Strategies to improve research capacity across European general practice: The views of members of EGPRN and Wonca Europe

Background: The effectiveness of any national healthcare system is highly correlated with the strength of primary care within that system. A strong research basis is essential for a firm and vibrant primary care system. General practitioners (GPs) are at the centre of most primary care systems.

Objectives: To inform on actions required to increase research capacity in general practice, particularly in low capacity countries, we collected information from the members of the European General Practice Research Network (EGPRN) and the European World Organization of Family Doctors (Wonca).

Methods: A qualitative design including eight semi-structured interviews and two discursive workshops were undertaken with members of EGPRN and Wonca Europe. Appreciative inquiry methods were utilized. Krueger’s (1994) framework analysis approach was used to analyse the data.

Results: Research performance in general practice requires improvements in the following areas: visibility of research; knowledge acquisition; mentoring and exchange; networking and research networks; collaboration with industry, authorities and other stakeholders. Research capacity building (RCB) strategies need to be both flexible and financially supported. Leadership and collaboration are crucial.

Conclusion: Members of the GP research community see the clear need for both national and international primary care research networks to facilitate appropriate RCB interventions. These interventions should be multifaceted, responding to needs at different levels and tailored to the context where they are to be implemented.     

B-cell maturation antigen-specific chimeric antigen receptor T cells for multiple myeloma: Clinical experience and future perspectives

Despite major advances in the treatment of multiple myeloma (MM), it remains a largely incurable disease with long-term control often dependent on continuous therapy. More effective, better tolerated treatments are therefore required to achieve durable remissions and to improve the quality of life of MM patients. Adoptive immunotherapy employing T cells expressing chimeric antigen receptors (CAR) is currently among the most promising treatment approaches in cancer. Within the target portfolio for MM immunotherapy, B-cell maturation antigen (BCMA) is among the most widely studied target antigens. BCMA is consistently expressed on MM cells and, importantly, is not expressed in critical healthy tissue. For this reason, it is an ideal target for MM immunotherapy. Several clinical trials evaluating different BCMA-targeting CAR constructs have been initiated and early results are very promising. However, in this rapidly developing clinical landscape, the ultimate role of BCMA-specific CAR-T cell therapy remains unclear. In this review, we will summarize currently available clinical data on BCMA-directed CAR-T cells and discuss potential future perspective for this promising treatment approach in MM.     

Substantial Volume Changes and Plan Adaptations During Preoperative Radiation Therapy in Extremity Soft Tissue Sarcoma Patients

Purpose

Many authors suggest that extremity soft tissue sarcomas (ESTS) do not change significantly in size during preoperative radiation therapy (RT). This cone beam computed tomography study investigates the justification to deliver the entire course with 1 initial RT plan by observing anatomic changes during RT.

Eugenics,Epigenetics, and Obesity Predisposition among Mexican Mestizos

ABSTRACT

We compare the discourses on obesity found in early- and mid-twentieth century Mexican public discourse with those of Mexican geneticists and doctors today. We argue that postgenomic shifts towards non-determinism, apparently contained in current openness to epigenetics, need to be considered alongside the persistence of racialized genetic determinisms, and alongside the potential for epigenetic environmental determinisms. By exploring the environmentalist explanations of earlier eugenic thinking about obesity, we trace continuities in the gendered and racialized framings of obesity, which risk stigmatizing indigenous ancestry and attributing blame to individual mothers.     

Re‐structuring the negotiated order of the hospital

Researchers continue to lament the lack of organisational focus in the sociology of health and illness. Although studies have increasingly focused on boundaries between organizations, little such research has focused on the formal boundaries within the hospital itself. Given its dramatic compartmentalisation, and continuing prevalence in health systems, the lack of organisational perspective in hospital research limits insights into the effects (as well as the construction) of the order of health work and care. With a greater emphasis on ‘ordering’ in the concept of negotiated order, the aim of this study is to examine the manifestation and consequences of the formal boundaries of hospital departments. Fieldwork featured 12 months of ethnography, including formal and informal observations, 80 audio‐recorded, semi‐structured interviews, and 56 field interviews, in the Emergency Departments (EDs) of two tertiary referral hospitals. Compared with in‐patient hospital departments, the ED has limited legitimacy claims of organ‐specific knowledge to transfer patients out of the ED. The manifestation of specialised knowledge hierarchies in organisational structures disadvantages patients who are older and who have chronic conditions, underpinning the argument that effects as well as the negotiation of stable organisational orders deserve increased attention in the sociology of health and illness.     

Prexasertib (LY2606368) reduces clonogenic survival by inducing apoptosis in primary patient-derived osteosarcoma cells and synergizes with cisplatin and talazoparib

Progress in the systemic control of osteosarcoma has been limited over the past decades thus indicating the urgent clinical need for the development of novel treatment strategies. Therefore, we have recently developed new preclinical models to study promising novel agents for the treatment of pediatric osteosarcoma. The checkpoint kinase (chk) inhibitor prexasertib (LY2606368) and its salt form (LSN2940930) have recently been shown to be active in adult and pediatric malignancies, including sarcoma. We have now tested the potency of prexasertib in clonogenic survival assays in two new lines of primary patient-derived osteosarcoma cells and in two established osteosarcoma cell lines as a single agent and in combination with cisplatin and the poly ADP-ribose polymerase (PARP) inhibitor talazoparib. Prexasertib alone results in strongly reduced clonogenic survival at low nanomolar concentrations and acts by affecting cell cycle progression, induction of apoptosis and induction of double-stranded DNA breakage at concentrations that are well below clinically tolerable and safe plasma concentrations. In combination with cisplatin and talazoparib, prexasertib acts in a synergistic fashion. Chk1 inhibition by prexasertib and its combination with the DNA damaging agent cisplatin and the PARP-inhibitor talazoparib thus emerges as a potential new treatment option for pediatric osteosarcoma which will now have to be tested in preclinical primary patient derived in vivo models and clinical studies.