The Evidence for Caries Management by Risk Assessment (CAMBRA®).

A system for Caries Management by Risk Assessment (CAMBRA®) has been developed in California. The purpose of this article is to summarize the science behind the methodology, the history of the development of CAMBRA, and the outcomes of clinical application. The CAMBRA caries risk assessment (CRA) tool for ages 6 y through adult has been used at the University of California, San Francisco (UCSF), for 14 y, and outcome studies involving thousands of patients have been conducted. Three outcomes assessments, each on different patient cohorts, demonstrated a clear relationship between CAMBRA-CRA risk levels of low, moderate, high, and extreme with cavitation or lesions into dentin (by radiograph) at follow-up. This validated risk prediction tool has been updated with time and is now routinely used at UCSF and in other settings worldwide as part of normal clinical practice. The CAMBRA-CRA tool for 0- to 5-y-olds has demonstrated similar predictive validity and is in routine use. The addition of chemical therapy (antibacterial plus fluoride) to the traditional restorative treatment plan, based on caries risk status, has been shown to reduce the caries increment by about 20% to 38% in high-caries-risk adult patients. The chemical therapy used for high-risk patients is a combination of daily antibacterial therapy (0.12% w/v chlorhexidine gluconate mouth rinse) and twice-daily high-concentration fluoride toothpaste (5,000 ppm F), both for home use. These outcomes assessments provide the evidence to use these CRA tools with confidence. Caries can be managed by adding chemical therapy, based on the assessed caries risk level, coupled with necessary restorative procedures. For high- and extreme-risk patients, a combination of antibacterial and fluoride therapy is necessary. The fluoride therapy must be supplemented by antibacterial therapy to reduce the bacterial challenge, modify the biofilm, and provide prevention rather than continued caries progression.

Changes in Caries Risk in a Practice-Based Randomized Controlled Trial.

To demonstrate that Caries Management by Risk Assessment (CAMBRA) can be successfully implemented in dental practice, 30 dentists were recruited to perform a 2-y CAMBRA trial. Twenty-one dentists (18 private practices, 3 community clinics) participated in a randomized, controlled, parallel-arm, double-blind clinical trial with individual-level assignment of 460 participants to standard of care (control) versus active CAMBRA treatment (intervention). Control or active antimicrobial and remineralizing agents were dispensed at baseline and 6-, 12-, 18-, and 24-mo recall visits according to risk level and assigned treatment arm. Primary outcome measure was dentist-determined caries risk level at recall. Among initially high-risk participants, secondary outcomes were recorded disease indicators. Generalized estimating equations were used to fit log-linear models for each outcome while accounting for repeated measurements. At 24 mo, follow-up rates were 34.3% for high-risk participants (32.1% intervention, 37.1% control) and 44.2% for low-risk participants (38.7% intervention, 49.5% control). Among 242 participants classified as high caries risk at baseline (137 intervention, 105 control), a lower percentage of participants remained at high risk in the intervention group (statistically significant at all time points). At 24 mo, 25% in the intervention group and 54% in the control group remained at high risk ( P = 0.003). Among 192 participants initially classified as low risk (93 intervention, 99 control), most participants remained at low risk. At 24 mo, 89% in the intervention group and 71% in the control group were low caries risk ( P = 0.18). The percentage of initially high-risk participants with recorded disease indicators decreased over time in both intervention and control groups, being always lower for the intervention group (statistically significant at the 12- and 18-mo time point). In this practice-based clinical trial, a significantly greater percentage of high-caries-risk participants were classified at a lower risk level after CAMBRA preventive therapies were provided. Most participants initially assessed at low caries risk stayed at low risk (ClinicalTrials.gov NCT01176396).

Near-UV laser treatment of extrinsic dental enamel stains.

BACKGROUND AND OBJECTIVES: The selective ablation of extrinsic dental enamel stains using a 400-nm laser is evaluated at several fluences for completely removing stains with minimal damage to the underlying enamel. STUDY DESIGN/MATERIALS AND METHODS: A frequency-doubled Ti:sapphire laser (400-nm wavelength, 60-nanosecond pulse duration, 10-Hz repetition rate) was used to treat 10 extracted human teeth with extrinsic enamel staining. Each tooth was irradiated perpendicular to the surface in a back-and-forth motion over a 1-mm length using an ∼300-µm-diam 10th-order super-Gaussian beam with fluences ranging from 0.8 to 6.4 J/cm(2) . Laser triangulation determined stain depth and volume removed by measuring 3D surface images before and after irradiation. Scanning electron microscopy evaluated the surface roughness of enamel following stain removal. Fluorescence spectroscopy measured spectra of unbleached and photobleached stains in the spectral range of 600-800 nm. RESULTS: Extrinsic enamel stains are removed with laser fluences between 0.8 and 6.4 J/cm(2) . Stains removed on sound enamel leave behind a smooth enamel surface. Stain removal in areas with signs of earlier cariogenic acid attacks resulted in isolated and randomly located laser-induced, 50-µm-diam enamel pits. These pits contain 0.5-µm diam, smooth craters indicative of heat transfer from the stain to the enamel and subsequent melting and water droplet ejection. Ablation stalling of enamel stains is typically observed at low fluences (<3 J/cm(2) ) and is accompanied by a drastic reduction in porphyrin fluorescence from the Soret band. CONCLUSION: Laser ablation of extrinsic enamel stains at 400 nm is observed to be most efficient above 3 J/cm(2) with minimal damage to the underlying enamel. Unsound underlying enamel is also observed to be selectively removed after irradiation.

A randomized clinical trial of anticaries therapies targeted according to risk assessment (caries management by risk assessment).

This randomized parallel group clinical trial assessed whether combined antibacterial and fluoride therapy benefits the balance between caries pathological and protective factors. Eligible, enrolled adults (n = 231), with 1-7 baseline cavitated teeth, attending a dental school clinic were randomly assigned to a control or intervention group. Salivary mutans streptococci (MS), lactobacilli (LB), fluoride (F) level, and resulting caries risk status (low or high) assays were determined at baseline and every 6 months. After baseline, all cavitated teeth were restored. An examiner masked to group conducted caries exams at baseline and 2 years after completing restorations. The intervention group used fluoride dentifrice (1,100 ppm F as NaF), 0.12% chlorhexidine gluconate rinse based upon bacterial challenge (MS and LB), and 0.05% NaF rinse based upon salivary F. For the primary outcome, mean caries increment, no statistically significant difference was observed (24% difference between control and intervention groups, p = 0.101). However, the supplemental adjusted zero-inflated Poisson caries increment (change in DMFS) model showed the intervention group had a statistically significantly 24% lower mean than the control group (p = 0.020). Overall, caries risk reduced significantly in intervention versus control over 2 years (baseline adjusted generalized linear mixed models odds ratio, aOR = 3.45; 95% CI: 1.67, 7.13). Change in MS bacterial challenge differed significantly between groups (aOR = 6.70; 95% CI: 2.96, 15.13) but not for LB or F. Targeted antibacterial and fluoride therapy based on salivary microbial and fluoride levels favorably altered the balance between pathological and protective caries risk factors.

The role of remineralizing and anticaries agents in caries management.

The first ICNARA conference (International Conference on Novel Anticaries and Remineralizing Agents) was held in Chile in January, 2008, and the proceedings were published in Advances in Dental Research (Volume 21, 2009). That issue of Advances summarized the state of the science and set a research agenda for the future for two key components of caries management, namely, antibacterial agents and remineralizing agents. The second conference (ICNARA 2, January 2012) provided an update on science and new directions for research and clinical practice. Over the past decade, renewed efforts have been made across the world to establish proven methods of caries risk assessment and to provide direction for improved methods of caries management based upon risk levels. Evidence-based caries risk assessment tools are now available. The need for improved therapy to reduce the bacterial challenge that initiates the caries process, and to enhance remineralization, is now very clear. Fluoride therapy alone is insufficient to control the caries process in high-risk individuals. New remineralizing and anticaries products and new delivery systems are in development, and ICNARA 2 presents future technology for the management of dental caries.

Clinical efficacy and effects of xylitol wipes on bacterial virulence.

The aim of the study was to investigate whether xylitol-wipe use in young children prevented caries by affecting bacterial virulence. In a double-blinded randomized controlled clinical trial, 44 mother-child pairs were randomized to xylitol-wipe or placebo-wipe groups. Salivary mutans streptococci levels were enumerated at baseline, 6 months, and one year. Ten mutans streptococci colonies were isolated and genotyped from each saliva sample. Genotype-colonization stability, xylitol sensitivity, and biofilm formation of these isolates were studied. Despite a significant reduction in new caries at one year in the xylitol-wipe group, no significant differences were found between the two groups in levels of mutans streptococci. Children in the xylitol-wipe group had significantly fewer retained genotypes (p = 0.06) and more transient genotypes of mutans streptococci (p = 0.05) than those in the placebo-wipe group. At one year, there was no significant difference in the prevalence of xylitol-resistant genotypes or in biofilm formation ability of mutans streptococci isolates between the two groups. The mechanism of the caries-preventive effect of xylitol-wipe use may be related to the stability of mutans streptococci colonization. Further studies with genomic characterization methods are needed to determine specific gene(s) that account for the caries-preventive effect of xylitol.

Strategic protein target analysis for developing drugs to stop dental caries.

Dental caries is the most common disease to cause irreversible damage in humans. Several therapeutic agents are available to treat or prevent dental caries, but none besides fluoride has significantly influenced the disease burden globally. Etiologic mechanisms of the mutans group streptococci and specific Lactobacillus species have been characterized to various degrees of detail, from identification of physiologic processes to specific proteins. Here, we analyze the entire Streptococcus mutans proteome for potential drug targets by investigating their uniqueness with respect to non-cariogenic dental plaque bacteria, quality of protein structure models, and the likelihood of finding a drug for the active site. Our results suggest specific targets for rational drug discovery, including 15 known virulence factors, 16 proteins for which crystallographic structures are available, and 84 previously uncharacterized proteins, with various levels of similarity to homologs in dental plaque bacteria. This analysis provides a map to streamline the process of clinical development of effective multispecies pharmacologic interventions for dental caries.

Effect of sublethal CO2 laser irradiation on gene expression of streptococcus mutans immobilized in a biofilm.

Streptococcus mutans colonizing on tooth surfaces is one of the major causative agents of human dental caries. Despite numerous studies conducted on lasers and oral tissue interactions, little is known about the effect of laser energy on S. mutans gene expression in a biofilm form. The aim of this study was to investigate the effect of sublethal energies of CO(2) laser on biofilm and gene expression of the oral bacteria S. mutans immobilized in biofilm. S. mutans biofilm was irradiated with CO(2) laser. Vitality and construction of the biofilm were observed by confocal laser scanning microscopy and scanning electron microscopy. The effect of laser irradiation on gene expression was evaluated by DNA microarray. CO(2) laser irradiation had a dose effect on the viability of S. mutans immobilized in biofilm. A nonsignificant lethal effect was observed at 31 J/cm(2) while at higher energy of 70 and 144 J/cm(2) an antibacterial effect was recorded. The mode of antibacterial action seems to be from the inner layers toward the outer layer of the biofilm, indicating the influence of the surface on the killing effect. At 31 J/cm(2), microarray analysis indicated a moderate effect on S. mutans gene expression due to CO(2) laser irradiation, mainly down-regulating genes related to bacterial stress response. In conclusion, laser irradiation at sublethal energy had an effect on gene expression of S. mutans.

The top 100 most cited manuscripts in bladder cancer: A bibliometric analysis (review article).

BACKGROUND: Bladder cancer is one of the top 10 frequently occurring neoplasms worldwide and is responsible for over 150,000 deaths per annum. Bibliometric analysis helps further our knowledge of bladder cancer research, topics and trends. It is useful to identify the most influential articles and its impact pertinent to this field that has helped mould our understanding and management of bladder cancer. MATERIALS AND METHODS: Search terms related to bladder cancer were compiled and used to interrogate the Thompson Reuters Web of Science indexing database. The 100 most cited manuscripts in the English language were identified and further evaluated by theme, manuscript type, journal, year of publication, author and institution. RESULTS: The Web of Science search returned a total of 47,381 manuscripts. The median number of citations among the top 100 was 515, ranging from 2257 to 352. The greatest number of manuscripts in the top 100 were published in the Journal of Urology (n = 15), followed by the Journal of Clinical Oncology (n = 14) and European Urology (n = 13). The most cited paper (Stein et al. Journal of Clinical Oncology 2001, 2257 citations) reported on the long term outcomes from a large cohort of patients that underwent radical cystectomy and bilateral pelvic lymphadenectomy for transitional cell carcinoma. The most prevalent theme was the pathobiology of bladder cancer (n = 37) followed by oncological treatment (n = 17). The majority of manuscripts were of original research (n = 79) mainly based on basic science study design and published from institutions in the USA. CONCLUSION: The pathobiology and oncological treatment of bladder cancer were the areas with most citations within the top 100. This bibliometric analysis has identified influential articles in the field on bladder cancer, which provides a useful guide to authors as to what type of article constitutes a highly citable publication in this subject.

Sex cord stromal testicular tumors: a clinical series--uniformly stage I disease.

PURPOSE: Sex cord stromal testicular tumors are rare. Historically 10% of lesions are said to be malignant but to our knowledge there are no clinical or histological features that can accurately predict potential malignant behavior. Because of this, groups at some centers have advocated prophylactic retroperitoneal lymph node dissection in patients with clinical stage I disease. We reviewed our experience with these tumors to determine whether this policy is justified. MATERIALS AND METHODS: We retrospectively reviewed the records of all 38 men older than 18 years with sex cord stromal testicular tumors who were referred to the Wessex regional cancer center for treatment or pathological review during the 25-year period of 1982 to 2006. We then compared our series with a malignant sex cord stromal testicular tumor database generated from the world literature. RESULTS: All Wessex patients were treated with excision of the primary tumor alone and metastatic disease developed in none. All remained disease-free with an overall median survival of 6.8 years (range 1.4 to 25). Features in the literature favoring malignant behavior, ie metastatic disease, included larger tumors (mean 6.43 vs 1.71 cm), a high mitotic rate, tumor necrosis, angiolymphatic invasion, infiltrative margins and extratesticular extension (each p <0.0001). The malignant group had an overall median survival of 2.3 years (range 0.02 to 17.3). CONCLUSIONS: No patient had disease progression in our study, which is to our knowledge the largest reported United Kingdom series of sex cord stromal testicular tumors. Our data suggest that malignancy is uncommon and prophylactic retroperitoneal lymph node dissection is unjustified for clinical stage I disease.

Demineralization of porous solids.

When a porous ionic solid is placed in acid, the acid will dissolve surface material. When this dissolved material and the acid diffuse into the solid's pores, they can precipitate more solid. If the acid is buffered, the diffusing species can bring about precipitation in some regions and dissolution in others. When the porous solid contains several chemical species, the diffusion can precipitate one species and dissolve another. The results have implications for the demineralization of teeth.

Cross-sectional study of the prevalence, causes and management of hospital-onset diarrhoea.

BACKGROUND: The National Health Service in England advises hospitals collect data on hospital-onset diarrhoea (HOD). Contemporaneous data on HOD are lacking. AIM: To investigate prevalence, aetiology and management of HOD on medical, surgical and elderly-care wards. METHODS: A cross-sectional study in a volunteer sample of UK hospitals, which collected data on one winter and one summer day in 2016. Patients admitted ≥72 h were screened for HOD (definition: ≥2 episodes of Bristol Stool Type 5-7 the day before the study, with diarrhoea onset >48 h after admission). Data on HOD aetiology and management were collected prospectively. FINDINGS: Data were collected on 141 wards in 32 hospitals (16 acute, 16 teaching). Point-prevalence of HOD was 4.5% (230/5142 patients; 95% confidence interval (CI) 3.9-5.0%). Teaching hospital HOD prevalence (5.9%, 95% CI 5.1-6.9%) was twice that of acute hospitals (2.8%, 95% CI 2.1-3.5%; odds ratio 2.2, 95% CI 1.7-3.0). At least one potential cause was identified in 222/230 patients (97%): 107 (47%) had a relevant underlying condition, 125 (54%) were taking antimicrobials, and 195 (85%) other medication known to cause diarrhoea. Nine of 75 tested patients were Clostridium difficile toxin positive (4%). Eighty (35%) patients had a documented medical assessment of diarrhoea. Documentation of HOD in medical notes correlated with testing for C. difficile (78% of those tested vs 38% not tested, P<0.001). One-hundred and forty-four (63%) patients were not isolated following diarrhoea onset. CONCLUSION: HOD is a prevalent symptom affecting thousands of patients across the UK health system each day. Most patients had multiple potential causes of HOD, mainly iatrogenic, but only a third had medical assessment. Most were not tested for C. difficile and were not isolated.

Effects of fluoride dentifrices on enamel lesion formation.

An in vitro pH cycling model was used to test the hypothesis that the effects of 3 different fluoride compounds on de/remineralization are a function of the free fluoride ion concentration. Groups of 10 human enamel specimens were treated with one of: (a) amine fluoride (AmF), 1250 ppm F; (b) sodium monofluorophosphate (NaMFP), 1000 ppm F; (c) sodium fluoride (NaF), 1100 ppm F; (d) NaF, 250 ppm F; (e) Placebo (< 1 ppm F) dentifrices; or with aqueous solutions (f) NaF 900 ppm F or (g) NaF 30 ppm F. Lesions were assessed by cross-sectional microhardness. Mean +/- SEM DeltaZ (vol.% x microm) values of 3 dentifrices were: (a) 344 +/- 155, (b) 4259 +/- 257, and (c) 591 +/- 83. The AmF (1250 ppm F) was not statistically significantly different from the NaF (1100 ppm F) dentifrice in this model. The NaMFP (1000 ppm F) dentifrice, without hydrolysis, had only the same efficacy as the NaF (30 ppm F) aqueous solution.

Effects of fluoride on the interactions between amelogenin and apatite crystals.

Fluorosed enamel is more porous and less mineralized, possibly related to altered amelogenin-modulated crystal growth. The purpose of this study was to examine the role of fluoride in interactions between amelogenin and apatite crystals. Recombinant human amelogenin (rh174) was bound to carbonated hydroxyapatite containing various amounts of fluoride, and analyzed by protein assay, SDS PAGE, and AFM. Interactions between rh174 and fluoride were assayed by isothermal titration calorimetry (ITC). The initial binding rate of rh174, as well as total amount of rh174 bound to fluoride-containing carbonated hydroxyapatite, was greater than that in the control carbonated hydroxyapatite. Fluoride in solution at physiologic (5.3 micromolar, or 0.1 ppm) concentrations showed no significant effect on binding, but higher fluoride levels significantly decreased protein binding. ITC showed no interactions between fluoride and rh174. These results suggest that fluoride incorporation into the crystal lattice alters the crystal surface to enhance amelogenin binding, with no direct interactions between fluoride and amelogenin.

Dental caries: a dynamic disease process.

Abstract Dental caries is a transmissible bacterial disease process caused by acids from bacterial metabolism diffusing into enamel and dentine and dissolving the mineral. The bacteria responsible produce organic acids as a by-product of their metabolism of fermentable carbohydrates. The caries process is a continuum resulting from many cycles of demineralization and remineralization. Demineralization begins at the atomic level at the crystal surface inside the enamel or dentine and can continue unless halted with the end-point being cavitation. There are many possibilities to intervene in this continuing process to arrest or reverse the progress of the lesion. Remineralization is the natural repair process for non-cavitated lesions, and relies on calcium and phosphate ions assisted by fluoride to rebuild a new surface on existing crystal remnants in subsurface lesions remaining after demineralization. These remineralized crystals are acid resistant, being much less soluble than the original mineral.

Renal cell carcinoma in a horseshoe kidney presenting as an acute, left sided varicocele.

We present a rare case of renal cell carcinoma (RCC) in a horseshoe kidney presenting as an acute left sided varicocele. A left sided varicocele is a well-described presentation of RCC, usually caused by tumour thrombus extending along the renal vein with resultant testicular vein occlusion. However, in our case a tumour in the lower pole of a horseshoe kidney caused an acute varicocele by direct involvement and occlusion of the testicular vein.

Caries risk/susceptibility assessment: its value in minimum intervention oral healthcare.

This narrative review describes the intimate connection between minimum intervention (MI) oral healthcare and caries risk/susceptibility assessment (CRA). Indeed CRA is the corner stone of an MI care plan, allowing the determination of the appropriate interventions (non-invasive as well as invasive [restorative]) and recall consultation strategies. Various CRA protocols/models have been developed to assist the oral healthcare practitioner/team in a logical systematic approach to synthesising information about a disease that has a multifactorial aetiology. Despite the criticisms toward the lack of clear-cut validation of the proposed protocols/models, CRA still has great potential to enhance patient care by allowing the oral healthcare practitioner/team and the patient to understand the specific reasons for their caries activity and to tailor their care plans and recall intervals accordingly.

Furosemide reverses multidrug resistance status in bladder cancer cells in vitro.

BACKGROUND: Multidrug resistance (MDR) has a potentially serious influence on cancer treatment and should be taken into consideration in the design and application of therapeutic regimens. It is mediated through the activity of cellular pumps. AIM: To investigate whether furosemide, itself a pump-blocker, reverses MDR in an in vitro model. MATERIALS AND METHODS: An MDR bladder cancer cell line (MGH-u 1R) and its parental (drug sensitive) clone were exposed to epirubicin and furosemide, with the concentration of one drug fixed and that of the other serially diluted in a 96-well plate format. Both drugs formed the variable component in separate experiments. After a 1-h exposure, the cells were washed and replenished with fresh medium. To examine the toxicity of epirubicin and furosemide separately and in combination, monotetrazolium-based assays were carried out. Intracellular epirubicin distribution was assessed by confocal microscopy as a second index of resistance status after in vitro exposure. RESULTS: MGH-u 1R cells incubated with furosemide showed distribution of drug similar to that in the parental cells (MGH-u 1 sensitive). Controls (without furosemide) continued to show a resistant pattern of fluorescence. In cytotoxicity assays furosemide appeared substantially non-toxic. Resistant cells in the toxicity titration experiments showed increased resistance to levels of furosemide over 500 mug/ml. Parental cells were made only marginally more sensitive against increased background toxicity. CONCLUSION: Furosemide is effective in reversing MDR status in bladder cancer cell lines in vitro. It may also have an increment of intrinsic cytotoxicity, but only at higher concentrations. We propose a potential for further investigation of furosemide as an adjunct to chemotherapy for superficial bladder cancer.

In situ mineral loss inhibition by CO2 laser and fluoride.

Laser and fluoride treatments have been shown to inhibit enamel demineralization in the laboratory. However, the intra-oral effects of this association have not been tested. This study assessed in situ the effect of a Transversely Excited Atmospheric CO2 laser (lambda = 9.6 mum) and the use of pressure fluoridated dentifrice on enamel demineralization. During two 14-day phases, 17 volunteers wore palatal appliances containing human enamel slabs assigned to treatment groups, as follows: (1) non-fluoride dentifrice, (2) CO2 laser irradiation plus non-fluoride dentifrice, (3) fluoride dentifrice, and (4) CO2 laser irradiation plus fluoride dentifrice. A 20% sucrose solution was dripped onto the slabs 8 times per day. The specimens treated with laser and/or fluoridated dentifrice presented a significantly lower mineral loss when compared with those from the non-fluoride dentifrice group. The results suggested that CO2 laser treatment of enamel inhibits demineralization in the human mouth, being more effective when associated with fluoride.