ABSTRACT
Dilated cardiomyopathy (DCM) is a disorder of cardiac ventricular dilation and contractile dysfunction that often progresses to heart failure. Multiple genes have been associated with DCM, including SCN5A which has been linked to 2 % of all DCM cases. Peripheral mononuclear blood cells from DCM patients with SCN5A variants (c.2440C>T and c.665G>A) were utilized to generate two human induced pluripotent stem cell (iPSC) lines. Both lines exhibited typical iPSC morphology, expressed pluripotency markers, normal karyotypes, and trilineage differentiation capabilities. These lines offer valuable resources for investigating the mechanism of SCN5A-associated DCM, facilitating studies of ion channel protein involvement in the disease.
Subject(s)
Cardiomyopathy, Dilated , Induced Pluripotent Stem Cells , NAV1.5 Voltage-Gated Sodium Channel , Humans , Cardiomyopathy, Dilated/genetics , Cardiomyopathy, Dilated/pathology , Induced Pluripotent Stem Cells/metabolism , NAV1.5 Voltage-Gated Sodium Channel/genetics , NAV1.5 Voltage-Gated Sodium Channel/metabolism , Cell Differentiation , Male , Cell Line , FemaleABSTRACT
Familial hypercholesterolemia (FH) is a genetic disorder affecting the metabolism of lipoprotein, characterized by elevated levels of plasma concentrations of low-density lipoprotein cholesterol (LDLC). The most common FH cause is mutations within the gene that encodes for the LDL receptor (LDLR) protein. Two induced pluripotent stem cell (iPSC) lines were generated from patients with FH, each carrying a single heterozygous mutation in the LDLR gene, one is a missense mutation, c.631C > T, and the other is a splice-site mutation, c.313 + 1G > A. Both iPSC lines exhibited strong expression of pluripotency markers, demonstrated the ability to differentiate into derivatives of the three germ layers, and maintained normal karyotypes. These derived iPSC lines represent powerful tools for in vitro modeling FH and offer a promising platform for therapeutic development.
Subject(s)
Heterozygote , Hyperlipoproteinemia Type II , Induced Pluripotent Stem Cells , Mutation , Receptors, LDL , Induced Pluripotent Stem Cells/metabolism , Receptors, LDL/genetics , Receptors, LDL/metabolism , Humans , Hyperlipoproteinemia Type II/genetics , Hyperlipoproteinemia Type II/metabolism , Cell Line , Male , Female , Cell DifferentiationABSTRACT
Williams syndrome (WS) is a relatively rare genetic disorder. It arises from a microdeletion in chromosome 7q11.23, resulting in the loss of one copy of more than 20 genes. Disorders in multiple systems, including cardiovascular and nervous systems, occur in patients with WS. Here, we generated two human induced pluripotent stem cell (iPSC) lines from WS patients. Both lines expressed pluripotency markers at gene and protein levels. They possessed normal karyotypes and the potential to differentiate into three germ layers. They serve as a useful tool to study disease mechanism, test drugs, and identify promising therapeutics for patients with WS.
Subject(s)
Induced Pluripotent Stem Cells , Williams Syndrome , Williams Syndrome/genetics , Williams Syndrome/pathology , Humans , Induced Pluripotent Stem Cells/metabolism , Cell Line , Cell Differentiation , Male , FemaleABSTRACT
PURPOSE: Self-assessment of a physician's performance in both procedure and non-procedural activities can be used to identify their deficiencies to allow for appropriate corrective measures. Physicians are inaccurate in their self-assessments, which may compromise opportunities for self- development. To improve this accuracy, video-based interventions of physicians watching their own performance, an experts' performance or both, have been proposed to inform their self-assessment. We conducted a systematic review of the effectiveness of video-based interventions targeting improved self-assessment accuracy among physicians. MATERIALS AND METHODS: The authors performed a systematic search of MEDLINE, Embase, EBM reviews, and Scopus databases from inception to August 23, 2022, using combinations of terms for "self-assessment", "video-recording", and "physician". Eligible studies were empirical investigations assessing the effect of video-based interventions on physicians' self-assessment accuracy with a comparison of self-assessment accuracy pre- and post- video intervention. We defined self-assessment accuracy as a "direct comparison between an external evaluator and self-assessment that was quantified using formal statistical analysis". Two reviewers independently screened records, extracted data, assessed risk of bias, and evaluated quality of evidence. A narrative synthesis was conducted, as variable outcomes precluded a meta-analysis. RESULTS: A total of 2,376 papers were initially retrieved. Of these, 22 papers were selected for full-text review; a final 9 studies met inclusion criteria for data extraction. Across studies, 240 participants from 5 specialties were represented. Video-based interventions included self-video review (8/9), benchmark video review (3/9), and/or a combination of both types (1/9). Five out of nine studies reported that participants had inaccurate self-assessment at baseline. After the intervention, 5 of 9 studies found a statistically significant improvement in self-assessment accuracy. CONCLUSIONS: Overall, current data suggests video-based interventions can improve self-assessment accuracy. Benchmark video review may enable physicians to improve self-assessment accuracy, especially for those with limited experience performing a particular clinical skill. In contrast, self-video review may be able to provide improvement in self-assessment accuracy for more experience physicians. Future research should use standardized methods of comparison for self-assessment accuracy, such as the Bland-Altman analysis, to facilitate meta-analytic summation.
Subject(s)
Physicians , Humans , Self-Assessment , Clinical CompetenceABSTRACT
BACKGROUND: Assessment is necessary to ensure both attainment and maintenance of competency in gastrointestinal (GI) endoscopy, and this can be accomplished through self-assessment. We conducted a systematic review with meta-analysis to evaluate the accuracy of self-assessment among GI endoscopists. METHODS: This was an individual participant data meta-analysis of studies that investigated self-assessment of endoscopic competency. We performed a systematic search of the following databases: Ovid MEDLINE, Ovid EMBASE, Wiley Cochrane CENTRAL, and ProQuest Education Resources Information Center. We included studies if they were primary investigations of self-assessment accuracy in GI endoscopy that used statistical analyses to determine accuracy. We conducted a meta-analysis of studies using a limits of agreement (LoA) approach to meta-analysis of Bland-Altman studies. RESULTS: After removing duplicate entries, we screened 7138 records. After full-text review, we included 16 studies for qualitative analysis and three for meta-analysis. In the meta-analysis, we found that the LoA were wide (-41.0â% to 34.0â%) and beyond the clinically acceptable difference. Subgroup analyses found that both novice and intermediate endoscopists had wide LoA (-45.0â% to 35.1â% and -54.7â% to 46.5â%, respectively) and expert endoscopists had narrow LoA (-14.2â% to 21.4â%). CONCLUSIONS: GI endoscopists are inaccurate in self-assessment of their endoscopic competency. Subgroup analyses demonstrated that novice and intermediate endoscopists were inaccurate, while expert endoscopists have accurate self-assessment. While we advise against the sole use of self-assessment among novice and intermediate endoscopists, expert endoscopists may wish to integrate it into their practice.
Subject(s)
Endoscopy, Gastrointestinal , Self-Assessment , Humans , Endoscopy, Gastrointestinal/education , EndoscopyABSTRACT
Background: Propensity score matching (PSM), a statistical technique that estimates a treatment effect by accounting for predictor covariates, has been used to evaluate biologics for inflammatory bowel disease (IBD). Financial conflicts of interest are prevalent in the marketing of biologic medications. It is unclear whether this burden of conflicts is present among authors of PSM studies comparing IBD biologics and biosimilars. Objective: This study was aimed to determine the prevalence of financial conflicts of interest among authors of PSM studies evaluating IBD biologics and biosimilars. Methods: We conducted a systematic search for PSM studies comparing biologics and biosimilars in IBD treatment. We identified 21 eligible studies. Two independent authors extracted self-declared conflicts from the disclosures section. Each participating author was searched on the Centers for Medicare & Medicaid Services Open Payments to identify payment amounts and undisclosed conflicts. Primary outcome was the prevalence of author conflicts. Secondary analyses assessed for an association between conflict prevalence and reporting of positive outcomes. Results: Among 283 authors, conflicts were present among 41.0% (116 of 283). Twenty-three per cent (27 of 116) of author conflicts involved undisclosed payments. Studies with positive outcomes were significantly more likely to include conflicted authors than neutral studies (relative risk = 2.34, 95% confidence interval: 1.71 to 3.21, P < 0.001). Conclusions: Overall, we found a high burden of undisclosed conflicts among authors of PSM studies comparing IBD biologics and biosimilars. Given the importance of PSM studies as a means for biologic comparison and the potential for undue industry influence from these payments, authors should ensure greater transparency with reporting of industry relationships.
ABSTRACT
Background and study aims Endoscopists are at high risk of musculoskeletal pain and injuries (MSPI). Recently, ergonomics has emerged as an area of interest to reduce and prevent the incidence of MSPI in endoscopy. The aim of this systematic review was to determine educational interventions using ergonomic strategies that target reduction of endoscopist MSPI from gastrointestinal endoscopy. Methods In December 2020, we conducted a systematic search in MEDLINE, EMBASE, PsycINFO, Web of Science, Scopus, the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Reviews for articles published from inception to December 16, 2020.âStudies were included if they investigated educational interventions aimed at changing knowledge and/or behaviors related to ergonomics in gastrointestinal endoscopy. After screening and full-text review, we extracted data on study design, participants, type of training, and assessment of primary outcomes. We evaluated study quality with the Medical Education Research Study Quality Instrument (MERSQI). Results Of the initial 575 records identified in the search, five met inclusion criteria for qualitative synthesis. We found that most studies (nâ=â4/5, 80â%) were single-arm interventional studies that were conducted in simulated and/or clinical settings. The most common types of interventions were didactic sessions and/or videos (nâ=â4/5, 80%). Two (40â%) studies used both standardized assessment studies and formal statistical analyses. The mean MERSQI score was 9.7. Conclusions There is emerging literature demonstrating the effectiveness of interventions to improve ergonomics in gastrointestinal endoscopy.
ABSTRACT
BACKGROUND: Since 2008, the Canadian Institutes of Health Research (CIHR) has mandated that studies it funds either in whole or in part are required to publish their results as open access (OA) within 12 months of publication using either online repositories and/or OA journals. Yet, there is evidence that authors are poorly compliant with this mandate. Specifically, there has been an apparent decrease in OA publication after 2015, which coincides with a change in the OA policy during the same year. One particular policy change that may have contributed to this decline was lifting the requirement that authors deposit their article in an OA repository immediately upon publication. We investigated the proportion of OA compliance of CIHR-funded studies in the period before and after the policy change of 2015 with manual confirmation of both CIHR funding and OA status. METHODS AND FINDINGS: We identified CIHR-funded studies published between the years 2014 to 2017 using a comprehensive search in the Web of Science (WoS). We took a stratified random sample from all four years (i.e. 2014 to 2017), with 250 studies from each year. Two authors independently reviewed the final full-text publications retrieved from the journal web page to determine to confirm CIHR funding, as indicated in the acknowledgements or elsewhere in the paper. For each study, we also collected bibliometric data that included citation count and Altmetric attention score Statistical analyses were conducted using two-tailed Fisher's exact test with relative risk (RR). Among the 851 receiving CIHR funding published from 2014 to 2017, the percentage of CIHR-funded studies published as OA significantly decreased from 79.6% in 2014 to 70.3% in 2017 (RR = 0.88, 95% CI: 0.79-0.99, P = 0.028). When considering all four years, there was no significant difference in the percentage of CIHR-funded studies published as OA in both 2014 and 2015 compared to both 2016 and 2017 (RR = 0.97, 95% CI: 0.90-1.05, P = 0.493). Additionally, OA publications had significantly higher citation count (both in year of publication and in total) and higher attention scores (P<0.05). CONCLUSIONS: Overall, we found that there was a significant decrease in the proportion of CIHR funded studies published as OA from 2014 compared to 2017, though this difference did not persist when comparing both 2014-2015 to 2016-2017. The primary limitation was the reliance of self-reported data from authors on CIHR funding status. We posit that this decrease may be attributable to CIHR's OA policy change in 2015. Further exploration is warranted to both validate these studies using a larger dataset and, if valid, investigate the effects of potential interventions to improve the OA compliance, such as use of a CIHR publication database, and reinstatement of a policy for authors to immediately submit their findings to OA repositories upon publication.
Subject(s)
Biomedical Research/economics , Open Access Publishing , Canada , Databases, Factual , Open Access Publishing/trends , Research Support as TopicABSTRACT
BACKGROUND: Financial conflicts of interest (FCOIs) are widespread in inflammatory bowel disease (IBD) and may be particularly important in point-of-care (POC) resources, such as UpToDate, that are used to aid clinical decision making. In this study, we determined the prevalence of industry payments from companies making biologic medications for IBD to contributors of UpToDate articles on IBD. METHODS: This cross-sectional analysis included UpToDate articles that mention the use of biologic medications for IBD. We collected the names of the contributors (authors and editors) and their disclosures on UpToDate. We then searched for their names on the Center for Medicare and Medicaid Open Payments database and compared the payment information from 2013 to 2018 with UpToDate's disclosures. We presented data per episode, which describes one instance of participation by one person in one article, regardless of whether that person contributed to multiple articles. RESULTS: We identified 23 articles on the treatment of Crohn's disease and ulcerative colitis that mentioned the use of biologic medications, with 86 total episodes. Sixty-two (72%) episodes involved FCOIs. The median payment associated with each episode was $$55 (interquartile range = $44 to $145,241). Contributors did not fully disclose FCOIs in 41 (48%) episodes. Deputy editors, who are required to be free of FCOIs, in general did not have substantial episodes involving FCOI. CONCLUSIONS: We found that UpToDate articles on inflammatory bowel disease involve substantial FCOI, many of which are not disclosed. The presence of these FCOIs may hamper trust in the objectivity of treatment recommendations.
ABSTRACT
BACKGROUND: The quality of case reports, which are often the first reported evidence for a disease, may be negatively affected by a rush to publication early in a pandemic. We aimed to determine the completeness of reporting (COR) for case reports published on coronavirus disease 2019 (COVID-19). METHODS: We conducted a systematic search of the PubMed database for all single-patient case reports of confirmed COVID-19 published from Jan. 1 to Apr. 24, 2020. All included case reports were assessed for adherence to the CARE (Case Report) 31-item checklist, which was used to create a composite COR score. The primary outcome was the mean COR score assessed by 2 independent raters. Secondary outcomes included whether there was a change in overall COR score with certain publication factors (e.g., publication date) and whether there was a linear relation between COR and citation count and between COR scores and social media attention. RESULTS: Our search identified 196 studies that were published in 114 unique journals. We found that the overall mean COR score was 54.4%. No one case report included all of the 31 CARE checklist items. There was no significant correlation between COR with either citation count or social media attention. INTERPRETATION: We found that the overall COR for case reports on COVID-19 was poor. We suggest that journals adopt common case-reporting standards to improve reporting quality.