CD47, a broadly expressed cell surface protein, inhibits cell phagocytosis via interaction with phagocyte-expressed SIRPα. A variety of hematological malignancies demonstrate elevated CD47 expression, suggesting that CD47 may mediate immune escape. We discovered three unique CD47-SIRPα blocking anti-CD47 monoclonal antibodies (mAbs) with low nano-molar affinity to human and cynomolgus monkey CD47, and no hemagglutination and platelet aggregation activity. To characterize the anti-cancer activity elicited by blocking CD47, the mAbs were cloned into effector function silent and competent Fc backbones. Effector function competent mAbs demonstrated potent activity in vitro and in vivo, while effector function silent mAbs demonstrated minimal activity, indicating that blocking CD47 only leads to a therapeutic effect in the presence of Fc effector function. A non-human primate study revealed that the effector function competent mAb IgG1 C47B222-(CHO) decreased red blood cells (RBC), hematocrit and hemoglobin by >40% at 1 mg/kg, whereas the effector function silent mAb IgG2σ C47B222-(CHO) had minimal impact on RBC indices at 1 and 10 mg/kg. Taken together, our findings suggest that targeting CD47 is an attractive therapeutic anti-cancer approach. However, the anti-cancer activity observed with anti-CD47 mAbs is Fc effector dependent as are the side effects observed on RBC indices.

BackgroundMedical Research Council (MRC) guidance identifies implementation as a key element of the development and evaluation process for complex healthcare interventions. Implementation is itself a complex process involving the mobilization of human, material, and organizational resources to change practice within settings that have pre-existing structures, historical patterns of relationships, and routinized ways of working. Process evaluations enable researchers and clinicians to understand how implementation proceeds and what factors impact on intended program change. A qualitative process evaluation of the pragmatic cluster randomized controlled trial; Training Caregivers after Stroke was conducted to examine how professionals were engaged in the work of delivering training; how they reached and involved caregivers for whom the intervention was most appropriate; how did those on whom training was targeted experience and respond to it. Normalization Process Theory, which focuses attention on implementing and embedding program change, was used as a sensitizing framework to examine selected findings.ResultsContextual factors including organizational history and team relationships, external policy, and service development initiatives, impinged on implementation of the caregiver training program in unintended ways that could not have been predicted through focus on mechanisms of individual and collective action at unit level. Factors that facilitated or impeded the effectiveness of the cascade training model used, whether and how stroke unit teams made sense of and engaged individually and collectively with a complex caregiver training intervention, and what impact these factors had on embedding the intervention in routine stroke unit practice were identified.ConclusionsWhere implementation of complex interventions depends on multiple providers, time needs to be invested in reaching agreement on who will take responsibility for delivery of specific components and in determining how implementation and its effectiveness will be monitored. This goes beyond concern with intervention fidelity; explicit consideration also needs to be given to the implementation process in terms of how program change can be effected at organizational, practice, and service delivery levels. Normalization Process Theory’s constructs help identify vulnerable features of implementation processes in respect of the work involved in embedding complex interventions.

Oncology nurses play a pivotal role in the care of patients receiving chemotherapy and are in a prime position to facilitate better care of patients experiencing chemotherapy-induced nausea and vomiting (CINV). However, to do so, they must be kept well apprised of the most recent guidelines, the latest developments in CINV therapy, and the expanding knowledge of CINV pathophysiology. In April 2008, a roundtable meeting of experts in the field of CINV was convened after a detailed needs assessment revealed a knowledge gap in CINV management on the part of oncology nurses. The review found that many practitioners significantly underestimated the occurrence of CINV (particularly of delayed symptoms), and others failed to implement evidence-based guidelines. Presentations included CINV pathophysiology, the significance of CINV prophylaxis, evidence-based guidelines, current treatment options and future therapies, practical nursing considerations in CINV, and CINV learning gaps among oncology nurses, with the topics then discussed by the panel at large.

ObjectiveTo evaluate the process of implementation of the modified London Stroke Carers Training Course (LSCTC) in the Training Caregivers After Stroke (TRACS) cluster randomised trial and contribute to the interpretation of the TRACS trial results. The LSCTC was a structured competency-based training programme designed to help develop the knowledge and skills (eg, patient handling or transfer skills) essential for the day-to-day management of disabled survivors of stroke. The LSCTC comprised 14 components, 6 were mandatory (and delivered to all) and 8 non-mandatory, to be delivered based on individual assessment of caregiver need.DesignProcess evaluation using non-participant observation, documentary analysis and semistructured interviews.ParticipantsPatients with stroke (n=38), caregivers (n=38), stroke unit staff (n=53).Settings10 of the 36 stroke units participating in the TRACS trial in four English regions (Yorkshire, North West, South East and South West, Peninsula).ResultsPreparatory cascade training on delivery of the LSCTC did not reach all staff and did not lead to multidisciplinary team (MDT) wide understanding of, engagement with or commitment to the LSCTC. Although senior therapists in most intervention units observed developed ownership of the LSCTC, MDT working led to separation rather than integration of delivery of LSCTC elements. Organisational features of stroke units and professionals’ patient-focused practices limited the involvement of caregivers. Caregivers were often invited to observe therapy or care being provided by professionals but had few opportunities to make sense of, or to develop knowledge and stroke-specific skills provided by the LSCTC. Where provided, caregiver training came very late in the inpatient stay. Assessment and development of caregiver competence was not commonly observed.ConclusionsContextual factors including service improvement pressures and staff perceptions of the necessity for and work required in caregiver training impacted negatively on implementation of the caregiver training intervention. Structured caregiver training programmes such as the LSCTC are unlikely to be practical in settings with short inpatient stays. Stroke units where early supported discharge is in place potentially offer a more effective vehicle for introducing competency based caregiver training.LINKED TRACS Cluster randomised controlled trial numberISRCTN49208824.

There is a tension between the duty of care and the duty to recognise autonomy at the level of service delivery in residential homes. Support workers attempt to manage this tension; however, further work needs to be done by both residential services and policy makers to facilitate the reconciliation of the duty of care with the duty to recognise service users' autonomy in practice.