Acceptable Risks in Pediatric Research: Views of the US Public

BACKGROUND AND OBJECTIVES: Critics argue that it is unethical to expose children to research risks for the benefit of others, whereas many regulations permit “net-risk” pediatric research but only when the risks are minimal. In the present survey, we assessed whether the US public agrees with these views and whether the US public’s views regarding the acceptability of net-risk pediatric research are influenced by its social value. METHODS: A 15-minute survey of a nationally representative sample of US adults. Participants were randomly assigned to 1 of 4 hypothetical scenarios involving procedures that pose increasing levels of risk. To assess whether respondents’ views on the acceptability of the risks is influenced by the social value of the research, in each of the 4 scenarios we described the respective procedure being used in 3 studies with increasing levels of social value. RESULTS: A total 1658 of the 2508 individuals who were sent the survey link participated (response rate = 66.1%). Approximately 91% approved of a research blood draw in minors, and ∼69% approved of a research bone marrow biopsy. The proportion who indicated that the respective procedure was acceptable increased as the study’s social value increased. This effect was significantly stronger for studies which pose greater risks compared with studies with lower risks (P < .001). CONCLUSIONS: The vast majority of the US public supports net-risk pediatric research that poses minimal risk, and a majority supports net-risk pediatric research that poses somewhat greater risks, provided it has high social value. These findings offer important information for assessing when it is acceptable to conduct net-risk pediatric research.

PERFORM: A Metric for Evaluating Autonomous System Performance in Marine Testbed Environments Using Interval Type-2 Fuzzy Logic

Trust and confidence in autonomous behavior is required to send autonomous vehicles into operational missions. The authors introduce the Performance Evaluation and Review Framework Of Robotic Missions (PERFORM), a framework to enable a rigorous and replicable autonomy test environment, thereby filling the void between that of merely simulating autonomy and that of completing true field missions. A generic architecture for defining the missions under test is proposed and a unique Interval Type-2 Fuzzy Logic approach is used as the foundation for the mathematically rigorous autonomy evaluation framework. The test environment is designed to aid in (1) new technology development (i.e., providing direct comparisons and quantitative evaluations between autonomy algorithms), (2) the validation of the performance of specific autonomous platforms, and (3) the selection of the appropriate robotic platform(s) for a given mission type (e.g., for surveying, surveillance, search and rescue). Three case studies are presented to apply the metric to various test scenarios. Results demonstrate the flexibility of the technique with the ability to tailor tests to the user’s design requirements accounting for different priorities related to acceptable risks and goals of a given mission.

Potential Human Exposure to Mercury (Hg) in a Chlor-Alkali Plant Impacted Zone: Risk Characterization Using Updated Site Assessment Data

Industrial activities have resulted in severe environmental contamination that may expose rural and urban populations to unacceptable health risks. For example, chlor-alkali plants (CAPs) have historically contributed mercury (Hg) contamination in different environmental compartments. One such site (a burden from the Soviet Union) is located in an industrial complex in Pavlodar, Kazakhstan. Earlier studies showed the CAP operating in the second half of the twentieth century caused elevated Hg levels in soil, water, air, and biota. However, follow-up studies with thorough risk characterization are missing. The present study aims to provide a detailed risk characterization based on the data from a recent site assessment around the former CAP. The ⅀HI (hazard index) ranged from 9.30 × 10−4 to 0.125 (deterministic method) and from 5.19 × 10−4 to 2.54 × 10−2 (probabilistic method). The results indicate acceptable excess human health risks from exposure to Hg contamination in the region, i.e., exposure to other Hg sources not considered. Air inhalation and soil ingestion pathways contributed to the highest ⅀HI values (up to 99.9% and 92.0%, respectively). The residential exposure scenario (among four) presented the greatest human health risks, with ⅀HI values ranging from 1.23 × 10−2 to 0.125. Although the local urban and rural population is exposed to acceptable risks coming from exposure to Hg-contaminated environmental media, an assessment of contamination directly on the former CAP site on the industrial complex could not be performed due to access prohibition. Furthermore, the risks from ingesting contaminated fish were not covered as methyl-Hg was not targeted. An additional assessment may be needed for the scenarios of exposure of workers on the industrial complex and of the local population consuming fish from contaminated Lake Balkyldak. Studies on the fate and transport of Hg in the contaminated ecosystem are also recommended considering Hg methylation and subsequent bioaccumulation in the food chain.

The anthropic risks, climate change and coronavirus pandemic (COVID-19)

Risks have always been present throughout human history, however, today are qualitatively different, as many of them are anthropic (human-made). The fact that people are exposed to dangers for which they have no decision-making capacity depended on knowledge they often do not have in order to decide on possible acceptable risks. The pandemic situation we face now brings light on human-made risks; came and lifted the veil, if there were any doubts, about the impact on the quality of life on the Planet, as consequence of human decisions and behaviour. Two types of human-made risks will be addressed: climate change and the pandemic caused by the coronavirus (SARS-CoV-2); reflecting on the exposure of structural vulnerabilities, these risks bring forth the importance of social capital and social networks in reducing vulnerabilities, the investment in science and its dissemination, and prevention, as preparedness for future risks, promoting resilience. Thus, governance relationships between States, economic models and resilient communities will also be addressed.

Redo MIDCAB in a Septuagenarian in our Setting, Fantasy or Fact? - A Case Report

Worldwide growth in elderly population has led to an upsurge in the number of septuagenarian (>70 years of age) patients requiring surgical treatment for coronary artery disease. Elective coronary artery bypass grafting (CABG) in the older patients are associated with acceptable risks of adverse events and should be undertaken for appropriate indications without unnecessary hesitation. Redo coronary surgeries carries one of the highest mortality rates amongst redo cardiac surgeries, both separately or in combination with other pathologies. As a result, minimally-invasive direct coronary artery bypass (MIDCAB), was preferred to avoid the complications of re-sternotomy. We hereby present a case report of a septuagenarian patient with post CABG (2014) unstable angina with old myocardial infarction (extensive anterior) who was treated successfully, by us and to our best knowledge in the published articles this is probably the first time, a re-do MIDCAB technique has been implemented in our country. Bangladesh Heart Journal 2021; 36(2): 145-150

Comprehensive review of the recent advances in devices for endovascular treatment of complex brain aneurysms

The International Subarachnoid Aneurysm Trial (ISAT) showed superiority for endovascular treatment of ruptured aneurysms and technology has since moved on rapidly. Many approaches and technology now exist for the endovascular management of ruptured and unruptured intracranial aneurysms, which reflects their varied nature – there is no one-size-fits-all technique. We aim to provide an overview of the various classes of device and the major developments over the past decade. Coiling is the oldest of the technology and continues to demonstrate high levels of occlusion and acceptable risks, making it the default treatment choice, particularly in the acutely ruptured aneurysm setting. Advances on coiling include the use of adjuncts such as balloons, stents and fully retrievable temporary neck-bridging devices, which have facilitated the treatment of more complex aneurysms. Flow divertors have also revolutionised complex aneurysm treatment with small added risk in acute aneurysm treatment and seek to remodel the aneurysm–vessel interface without accessing the aneurysm sac. The latest development and most promising avenue appears to be intrasaccular flow disrupting devices like WEB, Contour and Neqstent that provide excellent opportunities to treat wide neck complex aneurysm with minimal mortality and morbidity and good occlusion rates and may in future replace a significant number of stent-assisted coiling too.

Impact of lenvatinib on renal function: long-term analysis of differentiated thyroid cancer patients

Background Because lenvatinib is well known to induce proteinuria by blocking the vascular endothelial growth factor (VEGF) pathway, renal function is a concern with long-term administration of lenvatinib. The long-term effects of lenvatinib on renal function in patients with advanced differentiated thyroid carcinoma (DTC) were analyzed. Method This study involved 40 DTC patients who continued lenvatinib therapy for ≥6 months. Estimated glomerular filtration rate (eGFR) was calculated as an indicator of renal function. The temporal course of eGFR, effects of baseline eGFR on eGFR changes, and factors affecting renal impairment were investigated. Results The overall cohort showed sustainable decreases in eGFR, with decreased values of 11.4, 18.3, and 21.0 mL/min/1.73 m2 at 24, 36, and 48 months after starting treatment, respectively. No differences in eGFR decrease every 6 months were seen for three groups classified by baseline eGFR ≥90 mL/min/1.73 m2 (n = 6), < 90 but ≥60 mL/min/1.73 m2 (n = 26), or < 60 but ≥45 mL/min/1.73 m2 (n = 8). Grade 3 proteinuria was associated with declines in eGFR (p = 0.0283). Long observation period was also associated with decreases in eGFR (p = 0.0115), indicating that eGFR may decrease in a time-dependent manner. Conclusion Lenvatinib can induce declines in eGFR, particularly with treatment duration > 2 years, regardless of baseline eGFR. Proteinuria is a risk factor for declines in eGFR. Patients who start lenvatinib with better renal function show a renal reserve capacity, prolonging clinical outcomes. Decision-making protocols must balance the benefits of lenvatinib continuation with acceptable risks of harm.

SCIENTIFIC AND METHODOLOGICAL APPROACH TO INTEGRATION OF QUALITY MANAGEMENT UNDER CONDITIONS OF RISKS IN THE CONSTRUCTION INDUSTRY

Purpose. Justification of the appropriateness of use in terms of efficiency for a construction company, the process of integrating quality management and risk management. Determination of the principles of applying an integrative management model, modules for managing the quality of construction in conditions of risks based on a dynamic system. Methodology. Analysis and generalization of scientific research, practical approaches to quality management and risk management of construction projects, the use of the integration method and the method of identification of QM and RM processes, which makes it possible to substantiate the possibility of developing an integrated approach and determine the principles of applying an integrated quality management model in the face of risks. Results. The study substantiated the feasibility of using an integrative model of risk and quality management in construction, which allows the QM and RM processes to be aligned with the project efficiency criteria, and makes it possible to eliminate contradictions between the quality requirements for the construction object and the level of acceptable risks, and also aligns them with the efficiency requirements for developer. Originality. The principles of quality and risk management are determined, which are prerequisites for the integration of QM and RM processes; modules and levels of implementation of an integrated model of quality management in a risk environment, taking into account the requirements of project efficiency. Practical value. The use of an integrated approach aimed at combining quality management modules for projects and risks in the construction industry will allow to level all the contradictions of these processes in practical implementation, to harmonize with the efficiency requirements for projects and balance the costs of ensuring the planned quality level, provided that the acceptable level of risks is observed.

Perspective of Adults With Neurofibromatosis 1 and Cutaneous Neurofibromas: Implications for Clinical Trials

Objective:To assess the perspectives of adults with neurofibromatosis 1 (NF1) regarding cutaneous neurofibroma (cNF) morbidity, treatment options, and acceptable risks-benefits to facilitate the design of patient-centered clinical trials.Methods:An online survey developed by multi-disciplinary experts and patient representatives of the Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) cNF working group. The survey was distributed to adults with NF1 (n=3734) in the largest international database of individuals with any form of NF. Eligibility criteria included: self-reported NF1 diagnosis, ≥18 years, ≥1 cNF, and ability to read English.Results:548 adults with NF1 responded to the survey. Respondents ranked appearance, number, and then location as the most bothersome features of raised cNFs. Seventy-five percent of respondents considered a partial decrease of 33-66% in the number or size of cNFs as a meaningful response to experimental treatments. Most respondents (48-58%) were willing to try available cNF treatments but were not aware of options outside of surgical removal. Regarding experimental agents, respondents favored topical then oral medications. Most individuals (>65%) reported being “very much” or “extremely willing” to try experimental treatments, especially those with the highest cNF burden. Many respondents were not willing to tolerate side effects like nausea/vomiting (51%) and rash (46%). The greatest barriers to participation in cNF clinical trials were cost of participation and time off work.Conclusions:Most adults with NF1 are willing to consider experimental therapies for treatment of cNFs. These data will guide the design of patient-centered clinical trials for adults with cNFs.

Estimating the impact of control measures to prevent outbreaks of COVID-19 associated with air travel into a COVID-19-free country

We aimed to estimate the risk of COVID-19 outbreaks associated with air travel to a COVID-19-free country [New Zealand (NZ)]. A stochastic version of the SEIR model CovidSIM v1.1, designed specifically for COVID-19 was utilised. We first considered historical data for Australia before it eliminated COVID-19 (equivalent to an outbreak generating 74 new cases/day) and one flight per day to NZ with no interventions in place. This gave a median time to an outbreak of 0.2 years (95% range of simulation results: 3 days to 1.1 years) or a mean of 110 flights per outbreak. However, the combined use of a pre-flight PCR test of saliva, three subsequent PCR tests (on days 1, 3 and 12 in NZ), and various other interventions (mask use and contact tracing) reduced this risk to one outbreak after a median of 1.5 years (20 days to 8.1 years). A pre-flight test plus 14 days quarantine was an even more effective strategy (4.9 years; 2,594 flights). For a much lower prevalence (representing only two new community cases per week in the whole of Australia), the annual risk of an outbreak with no interventions was 1.2% and had a median time to an outbreak of 56 years. In contrast the risks associated with travellers from Japan and the United States was very much higher and would need quarantine or other restrictions. Collectively, these results suggest that multi-layered interventions can markedly reduce the risk of importing the pandemic virus via air travel into a COVID-19-free nation. For some low-risk source countries, there is the potential to replace 14-day quarantine with alternative interventions. However, all approaches require public and policy deliberation about acceptable risks, and continuous careful management and evaluation.