Citations

Purpose Many patients with high-risk non–muscle-invasive bladder cancer (NMIBC) are either refractory to bacillus Calmette-Guerin (BCG) treatment or may experience disease relapse. We assessed the efficacy and safety of recombinant adenovirus interferon alfa with Syn3 (rAd–IFNα/Syn3), a replication-deficient recombinant adenovirus gene transfer vector, for patients with high-grade (HG) BCG-refractory or relapsed NMIBC. Methods In this open-label, multicenter (n = 13), parallel-arm, phase II study ( ClinicalTrials.gov identifier: NCT01687244), 43 patients with HG BCG-refractory or relapsed NMIBC received intravesical rAd–IFNα/Syn3 (randomly assigned 1:1 to 1 × 10 11 viral particles (vp)/mL or 3 × 10 11 vp/mL). Patients who responded at months 3, 6, and 9 were retreated at months 4, 7, and 10. The primary end point was 12-month HG recurrence-free survival (RFS). All patients who received at least one dose were included in efficacy and safety analyses. Results Forty patients received rAd–IFNα/Syn3 (1 × 10 11 vp/mL, n = 21; 3 × 10 11 vp/mL, n = 19) between November 5, 2012, and April 8, 2015. Fourteen patients (35.0%; 90% CI, 22.6% to 49.2%) remained free of HG recurrence 12 months after initial treatment. Comparable 12-month HG RFS was noted for both doses. Of these 14 patients, two experienced recurrence at 21 and 28 months, respectively, after treatment initiation, and one died as a result of an upper tract tumor at 17 months without a recurrence. rAd–IFNα/Syn3 was well tolerated; no grade four or five adverse events (AEs) occurred, and no patient discontinued treatment because of an adverse event. The most frequently reported drug-related AEs were micturition urgency (n = 16; 40%), dysuria (n = 16; 40%), fatigue (n = 13; 32.5%), pollakiuria (n = 11; 28%), and hematuria and nocturia (n = 10 each; 25%). Conclusion rAd—IFNα/Syn3 was well tolerated. It demonstrated promising efficacy for patients with HG NMIBC after BCG therapy who were unable or unwilling to undergo radical cystectomy.

Abstract Introduction Identifying at what point atrophy rates first change in Alzheimer's disease is important for informing design of presymptomatic trials. Methods Serial T1‐weighted magnetic resonance imaging scans of 94 participants (28 noncarriers, 66 carriers) from the Dominantly Inherited Alzheimer Network were used to measure brain, ventricular, and hippocampal atrophy rates. For each structure, nonlinear mixed‐effects models estimated the change‐points when atrophy rates deviate from normal and the rates of change before and after this point. Results Atrophy increased after the change‐point, which occurred 1–1.5 years (assuming a single step change in atrophy rate) or 3–8 years (assuming gradual acceleration of atrophy) before expected symptom onset. At expected symptom onset, estimated atrophy rates were at least 3.6 times than those before the change‐point. Discussion Atrophy rates are pathologically increased up to seven years before “expected onset”. During this period, atrophy rates may be useful for inclusion and tracking of disease progression.

Purpose To determine the past experiences with, current use of, and anticipated use of online learning and simulation-based education among practicing U.S. physicians, and how findings vary by age. Method The authors surveyed 4,648 randomly sampled board-certified U.S. physicians, September 2015 to April 2016, using Internet-based and paper questionnaires. Survey items (some optional) addressed past and current technology usage, perceived technology effectiveness, and anticipated future use of specific technology innovations. Results Of 988 respondents, 444 completed optional items. Of these, 429/442 (97.1%) had used online learning and 372/442 (84.2%) had used simulation-based education in the past five years. Desire for more online learning was modest (mean [standard deviation], 4.6 [1.5]; 1 = strongly disagree, 7 = strongly agree), as was desire for more simulation-based education (4.2 [1.7]). Both online learning and simulation-based education were perceived as effective (5.2 [1.4]; 5.0 [1.4]). Physicians believed they possess adequate skills for online learning (5.8 [1.2]) and that point-of-care learning is vital to effective patient care (5.3 [1.3]). Only 39.0% used objective performance data to guide their learning choices, although 64.6% agreed that such information would be useful. The highest-rated innovations included a central repository for listing educational opportunities and tracking continuing education credits, an app to award credit for answering patient-focused questions, 5-minute and 20-minute clinical updates, and an e-mailed “question of the week.” Responses to most survey items were similar across age groups. Conclusions Practicing physicians generally seem receptive and prepared to use a variety of educational technologies, regardless of age.

Purpose To characterize reporting of P values, confidence intervals (CIs), and statistical power in health professions education research (HPER) through manual and computerized analysis of published research reports. Method The authors searched PubMed, Embase, and CINAHL in May 2016, for comparative research studies. For manual analysis of abstracts and main texts, they randomly sampled 250 HPER reports published in 1985, 1995, 2005, and 2015, and 100 biomedical research reports published in 1985 and 2015. Automated computerized analysis of abstracts included all HPER reports published 1970–2015. Results In the 2015 HPER sample, P values were reported in 69/100 abstracts and 94 main texts. CIs were reported in 6 abstracts and 22 main texts. Most P values (≥77%) were ≤.05. Across all years, 60/164 two-group HPER studies had ≥80% power to detect a between-group difference of 0.5 standard deviations. From 1985 to 2015, the proportion of HPER abstracts reporting a CI did not change significantly (odds ratio [OR] 2.87; 95% CI 1.04, 7.88) whereas that of main texts reporting a CI increased (OR 1.96; 95% CI 1.39, 2.78). Comparison with biomedical studies revealed similar reporting of P values, but more frequent use of CIs in biomedicine. Automated analysis of 56,440 HPER abstracts found 14,867 (26.3%) reporting a P value, 3,024 (5.4%) reporting a CI, and increased reporting of P values and CIs from 1970 to 2015. Conclusions P values are ubiquitous in HPER, CIs are rarely reported, and most studies are underpowered. Most reported P values would be considered statistically significant.

Objectives: To compare the diagnostic yield of high-resolution volumetric T2-weighted MRI (HRT2-MRI) with high-resolution computed tomography (HRCT) for diagnosis of large vestibular aqueduct (LVA). Study Design: Three board-certified neuroradiologists performed an independent, blinded radiological review for diagnosing LVA with 2:1 age-matched controls on patients with both HRCT and HRT2-MRI imaging. Setting: Tertiary referral center. Patients: All patients between 2002 and 2016 with hearing loss who underwent both HRCT and HRT2-MRI and were diagnosed with LVA on either modality. Main Outcome Measures: Concordance rate for LVA between HRCT and HRT2-MRI. Results: Concordance rate for HRCT and HRT2-MRI for diagnosing LVA was 88% (124/141) when assessing both the midpoint and external aperture diameters. Fifteen ears had LVA on computed tomography (CT), but not on magnetic resonance imaging (MRI); in comparison, two ears had LVA on MRI, but not on CT (p = 0.002). Excellent inter-rater reliability among the three radiologists was demonstrated. Conclusion: Historically, HRCT has been the imaging modality of choice for diagnosing LVA. Although a higher concordance rate of HRT2-MRI was found compared with previous studies utilizing earlier MRI technology, HRCT still detected a larger number of patients with clinically significant hearing loss compared with MRI. Given the high concordance rate and efficacy of both modalities in diagnosing LVA, the ultimate decision of which modality to choose may depend on other patient-specific and clinical factors.

OBJECTIVEThe management of vestibular schwannoma (VS) remains controversial. One commonly cited advantage of microsurgery over other treatment modalities is that tumor removal provides the greatest chance of long-term cure. However, there are very few publications with long-term follow-up to support this assertion. The purpose of the current study is to report the very long-term risk of recurrence among a large historical cohort of patients who underwent microsurgical resection.METHODSThe authors retrospectively reviewed the medical records of patients who had undergone primary microsurgical resection of unilateral VS via a retrosigmoid approach performed by a single neurosurgeon-neurotologist team between January 1980 and December 1999. Complete tumor removal was designated gross-total resection (GTR), and anything less than complete removal was designated subtotal resection (STR). The primary end point was radiological recurrence-free survival. Time-to-event analyses were performed to identify factors associated with recurrence.RESULTSFour hundred fourteen patients met the study inclusion criteria and were analyzed. Overall, 67 patients experienced recurrence at a median of 6.9 years following resection (IQR 3.9–12.1, range 1.2–22.5 years). Estimated recurrence-free survival rates at 5, 10, 15, and 20 years following resection were 93% (95% CI 91–96, 248 patients still at risk), 78% (72–85, 88), 68% (60–77, 47), and 51% (41–64, 22), respectively. The strongest predictor of recurrence was extent of resection, with patients who underwent STR having a nearly 11-fold greater risk of recurrence than the patients treated with GTR (HR 10.55, p < 0.001). Among the 18 patients treated with STR, 15 experienced recurrence at a median of 2.7 years following resection (IQR 1.9–8.9, range 1.2–18.7). Estimated recurrence-free survival rates at 5, 10, 15, and 20 years following GTR were 96% (95% CI 93–98, 241 patients still at risk), 82% (77–89, 86), 73% (65–81, 46), and 56% (45–70, 22), respectively. Estimated recurrence-free survival rates at 5, 10, and 15 years following STR were 47% (95% CI 28–78, 7 patients still at risk), 17% (5–55, 2), and 8% (1–52, 1), respectively.CONCLUSIONSLong-term surveillance is required following microsurgical resection of VS even after GTR. Subtotal resection alone should not be considered a definitive long-term cure. These data emphasize the importance of long-term follow-up when reporting tumor control outcomes for VS.