Estimating time-to-onset of adverse drug reactions from spontaneous reporting databases.

International audienceBACKGROUND: Analyzing time-to-onset of adverse drug reactions from treatment exposure contributes to meeting pharmacovigilance objectives, i.e. identification and prevention. Post-marketing data are available from reporting systems. Times-to-onset from such databases are right-truncated because some patients who were exposed to the drug and who will eventually develop the adverse drug reaction may do it after the time of analysis and thus are not included in the data. Acknowledgment of the developments adapted to right-truncated data is not widespread and these methods have never been used in pharmacovigilance. We assess the use of appropriate methods as well as the consequences of not taking right truncation into account (naïve approach) on parametric maximum likelihood estimation of time-to-onset distribution. METHODS: Both approaches, naïve or taking right truncation into account, were compared with a simulation study. We used twelve scenarios for the exponential distribution and twenty-four for the Weibull and log-logistic distributions. These scenarios are defined by a set of parameters: the parameters of the time-to-onset distribution, the probability of this distribution falling within an observable values interval and the sample size. An application to reported lymphoma after anti TNF-¿ treatment from the French pharmacovigilance is presented. RESULTS: The simulation study shows that the bias and the mean squared error might in some instances be unacceptably large when right truncation is not considered while the truncation-based estimator shows always better and often satisfactory performances and the gap may be large. For the real dataset, the estimated expected time-to-onset leads to a minimum difference of 58 weeks between both approaches, which is not negligible. This difference is obtained for the Weibull model, under which the estimated probability of this distribution falling within an observable values interval is not far from 1. CONCLUSIONS: It is necessary to take right truncation into account for estimating time-to-onset of adverse drug reactions from spontaneous reporting databases

On the construction of model Hamiltonians for adiabatic quantum computation and its application to finding low energy conformations of lattice protein models

In this report, we explore the use of a quantum optimization algorithm for obtaining low energy conformations of protein models. We discuss mappings between protein models and optimization variables, which are in turn mapped to a system of coupled quantum bits. General strategies are given for constructing Hamiltonians to be used to solve optimization problems of physical/chemical/biological interest via quantum computation by adiabatic evolution. As an example, we implement the Hamiltonian corresponding to the Hydrophobic-Polar (HP) model for protein folding. Furthermore, we present an approach to reduce the resulting Hamiltonian to two-body terms gearing towards an experimental realization.Comment: 35 pages, 8 figure

Classical Ising model test for quantum circuits

We exploit a recently constructed mapping between quantum circuits and graphs in order to prove that circuits corresponding to certain planar graphs can be efficiently simulated classically. The proof uses an expression for the Ising model partition function in terms of quadratically signed weight enumerators (QWGTs), which are polynomials that arise naturally in an expansion of quantum circuits in terms of rotations involving Pauli matrices. We combine this expression with a known efficient classical algorithm for the Ising partition function of any planar graph in the absence of an external magnetic field, and the Robertson-Seymour theorem from graph theory. We give as an example a set of quantum circuits with a small number of non-nearest neighbor gates which admit an efficient classical simulation.Comment: 17 pages, 2 figures. v2: main result strengthened by removing oracular settin

COVID‐19: The immediate response of European academic dental institutions and future implications for dental education

The COVID‐19 pandemic has had an immediate and dramatic impact on dental education. The Association of Dental Education in Europe decided to carry out an investigation to assess the immediate response of European Academic Dental Institutions. An online survey was sent to both member and non‐member dental schools to investigate the impact on non‐clinical and clinical education, assessment and the well‐being/pastoral care measures implemented. The preliminary findings and discussion are presented in this paper, for the responses collected between the 25th March and 5th April 2020. The survey at this time of publication is ongoing and detailed results can be accessed https://adee.org/covid-19-european-dental-education%E2%80%99s-immediate-response

Net Efficacy Adjusted for Risk (NEAR): A Simple Procedure for Measuring Risk:Benefit Balance

BACKGROUND: Although several mathematical models have been proposed to assess the risk:benefit of drugs in one measure, their use in practice has been rather limited. Our objective was to design a simple, easily applicable model. In this respect, measuring the proportion of patients who respond favorably to treatment without being affected by adverse drug reactions (ADR) could be a suitable endpoint. However, remarkably few published clinical trials report the data required to calculate this proportion. As an approach to the problem, we calculated the expected proportion of this type of patients. METHODOLOGY/PRINCIPAL FINDINGS: Theoretically, responders without ADR may be obtained by multiplying the total number of responders by the total number of subjects that did not suffer ADR, and dividing the product by the total number of subjects studied. When two drugs are studied, the same calculation may be repeated for the second drug. Then, by constructing a 2 x 2 table with the expected frequencies of responders with and without ADR, and non-responders with and without ADR, the odds ratio and relative risk with their confidence intervals may be easily calculated and graphically represented on a logarithmic scale. Such measures represent "net efficacy adjusted for risk" (NEAR). We assayed the model with results extracted from several published clinical trials or meta-analyses. On comparing our results with those originally reported by the authors, marked differences were found in some cases, with ADR arising as a relevant factor to balance the clinical benefit obtained. The particular features of the adverse reaction that must be weighed against benefit is discussed in the paper. CONCLUSION: NEAR representing overall risk-benefit may contribute to improving knowledge of drug clinical usefulness. As most published clinical trials tend to overestimate benefits and underestimate toxicity, our measure represents an effort to change this trend

Fluoride supplements (tablets, drops, lozenges or chewing gums) for preventing dental caries in children.

BACKGROUND: Dietary fluoride supplements were first introduced to provide systemic fluoride in areas where water fluoridation is not available. Since 1990, the use of fluoride supplements in caries prevention has been re-evaluated in several countries. OBJECTIVES: To evaluate the efficacy of fluoride supplements for preventing dental caries in children. SEARCH METHODS: We searched the Cochrane Oral Health Group's Trials Register (to 12 October 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 3), MEDLINE via OVID (1950 to 12 October 2011), EMBASE via OVID (1980 to 12 October 2011), WHOLIS/PAHO/MEDCARIB/LILACS/BBO via BIREME (1982 to 12 October 2011), and Current Controlled Trials (to 12 October 2011). We handsearched reference lists of articles and contacted selected authors. SELECTION CRITERIA: We included randomised or quasi-randomised controlled trials comparing, with minimum follow-up of 2 years, fluoride supplements (tablets, drops, lozenges) with no fluoride supplement or with other preventive measures such as topical fluorides in children less than 16 years of age at the start. The main outcome was caries increment measured by the change in decayed, missing and filled tooth surfaces (DMFS). DATA COLLECTION AND ANALYSIS: Two review authors, independently and in duplicate, assessed the eligibility of studies for inclusion, and carried out risk of bias assessment and data extraction. In the event of disagreement, we sought consensus and consulted a third review author. We contacted trial authors for missing information. We used the prevented fraction (PF) as a metric for evaluating the efficacy of the intervention. The PF is defined as the mean caries increment in controls minus mean caries increment in the treated group divided by mean caries increment in controls. We conducted random-effects meta-analyses when data could be pooled. We assessed heterogeneity in the results of the studies by examining forest plots and by using formal tests for homogeneity. We recorded adverse effects (fluorosis) when the studies provided relevant data. MAIN RESULTS: We included 11 studies in the review involving 7196 children.In permanent teeth, when fluoride supplements were compared with no fluoride supplement (three studies), the use of fluoride supplements was associated with a 24% (95% confidence interval (CI) 16 to 33%) reduction in decayed, missing and filled surfaces (D(M)FS). The effect of fluoride supplements was unclear on deciduous or primary teeth. In one study, no caries-inhibiting effect was observed on deciduous teeth while in another study, the use of fluoride supplements was associated with a substantial reduction in caries increment.When fluoride supplements were compared with topical fluorides or with other preventive measures, there was no differential effect on permanent or deciduous teeth.The review found limited information on the adverse effects associated with the use of fluoride supplements. AUTHORS' CONCLUSIONS: This review suggests that the use of fluoride supplements is associated with a reduction in caries increment when compared with no fluoride supplement in permanent teeth. The effect of fluoride supplements was unclear on deciduous teeth. When compared with the administration of topical fluorides, no differential effect was observed. We rated 10 trials as being at unclear risk of bias and one at high risk of bias, and therefore the trials provide weak evidence about the efficacy of fluoride supplements

Validation of a Persian version of the OIDP index

BACKGROUND: Measuring the impacts of oral conditions on quality of life is an important part of oral health needs assessment. For this purpose a variety of oral health-related quality of life instruments have been developed. To use a scale in a new context or with a different groups of people, it is necessary to re-establish its psychometric properties. The objectives of this study are to develop and test the reliability and validity of the Persian version of Oral Impacts on Daily Performances (OIDP) index. METHODS: The Persian version of OIDP index was developed through a linguistic translation exercise. The psychometric properties of the Persian version of OIDP were evaluated in terms of face, content, construct and criterion validity in addition to internal and test-retest reliability. A convenience sample of 285 working adults aged 20–50 living in Mashad was recruited (91% response rate) to evaluate the Persian version. RESULTS: The Persian version of OIDP had excellent validity and reliability charactersitics. Weighted Kappa was 0.91. Cronbachs alpha coefficient was 0.79. The index showed significant associations with self-rated oral and general health status, as well as perceived dental treatment needs, satisfaction with mouth and prevalence of pain in mouth (P < 0.001). 64.9% of subjects had an oral impact on their daily performances. The most prevalent performance affected was eating, followed by major work or role and sleeping. CONCLUSION: The Persian version of OIDP index is a valid and reliable measure for use in 20 to 50 year old working Iranians

Efficient Reconstruction of Metabolic Pathways by Bidirectional Chemical Search

One of the main challenges in systems biology is the establishment of the metabolome: a catalogue of the metabolites and biochemical reactions present in a specific organism. Current knowledge of biochemical pathways as stored in public databases such as KEGG, is based on carefully curated genomic evidence for the presence of specific metabolites and enzymes that activate particular biochemical reactions. In this paper, we present an efficient method to build a substantial portion of the artificial chemistry defined by the metabolites and biochemical reactions in a given metabolic pathway, which is based on bidirectional chemical search. Computational results on the pathways stored in KEGG reveal novel biochemical pathways

Frequency and Risk Indicators of Tooth Decay among Pregnant Women in France: A Cross-Sectional Analysis

INTRODUCTION: Little is known on the prevalence of tooth decay among pregnant women. Better knowledge of tooth decay risk indicators during pregnancy could help to develop follow-up protocols for women at risk, along with better prevention strategies. The aim of this study was to assess the frequency of tooth decay and the number of decayed teeth per woman in a large sample of pregnant women in France, and to study associated risk indicators. METHODS: A secondary cross-sectional analysis of data from a French multicentre case-control study was performed. The sample was composed of 1094 at-term women of six maternity units. A dental examination was carried out within 2 to 4 days post-partum. Socio-demographic and behavioural characteristics were obtained through a standardised interview with the women. Medical characteristics were obtained from the women's medical records. Risk indicators associated with tooth decay were identified using a negative binomial hurdle model. RESULTS: 51.6% of the women had tooth decay. The mean number of decayed teeth among women having at least one was 3.1 (s.d. = 2.8). Having tooth decay was statistically associated with lower age (aOR = 1.58, 95%CI [1.03,2.45]), lower educational level (aOR = 1.53, 95%CI [1.06,2.23]) and dental plaque (aOR = 1.75, 95%CI [1.27,2.41]). The number of decayed teeth was associated with the same risk indicators and with non-French nationality and inadequate prenatal care. DISCUSSION: The frequency of tooth decay and the number of decayed teeth among pregnant women were high. Oral health promotion programmes must continue to inform women and care providers about the importance of dental care before, during and after pregnancy. Future research should also assess the effectiveness of public policies related to oral health in target populations of pregnant women facing challenging social or economic situations