Irish Health Research Regulations (HRRs) were introduced following the European Union (EU) General Data Protection Regulation (GDPR) in 2018. The HRRs described specific supplementary regulatory requirements for research regarding governance, processes and procedure that impact on several facets of research. The numerous problems that the HRRs and particularly “explicit consent” inadvertently created were presented under the auspices of the Irish Academy of Medical Sciences (IAMS) on November 25, 2019, at the Royal College of Surgeons in Ireland.

The objective of this review was to obtain feedback and to examine the impact of GDPR and the HRRs on health research in Ireland in order to determine whether the preliminary feedback, presented at the IAMS meetings, was reflected at a national level.

Individuals from the research community were invited to provide feedback on the impact, if any, of the HRRs on health research. Retrospective patient recruitment and consent outside a hospital setting for a multi-institutional Breast Predict study (funded by the Irish Cancer Society) were also analysed.

Feedback replicated the issues presented at the IAMS with additional concerns identified. Only 20% of the original target population (n = 1987) could be included in the Breast Predict study.

Our results confirm that the HRRs have had a significantly negative impact on health research in Ireland. Urgent meaningful engagement between patient advocate groups, the research community and legislators would help ameliorate these impacts.

Our results confirm that the HRRs have had a significantly negative impact on health research in Ireland. Urgent meaningful engagement between patient advocate groups, the research community and legislators would help ameliorate these impacts.

The aim of this study was to evaluate the efficacy and safety of ultra-rapid lispro (URLi) versus lispro in a subgroup analysis of Japanese adults with type 2 diabetes mellitus (T2DM) from the phase 3 PRONTO-T2D trial.

After an 8-week lead-in period during which patients transitioned to insulin lispro 3 times a day before main meals in association with basal insulin (glargine or degludec), the patients were randomized to 26weeks of double-blind URLi or lispro injected immediately prior to meals. The primary endpoint was change in hemoglobin A1c (HbA1c) from baseline to week 26 between URLi and lispro. The multiplicity-adjusted objectives were 1- and 2-h postprandial glucose (PPG) excursions after a test meal and change in HbA1c from baseline to week 26 in the URLi and lispro groups.

Results were obtained from prespecified exploratory analyses of 26-week data in Japanese patients randomized to receive URLi (n = 47) or lispro (n = 46). Mean baseline HbA1c levels significantly improved during the lead-in pcemic control when administered immediately before a meal in Japanese patients with T2DM. URLi was well tolerated in this population.

ClinicalTrials.gov, NCT03214380.

ClinicalTrials.gov, NCT03214380.

We evaluated the efficacy and safety of ultra-rapid lispro (URLi) in comparison to lispro in a subgroup analysis of Japanese adults with type1 diabetes mellitus from the phase3 PRONTO-T1D trial.

After an 8-week lead-in to optimize basal insulin treatment, patients were randomized to 52-week double-blind mealtime URLi or lispro, or 26-week open-label postmeal URLi. The primary endpoint was change in hemoglobin A1c (HbA1c) from baseline (week0) to week26 between mealtime URLi and lispro. The multiplicity adjusted objectives were 1- and 2-h postprandial glucose (PPG) excursions after a meal test between mealtime URLi and lispro, and change in HbA1c from baseline to week26 between postmeal URLi and mealtime lispro.

This manuscript presents pre-specified exploratory analyses of 26-week data from Japanese patients randomized to double-blind URLi (n = 62) or lispro (n = 59), or open-label URLi (n = 46). ML133 concentration Mean baseline HbA1c levels were 7.52% for mealtime URLi, 7.44% for lispro, and 7.51% for postmeal URLi at randomization. At week26, the least squares mean (LSM) difference compared to lispro was 0.04% (95% confidence interval [CI] - 0.14 to 0.22) for mealtime URLi, and 0.16% (95% CI - 0.04 to 0.35) for postmeal URLi. In comparison to lispro, mealtime URLi resulted in statistically significantly lower 1- and 2-h PPG excursions during the mixed-meal tolerance test. LSM differences were - 40.5mg/dL, 95% CI - 59.5 to 21.4 (- 2.25mmol/L, 95% CI - 3.3 to - 1.2) for 1-h PPG excursions and - 51.7mg/dL, 95% CI - 81.7 to -21.8 (- 2.87mmol/L, 95% CI - 4.5 to - 1.2) for 2-h PPG excursions at week26. There were no significant treatment differences in rates of severe/overall hypoglycemia, or incidence of treatment-emergent adverse events.

Mealtime and postmeal URLi provide effective and comparable glycemic control in Japanese patients. Mealtime URLi demonstrated more effective PPG control compared to lispro.

ClinicalTrials.gov, NCT03214367.

ClinicalTrials.gov, NCT03214367.The great saphenous vein (GSV) has served as a coronary artery bypass graft (CABG) conduit for over 50 years. Despite prevalent use, first-year failure rates remain high compared to arterial autograft options. Amongst other factors, vein graft failure can be attributed to material and mechanical mismatching that lead to apoptosis, inflammation, and intimal-medial hyperplasia. Through the implementation of the continuum mechanical-based theory of “stress-mediated growth and remodeling,” we hypothesize that the mechanical properties of porcine GSV grafts can be favorably tuned for CABG applications prior to implantation using a prolonged but gradual transition from venous to arterial loading conditions in an inflammatory and thrombogenic deficient environment. To test this hypothesis, we used a hemodynamic-mimetic perfusion bioreactor to guide remodeling through stepwise incremental changes in pressure and flow over the course of 21-day cultures. Biaxial mechanical testing of vessels pre- and post-remodeling was performed, with results fit to structurally-motivated constitutive models using non-parametric bootstrapping. The theory of “small-on-large” was used to describe appropriate stiffness moduli, while histology and viability assays confirmed microstructural adaptations and vessel viability. Results suggest that stepwise transition from venous-to-arterial conditions results in a partial restoration of circumferential stretch and circumferential, but not axial, stress through vessel dilation and wall thickening in a primarily outward remodeling process. These remodeled tissues also exhibited decreased mechanical isotropy and circumferential, but not axial, stiffening. In contrast, only increases in axial stiffness were observed using culture under venous perfusion conditions and those tissues experienced moderate intimal resorption.