Personalized 3D printed scaffolds:The ethical aspects

Personalized 3D printed scaffolds are a new generation of implants for tissue engineering and regenerative medicine purposes. Scaffolds support cell growth, providing an artificial extracellular matrix for tissue repair and regeneration and can biodegrade once cells have assumed their physiological and structural roles. The ethical challenges and opportunities of these implants should be mapped in parallel with the life cycle of the scaffold to assist their development and implementation in a responsible, safe, and ethically sound manner. This article provides an overview of these relevant ethical aspects. We identified nine themes which were linked to three stages of the life cycle of the scaffold: the development process, clinical testing, and the implementation process. The described ethical issues are related to good research and clinical practices, such as privacy issues concerning digitalization, first-in-human trials, responsibility and commercialization. At the same time, this article also creates awareness for underexplored ethical issues, such as irreversibility, embodiment and the ontological status of these scaffolds. Moreover, it exemplifies how to include gender in the ethical assessment of new technologies. These issues are important for responsible development and implementation of personalized 3D printed scaffolds and in need of more attention within the additive manufacturing and tissue engineering field. Moreover, the insights of this review reveal unresolved qualitative empirical and normative questions that could further deepen the understanding and co-creation of the ethical implications of this new generation of implants.</p

A value hierarchy for inclusive design of heart valve implants in regenerative medicine

Aim: This paper investigates the conditions for inclusive design of regenerative medicine interventions from a bioethical perspective, taking regenerative valve implants as a showcase. Methods: A value hierarchy is construed to translate the value of justice into norms and design requirements for inclusive design of regenerative valve implants. Results: Three norms are proposed and translated into design requirements: regenerative valve implants should be designed to promote equal opportunity to good health for all potential users; equal respect for all potential users should be shown; and the implants should be designed to be accessible to everyone in need. Conclusion: The norms and design requirements help to design regenerative valve implants that are appropriate, respectful and available for everyone in need.</p

Healthcare professionals' self-reported experiences and preferences related to direct healthcare professional communications:a survey conducted in the Netherlands

Background: In Europe, Direct Healthcare Professional Communications (DHPCs) are important tools to inform healthcare professionals of serious, new drug safety issues. However, this tool has not always been successful in effectively communicating the desired actions to healthcare professionals. Objective: The aim of this study was to explore healthcare providers' experiences and their preferences for improvement of risk communication, comparing views of general practitioners (GPs), internists, community pharmacists and hospital pharmacists. Methods: A questionnaire was developed and pilot tested to assess experiences and preferences of Dutch healthcare professionals with DHPCs. The questionnaire and two reminders were sent to a random sample of 3488 GPs, internists and community and hospital pharmacists in the Netherlands. Descriptive statistics were used to describe demographic characteristics of the respondents. Chi squares, ANOVAs and the Wilcoxon signed rank test were used, when appropriate, to compare healthcare professional groups. Results: The overall response rate was 34% (N=1141, ranging from 24% for internists to 46% for community pharmacists). Healthcare providers trusted safety information more when provided by the Dutch Medicines Evaluation Board (MEB) than by the pharmaceutical industry. This was more the case for GPs than for the other healthcare professionals. Respondents preferred safety information to be issued by the MEB, the Dutch Pharmacovigilance Center or their own professional associations. The preferred alternative channels of drug safety information were e-mail, medical journals and electronic prescribing systems. Conclusions: Safety information of drugs does not always reach healthcare professionals through DHPCs. To improve current risk communication of drug safety issues, alternative and/or additional methods of risk communication should be developed using electronic methods and medical journals. Moreover, (additional) risk communication coming from an independent source such as the MEB should be considered. Special effort is needed to reach GPs

Was it worth it? Benefits of transcatheter aortic valve implantation from a patient's perspective:Benefits of transcatheter aortic valve implantation from a patient's perspective

OBJECTIVES: Transcatheter aortic valve implantation (TAVI) is an important treatment option for patients with severe aortic stenosis. To improve patient selection, shared decision‐making is recommended to elicit patients' treatment expectations and goals. We assessed patients' expectations and goals before TAVI treatment and whether these were met after treatment. Additionally, we evaluated how meeting these goals aligned with quality of life and functional recovery. DESIGN: A mixed method study. SETTING: An academic medical center. PARTICIPANTS: Seventy‐four patients undergoing TAVI between 2015 and 2017. MEASUREMENTS: Patients' expectations and goals were assessed qualitatively before treatment. Six to twelve months post procedure, quality of life was measured with the EuroQuol‐5D and any change in the number of dependencies in (instrumental) activities of daily living was assessed. RESULTS: Mean age of patients was 81.5 years, and 37.8% were male. Regaining the ability to engage in a specific hobby or activity was the most important treatment goal (33 patients, 54.1%), followed by reducing symptoms (19 patients 31.1%). 66.2% of patients stated that their treatment goal was met. Quality of life was higher in this group, as compared with patients who had not met their treatment goal. Twenty‐three patients (31.1%) showed functional improvement. CONCLUSION: TAVI patients were quite capable of eliciting treatment goals and a majority stated, after treatment, that these had been met patients' experience of treatment benefits regarding these goals had poor alignment with functional outcomes. This raises questions regarding relevant outcome measurements in this population, and could aid in improving shared decision‐making and patient selection for TAVI

Modest effect of p53, EGFR and HER-2/neu on prognosis in epithelial ovarian cancer: a meta-analysis

Background: P53, egfr and her-2/neu are the most frequently studied molecular biological parameters in epithelial ovarian cancer, but their prognostic impact is still unequivocal. We performed a meta-analysis to more precisely estimate their prognostic significance. Methods: Published studies that investigated the association between p53, egfr and her-2/neu status and survival were identified. Meta-analysis was performed using a dersimonian-laird model. Publication bias was investigated using funnel plots and sources of heterogeneity were identified using meta-regression analysis. Results: A total of 62 studies were included for p53, 15 for egfr and 20 for her-2/neu. P53, egfr and her-2/neu status had a modest effect on overall survival (Pooled hr 1.47, 95% Ci 1.33-1.61 For p53; Hr 1.65, 95% Ci 1.25-2.19 For egfr and hr 1.67, 95% Ci 1.34-2.08 For her-2/neu). Meta-regression analysis for p53 showed that figo stage distribution influenced study outcome. For egfr and her-2/neu, considerable publication bias was present. Conclusions: Although p53, egfr and her-2/neu status modestly influences survival, these markers are, by themselves, unlikely to be useful as prognostic markers in clinical practice. Our study highlights the need for well-defined, prospective clinical trials and more complete reporting of results of prognostic factor studies. British journal of cancer ( 2009) 101, 149-159. Doi: 10.1038/Sj.Bjc.6605112 Www.Bjcancer.Com published online 9 june 2009 (C) 2009 Cancer research uk

Additional safety risk to exceptionally approved drugs in Europe?

AIMS Regulatory requirements for new drugs have increased. Special approval procedures with priority assessment are possible for drugs with clear 'unmet medical need'. We question whether these Exceptional Circumstances (EC) or Conditional Approval (CA) procedures have led to a higher probability of serious safety issues. METHODS A retrospective cohort study was performed of new drugs approved in Europe between 1999 and 2009. The determinant was EC/CA vs. standard procedure approval. Outcome variables were frequency and timing of a first Direct Healthcare Professional Communication (DHPC). An association between approval procedure and the time from market approval to DHPC was assessed using Kaplan-Meyer survival analysis and Cox-regression to correct for covariates. RESULTS In total 289 new drugs were approved. Forty-six (16.4%) were approved under EC or CA, of which seven received a DHPC (15%). This was similar to the standard approval drugs (243), of which 33 received one or more DHPC (14%, P = 0.77). The probability of acquiring a DHPC for standard approval drugs vs. EC/CA drugs during 11-year follow-up is 22% (95% CI 14%, 29%) and 26% (95% CI 8%, 44%), respectively (log-rank P = 0.726). This difference remained not significant in the Cox-regression model: hazard ratio 0.94 (95% CI 0.40, 2.20). Only drug type was identified as a confounding covariate. CONCLUSION The EC/CA procedure is not associated with a higher probability of DHPCs despite limited clinical development data. These data do not support the view that early drug approval increases the risk of serious safety issues emerging after market approval