Master File Research Articles

The impact of the COVID-19 pandemic on the labour market outcomes of Indigenous persons living off-reserve in Canada

The recent COVID-19 pandemic had an impact on the labour force activity of many, but the effect of the crisis on the labour market outcomes of Indigenous peoples in Canada is relatively understudied. Using data from the master files of the Canadian Labour Force Survey (LFS), this analysis first considers the relative probability of four mutually exclusive labour force states: employed; unemployed; not in the labour force, but not discouraged; and not in the labour force due to being a discouraged worker. Differences in hours worked as well as earnings comparing Indigenous and non-Indigenous workers are then examined. The findings reveal that, regardless of the COVID-19 pandemic, Indigenous Canadians were relatively more likely to be either unemployed or not in the labour force (including being a discouraged worker) than to be employed as compared to their non-Indigenous counterparts. Indigenous workers earned roughly 3 percent less than their non-Indigenous counterparts. The earnings penalty experienced by Indigenous workers, was slightly smaller at the bottom of the wage distribution at 2 percent, increasing to roughly 3.3 percent at the top 90th percentile of the earnings function. During the COVID-19 period, while the risk of unemployment was lower for Indigenous persons, the risk of being a discouraged worker was even higher for Indigenous Canadians during the pandemic. Using an ad-hoc supplement to the LFS conducted by Statistics Canada in response to the pandemic, this study finds that Indigenous respondents were less likely than non-Indigenous respondents to either work from home or receive any form of Canada relief benefit from April 2020 to October 2021. The implications of these findings suggest a role for policy makers to improve access to funding supports for Indigenous workers and students seeking to pursue higher education to improve labour market outcomes. Additionally, employers play an important role in ensuring that Indigenous workers have fair access to job opportunities.

Specific aspects of bacteriophage regulation: international practices and future developments

INTRODUCTION. The increasing prevalence of multidrug-resistant strains of pathogens determines the need for fundamentally new antibacterial agents, including bacteriophage preparations. The consistent implementation of phage therapy is hindered by the lack of generally accepted standardised regulatory documents governing the legal and methodological aspects of the production and preclinical and clinical studies of bacteriophage preparations.AIM. This study aimed to analyse the international experience with the production and lifecycle management of bacteriophage preparations, as well as the main regulatory requirements for the control of their quality, safety, and efficacy.DISCUSSION. It is difficult to develop virulent bacteriophage preparations in accordance with the existing requirements for other medicinal products because of the biological characteristics of bacteriophages, the wide variety of bacteriophage strains, and the potential for rapid changes both in the bacteriophage population and in the pathogen population. Therefore, it is reasonable to develop streamlined marketing authorisation routes for phage therapies and methods for the assessment of their safety and efficacy. As part of these efforts, it is necessary to assess the adverse events specific to this group of medicinal products, such as the risks of lysogeny, resistance to bacteriophages, and antibiotic resistance gene transfer between bacterial strains. The pharmaceutical development of bacteriophage preparations can be based on several approaches. Many countries worldwide, including the United States, are implementing the concept of Quality by Design, considering approaches based on the Biological Master File, and conducting Expanded Access programmes. The Active Substance Master File procedure allows the submission of a separate document package covering only part of the registration dossier for regulatory approval. Expanded Access programmes provide individual patients with access to innovative medicinal products without approved treatment protocols. In the Russian Federation, the commercial production of bacteriophage medicinal products is conducted in accordance with the quality standards specified in the State Pharmacopoeia of the Russian Federation.CONCLUSIONS. There are fundamental differences in the approaches to phage therapy and its regulation around the world and in the Russian Federation. It is reasonable to supplement the current national guidelines for the safety and efficacy evaluation of bacteriophage preparations, in particular, to specify the requirements for conducting preclinical studies.

Incidence of cardiovascular disease in a cohort of mine workers exposed to ultrafine aluminum powder in Ontario, Canada.

A retrospective cohort study was conducted to estimate associations between an ultrafine aluminum powder, McIntyre Powder (MP), and cardiovascular disease incidence in a cohort of mine workers from Ontario, Canada. Disease outcomes included ischemic heart disease (IHD), acute myocardial infarction (AMI), congestive heart failure (CHF), and strokes and transient ischemic attacks (STIA). Using work history records from the Ontario Mining Master File (MMF) mine workers were followed for disease incidence in administrative health records. The analysis included 25,813 mine workers who were exposed to MP between 1943 and 1979 and followed for cardiovascular disease (CVD) diagnoses between 2006 and 2018. Cardiovascular disease cases were ascertained using physician, hospital, and ambulatory care records. Poisson regression models were used to estimate age and birth-year adjusted incidence rate ratios (RR) and 95% confidence intervals (CI) for associations between MP exposure and CVD outcomes. Ever-exposure to MP was positively associated with modest increases in the incidence rate of IHD, AMI, and CHF, but not STIA, using both assessment approaches. Duration of self-reported MP exposure was positively associated with monotonically increasing rates of IHD and AMI compared to never-exposed miners, with the greatest association observed among miners with >20 years of exposure (for IHD: RR 1.24, 95% CI: 0.91-1.68; and for AMI: RR 1.52, 95% CI 1.01-2.28). Mine workers ever-exposed to MP had modestly elevated rates of CVD. The rate of CVD diagnoses appeared to increase with longer duration of exposure when assessed by both self-reported exposure and through historical records.

Regulatory requirement and filling procedure of drug master file in India under central drug standard control organization (CDSCO) in comparison with South Korea

The Drug master file (DMF) is a type of Confidential file that submitted to regulatory authorities about the ingredients, process, packing and storage of any drugs intended to human use. Drug master file plays an important role in production of drug. The Indian regulatory agency is a CDSCO that manages and encourage DMFs in India and in South Korea MFDS manages the DMFs. Unveiling the difference in regulatory requirements and filling procedure of DMF in India and South Korea as per CDSCO and MFDS respectively. Make certain the Protection, Grade, and Effectiveness of Drug Products.

Cesarean delivery, labor duration, and mothers’ mortality risk over 50 years of follow-up

BackgroundPregnancy complications have been recognized as a window to future health. Though cesarean delivery is common, it is unknown whether labor duration and mode of delivery are associated with maternal long-term mortality. ObjectiveTo examine whether labor duration and mode of delivery were associated with all-cause and cause-specific mortality. Study DesignParticipants were mothers from the multisite Collaborative Perinatal Project (CPP) cohort (1959–1966; n=43,646, limited to last CPP delivery). We ascertained all-cause and specific causes of death as of 2016 via linkage to the National Death Index and Social Security Death Master File. Hazard ratios (HR) testing mode of delivery and labor duration were estimated using Cox proportional hazards models adjusted for demographic and clinical characteristics. We further stratified analyses by parity. ResultsAmong participants with a recorded delivery mode, 5.9% (2486/42,335) had a cesarean delivery. Participants who had a cesarean were older (26.9 vs 24.3 years), with higher body mass index (24.0 vs 22.7 kg/m2), were less likely to be nulliparous (21% vs 30%), and more likely to have a household income of at least $6000 (22% vs 17%), to smoke ≥1 pack/d (18% vs 15%), to have diabetes mellitus (12% vs 1%) and to have a prior medical condition (47% vs 34%), compared to participants with a vaginal delivery. Delivery mode was similar by race/ethnicity, marital status, and education. Median labor duration was 395 minutes among participants who had an intrapartum cesarean delivery and 350 minutes among participants delivered vaginally. By 2016, 52.2% of participants with a cesarean delivery and 38.5% of participants with a vaginal delivery had died. Cesarean vs vaginal delivery was significantly associated with increased risk for all-cause mortality (HR=1.16 (95% confidence interval [CI]: 1.09, 1.23); in nulliparas, HR=1.27 (95% CI: 1.09, 1.47); in multiparas, HR=1.13 (95% CI: 1.06, 1.21) as well as increased risk of death from cardiovascular disease, diabetes, respiratory disease, infection, and kidney disease. Associations with death from cardiovascular disease, infection, and kidney disease were stronger for multiparas than nulliparas, though the association with death from diabetes was stronger among nulliparas. Labor duration was not significantly related to overall mortality. ConclusionIn a historic United States cohort with a low cesarean delivery rate, cesarean delivery was an indicator for subsequent increased mortality risk, particularly related to cardiovascular disease and diabetes. Future studies with long-term follow-up are warranted given the current high prevalence of cesarean delivery.

Evolution of ad hoc and routine data linkage in Australia

Australia has a rich history of utilising linked administrative data for health and human services research. The Population Health Research Network (PHRN), established in 2009, has developed national population-based data linkage capability and infrastructure. Australia-wide, specialist data linkage units have successfully linked their core population health data for over a decade, and within the network over 200 data collections are routinely linked. Data collections are typically classified as either routinely linked or linked on a project-by-project, ad hoc basis. Over time, linkage of data collections that were originally considered ad hoc, for example some longitudinal cohorts and clinical registries, has become ‘routine’. This paper reports on findings of a study that evaluated the volume and proportion of data linkage requests that have been facilitated through the PHRN over the past 5 years that include ad hoc linkage. The paper also reports on the type of data collections that have been linked on an ad hoc basis and details the type of research projects and fields of research currently supported via ad hoc linkage. Quantifying and characterising the type and most sought-after data collections for ad hoc linkage and the breadth of research being undertaken informs future planning and resource allocation for expanding the Australian national linkage capability. This paper explores the integration of ad hoc data linkage within the evolving landscape of expanded master linkage files and national linked data assets, responding to a growing range of data sources and research that could benefit from population-based data linkage.

Implementing Linkage Quality Assessments in Large-Scale Privacy Preserving Infrastructure: Did we kill them a second time and why are there zombies?

The National Clinical Cohort Collaborative (N3C) uses privacy-preserving record linkage (PPRL) to formulate longitudinal patient histories and for de-duplication across disparate data including electronic health records, administrative claims, and mortality data. The N3C employs a linkage honest broker implementation model which separates the entity holding de-identified PPRL tokens, from the entity holding the substantive data payloads. As a result of this data governance structure, linkage quality assessments are necessarily distributed into 2 distinct processes: 1) Linkage Honest Broker receipt and processing of linkages, 2) Data Aggregation entity assembling data based on received linkage crosswalks. Data is released on a weekly basis. This presentation will focus on Step 2 for the Mortality data linkages where the downstream data linkage pipelines must assess linkage quality across several dimensions of quality, focused on plausibility. There are 4 types of mortality data spanning the electronic health record, government Social Security Administration death master files, third-party obituary data, and administrative claims. Each of these sources has different levels of authoritativeness and data latency, compounding the challenges of reconciling fact of death including accurate death reporting dates. To address these challenges, we implemented an automated linkage quality pipeline which generates reports that assess linkage plausibility across the various data types, classifying concordance and discordance between data sources including age, dates of death, surfacing plausible and non-plausible activities post-death. Sharing our real-world implementation will aid conference attendees in understanding how to plan for such activities when considering specific implementation models for privacy-preserving linkages.

Microwave-assisted green synthesis and molecular docking study of some new 4-thiazolidinone derivatives as possible bioactive agents

We have developed an economical and environmentally friendly microwave-assisted efficient method for the synthesis of a series of new 4-oxo-thiazolidine derivatives (4a-d). The method involves microwave irradiated cyclocondensation reaction of Schiff bases (3a-d) and thioglycolic acid in drug master file (DMF). 4-oxo-thiazolidine derivatives (4a-d) was also synthe 4-Oxo-Thiazolidine derivatives were also synthesized by conventional heating procedures and consequence were Compared with Microwave assisted green method. The results suggest that microwave-assisted syntheses lead to higher yields within very short reaction times. Antimicrobial screening of all the synthesized compounds was carried out using Gram-positive strains Staphylococcus aureus and Gram-negative strain encompassing Escherichia coli, Proteus vulgaris, and Salmonella typhi. The results were compared with the standard drug chloramphenicol. All the synthesized compounds were subsequently examined using molecular docking experiments against peptide deformylase (PDB ID: 1G2A), which evaluates the binding interaction of ligands with enzyme active sites.. KEYWORDS :Microwave irradiation, Thiazolidinone, Molecular docking, Peptide deformylase, Antimicrobial screening.

Submission of Documents on the Pharmacovigilance System as Part of the Registration Dossier within the Framework of the EAEU Procedures: Analysis of Requirements and Typical Errors

INTRODUCTION. Documents on the pharmacovigilance system of the marketing authorisation holder (MAH), including the Pharmacovigilance System Master File (PSMF) and the PSMF-based summary of the pharmacovigilance system (SPS), are a mandatory component of the registration dossier for a medicinal product. Applicants must submit and update these documents in strict accordance with the legislation of the Eurasian Economic Union (EAEU). Systematisation of the requirements for drafting and submitting documents on the pharmacovigilance system will help applicants streamline the documentation process.AIM. This study aimed to analyse the requirements for submitting either the PSMF or the SPS, depending on the EAEU marketing authorisation procedure, and to describe typical errors made by applicants when submitting these documents.DISCUSSION. The content of dossier documents on the pharmacovigilance system is regulated by the Rules of Good Pharmacovigilance Practice of the Eurasian Economic Union (Decision No. 87 of the Council of the Eurasian Economic Commission (EEC) dated 3 November 2016), and their submission is governed by the Rules of Marketing Authorisation and Assessment of Medicinal Products for Human Use (EEC Council Decision No. 78 dated 3 November 2016). MAHs are required to keep documents on the pharmacovigilance system and the corresponding registration dossiers up to date. This article summarises the specific requirements for submitting either the PSMF or the SPS, depending on the EAEU marketing authorisation procedure. Additionally, this article highlights typical errors made by MAHs when preparing documents on the pharmacovigilance system. According to the EAEU Rules of Good Pharmacovigilance Practice, the first application submitted for marketing authorisation of a medicinal product in the EAEU should include the PSMF, and subsequent applications should include the SPS as part of the registration dossier. Changes to the pharmacovigilance documents should be made in accordance with the classifier (EEC Council Decision No. 78 dated 3 November 2016).CONCLUSIONS. This analysis of the requirements for the PSMF or the SPS as part of various marketing authorisation procedures will facilitate compliance with the requirements of the EAEU legislative acts and ensure correct submission of necessary documents on the pharmacovigilance system by applicants. In addition, regulatory authorities will make fewer requests to submit missing information and grant more marketing authorisations.

Trends in the Completeness and Validity of Sources of Death Data Against the National Death Index From 2010 to 2018.

We investigated time trends in validation performance characteristics for six sources of death data available within the Healthcare Integrated Research Database (HIRD) over 8 years. We conducted a secondary analysis of a cohort of advanced cancer patients with linked National Death Index (NDI) data identified in the HIRD between 2010 and 2018. We calculated sensitivity, specificity, positive predictive value, and negative predictive value for six sources of death status data and an algorithm combining data from available sources using NDI data as the reference standard. Measures were calculated for each year of the study including all members in the cohort for at least 1 day in that year. We identified 27 396 deaths from any source among 40 692 cohort members. Between 2010 and 2018, the sensitivity of the Death Master File (DMF) decreased from 0.77 (95% CI = 0.76, 0.79) to 0.12 (95% CI = 0.11, 0.14). In contrast, the sensitivity of online obituary data increased from 0.43 (95% CI = 0.41, 0.45) in 2012 to 0.71 (95% CI = 0.68, 0.73) in 2018. The sensitivity of the composite algorithm remained above 0.83 throughout the study period. PPV was observed to be high from 2010 to 2016 and decrease thereafter for all sources. Specificity and NPV remained at high levels throughout the study. We observed that the sensitivity of mortality data sources compared with the NDI could change substantially between 2010 and 2018. Other validation characteristics were less variable. Combining multiple sources of mortality data may be necessary to achieve adequate performance particularly for multiyear studies.

Mortality Risk of Low BMI in Life Insurance Applicants.

-This study seeks to quantify the mortality effect of low levels of body mass index (BMI) on life insurance applicants who, based on their laboratory profile and other information, appear to be suitable for life insurance coverage. -It has been demonstrated that low BMI is associated with higher mortality risk than normal or near-normal BMI. -Data were collected from over 4.7 million life insurance applicants with available BMI tested between 1995 and 2021, and vital status was assessed via the Social Security Death Master File. Cox models treating BMI as continuous and as a categorical variable were constructed, controlling for age, and split by sex after excluding those with laboratory or biometric test results, which were far enough outside the normal range to imply elevated mortality. -Models treating BMI as a continuous variable and allowing an interaction term for age showed that low BMI was strongly associated with mortality at ages 50 and above in both sexes. In the categorical models, only the lowest category of BMI (below the 1st percentile) in men aged 40-60, the lowest 2 categories (below the 5th percentile) in women aged 40-60, and the lowest 3 categories (below the 10th percentile) in those aged 60-80 years, were significantly associated with elevated mortality. No elevated mortality was detected in those under age 40 with low BMI. -Based on this study, low BMI is associated with elevated mortality in otherwise healthy applicants, but this association is dependent on age.

Effect of printing technology and orientation on the accuracy of three-dimensional printed retainers.

To evaluate the impact of printer technology and print orientation on the accuracy of directly printed retainers. Digital retainers were printed with two different printing technologies: digital light processing (DLP) and stereolithography (SLA), using two different orientations: 0° and 90°. After printing, the retainers (n = 40) were scanned using cone-beam computed tomography. The DICOM files were then converted into standard tessellation language (STL) files. Comparison of the printed retainers with a master file was done by superimposition using a three-dimensional (3D) best-fit tool in Geomagic software. A ±0.25 mm tolerance was set to detect differences between the superimposed files. Statistical analysis was conducted (Kruskal-Wallis and Wilcoxon-Mann-Whitney tests, with Bonferroni correction). The lowest median average deviation was observed for the DLP horizontally printed models (median, [interquartile range (IQR)] = 0.01 mm, [-0.01, 0.02]) followed by the SLA horizontally printed retainers (median, [IQR] = 0.05 mm, [0.03, 0.07]). The highest median inside the tolerance levels ratio was observed for the horizontally SLA printed retainers (median, [IQR] = 78.9%, [74.4, 82.4%]) followed by the horizontally DLP printed retainers (median, [IQR] = 78.2%, [74.5, 80.7%]). Both technologies (DLP and SLA) showed 3D printed results compatible with orthodontic clinical needs. Printing orientation was more important than printer type regarding its accuracy. Additional studies are needed to evaluate the accuracy of direct printed appliances clinically.

Dossier submission in the UK after Brexit

The withdrawal of the United Kingdom (UK) from the European Union (EU), commonly known as Brexit, occurred on January 31, 2020, triggering a transition period until December 31, 2020, during which the UK and EU negotiated their future relationship. Brexit has brought significant changes to regulatory frameworks, particularly in the pharmaceutical sector. This article examines the transition of dossier submission procedures in the UK following Brexit, focusing on the implications for marketing authorizations (MAs) and pharmacovigilance. The Medicines and Healthcare Products Regulatory Agency (MHRA) transitioned to an independent regulatory body, establishing new guidelines for pharmaceutical companies seeking MAs in the UK. Key changes in marketing authorization routes include the conversion of centrally authorized products (CAPs) to UK MAs, the introduction of the Decentralized and Mutual Recognition Reliance Procedure (MRDCRP), and the implementation of a 150-day assessment timeline for national procedures. This article compares dossier requirements before and after Brexit in the UK and highlights pharmacovigilance requirements post-Brexit, emphasizing adjustments to reporting obligations, Qualified Person for Pharmacovigilance (QPPV) responsibilities, and the establishment of UK-specific Pharmacovigilance System Master Files (PSMFs). Additionally, it addresses the dossier Module 1 administrative information requirements to provide a comprehensive overview of the changes in regulatory procedures in the UK pharmaceutical sector following Brexit. Overall, the article aims to serve as a valuable resource for industry professionals, regulatory experts, and other stakeholders seeking clarity on the regulatory changes and their implications for pharmaceutical products in the UK following Brexit.

Prosthetic outcomes after amputation and the impact of mobility level on survival

ObjectiveLower extremity amputation continues to be necessary in a significant number of patients with peripheral vascular disease. The 5-year survival following lower limb loss is markedly reduced. Many of these patients are never fitted with a prosthesis, and there is a dearth of knowledge regarding the barriers to prosthetic attainment. The goal of this study was to identify the risk factors for not receiving a prosthesis and the effect of mobility level on survival following major amputation. MethodsThis was a retrospective analysis of all patients that underwent lower extremity amputation by surgeons in our practice from January 1, 2010, to December 31, 2019. Abstracted data included: age, sex, race, body mass index, comorbidities, American Society of Anesthesiologists score, statin use, level of amputation, stump revision, fitting for prosthesis, type of prosthesis, and the United States’ Medicare Functional Classification Level, also called K level. Survival was determined using a combination of sources, including the Social Security Death Master File, searches of multiple genealogic registries, and general internet searches. Multivariable logistic regression was used to determine risk factors associated with prosthesis attainment. Multivariable Cox proportional hazard regression with time-dependent covariates was performed to assess risk factors associated with 5-year mortality. ResultsA total of 464 patients were included in this study. The mean age was 65 years, and mean body mass index was 27 kg/m2. The majority of patients were male (68%), White (56%), diabetic (62%), and hypertensive (76%), and underwent below-the-knee amputation (69%). Prosthetic attainment occurred in 185 (40%). On multivariable analysis, age >81 years and current tobacco use were associated with no prosthetic fitting. Overall 5-year survival was 41.9% (95% confidence interval [CI], 37.6%-46.6%) (below-the-knee amputation, 47.7% [95% CI, 42.5%-53.5%]; above-the-knee amputation, 28.7% [95% CI, 22.1%-37.2%]). On multivariable analysis, age >60 years, congestive heart failure, above-the-knee amputation, and no prosthetic attainment were associated with decreased survival. Increasing K level was incrementally associated with improved survival. ConclusionsThis study has identified several patient factors associated with prosthetic attainment, as well as multiple factors predictive of reduced survival after amputation. Being referred for prosthetic fitting was associated with improved survival not explained by patient characteristics and comorbidities. The Medicare Functional Classification Level K level predicts survival. More research is needed to determine the barriers to prosthetic attainment and if improving a patients K level will improve survival.

Comparative Evaluation of Solite RS3 and HyFlex Remover Retreatment Files in Conserving Remaining Dentin Thickness During Endodontic Retreatment Using Cone Beam Computed Tomography: An In Vitro Analysis.

Introduction Non-surgical retreatment is seen as a conservative choice for dealing with recurrent infections, instead of opting for periapical surgery. The retreatment processes should be promptly and efficiently carried out, utilizing a suitable armamentarium. The objective of this experiment is to evaluate the quantity of root dentin that remains following the removal of gutta-percha (GP) from the root canal employing two distinct retreatment files. Materials and methods Sixty single-rooted teeth were selected for the examination. The process of shaping and cleaning was performed using the step-back approach, with a master apical file size of 40. The smear layer was effectively eliminated by rinsing with a solution of 3% sodium hypochlorite and 17% ethylenediaminetetraacetic acid. Paper points were employed to desiccate the canals. The obturation process involved the utilization of the lateral compaction technique with the AH Plus sealer (Dentsply Sirona, NC, USA). The teeth were classified into two groups: Group I (n=30) underwent retreatment using HyFlex Remover (Coletene India, Pvt., Ltd.), whereas Group II (n=30) received therapy with Solite RS3 retreatment files (Solite Dental in Chennai, India). The remaining dentin thickness (RDT) was assessed by cone beam computed tomography at levels 3, 6, and 9 mm from the cemento enamel junction after the removal of GP. The acquired data underwent examination using an independent t-test to determine statistical significance. Results The findings demonstrate that the utilization of Solite RS3 files led to a higher level of dentin thickness remaining at 3 mm, 6 mm, and 9 mm on the mesial side in comparison to HyFlex Remover retreatment files. The observed difference was found to be statistically significant at a significance level of p<0.05 on the mesial side. Nevertheless, there was no notable disparity seen between the two file types at these three levels on the distal side (p>0.05). Conclusion Based on the obtained results of the study, it can be concluded that Solite RS3 files show promise in preserving the RDT. However, further studies encompassing diverse parameters are needed to establish a conclusive and definitive conclusion.

Comparative evaluation of incidence of dentinal defects after root canal preparation using three different endodontic retreatment systems - An in vitro study.

Safe and efficient removal of all root filling materials from the root canal system without compromising radicular dentin structure is essential for optimal nonsurgical retreatment. The aim of this study was to evaluate and compare the incidence of dentinal defects caused during root canal filling removal using conventional, rotary, and reciprocating retreatment file systems. A detailed protocol explaining purpose and procedures of the study was submitted to the Institutional Ethics Committee and ethical clearance obtained. Sixty human maxillary permanent central incisors were collected and decoronated to 12-mm standardized length. The canals prepared up to a master apical file size F3 with Protaper hand files, obturated using AH plus sealer, examined under the stereomicroscope (×40 magnification): Group I: Control (n = 15), Group II: Conventional (n = 15), Group III: Protaper Universal Retreatment Files (n = 15), and Group IV: Reciproc Blue (n = 15). After instrumentation, teeth were sectioned at 3, 6, and 9 mm from the apex to evaluate the presence of dentinal defects under the stereomicroscope. Statistics were performed using the SPSS, version, 25 (SPSS Inc., Chicago, IL, USA). Initially, normality test was done using the Shapiro-Wilk test and data were not normally distributed followed by Kruskal-Wallis test. P < 0.05 is considered statistically significant. Maximum percentage increase in dentinal defects was observed in Protaper Universal Retreatment Files followed by Conventional method and Reciproc Blue. Significantly Reciproc Blue reduced the incidence of dentinal defects after root canal preparation.

The Role of Model Master Files for Sharing, Acceptance, and Communication with FDA.

With the evolving role of Model Integrated Evidence (MIE) in generic drug development and regulatory applications, the need for improving Model Sharing, Acceptance, and Communication with the FDA is warranted. Model Master File (MMF) refers to a quantitative model or a modeling platform that has undergone sufficient model Verification & Validation to be recognized as sharable intellectual property that is acceptable for regulatory purposes. MMF provides a framework for regulatorily acceptable modeling practice, which can be used with confidence to support MIE by both the industry and the U.S. Food and Drug Administration (FDA). In 2022, the FDA and the Center for Research on Complex Generics (CRCG) hosted a virtual public workshop to discuss the best practices for utilizing modeling approaches to support generic product development. This report summarizes the presentations and panel discussions of the workshop symposium entitled "Model Sharing, Acceptance, and Communication with the FDA". The symposium and this report serve as a kick-off discussion for further utilities of MMF and best practices of utilizing MMF in drug development and regulatory submissions. The potential advantages of MMFs have garnered acknowledgment from model developers, industries, and the FDA throughout the workshop. To foster a unified comprehension of MMFs and establish best practices for their application, further dialogue and cooperation among stakeholders are imperative. To this end, a subsequent workshop is scheduled for May 2-3, 2024, in Rockville, Maryland, aiming to delve into the practical facets and best practices of MMFs pertinent to regulatory submissions involving modeling and simulation methodologies.

Overview and Design of the Child Maltreatment in Military Families Life Course Study

Objective This report presents an overview of the objectives, design, and analytic strategy of the Child Maltreatment in Military Families Life Course Study, an investigation of factors associated with child maltreatment in active duty military families. Method The study uses a case-control retrospective research design and discrete-time survival methodology to examine service member demographic characteristics, family characteristics, military-related characteristics, and military family life events associated with child maltreatment incidents that meet the Department of Defense definition of child abuse or neglect. The sample includes all active duty families with a first occurrence of child maltreatment anytime between Fiscal Year (FY) 2009 and FY 2018 (n = 28,684), and a representative sample of control families with children under age of 18 during the same period (n = 589,417). Analyses include child maltreatment and domestic abuse data from the Family Advocacy Program Central Registry; sponsor socio-demographic, military-related, and family data from the Active Duty Military Personnel Master and Defense Enrollment Eligibility Reporting System data files; deployment data from the Contingency Tracking System; and mental health data from the Medical Data Repository. Results and Conclusions Study results identify risk and protective factors associated with child maltreatment in military families, subgroups at elevated risk of child maltreatment, and periods of heightened risk during the military family life course. These results are expected to improve the ability to identify families most at-risk for particular types of child maltreatment and inform prevention strategies that promote the health and safety of military families.

Testing a Cloud-Based Model for Active Surveillance of Medical Devices with Analyses of Coronary Stent Safety Using the Data Extraction and Longitudinal Trend Analysis (DELTA) System.

To demonstrate the use of the Data Extraction and Longitudinal Trend Analysis (DELTA) system in the National Evaluation System for health Technology's (NEST) medical device surveillance cloud environment by analyzing coronary stent safety using real world clinical data and comparing results to clinical trial findings. Electronic health record (EHR) data from two health systems, the Social Security Death Master File, and device databases were ingested into the NEST cloud, and safety analyses of two stents were performed using DELTA. This is an observational study of patients receiving zotarolimus drug-eluting coronary stents (ZES) or everolimus eluting coronary stents (EES) between July 1, 2015 and December 31, 2017. After exclusions, 3334 patients receiving EES and 1002 receiving ZES were available for study. Analysis using inverse probability weighting showed no significant difference in one-year mortality or major adverse cardiac events (MACE) for EES compared to ZES [Mortality Odds Ratio 0.94 (95% CI 0.81-1.175); p = 0.780] [MACE Odds Ratio 1.04 (95% CI 0.92-1.16; p = 0.551]). Analysis using propensity matching showed no significant difference in EES one-year mortality (547 of 992 alive and available after censoring) compared to ZES (546 of 992) [Log-Rank statistic 0.3348 (p = 0.563)]. Automated cloud-based medical device safety surveillance using EHR data is feasible and was efficiently performed using DELTA. No statistically significant differences in 1-year safety outcomes between ZES and EES were identified using two statistical approaches, consistent with randomized trial findings.

Systematic review on social/moral competence interventions in Physical Education

Abstract Study aim: This systematic review drew the significant findings of carefully selected interventions to promote the social and moral competence (SC and MC, respectively) of children and adolescents mostly by investigating the effect of these interventions and focusing on strategies used. Material and methods: A number of English written, electronic databases (e.g., EBSCO, EBSCOhost Web, ERIC, Master FILE Premier, SPORT, SPORT Discus, and Web of Science) and grey literature – from 2005 to the present – were consulted from September 2021 to December 2021. School-based intervention studies that assessed moral competence (MC) or social competence (SC) were eligible for inclusion. The studies were stratified by pre-school and primary school children (&lt;12 years of age) and adolescents (≥12 years of age). A total of N = 24 documents referring to different intervention studies were included in the review. N = 10 interventions focused on children; while N = 14 targeted adolescents. Results: The most used strategies in the interventions were the ones that included components of MC or evaluated SC using specific protocols and tools. Conclusions: This review pointed at socio-emotional and moral skills which remained underdeveloped in school children unless physical education (PE) teachers adjusted teaching contents and methods during instruction; and implement them into interventions with strategies that targeted elements fostering the sound socio-moral development of a child into adulthood. A model-based approach appeared to be the most, but not the only effective designs in the examined interventions.