periodontitis stage 4 grade c treatment

She previously taught in two dental hygiene programs as clinical and didactic faculty. future research directions and describes possible research applications. There are early radiographic signs of periodontitis. The four stages (stage 1-4) of periodontitis are determined by several variables. Dent Update. Periodontitis exists in different forms, and its etiology is related to multiple component causes. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). ; Schroeder, H.E. J Dent. Patients in stage I, stage II, and grade A had no TLPD during the total treatment period. The aim of this study was to understand if important factors such as smoking, gender, age, plaque, pus, and probing pocket depth could influence the histomorphological pattern of generalized stage III-IV, grade C periodontitis (GPIII-IVC), which is a particular form of periodontitis. 2014;65(1):107-33. Clinicians should initially assume Grade B disease and seek specific evidence to shift towards grade A or C, if available. Bacterial plaque on the crown surface of a tooth constantly presents antigen to the marginal gingiva, stimulating an inflammatory response and resulting in gingivitis. A., Melis, M., & Zawawi, K. H. (2021). Patients in stage IV, grade C had TLPD rates of 0.24 0.31, 0.15 0.24 (number of teeth/patient/year . Our results showed that the vascular area was also more than halved in subjects with residual plaque on tooth surfaces. 0000101613 00000 n All rights reserved. Sarah has clinical experience in both the private and public health sectors. The guidelines can be followed so consistent diagnosing can occur. The association between periodontal disease and the risk of myocardial infarction: a pooled analysis of observational studies. Gingivitis is common in dogs and cats and refers to inflammation of the gingiva in response to plaque antigen. . analyzed the data; L.R. Prakash et al. Methods: 0000048012 00000 n A stage 2 mobility is present when tooth mobility is increased in any direction other than axial over a distance of >0.5 mm and up to 1 mm. The guidelines have not been updated since 1999, so this is a pretty big deal! Lastly, certain risk factors are associated with progressive bone loss including smoking and diabetes. Step 2: Establish Stage is divided into two sections. Martin-Cabezas R, Seelam N, Petit C, et al. 0000056826 00000 n 0000001308 00000 n The goal of periodontal treatment is to eliminate dysbiotic plaque biofilm from the tooth surface and to establish an environment that allows the maintenance of health. Published by John Wiley & Sons Ltd. A stage 3 furcation involvement exists when a periodontal probe extends under the crown of a multirooted tooth, through and through from one side of the furcation out the other. For Content on this Oral Health Topic page is for informational purposes only. 0000030272 00000 n Get Directions Disclaimer. Use for phrases . The bacteria in plaque are predominantly nonmotile, gram-positive aerobes, including Staphylococcus spp and Streptococcus spp, but many others are also present. No special 3. Staging intends to classify the severity and extent of a patients disease based on a measurable amount of destroyed/damaged tissue from periodontitis. Stage 1: There is gingivitis only, without attachment loss; the height and architecture of the alveolar margin are normal. Methods and Results A 62-year-old South Asian female presented with unstable Stage IV Grade C periodontitis, poor oral hygiene and multiple autoimmune conditions including oral lichen planus. Oral Microbiome, Oral Health and Systemic Health: A Multidirectional Link. Some dogs and cats may not allow regular toothbrushing, so the plaque should be removed by wiping with a gauze pad at least every second or third day. Know, V.; Caton, J.C. Commentary: Prognosis revisited a system for assigning periodontal prognosis. J. Clin. Liu Z, Gao X, Liang L, Zhou X, Han X, Yang T, Huang K, Lin Y, Deng S, Wang Z, Wang C. J Inflamm Res. ); diagnosis of GPIIIIVC [. 0000028483 00000 n 2013;26(2):84-8. Buffoli, B.; Garzetti, G.; Calza, S.; Scotti, E.; Borsani, E.; Cappa, V.; Rimondini, L.; Mensi, M. Periodontitis Stage IIIIV, Grade C and Correlated Factors: A Histomorphometric Study. An official website of the United States government. Dementias: Periodontitis and periodontal pathogens have been associated with dementias and Alzheimers Disease. Today's Digital Media, LLC d/b/a Today's RDH, New AAP Periodontal Classification Guidelines, Periodontal Maintenance: Taking the Guesswork out of the 4910, Top 10 Essentials for Every Hygienists Toolkit, http://perio.org/sites/default/files/files/Staging%20and%20Grading%20Periodontitis.pdf, Periodontal Inflammation Linked to Vision Loss. F: 904-249-8554, 1409 Kingsley Avenue, Suite 9A, Females showed a significant increase in inflammatory infiltrate compared to males (6.29% vs. 2.28%. The data show that the test group achieved better results, with greater reductions in PPD, gains in CAL, and decreases in BDH, BDD, MD BDW, BLBDW, and BDV. Association between periodontitis and arterial hypertension: A systematic review and meta-analysis. Pathogenesis of inflammatory periodontal disease. The owner might falsely believe the condition has been treated, while periodontal disease continues to thrive. Hu KF, Ho YP, Ho KY, Wu YM, Wang WC, Chou YH. Deep infrabony defects in multirooted teeth with bone loss that undermines a furcation can infect the pulp through a furcation canal, resulting in secondary endodontic disease. Considering the involvement of these two processes in GPIIIIVC pathogenesis, the aim of our study was to evaluate these histomorphological alterations in relation to some important factors (e.g., smoking, gender, age, plaque, pus, and PPD (probing pocket depth)), known as periodontal disease-associated factors. Vladau, M.; Cimpean, A.M.; Balica, R.A.; Jitariu, A.A.; Popovici, R.A.; Raica, M. VEGF/VEGFR2 Axis in Periodontal Disease Progression and Angiogenesis: Basic Approach for a New Therapeutic Strategy. 0000110265 00000 n 0000065735 00000 n Periodont. The American Academy of Periodontology defines non-surgical treatment as the professional removal of supragingival and subgingival bacterial plaque or biofilm and calculus, which provides a biologically acceptable root surface, as well as patient adoption of a comprehensive daily plaque or biofilm control routine. Newman and Carranzas Clinical Periodontology. The .gov means its official. ( A , B ): Hematoxylin and eosin staining (100) showing inflammatory cells, MeSH sharing sensitive information, make sure youre on a federal the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, J Public Health Dent 2013;73(2):112-9. 2022 Dec 10;10(12):2505. doi: 10.3390/healthcare10122505. -, Tonetti M.S., Greenwell H., Kornman K.S. BMC Oral Health 2019;19(1):176. By including these grade modifiers, your periodontist can discuss taking an active role in the management of these conditions as well. Clinical periodontal measurements, real-time PoC aMMP-8, IFMA aMMP-8, and Western immunoblot analyses were performed before and 1 month after anti-infective scaling and root planing periodontal treatment. Staging and grading of periodontitis: Framework and proposal of a new classification and case definition. They would understand the severity of condition, urgency of consulting the dentist for treatment and that involvement of periodontist in treatment is necessary. Jepsen K, Jerve-Storm PM, Henrichs I, Lensing I, Mller AL, Cosgarea R, Keilig L, Bourauel C, Jepsen S. Clin Oral Investig. A stage 2 furcation involvement exists when a periodontal probe extends greater than halfway under the crown of a multirooted tooth with attachment loss but not through and through. The AAP released two documents titled Three Steps to Staging and Grading a Patient and Staging and Grading Periodontitis. A quick synopsis of the three stages are as follows; Step 1: Initial Case Overview to Assess Disease, the recommendation is to conduct a screening consisting of radiographs, probing depths, and missing teeth. J Clin Periodontol 2018;45 Suppl 20:S1-S8. Cornelini, R.; Artese, L.; Rubini, C.; Fioroni, M.; Ferrero, G.; Santinelli, A.; Piattelli, A. Vascular endothelial growth factor and microvessel density around healthy and failing dental implants. contributed reagents/materials/analysis tools; B.B. Combined periodontal and prosthodontic treatment demands of patients require a structured coordination of pretreatments and an adequate choice of restorations. Background: Int J Periodontics Restorative Dent. Risk factor analysis is used as grade modier. In Graetz's study, risk factors were not documented, and diabetic patients were de . The aim of this article is to report a comprehensive periodontal treatment in a 23-year-old male who was referred to the periodontology department due to complaints of tooth mobility and gum infections diagnosed with generalized stage IV, grade C periodontitis according to the clinical, systemic, and family history features observed. 2023 Jan 17;16:235-244. doi: 10.2147/JIR.S395777. PMC A stage 1 mobility is present when tooth mobility is increased in any direction other than axial over a distance of >0.2 mm and up to 0.5 mm. clinical guideline; dental implant; orthodontic; periodontitis; prosthodontic; stage IV. Int. Ramesh A, Ravi S, Kaarthikeyan G. Comprehensive rehabilitation using dental implants in generalized aggressive periodontitis. %i}F/5>e3cv4qg j. Periodontal disease is classified in stages. More importantly, predisposing factors should be identified and removed. https://doi.org/10.3390/biomedicines7020043, Buffoli, Barbara, Gianluca Garzetti, Stefano Calza, Eleonora Scotti, Elisa Borsani, Veronica Cappa, Lia Rimondini, and Magda Mensi. Sarah Ostrander, RDH, MS, is a Clinical Educator in Global Curriculum Development. Sarah has received her associate, bachelor and master degrees in dental hygiene with an education focus. Int Dent J 2021;71(6):462-76. Jepsen S, Caton JG, Albandar JM, et al. Manresa C, Sanz-Miralles EC, Twigg J, Bravo M. Supportive periodontal therapy (SPT) for maintaining the dentition in adults treated for periodontitis. %PDF-1.4 % QUIZ: How Much Do You Know about Polishing? Journal of Dental Research, 85(6), 547-551. With this assumption, we decided to discuss the results factor by factor for simplifying the comprehension. Evidence of the association of periodontitis with systemic conditions is mixed (see the related Oral Health Topic page, Oral/Systemic Health). Prakash, P.; Rath, S.; Mukherjee, M.; Malik, A.; Boruah, D.; Sahoo, N.K. Maxillary canine teeth with pockets on their palatal side that have already progressed to form an oronasal fistula require extraction and oronasal fistula repair. West N, Chapple I, Claydon N, D'Aiuto F, Donos N, Ide M, Needleman I, Kebschull M; British Society of Periodontology and Implant Dentistry Guideline Group Participants. . The current classification system was endorsed by the American Dental Association in 2021. Recent epidemiologic trends in periodontitis in the USA. ; Lee, J.H. Generalized periodontitis Stage IV Grade C Immunology of periodontitis Innate immunity: In innate immunity, the role of neutrophils, Toll-like receptors and defensins has been well studied. Federal government websites often end in .gov or .mil. 0000027419 00000 n ; E.S. Stage 2: There is early periodontitis with < 25% of attachment loss or, at most, there is a stage 1 furcation involvement in multirooted teeth (see below). Depending on disease distribution and extent, periodontitis can be categorized into a localized (<30% of teeth involved) generalized or molar/incisor pattern [, The worst periodontal condition is evident in patients with generalized stage IIIIV, grade C periodontitis. Results: Females showed a significant increase in the percentage of inflammatory cells compared to males (6.29% vs. 2.28%, Periodontitis is a disease that, if untreated, leads to serious functional and aesthetic impairments, as well as a strong conditioning of social life, resulting in impairment in life quality [, This disease is characterized by a microbially-associated, host-mediated inflammation that results in the loss of periodontal attachment, clinically detected as clinical attachment loss (CAL) [, In 2018, the American Academy of Periodontology and the European Federation of Periodontology published a new classification of periodontal diseases. . Prevention of periodontitis is more complicated. ; M.M. Preshaw, P.M.; Henne, K.; Taylor, J.J.; Valentine, R.A.; Conrads, G. Age-related changes in immune function (immune senescence) in caries and periodontal diseases: A systematic review. The inclusion criteria were age older than 18 years; no systemic illnesses or disorders; no medical treatment that may impair healing (immunodepression, immunosuppression, diabetes, etc. official website and that any information you provide is encrypted Eke PI, Borgnakke WS, Genco RJ. 2015;69:717. 22. Chapple ILC, Mealey BL, Van Dyke TE, et al. Results: The S3 Level CPG for the treatment of stage IV periodontitis culminated in recommendations for different interventions, including orthodontic tooth movement, tooth splinting,. Journal of Dental Research, 79(9), 1659-1663. ; Greenwell, H.; Kornman, K.S. A systematic review and meta-analysis. 2021 Mar 18;10(6):1262. doi: 10.3390/jcm10061262. Before 0000094964 00000 n Journal of Public Health Dentistry, 81(3), 206-213. Editors select a small number of articles recently published in the journal that they believe will be particularly Papapanou PN, Sanz M, Buduneli N, et al. generalized). Malinowski, B.; Wsierska, A.; Zalewska, K.; Sokoowska, M.M. 2017 Jun;44(6):612-9. A summary of current work. Periodontitis Stage III-IV, Grade C and Correlated Factors: A Histomorphometric Study Authors Barbara Buffoli 1 , Gianluca Garzetti 2 , Stefano Calza 3 , Eleonora Scotti 4 , Elisa Borsani 5 , Veronica Cappa 6 7 , Lia Rimondini 8 9 , Magda Mensi 10 Affiliations Stage 3-4, Grade C periodontitis (at least one site with probing depth (PD) and clinical attachment level (CAL) 5 mm in their incisors and/or first molars and at least 6 other teeth with similar PD and CAL measurements, with alveolar bone loss confirmed by radiography; familial aggregation; presence of 16 teeth; Stefanski S, Svensson B, Thor A. Implant survival following sinus membrane elevation without grafting and immediate implant installation with a one-stage technique: an up-to-40-month evaluation. Periodontal disease and cancer: Epidemiologic studies and possible mechanisms. 8600 Rockville Pike Get Directions The percentage of inflammatory cells and the vascular area were measured and evaluated in relation to each periodontal disease-associated factor. The loss of periodontal attachment is < 25% as measured by probing of the clinical attachment level or by radiographic determination of the distance of the alveolar margin from the cementoenamel junction relative to the length of the root. The percentage of inflammatory cells and the vascular area were measured and evaluated in relation to each periodontal disease-associated factor. Lang, N.P. Prior to treatment planning, it is critically important to undertake a definitive and comprehensive diagnosis and case evaluation, obtain relevant patient information, and engage in frequent re-evaluations during and after treatment. A 2018 systematic review by Graziani et al. All in all, this Staging and Grading system helps your periodontist provide a patient-centered evaluation and treatment plan as well as an effective way to communicate more clearly with our patients. Effects of smoking on non-surgical periodontal therapy in patients with periodontitis Stage III or IV, and Grade C. Chronic Periodontitis Prevention, Diagnosis and Treatment: A Systematic Review [Internet]. Maintenance visit regularity has a different impact on periodontitis-related tooth loss depending on patient staging and grading. Kwon T, Lamster IB, Levin L. Current Concepts in the Management of Periodontitis. 2022 Dec 16;12(12):2131. doi: 10.3390/life12122131. Int J Dent Hyg. Associations, though not causal relationships, with periodontitis have been suggested for several conditions: Notably, the 2017 system published by AAP/EFP eliminates use of the diagnostic categories Chronic and Aggressive periodontitis. Extent and distribution can be further subdivided into localized (<30% of teeth involved) or generalized (>30% of teeth involved). J Clin Periodontol 2021;48(8):1008-18. Chronic kidney disease: Although there is no evidence on causal association, studies have shown a high periodontitis prevalence in chronic kidney disease populations also demonstrating racial and ethnic disparities. Despite the bone damage, the amount of bone loss in this stage of periodontal disease is minor so that usually no additional treatment is required. A new classification scheme for periodontal and peri-implant diseases and conditions Introduction and key changes from the 1999 classification. doi: 10.1111/jcpe.12945. The most significant effect is related to smoking in patients with a similar periodontal condition. ; Sanz, M.; Tonetti, M. A new classification scheme for periodontal and peri-implant diseases and conditionsIntroduction and key changes from the 1999 classification. F: 904-443-7012, 252 15th Avenue South, If the plaque becomes very thick because of poor oral hygiene and oxygen within the plaque is depleted, the bacterial population can become more pathogenic, with a higher percentage of nonmotile, gram-negative anaerobic rods. ; Michalowicz, B.S. Due to the high number of zeros, the gingival recession was summarized both as the percentage of zero values and the geometric mean and sd of non-zero values. Considering the presence/absence of pus, no significant differences were observed. Supportive periodontal treatment: Pocket depth changes and tooth loss. Periodontal disease increases with age, 70.1% of adults 65 years and older have . Rheumatoid arthritis: A 2020 systematic review indicates that periodontitis may increase the risk of developing rheumatoid arthritis. J Med Case Rep. 2015;9:211. Your IP: Subsiding of Periodontitis in the Permanent Dentition in Individuals with Papillon-Lefvre Syndrome through Specific Periodontal Treatment: A Systematic Review. Pihlstrom, B.L. Stage IV periodontitis shares the severity and complexity characteristics of stage III periodontitis, but includes the anatomical and functional sequelae of tooth and periodontal attachment loss (tooth flaring and drifting, bite collapse, etc. 0000099634 00000 n Wang Q, Sun Y, Zhou T, Jiang C, A L, Xu W. Front Cell Infect Microbiol. In these situations, significantly rapid progressive damage to the attachment apparatus, which can lead (especially in stage IV) to tooth loss and occlusion impairment, is appreciated [, About the etiology of this pathology, periodontitis is a complex disease with a genetic and epigenetic basis and/or causes related to patient behaviors (e.g., medications or environmental factors), which contribute to the progression of the periodontal lesion. . The goal of periodontal treatment is to eliminate dysbiotic plaque biofilm from the tooth surface and to establish an environment that allows the maintenance of health. Appropriate care: Periodontal therapy* including periodontal surgery will only be successful if the client is committed to consistently administering home dental care. The recently published clinical practice guideline (CPG) for the treatment of periodontitis in stages I-III provided evidence-based recommendations for the treatment of periodontitis patients, defined according to the 2018 classification. Tonetti, M. S. (2018). ; E.B. The results are reported as the estimates and 95% confidence intervals. ; Bursiewicz, W.; Socha, M.; Ozorowski, M.; Pawlak-Osiska, K.; Wiciski, M. The role of Tannerella forsythia and Porphyromonas gingivalis in pathogenesis of esophageal cancer. J Periodontol 2018;89 Suppl 1:S74-S84. Under the 2017 system, the current categories of periodontitis are3, Necrotizing periodontal diseases feature papilla necrosis, bleeding, and pain, and are associated with impaired immune response,3 Periodontitis as a manifestation of systemic disease focuses on diseases and conditions other than diabetes (e.g., genetic disorders, neoplasms, and other metabolic and endocrine disorders).4, 20. Shin, Y.J. Velidandla S, Bodduru R, Birra V, Jain Y, Valluri R, Ealla KKR. J Am Dent Assoc 2015;146(7):525-35. Distribution of Periodontal Pockets Among Smokers and Nonsmokers in Patients with Chronic Periodontitis: A Cross-sectional Study. Zhonghua Kou Qiang Yi Xue Za Zhi. 8 The host response to the bacterial challenge leads to clinical signs such as deep pockets, bleeding on probing, gingival recession, and tooth mobility, which can ultimately cause tooth loss. most exciting work published in the various research areas of the journal. 8600 Rockville Pike 2007 Dec;78(12):2229-37. During the one and two-year follow-ups, the teeth and implants did not show any signs of instability, attachment loss or bone loss. doi: 10.1111/prd.12104. Extensive disease seen in younger patients or with minimal bacterial deposits represents a high rate of progression (Grade C). Grade of periodontitis is estimated with direct or indirect evidence of progression rate in three categories: slow, moderate and rapid progression (Grade A-C). 2005;366:18091820. Affiliations. 0000101987 00000 n This can reverse gingivitis, returning the gingiva to a healthy, uninflamed state. If the gingivitis does not resolve, further examination should be performed to identify additional complicating conditions such as persistent subgingival plaque and calculus or the presence of predisposing factor(s). [Introduction and interpretation of the European Federation of Periodontology S3 level clinical practice guideline for treatment of periodontitis]. Age, gender, smoking habits, and clinical and dental history were collected during clinical assessments. Clin Oral Implants Res. A separate guideline covering the treatment of Stage IV periodontitis will be published. Dental cleaning on an awake animal improves the cosmetic appearance of the tooth crowns but does not improve periodontal health. All articles published by MDPI are made immediately available worldwide under an open access license. Dementia and the Risk of Periodontitis: A Population-Based Cohort Study. This treatment of periodontal disease can be non-surgical or surgical with the optimal treatment being based on individual patient, site, and systemic factors. The teeth should be brushed daily to remove plaque and prevent calculus (tartar) accumulation. Get Directions Periodontol 2000 2020;83(1):213-33. A pet dog or cat can function perfectly fine without teeth. and M.M. 0000029838 00000 n Epub 2021 Jul 19. Clin Oral Implants Res. Deas DE, Mealey BL. J Formos Med Assoc. Background: Sex differences in destructive periodontal disease: Exploring the biologic basis. The site is secure. Materials and methods: Careers. https://doi.org/10.3390/biomedicines7020043, Subscribe to receive issue release notifications and newsletters from MDPI journals, You can make submissions to other journals. Periodontitis is a more severe disease that involves inflammation of the periodontal ligament and alveolar bone, eventually causing loss of attachment (periodontal pocketing, gingival recession, bone resorption). Int J Periodontics Restorative Dent. 2000. The American Academy of Periodontology (AAP) announced new periodontal classifications for the AAP Guidelines. 2017 Mar-Apr;21(2):160-3. Periodontitis is much more common in certain dog and cat breeds, but it can affect any individual. American Academy of Periodontology Surgical Procedures. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). 0000026481 00000 n Keywords: 16 38 Peri-implant diseases and conditions: Consensus report of workgroup 4 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. Mengel R, Behle M, Flores-de-Jacoby L. Osseointegrated implants in subjects treated for generalized aggressive periodontitis: 10-year results of a prospective, long-term cohort study. GPIIIIVC patients have been chosen to better define the histomorphological characteristics of a low prevalence illness. Periodontal disease is a chronic infection that can result in the destruction of tooth-supporting structures (i.e., the gingiva, periodontal ligament, and/or alveolar bone) and eventual tooth loss.6, According to analysis of data from the National Health and Nutrition Examination Survey (NHANES) collected from 2009 to 2014, roughly 42% of dentate adults 30 years of age or older in the United States have some form of periodontitis (mild, moderate or severe).7 The prevalence of periodontitis increases with age; it is significantly more common in males than in females, and in non-Hispanic Blacks and Hispanics than non-Hispanic whites.7. 2022 May;52(3):511-525. hb``f``g`e`\ @16s0080 ^`K'4m`6GH00@QegVc4kX71j0~dH'X!~uZ)FB Z00% (; J( endstream endobj 17 0 obj <>>> endobj 18 0 obj <>/Font<>/ProcSet[/PDF/Text]/Properties<>>>/Rotate 0/TrimBox[0.0 0.0 792.0 612.0]/Type/Page>> endobj 19 0 obj <> endobj 20 0 obj <>stream Jambhekar S, Kernen F, Bidra AS. ; Albandar, J.M. Cochrane Database Syst Rev 2018;1:CD009376. ed. Kamil W, Al Bayati L, Hussin AS, Hassan H. Reconstruction of advanced bone defect associated with severely compromised maxillary anterior teeth in aggressive periodontitis: a case report. ; Mealey, B.L. The .gov means its official. Al-Zahrani, M. S., Alhassani, A. The charts below provide an overview. Within the limitations of the present studythe sample sizeour results show a significant decrease in the percentage of the vascular area in association with smoking, age, and plaque and of inflammatory cell percentage in association with gender and smoking. Durable bonds at the adhesive/dentin interface: an impossible mission or simply a moving target. Awad, M. A., Locker, D., Korner-Bitensky, N., & Feine, J. S. (2000). Measuring the effect of intra-oral implant rehabilitation on health-related quality of life in a randomized controlled clinical trial. Feature papers are submitted upon individual invitation or recommendation by the scientific editors and must receive Before ; Kim, H.D. Use OR to account for alternate terms While associations between periodontitis and various systemic conditions and diseases have been suggested by research, evidence of causality is mixed and the strength of the evidence differs for various conditions. For mild to moderate periodontitis, the focus will be on clinical attachment loss (CAL). Caton JG, Armitage G, Berglundh T, et al. articles published under an open access Creative Common CC BY license, any part of the article may be reused without MeSH The vascular area was also more than halved in subjects with residual plaque on tooth surfaces (0.74% vs. 0.36%, p-value = 0.0005).

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