No Dentistry Nobel Laureate

UPDATE below.

When I was approached by the Nobel Committee at Sweden’s Karolinska Institute in October last year, probably as having been recognized as “[h]older of [an] established post as full Professor[s] at the faculties of medicine in Sweden [or] holder[s] of similar post[s] at the faculties of medicine or similar institutions in Denmark, Finland, Iceland and Norway”; and invited to nominate a possible candidate for the Physiology and Medicine award 2017, I was wondering whether there would be a dentist who might deserve the honor.

According to Alfred Nobel’s (1833-1896) will,

[t]he said interest shall be divided into five equal parts, which shall be apportioned as follows: /- – -/ one part to the person who shall have made the most important discovery within the domain of physiology or medicine …

Well, I checked out most prolific and highly cited dentistry professionals (of course with a focus on Perio), made myself aware of previous years’ laureates, and immediately noticed there was none. Dentistry has made advances in the past hundred years or so, no doubt. But, when considering Perio (my field of interest), it might in fact be questioned whether our understanding of the pathogenesis of periodontal diseases has witnessed fundamental breakthroughs after, say, the late 1970s. Whether basic principles of treatment have changed. As a matter of fact, innovations, such as regenerative treatment, had no lasting effect as respective methods may be applied in a minority of lesions, i.e. deep infrabony lesions and a few furcation involvements only. And the main issues, prevention and treatment of more aggressive forms, seem to be yet unresolved. What appears to thrill both young and old dentists right now is a one-hundred-year-old claim of focal infection, the so-called Perio-Systemic link.

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Study on Possible Data Fabrication in Numerous Randomized Controlled Trials Casts Shade of Doubt on Highly Cited Perio-Systemic Paper

In a recent analysis of thousands of randomized controlled trials (RCT) in eight journals a simple method was offered which might enable skeptical scientist identification of data fabrication. Editor of the Anaesthesia journal John B. Carlisle of Torbay Hospital, UK, looked at baseline differences of means in more than 5000 randomized controlled trials, mainly in the field of Anesthesiology, but also more than 500 published in JAMA and more than 900 published in the New England Journal of Medicine [1]. His study went online earlier this week. Analyzed articles were published between 2000 and 2015. In brief, if randomization was successful, baseline differences should be small. Giving p-values for baseline differences (in order to indicate successful randomization) is actually discouraged since they are not really interpretable, but Carlisle calculated them anyway. If the null hypothesis is true, p-values have a uniform distribution. So p-values between 0 and 1 would be equally likely.

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Joint EFP-IDF Workshop on the Perio-Diabetes Link

Last weekend, EFP and International Diabetes  Federation (IDF) delegates, in partnership with Sunstar, had met in Madrid and had worked on guidelines for dentists, medical doctors and patients with periodontitis and/or diabetes. The EFP website features some key findings when reviewing the literature. In particular, it is claimed that,

evidence suggests that periodontitis patients have a higher chance of developing pre-diabetes and type-2 diabetes and that people with periodontitis and diabetes have more difficulty in keeping their blood-sugar levels under control. Furthermore, patients with both diseases are more likely to develop diabetic complications than people with diabetes without periodontitis.

Current evidence indicates that in people with diabetes, periodontal therapy accompanied by effective self-performed oral hygiene at home is both safe and effective – even in people with poorly controlled diabetes. Similarly, there is consistent evidence that periodontal therapy reduces blood-sugar levels in people with diabetes and periodontitis. (Emphasis added.)

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A Restrictive Approach to the Use of Antibiotics in Periodontics

According to Dr. Bjarne Klausen from Esbjerg, Danish National Clinical Guidelines for the use of antibiotics in dental practice had recently been finalized. See a quick guide here [pdf]. As regards periodontal infection, he writes,

We formulated a focused question that was in line with the Scandinavian consensus: Should prescription of antibiotics be considered in patients with sufficient oral hygiene, if their periodontal condition does not respond to conventional treatment?

Well, they did not find a single relevant study. How’s that? Isn’t it so that dozens if not hundreds of studies had been performed since the early discovery by Jørgen Slots in Copenhagen identifying an unidentified gram-negative rod in abundance in what was then localized juvenile periodontitis? Soon later it was clear that this bug was Actinobacillus (now Aggregatibacter) actinomycetemcomitans, and that it could best be targeted by systemic antibiotics in conjunction with traditional mechanical/surgical periodontal treatment. Soon after a couple of case series by  van Winkelhoff et al. in 1989 and 1992, Amoxicillin plus Metronidazole (the infamous “van Winkelhoff cocktail”) became extremely popular and has since then been mentioned in national guidelines for the treatment of severe periodontitis where A. actinomycetemcomitans could be found in abundance.

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Periodontal Myths And Mysteries Series (VI) Discoveries

In a recent commentary in the Journal of Periodontology, Merchant and Josey (2016) had suggested directed acyclic graphs to better comprehend the partly conflicting results from randomized controlled trials (RCT) on diabetic control after periodontal treatment in diabetic patients. In particular the influence of obesity caught their attention.

As a matter of fact, a remarkable number of systematic reviews (whose varying quality have recently been reviewed in at least two further SRs of SRs) have shown that numerous small-scale, single-center, often poorly designed RCTs had shown that the marker for diabetic control, HbA1c, might be reduced by, say 0.4% 3 months after in essence non-surgical periodontal therapy. The only large-scale, multi-center trial (DPTT) by Engebretson et al. (2013) couldn’t confirm that, though, which sparked harsh criticism of a large number of our thought leaders. A professor in the Department of Epidemiology and Biostatistics at the University of South Carolina, Columbia, Dr. Anwar Merchant himself had written a letter to the editors of JAMA pointing first to the fact that most participants in the paper by Engebretson et al. were utterly obese. He had further noticed that, “[i]n RCTs conducted among mostly nonobese individuals, periodontal treatment has been shown to reduce systemic inflammation2,4 and improve glycemic control among those with type 2 diabetes.2 However, periodontal treatment has not been shown to affect glycemic control in RCTs conducted among predominantly obese individuals with type 2 diabetes.1,3

Obesity is positively correlated with inflammatory markers in the blood and strongly related to insulin resistance and metabolic dysregulation mediated by chronic systemic inflammation.5 These findings, taken together with results from RCTs evaluating the effects of periodontal treatment, suggest that the lack of effect of periodontal treatment on glycemic control observed in the study by Engebretson et al may be attributed to the high level of obesity in the study population. Therefore, the findings may be generalizable only to predominantly obese populations with type 2 diabetes.

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