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The TOPAZ-1 phase III trial showed a survival benefit with durvalumab plus gemcitabine and cisplatin in patients with advanced biliary tract cancer (BTC). To understand this combination's real-world efficacy and tolerability, we conducted a global multicenter retrospective analysis of its first-line treatment outcomes. We included patients with unresectable, locally advanced, or metastatic BTC treated with durvalumab, gemcitabine, and cisplatin at 39 sites in 11 countries (Europe, the United States, and Asia). The primary endpoint was overall survival (OS). 666 patients were enrolled. Median OS was 15.1 months and median PFS was 8.2 months. The investigator-assessed overall response rate was 32.7 %, with stable disease in 45.2 % of patients. High baseline CEA levels, ECOG PS > 0, metastatic disease, and NLR > 3 were associated with poor survival. Any grade adverse events (AEs) occurred in 92.9 % of patients (grade >2: 46.6 %). Immune-related AEs (irAEs) occurred in 20.0 % (grade >2: 2.5 %). Three deaths (0.5 %) were deemed treatment-related, none linked to immunotherapy. Common irAEs were rash (8.2 % all grades; 0.3 % grade >2), itching (10.3 % all grades; 0.2 % grade >2), and hypothyroidism (5.1 % all grades; 0.3 % grade >2). Durvalumab discontinuation rate due to AEs was 1.5 %. ESMO-recommended genes were analyzed and no outcome differences were found. A comparative analysis with a historical cohort of patients treated with chemotherapy alone confirmed the positive survival impact of durvalumab in combination with cisplatin/gemcitabine. This first global real-world analysis largely confirmed the TOPAZ-1 findings, supporting gemcitabine, cisplatin, and durvalumab as a first-line standard of care for patients with advanced BTC. • Real-world evidence is gaining momentum in clinical oncology in recent years. • Durvalumab improved survival in patients with advanced biliary tract cancer. • 666 patients were treated: median OS of 15.1 months and median PFS of 8.2 months. • The results confirmed the results achieved in the TOPAZ-1 trial. [ABSTRACT FROM AUTHOR]

In this paper, I use a large set of macroeconomic and financial predictors to forecast US recession periods. I adopt Bayesian methodology with shrinkage in the parameters of the probit model for the binary time series tracking the state of the economy. The in-sample and out-of-sample results show that utilizing a large cross-section of indicators yields superior US recession forecasts in comparison to a number of parsimonious benchmark models. Moreover, the datarich probit model gives similar accuracy to the factor-based model for the 1-month-ahead forecasts, while it provides superior performance for 1-year-ahead predictions. Finally, in a pseudo-real-time application for the Great Recession, I find that the large probit model with shrinkage is able to pick up the recession signals in a timely fashion and does well in comparison to the more parsimonious specification and to nonparametric alternatives. [ABSTRACT FROM AUTHOR]

This study examines the association between fair value measurements and the cost of equity capital under different fair value valuation methods, and assesses the impact of corporate governance on this relationship for US financial firms. We find that firms' cost of equity capital is negatively associated with more verifiable fair value assets and positively related to less verifiable fair value assets. Furthermore, the positive association between less verifiable fair value assets and the cost of equity capital is mitigated under better corporate governance. The differential impact between more and less verifiable assets becomes smaller for firms with stronger governance. Our findings contribute to the ongoing debate on fair value regulation by investigating the economic consequences of adopting Statement of Financial Accounting Standards No. 157, Fair Value Measurements (SFAS 157) and the importance of audit committee financial expertise on fair value reporting. We also provide evidence on the importance of board independence, internal control strength, auditor industry specialists, and audit committee financial experts in fair value reporting. [ABSTRACT FROM AUTHOR]

Background Uncertainty exists regarding the prevalence and moderators of migraine comorbidity among people with bipolar disorder (BD). We conducted a meta-analysis and meta-regression to investigate the prevalence and moderators of migraine among people with BD. Method Two authors independently searched major electronic databases from inception till 02/2015. Articles were included that reported the prevalence of migraine in people with BD with or without a control group. A random effects meta-analysis and exploratory meta-regression were conducted. Results Fourteen studies were included encompassing 3976 individuals with BD (mean age 35.5 years, SD 7.6, 29% male). The overall pooled prevalence of migraine was 34.8% (95% CI=25.54–44.69). The prevalence of migraine was higher among people with BD-II (54.17%, 95% CI=31.52–75.95, n =742) compared to BD-I (32.7%, 95% CI=18.16–49.19, n =2138, z =3.97, p <0.0001). The prevalence of migraine was 33.9% (95% CI=26.02–42.44), 39.5% (95% CI=18.81–62.39) and 47.11% (95% CI=22.24–72.77) in North America, Europe and South America respectively. The prevalence of migraine was higher when classified according to recognized criteria at 47.91% (95% CI=32.51–63.5) compared to non-recognized criteria (20.0%, 95% CI=12.44–29.06, z =−8.40, p <0.0001). Meta regression suggests mean age may be a potential moderator. Conclusion Migraine is common and burdensome among people with BD. People with BD-II appear to be particularly affected. Nonetheless, future research is required to better understand these relationships, with a special emphasis toward the course specifiers of comorbid migraine cases of either BD-I vs. BD-II. [ABSTRACT FROM AUTHOR]