Currently, and apparently, data of a large study, which has been collected in the U.S. and Sweden between 1999 and 2004, is being published in two series of papers. The purpose is to report clinical and microbiological observations made in a randomized controlled trial in which seven different treatments (periodontal surgery, systemic amoxicillin and metronidazole, topical tetracycline fibers, and all combinations) were compared to standard periodontal therapy, i.e., scaling and root planing alone, in hundreds of patients with chronic periodontitis. A criticized traditional approach to data analysis where huge numbers of site-specific data were aggregated at the patient level (and highly valuable site-specific data is lost) seems to be published in our major journal, Journal of Clinical Periodontology, see, for example, the most recent paper by Socransky et al. (2013). Site-specific data analyses, at least seemingly taking into account the hierarchical structure and non-independence of observations made in a given subject are dealt with in papers which appear in the open access Journal of Oral Microbiology. I had critically commented on the previous paper by Mdala et al. (2012) [pdf] on multilevel modeling on clinical parameters after eight different treatment modalities before on this blog, see here. There I wrote,
Unfortunately, the random parts in the models (whose design has to be considered insufficient) are not explained or even shown […] although one would like to see variance partition at the subject, tooth, and site levels, and whether common rules of thumb in decision making mainly based on site-specific clinical features hold. Frequently reported problems with extrabinomial variation, in particular underdispersion, in multilevel logistic regression models of periodontal data […] are not discussed. The main purpose of applying rather sophisticated models apparently was estimation based on just fixed effects rather than previous simple calculation of averages.
The new paper by Mdala et al. (2013) [pdf] on bacterial counts after complex treatment of chronic periodontitis, which erroneously keeps “multilevel analysis” in the title, has abandoned the idea of multilevel modeling of bacterial data. Instead, authors turn to the more traditional approach of marginal models such as Generalized Estimating Equations (GEE). GEE, which correctly takes into account the non-independence of observations made in a given subject, may indeed be preferred when interest is mainly on the effect of explanatory variables on the response, and correlation structure is rather considered a nuisance. On the other hand, the main advantage of multilevel modeling as exercised in the previous paper by Mdala et al. (2012), with its unbiased dealing with the hierarchical structure of the data is, besides obtaining correct estimates of fixed effects, an analysis of the random part of the model, i.e., variances and covariances. It may indeed provide new and deep insights into phenomena and mechanisms operating at the level of interest, the periodontal site.
The American Academy of Periodontology features this month a paper by Eick et al. on hyaluronic acid (e.g. Gengigel, Merz Dental, Germany) as an adjunct after scaling and root planing. It might be interesting to search for comparable randomized clinical trials in order to get a clue as to whether application during and after phase (I) therapy (the hygienic phase) may in fact be recommended.
Hyaluronic acid is a linear polysaccharide of the extracellular matrix of several tissues including connective tissues of the periodontium. History, chemistry, origin in the body and its metabolism, and its unique physiochemical and biological properties have recently been reviewed by Dahiya and Kamal (2013).
Only papers written in English were sought using the focused question (PICO): “In patients with chronic periodontitis, does the adjunct application of hyarulonic acid during and after periodontal scaling and root planing lead to better results as regards periodontal probing parameters probing depth and/or clinical attachment loss than scaling and root planing alone.” Only studies of a minimum of 3 months duration were considered since at that time periodontal reevaluation maybe conducted and, if needed, further treatment planned.
As a rule, the list of items which outlined in the PRISMA statement was checked, i.e. preferred reporting items for systematic reviews and meta-analyses (PRISMA). A PubMed search using (“hyaluronic acid”[MeSH Terms] OR (“hyaluronic”[All Fields] AND “acid”[All Fields]) OR “hyaluronic acid”[All Fields]) AND (“periodontitis”[MeSH Terms] OR “periodontitis”[All Fields]) yields 34 papers. In total, five RCTs could be identified where adjunct hyaluronic acid was compared with scaling and root planing alone in patients with chronic periodontitis, Eick et al. (2013), Bevilacqua et al. (2012), Gontiya and Galgali (2012), Johannsen et al. (2009), and Xu et al. (2004). Note that the paper by Xu et al. (2004) had been republished in Chinese the same year. The pilot study by Pilloni et al. (2011) was not considered since only results of adjunct application of hyaluronic acid after toothbrushing were reported as compared to toothbrushing alone in patients with shallow pockets.