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Institute
- Fakultät für Gesundheitswissenschaften (99) (remove)
Genetic engineering has provided humans the ability to transform organisms by direct manipulation of genomes within a broad range of applications including agriculture (e.g., GM crops), and the pharmaceutical industry (e.g., insulin production). Developments within the last 10 years have produced new tools for genome editing (e.g., CRISPR/Cas9) that can achieve much greater precision than previous forms of genetic engineering. Moreover, these tools could offer the potential for interventions on humans and for both clinical and non-clinical purposes, resulting in a broad scope of applicability. However, their promising abilities and potential uses (including their applicability in humans for either somatic or heritable genome editing interventions) greatly increase their potential societal impacts and, as such, have brought an urgency to ethical and regulatory discussions about the application of such technology in our society. In this article, we explore different arguments (pragmatic, sociopolitical and categorical) that have been made in support of or in opposition to the new technologies of genome editing and their impact on the debate of the permissibility or otherwise of human heritable genome editing interventions in the future. For this purpose, reference is made to discussions on genetic engineering that have taken place in the field of bioethics since the 1980s. Our analysis shows that the dominance of categorical arguments has been reversed in favour of pragmatic arguments such as safety concerns. However, when it comes to involving the public in ethical discourse, we consider it crucial widening the debate beyond such pragmatic considerations. In this article, we explore some of the key categorical as well sociopolitical considerations raised by the potential uses of heritable genome editing interventions, as these considerations underline many of the societal concerns and values crucial for public engagement. We also highlight how pragmatic considerations, despite their increasing importance in the work of recent authoritative sources, are unlikely to be the result of progress on outstanding categorical issues, but rather reflect the limited progress on these aspects and/or pressures in regulating the use of the technology.
Analysis of physicians' probability estimates of a medical outcome based on a sequence of events
(2022)
A basic law of probability is that the probability of a conjunction of 2 independent events is the product of both components and cannot exceed the likelihood of either component. When this basic law is violated, it is known as the conjunction fallacy. In clinical practice, the conjunction fallacy may arise when physicians estimate the probability of the overall outcome that requires >= 2 steps to be successful. For example, if a successful procedure requires the success of step A and step B, then the probability of overall success of the procedure cannot exceed the likelihood of success of either step A or step B. The aim of this study was to determine whether physicians could correctly estimate the overall probability of success from 2 independent events. <br /> This was a 3-part, Internet-based survey study designed to evaluate the presence of the conjunction fallacy in 2 separate obstetric contexts and 1 pulmonary context. Respondents were board-certified or board-eligible physicians in obstetrics and gynecology and pulmonary, recruited from a commercial survey service. In each context, physicians were presented with scenarios related to their medical specialty and asked to judge the probability of the overall outcome, or conjunction, and of the 2 individual events, or conjuncts. <br /> The first substudy, conducted April 2-4, 2021, described a delivery in brow presentation discovered during labor. To assess the overall probability of a successful spontaneous vaginal delivery, an obstetrician must consider the likelihood of the brow presentation converting to a deliverable position and the likelihood of vaginal delivery from the converted position. The second substudy, conducted November 2-11, 2021, described the diagnostic evaluation of pulmonary nodule discovered incidentally. To assess the overall probability that a biopsy reveals cancer, the physician must consider the likelihood that the nodule is cancerous and the likelihood that the biopsy successfully and accurately detects cancer. The third study, conducted May 13-19, 2021, modified the first substudy and asked responding obstetricians to consider the likelihood of the individual conjuncts before estimating the overall probability of successful vaginal delivery. <br /> The survey included responses from 215 physicians: 66% were male and 34% were female with a mean (SD) age of 53.6 (9.5) years and mean time since obtaining a medical degree of 27.5 (10.6) years. Overall, 78.1% of physicians committed the conjunction fallacy, estimating that the overall probability of success was greater than the likelihood of at least 1 of the 2 conjuncts. In the first substudy, 74.6% of 67 obstetricians committed the conjunction fallacy; respondents overestimated the combined probability by 12.8% (95% confidence interval [CI], 9.6%-16.1%), compared with the product of the 2 estimated conjuncts with statistically significant deviation (t66 = 7.94; P < 0.001; Cohen d = 0.97 [95% CI, 0.68-1.26]). In the second substudy, 86.9% of 84 pulmonologists committed the conjunction fallacy; respondents overestimated the combined probability by 19.8% (95% CI, 16.6%-23.0%), with statistically significant deviation of (t83 = 7.94; P < 0.001; Cohen d = 1.34 [95% CI, 1.04-1.64]). In the third substudy, 70.3% of 64 committed the conjunction fallacy; respondents overestimated the combined probability by 18.0% (95% CI, 13.4%-22.5%) with statistically significant deviation (t63 = 7.89; P < 0.001; Cohen d = 0.99 [95% CI, 0.68-1.28]). <br /> In this study, it was common for seasoned obstetricians and pulmonologists to commit the conjunction fallacy. Given that physicians often need to estimate the successful outcome of a multistep procedure, they may be doing so in a flawed manner that may negatively impact decision-making.
Frailty assessment is recommended before elective transcatheter aortic valve implantation (TAVI) to determine post-interventional prognosis. Several studies have investigated frailty in TAVI-patients using numerous assessments; however, it remains unclear which is the most appropriate tool for clinical practice. Therefore, we evaluate which frailty assessment is mainly used and meaningful for ≤30-day and ≥1-year prognosis in TAVI patients. Randomized controlled or observational studies (prospective/retrospective) investigating all-cause mortality in older (≥70 years) TAVI patients were identified (PubMed; May 2020). In total, 79 studies investigating frailty with 49 different assessments were included. As single markers of frailty, mostly gait speed (23 studies) and serum albumin (16 studies) were used. Higher risk of 1-year mortality was predicted by slower gait speed (highest Hazard Ratios (HR): 14.71; 95% confidence interval (CI) 6.50–33.30) and lower serum albumin level (highest HR: 3.12; 95% CI 1.80–5.42). Composite indices (five items; seven studies) were associated with 30-day (highest Odds Ratio (OR): 15.30; 95% CI 2.71–86.10) and 1-year mortality (highest OR: 2.75; 95% CI 1.55–4.87). In conclusion, single markers of frailty, in particular gait speed, were widely used to predict 1-year mortality. Composite indices were appropriate, as well as a comprehensive assessment of frailty. View Full-Text
Frailty assessment is recommended before elective transcatheter aortic valve implantation (TAVI) to determine post-interventional prognosis. Several studies have investigated frailty in TAVI-patients using numerous assessments; however, it remains unclear which is the most appropriate tool for clinical practice. Therefore, we evaluate which frailty assessment is mainly used and meaningful for ≤30-day and ≥1-year prognosis in TAVI patients. Randomized controlled or observational studies (prospective/retrospective) investigating all-cause mortality in older (≥70 years) TAVI patients were identified (PubMed; May 2020). In total, 79 studies investigating frailty with 49 different assessments were included. As single markers of frailty, mostly gait speed (23 studies) and serum albumin (16 studies) were used. Higher risk of 1-year mortality was predicted by slower gait speed (highest Hazard Ratios (HR): 14.71; 95% confidence interval (CI) 6.50–33.30) and lower serum albumin level (highest HR: 3.12; 95% CI 1.80–5.42). Composite indices (five items; seven studies) were associated with 30-day (highest Odds Ratio (OR): 15.30; 95% CI 2.71–86.10) and 1-year mortality (highest OR: 2.75; 95% CI 1.55–4.87). In conclusion, single markers of frailty, in particular gait speed, were widely used to predict 1-year mortality. Composite indices were appropriate, as well as a comprehensive assessment of frailty. View Full-Text
Introduction
Elderly patients after hospitalisation for acute events on account of age-related diseases (eg, joint or heart valve replacement surgery) are often characterised by a remarkably reduced functional health. Multicomponent rehabilitation (MR) is considered an appropriate approach to restore the functioning of these patients. However, its efficacy in improving functioning-related outcomes such as care dependency, activities of daily living (ADL), physical function and health-related quality of life (HRQL) remains unclarified. We outline the research framework of a scoping review designed to map the available evidence of the effects of MR on the independence and functional capacity of elderly patients hospitalised for age-related diseases in four main medical specialties beyond geriatrics.
Methods and analysis
The biomedical databases (PubMed, Cochrane Library, ICTRP Search Platform, ClinicalTrials) and additionally Google Scholar will be systematically searched for studies comparing centre-based MR with usual care in patients ≥75 years of age, hospitalised for common acute events due to age-related diseases (eg, joint replacement, stroke) in one of the specialties of orthopaedics, oncology, cardiology or neurology. MR is defined as exercise training and at least one additional component (eg, nutritional counselling), starting within 3 months after hospital discharge. Randomised controlled trials as well as prospective and retrospective controlled cohort studies will be included from inception and without language restriction. Studies investigating patients <75 years, other specialties (eg, geriatrics), rehabilitation definition or differently designed will be excluded. Care dependency after at least a 6-month follow-up is set as the primary outcome. Physical function, HRQL, ADL, rehospitalisation and mortality will be additionally considered. Data for each outcome will be summarised, stratified by specialty, study design and type of assessment. Furthermore, quality assessment of the included studies will be performed.
Ethics and dissemination
Ethical approval is not required. Findings will be published in a peer-reviewed journal and presented at national and/or international congresses.
Introduction Airway infection with pathogens and its associated pulmonary exacerbations (PEX) are the major causes of morbidity and premature death in cystic fibrosis (CF). Preventing or postponing chronic infections requires early diagnosis. However, limitations of conventional microbiology-based methods can hamper identification of exacerbations and specific pathogen detection. Analyzing volatile organic compounds (VOCs) in breath samples may be an interesting tool in this regard, as VOC-biomarkers can characterize specific airway infections in CF. Areas covered We address the current achievements in VOC-analysis and discuss studies assessing VOC-biomarkers and fingerprints, i.e. a combination of multiple VOCs, in breath samples aiming at pathogen and PEX detection in people with CF (pwCF). We aim to provide bases for further research in this interesting field. Expert opinion Overall, VOC-based analysis is a promising tool for diagnosis of infection and inflammation with potential to monitor disease progression in pwCF. Advantages over conventional diagnostic methods, including easy and non-invasive sampling procedures, may help to drive prompt, suitable therapeutic approaches in the future. Our review shall encourage further research, including validation of VOC-based methods. Specifically, longitudinal validation under standardized conditions is of interest in order to ensure repeatability and enable inclusion in CF diagnostic routine.
Introduction Vagally mediated heart rate variability is an index of autonomic nervous system activity that is associated with a large variety of outcome variables including psychopathology and self-regulation. While practicing heart rate variability biofeedback over several weeks has been reliably associated with a number of positive outcomes, its acute effects are not well known. As the strongest association with vagally mediated heart rate variability has been found particularly within the attention-related subdomain of self-regulation, we investigated the acute effect of heart rate variability biofeedback on attentional control using the revised Attention Network Test.
Methods Fifty-six participants were tested in two sessions. In one session each participant received a heart rate variability biofeedback intervention, and in the other session a control intervention of paced breathing at a normal ventilation rate. After the biofeedback or control intervention, participants completed the Attention Network Test using the Orienting Score as a measure of attentional control.
Results Mixed models revealed that higher resting baseline vagally mediated heart rate variability was associated with better performance in attentional control, which suggests more efficient direction of attention to target stimuli. There was no significant main effect of the intervention on attentional control. However, an interaction effect indicated better performance in attentional control after biofeedback in individuals who reported higher current stress levels.
Discussion The results point to acute beneficial effects of heart rate variability biofeedback on cognitive performance in highly stressed individuals. Although promising, the results need to be replicated in larger or more targeted samples in order to reach stronger conclusions about the effects.
Jenseits der Klinik
(2021)
Unser Beitrag stellt ein interaktives Ethik-Konzept vor, das in Zusammenarbeit der BruderhausDiakonie Reutlingen und der Universität Tübingen entwickelt wurde, um den Eigenheiten und Bedarfen einer komplexen Organisationsstruktur gerecht zu werden, die mehrere Geschäftsfelder und Standorte unter sich vereint. Wir skizzieren die Grundzüge des interaktiven Nijmegener Modells, in dem die Kooperation eines auf Leitungsebene angesiedelten Komitees und situationsbezogener Fallbesprechungen ein fruchtbares Zusammenspiel zweier unverzichtbarer Reflexionsweisen bewirken soll („Top-Down“/„Bottom-Up“). Wir zeigen auf, welche Herausforderungen sich bei der Implementierung dieses Modells in die konkrete Aufbauorganisation der BruderhausDiakonie ergaben, und mit welchen konzeptionellen oder „implementationstechnischen“ Mitteln ihnen begegnet wurde. Im Zentrum steht dabei die Erweiterung des Nijmegener Modells um ein Verbindungselement, welches die Zusammenarbeit zwischen zentralem Ausschuss und dezentralen Fallbesprechungen koordiniert und das interaktive Moment des Modells erst ermöglicht.
The study investigated the incidence of Achilles and patellar tendinopathy in adolescent elite athletes and non-athletic controls. Furthermore, predictive and associated factors for tendinopathy development were analyzed. The prospective study consisted of two measurement days (M1/M2) with an interval of 3.2 +/- 0.9 years. 157 athletes (12.1 +/- 0.7 years) and 25 controls (13.3 +/- 0.6 years) without Achilles/patellar tendinopathy were included at Ml. Clinical and ultrasound examinations of both Achilles (AT) and patellar tendons (PT) were performed. Main outcome measures were incidence tendinopathy and structural intratendinous alterations (hypo-/hyperechogenicity, vascularization) at M2 [%]. Incidence of Achilles tendinopathy was 1% in athletes and 0% in controls. Patellar tendinopathy was more frequent in athletes (13 %)than in controls (4%). Incidence of intratendinous alterations in ATs was 1-2% in athletes and 0 % in controls, whereas in PTs it was 4-6 % in both groups (p >0.05). Intratendinous alterations at M2 were associated with patellar tendinopathy in athletes (p <= 0.01). Intratendinous alterations at M1, anthropometric data, training amount, sports or sex did not predict tendinopathy development (p>0.05). Incidence often dinopathy and intratendinous alterations in adolescent athletes is low in ATs and more common in PTs. Development of intratendinous alterations in PT is associated with tend in opathy. However, predictive factors could not be identified.