Back to the future: the amazing journey of the therapeutic anti-leukemia enzyme asparaginase Erwinia chrysanthemi.

For several decades, asparaginase has been considered world-wide as an essential component of combination chemotherapy for the treatment of childhood acute lymphoblastic leukemia (ALL). Discovered over 60 years ago, two main unmanipulated asparaginase products originated from primary bacteria sources, namely Escherichia coli and Erwinia chrysanthemi, have been available for clinical use. A pegylated product of the Escherichia coli asparaginase was subsequently developed and is now the main product used by several international co-operative groups. The various asparaginase products all display the same mechanism of action (hydrolysis of circulating asparagine) and are associated with similar efficacy and toxicity patterns. However, their different pharmacokinetics, pharmacodynamics and immunological properties require distinctive modalities of application and monitoring. Erwinia chrysanthemi asparaginase was initially used as a first-line product, but subsequently became a preferred second-line product for children who experienced immunological reactions to the Escherichia coli asparaginase products. An asparaginase product displaying the same characteristics of the Erwinia chrysanthemi asparaginase has recently been produced by use of recombinant technology, thus securing a preparation available for use as an alternative, or as a back-up in case of shortages, for the non-recombinant product. The long journey of the Erwinia chrysanthemi asparaginase product as it has developed throughout the last several decades has made it possible for almost every child and adult with ALL to complete the asparaginase-based protocol treatment when an immunological reaction has occurred to any Escherichia coli asparaginase product.

Perceptions and Motivation Regarding Performing Research in Physicians Specializing in Care for Older Adults Involved in a Mandatory Evidence-Based Medicine Training Study: A Mixed-Methods Study.

Purpose: Evidence underpinning treatment of older persons with complex conditions is often sparse, and involving more early career physicians committed to optimizing care for older adults may help increase a relevant evidence base. We examined perception of and motivation to conduct research in physicians (residents) specializing in care of older adults. Subjects and Methods: Residents of an academic medical centre in the Netherlands enrolled in a 3-year training programme. The programme includes a mandatory evidence-based medicine (EBM) training study on pain and discomfort in cognitively impaired nursing home patients, in which residents perform their research over the 3-year duration of the programme. We employed a mixed-methods design with survey and qualitative interviews (December 2019-April 2020). The survey included validated scales with agreement response options rated 1-7. Qualitative interviews were underpinned by interpretative phenomenological analysis. Results: Of 38 invited residents, 23 (15 females) participated. The mean score on perceptions of research was 4.1 (SD 0.8); on intrinsic motivation 4.8 (SD 1.0); on extrinsic motivation 4.3, with a higher SD of 1.4. Eight interviews also showed diversity in the extent to which residents felt equipped to conduct the mandatory EBM training study, and research more generally, which was related to previous experiences performing research. The residents generally did not anticipate conducting research themselves despite recognizing the benefits of training in research. Conclusion: Perceptions and motivation of the residents specializing in care of older people to conduct research, although considered relevant to their practice, were not very positive. The study results in recommendations to motivate physicians in geriatrics training to conduct research, eg through personalized boosting of self-efficacy. This is crucial to motivate future physicians to contribute to research relevant to older people in more ways than just delivering data for research conceived by (non-clinical) researchers.

Independent factors associated with long-term functional outcomes in patients with a proximal femoral fracture: A systematic review.

INTRODUCTION: The current understanding of prognostic factors of functional recovery after a proximal femoral fracture is limited, and enhancements could improve the prognostic accuracy and target subgroups for additional care strategies. This systematic review aims to identify all studied factors with an independent prognostic value for the long-term functional recovery of patients with a proximal femoral fracture. MATERIALS AND METHODS: Observational studies with multivariate analyses on prognostic factors of long-term functional outcome after proximal femoral fractures were obtained through an electronic search performed on November 9, 2018. RESULTS: In the 31 included articles, thirteen prognostic factors were studied by at least two independent studies and an additional ten by only one study. Age, comorbidity, functionality and cognition were factors for which the majority of studies indicated a significant effect. The majority of studies which included sex as a factor found no significant effect. The level of evidence for the remaining factors was deemed too low to be conclusive on their relevance for long-term functional outcome. CONCLUSION: The identified factors showed overlap with prognostic factors of short-term functional outcomes and mortality. The validity and applicability of prognostic models based on these factors may be of interest for future research.