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Objective: To assess the bioequivalence of an ezetimibe/simvastatin (EZE/SIMVA) combination tablet compared to the coadministration of ezetimibe and simvastatin as separate tablets (EZE + SIMVA). Methods: In this open-label, randomized, 2-part, 2-period cross over study, 96 healthy subjects were randomly assigned to participate in each part of the study (Part I or II), with each part consisting of 2 single-dose treatment periods separated by a 14-day washout. Part I consisted of Treatments A (EZE 10 mg + SIMVA 10 mg) and B (EZE/SIMVA 10/10 mg/mg) and Part II consisted of Treatments C (EZE 10 mg + SIMVA 80 mg) and D (EZE/SIMVA 10/80 mg/mg). Blood samples were collected up to 96 hours post-dose for determination of ezetimibe, total ezetimibe (ezetimibe + ezetimibe glucuronide), simvastatin and simvastatin acid (the most prevalent active metabolite of simvastatin) concentrations. Ezetimibe and simvastatin acid AUC(0-last) were predefined as primary endpoints and ezetimibe and simvastatin acid Cmax were secondary endpoints. Bioequivalence was achieved if 90% confidence intervals (CI) for the geometric mean ratios (GMR) (single tablet/coadministration) of AUC(0-last) and Cmax fell within prespecified bounds of (0.80, 1.25). Results: The GMRs of the AUC(0-last) and Cmax for ezetimibe and simvastatin acid fell within the bioequivalence limits (0.80, 1.25). EZE/SIMVA and EZE + SIMVA were generally well tolerated. Conclusions: The low est and highest dosage strengths of EZE/SIMVA tablet were bioequivalent to the individual drug components administered together. Given the exact weight multiples of the EZE/SIMVA tablet and linear pharmacokinetics of simvastatin across the marketed dose range, bioequivalence of the intermediate tablet strengths (EZE/SIMVA 10/20 mg/mg and EZE/SIMVA 10/40 mg/mg) was inferred, although these dos ages were not tested directly. These results indicate that the safety and efficacy profile of EZE + SIMVA coadministration therapy can be applied to treatment with the EZE/SIMVA tab let across the clinical dose range. [ABSTRACT FROM AUTHOR]

1. The disposition and metabolism of ertapenem, a carbapenem antibiotic, was examined in rat, monkey and man. Sprague-Dawley rats and Rhesus monkeys were given, by intravenous administration, radiolabelled doses of ertapenem (60 and 30mgkg-1, respectively), and healthy normal volunteers received a single fixed dose of 1000 mg. Urine and faeces were collected for determination of total radioactivity. 2. In healthy volunteers, [14C]ertapenem was eliminated by a combination of hydrolytic metabolism to a beta-lactam ring-opened derivative and renal excretion of unchanged drug. Approximately equal amounts were excreted as a beta-lactam ring-opened metabolite and unchanged drug (36.7 and 37.5% of dose, respectively). A secondary amide hydrolysis product accounted for about 1% of the dose in man. About 10% of the administered radioactivity was recovered in faeces, which suggested that a minor fraction underwent biliary and/or intestinal excretion. 3. In animals, a greater fraction of the dose was eliminated via metabolism; excretion of unchanged drug accounted for 17 and 5% of dose in rats and monkeys, respectively. In monkeys, the beta-lactam ring-opened and amide hydrolysis metabolites accounted for 74.8 and 7.59% of the dose, respectively, whereas in rats, these metabolites accounted for 31.9 and 20% of dose, respectively. 4. In vitro studies with fresh rat tissue homogenates indicated that lung and kidney were the primary organs involved in mediating formation of the beta-lactam ring-opened metabolite. The specific inhibitor of dehydropeptidase-I, cilastatin, inhibited the in vivo and in vitro metabolism of ertapenem in rats, which suggested strongly that the hydrolysis of ertapenem in lung and kidney was mediated by this enzyme. [ABSTRACT FROM AUTHOR]

Background. Obesity is associated with an increased risk of rotator cuff tears and impaired tendon healing after surgery. This study aimed: 1) to investigate the influence of patient body mass index (BMI) on cellular function in tenocytes derived from diseased torn human rotator cuff; 2) to determine if BMI altered the response of tenocytes to tenogenic growth factors. Methods. Tenocytes were isolated from torn supraspinatus tendons of patients undergoing rotator cuff surgery. Tenocyte growth and collagen production were determined by alamarBlue and Sirius red assays, respectively, at baseline and in the presence of IGF-1, TGF-β and PDGF after 72 hours. Changes in the relative expression of genes important in tenocyte, chondrocyte and osteoblast biology were determined using real-time PCR. Correlation analyses were performed between patient BMI and tenocyte function and gene expression. Results. BMI had no direct effect on tenocytes with no significant correlations between patient BMI and cellular behaviour, gene expression or response to growth factor treatment. Higher cellular growth and collagen production were observed in response to PDGF and TGF-β treatment, while IGF-1 had minimal effect. TGF-β was associated with higher expression of tenocyte-related genes, collagen Iα and scleraxis, while PDGF resulted in higher expression of adipose marker, PPAR-γ, suggesting it may be promoting de-differentiation from a tenocytic phenotype. Conclusions. In summary, BMI does not influence tenocyte growth, collagen synthesis or gene expression profile ex vivo. These findings have significant clinical implications, as they suggest that growth factor treatment will be effective in patients independent of BMI. [ABSTRACT FROM AUTHOR]

Purpose: Mastering non-technical skills (NTS) is a fundamental part of the training of new physicians to perform effectively and safely in the medical practice environment. Ideally, they learn these skills during medical school. Decentralized medical education is being implemented increasingly worldwide. Two of the three training sites studied, Bodø (a regional hospital) and Finnmark (a rural local hospital), implemented decentralized medical education. The third training site was the main campus in Tromsø, located at an urban university hospital. The training in Finnmark emphasised training in non-technical skills using simulation to a larger extent than the two other university campuses. This study aimed to compare the NTS performance of medical students in their last year of education at three different training sites of the same university., Methods: This blinded cohort study included students from the three training sites who participated in identical multi-professional simulations over a six-year period. Eight raters evaluated the video recordings of eight students from each training site using the Norwegian Medical Students Non-Technical Skills (NorMS-NTS) tool. The NorMS-NTS tool, which comprises four categories and 13 elements, assesses the NTS of Norwegian medical students and assigns an overall global score. Pairwise significant differences in the NTS performance levels between the training sites studied were assessed using Tukey's test., Results: The overall NTS performance levels of the medical students from Finnmark (mean 4.5) were significantly higher than those of the students from Tromsø (mean 3.8) and Bodø (mean 3.5). Similarly, the NTS performance levels at category-level of the students in Finnmark were significantly higher than those of the students from Bodø and Tromsø. Except for one category, no significant differences were observed between the students from Bodø and Tromsø in terms of the overall or category-level NTS performance., Conclusion: The NTS performance levels of the medical students from Finnmark, which implements rural, decentralized medical education, were significantly higher than those of the students from Tromsø and Bodø., (© 2024. The Author(s).)

Objectives: Objective risk communication tools can supplement clinical judgement and support the understanding of potential health risks. This study used the Theoretical Domains Framework (TDF) to identify barriers and facilitators to implementing a risk communication aid within primary care dental consultations., Methods: Dentists (N = 13), recruited via a dental practice database and through professional contacts were interviewed using a TDF-informed semi-structured interview schedule. Data were analysed inductively and deductively coding the themes using the TDF., Results: Eight theoretical domains (environmental context and resources; beliefs about consequences; goals; memory, attention, and decision processes; optimism; reinforcement; social influences and behavioural regulation) and thirteen sub-themes were identified. Insufficient resources and patient factors were commonly encountered barriers and led to increasing pressure to prioritise other tasks. Whilst dentists had a favourable view towards a risk communication aid and acknowledged its benefits, some were sceptical about its ability to facilitate behaviour change. Self-monitoring strategies and colleague support facilitated tool usage., Conclusions: This study identified six barriers and seven facilitators to implementing a risk communication tool within primary care dental settings. Dentists appreciated the value of using a risk communication tool during dental consultations, although some required further support to integrate the tool into practice., Clinical Significance: Our findings provide a sound theoretical base for interventions aimed at facilitating patient behaviour change through the use of risk communication in dentistry. Further research should apply behavioural science to support the implementation of the tool in clinical practice., Competing Interests: Declaration of competing interest MN and their dental practice have financial links to DenPlan. DEPPA is used in private dental clinics which participate in the DenPlan insurance scheme. There are no other competing interests to report., (Copyright © 2024. Published by Elsevier Ltd.)

Background: The Endometriosis Health Profiles (EHPs), the EHP-30 and EHP-5, are patient-reported outcome measures that were developed to measure the health-related quality of life (HRQoL) of women living with endometriosis. Prior to their development, a systematic review was undertaken which identified that the HRQoL of women living with endometriosis was poorly understood, with only three medical and one surgical study identified., Objective and Rationale: The 20-year anniversary of the EHP-30 provided a timely opportunity to assess how the tools have been used and explore what the findings tell us about the impact of endometriosis and its associated treatments upon women's QoL. Applying robust systematic review methodology, following PRISMA guidelines, we sought to answer: How many studies have used the EHP and for what purpose?; What are the demographic characteristics and international context of the studies?; What is the methodological nature and quality of the studies?; Which interventions have been assessed and what are the reported EHP outcomes?; and Can the EHP outcomes of these interventions be analysed using a meta-analysis and, if so, what do the results show?, Search Methods: The electronic databases MEDLINE, CINAHL, PsycINFO, PubMed, and Google Scholar were searched from the year the EHP was first published, in 2001 to 26 February 2020 using the search terms 'EHP30', 'EHP5', 'EHP-30', 'EHP-5', 'endometriosis health profile 30', and 'endometriosis health profile 5'. We updated the searches on 9 April 2021. All included studies were quality assessed using the Mixed Methods Appraisal Tool (MMAT)., Outcomes: The review included 139 papers. In clinical intervention studies, the EHPs were deployed most frequently to measure the outcomes of medical (n = 35) and surgical (n = 21) treatment. The EHPs were also used in 13 other intervention studies, 29 non-interventional studies, 32 psychometric/cross cultural validation studies; six diagnostic studies, and in three other studies to measure outcomes in related conditions. They were mainly deployed in studies undertaken in Europe and North America. Overall, regardless of the nature of the intervention, most women reported improvements in HRQoL after treatment. Surgical interventions generally resulted in significant improvements for the longest amount of time. There was also evidence that when participants stopped taking medication their EHP scores worsened, perhaps reinforcing the temporary impact of medical treatment. Younger patients reported more negative impact upon their HRQoL. Further evidence using classical test theory to support the EHPs' robust psychometric properties, including acceptability, dimensionality, reliability, validity (including cross-cultural), and responsiveness, was demonstrated, particularly for the EHP-30. Strikingly, using anchor-based methods, EHP-30 responsiveness studies demonstrate the largest mean changes in the 'control and powerlessness' domain post-intervention, followed by 'pain'. MMAT outcomes indicated the quality of the papers was good, with the exception of five studies. A meta-analysis was not undertaken owing to the heterogeneity of the interventions and papers included in this review., Wider Implications: Women with endometriosis face a lifetime of surgical and/or medical interventions to keep the condition under control. Less invasive treatments that can lead to improved longer term physical and psycho-social outcomes are needed. The EHPs are reliable, valid, acceptable, and responsive tools, but more assessment of EHP outcomes using modern psychometric methods and in the context of women from ethnically diverse backgrounds and in routine clinical care would be beneficial. Given the brevity of the EHP-5, it may be the most appropriate version to use in routine clinical practice, whereas the longer EHP-30, which provides more granularity, is more appropriate for research., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Background: The NorMS-NTS tool is an assessment tool for assessing Norwegian medical students' non-technical skills (NTS). The NorMS-NTS was designed to provide student feedback, training evaluations, and skill-level comparisons among students at different study sites. Rather than requiring extensive rater training, the tool should capably suit the needs of busy doctors as near-peer educators. The aim of this study was to examine the usability and preliminary assess validity of the NorMS-NTS tool when used by novice raters., Methods: This study focused on the usability of the assessment tool and its internal structure. Three raters used the NorMS-NTS tool to individually rate the team leader, a medical student, in 20 video-recorded multi-professional simulation-based team trainings. Based on these ratings, we examined the tools' internal structure by calculating the intraclass correlation coefficient (ICC) (version 3.1) interrater reliability, internal consistency, and observability. After the rating process was completed, the raters answered a questionnaire about the tool's usability., Results: The ICC agreement and the sum of the overall global scores for all raters were fair: ICC (3,1) = 0.53. The correlation coefficients for the pooled raters were in the range of 0.77-0.91. Cronbach's alpha for elements, categories and global score were mostly above 0.90. The observability was high (95%-100%). All the raters found the tool easy to use, none of the elements were redundant, and the written instructions were helpful. The raters also found the tool easier to use once they had acclimated to it. All the raters stated that they could use the tool for both training and teaching., Conclusions: The observed ICC agreement was 0.08 below the suggested ICC level for formative assessment (above 0.60). However, we know that the suggestion is based on the average ICC, which is always higher than a single-measure ICC. There are currently no suggested levels for single-measure ICC, but other validated NTS tools have single-measure ICC in the same range. We consider NorMS-NTS as a usable tool for formative assessment of Norwegian medical students' non-technical skills during multi-professional team training by raters who are new to the tool. It is necessary to further examine validity and the consequences of the tool to fully validate it for formative assessments., (© 2023. The Author(s).)