The prescribable drugs with efficacy in experimental epilepsies (PDE3) database for drug repurposing research in epilepsy.

OBJECTIVE: Current antiepileptic drugs (AEDs) have several shortcomings. For example, they fail to control seizures in 30% of patients. Hence, there is a need to identify new AEDs. Drug repurposing is the discovery of new indications for approved drugs. This drug "recycling" offers the potential of significant savings in the time and cost of drug development. Many drugs licensed for other indications exhibit antiepileptic efficacy in animal models. Our aim was to create a database of "prescribable" drugs, approved for other conditions, with published evidence of efficacy in animal models of epilepsy, and to collate data that would assist in choosing the most promising candidates for drug repurposing. METHODS: The database was created by the following: (1) computational literature-mining using novel software that identifies Medline abstracts containing the name of a prescribable drug, a rodent model of epilepsy, and a phrase indicating seizure reduction; then (2) crowdsourced manual curation of the identified abstracts. RESULTS: The final database includes 173 drugs and 500 abstracts. It is made freely available at www.liverpool.ac.uk/D3RE/PDE3. The database is reliable: 94% of the included drugs have corroborative evidence of efficacy in animal models (for example, evidence from multiple independent studies). The database includes many drugs that are appealing candidates for repurposing, as they are widely accepted by prescribers and patients-the database includes half of the 20 most commonly prescribed drugs in England-and they target many proteins involved in epilepsy but not targeted by current AEDs. It is important to note that the drugs are of potential relevance to human epilepsy-the database is highly enriched with drugs that target proteins of known causal human epilepsy genes (Fisher's exact test P-value < 3 × 10-5 ). We present data to help prioritize the most promising candidates for repurposing from the database. SIGNIFICANCE: The PDE3 database is an important new resource for drug repurposing research in epilepsy.

The importance of a go-to-market strategy in the commercialisation of cellular immunotherapies.

Cellular immunotherapy (CIT) has both demonstrated outstanding levels of efficacy in cancer and presented unique commercialisation challenges. A historical analysis of go-to-market (G2M) strategies used to develop the first chimeric antigen receptor T cells (CAR-Ts) can offer insight into how companies leverage partnership or independence to ensure commercial success. Collaboration-based strategies, such as partnerships, acquisitions, and licensing deals, have predominated in the industry to maximise revenue and patient access. Manufacturing, logistical, and regulatory challenges have hindered independent commercialisation. Nonetheless, the industry is adapting to these challenges: novel technologies show superior affordability and implementability, and commercial solutions organisations (CSOs) increasingly help CIT companies navigate through commercialisation issues independently. G2M strategies in this industry are therefore likely to evolve, with independence becoming a feasible strategy for commercial success.

Blowing the whistle: Perceptions of surgical staff and medical students in a public South African hospital.

Whistleblowing is defined as raising a concern about wrong doing and has gained prominence in the UK National Health Service (NHS) following the publication of the Francis Report (the report of the Mid-Staffordshire NHS Foundation Trust Public Inquiry) in 2013. The report revealed that lack of diligence and a reluctance to speak out about poor practice amongst staff had contributed to increased patient morbidity and mortality. In the wake of this report, a new framework was introduced by the NHS to help workers raise concerns regarding other staff and poor working practices in general. Nevertheless, it has been suggested that this new framework has not helped to increase whistleblowing or prevented staff who do raise concerns from being penalised. Furthermore, it has been claimed that such implementations will encourage defensive medicine and reduce the willingness of staff to report concerns, despite the important role of whistleblowing in helping to prevent catastrophic events and improve care. Further research is required to understand why healthcare professionals are reticent regarding whistleblowing. Moreover, while some research in the nursing and allied health community exists, this study is important as it adds to the limited evidence amongst medical students and staff in general.