COVID 19 and its effects on pediatric orthopaedic clinical trials

Background: Clinical trials for the treatment of pediatric orthopaedics are critical to enhance the quality of life of these children. In response to the COVID-19 pandemic, the FDA updated guidance on conducting clinical trials to prioritize patient safety; however the degree to which the pandemic disrupted pediatric orthopaedic-related clinical trials is unknown. Thus, our objective is to quantify the number of these trials disrupted due to the COVID-19 pandemic.Methods: We searched ClinicalTrials.gov for ongoing and discontinued trials between 01/01/2020 - 10/31/2021. Trials were screened for relevance to the study and the number of participants, trial location, funding source, and reason for discontinuation. Associations between reasons for termination, funding source, trial location, and the number of participants enrolled were evaluated using MannWhitney U tests or ANOVA, where appropriate.Results: Our search returned 544 trials, of which 128 were included with a total of 15,194 participants. Of the included Pediatric trials of orthopaedic conditions, 9 were discontinued with a total of 497 participants. Of the 9 discontinued trials, 1 of 3 stated COVID-19 as a reason. Mann-Whitney U tests and ANOVA showed no statistically significant difference in enrollment between trials discontinued due to COVID-19 compared to other discontinued trials, nor among funding or location.Conclusion: Our study shows 33% of discontinued pediatric orthopaedic-related clinical trials cited COVID-19 as a reason for discontinuation; however, only 12% of all children enrolled in discontinued trials. Findings from this study highlight the importance of developing strategies for safely continuing clinical research amid global emergencies that will almost certainly arise in the future

Measuring the Effectiveness of Photoresponsive Nanocomposite Coatings on Aircraft Windshields to Mitigate Laser Intensity

In 2004, pilots reported 46 laser illumination events to the Federal Aviation Administration (FAA), with the number increasing to approximately 3,600 in 2011. Since that time, the number of reported laser incidents has ranged from 3,500 to 4,000. Previous studies indicate the potential for flight crewmember distraction from bright laser light being introduced to the cockpit. Compositional variations of the photoresponsive nanocomposite coatings were applied to an aircraft windscreen using a modified liquid dispersion/heating curing process. The attenuating effects of the deposited films on laser light intensity were evaluated using an optical power meter and the resultant laser intensity data through treated and untreated windscreens was collected. Data revealed a reduction in laser intensity (36–88%) in the presence of the engineered photoresponsive nanocomposite films. Results lend support of the view that the addition of transparent laser attenuating films applied to aircraft windscreens may improve flight safety, and reduce the risk from distraction or disruption of flight crewmembers’ vision

Antiproliferative activity of ecteinascidin 743 is dependent upon transcription-coupled nucleotide-excision repair.

International audienceWhile investigating the novel anticancer drug ecteinascidin 743 (Et743), a natural marine product isolated from the Caribbean sea squirt, we discovered a new cell-killing mechanism mediated by DNA nucleotide excision repair (NER). A cancer cell line selected for resistance to Et743 had chromosome alterations in a region that included the gene implicated in the hereditary disease xeroderma pigmentosum (XPG, also known as Ercc5). Complementation with wild-type XPG restored the drug sensitivity. Xeroderma pigmentosum cells deficient in the NER genes XPG, XPA, XPD or XPF were resistant to Et743, and sensitivity was restored by complementation with wild-type genes. Moreover, studies of cells deficient in XPC or in the genes implicated in Cockayne syndrome (CSA and CSB) indicated that the drug sensitivity is specifically dependent on the transcription-coupled pathway of NER. We found that Et743 interacts with the transcription-coupled NER machinery to induce lethal DNA strand breaks

Mapping the human genetic architecture of COVID-19

The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3–7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease

Potentially inappropriate medication in the elderly in Germany: an economic appraisal of the PRISCUS list

BACKGROUND: Several lists of potentially inappropriate medication (PIM) for elderly patients have been developed worldwide in recent years. Those lists intend to reduce prescriptions of drugs that carry an unnecessarily high risk of adverse drug events in elderly patients. In 2010, an expert panel published the PRISCUS list for the German drug market. This study calculates the amount of drug reimbursement for PIM in Germany and potential cost effects from the perspective of statutory health insurance when these are replaced by the substitutes recommended by the PRISCUS list. METHODS: Register-based data for the 30 top-selling drugs on the PRISCUS list in 2009 for patients greater than or equal to 65 years of age were provided by the Scientific Institute of the German Local Health Care Fund. We calculated the percentage of sales and defined daily doses for patients greater than or equal to 65 years of age compared with the total statutory health insurance population. Reimbursement costs for the recommended substitutions were estimated by considering different scenarios. RESULTS: In 2009, drug reimbursement for the 30 top-selling PIM prescribed to patients greater than or equal to 65 years of age were calculated to be €305.7 million. Prescribing the recommended substitution medication instead of PIM would lead to an increased total reimbursement cost for the German health care system ranging between from €325.9 million to €810.0 million. CONCLUSIONS: The results show that the substitution of PIM by medication deemed to be more appropriate for the elderly comes along with additional costs. Consequently, there is no short-term incentive for doing so from a payer perspective. Future studies have to consider the long-term effects and other sectors