Tools for the Diagnosis of Herpes Simplex Virus 1/2: Systematic Review of Studies Published Between 2012 and 2018.

BACKGROUND: Herpes simplex virus (HSV)-1 and HSV-2 are common infections affecting the global population, with HSV-1 estimated to affect 67% of the global population. HSV can have rare but severe manifestations, such as encephalitis and neonatal herpes, necessitating the use of reliable and accurate diagnostic tools for the detection of the viruses. Currently used HSV diagnostic tools require highly specialized skills and availability of a laboratory setting but may lack sensitivity. The numerous recently developed HSV diagnostic tools need to be identified and compared in a systematic way to make the best decision about which diagnostic tool to use. The diagnosis of HSV is essential for prompt treatment with antivirals. To select the best test for a patient, knowledge of the performance and limitations of each test is critical. OBJECTIVE: This systematic review has summarized recent studies evaluating HSV-1 and HSV-2 diagnostic tools. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, selection criteria, data extraction, and data analysis were determined before the commencement of the study. Studies assessing the specificity/sensitivity of HSV-1 or HSV-2 diagnostic tools published between 2012 and 2018 were included. Quality assessment of included studies was performed using the quality assessment of diagnostic accuracy studies (QUADAS-2) tool. RESULTS: Searches of the PubMed database yielded 264 studies; 11 studies included 11 molecular assays, and 8 studies included 19 different serological assays for the detection of HSV-1, HSV-2, or both. A greater proportion of molecular assay-based tools are being developed by commercial entities. Studies that tested molecular assays mostly focused on cutaneous and mucosal HSV infections (n=13); 2 studies focused on ocular disease, whereas only 1 study focused on the central nervous system manifestations. The Simplexa HSV 1 & 2 Direct is currently the only Food and Drug Administration-approved device for use on cerebrospinal fluid. No tools focused on prenatal screening. We also present performance metrics of tests for benchmarking of future technology. Most of the included studies had a high risk of bias rating in half of the QUADAS-2 tool risk of bias domains. CONCLUSIONS: The use of serologic tests to diagnose genital lesions is inappropriate because positive results may be due to chronic infection, whereas negative results may overlook recent infection. The incidence of acute infections is rising. As these infections present the greatest risk to fetuses, work needs to be done to prevent vertical transfer. Prenatal screening for primary infection and subsequent medical intervention will assist in lowering the rate of neonatal herpes. In conclusion, HSV diagnosis is moving away from culture-based methods to serology-based or polymerase chain reaction-based methods. Sensitive, rapid, and efficient HSV diagnostic tools should be adopted for the prevention of acute infections and neonatal herpes.

The Reporting Items for Patent Landscapes statement.

The reporting quality of patent landscapes is inadequate. The Reporting Items for Patent Landscapes (RIPL) checklist can improve reporting quality.

Adipose-Derived Stem Cells in Aesthetic Surgery: A Mixed Methods Evaluation of the Current Clinical Trial, Intellectual Property, and Regulatory Landscape.

BACKGROUND: Adipose tissue, which can be readily harvested via a number of liposuction techniques, offers an easily accessible and abundant source of adipose-derived stem cells (ASCs). Consequently, ASCs have become an increasingly popular reconstructive option and a novel means of aesthetic soft tissue augmentation. OBJECTIVES: This paper examines recent advances in the aesthetic surgery field, extending beyond traditional review formats to incorporate a comprehensive analysis of current clinical trials, adoption status, and the commercialization pathway. METHODS: Keyword searches were carried out on clinical trial databases to search for trials using ASCs for aesthetic indications. An intellectual property landscape was created using commercial software (Thomson Reuters Thomson Innovation, New York, NY). Analysis of who is claiming what in respect of ASC use in aesthetic surgery for commercial purposes was analyzed by reviewing the patent landscape in relation to these techniques. Key international regulatory guidelines were also summarized. RESULTS: Completed clinical trials lacked robust controls, employed small sample sizes, and lacked long-term follow-up data. Ongoing clinical trials still do not address such issues. In recent years, claims to intellectual property ownership have increased in the "aesthetic stem cell" domain, reflecting commercial interest in the area. However, significant translational barriers remain including regulatory challenges and ethical considerations. CONCLUSIONS: Further rigorous randomized controlled trials are required to delineate long-term clinical efficacy and safety. Providers should consider the introduction of patient reported outcome metrics to facilitate clinical adoption. Robust regulatory and ethical policies concerning stem cells and aesthetic surgery should be devised to discourage further growth of "stem cell tourism."

CAR-T Cells: A Systematic Review and Mixed Methods Analysis of the Clinical Trial Landscape.

CAR-T cells are a promising new therapy that offer significant advantages compared with conventional immunotherapies. This systematic review and clinical trial landscape identifies and critiques published CAR-T cell clinical trials and examines the critical factors required to enable CAR-T cells to become a standard therapy. A review of the literature was conducted to identify suitable studies from the MEDLINE and Ovid bibliographic databases. The literature and database searches identified 20 studies for inclusion. The average number of participants per clinical trial examined was 11 patients. All studies included in this systematic review investigated CAR-T cells and were prospective, uncontrolled clinical studies. Leukemia is the most common cancer subtype and accounts for 57.4% (n = 120) of disease indications. The majority of studies used an autologous cell source (85%, n = 17) rather than an allogeneic cell source. Translational challenges encompass technical considerations relating to CAR-T cell development, manufacturing practicability, clinical trial approaches, CAR-T cell quality and persistence, and patient management.

Regulatory Considerations for Gene Therapy Products in the US, EU, and Japan.

Developers of gene therapy products (GTPs) must adhere to additional regulation beyond that of traditional small-molecule therapeutics, due to the unique mechanism-of-action of GTPs and the subsequent novel risks arisen. We have provided herein a summary of the regulatory structure under which GTPs fall in the United States, the European Union, and Japan, and a comprehensive overview of the regulatory guidance applicable to the developer of GTP. Understanding the regulatory requirements for seeking GTP market approval in these major jurisdictions is crucial for an effective and expedient path to market. The novel challenges facing GTP developers is highlighted by a case study of alipogene tiparvovec (Glybera).

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

BACKGROUND: 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. METHODS/DESIGN: Eight 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. DISCUSSION: Through 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.

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.

Open Access Could Transform Drug Discovery: A Case Study of JQ1.

INTRODUCTION: The cost to develop a new drug from target discovery to market is a staggering $1.8 billion, largely due to the very high attrition rate of drug candidates and the lengthy transition times during development. Open access is an emerging model of open innovation that places no restriction on the use of information and has the potential to accelerate the development of new drugs. AREAS COVERED: To date, no quantitative assessment has yet taken place to determine the effects and viability of open access on the process of drug translation. This need is addressed within this study. The literature and intellectual property landscapes of the drug candidate JQ1, which was made available on an open access basis when discovered, and conventionally developed equivalents that were not are compared using the Web of Science and Thomson Innovation software, respectively. EXPERT OPINION: Results demonstrate that openly sharing the JQ1 molecule led to a greater uptake by a wider and more multi-disciplinary research community. A comparative analysis of the patent landscapes for each candidate also found that the broader scientific diaspora of the publically released JQ1 data enhanced innovation, evidenced by a greater number of downstream patents filed in relation to JQ1. The authors' findings counter the notion that open access drug discovery would leak commercial intellectual property. On the contrary, JQ1 serves as a test case to evidence that open access drug discovery can be an economic model that potentially improves efficiency and cost of drug discovery and its subsequent commercialization.

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.