Needs for re-intervention on restored teeth in adults: a practice-based study.

OBJECTIVES: Evaluate the need for re-intervention on dental coronal restorations in adults seen in a network of general dental practitioners (ReCOL).  MATERIALS AND METHODS: This observational, cross-sectional, multicenter study involved 40 practitioners and 400 patients. Coronal restoration failures (needing re-intervention for unsatisfactory outcomes) were assessed with a simplified rating scale of seven criteria from the FDI World Dental Federation. The oral health status, the risk factors, and Oral Health Impact Profile-14 were also examined. Previous restoration characteristics (extent, technique, material) were analyzed according to the need for re-intervention (yes/no), the age group, and the risk profile. Qualitative variables were compared between "re-intervention" and "no re-intervention" group using Fisher exact test. RESULTS: The need for re-intervention was estimated at 74% (95% CI: 70; 79); it increased with age (49 to 90%), unfavorable risk profile (82 vs. 62%), and extent of the filling (32, 39, 44, and 44% on 1, 2, 3 surfaces, and crowns, respectively). More posterior than anterior teeth were restored (median per patient: 6 vs. 1) or needed re-intervention (median per patient: 1 vs. 0). CONCLUSIONS: The needs for re-intervention in adults are still high within a context of ever-changing materials and techniques, simplified and rationalized decision-makings, and demands for patient involvement. CLINICAL RELEVANCE: Meeting these needs requires the following: (i) consensus definitions and assessment methods for "failure" and (ii) reliable feedbacks on materials, procedures, and satisfaction. Building large and detailed databases fed by networks of motivated practitioners will help analyzing complex success/failure data by artificial intelligence and guiding treatment and research.

Adherence to cysteamine in nephropathic cystinosis: A unique electronic monitoring experience for a better understanding. A prospective cohort study: CrYSTobs.

INTRODUCTION: In nephropathic cystinosis (NC), adherence to cysteamine remains challenging; poor adherence is worsening the disease progression with a decline of kidney function and increase of extrarenal morbidities. Our objective was to describe adherence to cysteamine in NC patients, using electronic monitoring systems. METHODS: Patients with confirmed NC, aged > 4 years and receiving oral cysteamine (short acting or delayed release formulation as standard of care) from 3 French reference centers, were included. Adherence to treatment was primarily assessed as the percentage of days with a good adherence score, adherence score rating from 0 (poor) to 2 (good). A descriptive analysis was performed after 1-year follow-up. RESULTS: Seventeen patients (10 girls, median age: 13.9 (5.4-33.0) years) were included. Median age at diagnosis was 17.0 (3.0-76.9) months and age at start of cysteamine was 21.0 (15.5-116.3) months. Median daily dose of cysteamine was 1.05 (0.55-1.63) g/m2/day. Over the year, the median percentage of days with a good adherence score was 80 (1-99)% decreasing to 68 (1-99)% in patients > 11 years old. The median of average number of hours covered by treatment in a day was 22.5 (6.1-23.9) versus 14.9 (9.2-20.5) hours for delayed release versus short acting cysteamine. CONCLUSION: Our data are the first describing a rather good adherence to cysteamine, decreasing in adolescents and adults. We described a potential interest of the delayed release formulation. Our data highlight the need for a multidisciplinary approach including therapeutic education and individualized approaches in NC patients transitioning to adulthood. Graphical abstract.

A double-blind placebo-controlled randomised trial of omega-3 supplementation in children with moderate ADHD symptoms.

OBJECTIVE: Clinical trials and inconclusive meta-analyses have investigated the effects of omega-3 supplements in children with Attention-Deficit Hyperactivity Disorder (ADHD). We performed a randomised placebo-controlled trial to evaluate the efficacy of omega-3 fatty acids. METHODS: Children aged 6-15 years with established diagnosis of ADHD were randomised 1:1 to receive either supplements containing docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) or a placebo for 3 months. Psychotropic or omega-3-containing treatments were not authorised during the study. The primary outcome was the change in the Attention-Deficit Hyperactivity Disorder Rating Scale version 4 (ADHD-RS-IV). Other outcomes included safety, lexical level (Alouette test), attention (Test of Attentional Performance for Children-KiTAP), anxiety (48-item Conners Parent Rating Scale-Revised-CPRS-R), and depression (Children's Depression Inventory-CDI). RESULTS: Between 2009 and 2011, 162 children were included in five French child psychiatry centres. The mean age was 9.90 (SD 2.62) years and 78.4% were boys. The inclusion ADHD-RS-IV at was 37.31 (SD 8.40). The total ADHD-RS-IV score reduction was greater in the placebo group than in the DHA-EPA group: -19 (-26, -12)  % and -9.7 (-16.6, -2.9) %, respectively, p = 0.039. The other components of the Conners score had a similar variation but the differences between groups were not significant. Two patients in the DHA-EPA group and none in the placebo group experienced a severe adverse event (hospitalisation for worsening ADHD symptoms). CONCLUSION: This study did not show any beneficial effect of omega-3 supplement in children with mild ADHD symptoms.

Combining mathematical modeling and deep learning to make rapid and explainable predictions of the patient-specific response to anticoagulant therapy under venous flow.

Anticoagulant drugs are commonly prescribed to prevent hypercoagulable states in patients with venous thromboembolism. The choice of the most efficient anticoagulant and the appropriate dosage regimen remain a complex problem because of the intersubject variability in the coagulation kinetics and the effect of blood flow. The rapid assessment of the patient-specific response to anticoagulant regimens would assist clinical decision-making and ensure efficient management of coagulopathy. In this work, we introduce a novel approach that combines computational modeling and deep learning for the fast prediction of the patient-specific response to anticoagulant regimens. We extend a previously developed model to explore the spatio-temporal dynamics of thrombin generation and thrombus formation under anticoagulation therapy. Using a 1D version of the model, we generate a dataset of thrombus formation for thousands of virtual patients by varying key parameters in their physiological range. We use this dataset to train an artificial neural network (ANN) and we use it to predict patient's response to anticoagulant therapy under flow. The algorithm is available and can be accessed through the link: https://github.com/MPS7/ML_coag. It yields an accuracy of 96 % which suggests that its usefulness can be assessed in a randomized clinical trial. The exploration of the model dynamics explains the decisions taken by the algorithm.

Effect of periodontal treatment on the glomerular filtration rate, reduction of inflammatory markers and mortality in patients with chronic kidney disease: A systematic review.

AIM: To assess the effect of periodontal treatment (PT) on glomerular filtration rate (GFR), systemic inflammation, or mortality in patients with chronic kidney disease (CKD). METHODS: A literature search was performed on PubMed and Web of Science databases on articles published until December 2019. The PRISMA guidelines were used throughout the manuscript. RESULTS: Of the total studies found, only 18 met the inclusion criteria; four retrospective and 14 prospective studies (including 3 randomized controlled trials-RCT). After PT, 3 studies investigated GFR, 2 found significant improvement; 11 (including 2 RCTs) investigated C-reactive protein levels, 9 found a significant improvement (including the 2 RCTs); 5 (including 3 RCTs) investigated Interleukine-6 level, 4 found a significant improvement (including 2 RCTs) and 2 studies evaluated mortality, one (retrospective study) found a significant difference. CONCLUSIONS: Within the limitations of the present study, PT seems to improve CKD status, especially by reducing the systemic inflammation. Further RCTs are needed to confirm the results and specifically assess the influence of different types of PT in CKD patients. Taking into consideration the ability of PT to prevent further tooth loss and denutrition, early management of periodontitis is extremely important in patients with impaired renal function.

A methodological framework for drug development in rare diseases. The CRESim program: Epilogue and perspectives.

Based on the 'European Child-Rare-Euro-Simulation' (CRESim) project, this article proposes a generalizable strategy utilizing datasets analysis in combination with modeling and simulation, in order to optimize the clinical drug development applied in the field of rare diseases. The global process includes: (i) the simulation of a realistic virtual population of patients (modeled from a real dataset of patients), (ii) the modeling of disease pathophysiological components and of pharmacokinetic-pharmacodynamic relations of the drug(s) of interest, (iii) the modeling of several randomized controlled clinical trials (RCTs) designs and (iv) the analysis of the results (multi-dimensional approach for RCTs durations and precision of the estimation of the treatment effect). However, whereas modeling and numerical simulation may provide supplementary tools for drug development, they cannot be considered as a substitute for RCTs performed in 'real' patients.

A mathematical model to quantify the effects of platelet count, shear rate, and injury size on the initiation of blood coagulation under venous flow conditions.

Platelets upregulate the generation of thrombin and reinforce the fibrin clot which increases the incidence risk of venous thromboembolism (VTE). However, the role of platelets in the pathogenesis of venous cardiovascular diseases remains hard to quantify. An experimentally validated model of thrombin generation dynamics is formulated. The model predicts that a high platelet count increases the peak value of generated thrombin as well as the endogenous thrombin potential (ETP) as reported in experimental data. To investigate the effects of platelets density, shear rate, and wound size on the initiation of blood coagulation, we calibrate a previously developed model of venous thrombus formation and implement it in 3D using a novel cell-centered finite-volume solver. We conduct numerical simulations to reproduce in vitro experiments of blood coagulation in microfluidic capillaries. Then, we derive a reduced one-equation model of thrombin distribution from the previous model under simplifying hypotheses and we use it to determine the conditions of clotting initiation on the platelet count, the shear rate, and the plasma composition. The initiation of clotting also exhibits a threshold response to the size of the wounded region in good agreement with the reported experimental findings.

Effect of Non-Steroidal Anti-Inflammatory Drugs on Sport Performance Indices in Healthy People: a Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are medications that are frequently used by athletes. There may also be some abuse of these substances, although it is unclear whether NSAIDs in fact enhance performance. We performed a systematic review and meta-analysis to evaluate the effect of NSAIDs on sport performance indices. METHODS: We selected randomized trials from the PubMed and Cochrane Library databases investigating the effects of NSAIDs on sport performance. Volunteers could be healthy adult men and women. Any NSAID, administered by any route, taken prior to any type of exercise, and for any duration could be used. The control intervention could be a placebo, an active substance, or no intervention. We included double-blind, single-blind, and open-label studies. The primary outcome was the maximum performance in exercises as defined in each study. The secondary outcomes were the time until self-reported exhaustion and the self-reported pain. RESULTS: Among 1631 records, we retained thirteen parallel-group and ten crossover studies, totaling 366 and 148 subjects, respectively. They were disparate regarding treatments, dose and duration, and the type of exercise. There was neither significant difference in the maximum performance between NSAIDs and control groups nor in the time until exhaustion nor in self-perceived pain. CONCLUSIONS: The existence of an ergogenic effect of NSAIDs on sport performance indices was unable to be concluded, since the level of evidence of the studies is low, the doses tested, and the exercises performed are very heterogeneous and far from those observed in real-life practices. More studies are required.

Collaboration between academics, small pharmaceutical company and patient organizations in the development of a new formulation of cysteamine in nephropathic cystinosis: A successful story.

Rare diseases usually concern small and disseminated population. Implementing clinical research with the right design, outcomes measures and the recruitment of patients are challenges. Collaborations, training and multidisciplinary approach are often required. In this article, we provide an overview of a successful collaboration in nephropathic cystinosis (NC), focusing on what was the key of success, the interactions between academics, the pharmaceutical company and patients organizations. NC is considered as a very rare disease. In 2010, a new formulation of cysteamine, the only available treatment to improve renal outcome of the disease, was proposed by a small American company. Studies were implemented in France under the coordination of an expert of the disease and the clinical investigation center of Lyon. The collaboration resulted in a good recruitment and retention of the patients in the study and most of all in the availability of the new formulation in France. Patients could have facilitated the research by being involved in the early stages of the studies. Involving patients and public early in the process is particularly important in rare diseases as the patient is a great source of knowledge and has his own expectations. Priorities of research, design, conduct and reporting of clinical trials can be defined in collaboration with adults but also with young patients or public, the first concerned in rare diseases. This concept is still to be developed and improved especially with paediatric patients.

SCORE should be preferred to Framingham to predict cardiovascular death in French population.

BACKGROUND: Numerous studies have examined the validity of available scores to predict the absolute cardiovascular risk. DESIGN: We developed a virtual population based on data representative of the French population and compared the performances of the two most popular risk equations to predict cardiovascular death: Framingham and SCORE. METHODS: A population was built based on official French demographic statistics and summarized data from representative observational studies. The 10-year coronary and cardiovascular death risk and their ratio were computed for each individual by SCORE and Framingham equations. The resulting rates were compared with those derived from national vital statistics. RESULTS: Framingham overestimated French coronary deaths by 2.8 in men and 1.9 in women, and cardiovascular deaths by 1.5 in men and 1.3 in women. SCORE overestimated coronary death by 1.6 in men and 1.7 in women, and underestimated cardiovascular death by 0.94 in men and 0.85 in women. Our results revealed an exaggerated representation of coronary among cardiovascular death predicted by Framingham, with coronary death exceeding cardiovascular death in some individual profiles. Sensitivity analyses gave some insights to explain the internal inconsistency of the Framingham equations. CONCLUSION: Evidence is that SCORE should be preferred to Framingham to predict cardiovascular death risk in French population. This discrepancy between prediction scores is likely to be observed in other populations. To improve the validation of risk equations, specific guidelines should be issued to harmonize the outcomes definition across epidemiologic studies. Prediction models should be calibrated for risk differences in the space and time dimensions.

Revisiting the relationship between baseline risk and risk under treatment.

BACKGROUND: In medical practice, it is generally accepted that the 'effect model' describing the relationship between baseline risk and risk under treatment is linear, i.e. 'relative risk' is constant. Absolute benefit is then proportional to a patient's baseline risk and the treatment is most effective among high-risk patients. Alternatively, the 'effect model' becomes curvilinear when 'odds ratio' is considered to be constant. However these two models are based on purely empirical considerations, and there is still no theoretical approach to support either the linear or the non-linear relation. PRESENTATION OF THE HYPOTHESIS: From logistic and sigmoidal Emax (Hill) models, we derived a phenomenological model which includes the possibility of integrating both beneficial and harmful effects. Instead of a linear relation, our model suggests that the relationship is curvilinear i.e. the moderate-risk patients gain most from the treatment in opposition to those with low or high risk. TESTING THE HYPOTHESIS: Two approaches can be proposed to investigate in practice such a model. The retrospective one is to perform a meta-analysis of clinical trials with subgroups of patients including a great range of baseline risks. The prospective one is to perform a large clinical trial in which patients are recruited according to several prestratified diverse and high risk groups. IMPLICATIONS OF THE HYPOTHESIS: For the quantification of the treatment effect and considering such a model, the discrepancy between odds ratio and relative risk may be related not only to the level of risk under control conditions, but also to the characteristics of the dose-effect relation and the amount of dose administered. In the proposed approach, OR may be considered as constant in the whole range of Rc, and depending only on the intrinsic characteristics of the treatment. Therefore, OR should be preferred rather than RR to summarize information on treatment efficacy.

New insights on the relation between untreated and treated outcomes for a given therapy effect model is not necessarily linear.

BACKGROUND AND OBJECTIVES: A relation between the size of treatment efficacy and severity of the disease has been postulated and observed as linear for a few therapies. We have called this relation the effect model. Our objectives were to demonstrate that the relation is general and not necessarily linear. STUDY DESIGN AND SETTING: We extend the number of observed effect model. Then we established three numerical models of treatment activity corresponding to the three modes of action we have identified. Using these models, we simulated the relation. RESULTS: Empirical evidence confirms the effect model and suggests that it may be linear over a short range of event frequency. However, it provides an incomplete understanding of the phenomenon because of the inescapable limitations of data from randomized clinical trials. Numerical modeling and simulation show that the real effect model is likely to be more complicated. It is probably linear only in rare instances. The effect model is general. It depends on factors related to the individual, disease and outcome. CONCLUSION: Contrarily to common, assumption, since the effect model is often curvilinear, the relative risk cannot be granted as constant. The effect model should be taken into account when discovering and developing new therapies, when making, health care policy decisions or adjusting clinical decisions to the patient risk profile.

Blockade of the renin-angiotensin-aldosterone system in patients with arrhythmogenic right ventricular dysplasia: A double-blind, multicenter, prospective, randomized, genotype-driven study (BRAVE study).

Arrhythmogenic right ventricular dysplasia (ARVD) is a rare cardiomyopathy characterized by the progressive replacement of cardiomyocytes by fatty and fibrous tissue in the right ventricle (RV). These infiltrations lead to cardiac electrical instability and ventricular arrhythmia. Current treatment for ARVD is empirical and essentially based on treatment of arrhythmia. Thus, there is no validated treatment that will prevent the deterioration of RV function in patients with ARVD. The aim of the BRAVE study is to evaluate the effect of ramipril, an angiotensin-converting enzyme inhibitor, on ventricular myocardial remodeling and arrhythmia burden in patients with ARVD. Despite the fact that myocardial fibrosis is one of the structural hallmarks of ARVD, no study has tested an antifibrotic drug in ARVD patients. The trial is a double-blind, parallel, multicenter, prospective, randomized, phase 4 drug study. Patients will be randomized into 2 groups, ramipril or placebo. The 120 patients (60 per group) will be enrolled by 26 centers in France. Patients will be followed up every 6 months for 3 years. The 2 co-primary endpoints are defined as the difference of telediastolic RV volume measured by magnetic resonance imaging between baseline and 3 years of follow-up, and the change in arrhythmia burden during the 3 years of follow-up. A decrease in RV and/or left ventricular deterioration and in arrhythmia burden are expected in ARVD patients treated with ramipril. This reduction will improve quality of life of patients and will reduce the number of hospitalizations and the risk of terminal heart failure.

A comparison of the NCEP-ATPIII, IDF and AHA/NHLBI metabolic syndrome definitions with relation to early carotid atherosclerosis in subjects with hypercholesterolemia or at risk of CVD: evidence for sex-specific differences.

The metabolic syndrome is associated with increased risk of cardiovascular disease. However, the association between metabolic syndrome and atherosclerosis in hypercholesterolemic patients remains unknown. We examined the association between carotid atherosclerosis and metabolic syndrome definitions using the NCEP-ATPIII, International Diabetes Federation (IDF) and American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) definitions in 1782 subjects at risk of cardiovascular disease including 926 with hypercholesterolemia (LDL cholesterol > or =160 mg/dL; mean=203 mg/dL). Irrespective of definition, carotid intima-media thickness was significantly higher in both men and women diagnosed with the MetS compared to those without MetS. This relationship persists in males with hypercholesterolemia, independently of LDL cholesterol level. Regression analyses, both unadjusted and adjusted for traditional risk factors, indicate that in males the AHA/NHLBI definition, and in females the IDF definition are the strongest predictors of carotid atherosclerosis. These results highlight important gender differences that exist in the current clinical definitions of the metabolic syndrome, with regards to predicting early atherosclerotic lesions. In addition, this study shows that in males with hypercholesterolemia, MetS is independently associated with increased atherosclerosis, supporting screening for MetS among people at risk of CVD.

Evaluation of two evidence-based knowledge transfer interventions for physicians. A cluster randomized controlled factorial design trial: the CardioDAS Study.

To investigate the potential benefits of two modes of evidence-based knowledge transfer ('active' and 'passive' modes) in terms of improvement of intention of prescription, knowledge, and real prescription in practice, we performed an open randomized controlled trial (CardioDAS) using a factorial design (two tested interventions: 'active' and 'passive' knowledge transfer) and a hierarchical structure (cluster of physicians for each department level). The participants were cardiologists working in French public hospitals. In the 'passive' transfer group, cardiologists received evidence-based knowledge material (available on Internet) every week for a duration of 1 year. In the 'active' transfer group, two knowledge brokers (EA, PN) visited the participating departments (every 2 months for 1 year, 2 h per visit). The primary outcome consisted in the adjusted absolute mean variation of score (difference between post- and pre-study session) of answers to simulated cases assessing the intention to prescribe. Secondary outcomes were the variation of answers to a multiple-choice questionnaire (MCQ) assessing knowledge and of the conformity of real prescriptions to evidence-based reference assessing the behavioral change. Twenty-two French units (departments) of cardiology were randomized (72 participating cardiologists). In the 'active' transfer group, the primary outcome was more improved than that in the control (P = 0.031 at the department level, absolute mean improvement of 5 points/100). The change in knowledge transfer (MCQ) was also significant (P = 0.039 at the department level, absolute mean improvement of 6 points/100). However, no benefit was shown in terms of prescription conformity to evidence. For the 'passive' mode of knowledge transfer and for the three outcomes considered, no improvement was identified. CardioDAS findings confirm that 'active' knowledge transfer has some impact on participants' intent to prescribe and knowledge, but no effect on behavioral outcome. 'Passive' transfer seems far less efficient. In addition, the size of the benefit remains small and its consequences limited in practice.

New tools to measure discrepancy between prescribing practices and guideline recommendations.

OBJECTIVE: To study the performance of a new method designed to measure discrepancy between real prescriptions and evidence-based reference treatments. METHODS: Two different indices (additive and multiplicative) are proposed to summarize deviation between prescription and reference. Deviations thought to be observed in a population of prescribers are simulated in diverse hypothetical situations in the presence or absence of evidence-based references. The performances of both indices are compared and their sensitivities to change are explored. RESULTS: Both indices are sensitive to variation in prescriber behaviour. The additive index allows a more accurate analysis of deviation while the multiplicative index is simpler to implement and interpret but more sensitive to change. CONCLUSION: The two deviation indices may be used as new tools in surveys or trials dealing with prescribing practices.

Compliance-guided therapy : a new insight into the potential role of clinical pharmacologists.

BACKGROUND AND OBJECTIVE: In the field of drug noncompliance, we investigated an original approach that could give the prescribing physician, in collaboration with a clinical pharmacologist, an active role. The aim here is for the prescribing physician to take compliance into account so as to provide an optimised prescription (choice of molecule prescribed and its rhythm of administration) adapted to each patient. The example considered is that of oral anticoagulant treatment prescribed long-term. METHODS: In order to investigate the choice of the best molecule and treatment regimen for a given noncompliance pattern, we performed an in silico study with two oral anticoagulant agents, warfarin and acenocoumarol, each taken in one or two daily doses. Three linked models were used: the first model generated specific noncompliance patterns, the second model described the pharmacokinetics of oral anticoagulant agents and the third model summarised the pharmacokinetic-pharmacodynamic relations. RESULTS: Considering different patterns of noncompliance (including timing errors in drug intake and the phenomenon of drug holidays) and comparing warfarin with acenocoumarol, we identified different situations in which one agent (prescribed once or twice daily) could clearly minimise both the thromboembolic and haemorrhagic risks. However, for some specific noncompliance patterns, the choice of the optimal therapy should also be guided by the basal individual thromboembolic and haemorrhagic risks. CONCLUSION: Individualisation of drug therapy involves both drug dose and drug choice. In addition to the classical approach (i.e. drug level measurements, enzyme assays and even genetic sequence data), our study suggests that compliance-guided therapy may represent a potential, evolving way for the individualisation of prescriptions.

An in silico approach helped to identify the best experimental design, population, and outcome for future randomized clinical trials.

OBJECTIVES: The main objective of our work was to compare different randomized clinical trial (RCT) experimental designs in terms of power, accuracy of the estimation of treatment effect, and number of patients receiving active treatment using in silico simulations. STUDY DESIGN AND SETTING: A virtual population of patients was simulated and randomized in potential clinical trials. Treatment effect was modeled using a dose-effect relation for quantitative or qualitative outcomes. Different experimental designs were considered, and performances between designs were compared. One thousand clinical trials were simulated for each design based on an example of modeled disease. RESULTS: According to simulation results, the number of patients needed to reach 80% power was 50 for crossover, 60 for parallel or randomized withdrawal, 65 for drop the loser (DL), and 70 for early escape or play the winner (PW). For a given sample size, each design had its own advantage: low duration (parallel, early escape), high statistical power and precision (crossover), and higher number of patients receiving the active treatment (PW and DL). CONCLUSION: Our approach can help to identify the best experimental design, population, and outcome for future RCTs. This may be particularly useful for drug development in rare diseases, theragnostic approaches, or personalized medicine.

One-step partial or complete caries removal and bonding with antibacterial or traditional self-etch adhesives: study protocol for a randomized controlled trial.

BACKGROUND: Current concepts in conservative dentistry advocate minimally invasive dentistry and pulp vitality preservation. Moreover, complete removal of carious dentin in deep carious lesions often leads to pulp exposure and root canal treatment, despite the absence of irreversible pulp inflammation. For years, partial caries removal has been performed on primary teeth, but little evidence supports its effectiveness for permanent teeth. Furthermore, the recent development of new antibacterial adhesive systems could be interesting in the treatment of such lesions. The objectives of this study are to compare the effectiveness of partial versus complete carious dentin removal in deep lesions (primary objective) and the use of an antibacterial versus a traditional two-step self-etch adhesive system (main secondary objective). METHODS/DESIGN: The DEep CAries Treatment (DECAT) study protocol is a multicenter, randomized, controlled superiority trial comparing partial versus complete caries removal followed by adhesive restoration. The minimum sample size required is 464 patients. Two successive randomizations will be performed (allocation ratio 1:1): the first for the type of excavation (partial versus complete) and the second (if no root canal treatment is required) for the type of adhesive (antibacterial versus traditional). For the two objectives, the outcome is the success of the treatment after 1 year, measured according to a composite outcome of five FDI criteria: material fracture and retention, marginal adaptation, radiographic examination (including apical pathologies), postoperative sensitivity and tooth vitality, and carious lesion recurrence. DISCUSSION: The study will investigate the interest of a conservative approach for the management of deep carious lesions in terms of dentin excavation and bioactive adhesive systems. The results may help practitioners achieve the most efficient restorative procedure to maintain pulp vitality and increase the restoration longevity. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02286388 . Registered in November 2014.

Anxiety and depression are associated with unhealthy lifestyle in patients at risk of cardiovascular disease.

Adherence to lifestyle recommendations for prevention of cardiovascular disease remains a critical issue. We examined the association of anxiety and depression with healthy behaviors in a large population of subjects at risk of cardiovascular disease. We studied 1612 consecutive subjects referred for evaluation of cardiovascular risk factors. Separated scores reflecting unhealthy behaviors (physical inactivity, smoking and poor diet) were combined to produce a global unhealthy lifestyle score. The Hospital Anxiety and Depression scale (HAD) was used to assess both anxiety and depression. Both anxiety and depression were significantly associated with physical inactivity in both sexes and with an unhealthy diet in men but not in women. Anxiety and depression were both significantly correlated to smoking habits in men whereas only depression was related to smoking in women. In both sexes, the global score reflecting unhealthy lifestyles was positively associated with the degree of anxiety and depression. In multivariate analysis, both anxiety and depression appeared as independent determinant of unhealthy lifestyle in both sexes, with a stronger influence for depression. Depression and to a lesser extent anxiety are associated with a cluster of unhealthy behaviors in subjects at risk of cardiovascular disease, suggesting the difficulty of modifying lifestyle in patients with anxious-depressive disorders.