Participants’ perspectives and preferences on clinical trial result dissemination: The TRUST Thyroid Trial experience

Background: While there is an increasing consensus that clinical trial results should be shared with trial participants, there is a lack of evidence on the most appropriate methods. The aim of this study is to use a patient and public involvement (PPI) approach to identify, develop and evaluate a patient-preferred method of receiving results of the Thyroid Hormone Replacement for Subclinical Hypo-Thyroidism Trial (TRUST). Methods: This is a mixed methods study with three consecutive phases. Phase 1 iteratively developed a patient-preferred result method using semi-structured focus groups and a consensus-orientated-decision model, a PPI group to refine the method and adult literacy review for plain English assessment. Phase 2 was a single-blind parallel group trial. Irish TRUST participants were randomised to the intervention (patient-preferred method) and control group (standard method developed by lead study site). Phase 3 used a patient understanding questionnaire to compare patient understanding of results between the two methods. Results: Patients want to receive results of clinical trials, with qualitative findings indicating three key themes including ‘acknowledgement of individual contribution’, ‘contributing for a collective benefit’ and ‘receiving accessible and easy to understand results’. Building on these findings, a patient-preferred method of receiving results was developed as described above. TRUST participants (n=101) were randomised to the intervention. The questionnaire response rate was 74% for the intervention group and 62% for the control group. There were no differences in patient understanding between the two methods. Conclusions: We have demonstrated that it is feasible to conduct PPI with regard to the dissemination of results. The study identified and developed a patient-preferred method of receiving clinical trial results for older adults over 65 years. Although, in this study PPI did not influence patients’ final understanding of results, it provides a record of the process of conducting PPI within the clinical trial setting

iRFP is a real time marker for transformation based assays in high content screening

Anchorage independent growth is one of the hallmarks of oncogenic transformation. Here we show that infrared fluorescent protein (iRFP) based assays allow accurate and unbiased determination of colony formation and anchorage independent growth over time. This protocol is particularly compatible with high throughput systems, in contrast to traditional methods which are often labor-intensive, subjective to bias and do not allow further analysis using the same cells. Transformation in a single layer soft agar assay could be documented as early as 2 to 3 days in a 96 well format, which can be easily combined with standard transfection, infection and compound screening setups to allow for high throughput screening to identify therapeutic targets

Over Two-Thirds of Opioid Overdose Victims in Canada were Employed Before They Died

As in the United States, drug overdose is the leading cause of unnatural death in Canada, with most overdoses involving opioids. The authors of this brief quantify the lost labor productivity from opioid overdoses in Canada. They show that from 2016 to 2019, over two-thirds of opioid overdose victims were working and contributing to the economy before they died, with those employed in construction, trades, and transportation having the highest opioid overdose rates. The authors argue that destigmatizing drug use, ensuring a safe supply, and improving access to medical care and take-home Naloxone kits are critical for reducing overdose deaths

Study within a trial (SWAT) protocol. Participants' perspectives and preferences on clinical trial result dissemination: The TRUST Thyroid Trial experience.

INTRODUCTION: Dissemination of results of randomised controlled trials is traditionally limited to academic and professional groups rather than clinical trial participants. While there is increasing consensus that results should be communicated to trial participants, there is a lack of evidence on the most appropriate methods of dissemination. This study within a trial (SWAT) aims to address this gap by using a public and patient involvement (PPI) approach to identify, develop and evaluate a patient-preferred method of receiving trial results of the Thyroid Hormone Replacement for Subclinical Hypothyroidism Trial (TRUST). METHODS: An experimental (intervention) study will be conducted using mixed methods to inform the development of and evaluation of a patient-preferred method of communication of trial results. The study will involve three consecutive phases. In the first phase, focus groups of trial participants will be conducted to identify a patient-preferred method of receiving trial results. The method will be developed and then assessed and refined by a patient and public expert group. In the second phase participants will be randomly assigned to the intervention (patient-preferred method) and comparison groups (standard dissemination method as developed by the lead study site in Glasgow, Scotland). In the third phase, a quantitative questionnaire will be used to measure and compare patient understanding of trial results between the two groups. DISCUSSION: This protocol provides a template for other trialists who wish to enhance patient and public involvement and additionally, will provide empirical evidence on how trialists should best disseminate study results to their participants

Embryological-origin-dependent differences in homeobox expression in adult aorta: role in regional phenotypic variability and regulation of NF-κB activity

OBJECTIVE: Different vascular beds show differing susceptibility to the development of atherosclerosis, but the molecular mechanisms underlying these differences are incompletely understood. This study aims to identify factors that contribute to the phenotypic heterogeneity of distinct regions of the adult vasculature. APPROACH AND RESULTS: High-throughput mRNA profiling in adult mice reveals higher expression of the homeobox paralogous genes 6 to 10 (Hox6-10) in the athero-resistant thoracic aorta (TA) than in the athero-susceptible aortic arch (AA). Higher homeobox gene expression also occurs in rat and porcine TA, and is maintained in primary smooth muscle cells isolated from TA (TA-SMCs) compared with cells from AA (AA-SMCs). This region-specific homeobox gene expression pattern is also observed in human embryonic stem cells differentiated into neuroectoderm-SMCs and paraxial mesoderm-SMCs, which give rise to AA-SMCs and TA-SMCs, respectively. We also find that, compared with AA and AA-SMCs, TA and TA-SMCs have lower activity of the proinflammatory and proatherogenic nuclear factor-κB (NF-κB) and lower expression of NF-κB target genes, at least in part attributable to HOXA9-dependent inhibition. Conversely, NF-κB inhibits HOXA9 promoter activity and mRNA expression in SMCs. CONCLUSION: Our findings support a model of Hox6-10-specified positional identity in the adult vasculature that is established by embryonic cues independently of environmental factors and is conserved in different mammalian species. Differential homeobox gene expression contributes to maintaining phenotypic differences between SMCs from athero-resistant and athero-susceptible regions, at least in part through feedback regulatory mechanisms involving inflammatory mediators, for example, reciprocal inhibition between HOXA9 and NF-κB.The authors’ laboratories Sources of Funding supported are by grants from the Ministerio de Economía y Competitividad (MINECO; SAF201016044), Instituto de Salud Carlos III (ISCIII; RD/06/0014/0021, RD12/0042/0028), the Belgian Society of Cardiology (Dr. Léon Dumont Prize 2010), the European Commission (Liphos-317916), the Wellcome Trust (WT078390MA), and the Cambridge Biomedical Research Center. C. Cheung was sponsored by the Agency for Science, Technology and Research (Singapore). J.M. GonzálezGranado and P. Fernández received salary support from the ISCIII (CP11/00145 and CD07/00021, respectively). The CNIC is supported by MINECO and Pro-CNIC Foundation.S

Does the Shape of the L5 Vertebral Body Depend on the Height of CT Slices in the Pedicle?

The shape of the L5 vertebral body was analyzed using a computerized tomography (CT) scan. OBJECTIVE: The aim of this study is to determine if the vertebral L5 body shape varies depending on the height of the CT slices through the L5 pedicle. SUMMARY OF BACKGROUND DATA: The morphometry of L5 has been studied to help the introduction of pedicular screws. The shape of the vertebral body has been seldom looked into, and the findings obtained show a triangular shape and hemispherical shape, supposedly owing to interpersonal variability. The hemisphere shape enables pedicular screws to be introduced nonconvergently, whereas the triangular shape enables pedicular screws to be introduced at a convergent angle but posing the risk of cortical perforation unless these guidelines are followed. METHODS: Abdominal CT multicut with 64 crowns was performed in 101 consecutive patients with diverse indications. Width of CT slices was with a 1-mm reconstruction increase. We selected one axial slice that passed through the upper part of the pedicle and another one that passed through the lower part of the pedicle and compared next parameters in both cuts: pedicular cortical width, pedicular endostal width, pedicular angle, vertebral body length, vertebral body width, vertebral perimeter angles, and visual appearance of vertebral body shape. RESULTS: We found statistical differences between all values except the anterior vertebral perimeter angle on comparing values of upper part with values of lower part and visual vertebral body shape was different in 93% of vertebrae. In the upper part the vertebral body is hemispherical whereas in the lower part it is triangular. CONCLUSION: In most cases, the vertebral body shape is hemispherical in the upper part of the pedicle and triangular in the lower part of the pedicle. It means that in the lower part pedicular screws must be introduced at a more convergent angle than in the upper part if we do not want to break any cortical of the vertebral body