BMJ open
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NKR-2 are autologous T cells genetically modified to express a chimeric antigen receptor (CAR) comprising a fusion of the natural killer group 2D (NKG2D) receptor with the CD3ζ signalling domain, which associates with the adaptor molecule DNAX-activating protein of 10 kDa (DAP10) to provide co-stimulatory signal upon ligand binding. NKG2D binds eight different ligands expressed on the cell surface of many tumour cells and which are normally absent on non-neoplastic cells. In preclinical studies, NKR-2 demonstrated long-term antitumour activity towards a breadth of tumour indications, with maximum efficacy observed after multiple NKR-2 administrations. Importantly, NKR-2 targeted tumour cells and tumour neovasculature and the local tumour immunosuppressive microenvironment and this mechanism of action of NKR-2 was established in the absence of preconditioning. ⋯ Ethical approval has been obtained at all sites. Written informed consent will be taken from all participants. The results of this study will be disseminated through presentation at international scientific conferences and reported in peer-reviewed scientific journals.
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The misuse and abuse of prescription opioids (POs) is an epidemic in the USA today. Many states have implemented legislation to curb the use of POs resulting from inappropriate prescribing. Indiana legislated opioid prescribing rules that went into effect in December 2013. The rules changed how chronic pain is managed by healthcare providers. This qualitative study aims to evaluate the impact of Indiana's opioid prescription legislation on the patient experiences around pain management. ⋯ As a result of the changes in pain management practice, some patients experienced significant challenges. Further studies into the magnitude of this change are necessary. In addition, exploring methods for regulating prescribing while assuring adequate access to pain management is crucial.
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From April 2015, NHS England (NHSE) started to devolve responsibility for commissioning primary care services to clinical commissioning groups (CCGs). The aim of this paper is to explore how CCGs are managing potential conflicts of interest associated with groups of GPs commissioning themselves or their practices to provide services. ⋯ Devolving responsibility for primary care co-commissioning to CCGs created a structural conflict of interest. The NHSE statutory guidance should be refined and clarified so that CCGs can properly manage conflicts of interest. Non-clinician members of committees involved in commissioning primary care require training in order to make decisions requiring clinical input in the absence of GPs.
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Review
Quality of reporting of pilot and feasibility cluster randomised trials: a systematic review.
To systematically review the quality of reporting of pilot and feasibility of cluster randomised trials (CRTs). In particular, to assess (1) the number of pilot CRTs conducted between 1 January 2011 and 31 December 2014, (2) whether objectives and methods are appropriate and (3) reporting quality. ⋯ That only 18 pilot CRTs were identified necessitates increased awareness of the importance of conducting and publishing pilot CRTs and improved reporting. Pilot CRTs should primarily be assessing feasibility, avoiding formal hypothesis testing for effectiveness/efficacy and reporting reasons for the pilot, sample size rationale and progression criteria, as well as enrolment of clusters, and how the cluster design affects design aspects. We recommend adherence to the CONSORT extensions for pilot trials and CRTs.
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To report the clinical features and prognosis of drug-associatedacute respiratory distress syndrome (ARDS). ⋯ Although more severe lung damage with fibroproliferation was observed in patients with drug-associated ARDS, ventilator weaning was earlier, and their prognosis was better than the others. Further well-designed prospective studies are needed.