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Diagnosis of the condition of the dental pulp a systematic review
- 1. Review Diagnosis of the condition of the dental pulp: a systematic review I. A. Meja`re1,2 , S. Axelsson2 , T. Davidson2,3 , F. Frisk4,5 , M. Hakeberg6 , T. Kvist5 , A. Norlund2 , A. Petersson7 , I. Portenier8 , H. Sandberg9 , S. Tranæus2 & G. Bergenholtz5 1 Department of Pediatric Dentistry, Faculty of Odontology, Malmo¨ University; 2 SBU (Swedish Council on Health Technology Assessment), Stockholm; 3 Center for Medical Technology Assessment, Linko¨ping University, Linko¨ping; 4 Department of Endodontology/Periodontology, The Institute for Postgraduate Dental Education, Jo¨nko¨ping; 5 Department of Endodontology, Institution of Odontology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg; 6 Department of Behavioral and Community Dentistry, Institute of Odontology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg; 7 Department of Oral and Maxillofacial Radiology, Faculty of Odontology, Malmo¨ University, Malmo¨, Sweden; 8 Division of Cariology and Endodontics, School of Dentistry, University of Geneva, Geneva, Switzerland; and 9 Karolinska Institutet, Stockholm, Sweden Abstract Meja`re IA, Axelsson S, Davidson T, Frisk F, Hakeberg M, Kvist T, Norlund A, Petersson A, Portenier I, Sandberg H, Tranæus S, Bergenholtz G. Diagnosis of the condition of the dental pulp: a systematic review. International Endodontic Journal, 45, 597–613, 2012. The aim of this systematic review was to appraise the diagnostic accuracy of signs/symptoms and tests used to determine the condition of the pulp in teeth affected by deep caries, trauma or other types of injury. Radiographic methods were not included. The elec- tronic literature search included the databases PubMed, EMBASE, The Cochrane Central Register of Controlled Trials and Cochrane Reviews from January 1950 to June 2011. The complete search strategy is given in an Appendix S1 (available online as Supporting Informa- tion). In addition, hand searches were made. Two reviewers independently assessed abstracts and full-text articles. An article was read in full text if at least one of the two reviewers considered an abstract to be poten- tially relevant. Altogether, 155 articles were read in full text. Of these, 18 studies fulfilled pre-specified inclusion criteria. The quality of included articles was assessed using the QUADAS tool. Based on studies of high or moderate quality, the quality of evidence of each diagnostic method/test was rated in four levels accord- ing to GRADE. No study reached high quality; two were of moderate quality. The overall evidence was insuffi- cient to assess the value of toothache or abnormal reaction to heat/cold stimulation for determining the pulp condition. The same applies to methods for establishing pulp status, including electric or thermal pulp testing, or methods for measuring pulpal blood circulation. In general, there are major shortcomings in the design, conduct and reporting of studies in this domain of dental research. Keywords: accuracy, dental pulp disease, dental pulp test, diagnosis, sensitivity, specificity. Received 30 September 2011; accepted 30 December 2011 Introduction An accurate diagnosis of the condition of the pulp in teeth compromised by caries, dental procedures or other forms of injury is crucial for arriving at a proper treatment decision. Important information in this respect is whether the pulp is vital or necrotic. It is equally important to be able to determine whether the pulp is reversibly or irreversibly inflamed, especially in connection with a carious or traumatic exposure of the tissue. In other words, can the pulp heal and survive in a long-term perspective or is it damaged to the extent that it is not treatable and that root canal treatment is required? Correspondence: Ingegerd Meja`re, SBU, Statens Beredning fo¨r medicinsk Utva¨rdering, PO Box 3657, 103 59 Stockholm, Sweden (tel.: +46 84123242; e-mail address: mejare@sbu.se). doi:10.1111/j.1365-2591.2012.02016.x ª 2012 International Endodontic Journal International Endodontic Journal, 45, 597–613, 2012 597
- 2. Diagnostic information is gained from the patient’s history of pain or discomfort, experience of trauma or restorative procedures, clinical examinations, results of clinical tests and radiographic examination of the teeth and the surrounding tissues. A diagnosis is seldom based on a single finding, rather on a set of observa- tions. The clinical situation may be so complex that a proper diagnosis and treatment decision requires a diagnostic process consisting of several steps. A variety of methods are used to assess the condition of injured or diseased dental pulp. Whilst such methods have been reviewed thoroughly and repeatedly in many textbooks and narrative reviews, no consensus has been reached as to which method or combination of methods will give the most accurate information (Levin et al. 2009). The aim of this systematic review was to assess the diagnostic accuracy of contemporary methods used to assess the condition of the pulp in injured or diseased teeth. The review does not include assessments of the accuracy of radiographic methods; that is presented in a separate article (Petersson et al. 2011). This review is part of a more comprehensive systematic review published in Swedish by SBU (Swed- ish Council on Health Technology Assessment) cover- ing methods of diagnosis and treatment in endodontics (The Swedish Council on Health Technology Assess- ment (SBU) 2010). SBU is an independent government agency for the critical evaluation of methods for preventing, diagnosing and treating health problems. The following questions were addressed: • How accurate are different diagnostic methods for determining the condition of exposed vital pulps in teeth with different types of damage or injury (caries, trauma, restorative interventions or other causes)? • Are there clinical or biological markers that can determine the degree, severity and extent of inflam- mation of exposed vital pulp? • Are there methods that can predict the outcome of a treatment that aims at keeping the pulp vital, healthy and without symptoms? • How accurate are methods used to determine the sensibility and vitality of dental pulps, including methods to determine vascular function? Materials and methods Literature search and selection of articles The electronic literature search included the databases PubMed, EMBASE, The Cochrane Central Register of Controlled Trials and Cochrane Reviews from January 1950 to April 2010. A complementary search was made in June 2011. All languages were accepted, provided there was an abstract in English. The Mesh terms were ‘Dental pulp diseases/classification’, ‘Dental pulp diseases/diagnosis’, ‘Dental pulp test’ and ‘Tooth discoloration’. The complete search strategy is given in the Appendix S1 (available online as Supporting Information). The electronic searches resulted in 2131 abstracts (Fig. 1). Two reviewers (GB and IM) read the abstracts independently. An article was read in full text if at least one of the two reviewers considered an abstract to be potentially relevant. In addition to the electronic search, a hand search was made and references of narrative reviews, text books and articles in international journals not identified in the main search were included. The hand search resulted in another 33 articles. Grey literature was not included. The pre-specified inclusion/exclusion criteria are given in Table 1. Altogether, 155 articles were read in full text and assessed independently by the same two reviewers. Of the 155 articles, 137 did not fulfil the inclusion criteria and were excluded from further analysis. A list of excluded articles with the main reason for exclusion is given in the Appendix S2 (available online as Supporting Information). The remaining included articles (n = 18) were assessed using the QUADAS tool (Whiting et al. 2003). Data analysis Measures used to assess diagnostic accuracy The diagnostic accuracy (validity) of a test (index test) requires a reference standard (reference test) for com- parison. Such a reference standard should reflect the true condition as closely as possible. For pulp, histo- logical examination has often been used as the refer- ence standard. The relationship between positive and negative test results and the presence or absence of diseased pulp can be expressed as sensitivity and specificity. Sensitivity is the number of true positive tests divided by the total number of diseased pulps. Specificity is the number of true negative tests divided by the total number of healthy pulps. Other measures are predictive values and likelihood ratios. The positive predictive value is the number of true positive tests divided by the total number of positive tests, and the negative predictive value is the number of negative tests divided by the total number of negative tests. Likelihood ratio com- bines sensitivity and specificity and states how many Diagnosis of dental pulp Meja`re et al. International Endodontic Journal, 45, 597–613, 2012 ª 2012 International Endodontic Journal598
- 3. times more likely particular test results are in patients with disease than in those without disease. The positive likelihood ratio = the odds of a positive test result in patients with disease (sensitivity/1- specificity), and the negative likelihood ratio = the odds of a negative test result in patients with disease (1- sensitivity/specific- ity). The main outcome measures of this systematic review were sensitivity and specificity of individual studies. The intention was to pool sensitivity and specificity of reasonably homogeneous studies with high or moderate study quality. Rating quality of individual studies Each included study was rated high, moderate or low quality according to pre-specified criteria given in Table 2. Rating evidence across studies The quality of evidence of the diagnostic accuracy of each method/test was rated in four levels according to GRADE (Schu¨nemann et al. 2008, Guyatt et al. 2011): • High (¯¯¯¯): based on high- or moderate-quality studies containing no factors that weaken the overall judgement. • Moderate (¯¯¯s): based on high- or moderate- quality studies containing isolated factors that weaken the overall judgement. • Limited (¯¯ss): based on high- or moderate- quality studies containing factors that weaken the overall judgement. • Insufficient (¯sss): the evidence base is insuffi- cient when scientific evidence is lacking, the quality of available studies is low or studies of similar quality are contradictory. GRADE amounts to asking how much confidence one can have in a particular estimate of effect. Is it built on solid ground, or is it likely that new research findings will change the evidence in the foreseeable future? The rating starts at high, but confidence in the evidence may be lowered for several reasons, including limitations in study design and/or quality, inconsis- tency or indirectness of results, imprecision of estimates and probability of publication bias. Any disagreements about inclusion/exclusion criteria, rating quality of individual studies or quality of evidence of test methods were solved by consensus. A flow chart showing the results of the literature search and the outcome of the selection procedures is given in Fig. 1. Results Eighteen studies were included (Seltzer et al. 1963, Guthrie et al. 1965, Eidelman et al. 1968, Hasler & Mitchell 1970, Johnson et al. 1970, Koch & Nyborg 1970, Tyldesley & Mumford 1970, Garfunkel et al. Abstracts from electronic search 1. 2009-09-01 (n = 1883) 2. 2010-04-07 (n = 119) 3. 2011-06-28 (n =129) Excluded abstracts (not relevant) n = 2009 Articles in full text n = 122 Excluded articles (not relevant or not fulfilling inclusion criteria) n = 137 Included articles n = 18 Study quality: High n = 0 Study quality: Moderate n = 2 Study quality: Low n =16 Articles from other sources, i.e. reference lists n = 33 Figure 1 Flow chart showing the search strategy, excluded and included articles and study quality of included articles. Meja`re et al. Diagnosis of dental pulp ª 2012 International Endodontic Journal International Endodontic Journal, 45, 597–613, 2012 599
- 4. 1973, Dummer et al. 1980, Klausen et al. 1985, Olgart et al. 1988, Georgopoulou & Kerani 1989, Matsuo et al. 1996, Evans et al. 1999, Petersson et al. 1999, Kamburog˘lu & Paksoy 2005, Gopikrishna et al. 2007, Weisleder et al. 2009). Their main characteristics and quality rating are presented in Table 3. None of the studies satisfied the criteria for high quality, two were of moderate quality (Hasler & Mitchell 1970, Gop- ikrishna et al. 2007), and the remaining 16 studies were of low quality. Owing to the scarcity of studies of sufficient quality, no meta-analysis was performed. Based on the two studies of moderate quality, each investigated test method was rated for the quality of evidence according to the GRADE approach (Schu¨ne- mann et al. 2008), Tables 4 and 5. The 18 included studies can be divided into two categories: those designed to assess the accuracy of signs and symptoms of the inflammatory status of pulp, and those investi- gating the accuracy of methods for testing pulp vitality. Signs and symptoms as indicators of the inflammatory status of pulp Of 11 included studies, 10 were of low quality (Seltzer et al. 1963, Guthrie et al. 1965, Eidelman et al. 1968, Johnson et al. 1970, Koch & Nyborg 1970, Tyldesley & Mumford 1970, Dummer et al. 1980, Klausen et al. 1985, Matsuo et al. 1996, Kamburog˘lu & Paksoy 2005). The study of moderate quality (Hasler & Mitchell 1970) recorded normal or abnormal responses to cold, heat, electric pulp test (EPT) and percussion in 47 asymptomatic teeth with deep caries. The findings Table 1 Pre-specified inclusion and exclusion criteria Inclusion criteria Study design Cross-sectional, case–control, prospective cohort Population Patients that can be expected to undergo the examination or the tests in clinical praxis Index test Clinical signs or symptoms, other clinical information, clinical tests or biological markers Reference test Histological examination of the extracted tooth Histological examination of extirpated pulp tissue For deciding pulp vitality: the same criteria as above or inspecting/probing the exposed pulp tissue Immature teeth: radiographic examination combined with observing continued root development Prospective study design: symptoms combined with clinical and radiographic information were accepted Outcome measures Sensitivity, specificity, likelihood ratio, odds ratio (from multivariate analysis), ROC curves or AUC (area under the curve) Exclusion criteria Study design Retrospective Population In vitro or animal studies, cracked teeth Index test Product comparisons, tooth bleaching procedures Reference test Not defined or not acceptable according to inclusion criteria Outcome measures Other than inclusion criteria. An article was accepted if sensitivity and specificity were not reported, but contingency tables enabled calculation of these measures Table 2 Criteria of high, moderate and low study quality, mainly according to QUADAS (Whiting et al. 2003) High: small risk of bias Study design either cross-sectional or prospective. A case–control design was not accepted, because it usually overestimates diagnostic accuracy (Lijmer et al. 1999). Particular emphasis was put on the following items: Randomly or consecutively selected, adequately described patients involving a representative and clinically relevant sample (QUADAS items 1, 2) The index test should not form part of the reference standard (item 7) The index test and the reference standard should each be interpreted without knowledge of the results of the other (items 10, 11) The tests should be described in sufficient detail to permit replication (items 8, 9) Sample size in subgroups ‡30 Diagnostic accuracy presented as sensitivity and specificity Moderate: moderate risk of bias A case–control design was accepted as well as nonrandom or nonconsecutive enrolment of patients. Otherwise the same criteria as for high quality. A sample size of ‡20 in subgroups was accepted Low: high risk of selection and/or verification bias Criteria of moderate quality not met Diagnosis of dental pulp Meja`re et al. International Endodontic Journal, 45, 597–613, 2012 ª 2012 International Endodontic Journal600
- 5. were compared with the degree of pulp inflammation as assessed by histological examination after extraction of the tooth. There was no obvious association between any of the test results and the inflammatory condition of the pulp. Tenderness to percussion occurred in 80% (37/47) of the teeth without regard to the inflamma- tory status. All teeth having minimal or no pulp inflammation responded abnormally to either cold or heat provocation or both. The range of inflammation was substantial; 28% (13/47) of the teeth displayed either moderate or severe pulp inflammation. Thus, absence of painful symptoms such as toothache did not exclude the presence of a severe inflammatory involve- ment of the pulp. The histological examination revealed that 30% (14/47) of the teeth had carious pulp exposure (with no dentine separating the pulp from the caries lesion as measured histologically). Moderate to severe pulp inflammation was more frequent in these teeth (71%) compared with teeth without caries reaching the pulp. The sample is, however, relatively small, and the results have wide confidence intervals. Table 4 is based on the results of this study. The accuracy of isolated clinical symptoms or combinations of symptoms for differentiating between pulpitis, apical periodontitis and marginal periodon- titis was assessed in 74 patients with acute dental pain (Klausen et al. 1985). Probing the pulp after exposure was used as the reference test to distinguish between vital and nonvital pulps. Bursts of pain initiated by thermal provocation (cold or heat) were associated with vital pulp (pulpitis) in >75% of the teeth. Constant pain combined with a tooth that felt extruded was associated with pulp necrosis in >80% of the cases. Presence of toothache, response to percussion, cold or heat provocation or EPT were compared with the histological status of the pulp in 166 teeth extracted because of caries or other causes (Seltzer et al. 1963). The relationship between any of the signs and symp- toms and the inflammatory condition of the pulp (either low sensitivity or low specificity) was poor. The study has methodological shortcomings. The ability of various clinical signs and symptoms to predict the outcome of pulp capping was assessed in a prospective study (Matsuo et al. 1996). The material comprised 44 permanent teeth with pulp exposure after excavating deep caries. Pulps with profuse and linger- ing bleeding had a significantly poorer outcome than those with modest bleeding or a bleeding of short duration. Pre-operative pain of minor intensity did not affect the success rate. The sample is relatively small with wide confidence intervals, and the study has methodological shortcomings. To sum up, there is insufficient evidence to determine whether the presence, nature and duration of tooth- ache offer accurate information about the extent to which dental pulp is inflamed. The evidence base is also insufficient to assess the accuracy of other commonly used clinical markers of pulp inflammation (Table 4). Sensibility and vitality testing Electric pulp testing One study of moderate quality (Gopikrishna et al. 2007) examined 80 patients who had a single-rooted tooth affected by deep caries, indicating irreversible pulpitis, or in need of endodontic therapy for other reasons. Using direct visual inspection as the reference test, EPT correctly identified 71% of the necrotic pulps (sensitiv- ity) and 92% of the vital pulps (specificity). Table 5 is based on the results of this study. With one exception (Georgopoulou & Kerani 1989), all included studies on EPT (Seltzer et al. 1963, Johnson et al. 1970, Dummer et al. 1980, Olgart et al. 1988, Evans et al. 1999, Kamburog˘lu & Paksoy 2005, Weisleder et al. 2009) had a similar, high specificity (>90%). Sensitivity varied substantially in all included studies (range = 21–87%). Cold test In the same sample of 80 patients as described earlier (Gopikrishna et al. 2007), cold test with tetrafluoroe- thane correctly identified pulp necrosis in 81% of the teeth (sensitivity) and vital pulps in 92% (specificity). In the other included studies (Seltzer et al. 1963, Tyldesley & Mumford 1970, Garfunkel et al. 1973, Dummer et al. 1980, Olgart et al. 1988, Georgopoulou & Kerani 1989, Evans et al. 1999, Petersson et al. 1999, Kam- burog˘lu & Paksoy 2005, Weisleder et al. 2009), the specificity of a variety of cold tests ranged from 10 to 98%, whilst sensitivity with one exception reached >75%. Heat test Six studies (Seltzer et al. 1963, Garfunkel et al. 1973, Dummer et al. 1980, Olgart et al. 1988, Georgopoulou & Kerani 1989, Petersson et al. 1999), all of low quality, reported highly variable values of sensitivity and specificity for thermal provocation by heat. Combining tests Two studies examined the accuracy of combining tests (Seltzer et al. 1963, Weisleder et al. 2009). In one Meja`re et al. Diagnosis of dental pulp ª 2012 International Endodontic Journal International Endodontic Journal, 45, 597–613, 2012 601
- 13. study (Seltzer et al. 1963), combining cold and heat tests increased specificity compared with the results of each test separately, whilst sensitivity decreased. In the other study (Weisleder et al. 2009), the combina- tion of cold tests (carbon dioxide and Endo-ice) and EPT improved the ability to correctly identify necrotic pulps (sensitivity = 96%) and vital pulps (specific- ity = 92%). Both studies have methodological short- comings. Assessment of blood flow Two studies (Olgart et al. 1988, Evans et al. 1999) reported high sensitivity and specificity for laser Dopp- ler flowmetry (88–100% and 100%, respectively). The reference tests were visual inspection of the pulp in connection with subsequent endodontic therapy or conventional pulp vitality tests (cold, heat and EPT). Both studies suffer from methodological shortcomings. A study of moderate quality (Gopikrishna et al. 2007) compared pulse oximetry with direct inspection of the pulp (reference test). All non-vital pulps were correctly identified (sensitivity = 100%) and almost all vital pulps (specificity = 95%). Other clinical markers Only one study reported on the accuracy of sensibility to probing exposed dentin or a radiographically observed widened periodontal membrane for differentiating be- tween vital and necrotic pulps (Kamburog˘lu & Paksoy 2005). Both tests yielded perfect sensitivity and rela- tively high specificity (76–80%). The study has, how- ever, several methodological shortcomings. Table 4 Quality of evidence of the diagnostic accuracy of abnormal reaction to heat, cold, percussion test and discontinuity of dentin floor over the pulp for determining the status of vital pulp (no/minimal versus moderate/severe inflammation) in teeth with deep caries. Data from Hasler & Mitchell (1970) Test method Sample size (no of studies) Sensitivity (95% CI) Specificity (95% CI) Quality of evidence Rating according to Study design/quality, indirectness, consistency, precision, publication bias Heat 47 (1) 54 (29;77) 21 (10;37) ¯sss (insufficient) Study design/quality – 1 Precision – 1 One study – 1 Cold 47 (1) 85 (58;96) 12 (5;27) ¯sss (insufficient) Study design/quality – 1 Precision – 1 One study – 1 Percussion 47 (1) 77 (50;92) 21 (10;37) ¯sss (insufficient) Study design/quality – 1 Precision – 1 One study – 1 Pulp exposed by caries (discontinuity of dentin floor over the pulp). 47 (1) 77 (50;92) 88 (73;95) ¯sss (insufficient) Study design/quality – 1 Precision – 1 One study – 1 Table 5 Quality of evidence of the diagnostic accuracy of electric stimulation, pulse oximetry and cold test for determining pulp vitality. Data from Gopikrishna et al. (2007) Test method Sample size (no of studies) Sensitivity (95% CI) Specificity (95% CI) Quality of evidence Rating according to: Study design/quality, indirectness, consistency precision, publication bias Electric stimulation 80 (1) 71 (56;83) 92 (79;97) ¯sss (insufficient) Study design/quality – 1 Indirectness – 1 One study – 1 Pulse oximetry 80 (1) 100 (91;100) 95 (83;99) ¯sss (insufficient) Study design/quality – 1 Indirectness – 1 One study – 1 Cold 80 (1) 81 (67;90) 92 (79;97) ¯sss (insufficient) Study design/quality – 1 Indirectness – 1 One study – 1 Meja`re et al. Diagnosis of dental pulp ª 2012 International Endodontic Journal International Endodontic Journal, 45, 597–613, 2012 609
- 14. To conclude, there is insufficient evidence to deter- mine the diagnostic accuracy of tests used to assess pulp vitality (Table 5). Biological markers as indicators of pulp’s inflammatory status Whilst numerous efforts have been made to link biological markers of inflammation, including inflammatory medi- ators, to the inflammatory status of pulp, only one study satisfied the inclusion criteria (Guthrie et al. 1965). In this study, blood samples were taken from pulp exposures induced by caries or other injuries. The samples were analysed with regard to white blood cell counts. The cell counts correlated poorly with the extent of pulp inflam- mation as assessed by histology after tooth extraction (sensitivity = 36% and specificity = 64%). Hence, there is no scientific basis on which to assess the diagnostic value of biological markers to determine the condition of pulp in terms of reversible and irreversible pulpitis. Discussion The literature targeting the problem field addressed in this systematic review is extensive. However, most of the publications consist of narrative overviews describ- ing methods, techniques and materials for the clinical evaluation of the condition of pulp. In contrast, only a few studies were designed for assessing the accuracy of tests or methods. No systematic review that has critically evaluated the scientific literature correspond- ing to the research questions could be identified. It is worth noting that most of the included studies in the current review are out of date and relatively few have assessed novel test methods in a clinical context. A conceivable explanation for the lack of high- quality studies could be the difficulty in obtaining a good reference test. Dental pulp tissue is normally not available for direct inspection or for microscopic or other examinations, especially if the tooth is healthy and in no need of endodontic treatment or extraction. Formerly, such teeth were frequently available as they were extracted if decayed by caries rather than being treated endodontically. Healthy teeth were also often sacrificed for prosthodontic reasons. Today, access to such teeth is highly limited. Another explanation for the lack of studies of good quality may be that cross- sectional data have traditionally been regarded as the only means, whilst the benefit of a prospective study design has not been considered. Only one of the included studies used this design (Matsuo et al. 1996). Inflammatory mediator substances identified in pulps exposed by caries or other injuries, for example, prostaglandins (Cohen et al. 1985, Waterhouse et al. 2002), superoxide dismutase (Tulunoglu et al. 1998), TNF-alfa (Pezelj-Ribaric et al. 2002), substance P (Bowles et al. 2003) and MMPs (Zehnder et al. 2011), may indicate pulp status and have the potential to predict the outcome of treatment intended to maintain an exposed pulp vital and asymptomatic, for example, pulp capping or pulpotomy. Although markers of this nature have been correlated with clinical symptoms, no study satisfying the inclusion criteria could be identified. It must be recognized that the natural history of a caries-induced pulpitis is not well delineated and knowledge concerning the healing potential of injured pulp is restricted. Considering that infection is often the cause of inflammation, any inflamed pulp should be able to heal if the source of infection is eliminated, as is often the case in other body organs/systems. Thus, caries-induced pulpitis ought to be reversible and the pulp able to heal if caries is removed. An important pre- requisite is, however, that infectious elements have not established themselves permanently in the pulp cham- ber. No study of sufficient quality could be identified that assessed the relationship between markers of pulp infection and the outcome of conservative treatment (aimed at preserving pulp exposed by caries or other forms of injury). Quite a few studies assessed the accuracy of methods for testing pulp vitality; tests that initiate pain response to thermal or electric provocation have attracted most attention. Intact, healthy teeth are often used as the reference test without examining the true status of these pulps (other than a positive response to thermal and/or electric testing). This limits the value of such studies in that overall diagnostic studies using a case– control design overestimate test accuracy (Knottnerus 1995, Rutjes et al. 2006). Furthermore, the prevalence of pulps with severe inflammation and/or necrosis is relatively high in most of the studies because the samples often consist of referred patients or teeth scheduled for endodontic treatment or extraction. Results based on such samples have an inherent risk of so-called spectrum bias, implying that the study population may not represent patients who would be exposed to the test in daily clinical practice. Vitality testing may also already have been performed before referral. The effect of this is that the value of the test is partly ‘used-up’, a phenomenon sometimes called work-up bias (Begg 1987, Panzer et al. 1987). The Diagnosis of dental pulp Meja`re et al. International Endodontic Journal, 45, 597–613, 2012 ª 2012 International Endodontic Journal610
- 15. implication is that both sensitivity and specificity may change if the test is carried out on another spectrum of patients not exposed to such a prior selection process (Sackett & Haynes 2002). It follows that a careful description of the patient spectrum and how they are selected is crucial to enable proper assumptions about whether or not it is acceptable to generalize the results. Laser Doppler flowmetry was introduced more than 20 years ago and has been proposed as an alternative means of assessing pulp vitality. Yet, clinical applica- bility has still not been ascertained. The method is also expensive and requires technique-sensitive equipment. A study examining the feasibility of the method in clinical practice observed variable and uncertain results when the test conditions were not highly standardized (Roy et al. 2008). Another limitation is that the method is useful only in teeth with a pulp chamber positioned well above the gingival margin. Pulse oximetry is based on a simpler and less costly technology. Whilst promising, this method is also limited to teeth with pulp tissue well within the crown portion of the tooth. In general, there were major shortcomings in the design, conduct and reporting of studies. The extent to which they satisfied important quality criteria is illustrated in Fig. 2. The population was inadequately described in nearly all, and only one study used consecutively chosen patients. The use of nonconsec- utive patients tends to overestimate the accuracy of a diagnostic method (Lijmer et al. 1999, Rutjes et al. 2006). In half of the studies, the index tests and reference tests were insufficiently described. Few studies had two independent assessors of the reference test, which introduces an obvious risk for a biased assess- ment of the pulp’s condition. Another serious short- coming is that it was usually not possible to discern whether the reference test was interpreted indepen- dently and without knowledge of the results of the index test. If the assessors interpret the reference test knowing the results of the index test, there will be an increased risk of overestimating test accuracy (Lijmer et al. 1999). Precision (e.g. confidence intervals) of point estimates was not reported in any of the studies. In summary, there is a great need for improvement in the design, conduct and reporting of studies on diagnostic methods in endodontics. Tools for guiding the performance of such studies can be found in Standards for Reporting of Diagnostic Accuracy (Boss- uyt et al. 2003), which corresponds to the Consort Statement for randomised clinical studies (Moher et al. 2001). This systematic review has revealed critical gaps in knowledge concerning the effect of diagnostic tests commonly used to determine the condition of pulp. Thus, available research provides limited information 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100 % Representative patient spectrum Population adequately described Reference test classifies the target condition correctly Time interval between index- and reference test adequate Reference test applied on all or on a randomized sample of patients The same reference test irrespective of results of index test Index test adequately described Reference test adequately described Index test interpreted without knowledge of results of reference test Reference test interpreted without knowledge of results of index test Uninterpretable test results reported At least two independent examiners of reference test Reliability concerning reference test reported Precision of test results reported Yes NoUnclear Figure 2 Reporting of 14 quality criteria, modified after QUADAS (Whiting et al. 2003), of the 18 included studies regarding accuracy of pulp diagnosis. Percentage distribution of yes/unclear/no of each criterion. Meja`re et al. Diagnosis of dental pulp ª 2012 International Endodontic Journal International Endodontic Journal, 45, 597–613, 2012 611
- 16. about what distinguishes a treatable from a nontreat- able pulpal inflammation in teeth subjected to deep caries, trauma or other injury. Future research should focus on exploring methods that can disclose whether a vital but injured pulp can be maintained, or whether it should be removed and replaced with a root filling. Furthermore, the long-term benefit to the patient, which is the ultimate goal of any diagnostic procedure, should be evaluated. Conclusion The scientific evidence is insufficient (¯sss) to assess the accuracy of the following clinical signs, symptoms or tests used to determine the condition of pulp: • hypersensibility to heat, response to cold, electric stimulation or tenderness to percussion in asymp- tomatic teeth with deep caries lesions, • presence, character or duration of pain and • in terms of reversible/irreversible pulp inflamma- tion. The evidence base is also insufficient (¯sss) to assess the accuracy of the following: • combining tests to determine the condition of pulp, • electrical or thermal pulp testing or methods for measuring pulpal blood circulation to determine whether the pulp is vital or nonvital and • biological markers of pulp inflammation, infection or other tissue damage for predicting the outcome of treatment intended to maintain an exposed pulp vital and asymptomatic. Conflict of interest There were no conflicts of interest. References Begg CB (1987) Biases in the assessment of diagnostic tests. Statistics in Medicine 6, 411–23. Bossuyt PM, Reitsma JB, Bruns DE et al. (2003) Towards complete and accurate reporting of studies of diagnostic accuracy: the STARD initiative. British Medical Journal 326, 41–4. Bowles WR, Withrow JC, Lepinski AM, Hargreaves KM (2003) Tissue levels of immunoreactive substance P are increased in patients with irreversible pulpitis. Journal of Endodontics 29, 265–7. 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