Bis[2-(Methacryloyloxy) Ethyl] Phosphate as a Primer for Enamel and Dentine.

Dental resin composites are commonly used in the restorative management of teeth via adhesive bonding, which has evolved significantly over the past few decades. Although current self-etch bonding systems decrease the number of clinical steps, the acidic functional monomers employed exhibit a limited extent of demineralization of enamel in comparison to phosphoric acid etchants, and the resultant superficial ionic interactions are prone to hydrolysis. This study evaluates the etching of primers constituted with bis[2-(methacryloyloxy) ethyl] phosphate (BMEP) of dental hard tissue, interfacial characteristics, and inhibition of endogenous enzymes. We examine the incorporation of 2 concentrations of BMEP in the formulation of experimental primers used with a hydrophobic adhesive to constitute a 2-step self-etching bonding system and compare to a commercial 10-methacryloyloxydecyl dihydrogen phosphate (10-MDP)-containing system. The interaction of the primer with enamel and dentine was characterized using scanning electron, confocal laser scanning, and Raman microscopy while the polymerization reaction between the BMEP primers and hydroxyapatite was evaluated by Fourier-transform infrared spectroscopy. The inhibitory effect against matrix metalloproteinase (MMP) enzymes of these primers was studied and percentage of inhibition analyzed using 1-way analysis of variance and Tukey's post hoc test (P < 0.05). Results of the scanning electron microscopy micrographs demonstrated potent etching of both enamel and dentine with the formation of longer resin tags with BMEP primers compared to the 10-MDP-based system. The BMEP polymerized on interaction with pure hydroxyapatite in the dark, while the 10-MDP primer exhibited the formation of salts. Furthermore, BMEP primers were able to inhibit MMP activity in a dose-dependent manner. BMEP could be used as a self-etching primer on enamel and dentine, and the high degree of polymerization in the presence of hydroxyapatite can contribute to an increased quality of the resin polymer network, prompting resistance to gelatinolytic and collagenolytic degradation.

Consensus recommendations for optimizing biomarker testing to identify and treat advanced EGFR-mutated non-small-cell lung cancer.

The advent of personalized therapy for non-small-cell lung carcinoma (nsclc) has improved patient outcomes. Selection of appropriate targeted therapy for patients with nsclc now involves testing for multiple biomarkers, including EGFR. EGFR mutation status is required to optimally treat patients with nsclc, and thus timely and accurate biomarker testing is necessary. However, in Canada, there are currently no standardized processes or methods in place to ensure consistent testing implementation. That lack creates challenges in ensuring that all appropriate biomarkers are tested for each patient and that the medical oncologist receives the results for making informed treatment decisions in a timely way. An expert multidisciplinary working group was convened to create consensus recommendations about biomarker testing in advanced nsclc in Canada, with a primary focus on EGFR testing. Recognizing that there are biomarkers beyond EGFR that require timely identification, the expert multidisciplinary working group considered EGFR testing in the broader context of integration into complex lung biomarker testing. Primarily, the panel of experts recommends that all patients with nonsquamous nsclc, regardless of stage, should undergo comprehensive reflex biomarker testing at diagnosis with targeted next-generation sequencing. The panel also considered the EGFR testing algorithm and the challenges associated with the pre-analytic, analytic, and post-analytic elements of testing. Strategies for funding testing by reducing silos of single biomarker testing for EGFR and for optimally implementing the recommendations presented here and educating oncology professionals about them are also discussed.

Canadian consensus: a new systemic treatment algorithm for advanced EGFR-mutated non-small-cell lung cancer.

Background: Multiple clinical trials for the treatment of advanced EGFR-mutated non-small-cell lung cancer (nsclc) have recently been reported. As a result, the treatment algorithm has changed, and many important clinical questions have been raised:■ What is the optimal first-line treatment for patients with EGFR-mutated nsclc?■ What is preferred first-line treatment for patients with brain metastasis?■ What is the preferred second-line treatment for patients who received first-line first- or second-generation tyrosine kinase inhibitors (tkis)?■ What is the preferred treatment after osimertinib?■ What evidence do we have for treating patients whose tumours harbour uncommon EGFR mutations? Methods: A Canadian expert panel was convened to define the key clinical questions, review recent evidence, and discuss and agree on practice recommendations for the treatment of advanced EGFR-mutated nsclc. Results: The published overall survival results for osimertinib, combined with its central nervous system activity, have led to osimertinib becoming the preferred first-line treatment for patients with common EGFR mutations, including those with brain metastasis. Other agents could still have a role, especially when osimertinib is not available or not tolerated. Treatment in subsequent lines of therapy depends on the first-line therapy or on T790M mutation status. Treatment recommendations for patients whose tumours harbour uncommon EGFR mutations are guided mainly by retrospective and limited prospective evidence. Finally, the evidence for sequencing and combining tkis with chemotherapy, angiogenesis inhibitors, checkpoint inhibitors, and other new therapeutics is reviewed. Conclusions: This Canadian expert consensus statement and algorithm were driven by significant advances in the treatment of EGFR-mutated nsclc.

An investigation into the impact of tooth wear on the oral health related quality of life amongst adult dental patients in the United Kingdom, Malta and Australia.

OBJECTIVE: To investigate the relationship between levels of tooth wear scored using the Basic Erosive Wear Examination (BEWE) and the impact on the quality of life of adult dental patients. METHODS: BEWE assessments were performed on 319 new dentate adult patients attending the practices of 5 trained recruiters based in primary care in Malta (120), Australia (118) or the UK (81). Oral impacts on the quality of life were measured using a shortened form of the Oral Health Impact Profile (OHIP-26). Regression analysis were performed, adjusted for age, to estimate the relationship between the variables. Data were expressed as Confidence Intervals (95 % CI), p-values (values <0.05 were considered statistically significant) and adjusted R2 values. RESULTS: Overall, the sample had a mean age of 42.6 ±â€¯17.1 (range, 18-93 years), a mean cumulative BEWE score of 6.7 ±â€¯4.4 and a mean total OHIP-26 score of 1.84 ±â€¯0.59. For the cumulative sextant BEWE scores, 68.0 % of the participants scored ≤ 8, 24.5 % between 9 and 13 and 7.5 %, ≥ 14. A significant association was found between increasing BEWE score and the overall OHIP-26 total score (effect = 0.028; p = 0.002), implying a higher BEWE to be associated with a larger impact of oral conditions on daily life. CONCLUSION: Higher levels of tooth wear were significantly associated with a deteriorating oral-health related quality of life amongst the participants. CLINICAL RELEVANCE: When treatment planning for patients with tooth wear, it is appropriate to consider the psycho-social impact of the condition alongside other clinical findings.

Biomarkers of immune checkpoint inhibitor efficacy in cancer.

Immune checkpoint inhibitor-based therapies that target ctla-4, PD-1, or the PD-1 ligand PD-L1 have received approval in Canada and many parts of the world for the treatment of melanoma, renal cell cancer, urothelial cancer, classical Hodgkin lymphoma, and non-small-cell lung cancer. However only a small proportion of patients derive long-term clinical benefit. Here, we describe the biomarkers associated with the complex relationship between tumour-related immune stimulus, T cell-mediated immune response, and immune modulation of the microenvironment that can help to predict improved patient outcomes.

Crizotinib inhibition of ROS1-positive tumours in advanced non-small-cell lung cancer: a Canadian perspective.

The ros1 kinase is an oncogenic driver in non-small-cell lung cancer (nsclc). Fusion events involving the ROS1 gene are found in 1%-2% of nsclc patients and lead to deregulation of a tyrosine kinase-mediated multi-use intracellular signalling pathway, which then promotes the growth, proliferation, and progression of tumour cells. ROS1 fusion is a distinct molecular subtype of nsclc, found independently of other recognized driver mutations, and it is predominantly identified in younger patients (<50 years of age), women, never-smokers, and patients with adenocarcinoma histology. Targeted inhibition of the aberrant ros1 kinase with crizotinib is associated with increased progression-free survival (pfs) and improved quality-of-life measures. As the sole approved treatment for ROS1-rearranged nsclc, crizotinib has been demonstrated, through a variety of clinical trials and retrospective analyses, to be a safe, effective, well-tolerated, and appropriate treatment for patients having the ROS1 rearrangement. Canadian physicians endorse current guidelines which recommend that all patients with nonsquamous advanced nsclc, regardless of clinical characteristics, be tested for ROS1 rearrangement. Future integration of multigene testing panels into the standard of care could allow for efficient and cost-effective comprehensive testing of all patients with advanced nsclc. If a ROS1 rearrangement is found, treatment with crizotinib, preferably in the first-line setting, constitutes the standard of care, with other treatment options being investigated, as appropriate, should resistance to crizotinib develop.

A Canadian guideline on the use of next-generation sequencing in oncology.

Rapid advancements in next-generation sequencing (ngs) technology have created an unprecedented opportunity to decipher the molecular profile of tumours to more effectively prevent, diagnose, and treat cancer. Oncologists now have the option to order molecular tests that can guide treatment decisions. However, to date, most oncologists have received limited training in genomics, and they are now faced with the challenge of understanding how such tests and their interpretation align with patient management. Guidance on how to effectively use ngs technology is therefore needed to aid oncologists in applying the results of genomic tests. The Canadian guideline presented here describes best practices and unmet needs related to ngs-based testing for somatic variants in oncology, including clinical application, assay and sample selection, bioinformatics and interpretation of reports performed by laboratories, patient communication, and clinical trials.

Canadian consensus: oligoprogressive, pseudoprogressive, and oligometastatic non-small-cell lung cancer.

Background: Little evidence has been generated for how best to manage patients with non-small-cell lung cancer (nsclc) presenting with rarer clinical scenarios, including oligometastases, oligoprogression, and pseudoprogression. In each of those scenarios, oncologists have to consider how best to balance efficacy with quality of life, while maximizing the duration of each line of therapy and ensuring that patients are still eligible for later options, including clinical trial enrolment. Methods: An expert panel was convened to define the clinical questions. Using case-based presentations, consensus practice recommendations for each clinical scenario were generated through focused, evidence-based discussions. Results: Treatment strategies and best-practice or consensus recommendations are presented, with areas of consensus and areas of uncertainty identified. Conclusions: In each situation, treatment has to be tailored to suit the individual patient, but with the intent of extending and maximizing the use of each line of treatment, while keeping treatment options in reserve for later lines of therapy. Patient participation in clinical trials examining these issues should be encouraged.

Targeting the PD-1/PD-L1 axis for the treatment of non-small-cell lung cancer.

Lung cancer is the leading cause of cancer-specific death among Canadians, with non-small-cell lung cancer (nsclc) being the most common histologic variant. Despite advances in the understanding of the molecular biology of nsclc, the survival rate for this malignancy is still poor. It is now understood that, to evade detection and immune clearance, nsclc tumours overexpress the immunosuppressive checkpoint protein programmed death ligand 1 (PD-L1). Inhibiting the PD-1/PD-L1 axis with monoclonal antibodies has significantly changed the treatment landscape in nsclc during the last 5 years. Despite evidence of clinical response in some patients, only approximately 20% of patients obtain any durable benefit, and many of the patients who do respond ultimately relapse with drug-resistant disease. The identification of patients who are most likely to benefit from such therapy is therefore important. In the present review, we cover the basics of the PD-1/PD-L1 axis and its clinical significance in nsclc, biomarkers that are predictive of treatment response, relevant clinical trials of PD-1/PD-L1 blockade completed to date, and proposed mechanisms of acquired therapeutic resistance.

The restorative management of tooth wear involving the aesthetic zone.

The aim of this article is to describe a systematic approach that facilitates the establishment of a clear and appropriate diagnosis when a dentate patient presents with tooth wear involving their aesthetic zone. It will also detail the protocols that are required to allow for the development of an acceptable aesthetic prescription within the limits of the functional constraints presented by the patient (where active restorative intervention may be indicated), as well as to communicate the manner by which this information can be transferred to ultimately enable the successful and predictable rehabilitation of the affected areas. An overview will also be provided of the tooth-coloured dental materials and restorative techniques that have been commonly applied to deliver the predictable and effective dental care of worn teeth in the aesthetic zone.

An evaluation of the influence of teeth and the labial soft tissues on the perceived aesthetics of a smile.

Objective The aim of this study was to investigate how the lips and teeth may affect the perceived aesthetics of a given smile. Lips and teeth were collectively assessed in different fields of view to see how they may contribute to smile aesthetics. The perception of 'beauty' was assessed to determine whether differences existed between; dentists, non-dentists, males and females.Methods Five subjects were photographed to produce the following views: 1) retracted anterior teeth; 2) lips at rest; 3) zoomed smile; and 4) smile showing the lower face. Images were compiled in a survey questionnaire and shown to respondents who ranked the subjects in order of aesthetic appeal. Kendall's coefficient of concordance (W) and median rank scores were used to determine the statistical significance.Results All groups demonstrated statistically significant agreement in the perception of beauty. Both the teeth and lips seemed to contribute similarly to the attractiveness of a smile. Dentists seemed to be more influenced by teeth in a zoomed smile view, however, this was negated when viewing a broader field of view. All other groups showed no difference in perception of aesthetics with changing field of view.Conclusion Both lips and teeth seem to contribute to the aesthetic appeal of a smile. Dentists may have a tendency to place a disproportionate weight to teeth when assessing a smile close up.

The management of cracked tooth syndrome in dental practice.

Cracked tooth syndrome is a commonly encountered condition in dental practice which frequently causes diagnostic and management challenges. This paper provides an overview of the diagnosis of this condition and goes on to discuss current short and long-term management strategies applicable to dental practitioners. This paper also covers the diagnosis and management of this common condition and aims to inform clinicians of the current thinking, as well as to provide an overview of the techniques commonly used in managing cracked tooth syndrome.

Inferior alveolar neurovascular bundle repositioning: a retrospective analysis.

In this study, patients with an insufficient height of bone for implant placement in the posterior mandible were treated by repositioning of the inferior alveolar neurovascular bundle (IANVB). These patients were divided into two groups: those in group A (n=69) did not require a bone graft and implants were placed at the time of nerve repositioning; those in group B (n=9) received bone grafts in conjunction with nerve repositioning and implants were placed upon maturation of the grafts. One hundred and twenty-one nerves were repositioned in 78 patients and 308 implants were placed. Three implants failed within the first 10 months after placement. With a certainty of 95%, an estimated overall mean survival rate better than 97.8% was observed after a mean observation period of 84.5 months. The recovery of sensation was monitored using standardized tests. The recovery of sensation varied from 24h to 6 months. Five patients reported some residual altered sensation. The technique of repositioning the IANVB provides an effective way of treating the atrophic posterior mandible with acceptable morbidity and a high implant survival rate; however the risk of dysesthesia must be acknowledged and patients properly informed.

Canadian consensus: inhibition of ALK-positive tumours in advanced non-small-cell lung cancer.

Anaplastic lymphoma kinase (alk) is an oncogenic driver in non-small-cell lung cancer (nsclc). Chromosomal rearrangements involving the ALK gene occur in up to 4% of nonsquamous nsclc patients and lead to constitutive activation of the alk signalling pathway. ALK-positive nsclc is found in relatively young patients, with a median age of 50 years. Patients frequently have brain metastasis. Targeted inhibition of the alk pathway prolongs progression-free survival in patients with ALK-positive advanced nsclc. The results of several recent clinical trials confirm the efficacy and safety benefit of crizotinib and ceritinib in this population. Canadian oncologists support the following consensus statement: All patients with advanced nonsquamous nsclc (excluding pure neuroendocrine carcinoma) should be tested for the presence of an ALK rearrangement. If an ALK rearrangement is present, treatment with a targeted alk inhibitor in the first-line setting is recommended. As patients become resistant to first-generation alk inhibitors, other treatments, including second-generation alk inhibitors can be considered.

Clinical management of pathological tooth wear in general dental practice.

Due to the relatively slow pace and lack of symptoms with which tooth wear develops, patients will often not be aware of the presence of a wearing dentition and often present for treatment at an advanced stage. Thus, it is often challenging for the general dental practitioner to convey the diagnoses, whilst concomitantly emphasising the importance of disease management, as well as the consequences of no care. This article, and the associated session at the 2016 British Dental Conference &Exhibition, review the clinical management of pathological tooth wear in general dental practice.

A multi-centred clinical audit to describe the efficacy of direct supra-coronal splinting--a minimally invasive approach to the management of cracked tooth syndrome.

OBJECTIVES: This audit looked at the use of direct composite splinting to manage cracked tooth syndrome (CTS). METHODS: Patients who had been assessed as having CTS were offered the treatment of a directly bonded, composite overlay restoration placed in supra-occlusion. Cases were reviewed up to 3 months later. RESULTS: In all, 151 restorations were followed up in the audit of which 131 were successful at 3 months. The remaining 20 restorations failed due to pulp complications (11), failure of the composite (5) or intolerance to the high restoration (4). Of the 131, patients described transient problems with chewing (94), composite breakage (13), TMD (1), phonetics (1), increased mobility (1) and tender to chewing (1). CONCLUSIONS: This is a successful non-invasive method of managing CTS in the short term for patients willing to accept transient effects.

Current concepts on the management of tooth wear: part 3. Active restorative care 2: the management of generalised tooth wear.

Paper 3 of this series on the current concepts of tooth wear management will focus on the provision of active restorative intervention for cases presenting with generalised tooth wear. The use of both contemporary adhesive and traditional conventional techniques applied to treat cases of generalised tooth wear will be discussed, including a consideration of the merits and drawbacks of each approach respectively.

Current concepts on the management of tooth wear: part 4. An overview of the restorative techniques and dental materials commonly applied for the management of tooth wear.

This final article of the four part series on the current concepts of tooth wear will provide the reader with an evaluation of the data available in the contemporary literature with regards to the survival analysis of differing restorative materials, and their respective methods of application to treat tooth wear. It is vital that the dental operator is familiar with the role of differing materials which may be used to restore the worn dentition, some of which may prove to be more suitable for the management of particular patterns of tooth wear than others. The active management of tooth wear unfortunately commits the patient to a lifelong need for considerable maintenance, and it is imperative that this is understood from the outset.

Current concepts on the management of tooth wear: part 1. Assessment, treatment planning and strategies for the prevention and the passive management of tooth wear.

The aim of this series of four articles on tooth wear management is to provide the reader with the necessary information in order to be able to successfully manage cases of tooth wear, regardless of the cause, severity and location of the wear pattern seen. The content will largely focus on contemporary clinical techniques, illustrated where possible by case examples. Emphasis will be placed on 'additive adhesive techniques' utilising fixed prosthodontic protocols; however, cases of tooth wear amongst partially dentate patients involving the use of removable prostheses will also be described. The importance of patient consent and contingency planning will also be discussed. Paper 1 will describe the assessment of the wear patient, including the rationale for the planning of dental care. Also discussed will be the administration of preventative and passive management strategies for cases displaying tooth wear.

Current concepts on the management of tooth wear: part 2. Active restorative care 1: the management of localised tooth wear.

This second of the four part series of articles on the current concepts of tooth wear management will focus on the provision of active restorative care, where the implementation of a preventative, passive approach may prove insufficient to meet the patient's expectations, or indeed prove to be sufficiently adequate to address the extent of the underlying pathology to the desired level of clinical satisfaction. The active restorative management of cases presenting with localised tooth wear (of either the anterior, posterior, maxillary or mandibular variety) will be considered in depth in this paper, including a description of the commonly applied techniques and treatment strategies, where possible illustrated by case examples.