Tooth extraction, nonsurgical retreatment, and apical surgery are the 3 major first

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1 Impact of Diabetes Mellitus, Hypertension, and Coronary Artery Disease on Tooth Extraction after Nonsurgical Endodontic Treatment Chih-Hao Wang, MD, PhD,* Ling-Huey Chueh, DDS, MS, Shih-Chung Chen, DDS, Yen-Chen Feng, Chuhsing K. Hsiao, PhD, k and Chun-Pin Chiang, DDS, DMSc # ** Abstract Introduction: Limited prospective data are available on the long-term prognosis of teeth receiving nonsurgical root canal treatment (NSRCT) in patients with systemic diseases including diabetes mellitus (DM), hypertension (HT), and coronary artery disease (CAD). This prospective study aimed to elucidate the impact of systemic diseases on the risk of tooth extraction after NSRCT. Methods: A total of 49,334 NSRCT teeth were randomly selected from databank in October 2003 and were followed for 2 years for tooth extraction after NSRCT. Cox proportional hazards model was used to estimate the risk of tooth extraction after NSRCT. Results: Of the 49,334 teeth, 1592 (3.2%) were extracted during the 2-year follow-up period, yielding a 2-year tooth retention rate of 96.8%. We found that DM (hazard ratio [HR], 1.79), HT (HR, 1.75), and CAD (HR, 1.70) were significant risk factors for tooth extraction after NSRCT (all P values <.0001) in univariate Cox proportional analyses. After adjustment for age, gender, and tooth type in multivariate analyses, DM (HR, 1.29) and HT (HR, 1.18) remained as independent risk factors (both P values <.05). Simultaneous possession of 2 diseases of DM, HT, and CAD was a significant and robust predictor for an increased long-term risk of tooth extraction after NSRCT (P for trend <.001). Conclusions: An increased risk of tooth extraction after NSRCT is significantly associated with DM, HT, and CAD individually. Moreover, the constellation of systemic disease burden also manifests the importance in addition to other potential confounders. (J Endod 2011;37:1 5) Key Words Coronary artery disease, diabetes mellitus, endodontic outcome, hypertension, systemic disease, tooth extraction Tooth extraction, nonsurgical retreatment, and apical surgery are the 3 major first untoward events that occur after nonsurgical root canal treatment (NSRCT). Among the three, tooth extraction is the most common first untoward event after NSRCT (1 5). Previous studies have shown that 59% 73.5% of teeth with first untoward event are extracted during a follow-up period of 2 8 years (1 5). The majority of previous studies evaluated the dental-related reasons such as endodontic, prosthetic, or periodontal failure and tooth fracture for tooth extraction after NSRCT (1, 5 7). A few studies evaluated the effect of systemic diseases including diabetes mellitus (DM) or hypertension (HT) on endodontic treatment outcome (8 12). However, to the best of our knowledge there was no previous study specifically assessing the influence of systemic disease burden on the risk of tooth extraction after NSRCT. Several reasons motivated us to investigate the association of systemic diseases such as DM, HT, and coronary artery disease (CAD) with tooth extraction after NSRCT. First, patients with systemic diseases such as DM, HT, and CAD might have decreased tissue resistance to bacterial infection and reduced ability for tissue repair after NSRCT. Thus, the risk of tooth extraction after NSRCT might escalate in patients with DM, HT, or CAD. Second, DM, HT, and CAD are the 3 major causes of cardiovascular morbidity and mortality worldwide (13 15); therefore, the evaluation of an association between tooth extraction after NSRCT and DM, HT, and/or CAD would be essential from a theoretical and clinical standpoint. Third, a very large number of NSRCT patients from the databank of national health insurance organization in Taiwan can be accessed and cross-checked with their medical records to examine the impact of systemic diseases on the risk of tooth extraction after NSRCT. Therefore, an unprecedented large-scale prospective study on 49,334 teeth receiving NSRCT was conducted to assess the impact of systemic diseases on the risk of tooth extraction after NSRCT during a 2-year follow-up period. Materials and Methods Sample Size and Sampling Scheme The National Health Insurance (NHI) program, which provides compulsory universal health insurance, was implemented in Taiwan on March 1, As reported by the Bureau of National Health Insurance (BNHI) in 2003, the NHI program shelters approximately 96% of the population in Taiwan. This health plan encompasses nearly all medical treatments and a proportion of dental treatments including surgical and nonsurgical endodontic procedures. Most medical institutions (approximately 93%) in Taiwan have been contracted to the BNHI, and more than 96% of the shielded pop- From the *Department of Cardiology, Cardinal Tien Hospital and Department of Medicine, College of Medicine, Fu-Jen Catholic University, Taipei, Taiwan; Elite Dental Clinic and Poling Dental Clinic, Taipei, Taiwan; Department of Public Health and k Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei, Taiwan; and Graduate Institute of Oral Biology, # School of Dentistry, and **Dental Department of National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan. Address requests for reprints to Professor Chun-Pin Chiang, Department of Dentistry, National Taiwan University Hospital, No. 1 Chang-Te Street, Taipei 10048, Taiwan. address: cpchiang@ntu.edu.tw /$ - see front matter Copyright ª 2011 American Association of Endodontists. All rights reserved. doi: /j.joen JOE Volume 37, Number 1, January 2011 Systemic Diseases and Extraction of Endodontically Treated Teeth 1

2 ulations have used health services at least once through contracted medical institutions. Health providers need to claim for each treatment to the BNHI. Thus, large amounts of computerized medical and dental data for each insured individual have been reserved since March The BNHI database provides a unique opportunity to assess the influence of systemic diseases on tooth extraction after NSRCT. On the basis of the records in the databank of BNHI, a total of 1,789,676 teeth received NSRCT in 2003, of which 160,841 teeth completed NSRCT in October We performed a systematic sampling from the list of 160,841 teeth, with every third case selected after a random start (16). A total of 50,000 NSRCT teeth were selected and followed up for 2 years from the time point of treatment completion date of NSRCT in October 2003 to see whether these teeth were extracted after NSRCT. To perform parametric statistical tests when comparing differences among hospital-treated teeth, the number of extracted teeth has to be greater than 15 to satisfy the normality assumption. Moreover, because the overall 2-year tooth extraction rate after NSRCT was 3.125% in Taiwan (4) and only 6.8% of the extracted teeth were treated in hospitals rather than in clinics, a minimum of 7059 ( % 6.8% = 15) teeth receiving NSRCT were to be followed up for at least 2 years. In addition, there are 6 divisions of BNHI in Taiwan, and hospitals are contracted to 1 of the 6 divisions. Therefore, we needed to sample more than 42,354 (7059 6) teeth from all 6 areas. If the number 15 was replaced by 20, then the required sample size for follow-up became 56,472. We finally concluded to select 50,000 teeth for this study. All NSRCT patients included in this study were cross-checked with their medical database to see whether they also had systemic diseases including infectious, endocrine (except DM), metabolic, hepatic, renal, or congenital heart diseases, benign or malignant tumors, DM, HT, and CAD. DM was defined as having a fasting plasma glucose level $126 mg/ dl on 2 or more tests on different days, a random blood glucose level $200 mg/dl, hemoglobin A1c $6.5% (17), or a history of treated DM. HT was defined as having repeated elevated blood pressure with systolic blood pressure $140 mm Hg and diastolic blood pressure $90 mm Hg (18), or history of treated HT. CAD was diagnosed as having a history of receiving percutaneous coronary intervention or coronary artery bypass graft surgery, of narrowing or blockage of the coronary arteries shown by coronary angiography or multi-slice computed tomography, or of documented myocardial infarction or myoischemia revealed by electrocardiography (15, 19). All the teeth extracted after NSRCT during the 2-year follow-up period were retrieved by a linkage procedure with the dental databank for specific treatment codes of simple or complicated tooth extraction. These extracted teeth were enrolled, and their corresponding data were analyzed. Those teeth extracted within 1 day after initial NSRCT were excluded to avoid bias, because the majority of these teeth were extracted as a result of treatment technique failure instead of the impact of systemic diseases. Furthermore, if 2 or more teeth from the same individual were treated by NSRCT, only the initial tooth treated by NSRCT was included in this study. Fig. 1 shows the flowchart of sampling procedure. The final study population consisted of 49,334 patients. For each patient, because only 1 NSRCT tooth was selected and included in this study, the number of follow-up patients (49,334) was equal to the number of follow-up NSRCT teeth (49,334), and the following statistical analysis was conducted on the basis of these 49,334 NSRCT teeth. Statistical Analysis Univariate analysis was conducted with c 2 test. Trend test was carried out for various age groups and tooth types, respectively. Cox proportional hazards model was used to assess the impact of systemic Teeth with complete endodontic treatment in 2003, n = 1,789,676 teeth Endodontic treatment completed in October 2003, n = 160,841 teeth Systematic sampling, n = 50,000 teeth Select the first tooth per patient if multiple teeth were treated and selected, n = 49,341 patients Retrieve records of systemic diseases and remove incomplete data & deciduous teeth, n = 49,334 patients Figure 1. Sampling scheme. Final data for analysis, n = 49,334 patients, 1,592 teeth extracted in 2 years diseases on the risk of tooth extraction after NSRCT during a 2-year follow-up period. Confounding factors such as age, gender, and tooth types were adjusted in the Cox regression analyses. All statistical procedures were carried out by using SAS 9.1 (SAS Institute Inc, Morrisville, NC). A P value of less than.05 was considered statistically significant for each test. Results Among the 50,000 teeth randomly selected via systematic sampling procedure from the 160,841 teeth, 666 teeth including those with missing data or coding errors, deciduous teeth, and multiple teeth from 1 patient were excluded from the final study population (Fig. 1). Of the 49,334 NSRCT teeth, 1592 (3.2%) from 1592 patients (mean age, years) were extracted during the 2-year followup period, yielding a 2-year tooth retention rate of 96.8%. Systemic Diseases as Risk Factors After analyzing the relationship between each of the 14 systemic disease risk factors and tooth extraction after NSRCT with a Bonferroni adjustment for multiple comparison (P <.05/14 =.0036), we found significant association of an increased risk of tooth extraction after NSRCT with DM, HT, and CAD. Systemic diseases such as infectious, endocrine (except DM), metabolic, hepatic, renal, and congenital heart 2 Wang et al. JOE Volume 37, Number 1, January 2011

3 diseases as well as benign and malignant tumors were found to have no significant association with tooth extraction after NSRCT (data not shown). Thus, we focused on the impact of DM, HT, and CAD on tooth extraction after NSRCT. Of the 49,334 NSRCT patients, 4358 (8.13%) had DM, 9310 (18.97%) had HT, and 3795 (7.69%) had CAD (Table 1). In univariate Cox proportional hazards analyses, we found a significantly higher tooth extraction rate in patients with DM (5.30%; hazard ratio [HR], 1.79), HT (4.88%; HR, 1.75), or CAD (5.11%; HR, 1.70) than in patients without DM (3.03%), HT (2.84%), or CAD (3.07%) during a 2-year follow-up period (all P values <.0001), respectively. In addition, teeth in patients older than 30 years or with posterior teeth (premolars and molars) were predisposed to be extracted within 2 years after completion of NSRCT (Table 1). Impact of Constellation of Systemic Disease on the Outcome We further analyzed the impact of the 3 systemic diseases (DM, HT, and CAD) on tooth extraction after NSRCT by multivariate Cox proportional hazards model (Table 2). We found that after adjustment for age, gender, and tooth type in multivariate analyses with Cox regression models, DM and HT were still significantly associated with tooth extraction after completion of NSRCT. The adjusted HR was 1.29 (95% confidence interval [CI], ; P =.0008) for DM patients and 1.18 (95% CI, ; P =.015) for HT patients. In Table 3, we examined the disease burden by using Cox proportional regression model, and we found that the adjusted HR for patients with only 1 disease of DM, HT, or CAD was 1.19 (95% CI, ; P =.010), whereas the adjusted HR for patients with 2 diseases of DM, HT, and CAD was as high as 1.53 (95% CI, ; P <.0001). Discussion Epidemiologic studies have provided us some information on the relatively small group of teeth experiencing an untoward event after initial NSRCT. Lazarski et al (1) reported that 59% of 4212 teeth experiencing a first untoward event are extracted during a minimum followup interval of 2 years. Salehrabi and Rotstein (2) also demonstrated that 73.5% of 57,361 teeth with the first untoward event are extracted. Our previous 3 studies found that 61.5% 71.1% of the teeth with the first untoward event are extracted during the 5-year follow-up period (3 5). All of these 5 studies indicate that tooth extraction is the most common initial untoward event after NSRCT. Several dental-related risk factors might result in tooth extraction after NSRCT. Our previous study analyzed the 65 reasons for extraction of 56 teeth after NSRCT. We found that only 10.7% of NSRCT teeth are extracted as a result of endodontically related diseases, and 89.3% of NSRCT teeth are extracted as a result of nonendodontically related diseases such as periodontal diseases (26.8%), large decay or unrestorable tooth (46.4%), and tooth fracture (32.1%) (5). Vire (6) showed that tooth extractions after NSRCT procedures are due to prosthetic failure in 59.4% of cases, periodontal failure in 32% of cases, and endodontic failure in 8.6% of cases. Fuss et al (7) reported that the 3 major reasons for extraction of endodontically treated teeth are unrestorable teeth (43.5%), endodontic failure (21.1%), and vertical root fracture (10.9%). Lazarski et al (1) also demonstrated a significant influence of subsequent restoration and build-up on tooth extraction after NSRCT. The above-mentioned findings indicate that only a relatively small percentage (8.6% 21.1%) of NSRCT teeth are extracted as a result of endodontic failure. In addition to dental-related risk factors, this study further evaluated the systemic disease burden for tooth extraction after NSRCT. By using univariate Cox proportional hazards analyses, we found that DM, HT, and CAD were significant risk factors for tooth extraction after NSRCT. The multivariate analysis with Cox proportional hazards models revealed that DM and HT were independent risk factors for tooth extraction after NSRCT. It is well-known that DM patients are predisposed to have periodontal disease (20) and oral candidiasis (21, 22). DMinduced microangiopathy can lead to altered tissue metabolism, TABLE 1. Univariate Cox Proportional Hazards Analyses of Contributing Risk Factors Including Age and Gender of Patients, Tooth Type, and Systemic Disease for Tooth Extraction within 2 Years after Completion of NSRCT Tooth extraction after NSRCT Variables No. of patients No. Rates* HR (95% CI) P value Age (y) #30 14, , ( ) , ( ) >55 11, ( ) <.0001 Gender Female 28, Male 20, ( ).116 Tooth type Anterior 14, Premolar 15, ( ) Molar 19, ( ) <.0001 DM status Without 44, With 4, ( ) <.0001 HT status Without 40, With 9, ( ) <.0001 CAD status Without 45, With 3, ( ) <.0001 CAD, coronary artery disease; CI, confidence interval; DM, diabetes mellitus; HR, hazard ratio; HT, hypertension; NSRCT, nonsurgical root canal treatment. *Per 1000 person-years. P for trend test. Gender data were missing for 599 patients. JOE Volume 37, Number 1, January 2011 Systemic Diseases and Extraction of Endodontically Treated Teeth 3

4 TABLE 2. Multivariate Cox Proportional Hazards Analyses of Contributing Risk Factors Including Age and Gender of Patients, Tooth Type, and Systemic Disease for Tooth Extraction within 2 Years after Completion of NSRCT Variables HR adj (95% CI) P value Age (y) <.0001* # ( ) ( ) > ( ) Gender.532 Female Male 1.03 ( ) Tooth type <.0001* Anterior Premolar 1.44 ( ) Molar 2.52 ( ) Systemic disease Without systemic disease With DM 1.29 ( ).0008 With HT 1.18 ( ).015 With CAD 1.13 ( ).136 CAD, coronary artery disease; DM, diabetes mellitus; HR, hazard ratio; HT, hypertension; HR adj, multivariate-adjusted HR adjusted for age, gender, and tooth type; NSRCT, nonsurgical root canal treatment. *P for trend test. ischemia of local tissue, and reduced tissue resistance to infection (23). Moreover, macrophage and neutrophil inhibition might allow increased bacterial growth and dental plaque formation (24 26). A successful NSRCT can eradicate nearly all bacteria in the root canal system by mechanical and chemical debridement. In healthy individuals, the residual infection or inflammation in the periapical tissue after NSRCT might be overcome by their own immune systems. In contrast, in diabetic patients a small focus of residual infection in the periapical tissue after NSRCT might not be effectively eliminated by host s immune system and finally result in extraction of teeth after NSRCT. Indeed, previous studies have shown that men with type 2 TABLE 3. Multivariate Cox Proportional Hazards Analyses of Contributing Risk Factors Including Age and Gender of Patients, Tooth Type, and Systemic Disease Such as DM, HT, and CAD for Tooth Extraction within 2 Years after Completion of NSRCT Variables HR adj (95% CI) P value Age (y) < ( ) ( ) <.0001 > ( ) <.0001 Gender.551 Female Male 1.03 ( ) Tooth type Anterior Premolar 1.44 ( ) <.0001 Molar 2.51 ( ) <.0001 Systemic disease status No DM/HT/CAD Only 1 disease of 1.19 ( ).010 DM/HT/CAD Two diseases of DM/ HT/CAD 1.53 ( ) <.0001 CAD, coronary artery disease; CI, confidence interval; DM, diabetes mellitus; HR, hazard ratio; HT, hypertension; HR adj, multivariate-adjusted HR adjusted for age, gender, and tooth type; NSRCT, nonsurgical root canal treatment. diabetes who have endodontic treatments are more likely to have residual lesions after treatment (8). Patients with DM have increased periodontal disease of teeth with endodontic involvement compared with patients who do not have DM (10). Moreover, patients with DM have a reduced likelihood of success of endodontic treatment in cases with preoperative periradicular lesions (9, 10). In a 10-year retrospective study of endodontic treatment outcome, Mindiola et al (11) found that DM and/or HT might contribute to decreased retention of endodontically treated teeth in an American Indian population. The above-mentioned studies suggest the marked influence of systemic diseases such as DM and HT on endodontic treatment outcomes. On the contrary, Doyle et al (12) reported that NSRCT outcomes are affected by periradicular periodontitis, post placement, and overfilling but are not affected by DM. In this study, we found that premolars and molars had significantly higher tooth extraction rates than anterior teeth. Our previous study assessed the technique quality of NSRCT in Taiwan. We found that the frequency of teeth with good-quality endodontic work in anterior teeth (40.4%) or in the premolars (33%) is significantly greater than that in the molars (18.4%) (27). Significantly higher percentages of endodontically treated premolars or molars than anterior teeth reported having inadequate filling length or sealing density might explain why premolars and molars had significantly higher tooth extraction rates than anterior teeth in this study. In this study, the risk of tooth extraction after NSRCT was 1.79 for DM, 1.75 for HT, and 1.70 for CAD. These 3 risks are close to each other, which might reflect the comorbidity in patients with DM, HT, and CAD. For instance, it was reported that approximately 40% 60% of DM patients have comorbidity with HT (28). This study also showed that the adjusted HR was 1.29 for DM patients and 1.18 for HT patients. These 2 adjusted HRs were clinically significant as well. For patients with DM, the risk of extraction of the NSRCT teeth in 2 years is 30% higher than for those without DM. Similarly, patients with HT have almost 20% higher risk of extraction of the NSRCT teeth in 2 years than those without HT. Because the prevalence rate is as high as 11% for DM (29) and 26% (30) for HT in Taiwan, these DM or HT patients bear such risk of tooth loss that might affect their life quality afterwards. In this study, the individual data such as socioeconomic status and precarious oral habits such as tobacco smoking and alcohol drinking were not available. Thus, the Cox proportional hazards analyses were adjusted by age, gender, and tooth type only. The adjustment with limited variables might not be enough, and further studies with more individual data are worth pursuing. In conclusion, this study found that DM, HT, and CAD are all significant risk factors for tooth extraction after NSRCT in univariate analyses, and DM or HT was an independent risk factor for tooth extraction 2 years after NSRCT in multivariate analyses. Simultaneous possession of 2 diseases of DM, HT, and CAD was significantly associated with an elevated long-term risk of tooth extraction after NSRCT. We suggest that prospective case-control clinical studies have to be conducted in the future to further prove whether patients with DM, HT, or CAD really have a significantly higher risk for tooth extraction after NSRCT than those without DM, HT, or CAD. Acknowledgments The authors extend their thanks to the Bureau of National Heath Insurance in Taiwan for the help provided during the study. This research was supported by grant DOH95-HI-1001 from the Department of Health, the Executive Yuan, Taiwan. The authors deny any conflicts of interest related to this study. 4 Wang et al. JOE Volume 37, Number 1, January 2011

5 References 1. Lazarski MP, Walker WA, Flores CM, Schindler WG, Hargreaves KM. Epidemiological evaluation of the outcomes of nonsurgical root canal treatment in a large cohort of insured dental patients. J Endod 2001;27: Salehrabi R, Rotstein I. Endodontic treatment outcomes in a large patient population in the USA: an epidemiological study. J Endod 2004;30: Chen SC, Chueh LH, Hsiao CK, Tsai MY, Ho SC, Chiang CP. An epidemiological study of tooth retention after nonsurgical endodontic treatment in a large population in Taiwan. J Endod 2007;33: Chen SC, Chueh LH, Wu HP, Hsiao CK. Five-year follow-up study of tooth extraction after nonsurgical endodontic treatment in a large population in Taiwan. J Formos Med Assoc 2008;107: Chen SC, Chueh LH, Hsiao CK, Wu HP, Chiang CP. First untoward events and reasons for tooth extraction after nonsurgical endodontic treatment in Taiwan. J Endod 2008;34: Vire DE. Failure of endodontically treated teeth: classification and evaluation. J Endod 1991;17: Fuss Z, Lustig J, Tamse T. Prevalence of vertical root fractures in extracted endodontically treated teeth. Int Endod J 1999;32: Britto LR, Katz J, Guelmann M, Heft M. Periradicular radiographic assessment in diabetic and control individuals. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2003;96: Fouad AF. Diabetes mellitus as a modulating factor of endodontic infections. J Dent Educ 2003;67: Fouad AF, Burleson J. The effect of diabetes mellitus on endodontic treatment outcome: data from an electronic patient record. J Am Dent Assoc 2003;134: Mindiola MJ, Mickel AK, Sami C, Jones JJ, Lalumandier JA, Nelson SS. Endodontic treatment in an American Indian population: a 10-year retrospective study. J Endod 2006;32: Doyle SL, Hodges JS, Pesun IJ, Baisden MK, Bowles WR. Factors affecting outcomes for single-tooth implants and endodontic restorations. J Endod 2007;33: Wild SH, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for Diabetes Care 2004;27: Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J. Global burden of hypertension: analysis of worldwide data. Lancet 2005;365: Rosamond W, Flegal K, Furie K, et al. Heart disease and stroke statistics: 2008 update a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2008;117:e Thompson SK. Sampling. New York: John Wiley & Sons; Alberti KGMM, Zimmet PZ. WHO Consultation. Definition, diagnosis and classification of diabetes mellitus and its complications: part 1 diagnosis and classification of diabetes mellitus: provisional report of a WHO Consultation. Diabet Med 1998;15: Chobanian AV, Bakris GL, Black HR, et al. Seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure. Hypertension 2003;42: Prineas RJ, Crow RS, Zhang ZM. The Minnesota code manual of electrocardiographic findings: standards and procedures of measurement and classification. 2nd ed. London: Springer-Verlag London Limited; , Grossi SG, Genco RJ. Periodontal disease and diabetes mellitus: a two-way relationship. Ann Periodontol 1998;3: Ueta E, Osaki T, Yoneda K, Yamamoto T. Prevalence of diabetes mellitus in odontogenic infections and oral candidiasis: an analysis of neutrophil suppression. J Oral Pathol Med 1993;22: Soysa NS, Samaranayake LP, Ellepola ANB. Diabetes mellitus as a contributory factor in oral candidosis. Diabet Med 2005;23: Pierce GF. Inflammation in nonhealing diabetic wounds: the space-time continuum does matter. Am J Pathol 2001;159: Ferguson MM, Silverman S Jr. Endocrine disorders. In: Jones JH, Mason DK, eds. Oral manifestation of systemic disease. 2nd ed. London: Bailliere Tindall; 1990: Naghibi M, Smith RP, Baltch AL, et al. The effect of diabetes mellitus on chemotactic and bactericidal activity of human polymorphonuclear leukocytes. Diabetes Res Clin Pract 1987;4: Marhoffer W, Stein M, Maeser E, Federlin K. Impairment of polymorphonuclear leukocyte function and metabolic control of diabetes. Diabetes Care 1992;15: Chueh LH, Chen SC, Lee CM, et al. Technique quality of root canal treatment in Taiwan. Int Endod J 2003;36: Goldstein LB, Adams R, Becker K, et al. Primary prevention of ischemic stroke: a statement for healthcare professionals from the Stroke Council of the American Heart Association. Circulation 2001;103: Chou P, Chen HH, Hsiao KJ. Community-based epidemiological study on diabetes in Pu-Li, Taiwan. Diabetes Care 1992;15: Pan WH, Chang HY, Yeh WT, Hsiao SY, Huang YT. Prevalence, awareness, treatment and control of hypertension in Taiwan: results on nutrition and health survey in Taiwan (NAHSIT) J Hum Hypertens 2001;15: JOE Volume 37, Number 1, January 2011 Systemic Diseases and Extraction of Endodontically Treated Teeth 5

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