Different Evidence-Summaries have Implications for Contextualizing Findings of Meta-Analysis of Diagnostic Tests.
J Clin Epidemiol. 2019 Jan 14;:
Authors: Zgodic A, Schmid CH, Olkin I, Trikalinos TA
OBJECTIVE: To evaluate diagnostic tests, analysts use meta-analyses to provide inputs to parameters in decision models. Choosing parameter estimands from meta-analyses requires understanding the meta-analytic and decision-making contexts.
STUDY DESIGN AND SETTING: We expand on an analysis comparing positron emission tomography (PET), PET with computed tomography (PET/CT), and conventional workup (CW) in women with suspected recurrent breast cancer. We discuss Bayesian meta-analytic summaries (posterior mean over a set of existing studies, posterior estimate in an existing study, posterior predictive mean in a new study) used to estimate diagnostic test parameters (prevalence, sensitivity, specificity) needed to calculate quality-adjusted life years in a decision model contextualizing PET, PET/CT, and CW.
RESULTS: The mean and predictive mean give similar estimates, but the latter displays greater uncertainty. Namely, PET/CT outperforms CW on average but may not do better than CW when implemented in future settings.
CONCLUSION: Selecting estimands for decision model parameters from meta-analyses requires understanding the relationship between decision settings and meta-analysis studies' settings, specifically whether the former resemble one or all study settings or represent new settings. We provide an algorithm recommending appropriate estimands as input parameters in decision models for diagnostic tests to obtain output parameters consistent with the decision context.
PMID: 30654146 [PubMed - as supplied by publisher]
Improved patient-reported outcomes after autologous fat transplantation and corrective surgery after breast surgery.
J Plast Surg Hand Surg. 2019 Jan 17;:1-8
Authors: Lindegren A, Schultz I, Wickman M
BACKGROUND: Autologous fat transplantation (AFT) is being increasingly used to improve the results after breast-conserving surgery and breast reconstruction. However, studies on patient-reported outcomes (PROs) and health-related quality of life (HRQoL) after AFT are scarce. The aim of this prospective longitudinal case-series study was to assess PRO in women who had undergone AFT after surgery for breast cancer or risk-reducing mastectomy.
METHODS: Fifty women, who had undergone breast-conserving surgery or breast reconstruction, needing corrective surgery, were consecutively included between 2008 and 2013. A 20-item study-specific questionnaire (SSQ) and the Short Form Health Survey (SF-36) were used pre-operatively and 6 months, 1 year and 2 years post-operatively, to evaluate PRO and HRQoL.
RESULTS: The patients underwent three (1-4) AFT procedures, with the injection of 164 ml (median) (range 40-516) fat. Thirty-eight and 34 patients completed the study-specific questionnaire and the SF-36, respectively, both pre-operatively and after 2 years. Sixteen of the 20 items in the SSQ were improved after 2 years, including breast size (p < 0.0001), shape (p < 0.0001), appearance (p < 0.0001), softness of the breast (p = 0.001), pain in the region (p = 0.005), scarring from previous breast surgery (p < 0.001) and willingness to participate in public physical activities (p < 0.001). HRQoL did not largely differ before and after AFT, or between the study group and a reference population.
CONCLUSIONS: AFT alone or in combination with other corrective surgical procedures, improved PRO after breast-conserving surgery and breast reconstruction in both irradiated and non-irradiated women.
PMID: 30652957 [PubMed - as supplied by publisher]
Structure-Based Discovery of a Selective KDM5A Inhibitor that Exhibits Anti-Cancer Activity via Inducing Cell Cycle Arrest and Senescence in Breast Cancer Cell Lines.
Cancers (Basel). 2019 Jan 15;11(1):
Authors: Yang GJ, Ko CN, Zhong HJ, Leung CH, Ma DL
Breast cancer is the one of the most frequent causes of female cancer mortality. KDM5A, a histone demethylase, can increase the proliferation, metastasis, and drug resistance of cancers, including breast cancer, and is thus an important therapeutic target. In the present work, we performed hierarchical virtual screening towards the KDM5A catalytic pocket from a chemical library containing 90,000 compounds. Using multiple biochemical methods, the cyclopenta[c]chromen derivative 1 was identified as the top candidate for KDM5A demethylase inhibitory activity. Compared with the well-known KDM5 inhibitor CPI-455 (18), 1 exhibited higher potency against KDM5A and much higher selectivity for KDM5A over both KDM4A and other KDM5 family members (KDM5B and KDM5C). Additionally, compound 1 repressed the proliferation of various KDM5A-overexpressing breast cancer cell lines. Mechanistically, 1 promoted accumulation of p16 and p27 by blocking KDM5A-mediated H3K4me3 demethylation, leading to cell cycle arrest and senescence. To date, compound 1 is the first cyclopenta[c]chromen-based KDM5A inhibitor reported, and may serve as a novel motif for developing more selective and efficacious pharmacological molecules targeting KDM5A. In addition, our research provides a possible anti-cancer mechanism of KDM5A inhibitors and highlights the feasibility and significance of KDM5A as a therapeutic target for KDM5A-overexpressing breast cancer.
PMID: 30650517 [PubMed]