Educational needs of patients, families, and healthcare professionals to support the patient journey in haemophilia gene therapy in the UK

With the first gene therapies for haemophilia approved by the European Commission, the US Food and Drug Administration, and the Medicines and Healthcare products Regulatory Agency, it is important to consider the remaining unmet needs and challenges that may arise throughout patients’ treatment journeys. We discuss existing unmet needs and important considerations prior to, during, and following haemophilia gene therapy treatment in the UK, and propose potential next steps. Key areas for attention are education, psychological support, and guidance on implementation. Strategies are urgently required to fulfil these needs. An immediate priority for information providers should be comprehensive education for people with haemophilia (PWH) and healthcare professionals (HCPs). Greater access to resources and training in psychological services will be required throughout the treatment pathway. More specific guidance is required to define the implementation model, criteria for accreditation, and responsibilities of care centres. Furthermore, PWH may revisit discussions with HCPs multiple times pre-infusion, thus the patient journey is unlikely to be linear. Consideration of these challenges, and of potential strategies to address them, will be integral to optimising the future success of this promising therapy

A pilot study in humans of microneedle sensor arrays for continuous glucose monitoring

Although subcutaneously implanted continuous glucose monitoring (CGM) devices have been shown to support diabetes self-management, their uptake remains low due to a combination of high manufacturing cost and limited accuracy and precision arising from their invasiveness. To address these points, minimally invasive, a solid microneedle array-based sensor for continuous glucose monitoring is reported here. These intradermal solid microneedle CGM sensors are designed for low cost manufacturing. The tolerability and performance of these devices is demonstrated through clinical studies, both in healthy volunteers and participants with type 1 diabetes (T1D). The geometry of these solid microneedles allows them to penetrate dermal tissue without the need for an applicator. The outer surface of these solid microneedles are modified as glucose biosensors. The microneedles sit in the interstitial fluid of the skin compartment and monitor real-time changes in glucose concentration. Optical coherence tomography measurements revealed no major axial movement of the microneedles in the tissue. No significant adverse events were observed and low pain scores were reported when compared to catheter insertion, deeming it safe for clinical studies in T1D. These amperometric sensors also yielded currents that tracked venous blood glucose concentrations, showing a clinically acceptable correlation. Studies in people with T1D gave a mean absolute relative difference (MARD) of 9% (with respect to venous blood glucose) with over 94% of the data points in the A and B zones of the Clarke error grid. These findings provide baseline data for further device development and a larger clinical efficacy and acceptability study of this microneedle intradermal glucose sensor in T1D

Inelastic response of a simple arch dam due to differential foundation movements

Using ADINA, the inelastic response of a simple cylindrical arch dam of constant thickness and vertical banks due to differential foundation and abutment movements is analysed. Small displacements and strains are assumed. The mass concrete is idealized as an elasto-plastic material, where the yield stress in each element of the discretized dam is obtained from the biaxial failure envelope of concrete. A vertical ground movement is assumed, beginning at the centre of the arch and increasing linearly towards the abutment

Managing diabetes at high altitude: personal experience with support from a Multidisciplinary Physical Activity and Diabetes Clinic

Objective: Physical activity is important for wellbeing but can be challenging for people with diabetes. Data informing support of specialist activities such as climbing and high altitude trekking is limited. A 42-year-old man with type 1 diabetes (duration 30 years) attended a multidisciplinary Physical Activity and Diabetes clinic planning to climb Mont Blanc during the summer and trek to Everest Base Camp in the autumn. His aims were to complete these adventures without his diabetes impacting on their success. Methods: We report the information provided that enabled him to help safely facilitate his objectives, in particular the requirement for frequent checking of blood glucose levels, the effects of altitude on insulin dose requirements, and recognition that Acute Mountain Sicknes may mimic the symptoms of hypoglycemia and vice versa. Real-time continuous glucose monitoring was made available for his treks. Results: The effects of high altitude on blood glucose results and glycaemic variability whilst treated on multiple daily injections of insulin are reported. In addition, we present a first-person account of his experience and lessons learned from managing diabetes at high altitude. Conclusions: A dedicated multidisciplinary Physical Activity & Diabetes clinic delivering individualized, evidence based, patient- focused advice on the effects of altitude on blood glucose levels, and provision of real-time continuous glucose monitoring enabled uneventful completion of a trek to Everest Base Camp in a person with type 1 diabetes

IFPA Meeting 2010 Workshops Report II: Placental pathology; Trophoblast invasion; Fetal sex; Parasites and the placenta; Decidua and embryonic or fetal loss; Trophoblast differentiation and syncytialisation

Workshops are an important part of the IFPA annual meeting. At IFPA Meeting 2010 diverse topics were discussed in twelve themed workshops, six of which are summarized in this report. 1. The placental pathology workshop focused on clinical correlates of placenta accreta/percreta. 2. Mechanisms of regulation of trophoblast invasion and spiral artery remodeling were discussed in the trophoblast invasion workshop. 3. The fetal sex and intrauterine stress workshop explored recent work on placental sex differences and discussed them in the context of whether boys live dangerously in the womb.4. The workshop on parasites addressed inflammatory responses as a sign of interaction between placental tissue and parasites. 5. The decidua and embryonic/fetal loss workshop focused on key regulatory mediators in the decidua, embryo and fetus and how alterations in expression may contribute to different diseases and adverse conditions of pregnancy. 6. The trophoblast differentiation and syncytialisation workshop addressed the regulation of villous cytotrophoblast differentiation and how variations may lead to placental dysfunction and pregnancy complications. (C) 2011 Published by IFPA and Elsevier Ltd