The impact of design on research teams in health services: A case study of the significance of the design artifact for interdisciplinary research and the generation of theoretical and applied lines of inquiry

The development of patient communication tools in health services research often requires the skills of a designer who will give the tool its final, usable form. However, research teams frequently overlook the demands of implementation and focus instead on the delivery of content to the patient. In the study considered here, shared decision making in cancer treatment research was initiated by an interdisciplinary team without the participation of a designer. Once a designer began working on the team, the benefits she brought to the production of the designed artifact were evident. Design improved the team’s effectiveness through better communication, and allowed for further studies based on application and theory. Researchers responded positively to design and saw the potential for its application to a range of health research

“My Future is Now”: A Qualitative Study of Persons Living With Advanced Cancer

Objectives: Advance care planning (ACP) enables individuals to deliberate about future preferences for care based upon their values and beliefs about what is important in life. For many patients with advanced cancer, however, these critical conversations do not occur. A growing body of literature has examined the end-of-life wishes of seriously ill patients. Few studies have explored what is important to persons as they live with advanced cancer. The aim of the current study was to address this gap and to understand how clinicians can support patients’ efforts to live in the present and plan for the future. Methods: Transcriptions of interviews conducted with 36 patients diagnosed with advanced cancer were analyzed using immersion–crystallization, a qualitative research technique. Results: Four overarching themes were identified: (I) living in the face of death, (II) who I am, (III) my experience of cancer, and (IV) impact of my illness on others. Twelve subthemes are also reported. Significance of Results: These findings have significant implications for clinicians as they partner with patients to plan for the future. Our data suggest that clinicians consider the following 4 prompts: (1) “What is important to you now, knowing that you will die sooner than you want or expected?” (2) “Tell me about yourself.” (3) “Tell me in your own words about your experience with cancer care and treatment.” (4) “What impact has your illness had on others?” In honoring patients’ lived experiences, we may establish the mutual understanding necessary to providing high-quality care that supports patients’ priorities for life

Music Therapy Is Associated With Family Perception of More Spiritual Support and Decreased Breathing Problems in Cancer Patients Receiving Hospice Care

Context Music therapy is a common discretionary service offered within hospice; however, there are critical gaps in understanding the effects of music therapy on hospice quality indicators, such as family satisfaction with care. Objectives The purpose of this study was to examine whether music therapy affected family perception of patients' symptoms and family satisfaction with hospice care. Methods This was a retrospective, cross-sectional analysis of electronic medical records from 10,534 cancer patients cared for between 2006 and 2010 by a large national hospice. Logistic regression was used to estimate the effect of music therapy using propensity scores to adjust for non-random assignment. Results Overall, those receiving music therapy had higher odds of being female, having longer lengths of stay, and receiving more services other than music therapy, and lower odds of being married/partnered or receiving home care. Family satisfaction data were available for 1495 (14%) and were more likely available if the patient received music therapy (16% vs. 12%, P < 0.01). There were no differences in patient pain, anxiety, or overall satisfaction with care between those receiving music therapy vs. those not. Patients who received music therapy were more likely to report discussions about spirituality (odds ratio [OR] = 1.59, P = 0.01), had marginally less trouble breathing (OR = 0.77, P = 0.06), and were marginally more likely to receive the right amount of spiritual support (OR = 1.59, P = 0.06). Conclusion Music therapy was associated with perceptions of meaningful spiritual support and less trouble breathing. The results provide preliminary data for a prospective trial to optimize music therapy interventions for integration into clinical practice

Physicians in Postgraduate Training Characteristics and Support of Palliative Sedation for Existential Distress

Introduction: Palliative sedation for refractory existential distress (PS-ED) is ethically troubling but potentially critical to quality end-of-life (EOL) care. Physicians’ in postgraduate training support toward PS-ED is unknown nor is it known how empathy, hope, optimism, or intrinsic religious motivation (IRM) affect their support. These knowledge gaps hinder efforts to support physicians who struggle with patients’ EOL care preferences. Methods: One hundred thirty-four postgraduate physicians rated their support of PS for refractory physical pain (PS-PP) or PS-ED, ranked the importance of patient preferences in ethically challenging situations, and completed measures of empathy, hope, optimism, and IRM. Predictors of PS-ED and PS-PP support were examined using binary and multinomial logistic regression. Results: Only 22.7% of residents were very supportive of PS-ED, and 82.0% were very supportive of PS-PP. Support for PS-PP or PS-ED did not correlate with levels of empathy, hope, optimism, or IRM; however, for residents with lower IRM, greater optimism was associated with greater PS-ED support. In contrast, among residents with higher IRM, optimism was not associated with PS-ED support. Conclusions: Comparing current results to published surveys, a similar proportion of residents and practicing physicians support PS-ED and PS-PP. In contrast to practicing physicians, however, IRM does not directly influence residents’ supportiveness. The interaction between optimism and IRM suggests residents’ beliefs and characteristics are salient to their EOL decisions. End-of-life curricula should provide physicians opportunities to reflect on the personal and ethical factors that influence their support for PS-ED

Discussions of Life Expectancy Moderate Relationships between Prognosis and Anxiety or Depression in Men with Advanced Cancer

Purpose: Oncologists avoid prognostic discussions due to concerns about increasing patients' anxiety or depression. We sought to determine if perceived prognosis or extent of prognostic discussions predicted anxiety or depression and whether prognostic discussions moderated the relationship between prognosis and anxiety or depression. Methods: Men with advanced cancer and their oncologists estimated the likelihood of survival at 6 months and reported extent of prognostic discussions. Anxiety and depression were measured by the Hospital Anxiety and Depression Scale (HADS). Results: Men who died within 6 months reported higher scores on depression but not anxiety. Men who estimated a lower (10%–75%) likelihood of surviving at least 6 months were more depressed and anxious than men who estimated a higher (>90%) likelihood of survival. A similar relationship was seen with oncologists' prognostications. Men who reported having had full prognostic discussions with their oncologist had less depression compared with men who reported having had brief or no discussions. Men for whom the oncologists reported a full discussion had greater anxiety. The relationships between patient-perceived prognosis and depression or anxiety were moderated by extent of prognostic discussions as reported by the patient or oncologist, respectively. Conclusion: Full prognostic discussions are associated with less depression among men who perceive a poor prognosis. Anxiety is increased in men if the oncologists report a full discussion. Oncologists should engage in prognostic discussions but assess for increased anxiety to facilitate coping with advanced cancer

Consecutive epigenetically-active agent combinations act in ID1-RUNX3-TET2 and HOXA pathways for Flt3ITD+ve AML

Co-occurrence of Flt3ITD and TET2 mutations provoke an animal model of AML by epigenetic repression of Wnt pathway antagonists, including RUNX3, and by hyperexpression of ID1, encoding Wnt agonist. These affect HOXA over-expression and treatment resistance. A comparable epigenetic phenotype was identified among adult AML patients needing novel intervention. We chose combinations of targeted agents acting on distinct effectors, at the levels of both signal transduction and chromatin remodeling, in relapsed/refractory AML's, including Flt3ITD+ve, described with a signature of repressed tumor suppressor genes, involving Wnt antagonist RUNX3, occurring along with ID1 and HOXA over-expressions. We tracked patient response to combination of Flt3/Raf inhibitor, Sorafenib, and Vorinostat, pan-histone deacetylase inhibitor, without or with added Bortezomib, in consecutive phase I trials. A striking association of rapid objective remissions (near-complete, complete responses) was noted to accompany induced early pharmacodynamic changes within patient blasts in situ, involving these effectors, significantly linking RUNX3/Wnt antagonist de-repression (80%) and ID1 downregulation (85%), to a response, also preceded by profound HOXA9 repression. Response occurred in context of concurrent TET2 mutation/hypomorphy and Flt3ITD+ve mutation (83% of complete responses). Addition of Bortezomib to the combination was vital to attainment of complete response in Flt3ITD+ve cases exhibiting such Wnt pathway dysregulation

Practical recommendations on the use of lenalidomide in the management of myelodysplastic syndromes

Lenalidomide, an oral immunomodulatory agent, has received approval in the USA from the Food and Drug Administration (FDA) for the management of myelodysplastic syndromes (MDS) classified by the International Prognostic Scoring System (IPSS) as low risk or intermediate-1 risk and with a deletion 5q (del(5q)) cytogenetic abnormality. Although some patients with del(5q) have a relatively good prognosis, all del(5q) patients will become transfusion-dependent at some point during the course of their disease. The results of two clinical trials in more than 160 patients with MDS have demonstrated clear therapeutic benefits of lenalidomide, with >60% of patients achieving independence from transfusion during therapy, irrespective of age, prior therapy, sex, or disease-risk assessment. The recommendations presented in this review will aid the safe administration of lenalidomide for the treatment of patients with low-risk or intermediate-1-risk MDS and a del(5q) cytogenetic abnormality, and they will help physicians avoid unnecessary dose reduction or interruption, thus assuring the best efficacy for patients

Large-scale serum protein biomarker discovery in Duchenne muscular dystrophy.

Serum biomarkers in Duchenne muscular dystrophy (DMD) may provide deeper insights into disease pathogenesis, suggest new therapeutic approaches, serve as acute read-outs of drug effects, and be useful as surrogate outcome measures to predict later clinical benefit. In this study a large-scale biomarker discovery was performed on serum samples from patients with DMD and age-matched healthy volunteers using a modified aptamer-based proteomics technology. Levels of 1,125 proteins were quantified in serum samples from two independent DMD cohorts: cohort 1 (The Parent Project Muscular Dystrophy-Cincinnati Children's Hospital Medical Center), 42 patients with DMD and 28 age-matched normal volunteers; and cohort 2 (The Cooperative International Neuromuscular Research Group, Duchenne Natural History Study), 51 patients with DMD and 17 age-matched normal volunteers. Forty-four proteins showed significant differences that were consistent in both cohorts when comparing DMD patients and healthy volunteers at a 1% false-discovery rate, a large number of significant protein changes for such a small study. These biomarkers can be classified by known cellular processes and by age-dependent changes in protein concentration. Our findings demonstrate both the utility of this unbiased biomarker discovery approach and suggest potential new diagnostic and therapeutic avenues for ameliorating the burden of DMD and, we hope, other rare and devastating diseases

Independent Prognostic Significance of Monosomy 17 and Impact of Karyotype Complexity in Monosomal Karyotype/Complex Karyotype Acute Myeloid Leukemia: Results from Four ECOG-ACRIN Prospective Therapeutic Trials

The presence of a monosomal karyotype (MK+) and/or a complex karyotype (CK+) identifies subcategories of AML with poor prognosis. The prognostic significance of the most common monosomies (monosomy 5, monosomy 7, and monosomy 17) within MK+/CK+ AML is not well defined. We analyzed data from 1,592 AML patients age 17–93 years enrolled on ECOG-ACRIN therapeutic trials. The majority of MK+ patients (182/195; 93%) were MK+/CK+ with 87% (158/182) having ≥5 clonal abnormalities (CK≥ 5). MK+ patients with karyotype complexity ≤4 had a median overall survival (OS) of 0.4y compared to 1.0y for MK- with complexity ≤4 (p < 0.001), whereas no OS difference was seen in MK+ vs. MK- patients with CK≥ 5 (p = 0.82). Monosomy 5 (93%; 50/54) typically occurred within a highly complex karyotype and had no impact on OS (0.4y; p = 0.95). Monosomy 7 demonstrated no impact on OS in patients with CK≥ 5 (p = 0.39) or CK ≤ 4 (p = 0.44). Monosomy 17 appeared in 43% (68/158) of CK≥ 5 patients and demonstrated statistically significant worse OS (0.4y) compared to CK≥ 5 patients without monosomy 17 (0.5y; p = 0.012). Our data suggest that the prognostic impact of MK+ is limited to those with less complex karyotypes and that monosomy 17 may independently predict for worse survival in patients with AML