Effect of a 5000 ppm fluoride toothpaste and a 250 ppm fluoride mouth rinse on the demineralisation of dentin surfaces

Abstract Background The purpose of this study was to test the null hypothesis that there is no difference between the effect of (1) a 5000 ppm fluoride toothpaste, and (2) a 250 ppm fluoride mouth rinse on demineralized human dentin surfaces, against the alternative hypothesis of a difference. Findings Dentin specimens were obtained from the cervical regions of 45 extracted human third molars. Half the surface of each specimen was sealed with a self-etching adhesive system and served as the reference surface. The dentin specimens were randomly assigned to one of the three groups, 5000 ppm fluoride toothpaste (Duraphat), 250 ppm fluoride mouth rinse (Meridol) and distilled water (negative control). An intraoral appliance was made for one volunteer. In each test cycle, 15 specimens were inserted in the appliance and worn for 24 hours a day, over a period of three weeks. Once daily, the appliance was immersed in the agent being tested; either toothpaste slurry, mouth rinse or distilled water for 60 seconds. Demineralization was assessed in terms of lesion depth (μm) and mineral loss (vol. % × μm) by transversal microradiography. Data analysis was accomplished using Kolmogorov-Smirnov test and ANOVA (SPSS 12.0). Statistically significant differences for mineral loss and lesion depth were found between the toothpaste and the mouth rinse as well as between the toothpaste and the control group, but not between the mouth rinse and the control group. Conclusion Within the limitations of this study, the results suggest that treatment of demineralised dentin with a toothpaste containing 5000 ppm fluoride may considerably reduce mineral loss and lesion depth on exposed dentin.http://deepblue.lib.umich.edu/bitstream/2027.42/112660/1/13104_2009_Article_285.pd

Antidiabetic Medication Utilisation before and during Pregnancy in Switzerland between 2012 and 2019: An Administrative Claim Database from the MAMA Cohort.

BACKGROUND The incidence of diabetes mellitus (both pregestational and gestational) is increasing worldwide, and hyperglycemia during pregnancy is associated with adverse pregnancy outcomes. Evidence on the safety and efficacy of metformin during pregnancy has accumulated resulting in an increase in its prescription in many reports. AIMS We aimed to determine the prevalence of antidiabetic drug use (insulins and blood glucose-lowering drugs) before and during pregnancy in Switzerland and the changes therein during pregnancy and over time. METHODS We conducted a descriptive study using Swiss health insurance claims (2012-2019). We established the MAMA cohort by identifying deliveries and estimating the last menstrual period. We identified claims for any antidiabetic medication (ADM), insulins, blood glucose-lowering drugs, and individual substances within each class. We defined three groups of pattern use based on timing of dispensation: (1) dispensation of at least one ADM in the prepregnancy period and in or after trimester 2 (T2) (pregestational diabetes); (2) dispensation for the first time in or after T2 (GDM); and (3) dispensation in the prepregnancy period and no dispensation in or after T2 (discontinuers). Within the pregestational diabetes group, we further defined continuers (dispensation for the same group of ADM) and switchers (different ADM group dispensed in the prepregnancy period and in or after T2). RESULTS MAMA included 104,098 deliveries with a mean maternal age at delivery of 31.7. Antidiabetic dispensations among pregnancies with pregestational and gestational diabetes increased over time. Insulin was the most dispensed medication for both diseases. Between 2017 and 2019, less than 10% of pregnancies treated for pregestational diabetes continued metformin rather than switching to insulin. Metformin was offered to less than 2% of pregnancies to treat gestational diabetes (2017-2019). CONCLUSION Despite its position in the guidelines and the attractive alternative that metformin represents to patients who may encounter barriers with insulin therapy, there was reluctance to prescribe it

Reproductive Safety of Trazodone After Maternal Exposure in Early Pregnancy: A Comparative ENTIS Cohort Study.

Trazodone is indicated for the treatment of major depressive disorder, but more frequently prescribed off-label at lower doses for insomnia in women of childbearing age. The aim of this study was to assess the risks linked to trazodone exposure during pregnancy for which limited safety data are available. This multicenter, observational prospective cohort study compared pregnancy outcomes in women exposed to trazodone in early pregnancy against those in a reference group of women exposed to a selective serotonin reuptake inhibitors (SSRIs) between 1996 and 2021. The sample included 221 trazodone and 869 SSRI-exposed pregnancies. Exposure to trazodone in the first trimester was not associated with a significant difference in the risk of major congenital anomalies (trazodone [1/169, 0.6%]; SSRI [19/730, 2.6%]; adjusted odds ratio, 0.2; 95% confidence interval, 0.03-1.77). The cumulative incidences of live birth were 61% and 73% in the trazodone and reference group, respectively (25% vs 18% for pregnancy loss and 14% vs 10% for pregnancy termination). Trazodone exposure was not associated with a significantly increased risk of pregnancy termination and pregnancy loss. The rate of small for gestational age infants did not differ between the groups. This study did not reveal a significant difference in the risk of major congenital anomalies after first trimester exposure to trazodone, compared with SSRI exposure. Although this study is the largest so far, these results call for confirmation through further studies

Validation of a Novel Method to Assess the Clinical Quality of Information in Pregnancy-Related Pharmacovigilance Case Reports: A ConcePTION Project

Background: To assess the causal relationship between a medicinal product and a reported event, relevant information needs to be present. Information elements for assessing cases of exposure to medicinal products during pregnancy were predefined and used in a new tool to assess the quality of information. However, the extent in which the presence or absence of these predefined information elements is associated with the overall clinical quality of these cases, as evaluated by pharmacovigilance experts, remains uncertain. Objective: We aimed to validate a novel method to assess the clinical quality of information in real-world pregnancy pharmacovigilance case reports. Methods: The clinical quality of case reports regarding medicinal product exposure and pregnancy-related outcomes was appraised from spontaneous reports, literature, Teratology Information Services (UK and Switzerland), The Dutch Pregnancy Drug Register, the Gilenya pregnancy registry and the Enhanced PV programme of Novartis. Assessment was done by means of the novel standardised tool based on the presence and relevance of information, and by expert judgement. The novel tool was validated compared to the expert assessment as the gold standard expressed as the area under the receiver operating characteristic curves, after which the sensitivity and specificity were calculated using cross-tabulations. Inter-rater variability was determined by means of weighted Cohen’s kappa. Results: One hundred and eighty-six case reports were included. The clinical quality score as assessed by the novel method was divided into three categories with cut-off values of 45% (poor to intermediate) and 65% (intermediate to excellent). Sensitivity was 0.93 and 0.96 for poor to intermediate and intermediate to excellent, respectively. Specificity was respectively 0.52 and 0.73. Inter-rater variability was 0.65 (95% confidence interval 0.53–0.78) for the newly developed approach, and 0.40 (95% confidence interval 0.28–0.52) for the gold standard assessment. Conclusions: The tool described in this study using the presence and relevance of elements of information is the first designed, validated and standardised method for the assessment of the quality of information of case reports in pregnancy pharmacovigilance data. This method confers less inter-rater variability compared with a quality assessment by experts of pregnancy-related pharmacovigilance data

Validation of a Novel Method to Assess the Clinical Quality of Information in Pregnancy-Related Pharmacovigilance Case Reports: A ConcePTION Project

BACKGROUND: To assess the causal relationship between a medicinal product and a reported event, relevant information needs to be present. Information elements for assessing cases of exposure to medicinal products during pregnancy were predefined and used in a new tool to assess the quality of information. However, the extent in which the presence or absence of these predefined information elements is associated with the overall clinical quality of these cases, as evaluated by pharmacovigilance experts, remains uncertain. OBJECTIVE: We aimed to validate a novel method to assess the clinical quality of information in real-world pregnancy pharmacovigilance case reports. METHODS: The clinical quality of case reports regarding medicinal product exposure and pregnancy-related outcomes was appraised from spontaneous reports, literature, Teratology Information Services (UK and Switzerland), The Dutch Pregnancy Drug Register, the Gilenya pregnancy registry and the Enhanced PV programme of Novartis. Assessment was done by means of the novel standardised tool based on the presence and relevance of information, and by expert judgement. The novel tool was validated compared to the expert assessment as the gold standard expressed as the area under the receiver operating characteristic curves, after which the sensitivity and specificity were calculated using cross-tabulations. Inter-rater variability was determined by means of weighted Cohen's kappa. RESULTS: One hundred and eighty-six case reports were included. The clinical quality score as assessed by the novel method was divided into three categories with cut-off values of 45% (poor to intermediate) and 65% (intermediate to excellent). Sensitivity was 0.93 and 0.96 for poor to intermediate and intermediate to excellent, respectively. Specificity was respectively 0.52 and 0.73. Inter-rater variability was 0.65 (95% confidence interval 0.53-0.78) for the newly developed approach, and 0.40 (95% confidence interval 0.28-0.52) for the gold standard assessment. CONCLUSIONS: The tool described in this study using the presence and relevance of elements of information is the first designed, validated and standardised method for the assessment of the quality of information of case reports in pregnancy pharmacovigilance data. This method confers less inter-rater variability compared with a quality assessment by experts of pregnancy-related pharmacovigilance data

Improving Data Collection in Pregnancy Safety Studies: Towards Standardisation of Data Elements in Pregnancy Reports from Public and Private Partners, A Contribution from the ConcePTION Project.

INTRODUCTION AND OBJECTIVE The ConcePTION project aims to improve the way medication use during pregnancy is studied. This includes exploring the possibility of developing a distributed data processing and analysis infrastructure using a common data model that could form a foundational platform for future surveillance and research. A prerequisite would be that data from various data access providers (DAPs) can be harmonised according to an agreed set of standard rules concerning the structure and content of the data. To do so, a reference framework of core data elements (CDEs) recommended for primary data studies on drug safety during pregnancy was previously developed. The aim of this study was to assess the ability of several public and private DAPs using different primary data sources focusing on multiple sclerosis, as a pilot, to map their respective data variables and definitions with the CDE recommendations framework. METHODS Four pregnancy registries (Gilenya, Novartis; Aubagio, Sanofi; the Organization of Teratology Information Specialists [OTIS]; Aubagio, Sanofi; the Dutch Pregnancy Drug Register, Lareb), two enhanced pharmacovigilance programmes (Gilenya PRIM, Novartis; MAPLE-MS, Merck Healthcare KGaA) and four Teratology Information Services (UK TIS, Jerusalem TIS, Zerifin TIS, Swiss TIS) participated in the study. The ConcePTION primary data source CDE includes 51 items covering administrative functions, the description of pregnancy, maternal medical history, maternal illnesses arising in pregnancy, delivery details, and pregnancy and infant outcomes. For each variable in the CDE, the DAPs identified whether their variables were: identical to the one mentioned in the CDE; derived; similar but with a divergent definition; or not available. RESULTS The majority of the DAP data variables were either directly taken (85%, n = 305/357, range 73-94% between DAPs) or derived by combining different variables (12%, n = 42/357, range 0-24% between DAPs) to conform to the CDE variables and definitions. For very few of the DAP variables, alignment with the CDE items was not possible, either because of divergent definitions (1%, n = 3/357, range 0-2% between DAPs) or because the variables were not available (2%, n = 7/357, range 0-4% between DAPs). CONCLUSIONS Data access providers participating in this study presented a very high proportion of variables matching the CDE items, indicating that alignment of definitions and harmonisation of data analysis by different stakeholders to accelerate and strengthen pregnancy pharmacovigilance safety data analyses could be feasible

Pregnancy-related pelvic girdle pain: an update

A large number of scientists from a wide range of medical and surgical disciplines have reported on the existence and characteristics of the clinical syndrome of pelvic girdle pain during or after pregnancy. This syndrome refers to a musculoskeletal type of persistent pain localised at the anterior and/or posterior aspect of the pelvic ring. The pain may radiate across the hip joint and the thigh bones. The symptoms may begin either during the first trimester of pregnancy, at labour or even during the postpartum period. The physiological processes characterising this clinical entity remain obscure. In this review, the definition and epidemiology, as well as a proposed diagnostic algorithm and treatment options, are presented. Ongoing research is desirable to establish clear management strategies that are based on the pathophysiologic mechanisms responsible for the escalation of the syndrome's symptoms to a fraction of the population of pregnant women