David Pettitt

The Limitations of QALY: A Literature Review

Introduction: The Quality Adjusted Life Year (QALY) is a recognised metric used to evaluate new and innovative healthcare treatments and optimise resource allocation via rational and explicit methodologies. This review examines present limitations of the QALY metric and foreseeable challenges linked to the advancement of regenerative medicine. Methods: The extant literature was reviewed through electronic searches of four key databases; namely Medline, EMBASE, Econlit and Cochrane. Manuscripts were selected according to pre-determined inclusion criteria. Results: Three common themes emerged concerning the limitations of QALYs. These were ethical considerations, methodological issues and theoretical assumptions and context or disease specific considerations.

Cell assisted lipotransfer in breast augmentation and reconstruction: A systematic review of safety, efficacy, use of patient reported outcomes and study quality.

Background Cell assisted lipotransfer serves as a novel technique for both breast reconstruction and breast augmentation. This systematic review assesses the efficacy, safety and use of patient reported outcome measures in studies involving cell assisted lipotransfer. We also carry out an objective assessment of study quality focussing on recruitment, follow-up and provide an up-to-date clinical trial landscaping analysis. Methods Key electronic databases were searched according to PRISMA guidelines and pre-defined inclusion and exclusion criteria. Two independent reviewers examined the retrieved publications and performed data extraction. Results 3980 publications were identified. Following screening, 11 studies were included for full review, representing a total of 336 patients with a follow-up time ranging from six to 42 months. A degree of variation was noted in graft retention and reported satisfaction levels, although there were only three comparative studies with conflicting results. Complications occurred at a rate of 37%. Additionally, there was a paucity of objective outcomes assessments (e.g. 3D assessment modalities or validated patient reported outcome measures) in the selected studies. Conclusions Cell assisted lipotransfer is a surgical technique that is currently employed sparingly within the plastic & reconstructive surgery community. Presently, further technical and outcome standardization is required, in addition to rigorous randomized controlled trials and supporting long-term follow-up data to better determine procedural safety and efficacy. Routine use of more objective outcome measures, particularly 3D assessments and validated patient reported outcome measures, will also help facilitate wider clinical adoption and establish procedural utility.

Apert syndrome: A consensus on the management of Apert hands

INTRODUCTION Apert Syndrome is a congenital condition characterised by primary craniosynostosis, midfacial malformations and complex symmetrical malformations of the hands and feet. The hands demonstrate one of the most complex collections of congenital upper limb deformities, posing a significant challenge for the paediatric hand surgeon. This study examines the extant literature and current practice of the four UK specialist craniofacial units regarding the management of Apert hands in order to provide a basis for guideline development. METHODS The current literature was reviewed. Survey-type questionnaires were distributed to the four UK specialist craniofacial units and responses analysed. RESULTS Management of the Apert hand is largely dictated by the degree of malformation present. Although all units aim to achieve a five digit hand, variation in the timing of surgery, operative protocols and mobilisation policies exist. CONCLUSION The results of this study provide an interesting snapshot of the current management of Apert hands across four UK craniofacial surgery units. The four UK units remain congruent on most areas surrounding the management of Apert hands although some minor inter-unit variation exists. A multidisciplinary approach to management remains fundamental in optimising the regain of function and aesthetically acceptable hands.

Regulatory barriers to the advancement of precision medicine

ABSTRACT Precision medicine utilizes tailored diagnostic, prognostic and therapeutic strategies based on an individual’s molecular profile. Although it is gaining considerable traction and high-level political endorsement, it must overcome a number of translational hurdles, including regulatory barriers. At the core of precision medicine lies diagnostic tests and devices, however the regulatory classification of such products varies on a global basis. Navigating these convoluted regulatory pathways can be challenging – exacerbated by asymmetric technological advancement and regulatory progression. Both the EU and US are attempting to address such issues and newer concerns relating to direct-to-consumer testing. Flexible solutions are required to establish regulatory compliance across multiple countries and coordinated cross-collaboration initiatives need to empower technological development and globally harmonized regulation. The wider infrastructure, spanning beyond regulation, must also accommodate these changes and support subsequent clinical adoption, in order to firmly establish precision medicine in modern day medical practice.

A human bite.

A 26 year old man presented to the emergency department with a painful right ear after having been bitten three hours earlier during an altercation. He also reported receiving a blow to his right eye during the incident. He was normally fit and well and not taking any regular drugs. On examination, he was alert, orientated, and afebrile. His right ear and the immediate surrounding tissue were erythematous and swollen. Soft tissue from the helix was missing superiorly, and about a third of the skin covering the posterior surface of the auricle was absent. His right eye was purple and swollen, with conjunctival haemorrhage present. He had normal visual acuity and a score of 15 out of 15 on the Glasgow coma scale. ### 1 What are your most immediate concerns? #### Short answer The most immediate concern is the presence of a life threatening injury or fracture sustained through the head trauma. Human (and animal) bite wounds are also particularly susceptible to infection because of the multiple organisms found in saliva. #### Long answer The most immediate concern is the presence of a life threatening head injury and the next is the risk of infection. This patient sustained a traumatic insult to his right eye with periorbital bruising present on examination. The general principles of trauma management therefore apply. This should begin with an ABCDE (airway, breathing, circulation, disability, exposure) approach (according to Advanced Trauma Life Support guidelines) to rule out any life threatening injuries. The bruised eye should then be clinically assessed during the secondary survey, and …

An assessment of the factors affecting the commercialization of cell-based therapeutics: a systematic review protocol

BackgroundCellular-based therapies represent a platform technology within the rapidly expanding field of regenerative medicine and are distinct from conventional therapeutics—offering a unique approach to managing what were once considered untreatable diseases. Despite a significant increase in basic science activity within the cell therapy arena, alongside a growing portfolio of cell therapy trials and promising investment, the translation of cellular-based therapeutics from “bench to bedside” remains challenging, and the number of industry products available for widespread clinical use remains comparatively low. This systematic review identifies unique intrinsic and extrinsic barriers in the cell-based therapy domain.Methods/designEight electronic databases will be searched, specifically Medline, EMBASE (OvidSP), BIOSIS & Web of Science, Cochrane Library & HEED, EconLit (ProQuest), WHOLIS WHO Library Database, PAIS International (ProQuest), and Scopus. Addition to this gray literature was searched by manually reviewing relevant work. All identified articles will be subjected for review by two authors who will decide whether or not each article passes our inclusion/exclusion criteria. Eligible papers will subsequently be reviewed, and key data extracted into a pre-designed data extraction scorecard. An assessment of the perceived impact of broad commercial barriers to the adoption of cell-based therapies will be conducted. These broad categories will include manufacturing, regulation and intellectual property, reimbursement, clinical trials, clinical adoption, ethics, and business models. This will inform further discussion in the review. There is no PROSPERO registration number.DiscussionThrough a systematic search and appraisal of available literature, this review will identify key challenges in the commercialization pathway of cellular-based therapeutics and highlights significant barriers impeding successful clinical adoption. This will aid in creating an adaptable, acceptable, and harmonized approach supported by apposite regulatory frameworks and pertinent expertise throughout the respective stages of the adoption cycle to facilitate the adoption of new products and technologies in the industry.

718. Cell Therapy Commercialization: An Assessment of Translational Barriers

Cellular based therapies represent a platform technology within the rapidly expanding field of regenerative medicine and are distinct from conventional therapeutics - offering a unique approach to managing what were once considered untreatable diseases. Despite a significant increase in basic science activity within the cell therapy arena, alongside a growing portfolio of cell therapy trials and promising investment, the translation of cellular based therapeutics from “bench to bedside” remains challenging, and the number of industry products available for widespread clinical use remains comparatively low. This systematic review identifies unique intrinsic and extrinsic barriers in the cell based therapy domain. Key electronic databases were searched and manuscripts subjected to pre-defined inclusion and exclusion criteria. Two independent reviewers examined the retrieved publications, and performed data extraction. 3374 unique publications were identified. 138 of these qualified for full assessment and subsequent data extraction. A number of key themes were identified, enabling examination of current challenges and opportunities facing cell therapy development, including manufacturing, regulatory, reimbursement, ethical and clinical adoption issues. In addition to an up-to-date analysis of the current landscape, we discuss a number of pragmatic solutions to facilitate future development and translation.