A Cohort Study to Evaluate Genetic Predictors for Aromatase Inhibitor Musculoskeletal Symptoms (AIMSS): Results from ECOG-ACRIN E1Z11.

PURPOSE: Aromatase Inhibitor-Associated Musculoskeletal Symptoms (AIMSS) are common and frequently lead to AI discontinuation. Single nucleotide polymorphisms (SNPs) in candidate genes have been associated with AIMSS and AI discontinuation. E1Z11 is a prospective cohort study designed to validate associations between 10 SNPs and AI discontinuation due to AIMSS. PATIENTS AND METHODS: Postmenopausal women with stage I-III hormone receptor-positive breast cancer received anastrozole 1 mg daily and completed patient-reported outcomes (PRO) to assess AIMSS (Stanford Health Assessment Questionnaire; HAQ) at baseline, 3, 6, 9, and 12 months. We estimated that 40% of participants would develop AIMSS, and 25% would discontinue AI treatment within 12 months. Enrollment of 1,000 women with a fixed number per racial strata provided 80% power to detect an effect size of 1.5-4. SNPs were in ESR1 (rs2234693, rs2347868, rs9340835), CYP19A1 (rs1062033, rs4646), TCL1A (rs11849538, rs2369049, rs7158782, rs7159713), and HTR2A (rs2296972). RESULTS: Of 970 evaluable women, 43% developed AIMSS and 12% discontinued AI therapy within 12 months. While more Black and Asian women developed AIMSS compared to White women (49% vs 39%, p=0.017; 50% vs 39%, p=0.004, respectively), AI discontinuation rates were similar across groups. None of the SNPs were significantly associated with AIMSS or AI discontinuation in the overall population, or in distinct cohorts. The odds ratio for rs2296972 (HTR2A) approached significance for developing AIMSS. CONCLUSION: We were unable to prospectively validate candidate SNPs previously associated with AI discontinuation due to AIMSS. Future analyses will explore additional genetic markers, PRO predictors of AIMSS, and differences by race.

Validation of translated Obstetric Quality of Recovery (ObsQoR-10A) score after nonelective cesarean delivery (CD) in an Arabic-speaking population.

Background: The ObsQoR-11 is a validated scale that assesses recovery after cesarean delivery (CD). This observational study aimed to evaluate the psychometric properties of its Arabic version. Methods: The original ObsQoR-11 was translated into an Arabic version (ObsQoR-10A). All participants completed the ObsQoR-10A at 24 h and 48 h postoperatively after CD. Validity, reliability, responsiveness, and feasibility were assessed. Results: The ObsQoR-10A correlated with Global Health Numerical Rating Scale (NRS) at 24 h (R = 0.68, 95% CI: 0.56-0.80, P < 0.001) and at 48 h (R = 0.66, 95% CI: 0.54-0.78, P < 0.001) and differentiated between good and poor recovery (median scores at 24 h 88 vs. 71, P < 0.001; at 48 h 95.5 vs. 70, P < 0.001). ObsQoR-10A correlated with hospital length of stay at 24 h (R = -0.21, 95% CI: -0.40 to -0.02, P = 0.03) and at 48 h (R = -0.21, 95% CI: -0.40 to -0.03, P = 0.02); gestational age at 24 h (R = 0.22, 95% CI: 0.03-0.40, P = 0.02); change in hemoglobin at 24 h (R = -0.30, 95% CI: 0.51 to -0.10, P < 0.01); and total opioids at 48 h (R = -0.45, 95% CI: -0.62 to -0.27, P < 0.001). There was a significant difference between 24 h and 48 h postoperative ObsQoR-10A scores (median difference: -18; P < 0.001 which shows responsiveness). Other key measures included a Cronbach's alpha of 0.87, split-half 0.75, and intra-class correlation >0.62 with no floor or ceiling effects. Median (IQR) completion time was 3 (3-5) and 3 (2.5-3.5) minutes at 24 h and 48 h. Conclusions: ObsQoR-10A is a valid, reliable, responsive, and a clinically feasible tool in an Arabic-speaking obstetric population.

Impact of video games on ultrasound-guided regional anesthesia skills.

BACKGROUND: There is an association between video game practice and laparoscopic expertize in trainee surgeons. Ultrasound-guided regional anesthesia has many parallels with laparoscopic surgery. The aim of this study was to explore whether video game experience is associated with enhanced performance in a simulated ultrasound-guided task in novice operators. METHODS: In this prospective observational study, 60 medical student volunteers were recruited. Following characterization of video game experience, they underwent an assessment of visuospatial abilities. Following standardized teaching, the recruits' technical performance of an ultrasound-guided needle task was assessed for overall quality by global rating scale (GRS). RESULTS: Out of a total possible GRS score of 35, gamers compared with non-gamers demonstrated 5.2 (95% CI 1.9 to 8.4) units of better performance. Gamers also performed better in mental rotation test scores (difference 4.1, 95% CI 1.2 to 7.0) . CONCLUSION: Video game practice is associated with increased mental rotation ability and enhanced technical performance in a simulated ultrasound-guided task.

Adjuvant chemotherapy with or without bevacizumab in patients with resected non-small-cell lung cancer (E1505): an open-label, multicentre, randomised, phase 3 trial.

BACKGROUND: Adjuvant chemotherapy for resected early-stage non-small-cell lung cancer (NSCLC) provides a modest survival benefit. Bevacizumab, a monoclonal antibody directed against VEGF, improves outcomes when added to platinum-based chemotherapy in advanced-stage non-squamous NSCLC. We aimed to evaluate the addition of bevacizumab to adjuvant chemotherapy in early-stage resected NSCLC. METHODS: We did an open-label, randomised, phase 3 trial of adult patients (aged ≥18 years) with an Eastern Cooperative Oncology Group performance status of 0 or 1 and who had completely resected stage IB (≥4 cm) to IIIA (defined by the American Joint Committee on Cancer 6th edition) NSCLC. We enrolled patients from across the US National Clinical Trials Network, including patients from the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) affiliates in Europe and from the Canadian Cancer Trials Group, within 6-12 weeks of surgery. The chemotherapy regimen for each patient was selected before randomisation and administered intravenously; it consisted of four 21-day cycles of cisplatin (75 mg/m2 on day 1 in all regimens) in combination with investigator's choice of vinorelbine (30 mg/m2 on days 1 and 8), docetaxel (75 mg/m2 on day 1), gemcitabine (1200 mg/m2 on days 1 and 8), or pemetrexed (500 mg/m2 on day 1). Patients in the bevacizumab group received bevacizumab 15 mg/kg intravenously every 21 days starting with cycle 1 of chemotherapy and continuing for 1 year. We randomly allocated patients (1:1) to group A (chemotherapy alone) or group B (chemotherapy plus bevacizumab), centrally, using permuted blocks sizes and stratified by chemotherapy regimen, stage of disease, histology, and sex. No one was masked to treatment assignment, except the Data Safety and Monitoring Committee. The primary endpoint was overall survival, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00324805. FINDINGS: Between June 1, 2007, and Sept 20, 2013, 1501 patients were enrolled and randomly assigned to the two treatment groups: 749 to group A (chemotherapy alone) and 752 to group B (chemotherapy plus bevacizumab). 383 (26%) of 1458 patients (with complete staging information) had stage IB, 636 (44%) had stage II, and 439 (30%) had stage IIIA disease (stage of disease data were missing for 43 patients). Squamous cell histology was reported for 422 (28%) of 1501 patients. All four cisplatin-based chemotherapy regimens were used: 377 (25%) patients received vinorelbine, 343 (23%) received docetaxel, 283 (19%) received gemcitabine, and 497 (33%) received pemetrexed. At a median follow-up of 50·3 months (IQR 32·9-68·0), the estimated median overall survival in group A has not been reached, and in group B was 85·8 months (95% CI 74·9 to not reached); hazard ratio (group B vs group A) 0·99 (95% CI 0·82-1·19; p=0·90). Grade 3-5 toxicities of note (all attributions) that were reported more frequently in group B (the bevacizumab group) than in group A (chemotherapy alone) were overall worst grade (ie, all grade 3-5 toxicities; 496 [67%] of 738 in group A vs 610 [83%] of 735 in group B), hypertension (60 [8%] vs 219 [30%]), and neutropenia (241 [33%] vs 275 [37%]). The number of deaths on treatment did not differ between the groups (15 deaths in group A vs 19 in group B). Of these deaths, three in group A and ten in group B were considered at least possibly related to treatment. INTERPRETATION: Addition of bevacizumab to adjuvant chemotherapy did not improve overall survival for patients with surgically resected early-stage NSCLC. Bevacizumab does not have a role in this setting and should not be considered as an adjuvant therapy for patients with resected early-stage NSCLC. FUNDING: National Cancer Institute of the National Institutes of Health.

Visuospatial Ability as a Predictor of Novice Performance in Ultrasound-guided Regional Anesthesia.

BACKGROUND: Visuospatial ability correlates positively with novice performance of simple laparoscopic tasks. The aims of this study were to identify whether visuospatial ability could predict technical performance of an ultrasound-guided needle task by novice operators and to describe how emotional state, intelligence, and fear of failure impact on this. METHODS: Sixty medical student volunteers enrolled in this observational study. The authors used an instructional video to standardize training for ultrasound-guided needle advancement in a turkey breast model and assessed volunteers' performance independently by two assessors using composite error score (CES) and global rating scale (GRS). The authors assessed their "visuospatial ability" with mental rotation test (MRT), group embedded figures test, and Alice Heim group ability test. Emotional state was judged with UWIST Mood Adjective Checklist (UMACL), and fear of failure and general cognitive ability were judged with numerical reasoning test. RESULTS: High CES scores (high error rate) were associated with low MRT scores (ρ = -0.54; P < 0.001). Better GRS scores were associated with better MRT scores (ρ = 0.47; P < 0.001). Regarding emotions, GRS scores were low when anxiety levels were high (ρ = -0.35; P = 0.005) and CES scores (errors) were low when individuals reported feeling vigorous and active (ρ = -0.30; P = 0.01). CONCLUSIONS: An MRT predicts novice performance of an ultrasound-guided needling task on a turkey model and as a trait measure could be used as a tool to focus training resources on less-able individuals. Anxiety adversely affects performance. Therefore, both may prove useful in directing targeted training in ultrasound-guided regional anesthesia.