Citations

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.

AbstractIntroductionAppendicitis is a significant economic and healthcare burden in low‐, middle‐, and high‐income countries. We aimed to determine whether urban and rural patient status would affect outcomes in appendicitis in a combined population regardless of country of economic status. We hypothesize that patients from rural areas and both high‐ and low‐middle‐income countries would have disproportionate outcomes and duration of symptoms compared to their urban counterparts.MethodsAdults (≥18 years) with appendicitis during 2010–2016 in South Africa and USA were reviewed using multi‐institutional data. Baseline demographic, operative details, durations of stay, and complications (Clavien–Dindo index) were collected. AAST grades were assigned by two independent reviewers based on operative findings. Summary, univariate, and multivariable analyses of rural and urban patients in both countries were performed.ResultsThere were 2602 patients with a median interquartile range [IQR] of 26 [18–40] years; 45% were female. Initial management included McBurney incisions (n = 458, 18%), laparotomy (n = 915, 35%), laparoscopic appendectomy (n = 1185, 45%), and laparoscopy converted to laparotomy (n = 44, 2%). Comparing rural versus urban patient status, there were increased overall median [IQR] AAST grades (3 [1–5] vs. 2 [1–3], p = 0.001), prehospital duration of symptoms (2 [1–5] vs. 2 [1–3], p = 0.001), complications (44.3 vs. 23%, p = 0.001), and need for temporary abdominal closure (20.3 vs. 6.9%, p = 0.001).ConclusionDespite socioeconomic status and country of origin, patients from more rural environments demonstrate poorer outcomes notwithstanding significant differences in overall disease severity. The AAST grading system may serve a potential benchmark to recognize areas with disparate disease burdens. This information could be used for strategic improvements for surgeon placement and availability.

Alignment between institutions and graduate medical education (GME) regarding quality and safety initiatives (QI) has not been measured. The objective was to determine US internal medicine residency program directors’ (IM PDs) perceived resourcing for QI and alignment between GME and their institutions. A national survey of IM PDs was conducted in the Fall of 2013. Multivariable linear regression was used to test association between a novel Integration Score (IS) measuring alignment between GME and the institution via PD perceptions. The response rate was 72.6% (265/365). According to PDs, residents were highly engaged in QI (82%), but adequate funding (14%) and support personnel (37% to 61%) were lower. Higher IS correlated to reports of funding for QI (76.3% vs 54.5%, P = .012), QI personnel (67.3% vs 41.1%, P < .001), research experts (70.5% vs 50.0%, P < .001), and computer experts (69.0% vs 45.8%, P < .001) for QI assistance. Apparent mismatch between GME and institutional resources exists, and the IS may be useful in measuring GME–institutional leadership alignment in QI.

Background There are few data describing the longitudinal use of and adherence to heart failure medications following left ventricular assist device (LVAD) implantation. Methods and Results Using a large US commercial insurance database, patients who received an LVAD ( International Classification of Diseases, 9th Revision, Clinical Modification code 37.66) and survived to hospital discharge without heart transplantation between January 1, 2006, and March 31, 2015, were identified. Heart failure medication use from 3 months before 1‐year post‐ LVAD was examined using linked pharmacy claims. Differences in the proportion of patients taking heart failure medications post LVAD compared with pre LVAD were examined using McNemar test. Predictors of post‐ LVAD medication use and poor medication adherence (proportion of days covered <0.8) were identified via logistic regression. Among 362 patients (mean age, 57.4 years; 75.1% men), compared with pre LVAD , the proportion of patients taking anticoagulants and antiarrhythmics following LVAD increased; mineralocorticoid receptor antagonists, thiazide diuretics, and digoxin decreased; and β‐blockers, angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers, and loop diuretics did not change. Pre‐ LVAD medication use was associated with post‐ LVAD use across all medication classes. The proportion of patients with poor medication adherence was 28.8%, 39.0%, and 36.0% for β‐blockers, angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers, and anticoagulants, respectively. Many patients with poor adherence completely discontinued use of the medication. Conclusions Neurohormonal antagonist use after LVAD was inconsistent, perhaps reflecting uncertainty of therapeutic benefit in this population. Medication adherence post‐ LVAD was poor in many patients. Further work is needed to delineate the reasons for nonadherence after LVAD .

The Stop The Bleed initiative was developed by the Department of Homeland Security to educate lay providers in bleeding reduction strategies. The current study evaluated: (1)three tourniquet instructions using a simulated tourniquet task and (2)participant confidence levels in tourniquet use and lay provider training. Thirty participants with limited clinical experience applied a tourniquet to a simulated limb using one of three instruction sets. Twelve of these participants (40%) participated in a tourniquet training session and focus group to discuss each instruction set. Participants preferred the most simple and pictoral instruction set, and identified opportunities for improvement in each set. Participant confidence in tourniquet use increased significantly following the task and the focus group. After the focus group, participant confidence in instructing lay providers on proper tourniquet use significantly increased. Adding key steps, contextual pictures, and indicators of success to instructions could support lay providers stop the bleed in life-threatening situations.

Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurologic disorder with predictable challenges regarding disease progression and end-of-life care. These include need for respiratory and nutritional support. Little is known about how such choices impact end-of-life health service utilization for these patients. Using OptumLabs Data Warehouse, a large administrative claims database with more than 150 million privately insured, geographically diverse enrollees, we sought to explore outcomes associated with the use of enteral nutrition (EN). Patients were of age ≥18 years, with first ALS diagnosis during calendar years 2006-2012, and 6 months of continuous health plan coverage before first diagnosis. EN use was identified using procedure codes. Data were summarized descriptively. Among 1974 patients with ALS, mean age was 60.0 ± 12.5 years, 41.8% were women, and 9.7% demonstrated use of EN. Median time from ALS diagnosis to evidence of EN was 211 days (interquartile range [IQR]: 70-426). Those receiving EN had greater aggregate comorbidity (47% with Charlson-Deyo Comorbidity Index ≥ 3 vs only 27% in non-EN subset). In total, 38.1% of patients had at least 1 hospitalization, with median time to hospitalization of 162 days. Unfortunately, the EN group ended coverage a median of 155 days after EN started (IQR: 63.5-388), thereby limiting ability to capture outcomes. Although many ALS patients were identified, EN use was lower than expected, due to being earlier in disease trajectory and lost to follow-up with transition from private insurance. As such, databases exclusively including privately insured patients may be suboptimal for detecting late complications of protracted illnesses.

Abstract Purpose: Hyperactivation of AKT is common and associated with endocrine resistance in estrogen receptor–positive (ER+) breast cancer. The allosteric pan-AKT inhibitor MK-2206 induced apoptosis in PIK3CA-mutant ER+ breast cancer under estrogen-deprived condition in preclinical studies. This neoadjuvant phase II trial was therefore conducted to test the hypothesis that adding MK-2206 to anastrozole induces pathologic complete response (pCR) in PIK3CA mutant ER+ breast cancer. Experimental Design: Potential eligible patients with clinical stage II/III ER+/HER2− breast cancer were preregistered and received anastrozole (goserelin if premenopausal) for 28 days in cycle 0 pending tumor PIK3CA sequencing. Patients positive for PIK3CA mutation in the tumor were eligible to start MK-2206 (150 mg orally weekly, with prophylactic prednisone) on cycle 1 day 2 (C1D2) and to receive a maximum of four 28-day cycles of combination therapy before surgery. Serial biopsies were collected at preregistration, C1D1 and C1D17. Results: Fifty-one patients preregistered and 16 of 22 with PIK3CA-mutant tumors received study drug. Three patients went off study due to C1D17 Ki67 &gt;10% (n = 2) and toxicity (n = 1). Thirteen patients completed neoadjuvant therapy followed by surgery. No pCRs were observed. Rash was common. MK-2206 did not further suppress cell proliferation and did not induce apoptosis on C1D17 biopsies. Although AKT phosphorylation was reduced, PRAS40 phosphorylation at C1D17 after MK-2206 persisted. One patient acquired an ESR1 mutation at surgery. Conclusions: MK-2206 is unlikely to add to the efficacy of anastrozole alone in PIK3CA-mutant ER+ breast cancer and should not be studied further in the target patient population. Clin Cancer Res; 23(22); 6823–32. ©2017 AACR.