Citations

Purpose To identify common and overlapping themes among the interpersonal and communication skills (ICS), practice-based learning and improvement (PBLI), professionalism (PROF), and systems-based practice (SBP) milestones of the transitional year and 26 specialties. Method In May 2017, milestones were accessed from the Accreditation Council for Graduate Medical Education specialties website. A thematic analysis of the ICS, PBLI, PROF, and SBP milestones was performed to determine unique and common themes across these competencies and across specialties. Keywords from the common program requirements were initially applied as codes to the milestones. Codes were then grouped into common themes. Results Twenty-two themes were identified: 15 (68%) were unique to a given competency (3 related to ICS, 4 related to PBLI, 5 related to PROF, and 3 related to SBP), and 7 (32%) appeared in the milestones of more than one core competency. Eleven themes (50%) were used by 20 or more specialties, and 6 themes (27%) by 10 or fewer specialties. No theme was present across all specialties. Conclusions The ICS, PBLI, PROF, and SBP milestones contain multiple themes with areas of overlap among these four competencies and substantial variability across specialties. This variability may create differential expectations of residents across specialties, complicate faculty development, and make sharing assessment tools difficult. The thematic analysis provides important insights into how individual specialties interpret and operationalize the ICS, PBLI, PROF, and SBP competency domains and can inform future revisions of milestones to enable harmonization and shared understanding of these competencies across specialties where appropriate.

Background: Efforts to safely reduce length of stay for emergency department patients with symptoms suggestive of acute coronary syndrome (ACS) have had mixed success. Few system-wide efforts affecting multiple hospital emergency departments have ever been evaluated. We evaluated the effectiveness of a nationwide implementation of clinical pathways for potential ACS in disparate hospitals. Methods: This was a multicenter pragmatic stepped-wedge before-and-after trial in 7 New Zealand acute care hospitals with 31 332 patients investigated for suspected ACS with serial troponin measurements. The implementation was a clinical pathway for the assessment of patients with suspected ACS that included a clinical pathway document in paper or electronic format, structured risk stratification, specified time points for electrocardiographic and serial troponin testing within 3 hours of arrival, and directions for combining risk stratification and electrocardiographic and troponin testing in an accelerated diagnostic protocol. Implementation was monitored for >4 months and compared with usual care over the preceding 6 months. The main outcome measure was the odds of discharge within 6 hours of presentation Results: There were 11 529 participants in the preimplementation phase (range, 284–3465) and 19 803 in the postimplementation phase (range, 395–5039). Overall, the mean 6-hour discharge rate increased from 8.3% (range, 2.7%–37.7%) to 18.4% (6.8%–43.8%). The odds of being discharged within 6 hours increased after clinical pathway implementation. The odds ratio was 2.4 (95% confidence interval, 2.3–2.6). In patients without ACS, the median length of hospital stays decreased by 2.9 hours (95% confidence interval, 2.4–3.4). For patients discharged within 6 hours, there was no change in 30-day major adverse cardiac event rates (0.52% versus 0.44%; P =0.96). In these patients, no adverse event occurred when clinical pathways were correctly followed. Conclusions: Implementation of clinical pathways for suspected ACS reduced the length of stay and increased the proportions of patients safely discharged within 6 hours. Clinical Trial Registration: URL: https://www.anzctr.org.au/ (Australian and New Zealand Clinical Trials Registry). Unique identifier: ACTRN12617000381381.

182 Background: The purpose of this study was to examine the associations of three different measures of anxiety and depression with patient reported distress (PRD) level and survival after radiotherapy (RT). Methods: 518 patients who underwent RT between 2012 and 2016 were included in this retrospective study. PRD was assessed at the time of RT using the NCCN thermometer and a 30 question survey of distress related items. PRD and clinical and demographic data was retrospectively collected and analyzed. The three measures this study focused on that assessed patient anxiety and depression involved asking patients about their level of concern regarding feeling down, regarding loss of interest, and regarding feeling nervous. Associations between baseline patient characteristics and survival after start of RT were evaluated using single variable Cox proportional hazards regression models. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated. Associations of level of concern regarding patient anxiety/depression with survival after RT were evaluated using single variable and multivariable Cox proportional hazards regression models. Results: Overall, PRD level and concern regarding anxiety/depression were positively correlated (p < 0.001). Additionally, there was a significant association between level of concern regarding feeling down and palliative patients (p = 0.03). There was also a significant association between level of concern regarding loss of interest and palliative patients (p = 0.03), with level of concern highest for thorax, breast, and head and neck. There was also a significant different between level of concern regarding feeling nervous and gender (p = 0.05). There was not a significant difference between any of the three measures and survival after RT (all p ≥ 0.21). Conclusions: Anxiety and depression in patients receiving palliative and curative RT was associated with overall distress. Baseline screening of PRD may identify patients who would benefit from intervention to address the causes of their underlying anxiety and depression.

Objective Determinants of the increased risk of diffuse large B-cell lymphoma (DLBCL) in SLE are unclear. Using data from a recent lymphoma genome-wide association study (GWAS), we assessed whether certain lupus-related single nucleotide polymorphisms (SNPs) were also associated with DLBCL. Methods GWAS data on European Caucasians from the International Lymphoma Epidemiology Consortium (InterLymph) provided a total of 3857 DLBCL cases and 7666 general-population controls. Data were pooled in a random-effects meta-analysis. Results Among the 28 SLE-related SNPs investigated, the two most convincingly associated with risk of DLBCL included the CD40 SLE risk allele rs4810485 on chromosome 20q13 (OR per risk allele=1.09, 95% CI 1.02 to 1.16, p=0.0134), and the HLA SLE risk allele rs1270942 on chromosome 6p21.33 (OR per risk allele=1.17, 95% CI 1.01 to 1.36, p=0.0362). Of additional possible interest were rs2205960 and rs12537284. The rs2205960 SNP, related to a cytokine of the tumour necrosis factor superfamily TNFSF4, was associated with an OR per risk allele of 1.07, 95% CI 1.00 to 1.16, p=0.0549. The OR for the rs12537284 (chromosome 7q32, IRF5 gene) risk allele was 1.08, 95% CI 0.99 to 1.18, p=0.0765. Conclusions These data suggest several plausible genetic links between DLBCL and SLE.

AbstractUnderstanding how incompletely cleared primary tumors transition from minimal residual disease (MRD) into treatment-resistant, immune-invisible recurrences has major clinical significance. We show here that this transition is mediated through the subversion of two key elements of innate immunosurveillance. In the first, the role of TNFα changes from an antitumor effector against primary tumors into a growth promoter for MRD. Second, whereas primary tumors induced a natural killer (NK)–mediated cytokine response characterized by low IL6 and elevated IFNγ, PD-L1hi MRD cells promoted the secretion of IL6 but minimal IFNγ, inhibiting both NK-cell and T-cell surveillance. Tumor recurrence was promoted by trauma- or infection-like stimuli inducing VEGF and TNFα, which stimulated the growth of MRD tumors. Finally, therapies that blocked PD-1, TNFα, or NK cells delayed or prevented recurrence. These data show how innate immunosurveillance mechanisms, which control infection and growth of primary tumors, are exploited by recurrent, competent tumors and identify therapeutic targets in patients with MRD known to be at high risk of relapse. Cancer Immunol Res; 5(11); 1029–45. ©2017 AACR.

Generalized lipodystrophy (GL) is a rare inherited or acquired disease characterized by widespread loss of subcutaneous fat, leading to leptin deficiency, ectopic fat deposition, and severe metabolic abnormalities. Previous studies have shown the benefit of leptin replacement (metreleptin) in ameliorating metabolic complications, but little is known about the experience of metreleptin treatment outside of a research setting. We report on post-marketing clinical experience with metreleptin therapy in three patients with GL and marked hypoleptinemia, uncontrolled diabetes, and hypertriglyceridemia. After metreleptin treatment for 12–168 weeks, the mean glycated hemoglobin decreased from 10.9% to 5.8%, and serum triglycerides were normalized (a mean decline of 90%). These benefits were observed within weeks of starting therapy, were durable, and were accompanied by subjective improvements in quality of life, decreased need for concomitant medications, and no significant adverse effects. Metreleptin was safe and effective in normalizing certain severe metabolic abnormalities in the clinic setting.