ABSTRACT
BACKGROUND: Goals of care conversations are essential to delivery of goal concordant care. Infrequent and inconsistent goals of care documentation potentially limit delivery of goal concordant care. METHODS: At Kaiser Permanente San Francisco Cancer Center, a standardized documentation template was designed and implemented to increase goals of care documentation by oncologists. The centralized, prompt-based template included value clarification of the goals and values of advanced cancer patients beyond treatment preferences. Documented conversations using the template during the initial pilot period were reviewed to characterization the clinical context in which conversations were recorded. Common goals and motivators were also identified. RESULTS: A total of 178 advanced cancer patients had at least 1 documented conversation by a medical oncologist using the goals of care template. Oncologists consistently documented within the template goals of therapy and motivating factors in decision making. The most frequently documented goals of care were "Avoiding Pain and Suffering," "Physical Independence," and "Living as Long as Possible." The least recorded goal was "Comfort Focused Treatment Only." CONCLUSIONS: Review of oncologist documented goals of care conversations using a prompt-based template allowed for characterization of the clinical context, therapy goals and motivators of advanced cancer patients. Communication of goals of care conversations by oncologists using a standardized prompt-based template within a centralized location has the potential to improve delivery of goal concordant care.
ABSTRACT
Melanoma is a potentially fatal cancer with rising incidence over the last 50 years, associated with enhanced sun exposure and ultraviolet radiation. Its incidence is highest in people of European descent and the ageing population. There are multiple clinical and epidemiological variables affecting melanoma incidence and mortality, such as sex, ethnicity, UV exposure, anatomic site, and age. Although survival has improved in recent years due to advances in targeted and immunotherapies, new understanding of melanoma biology and disease progression is vital to improving clinical outcomes. Efforts to develop three-dimensional human skin equivalent models using biofabrication techniques, such as bioprinting, promise to deliver a better understanding of the complexity of melanoma and associated risk factors. These 3D skin models can be used as a platform for patient specific models and testing therapeutics.
ABSTRACT
Neural crest stem/progenitor cells (NCSCs) populate a variety of tissues, and their dysregulation is implicated in several human diseases including craniosynostosis and neuroblastoma. We hypothesised that small molecules that inhibit NCSC induction or differentiation may represent potential therapeutically relevant drugs in these disorders. We screened 640 FDA-approved compounds currently in clinical use for other conditions to identify those which disrupt development of NCSC-derived skeletal elements that form the zebrafish jaw. In the primary screen, we used heterozygous transgenic sox10:gfp zebrafish to directly visualise NCSC-derived jaw cartilage. We noted partial toxicity of this transgene in relation to jaw patterning, suggesting that our primary screen was sensitised for NCSC defects, and we confirmed 10 novel, 4 previously reported, and 2 functional analogue drug hits in wild-type embryos. Of these drugs, 9/14 and 7/14, respectively, are known to target pathways implicated in osteoarthritis pathogenesis or to cause reduced bone mineral density/increased fracture risk as side effects in patients treated for other conditions, suggesting that our screen enriched for pathways targeting skeletal tissue homeostasis. We selected one drug that inhibited NCSC induction and one drug that inhibits bone mineralisation for further detailed analyses which reflect our initial hypotheses. These drugs were leflunomide and cyclosporin A, respectively, and their functional analogues, teriflunomide and FK506 (tacrolimus). We identified their critical developmental windows of activity, showing that the severity of defects observed related to the timing, duration, and dose of treatment. While leflunomide has previously been shown to inhibit NCSC induction, we demonstrate additional later roles in cartilage remodelling. Both drugs altered expression of extracellular matrix metalloproteinases. As proof-of-concept, we also tested drug treatment of disease-relevant mammalian cells. While leflunomide treatment inhibited the viability of several human NCSC-derived neuroblastoma cell lines coincident with altered expression of genes involved in ribosome biogenesis and transcription, FK506 enhanced murine calvarial osteoblast differentiation and prevented fusion of the coronal suture in calvarial explants taken from Crouzon syndrome mice.
ABSTRACT
BACKGROUND: Patients with distal radius fractures (DRF) often have limited range-of-motion (ROM) in multiple planes of movement. No studies have comprehensively examined the impact of various ROM limitations on physical function. METHODS: We performed a multi-center, longitudinal study of 138 patients with conservatively managed DRF. ROM measures were taken at initial evaluation, and at 4 and 8 weeks later. Self-reported physical function was indexed by the Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH). RESULTS: Wrist extension, active thumb opposition and a full composite grip were amongst the strongest ROM measures associated with functional scores over time. However, wrist radial deviation and forearm pronation were non-significantly associated with functional scores. CONCLUSION: Given that ROM is potentially modifiable, the identification of important ROM measures associated with QuickDASH scores can potentially facilitate patient education and refine interventions to optimize functional recovery. Well-designed randomized intervention studies are however needed to confirm these association findings.
