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      Pre- and post-diagnostic β-blocker use and lung cancer survival: A population-based cohort study

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          Abstract

          Beta-blockers have been associated with decreased cancer mortality. However, evidence for lung cancer is sparse and reported beneficial effects might be based on biased analyses. In this so far largest study we investigated the association between β-blocker use and lung cancer survival. Therefore, patients with a lung cancer diagnosis between April 1998 and December 2011 were selected from a database linkage of the Netherlands Cancer Registry and the PHARMO Database Network. After matching eligible patients on the propensity score, adjusted hazard ratios (HRs) and corresponding 95% confidence intervals (CI) were calculated using Cox proportional hazards regression to investigate the association between pre-diagnostic and time-dependent β-blocker use and overall survival. Duration and dose-response analyses and stratified analyses by β-blocker type, histological subgroups and stage were conducted. Of 3,340 eligible lung cancer patients, 1437 (43%) took β-blockers four months prior to diagnosis. Pre-diagnostic β-blocker use was not associated with overall survival (HR 1.00 (0.92–1.08)) in the adjusted model. Time-dependent post-diagnostic analysis showed similar results with a HR of 1.03 (0.94–1.11). Trend analyses showed no association for cumulative dose (HR 0.99 (0.97–1.02)) and cumulative duration (HR 1.00 (0.96–1.05)). In conclusion, β-blocker use is not associated with reduced mortality among lung cancer patients.

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          A comparison of 12 algorithms for matching on the propensity score

          Propensity-score matching is increasingly being used to reduce the confounding that can occur in observational studies examining the effects of treatments or interventions on outcomes. We used Monte Carlo simulations to examine the following algorithms for forming matched pairs of treated and untreated subjects: optimal matching, greedy nearest neighbor matching without replacement, and greedy nearest neighbor matching without replacement within specified caliper widths. For each of the latter two algorithms, we examined four different sub-algorithms defined by the order in which treated subjects were selected for matching to an untreated subject: lowest to highest propensity score, highest to lowest propensity score, best match first, and random order. We also examined matching with replacement. We found that (i) nearest neighbor matching induced the same balance in baseline covariates as did optimal matching; (ii) when at least some of the covariates were continuous, caliper matching tended to induce balance on baseline covariates that was at least as good as the other algorithms; (iii) caliper matching tended to result in estimates of treatment effect with less bias compared with optimal and nearest neighbor matching; (iv) optimal and nearest neighbor matching resulted in estimates of treatment effect with negligibly less variability than did caliper matching; (v) caliper matching had amongst the best performance when assessed using mean squared error; (vi) the order in which treated subjects were selected for matching had at most a modest effect on estimation; and (vii) matching with replacement did not have superior performance compared with caliper matching without replacement. © 2013 The Authors. Statistics in Medicine published by John Wiley & Sons, Ltd.
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            Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer.

            This phase II trial investigated the safety and efficacy of two doses of bevacizumab, a monoclonal antibody to vascular endothelial growth factor, plus fluorouracil (FU)/leucovorin (LV) versus FU/LV alone in patients with metastatic colorectal cancer. One hundred four previously untreated patients with measurable metastatic colorectal cancer were randomly assigned to one of the following three treatment groups: 36 to FU (500 mg/m(2))/LV (500 mg/m(2)) alone, 35 to FU/LV + low-dose bevacizumab (5 mg/kg every 2 weeks), and 33 to FU/LV + high-dose bevacizumab (10 mg/kg every 2 weeks). FU/LV was given weekly for the first 6 weeks of each 8-week cycle. Compared with the FU/LV control arm, treatment with bevacizumab (at both dose levels) plus FU/LV resulted in higher response rates (control arm, 17%, 95% confidence interval [CI], 7% to 34%; low-dose arm, 40%, 95% CI, 24% to 58%; high-dose arm, 24%, 95% CI, 12% to 43%), longer median time to disease progression (control arm, 5.2 months, 95% CI, 3.5 to 5.6 months; low-dose arm, 9.0 months, 95% CI, 5.8 to 10.9 months; high-dose arm, 7.2 months, 95% CI, 3.8 to 9.2 months), and longer median survival (control arm, 13.8 months; 95% CI, 9.1 to 23.0 months; low-dose arm, 21.5 months, 95% CI, 17.3 to undetermined; high-dose arm, 16.1 months; 95% CI, 11.0 to 20.7 months). After cross-over, two of 22 patients had a partial response to bevacizumab alone. Thrombosis was the most significant adverse event and was fatal in one patient. Hypertension, proteinuria, and epistaxis were other potential safety concerns. The encouraging results of this randomized trial support further study of bevacizumab 5 mg/kg plus chemotherapy as first-line therapy for metastatic colorectal cancer.
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              A randomized, controlled trial of oral propranolol in infantile hemangioma.

              Oral propranolol has been used to treat complicated infantile hemangiomas, although data from randomized, controlled trials to inform its use are limited.
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                Author and article information

                Contributors
                h.brenner@dkfz.de
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                6 June 2017
                6 June 2017
                2017
                : 7
                : 2911
                Affiliations
                [1 ]ISNI 0000 0004 0492 0584, GRID grid.7497.d, Division of Clinical Epidemiology and Aging Research, , German Cancer Research Center (DKFZ), ; Heidelberg, Germany
                [2 ]ISNI 0000 0001 0328 4908, GRID grid.5253.1, Department of Clinical Pharmacology and Pharmacoepidemiology, , University Hospital of Heidelberg, ; Heidelberg, Germany
                [3 ]GRID grid.5963.9, Center for Medical Biometry and Medical Informatics, , Institute for Medical Biometry and Statistics, Medical Center, University of Freiburg, ; Freiburg, Germany
                [4 ]ISNI 0000 0004 1786 4649, GRID grid.418604.f, , PHARMO Institute for Drug Outcomes Research, ; Utrecht, The Netherlands
                [5 ]ISNI 0000 0004 0501 9982, GRID grid.470266.1, , Netherlands Comprehensive Cancer Organisation, ; Utrecht, The Netherlands
                [6 ]ISNI 0000 0001 0328 4908, GRID grid.5253.1, Division of Preventive Oncology, , National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ), ; Heidelberg, Germany
                [7 ]ISNI 0000 0004 0492 0584, GRID grid.7497.d, German Cancer Consortium (DKTK), , German Cancer Research Center (DKFZ), ; Heidelberg, Germany
                Author information
                http://orcid.org/0000-0003-0404-7394
                Article
                2913
                10.1038/s41598-017-02913-8
                5460218
                28588274
                b0b9dc44-bd69-413c-8d3a-0f359ea550ea
                © The Author(s) 2017

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 9 January 2017
                : 20 April 2017
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