study Design and Setting: Informed by an MID methodological survey, we added an alternative item—a subjective assessment of similarity of the constructs (i.e., construct proximity) between PROM and anchor—to the correlation item and generated principles for the assessment. We sampled 101 MIDs and analyzed the assessments performed by each pair of raters. By calculating weighted Cohen’s kappa, we assessed the reliability of the assessments.

Results: Construct proximity assessment is based on the anticipated association between the anchor and PROM constructs: the closer the anticipated association, the higher the rating. Our detailed principles address the most frequently used anchors: transition ratings, measures of satisfaction, other PROMs, and clinical measures. The assessments showed acceptable agreement (weighted kappa 0.74, 95% CI 0.55–0.94) between raters.

Conclusion: In the absence of a reported correlation coefficient, construct proximity assessment provides a useful alternative in the credibility assessment of anchor-based MID estimates.

DOI | PubMed

Wang Y, Devji T, Carrasco-Labra A, King MT, Terluin B, Terwee CB, Walsh M, Furukawa TA, Guyatt GH. A step-by-step approach for selecting an optimal minimal important difference. BMJ. 2023 May 26;381:e073822.

Researchers have proposed that the minimal important difference (MID), the smallest change or difference that patients perceive as important, could aid the interpretation of patient reported outcomes measure (PROM) scores. When multiple MIDs for a given PROM differ substantially, the selection of an optimal MID to aid interpretation could prove challenging. This article describes a systematic, step-by-step selection approach developed to resolve this problem. An optimal MID, at least, should be methodologically sound and should, as far as possible, match the intended application contexts. Therefore, this approach is geared to explaining the variability of the MIDs for the PROM of interest by the methodological rigor and contextualized factors influencing the MID application, and where appropriate, provides one optimal MID (i.e., the median of the selected estimates in a relatively narrow range).

DOI | PubMed

Miroshnychenko A, Azab M, Ibrahim S, Roldan Y, Diaz Martinez JP, Tamilselvan D, He L, Urquhart O, Tampi M, Polk DE, Moore PA, Hersh EV, Carrasco-Labra A, Brignardello-Petersen R. Analgesics for the management of acute dental pain in the pediatric population: A systematic review and meta-analysis. J Am Dent Assoc. 2023 May;154(5):403-416.e14.

Background: The authors assessed the clinical effectiveness of analgesics to manage acute pain after dental extractions and pain associated with irreversible pulpitis in children.

Types of Studies Reviewed: The authors searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and US Clinical Trials registry from inception through November 2020. They included randomized controlled trials comparing any pharmacologic interventions with each other and a placebo in pediatric participants undergoing dental extractions or experiencing irreversible pulpitis. After duplicate screening and data abstraction, the authors conducted random-effects meta-analyses. They assessed risk of bias using the Cochrane Risk of Bias 2.0 tool and certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluation approach.

Results: The authors included 6 randomized controlled trials reporting 8 comparisons. Ibuprofen may reduce pain intensity compared with acetaminophen (mean difference [MD], 0.27 points; 95% CI, -0.13 to 0.68; low certainty) and a placebo (MD, -0.19 points; 95% CI, -0.58 to 0.21; low certainty). Acetaminophen may reduce pain intensity compared with a placebo (MD, -0.13 points; 95% CI, -0.52 to 0.26; low certainty). Acetaminophen and ibuprofen combined probably reduce pain intensity compared with acetaminophen alone (MD, -0.75 points; 95% CI, -1.22 to -0.27; moderate certainty) and ibuprofen alone (MD, -0.01 points; 95% CI, -0.53 to 0.51; moderate certainty). There was very low certainty evidence regarding adverse effects.

Practical Implications: Several pharmacologic interventions alone or in combination may provide a beneficial effect when managing acute dental pain in children. There is a paucity of evidence regarding the use of analgesics to manage irreversible pulpitis.

Key Words: Acute dental pain; dental extraction; toothache; irreversible pulpitis; systematic review; nonsteroidal antiinflammatory; acetaminophen.

DOI| PubMed

Miroshnychenko, A., Ibrahim, S., Azab, M., Roldan, Y., Martinez, J. P. D., Tamilselvan, D., He, L., Little, J. W., Urquhart, O., Tampi, M., Polk, D. E., Moore, P. A., Hersh, E. V., Claytor, B., Carrasco-Labra, A., & Brignardello-Petersen, R. (2023). Acute Postoperative Pain Due to Dental Extraction in the Adult Population: A Systematic Review and Network Meta-analysis. J Dent Res, 220345221139230.

This study compares the effectiveness of pharmacological treatments to develop guidelines for the management of acute pain after tooth extraction. We searched Medline, EMBASE, CENTRAL, and US Clinical Trials registry on November 21, 2020. We included randomized clinical trials (RCTs) of participants undergoing dental extractions comparing 10 interventions, including acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, and combinations to placebo. After duplicate screening and data abstraction, we conducted a frequentist network meta-analysis for each outcome at 6 h (i.e., pain relief, total pain relief [TOTPAR], summed pain intensity difference [SPID], global efficacy rating, rescue analgesia, and adverse effects). We assessed the risk of bias using a modified Cochrane RoB 2.0 tool and the certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach. We implemented the analyses in RStudio version 3.5.3 and classified interventions from most to least beneficial or harmful. We included 82 RCTs. Fifty-six RCTs enrolling 9,095 participants found moderate- and high-certainty evidence that ibuprofen 200 to 400 mg plus acetaminophen 500 to 1,000 mg (mean difference compared to placebo [MDp], 1.68; 95% confidence interval [CI], 1.06–2.31), acetaminophen 650 mg plus oxycodone 10 mg (MDp, 1.19; 95% CI, 0.85–1.54), ibuprofen 400 mg (MDp, 1.31; 95% CI, 1.17–1.45), and naproxen 400–440 mg (MDp, 1.44; 95% CI, 1.07–1.80) were most effective for pain relief on a 0 to 4 scale. Oxycodone 5 mg, codeine 60 mg, and tramadol 37.5 mg plus acetaminophen 325 mg were no better than placebo. The results for TOTPAR, SPID, global efficacy rating, and rescue analgesia were similar. Based on low- and very low-certainty evidence, most interventions were classified as no more harmful than placebo for most adverse effects. Based on moderate- and high-certainty evidence, NSAIDs with or without acetaminophen result in better pain-related outcomes than opioids with or without acetaminophen (except acetaminophen 650 mg plus oxycodone 10 mg) or placebo.

DOI | PubMed

Verdugo-Paiva, F., Bonfill, X., Ortuno, D., Glick, M., & Carrasco-Labra, A. (2023). Policymakers’ Perceived Barriers and Facilitators in the Use Of Research Evidence in Oral Health Policies and Guidelines: A Qualitative Study Protocol. BMJ Open, 13(2), e066048.

Evidence-informed oral health policies are crucial to improving patient and population outcomes, but policymakers and organisational leaders infrequently systematically incorporate research evidence. Although there is indirect evidence regarding challenges in other healthcare sectors, the use of evidence-informed oral health policies remains unstudied in oral health. This study aims to assess policymakers’ perceived needs, barriers and facilitators in using research evidence to inform policies in oral health.

DOI | PubMed

Fisher, J., R. Berman, K. Buse, B. Doll. M. Glick, J. Metzl, and R. Touger-Decker. 2023. “Achieving Oral Health for All through Public Health Approaches, Interprofessional, and Transdisciplinary Education. “NAM Perspectives. Discussion Paper, National Academy of Medicine, Washington, DC.

This paper aims to use newly expanded definitions of oral health—from the World Health Organization and the FDI World Dental Federation (FDI) (Glick et al., 2016)—to describe opportunities for engaging policy- and decision-makers in ministries, departments of health, and other agencies around the concept of holistic oral health (i.e., mind, mouth, body, soul, and spirit) as it relates to the UN 2030 Agenda for Sustainable Development.

DOI| PubMed

Pilcher, L., Pahlke, S., Urquhart, O., O’Brien, K. K., & Carrasco-Labra, A. (2023). Plain language summary for “Direct materials for restoring caries lesions: systematic review and meta-analysis-a report of the American Dental Association Council on Scientific Affairs”. J Am Dent Assoc. online ahead of print.

The American Dental Association’s Council on Scientific Affairs and the American Dental Association Science and Research Institute’s Clinical and Translational Research program convened a panel of subject matter experts to develop a clinical practice guideline on restorative treatments for caries lesions. The upcoming guideline will present recommendations for direct restorative materials and carious tissue removal approaches for cavitated caries lesions on primary and permanent teeth. This systematic review and meta-analysis presents the evidence informing the effectiveness of different direct restorative materials and the certainty of the evidence.

PubMed | DOI

Pilcher, L., Pahlke, S., Urquhart, O., O’Brien, K. K., Dhar, V., Fontana, M., Gonzalez-Cabezas, C., Keels, M. A., Mascarenhas, A. K., Nascimento, M. M., Platt, J. A., Sabino, G. J., Slayton, R. L., Tinanoff, N., Young, D. A., Zero, D. T., Tampi, M. P., Purnell, D., Salazar, J., . . . Carrasco-Labra, A. (2023). Direct materials for restoring caries lesions: Systematic review and meta-analysis-a report of the American Dental Association Council on Scientific Affairs. J Am Dent Assoc. online ahead of print.

Background: The goal of restoring caries lesions is to protect the pulp, prevent progression of the disease process, and restore the form and function of the tooth. The purpose of this systematic review was to determine the effect of different direct restorative materials for treating cavitated caries lesions on anterior and posterior primary and permanent teeth.

Type of studies reviewed: The authors included parallel and split-mouth randomized controlled trials comparing the effectiveness of direct restorative materials commercially available in the United States placed in vital, nonendodontically treated primary and permanent teeth. Pairs of reviewers independently conducted study selection, data extraction, and assessments of risk of bias and certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluation approach. The authors conducted pair-wise meta-analyses to summarize the evidence and calculated measures of association and their 95% CIs.

Results: Thirty-eight randomized controlled trials were eligible for analysis, which included data on Class I and Class II restorations on primary teeth and Class I, Class II, Class III, Class V, and root surface restorations on permanent teeth. Included studies assessed the effect of amalgam, resin composite, compomer, conventional glass ionomer cement, resin-modified glass isomer cement, and preformed metal crowns. Moderate to very low certainty evidence suggested varying levels of effectiveness across restorative materials.

Conclusions and practical implications: Owing to a relatively low event rate across various outcomes indicating restoration failure, there was limited evidence to support important differences between direct restorative materials used in practice.

Keywords: American Dental Association; Evidence-based dentistry; dental caries; direct restorative materials; general dentistry; meta-analysis; pediatric dentistry; systematic review.

PubMed | DOI

Miroshnychenko, A., Ibrahim, S., Azab, M., Roldan, Y., Diaz Martinez, J. P., Tamilselvan, D., He, L., Urquhart, O., Tampi, M., Polk, D. E., Moore, P. A., Hersh, E. V.Carrasco-Labra, A., & Brignardello-Petersen, R. (2023). Injectable and topical local anesthetics for acute dental pain: 2 systematic reviews. J Am Dent Assoc, 154(1), 53-64 e14.

Background: Local anesthesia is essential for pain control in dentistry. The authors assessed the comparative effect of local anesthetics on acute dental pain after tooth extraction and in patients with symptomatic irreversible pulpitis.

Types of studies reviewed: The authors searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and the US Clinical Trials registry through November 21, 2020. The authors included randomized controlled trials (RCTs) comparing long- vs short-acting injectable anesthetics to reduce pain after tooth extraction (systematic review 1) and evaluated the effect of topical anesthetics in patients with symptomatic pulpitis (systematic review 2). Pairs of reviewers screened articles, abstracted data, and assessed risk of bias using a modified version of the Cochrane risk of bias 2.0 tool. The authors assessed the certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluation approach.

Results: Fourteen RCTs comparing long- vs short-acting local anesthetics suggest that bupivacaine may decrease the use of rescue analgesia and may not result in additional adverse effects (low certainty evidence). Bupivacaine probably reduces the amount of analgesic consumption compared with lidocaine with epinephrine (mean difference, -1.91 doses; 95% CI, -3.35 to -0.46; moderate certainty) and mepivacaine (mean difference, -1.58 doses; 95% CI, -2.21 to -0.95; moderate certainty). Five RCTs suggest that both benzocaine 10% and 20% may increase the number of people experiencing pain reduction compared with placebo when managing acute irreversible pulpitis (low certainty).

Practical implications: Bupivacaine may be superior to lidocaine with epinephrine and mepivacaine with regard to time to and amount of analgesic consumption. Benzocaine may be superior to placebo in reducing pain for 20 through 30 minutes after application.

Keywords: Short-acting local anesthetics; articaine; benzocaine; bupivacaine; lidocaine; long-acting local anesthetics; mepivacaine; post tooth extraction acute pain; symptomatic irreversible pulpitis.

PubMed | DOI


Baker, D., Giuliano, K. K., Thakkar-Samtani, M., Scannapieco, F. A., Glick, M., Restrepo, M. I., Heaton, L. J., & Frantsve-Hawley, J. (2022). The association between accessing dental services and nonventilator hospital-acquired pneumonia among 2019 Medicaid beneficiaries.

In this 2019 cross-sectional study, we analyzed hospital records for Medicaid beneficiaries who acquired nonventilator hospital-acquired pneumonia. The results suggest that preventive dental treatment in the 12 months prior or periodontal therapy in the 6 months prior to a hospitalization is associated with a reduced risk of NVHAP.

PubMed | DOI

Giuliano, K. K., Baker, D., Thakkar-Samtani, M., Glick, M., Restrepo, M. I., Scannapieco, F. A., Heaton, L. J., & Frantsve-Hawley, J. (2022). Incidence, mortality, and cost trends in nonventilator hospital-acquired pneumonia in medicaid beneficiaries, 2015-2019. Am J Infect Control.

Nonventilator hospital-acquired pneumonia is associated with substantial morbidity, mortality, and costs during an episode of acute care. We examined NVHAP incidence, mortality, and costs of Medicaid beneficiaries over a 5-year period (2015-2019). Overall NVHAP incidence was 2.63 per 1,000 patient days, and mortality was 7.76%, with an excess cost per NVHAP case of $20,189.

PubMed | DOI

Ahmad, P., Hussain, A., Carrasco-Labra, A., & Siqueira, W. L. (2022). Salivary Proteins as Dental Caries Biomarkers: A Systematic Review. Caries Res, 56(4), 385-398.

Salivary proteins play an important role in repairing mechanisms of damaged tissues and the maintenance of oral health. However, there is a dearth of information in the literature regarding the concentrations of salivary proteins in caries-free (CF) and caries-active (CA) subjects. Hence, this systematic review was conducted to update our previous systematic review published in 2013 that aimed to assess the association between caries and salivary proteins by comparing CF and CA individuals. Thereby, evaluating the possibility of whether salivary proteins can be regarded as biomarkers for caries. An extensive search of studies was conducted using PubMed, EMBASE, Clarivate Analytics’ Web of Science, and Elsevier’s Scopus between July 2012 and January 2022, without any language restriction. Manual searching in Google Scholar and evaluation of bibliographies of the included studies were also undertaken. The Newcastle-Ottawa Scale was used to assess the risk of bias (RoB) within the included studies. Of 22 included studies, 1,551 human subjects (range: 30-213 participants) were recruited, of which 848 individuals (54.7%) were CA and 703 (45.3%) were CF. Regarding the utilization of DMFT as the caries index, high variability was observed across different articles. A statistically significant increase in the salivary levels of alpha-amylase, acidic proline-rich protein-1, histatin-5, lactoperoxidase, and mucin-1 was found in CA patients, while the salivary levels of carbonic anhydrase 6, proteinase-3, and statherin were observed to be significantly increased in CF subjects. Conflicting results were found regarding the salivary levels of immunoglobulin A and total proteins among CA and CF subjects. The included studies were categorized as low RoB (n = 15), medium RoB (n = 4), and high RoB (n = 3). Due to significant heterogeneity among the included studies, no meta-analysis could be performed. In conclusion, the salivary levels of protein(s) might be a useful biomarker for caries diagnosis, especially alpha-amylase, acidic proline-rich protein-1, histatin-5, lactoperoxidase, mucin-1, carbonic anhydrase 6, proteinase-3, and statherin. However, their diagnostic value must be verified by large-scale prospective studies.

PubMed | DOI

Walsh, T., Macey, R., Ricketts, D., Carrasco Labra, A., Worthington, H., Sutton, A. J., Freeman, S., Glenny, A. M., Riley, P., Clarkson, J., & Cerullo, E. (2022). Enamel Caries Detection and Diagnosis: An Analysis of Systematic Reviews. J Dent Res, 101(3), 261-269.

Detection and diagnosis of caries-typically undertaken through a visual-tactile examination, often with supporting radiographic investigations-is commonly regarded as being broadly effective at detecting caries that has progressed into dentine and reached a threshold where restoration is necessary. With earlier detection comes an opportunity to stabilize disease or even remineralize the tooth surface, maximizing retention of tooth tissue and preventing a lifelong cycle of restoration. We undertook a formal comparative analysis of the diagnostic accuracy of different technologies to detect and inform the diagnosis of early caries using published Cochrane systematic reviews. Forming the basis of our comparative analysis were 5 Cochrane diagnostic test accuracy systematic reviews evaluating fluorescence, visual or visual-tactile classification systems, imaging, transillumination and optical coherence tomography, and electrical conductance or impedance technologies. Acceptable reference standards included histology, operative exploration, or enhanced visual assessment (with or without tooth separation) as appropriate. We conducted 2 analyses based on study design: a fully within-study, within-person analysis and a network meta-analysis based on direct and indirect comparisons. Nineteen studies provided data for the fully within-person analysis and 64 studies for the network meta-analysis. Of the 5 technologies evaluated, the greatest pairwise differences were observed in summary sensitivity points for imaging and all other technologies, but summary specificity points were broadly similar. For both analyses, the wide 95% prediction intervals indicated the uncertainty of future diagnostic accuracy across all technologies. The certainty of evidence was low, downgraded for study limitations, inconsistency, and indirectness. Summary estimates of diagnostic accuracy for most technologies indicate that the degree of certitude with which a decision is made regarding the presence or absence of disease may be enhanced with the use of such devices. However, given the broad prediction intervals, it is challenging to predict their accuracy in any future “real world” context.

PubMed | DOI

Frantsve-Hawley, J., Abt, E., Carrasco-Labra, A., Dawson, T., Michaels, M., Pahlke, S., Rindal, D. B., Spallek, H., & Weyant, R. J. (2022). Strategies for developing evidence-based clinical practice guidelines to foster implementation into dental practice. J Am Dent Assoc, 153(11), 1041-1052.

Background: Professional and other organizations, including oral health care organizations, have been developing evidence-based clinical practice guidelines (CPGs) to help providers incorporate the best available evidence into their clinical decision making. Although the rigor of guideline development has increased over time, ongoing challenges prevent the full adoption of CPGs into clinical practices that experience variability in provider expertise and opinion, patient flow pace, and use of electronic dental records. These challenges include lack of relevant evidence, failure to keep guidelines up to date, and failure to adopt strategies aimed at overcoming the barriers preventing implementation into clinical practice.

Results: This article provides a brief overview of strategies that can be used to overcome common challenges to guideline adoption. Such strategies include creating evidence-based CPGs that use additional sources of evidence and methods to inform guideline development and accelerate the guideline updating and dissemination process (that is, evidence directly from clinical practice, big data, patients’ values and preferences, and living guidelines) and applying implementation strategies that have been documented as improving translation of CPGs into routine clinical practice (that is, guideline implementability, implementation science, and computable guidelines).

Practical implications: Adopting newer strategies for developing and translating evidence into practice could lead to improvements in patient care and population health.

Keywords: Evidence-based dentistry; clinical practice guidelines; computable guidelines; evidence-based medicine; implementability; implementation science; learning health care systems; patients’ values and preferences.

PubMed | DOI

Glick, M., & Ackerman, M. (2022). Words and concepts matter. Quintessence Int, 53(9), 741-742.

PubMed | DOI

Glick, M., & Carrasco-Labra, A. (2022). Screening testing in health care: Getting it right. J Am Dent Assoc, 153(4), 365-370.

Background: There is a movement to engage oral health care professionals in administering tests to identify people at risk of developing contagious diseases and other medical conditions. The purpose of this overview was to provide clinicians with fundamental concepts to understand how to evaluate a screening test’s capability to give a correct result and its implications for practice (health outcomes).

Types of studies reviewed: The authors reviewed epidemiologic and statistical articles addressing the purpose of performing screening tests for medical conditions with a special emphasis on understanding and interpreting test results on the basis of specific test characteristics.

Results: Tests with different sensitivities and specificities will provide different probabilities of correctly classifying people with or without a disease of interest. By understanding how to interpret tests results and how to communicate the consequences (that is, impact on health outcomes) of positive and negative test results, oral health care professionals will be able to generate appropriate medical referrals and determine the need for further testing, as well as provide a public service.

Conclusions and practical implications: An understanding by oral health care professionals of how to interpret screening test results will benefit their patients substantially and, in the case of contagious diseases, the public at large.

Keywords: Screening tests; disease prevalence; negative predictive value; positive predictive value; sensitivity; specificity.

PubMed | DOI

Azab, M., Ibrahim, S., Li, A., Khosravirad, A., Carrasco-Labra, A., Zeng, L., & Brignardello-Petersen, R. (2022). Efficacy of secondary vs primary closure techniques for the prevention of postoperative complications after impacted mandibular third molar extractions: A systematic review update and meta-analysis. J Am Dent Assoc, 153(10), 943-956 e948.

Background: The aim of this systematic review was to determine whether secondary closure (SC) or primary closure (PC) is better at preventing postoperative complications after impacted mandibular third-molar extraction.

Types of studies reviewed: The authors sought randomized controlled trials comparing the effects of PC and SC on pain, swelling, trismus, infection, and bleeding after impacted mandibular third-molar extraction. Screening, data extraction, and risk of bias assessments were conducted independently and in duplicate. The reviewers pooled results across studies using a random-effects meta-analysis and assessed the certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluation approach.

Results: This review identified 785 unique citations and included 40 trials. Compared with PC, SC was found to have trivial benefits for pain at day 7 and trismus within 1 week (moderate certainty). The incidence of infection and bleeding did not differ importantly between techniques (moderate certainty). However, SC is probably associated with less swelling on day 1 (standardized mean difference, -0.98; 95% CI, -1.22 to -0.73; moderate certainty) and day 3 (standardized mean difference, -0.87; 95% CI, -1.16 to -0.59; moderate certainty). There was very low certainty evidence for pain on days 1 and 3 and low certainty evidence for swelling on day 7.

Conclusions and practical implications: Clinicians choosing between closure techniques should be aware that SC probably imparts an important benefit only for swelling at days 1 and 3. There seems to be a trivial difference between the techniques in other outcomes.

Keywords: Pain; postoperative complications; primary closure; secondary closure; swelling; third molar; trismus.

PubMed | DOI

Urquhart, O., DeLong, H. R., Ziegler, K. M., Pilcher, L., Pahlke, S., Tampi, M. P., O’Brien, K. K., Patton, L. L., Agrawal, N., Hofstede, T. M., Kademani, D., Lingen, M. W., Treister, N. S., Tsai, C. J., Carrasco-Labra, A., & Lipman, R. D. (2022). Effect of Preradiation Dental Intervention on Incidence of Osteoradionecrosis in Patients with Head and Neck Cancer: A Systematic Review and Meta-Analysis. J Am Dent Assoc, 153(10), 931-942 e932.

Background: The purpose of this systematic review was to examine whether dental intervention involving bone or soft-tissue manipulation preradiotherapy (pre-RT) is associated with lower rates of osteoradionecrosis of the jaw (ORNJ) in patients with head and neck cancer (HNC).

Types of studies reviewed: The authors included relevant studies from MEDLINE, Embase, and Cochrane Library, including observational studies published from 2007 through 2021 and involving adults who underwent dental intervention pre-RT for HNC. Authors assessed evidence certainty by using the Grading of Recommendations Assessment, Development, and Evaluation approach. Random-effects models were used to calculate pooled relative risk estimates and hazard ratios. When meta-analysis was not possible, study-level measures of association and narrative summaries of the evidence were reported.

Results: Twenty-two studies were included. From the pooled, unadjusted analysis, patients undergoing pre-RT extractions may have a 55% increased risk of experiencing ORNJ (relative risk, 1.55; 95% CI, 0.85 to 2.86; very low certainty); the unadjusted pooled hazard ratio was 3.19 (95% CI, 0.99 to 10.31; very low certainty), corresponding to a possible increased hazard of developing ORNJ (very low certainty). Findings for other pre-RT procedures manipulating bone or tissue relied on limited, observational studies with low or very low certainty evidence.

Conclusions: Mostly very low certainty evidence suggests that patients with HNC who need pre-RT dental intervention may have an increased risk of developing ORNJ compared with those who do not.

Practical implications: Maintaining optimal oral health may help reduce the need for urgent pre-RT dental treatment, potentially reducing ORNJ risk and minimizing delay of oncologic treatment in patients with HNC.

Keywords: Head and neck cancer; dental intervention; medically complex; osteoradionecrosis; radiation.

PubMed | DOI

Zhang, Y. Q., Jiao, R. M., Witt, C. M., Lao, L., Liu, J. P., Thabane, L., Sherman, K. J., Cummings, M., Richards, D. P., Kim, E. A., Kim, T. H., Lee, M. S., Wechsler, M. E., Brinkhaus, B., Mao, J. J., Smith, C. A., Gang, W. J., Liu, B. Y., Liu, Z. S., Zheng, H., Wu, J.N., Carrasco-Labra, A., Bhandar, M., Devereaux, P.J., Jing, X.H., Guyatt, G. (2022). How to Design High Quality Acupuncture Trials — A Consensus Informed By Evidence. BMJ, 376, e067476.

An international panel including patients, clinicians, researchers, acupuncture and surgery trialists, statisticians, and experts in clinical epidemiology and methodology have developed new guidance for randomized controlled trials in acupuncture. It addresses the most prevalent and critical concerns of current acupuncture trials and will help funding agencies, trial registers, and journal editors to evaluate the relevance, importance, and quality of submitted trial proposals and completed trials.

PubMed | DOI

Zhang, Y. Q., Lu, L., Xu, N., Tang, X., Shi, X., Carrasco-Labra, A., Schunemann, H., Chen, Y., Xia, J., Chen, G., Liu, J., Liu, B., Wang, J., Qaseem, A., Jing, X., Guyatt, G., & Zhao, H. (2022). Increasing the Usefulness of Acupuncture Guideline Recommendations. BMJ, 376, e070533.

Yu-Qing Zhang and colleagues examine the progress and pitfalls in guideline recommendations for acupuncture and provide suggestions for improvement.

PubMed | DOI

Carrasco-Labra, A., Devji, T., Qasim, A., Phillips, M., Johnston, B. C., Devasenapathy, N., Zeraatkar, D., Bhatt, M., Jin, X., Brignardello-Petersen, R., Urquhart, O., Foroutan, F., Schandelmaier, S., Pardo-Hernandez, H., Vernooij, R. W., Huang, H., Rizwan, Y., Siemieniuk, R., Lytvyn, L., . . . Guyatt, G. H. (2022). Serious Reporting Deficiencies Exist in Minimal Important Difference Studies: Current State and Suggestions for Improvement. J Clin Epidemiol, 150, 25-32.

Background and objectives: To evaluate reporting of minimal important difference (MID) estimates using anchor-based methods for patient-reported outcome measures (PROMs), and the association with reporting deficiencies on their credibility.

Methods: Systematic survey of primary studies empirically estimating MIDs. We searched Medline, EMBASE, PsycINFO, and the Patient-Reported Outcome and Quality of Life Instruments Database until October 2018. We evaluated study reporting, focusing on participants’ demographics, intervention(s), characteristics of PROMs and anchors, and MID estimation method(s). We assessed the impact of reporting issues on credibility of MID estimates.

Results: In 585 studies reporting on 5,324 MID estimates for 526 distinct PROMs, authors frequently failed to adequately report key characteristics of PROMs and MIDs, including minimum and maximum values of PROM scale, measure of variability accompanying the MID estimate and number of participants included in the MID calculation. Across MID estimates (n = 5,324), the most serious reporting issues impacting credibility included infrequent reporting of the correlation between the anchor and PROM (66%), inadequate details to judge precision of MID point estimate (13%), and insufficient information about the threshold used to ascertain MIDs (16%).

Conclusion: Serious issues of incomplete reporting in the MID literature threaten the optimal use of MID estimates to inform the magnitude of effects of interventions on PROMs.

Keywords: Anchor-based methods; Credibility; Minimal important difference; Patient-reported outcome; Reporting quality; Systematic survey.

PubMed | DOI

Wang, Y., Devji, T., Qasim, A., Hao, Q., Wong, V., Bhatt, M., Prasad, M., Wang, Y., Noori, A., Xiao, Y., Ghadimi, M., Lozano, L. E. C., Phillips, M. R., Carrasco-Labra, A., King, M., Terluin, B., Terwee, C. B., Walsh, M., Furukawa, T. A., & Guyatt, G. H. (2022). A Systematic Survey Identified Methodological Issues in Studies Estimating Anchor-Based Minimal Important Differences in Patient-Reported Outcomes. J Clin Epidemiol, 142, 144-151.

Objective: To systematically survey the literature addressing the reporting of studies estimating anchor-based minimal important differences (MIDs) and choice of optimal MIDs.

Study design and setting: We searched Medline, Embase and PsycINFO from 1987 to March 2020. Teams of two reviewers independently identified eligible publications and extracted quotations addressing relevant issues for reporting and/or selecting anchor-based MIDs. Using a coding list, we assigned the same code to quotations capturing similar or related issues. For each code, we generated an ‘item’, i.e., a specific phrase or sentence capturing the underlying concept. When multiple concepts existed under a single code, the team created multiple items for that code. We clustered codes addressing a broader methodological issue into a ‘category’ and classified items as relevant for reporting, relevant for selecting an anchor-based MID, or both.

Results: We identified 136 eligible publications that provided 6 categories (MID definition, anchors, patient-reported outcome measures, generalizability and statistics) and 24 codes. These codes contained 34 items related to reporting MID studies, of which 29 were also related to selecting MIDs.

Conclusion: The systematic survey identified items related to reporting of anchor-based MID studies and selecting optimal MIDs. These provide a conceptual framework to inform the design of studies related to MIDs, and a basis for developing a reporting standard and a selection approach for MIDs.

Keywords: Minimal important difference; Patient-reported outcome measure; systematic survey.

PubMed | DOI

Tsujimoto, Y., Fujii, T., Tsutsumi, Y., Kataoka, Y., Tajika, A., Okada, Y., Carrasco-Labra, A., Devji, T., Wang, Y., Guyatt, G. H., & Furukawa, T. A. (2022). Minimal Important Changes in Standard Deviation Units are Highly Variable and No Universally Applicable Value Can be Determined. J Clin Epidemiol, 145, 92-100.

Objectives: This study aims to describe the distribution of anchor-based minimal important change (MIC) estimates in standard deviation (SD) units and examine if the robustness of such estimates depends on the specific SD used or on the methodological credibility of the anchor-based estimates.

Design and setting: We included all anchor-based MIC estimates from studies published in MEDLINE and relevant literature databases upto October 2018. Each MIC was converted to SD units using baseline, endpoint, and change from baseline SDs. We performed a descriptive analysis of MICs in SD units and checked how the distribution would change if MICs with low methodological credibility were excluded from the analysis.

Results: We included 1,009 MIC estimates from 182 studies. The medians and interquartile ranges of MICs in SD units were 0.43 (0.25 to 0.69), 0.42 (0.22 to 0.70), and 0.51 (0.28 to 0.78) for baseline, endpoint, and change SD units, respectively. Some MICs were extremely large or small. The distribution did not change significantly after excluding MICs estimated by less credible methods.

Conclusions: The size of the universally applicable MIC in SD units could not be determined. Anchor-based MICs in SD units were widely distributed, with more than half in the range of 0.2 to 0.8.

Keywords: Minimal important change; anchor-based method; distribution-based method; effect size; patient-reported outcome.

PubMed | DOI

Tampi, M., Carrasco-Labra, A., O’Brien, K. K., Velandia-Gonzalez, M., & Brignardello-Petersen, R. (2022). Systematic Review on Reducing Missed Opportunities for Vaccinations in Latin America. Rev Panam Salud Publica, 46, e65.

Objectives: To estimate the prevalence of missed opportunities for vaccination (MOV) in Latin America and the effect of interventions targeting health systems, health workers, patients, and communities on MOV.

Methods: Searches were conducted in MEDLINE, EMBASE, CINAHL, and LILACS electronic databases and relevant organizations were contacted, including the Pan American Health Organization (PAHO), to identify studies meeting eligibility criteria. A pair of reviewers identified 27 randomized and non-randomized studies quantifying the effectiveness of any intervention for reducing MOV and 5 studies assessing the rate of MOV in Latin America. Results are reported narratively when criteria to pool results were not met, and the certainty of this evidence was assessed using the GRADE approach.

Results: Evidence suggests the rate of MOV in Latin America ranged from 5% to 37% with a pooled estimate of 17% (95% CI [9, 32]) (low certainty) and that monetary incentives to healthcare teams, training for healthcare teams on how to communicate with patients, and educational interventions for caregivers probably reduce MOV (moderate to very low certainty).

Conclusions: There is insufficient evidence supporting the implementation of any intervention as policy based only on the potential reduction of MOV without considering several factors, including costs, feasibility, acceptability, and equity.

Keywords: Latin America; Vaccination; immunization; vaccination coverage.

PubMed | DOI

France, K., & Glick, M. (2022). Long COVID and Oral Health Care Considerations. J Am Dent Assoc, 153(2), 167-174.

Background: People who have recovered from the initial severe acute respiratory syndrome coronavirus 2 infection are at risk of developing long COVID, a prolonged suite of signs and symptoms that may interfere with daily life and the ability to undergo routine oral health care.

Methods: The available literature on long COVID was reviewed and compiled to produce a review of the syndrome as currently understood. Articles were evaluated with a focus on how long COVID may affect the provision of oral health care and on ways in which treatment may need to be modified to best care for this vulnerable patient population.

Results: Long COVID includes a wide variety of symptoms, such as fatigue, shortness of breath, chest pain, risk of developing thromboembolism, and neurologic and psychiatric complications. These symptoms may arise at various times and in a wide range of patients, and they may necessitate modification of routine oral health care interventions.

Conclusions: Recommendations for the treatment of affected people in an oral health care setting are presented, including a thorough evaluation of the patient history and current status, understanding of how related symptoms may affect oral health care interventions, and which modifications to treatment are needed to provide safe and appropriate care.

Practical implications: Oral health care professionals must be aware of long COVID, an increasingly prevalent condition with a widely variable presentation and impact. Oral health care professionals should be prepared to treat these patients safely in an outpatient oral health setting.

Keywords: COVID-19; Long COVID; medically complex dental treatment; patient treatment.

PubMed | DOI


Glick, M., Wolff, M. S., & Carrasco-Labra, A. (2021). COVID-19 and scientific illiteracy, a syndemic. J Am Dent Assoc, 152(12), 967-968.

PubMed | DOI

Wolff, M. S., & Glick, M. (2021). COVID-19 Vaccination: To Lead by Example or an Opportunity Lost. J Dent Res, 100(13), 1421-1422.

Coronavirus disease 2019 (COVID-19) has created a global health emergency. Vaccine hesitancy and tremendous misinformation about the actual science are leaving the public with significant confusion. However, sound epidemiologic science is guiding us to a clear path toward mitigating this modern-day scourge. It is remarkable how putting an end to current COVID-19 outbreaks has such a simple solution-convincing the public to accept getting vaccinated. The dental research, dental education, and dental practice communities have a unique opportunity to act as trusted public exemplars as well as trusted interpreters of the science for the public.

PubMed | DOI



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