Creating a model of diseased artery damage and failure from healthy porcine aorta

Large quantities of diseased tissue are required in the research and development of new generations of medical devices, for example for use in physical testing. However, these are difficult to obtain. In contrast, porcine arteries are readily available as they are regarded as waste. Therefore, reliable means of creating from porcine tissue physical models of diseased human tissue that emulate well the associated mechanical changes would be valuable. To this end, we studied the effect on mechanical response of treating porcine thoracic aorta with collagenase, elastase and glutaraldehyde. The alterations in mechanical and failure properties were assessed via uniaxial tension testing. A constitutive model composed of the Gasser-Ogden-Holzapfel model, for elastic response, and a continuum damage model, for the failure, was also employed to provide a further basis for comparison (Calvo and Pena, 2006 and Gasser et al., 2006). For the concentrations used here it was found that: collagenase treated samples showed decreased fracture stress in the axial direction only; elastase treated samples showed increased fracture stress in the circumferential direction only; and glutaraldehyde samples showed no change in either direction. With respect to the proposed constitutive model, both collagenase and elastase had a strong effect on the fibre-related terms. The model more closely captured the tissue response in the circumferential direction, due to the smoother and sharper transition from damage initiation to complete failure in this direction. Finally, comparison of the results with those of tensile tests on diseased tissues suggests that these treatments indeed provide a basis for creation of physical models of diseased arteries

Controlled peel testing of a model tissue for diseased aorta

In this study, we examine the effect of collagenase, elastase and glutaraldehyde treatments on the response of porcine aorta to controlled peel testing. Specifically, the effects on the tissue׳s resistance to dissection, as quantified by critical energy release rate, are investigated. We further explore the utility of these treatments in creating model tissues whose properties emulate those of certain diseased tissues. Such model tissues would find application in, for example, development and physical testing of new endovascular devices. Controlled peel testing of fresh and treated aortic specimens was performed with a tensile testing apparatus. The resulting reaction force profiles and critical energy release rates were compared across sample classes. It was found that collagenase digestion significantly decreases resistance to peeling, elastase digestion has almost no effect, and glutaraldehyde significantly increases resistance. The implications of these findings for understanding mechanisms of disease-associated biomechanical changes, and for the creation of model tissues that emulate these changes are explored

Variation in minimum desired cardiovascular disease-free longevity benefit from statin and antihypertensive medications : A cross-sectional study of patient and primary care physician perspectives

Objective Expressing therapy benefit from a lifetime perspective, instead of only a 10-year perspective, is both more intuitive and of growing importance in doctor-patient communication. In cardiovascular disease (CVD) prevention, lifetime estimates are increasingly accessible via online decision tools. However, it is unclear what gain in life expectancy is considered meaningful by those who would use the estimates in clinical practice. We therefore quantified lifetime and 10-year benefit thresholds at which physicians and patients perceive statin and antihypertensive therapy as meaningful, and compared the thresholds with clinically attainable benefit. Design Cross-sectional study. Settings (1) continuing medical education conference in December 2016 for primary care physicians;(2) information session in April 2017 for patients. Participants 400 primary care physicians and 523 patients in the Netherlands. Outcome Months gain of CVD-free life expectancy at which lifelong statin therapy is perceived as meaningful, and months gain at which 10 years of statin and antihypertensive therapy is perceived as meaningful. Physicians were framed as users for lifelong and prescribers for 10-year therapy. Results Meaningful benefit was reported as median (IQR). Meaningful lifetime statin benefit was 24 months (IQR 23-36) in physicians (as users) and 42 months (IQR 12-42) in patients willing to consider therapy. Meaningful 10-year statin benefit was 12 months (IQR 10-12) for prescribing (physicians) and 14 months (IQR 10-14) for using (patients). Meaningful 10-year antihypertensive benefit was 12 months (IQR 8-12) for prescribing (physicians) and 14 months (IQR 10-14) for using (patients). Women desired greater benefit than men. Age, CVD status and co-medication had minimal effects on outcomes. Conclusion Both physicians and patients report a large variation in meaningful longevity benefit. Desired benefit differs between physicians and patients and exceeds what is clinically attainable. Clinicians should recognise these discrepancies when prescribing therapy and implement individualised medicine and shared decision-making. Decision tools could provide information on realistic therapy benefit

Variation in minimum desired cardiovascular disease-free longevity benefit from statin and antihypertensive medications : A cross-sectional study of patient and primary care physician perspectives

Objective Expressing therapy benefit from a lifetime perspective, instead of only a 10-year perspective, is both more intuitive and of growing importance in doctor-patient communication. In cardiovascular disease (CVD) prevention, lifetime estimates are increasingly accessible via online decision tools. However, it is unclear what gain in life expectancy is considered meaningful by those who would use the estimates in clinical practice. We therefore quantified lifetime and 10-year benefit thresholds at which physicians and patients perceive statin and antihypertensive therapy as meaningful, and compared the thresholds with clinically attainable benefit. Design Cross-sectional study. Settings (1) continuing medical education conference in December 2016 for primary care physicians;(2) information session in April 2017 for patients. Participants 400 primary care physicians and 523 patients in the Netherlands. Outcome Months gain of CVD-free life expectancy at which lifelong statin therapy is perceived as meaningful, and months gain at which 10 years of statin and antihypertensive therapy is perceived as meaningful. Physicians were framed as users for lifelong and prescribers for 10-year therapy. Results Meaningful benefit was reported as median (IQR). Meaningful lifetime statin benefit was 24 months (IQR 23-36) in physicians (as users) and 42 months (IQR 12-42) in patients willing to consider therapy. Meaningful 10-year statin benefit was 12 months (IQR 10-12) for prescribing (physicians) and 14 months (IQR 10-14) for using (patients). Meaningful 10-year antihypertensive benefit was 12 months (IQR 8-12) for prescribing (physicians) and 14 months (IQR 10-14) for using (patients). Women desired greater benefit than men. Age, CVD status and co-medication had minimal effects on outcomes. Conclusion Both physicians and patients report a large variation in meaningful longevity benefit. Desired benefit differs between physicians and patients and exceeds what is clinically attainable. Clinicians should recognise these discrepancies when prescribing therapy and implement individualised medicine and shared decision-making. Decision tools could provide information on realistic therapy benefit

Biallelic inactivation of BRCA2 in Fanconi anemia

Fanconi anemia (FA) is a rare autosomal recessive cancer susceptibility disorder characterized by cellular hypersensitivity to mitomycin C (MMC). Six FA genes have been cloned, but the gene or genes corresponding to FA subtypes B and D1 remain unidentified. Here we show that cell lines derived from FA-B and FA-D1 patients have biallelic mutations in BRCA2 and express truncated BRCA2 proteins. Functional complementation of FA-D1 fibroblasts with wild-type BRCA2 complementary DNA restores MMC resistance. Our results link the six cloned FA genes with BRCA1 and BRCA2 in a common pathway. Germ-line mutation of genes in this pathway may result in cancer risks similar to those observed in families with BRCA I or BRCA2 mutations

The effects of an online decision aid to support the reproductive decision-making process of genetically at risk couples—A pilot study

Couples at risk of transmitting a genetic disease to their offspring may experience doubts about their reproductive options. This study examines the effects of an online decision aid (DA) on the (joint) reproductive decision-making process of couples (not pregnant at time of inclusion) at risk of transmitting a genetic disease to their offspring. The primary outcome is decisional conflict, and secondary outcomes are knowledge, realistic expectations, deliberation, joint informed decision-making, and decisional self-efficacy. These outcomes were measured with a pretest–posttest design: before use (T0), after use (T1), and 2 weeks after use (T2) of the decision aid (DA). Usability of the DA was assessed at T1. Paired sample t-tests were used to compute differences between baseline and subsequent measurements. The comparisons of T0-T1 and T0-T2 indicate a significant reduction in mean decisional conflict scores with stronger effects for participants with high baseline decisional conflict scores. Furthermore, use of the DA led to increased knowledge, improved realistic expectations, and increased levels of deliberation, with higher increase in participants with low baseline scores. Decision self-efficacy only improved for participants with lower baseline scores. Participants indicated that the information in the DA was comprehensible and clearly organized. These first results indicate that this online DA is an appropriate tool to support couples at risk of transmitting a genetic disease and a desire to have (a) child(ren) in their reproductive decision-making process

The effects of an online decision aid to support the reproductive decision-making process of genetically at risk couples-A pilot study

Couples at risk of transmitting a genetic disease to their offspring may experience doubts about their reproductive options. This study examines the effects of an online decision aid (DA) on the (joint) reproductive decision-making process of couples (not pregnant at time of inclusion) at risk of transmitting a genetic disease to their offspring. The primary outcome is decisional conflict, and secondary outcomes are knowledge, realistic expectations, deliberation, joint informed decision-making, and decisional self-efficacy. These outcomes were measured with a pretest-posttest design: before use (T0), after use (T1), and 2 weeks after use (T2) of the decision aid (DA). Usability of the DA was assessed at T1. Paired sample t-tests were used to compute differences between baseline and subsequent measurements. The comparisons of T0-T1 and T0-T2 indicate a significant reduction in mean decisional conflict scores with stronger effects for participants with high baseline decisional conflict scores. Furthermore, use of the DA led to increased knowledge, improved realistic expectations, and increased levels of deliberation, with higher increase in participants with low baseline scores. Decision self-efficacy only improved for participants with lower baseline scores. Participants indicated that the information in the DA was comprehensible and clearly organized. These first results indicate that this online DA is an appropriate tool to support couples at risk of transmitting a genetic disease and a desire to have (a) child(ren) in their reproductive decision-making process