Ethics, economics and the regulation and adoption of new medical devices: case studies in pelvic floor surgery

<p>Abstract</p> <p>Background</p> <p>Concern has been growing in the academic literature and popular media about the licensing, introduction and adoption of surgical devices before full effectiveness and safety evidence is available to inform clinical practice. Our research will seek empirical survey evidence about the roles, responsibilities, and information and policy needs of the key stakeholders in the introduction into clinical practice of new surgical devices for pelvic floor surgery, in terms of the underlying ethical principals involved in the economic decision-making process, using the example of pelvic floor procedures.</p> <p>Methods/Design</p> <p>Our study involves three linked case studies using, as examples, selected pelvic floor surgery devices representing Health Canada device safety risk classes: low, medium and high risk. Data collection will focus on stakeholder roles and responsibilities, information and policy needs, and perceptions of those of other key stakeholders, in seeking and using evidence about new surgical devices when licensing and adopting them into practice. For each class of device, interviews will be used to seek the opinions of stakeholders. The following stakeholders and ethical and economic principles provide the theoretical framework for the study:</p> <p indent="1"><b>Stakeholders </b>- federal regulatory body, device manufacturers, clinicians, patients, health care institutions, provincial health departments, and professional societies. Clinical settings in two centres (in different provinces) will be included.</p> <p indent="1"><b>Ethics </b>- beneficence, non-maleficence, autonomy, justice.</p> <p indent="1"><b>Economics </b>- scarcity of resources, choices, opportunity costs.</p> <p>For each class of device, responses will be analysed to compare and contrast between stakeholders. Applied ethics and economic theory, analysis and critical interpretation will be used to further illuminate the case study material.</p> <p>Discussion</p> <p>The significance of our research in this new area of ethics will lie in providing recommendations for regulatory bodies, device manufacturers, clinicians, health care institutions, policy makers and professional societies, to ensure surgical patients receive sufficient information before providing consent for pelvic floor surgery. In addition, we shall provide a wealth of information for future study in other areas of surgery and clinical management, and provide suggestions for changes to health policy.</p

Quantitative Subcellular Proteome and Secretome Profiling of Influenza A Virus-Infected Human Primary Macrophages

Influenza A viruses are important pathogens that cause acute respiratory diseases and annual epidemics in humans. Macrophages recognize influenza A virus infection with their pattern recognition receptors, and are involved in the activation of proper innate immune response. Here, we have used high-throughput subcellular proteomics combined with bioinformatics to provide a global view of host cellular events that are activated in response to influenza A virus infection in human primary macrophages. We show that viral infection regulates the expression and/or subcellular localization of more than one thousand host proteins at early phases of infection. Our data reveals that there are dramatic changes in mitochondrial and nuclear proteomes in response to infection. We show that a rapid cytoplasmic leakage of lysosomal proteins, including cathepsins, followed by their secretion, contributes to inflammasome activation and apoptosis seen in the infected macrophages. Also, our results demonstrate that P2X7 receptor and src tyrosine kinase activity are essential for inflammasome activation during influenza A virus infection. Finally, we show that influenza A virus infection is associated with robust secretion of different danger-associated molecular patterns (DAMPs) suggesting an important role for DAMPs in host response to influenza A virus infection. In conclusion, our high-throughput quantitative proteomics study provides important new insight into host-response against influenza A virus infection in human primary macrophages

Global risk of deadly heat

Climate change can increase the risk of conditions that exceed human thermoregulatory capacity. Although numerous studies report increased mortality associated with extreme heat events, quantifying the global risk of heat-related mortality remains challenging due to a lack of comparable data on heat-related deaths. Here we conducted a global analysis of documented lethal heat events to identify the climatic conditions associated with human death and then quantified the current and projected occurrence of such deadly climatic conditions worldwide. We reviewed papers published between 1980 and 2014, and found 783 cases of excess human mortality associated with heat from 164 cities in 36 countries. Based on the climatic conditions of those lethal heat events, we identified a global threshold beyond which daily mean surface air temperature and relative humidity become deadly. Around 30% of the world’s population is currently exposed to climatic conditions exceeding this deadly threshold for at least 20 days a year. By 2100, this percentage is projected to increase to ~48% under a scenario with drastic reductions of greenhouse gas emissions and ~74% under a scenario of growing emissions. An increasing threat to human life from excess heat now seems almost inevitable, but will be greatly aggravated if greenhouse gases are not considerably reduced

Prevalence and risk factors for mesh erosion after laparoscopic-assisted sacrocolpopexy

Introduction and hypothesis: The purpose of this study is to identify risk factors for mesh erosion in women undergoing minimally invasive sacrocolpopexy (MISC). We hypothesize that erosion is higher in subjects undergoing concomitant hysterectomy. Methods: This is a retrospective cohort study of women who underwent MISC between November 2004 and January 2009. Demographics, operative techniques, and outcomes were abstracted from medical records. Multivariable regression identified odds of erosion. Results: Of 188 MISC procedures 19(10%) had erosions. Erosion was higher in those with total vaginal hysterectomy (TVH) compared to both post-hysterectomy (23% vs. 5%, p = 0.003) and supracervical hysterectomy (SCH) (23% vs. 5%, p = 0.109) groups. In multivariable regression, the odds of erosion for TVH was 5.67 (95% CI: 1.88-17.10) compared to post-hysterectomy. Smoking, the use of collagen-coated mesh, transvaginal dissection, and mesh attachment transvaginally were no longer significant in the multivariable regression model. Conclusion: Based on this study, surgeons should consider supracervical hysterectomy over total vaginal hysterectomy as the procedure of choice in association with MISC unless removal of the cervix is otherwise indicated. © 2010 The Author(s)