Citations

Background: Clinical management of sport-related concussion typically involves a symptom checklist, clinical examination of mental status, and neurocognitive testing. However, recent studies have identified unresolved, impaired sensorimotor function after athletes return to sport. A review and meta-analysis of all current literature regarding risk of subsequent musculoskeletal (MSK) injury after concussion has yet to be published in the medical literature. Purpose/Hypothesis: To determine the odds that athletes will sustain MSK injury after concussion. It was hypothesized a priori that concussion would increase the risk for MSK injury. Study Design: Systematic review and meta-analysis. Methods: PubMed and Google Scholar were searched from January 2000 to November 2017. Reference lists of the included studies were manually searched. Two reviewers independently searched the literature for studies published in English that reported MSK injury after athletes returned to play following a concussion. Two independent reviewers completed data extraction using PRISMA guidelines and assessed study quality using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies from the National Institutes of Health. Random effects meta-analyses were used to calculate odds ratio (OR) and incidence rate ratio (IRR) of MSK injury after concussion. The primary study outcome of interest was the number of athletes who sustained MSK injury after concussion. Results: Eight studies met inclusion criteria for meta-analysis. Meta-analysis results indicated that athletes who had a concussion had 2 times greater odds of sustaining a MSK injury than athletes without concussion (OR, 2.11; 95% CI, 1.46-3.06). In addition, athletes with concussion demonstrated a higher incidence of MSK injury after return to sport compared with nonconcussed athletes (IRR, 1.67; 95% CI, 1.42-1.96). Further analysis showed that both male and female athletes with concussion were at an increased risk of MSK injury compared with their respective same-sex, nonconcussed controls (OR > 1.56, P < .01). Conclusion: Based on the evidence of higher risk of MSK injuries after concussion, standard clinical assessments for athletes with concussion should include not only physical symptoms and cognitive function before return to sport but also neuromuscular risk factors associated with increased risk for MSK injuries.

Abstract Background: Endometrioid carcinoma (EC) and clear cell carcinoma (CC) histotypes of epithelial ovarian cancer are understudied compared with the more common high-grade serous carcinomas (HGSC). We therefore sought to characterize EC and CC transcriptomes in relation to HGSC. Methods: Following bioinformatics processing and gene abundance normalization, differential expression analysis of RNA sequence data collected on fresh-frozen tumors was completed with nonparametric statistical analysis methods (55 ECs, 19 CCs, 112 HGSCs). Association of gene expression with progression-free survival (PFS) was completed with Cox proportional hazards models. Eight additional multi-histotype expression array datasets (N = 852 patients) were used for replication. Results: In the discovery set, tumors generally clustered together by histotype. Thirty-two protein-coding genes were differentially expressed across histotype (P &lt; 1 × 10−10) and showed similar associations in replication datasets, including MAP2K6, KIAA1324, CDH1, ENTPD5, LAMB1, and DRAM1. Nine genes associated with PFS (P &lt; 0.0001) showed similar associations in replication datasets. In particular, we observed shorter PFS time for CC and EC patients with high gene expression for CCNB2, CORO2A, CSNK1G1, FRMD8, LIN54, LINC00664, PDK1, and PEX6, whereas, the converse was observed for HGSC patients. Conclusions: The results suggest important histotype differences that may aid in the development of treatment options, particularly those for patients with EC or CC. Impact: We present replicated findings on transcriptomic differences and how they relate to clinical outcome for two of the rarer ovarian cancer histotypes of EC and CC, along with comparison with the common histotype of HGSC. Cancer Epidemiol Biomarkers Prev; 27(9); 1101–9. ©2018 AACR.

ABSTRACT Several meta‐analyses have been published on the effectiveness of anterior cruciate ligament (ACL) injury prevention training programs to reduce ACL injury risk, with various degrees of risk reduction reported. The purpose of this research was to perform a systematic review and meta‐analysis of overlapping meta‐analyses evaluating the effectiveness of ACL injury prevention training programs so as to summarize the amount of reduction in risk for all ACL and non‐contact ACL injuries into a single source, and determine if there were sex differences in the relative efficacy of ACL injury prevention training programs. Five databases (Medline, PubMed, Embase, CINAHL, and Cochrane) were searched to identify meta‐analyses that evaluated the effectiveness of ACL injury prevention training programs on ACL injury risk. ACL injury data were extracted and the results from each meta‐analysis were combined using a summary meta‐analysis based on odds ratios (OR). Eight meta‐analyses met eligibility criteria. Six of the eight only included data for female athletes. Summary meta‐analysis showed an overall 50% reduction (OR = 0.5 [0.41–0.59]; I 2 = 15%) in the risk of all ACL injuries in all athletes and a 67% reduction (OR = 0.33 [0.27–0.41]; I 2 = 15%) for non‐contact ACL injuries in females. This paper combines all previous meta‐analyses into a single source and shows conclusive evidence that ACL injury prevention programs reduce the risk of all ACL injuries by half in all athletes and non‐contact ACL injuries by two‐thirds in female athletes. There is insufficient data to make conclusions as to the effectiveness of ACL injury prevention programs in male athletes. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2696–2708, 2018.

Introduction: In response to reported difficulties in selecting a Medicare Part D prescription drug plan, we designed a patient-centered online Part D plan selection tool (CHOICE1.0) to simplify the selection process and to provide personalized, expert recommendations. Methods: This ethnographic comparative usability study observed 44 patients using the first version of the tool during Medicare 2016 Open Enrollment. Participants were observed as they chose their drug plan using Medicare.gov and 1 of 3 versions of CHOICE1.0 that varied in amount of expert guidance. Descriptive statistics were used to analyze exit survey data. The observations were video-recorded, and field notes were analyzed thematically. Results: Participants were significantly more satisfied with CHOICE1.0 for choosing a plan, understanding information, and ease of use compared to Medicare.gov . Those using expert versions of CHOICE1.0 were more likely to indicate their intention to switch plans than those using Medicare.gov , though they wanted to know the source and content. Conclusion: The more patient-centered prescription drug choice tool improved user experience and enabled users to choose plans more consistent with expert recommendations.

Background: Anterior cruciate ligament (ACL) injury has a significant psychological effect, and a negative psychological state is a commonly cited reason for a reduction or cessation of sports participation after ACL reconstruction (ACLR) surgery. Purpose: To identify factors that contribute to an athlete’s psychological readiness to return to sport (RTS) after ACLR. Study Design: Cross-sectional study; Level of evidence, 3. Methods: A cohort of 635 athletes (389 male, 246 female) who underwent ACLR and had been cleared to RTS completed the Anterior Cruciate Ligament–Return to Sport After Injury (ACL-RSI) scale at an average 12 months (range, 11-24 months) after surgery. Demographics (age, sex), sporting outcomes (preinjury frequency), surgical timing (injury to surgery interval), clinical factors (laxity), functional measures (single-limb hop symmetry), and symptoms of pain and function (International Knee Documentation Committee subjective) were also taken, and univariate and multiple regression models were used to determine the association between these and the psychological readiness of the athlete to RTS (ACL-RSI scores). Data for the entire cohort were initially analyzed; then, patients were grouped according to whether they had returned to competitive sport, and the analysis repeated for each group (return/nonreturn). Results: Univariate analysis for the entire group showed that all of the following had a positive effect on psychological readiness: male sex (β = 5.8; 95% CI, 2-10), younger age (β = −0.2; 95% CI, –0.4 to 0.01), a shorter interval between injury and surgery (β = −0.1; 95% CI, −0.1 to −0.02), a higher frequency of preinjury sport participation (β = 5.4; 95% CI, 2-9), greater limb symmetry (β = 0.5; 95% CI, 0.3-0.6), and higher subjective knee scores (β = 1.3; 95% CI, 1.1-1.4). In the multivariate model, subjective knee scores and age significantly accounted for 37% of the variance in psychological readiness ( r 2 = 0.37, P < .0001). The only difference between the groups who had and had not returned to sport was that female sex was a significant contributor for the nonreturn group. Conclusion: Self-reported symptoms and function were most associated with psychological readiness to RTS after ACLR surgery. Male patients who participated frequently in sport before ACL injury had higher psychological readiness. Conversely, female patients had a more negative outlook and may therefore benefit more from interventions designed to facilitate a smooth transition back to sport.

Purpose FGFR genetic aberrations (GAs) occur in an estimated 10% to 16% of intrahepatic cholangiocarcinomas (CCAs). The natural history of CCA with FGFR GAs, the prognostic role of coexisting GAs, and the outcome with FGFR-targeted inhibitors are unknown. Patients and Methods Patients with CCA with FGFR GAs were identified using next-generation sequencing or fluorescence in situ hybridization from four tertiary cancer centers and compared with FGFR wild-type counterparts. Data reviewed included demographic, treatment, overall survival (OS), and GA data. Fisher’s exact test, Kaplan-Meier plots, and log-rank tests were used for statistical analysis. Results Three hundred seventy-seven patients with CCA were identified, and 95 had FGFR GAs. FGFR2 GA was most common (n = 74, with 63 fusions) and seen in intrahepatic CCA. In patients with CCA, FGFR GAs occurred more frequently in younger patients (≤ 40 years; 20%) compared with older patients (> 40 years; 6.7%; P < .001), presented at an earlier stage (TNM stage I/II v III/IV: 35.8% v 22%, respectively; P = .001), and were associated with a longer OS compared with patients without FGFR GAs (37 v 20 months, respectively; P < .001). This difference remained significant after excluding 36 patients treated with FGFR inhibitors. There was no OS difference ( P = .60) between CCA with FGFR2 fusions (n = 63) versus other FGFR GAs (n = 29). Patients with FGFR GAs had a better OS with FGFR-targeted therapy compared with standard treatment ( P = .01). BAP1 mutation was the most common coexisting mutation without prognostic impact, whereas TP53 ( P = .04) and CDKN2A/B ( P = .04) were correlated with a shorter OS. Conclusion CCA with FGFR GAs represents a unique subtype occurring in younger patients with an indolent disease course. FGFR-targeted therapy may have a positive impact on OS in this subgroup.

OBJECTIVEThe use of nerve transfers versus nerve grafting for neonatal brachial plexus palsy (NBPP) remains controversial. In adult brachial plexus injury, transfer of an ulnar fascicle to the biceps branch of the musculocutaneous nerve (Oberlin transfer) is reportedly superior to nerve grafting for restoration of elbow flexion. In pediatric patients with NBPP, recovery of elbow flexion and forearm supination is an indicator of resolved NBPP. Currently, limited evidence exists of outcomes for flexion and supination when comparing nerve transfer and nerve grafting for NBPP. Therefore, the authors compared 1-year postoperative outcomes for infants with NBPP who underwent Oberlin transfer versus nerve grafting.METHODSThis retrospective cohort study reviewed patients with NBPP who underwent Oberlin transfer (n = 19) and nerve grafting (n = 31) at a single institution between 2005 and 2015. A single surgeon conducted intraoperative exploration of the brachial plexus and determined the surgical nerve reconstruction strategy undertaken. Active range of motion was evaluated preoperatively and postoperatively at 1 year.RESULTSNo significant difference between treatment groups was observed with respect to the mean change (pre- to postoperatively) in elbow flexion in adduction and abduction and biceps strength. The Oberlin transfer group gained significantly more supination (100° vs 19°; p < 0.0001). Forearm pronation was maintained at 90° in the Oberlin transfer group whereas it was slightly improved in the grafting group (0° vs 32°; p = 0.02). Shoulder, wrist, and hand functions were comparable between treatment groups.CONCLUSIONSThe preliminary data from this study demonstrate that the Oberlin transfer confers an advantageous early recovery of forearm supination over grafting, with equivalent elbow flexion recovery. Further studies that monitor real-world arm usage will provide more insight into the most appropriate surgical strategy for NBPP.

Purpose No standard treatment exists for patients with cholangiocarcinoma for whom first-line gemcitabine-based therapy fails. Fibroblast growth factor receptor 2 ( FGFR2) fusions/translocations are present in 13% to 17% of intrahepatic cholangiocarcinomas. BGJ398, an orally bioavailable, selective pan-FGFR kinase inhibitor, has shown preliminary clinical activity against tumors with FGFR alterations. Methods A multicenter, open-label, phase II study ( ClinicalTrials.gov identifier: NCT02150967) evaluated BGJ398 antitumor activity in patients age ≥ 18 years with advanced or metastatic cholangiocarcinoma containing FGFR2 fusions or other FGFR alterations whose disease had progressed while receiving prior therapy. Patients received BGJ398 125 mg once daily for 21 days, then 7 days off (28-day cycles). The primary end point was investigator-assessed overall response rate. Results Sixty-one patients (35 women; median age, 57 years) with FGFR2 fusion (n = 48), mutation (n = 8), or amplification (n = 3) participated. At the prespecified data cutoff (June 30, 2016), 50 patients had discontinued treatment. All responsive tumors contained FGFR2 fusions. The overall response rate was 14.8% (18.8% FGFR2 fusions only), disease control rate was 75.4% (83.3% FGFR2 fusions only), and estimated median progression-free survival was 5.8 months (95% CI, 4.3 to 7.6 months). Adverse events included hyperphosphatemia (72.1% all grade), fatigue (36.1%), stomatitis (29.5%), and alopecia (26.2%). Grade 3 or 4 treatment-related adverse events occurred in 25 patients (41%) and included hyperphosphatemia (16.4%), stomatitis (6.6%), and palmar-plantar erythrodysesthesia (4.9%). Conclusion BGJ398 is a first-in-class FGFR kinase inhibitor with manageable toxicities that shows meaningful clinical activity against chemotherapy-refractory cholangiocarcinoma containing FGFR2 fusions. This promising antitumor activity supports continued development of BGJ398 in this highly selected patient population.

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.