Shear Stress Quantification in Tissue Engineering Bioreactor Heart Valves: A Computational Approach.

Tissue-engineered heart valves can grow, repair, and remodel after implantation, presenting a more favorable long-term solution compared to mechanical and porcine valves. Achieving functional engineered valve tissue requires the maturation of human cells seeded onto valve scaffolds under favorable growth conditions in bioreactors. The mechanical stress and strain on developing valve tissue caused by different pressure and flow conditions in bioreactors are currently unknown. The aim of this study is to quantify the wall shear stress (WSS) magnitude in heart valve prostheses under different valve geometries and bioreactor flow rates. To achieve this, this study used fluid-structure interaction simulations to obtain the valve's opening geometries during the systolic phase. These geometries were then used in computational fluid dynamics simulations with refined near-wall mesh elements and ranges of prescribed inlet flow rates. The data obtained included histograms and regression curves that characterized the distribution, peak, and median WSS for various flow rates and valve opening configurations. This study also found that the upper region of the valve near the commissures experienced higher WSS magnitudes than the rest of the valve.

Estimating Prevalence and Characteristics of Statin Intolerance among High and Very High Cardiovascular Risk Patients in Germany (2017 to 2020).

Statin intolerance (SI) (partial and absolute) could lead to suboptimal lipid management. The lack of a widely accepted definition of SI results into poor understanding of patient profiles and characteristics. This study aims to estimate SI and better understand patient characteristics, as reflected in clinical practice in Germany using supervised machine learning (ML) techniques. This retrospective cohort study utilized patient records from an outpatient setting in Germany in the IQVIA™ Disease Analyzer. Patients with a high cardiovascular risk, atherosclerotic cardiovascular disease, or hypercholesterolemia, and those on lipid-lowering therapies between 2017 and 2020 were included, and categorized as having "absolute" or "partial" SI. ML techniques were applied to calibrate prevalence estimates, derived from different rules and levels of confidence (high and low). The study included 292,603 patients, 6.4% and 2.8% had with high confidence absolute and partial SI, respectively. After deploying ML, SI prevalence increased approximately by 27% and 57% (p < 0.00001) in absolute and partial SI, respectively, eliciting a maximum estimate of 12.5% SI with high confidence. The use of advanced analytics to provide a complementary perspective to current prevalence estimates may inform the identification, optimal treatment, and pragmatic, patient-centered management of SI in Germany.

United States Investigational Device Exemption study of the Revolution Peripheral Atherectomy System.

OBJECTIVE: Atherectomy has become commonplace as an adjunct to interventional treatments for peripheral arterial disease, but the procedures have been complicated by risks including distal embolization and arterial perforation. This study aimed to examine the safety and effectiveness of a novel atherectomy system to treat femoropopliteal and below-knee peripheral arterial disease. METHODS: The Revolution Peripheral Atherectomy System (Rex Medical LP, Conshohocken, Pa) was studied in 121 patients with 148 femoropopliteal and below-knee lesions, enrolled at 17 United States institutions. Technical success was defined when the post-atherectomy angiographic stenosis was ≤50%, as assessed by an independent core laboratory. Major adverse events were adjudicated by an independent Clinical Events Committee. RESULTS: Among 148 site-identified target lesions in 121 patients, 21.4% were in the superficial femoral artery, 13.7% involved the popliteal artery, and 67.9% were in tibial arteries; 3.1% involved more than one segment. Technical success was 90.2%, with stenoses decreasing from 73% ± 19% at baseline to 42% ± 14% after atherectomy. Adjunctive treatment after atherectomy included angioplasty with uncoated balloons in 91%, drug-coated balloons in 11%, bare stent deployment in 8%, and drug-eluting stent placement in 3%. Procedural success (<30% residual stenosis) was achieved in 93.7% of target lesions. Complications during the procedure included one target vessel perforation and two distal embolizations; each of which were adjudicated by the Clinical Events Committee as unrelated to the device and were not visualized angiographically by the core laboratory. Freedom from major adverse events was 97.3% through 30 days. The Kaplan-Meier estimates of primary, assisted primary, and secondary patency were 81.6%, 87.7%, and 91.6% at 6 months, respectively. CONCLUSIONS: The use of the Revolution Peripheral Atherectomy System was associated with few procedural complications and a high rate of success at the index procedure and through 6 months.

mHealth Intervention to Improve Diabetes Risk Behaviors in India: A Prospective, Parallel Group Cohort Study.

BACKGROUND: In low/middle income countries like India, diabetes is prevalent and health care access limited. Most adults have a mobile phone, creating potential for mHealth interventions to improve public health. To examine the feasibility and initial evidence of effectiveness of mDiabetes, a text messaging program to improve diabetes risk behaviors, a global nonprofit organization (Arogya World) implemented mDiabetes among one million Indian adults. OBJECTIVE: A prospective, parallel cohort design was applied to examine whether mDiabetes improved fruit, vegetable, and fat intakes and exercise. METHODS: Intervention participants were randomly selected from the one million Nokia subscribers who elected to opt in to mDiabetes. Control group participants were randomly selected from non-Nokia mobile phone subscribers. mDiabetes participants received 56 text messages in their choice of 12 languages over 6 months; control participants received no contact. Messages were designed to motivate improvement in diabetes risk behaviors and increase awareness about the causes and complications of diabetes. Participant health behaviors (exercise and fruit, vegetable, and fat intake) were assessed between 2012 and 2013 via telephone surveys by blinded assessors at baseline and 6 months later. Data were cleaned and analyzed in 2014 and 2015. RESULTS: 982 participants in the intervention group and 943 in the control group consented to take the phone survey at baselne. At the end of the 6-month period, 611 (62.22%) in the intervention and 632 (67.02%) in the control group completed the follow-up telephone survey. Participants receiving texts demonstrated greater improvement in a health behavior composite score over 6 months, compared with those who received no messages F(1, 1238) = 30.181, P<.001, 95% CI, 0.251-0.531. Fewer intervention participants demonstrated health behavior decline compared with controls. Improved fruit, vegetable, and fat consumption (P<.01) but not exercise were observed in those receiving messages, as compared with controls. CONCLUSIONS: A text messaging intervention was feasible and showed initial evidence of effectiveness in improving diabetes-related health behaviors, demonstrating the potential to facilitate population-level behavior change in a low/middle income country. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ACTRN): 12615000423516; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=367946&isReview=true (Archived by WebCite at http://www.webcitation.org/6j5ptaJgF).

Mayo, Myriad, America Invents Act and BPCIA: how has the United States biopharmaceutical market been affected?

This paper discusses how the United States biopharmaceutical market has been affected by recent changes in patent law resulting from United States legislations (Biologics Price Competition and Innovation Act and the Leahy-Smith America Invents Act) and Supreme Court precedents (Mayo Collaborative Services v. Prometheus Laboratories, Inc. and Molecular Pathology v. Myriad Genetics). The authors interviewed eight key opinion leaders from the United States knowledgeable in biopharmaceuticals, including industry veterans, patent counsel, senior scientists and jurists. This paper summarizes the opinions of the key opinion leaders. This paper explains the impact of these Supreme Court decisions - i.e., broadening the exceptions to patent eligibility for law of nature and natural phenomenon - on biopharmaceutical innovations and provides future perspectives.

Interfacing of Science, Medicine and Law: The Stem Cell Patent Controversy in the United States and the European Union.

The patent eligibility of stem cells-particularly those derived from human embryos-has long been under debate in both the scientific and legal communities. On the basis of moral grounds, the European Patent Office (EPO) has refrained from granting patents for stem cells obtained through the destruction of human embryos. On the contrary, the United States Patent and Trademark Office (USPTO) has historically granted patents regarding the isolation and use of human embryonic and other stem cells. To date, these US patents remain valid despite an increasing onslaught of challenges in court. However, recent precedents established in US courts significantly narrow the scope of patent eligibility within biotechnology. This article compares the implications of recent legal changes on stem cell patent eligibility between the EU and US.

Scanning for chorionicity: comparison between sonographers and perinatologists.

OBJECTIVE: In most prenatal settings, twin pregnancies are initially evaluated by sonographers. Pregnancies diagnosed as monochorionic are subsequently referred to perinatologists or specialists in fetal medicine for the confirmation of chorionicity. In order to assess this screening strategy, we have compared the diagnosis of chorionicity made by the sonographers in the ultrasound department with the diagnosis done in the fetal medicine unit. METHODS: A cohort of women presenting with twin pregnancy and booked for prenatal care at University College London Hospitals over a 4-year period were investigated prospectively. All women were scanned at their initial visit at 11-14 weeks in the ultrasound department (US), and were subsequently referred to the Fetal Medicine Unit (FMU) for a second ultrasound evaluation. Ultrasound data were compared and diagnosis of chorionicity was confirmed by examination of the inter-twin membranes after delivery. RESULTS: Chorionicity was determined in 172 twin cases by the two different departments. The overall rate of concordant chorionicity determination between both units was 90.1%. The rate of discordant results in dichorionic pregnancies was extremely small, 1 in 119 pregnancies (0.8%). The rate of discordant results for monochorionic diamniotic pregnancies was 5.5%. Monoamniotic pregnancies were over-diagnosed by the US technicians. DISCUSSION: These results demonstrate that DC/DA chorionicity is accurately determined by sonographers at less than 14 weeks. In our opinion, it is both efficient and safe to rely on the diagnosis of the sonographers in DC/DA pregnancies in early pregnancy. In such pregnancies, a decision can be made either not to refer these patients for further evaluation of chorionicity by the fetal medicine team or to postpone the referral to after 14 weeks.