ABSTRACT
Background/Aims Effective symptom management may require the use of medications. Medication adherence may be hindered by formulation aspects, such as poor taste. Paediatric studies indicate, that despite concerns of swallowing solid dose forms, children prefer these to liquid forms. They find the solid dose forms more palatable. However, swallowing numerous solid dose forms, may present a significant 'pill' burden to patients and their care-givers. Filling empty gelatine capsules with requisite medications is seen and used as a way to address palatability, decrease pill burden and thereby increase compliance. Yet there is little evidence on the impact this practise may have on the effectiveness of over-encapsulated medicines. This study explored the effect of over-encapsulation on in vitro disintegration and dissolution, of some commonly used medicines in paediatric palliative care. Method Immediate release (Cyclizine Hydrochloride, Gabapentin, Paracetamol) and modified release preparations (Omeprazole, Diclofenac sodium) were over-encapsulated in size 00 gelatin and HPMC capsules (n=6). Dissolution and disintegration were tested according to Pharmacopeia standards. Statistical analyses, using Student's T-test and f1 and f2 tests (respectively) were applied to determine similarities or differences in disintegration or dissolution. Results Disintegration and dissolution was prolonged for all over-encapsulated immediate release preparations, especially when using HPMC capsules. However, percentage of drug dissolved met the acceptance criteria for immediate-release solid oral dosage. Over-encapsulation of modified release preparations did not lead to significant dissolution or disintegration changes. Conclusion Over-encapsulation, may delay medication release, especially for immediate release medicines however, medicine effectiveness may not be. Further studies are required before we can safely recommend use of over-encapsulation as an administration compliance aid.
ABSTRACT
Background Congenital athymia, due to complete DiGeorge syndrome (cDGS) or rare monogenic disorders affecting thymus development, is associated with profound T-cell lymphopaenia and susceptibility to opportunistic infections. Left untreated, athymia is fatal within 1-2 years. It can be successfully treated by thymus transplantation, using cultured thymic tissue obtained from infant donors when necessarily removed during cardiac surgery. In Europe, thymus transplantation is only offered at our centre. Following increased awareness and progressive international implementation of newborn screening (NBS) for severe combined immunodeficiency (SCID), we received a record number of referrals in 2020. Significant restrictions on worldwide travel and reallocation of healthcare resources during the COVID-19 pandemic resulted in the temporary interruption of international admissions. In order to facilitate the timely admission for this life-saving treatment, we developed a modified care pathway (MCP) to address the challenges identified at local, national and international levels. Objectives Optimisation of resource allocation to prevent negative impacts of delayed treatment in athymic infants during the COVID-19 pandemic. Continued delivery of high quality, complex patient care and positive patient experience through a MCP. Methods We conducted a service evaluation to assess the effectiveness of the MCP and the impact on time-to-admission for transplantation. We completed short interviews with accompanying parents and referring clinicians to survey their experience of the thymus transplantation programme during the pandemic. Results With the support of our Trust and NHS England, a MCP was agreed and implemented to ensure safe transfer, admission and repatriation. We regularly amended our admission protocol to reflect the evolving local and national infection prevention control (IPC) policies. We gained adherence from all referring teams and families, while observing the local requirements of the referring teams in 6 European countries and New Zealand. Due to the limited access to donor tissue, secondary to reduced elective cardiac surgery, admissions required optimised coordination between multidisciplinary teams to allow for thymus transplantation within 20 days of donor tissue collection and culture. From May 2020 to March 2021, 10 patients underwent thymus transplantation, reflecting a 50% increase in activity on previous years. The average time for referral-admission was 5 months. 4 patients were identified by NBS in their respective countries and in line with current SCID management guidelines, 2 of them were transplanted by the age of 4 months. One patient tested positive for SARS-CoV2 on return to their home country and made a full recovery. This prompted further changes in our transfer guidance and local IPC practice. Parental interviews highlighted anxieties around international travel, restricted hospital access for the second parent and non-aligned IPC practices in comparison with referring centres. Equally, they accepted and embraced the additional restrictions in order to access their child's essential and only, treatment option. Conclusions Upon prompt identification of challenges and risks to treatment delay for athymic infants during the COVID-19 pandemic, we overcame them in collaboration with referring centres, multi-disciplinary hospital teams and the patient families, resulting in the successful delivery of a record number of thymus transplant procedures following a MCP, maximising the opportunity for improved long-term outcomes.