Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) slows the progression of caries and remineralizes enamel subsurface lesions. The aim of this study was to determine the ability of CPP-ACP ...to increase the incorporation of fluoride into plaque and to promote enamel remineralization in situ. Randomized, double-blind, cross-over studies involved mouthrinses and dentifrices containing CPP-ACP and fluoride. The mouthrinses were used for 60 sec, three times/day for 5 days, and supragingival plaque was collected and analyzed for F. The dentifrices were rinsed as a water slurry for 60 sec four times/day for 14 days in an in situ model. The addition of 2% CPP-ACP to the 450-ppm-F mouthrinse significantly increased the incorporation of fluoride into plaque. The dentifrice containing 2% CPP-ACP produced a level of remineralization similar to that achieved with a dentifrice containing 2800 ppm F. The dentifrice containing 2% CPP-ACP plus 1100 ppm F was superior to all other formulations.
Dental caries is a highly prevalent diet-related disease and is a major public health problem. A goal of modern dentistry is to manage non-cavitated caries lesions non-invasively through ...remineralization in an attempt to prevent disease progression and improve aesthetics, strength, and function. Remineralization is defined as the process whereby calcium and phosphate ions are supplied from a source external to the tooth to promote ion deposition into crystal voids in demineralized enamel, to produce net mineral gain. Recently, a range of novel calcium-phosphate-based remineralization delivery systems has been developed for clinical application. These delivery systems include crystalline, unstabilized amorphous, or stabilized amorphous formulations of calcium phosphate. These systems are reviewed, and the technology with the most scientific evidence to support its clinical use is the remineralizing system utilizing casein phosphopeptides to stabilize and deliver bioavailable calcium, phosphate, and fluoride ions. The recent clinical evidence for this technology is presented and the mechanism of action discussed. Biomimetic approaches to stabilization of bioavailable calcium, phosphate, and fluoride ions and the localization of these ions to non-cavitated caries lesions for controlled remineralization show promise for the non-invasive management of dental caries.
Orthodontic patients have an increased risk of white-spot lesion formation. A clinical trial was conducted to test whether, in a post-orthodontic population using fluoride toothpastes and receiving ...supervised fluoride mouthrinses, more lesions would regress in participants using a remineralizing cream containing casein phosphopeptide- amorphous calcium phosphate compared with a placebo. Forty-five participants (aged 12–18 yrs) with 408 white-spot lesions were recruited, with 23 participants randomized to the remineralizing cream and 22 to the placebo. Product was applied twice daily after fluoride toothpaste use for 12 weeks. Clinical assessments were performed according to ICDAS II criteria. Transitions between examinations were coded as progressing, regressing, or stable. Ninety-two percent of lesions were assessed as code 2 or 3. For these lesions, 31% more had regressed with the remineralizing cream than with the placebo (OR = 2.3, P = 0.04) at 12 weeks. Significantly more post-orthodontic white-spot lesions regressed with the remineralizing cream compared with a placebo over 12 weeks.
There is compelling evidence that treponemes are involved in the etiology of several chronic diseases, including chronic periodontitis as well as other forms of periodontal disease. There are ...interesting parallels with other chronic diseases caused by treponemes that may indicate similar virulence characteristics. Chronic periodontitis is a polymicrobial disease, and recent animal studies indicate that co-infection of Treponema denticola with other periodontal pathogens can enhance alveolar bone resorption. The bacterium has a suite of molecular determinants that could enable it to cause tissue damage and subvert the host immune response. In addition to this, it has several non-classic virulence determinants that enable it to interact with other pathogenic bacteria and the host in ways that are likely to promote disease progression. Recent advances, especially in molecular-based methodologies, have greatly improved our knowledge of this bacterium and its role in disease.
Summary
Outer membrane vesicles (OMVs) are asymmetrical single bilayer membranous nanostructures produced by Gram‐negative bacteria important for bacterial interaction with the environment. ...Porphyromonas gingivalis, a keystone pathogen associated with chronic periodontitis, produces OMVs that act as a virulence factor secretion system contributing to its pathogenicity. Despite their biological importance, the mechanisms of OMV biogenesis have not been fully elucidated. The ~14 times more curvature of the OMV membrane than cell outer membrane (OM) indicates that OMV biogenesis requires energy expenditure for significant curvature of the OMV membrane. In P. gingivalis, we propose that this may be achieved by upregulating the production of certain inner or outer leaflet lipids, which causes localized outward curvature of the OM. This results in selection of anionic lipopolysaccharide (A‐LPS) and associated C‐terminal domain (CTD) ‐family proteins on the outer surface due to their ability to accommodate the curvature. Deacylation of A‐LPS may further enable increased curvature leading to OMV formation. Porphyromonas gingivalis OMVs that are selectively enriched in CTD‐family proteins, largely the gingipains, can support bacterial coaggregation, promote biofilm development and act as an intercessor for the transport of non‐motile bacteria by motile bacteria. The P. gingivalis OMVs are also believed to contribute to host interaction and colonization, evasion of immune defense mechanisms, and destruction of periodontal tissues. They may be crucial for both micro‐ and macronutrient capture, especially heme and probably other assimilable compounds for its own benefit and that of the wider biofilm community.
Summary
Background The British Association of Dermatologists (BAD) established a web‐based pharmacovigilance register to assess the long‐term safety of biologics prescribed for patients with severe ...psoriasis in September 2007. The BAD Biologic Interventions Register (BADBIR) also participates in the network of European psoriasis biologics registers (Psonet).
Objectives This prospective observational cohort study compares adult patients with psoriasis treated with biologics vs. a comparator group exposed to conventional systemic therapies.
Methods Following baseline data acquisition, clinicians record changes in therapy, disease activity and adverse events for 5 years (6‐monthly for 3 years, then annually thereafter). Patient details are flagged lifelong on the National Health Service Information Centre system to capture occurrence of malignancy or death. Primary study endpoints include malignancy, infection, serious adverse events and death. Collection of long‐term effectiveness data is a subsidiary aim.
Results By November 2011, the number of dermatology centres actively recruiting across the U.K. and Republic of Ireland had risen to 108 and a further 37 were actively engaged in the set‐up process. Of the 3176 patients enrolled in the study to date, 2193 were registered within the biologic cohort and 983 in the conventional systemic (nonbiologic‐exposed) cohort.
Conclusions A robust, high‐quality, web‐based register of biologic and conventional therapy for psoriasis has been established in the U.K. This is the largest project undertaken by the BAD. The data it will provide over the coming years will be invaluable to the safe use of biologics in clinical practice. A U.K.‐wide dermatology clinical research network has been established that provides a framework for future studies in other diseases.
Dental caries remains a major public health problem in most communities even though the prevalence of disease has decreased since the introduction of fluorides. The focus in caries research has ...recently shifted to the development of methodologies for the detection of the early stages of caries lesions and the non‐invasive treatment of these lesions. Topical fluoride ions, in the presence of calcium and phosphate ions, promote the formation of fluorapatite in tooth enamel by a process referred to as remineralization. The non‐invasive treatment of early caries lesions by remineralization has the potential to be a major advance in the clinical management of the disease. However, for net remineralization to occur adequate levels of calcium and phosphate ions must be available and this process is normally calcium phosphate limited. In recent times three calcium phosphate‐based remineralization systems have been developed and are now commercially available: a casein phosphopeptide stabilized amorphous calcium phosphate (RecaldentTM (CPP‐ACP), CASRN691364‐49‐5), an unstabilized amorphous calcium phosphate (ACP or EnamelonTM) and a bioactive glass containing calcium sodium phosphosilicate (NovaMinTM). The purpose of this review was to determine the scientific evidence to support a role for these remineralization systems in the non‐invasive treatment of early caries lesions. The review has revealed that there is evidence for an anticariogenic efficacy of the EnamelonTM technology for root caries and for the RecaldentTM technology in significantly slowing the progression of coronal caries and promoting the regression of lesions in randomized, controlled clinical trials. Hence the calcium phosphate‐based remineralization technologies show promise as adjunctive treatments to fluoride therapy in the non‐invasive management of early caries lesions.
Summary
Background
The ‘treat to target’ paradigm improves outcomes and reduces costs in chronic disease management but is not yet established in psoriasis.
Objectives
To identify treatment targets ...in psoriasis using two common measures of disease activity: Psoriasis Area and Severity Index (PASI) and Physician's Global Assessment (PGA).
Methods
Data from a multicentre longitudinal U.K. cohort of patients with psoriasis receiving systemic or biologic therapies (British Association of Dermatologists Biologics and Immunomodulators Register, BADBIR) were used to identify absolute PASI thresholds for 90% (PASI 90) and 75% (PASI 75) improvements in baseline disease activity, using receiver operating characteristic curves. The relationship between PGA (clear, almost clear, mild, moderate, moderate–severe, severe) and PASI (range 0–72) was described, and the concordance between absolute and relative definitions of response was determined. The same approach was used to establish treatment response and eligibility definitions based on PGA.
Results
Data from 13 422 patients were available (58% male, 91% white ethnicity, mean age 44·9 years), including over 23 000 longitudinal PASI and PGA scores. An absolute PASI ≤ 2 was concordant with PASI 90 and an absolute PASI ≤ 4 was concordant with PASI 75 in 90% and 88% of cases, respectively. These findings were robust to subgroups of timing of assessment, baseline disease severity and treatment modality. PASI and PGA were strongly correlated (Spearman's rank correlation coefficient 0·92). The median PASI increased from 0 (interquartile range 0–0, range 0–23) to 19 (interquartile range 15–25, range 0–64) for PGA clear to severe, respectively. PGA clear/almost clear was concordant with PASI ≤ 2 in 90% of cases, and PGA moderate–severe severe was concordant with the National Institute for Health and Care Excellence PASI eligibility criteria for biologics in 81% of cases.
Conclusions
An absolute PASI ≤ 2 and PGA clear/almost clear represent relevant disease end points to inform treat‐to‐target management strategies in psoriasis.
What's already known about this topic?
The most commonly used relative disease activity measure in psoriasis is ≥ 90% improvement in Psoriasis Area and Severity Index (PASI 90); however, it has several limitations including dependency on a baseline severity assessment.
Defining an absolute target disease activity end point in psoriasis has the potential to improve patient outcomes and reduce costs, as demonstrated by treat‐to‐target approaches in other chronic diseases such as hypertension and diabetes.
The Physician's Global Assessment (PGA) is a popular alternative measure of psoriasis severity in daily practice; however, its utility has not been formally assessed with respect to PASI.
What does this study add?
An absolute PASI ≤ 2 corresponds with PASI 90 response and is a relevant disease end point for treat‐to‐target approaches in psoriasis.
There is a strong correlation between PASI and PGA.
PGA moderate–severe/severe may serve as an alternative eligibility criterion for biologics to PASI‐based definitions, and PGA clear/almost clear is an appropriate alternative absolute treatment end point.
What are the clinical implications of this work?
Absolute PASI ≤ 2 and PGA clear/almost clear represent relevant disease end points to inform treat‐to‐target management strategies in psoriasis.
Linked Editorial: Takeshita. Br J Dermatol 2020; 182:1075–1076.
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