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Therefore, an effective handling of failure requires management to use appropriate interventions targeted at the challenges faced by that particular pattern of failure in the age of different firms.Purpose Painful metastatic bone involvement is common in advanced stages of many cancers. Between available radionuclides for bone pain palliation, no consensus has been reached on lutetium ethylenediaminetetramethylene phosphonate (177Lu-EDTMP) administration in this milieu. The aim of this study is to evaluate the treatment efficacy, safety profile, and toxicities of 177Lu-EDTMP in patients with metastatic bone involvement, according to the published literature. Methods A comprehensive literature search of PubMed/MEDLINE, Scopus, and Google Scholar databases was carried out to retrieve pertinent articles published until January 2019, concerning the clinical efficacy and safety of 177Lu-EDTMP for bone pain palliative purposes. [https://www.selleckchem.com/products/azd9291.html read more] Results Eight studies (172 patients) were included. This analysis revealed statistically significant effect of 177Lu-EDTMP therapy on the visual analog score (4.84% (95% CI 3.88-5.81; p  less then  0.001), bone palliative pain response (84%, 95% CI 75%-90%; p  less then  0.001), and Karnofsky performance status (21%, 95% CI 18%-24%; p  less then  0.001) overall (as well as in the high-dose and low-dose subgroups). Complete palliative pain response to treatment was observed in 32% (95% CI 16%-53%) of patients receiving 177Lu-EDTMP. Anemia was found to be the most common hematologic toxicity imposed by this therapeutic approach (grade I/II anemia in 24% (95% CI 14%-38%; p  less then  0.001) and grade III/IV anemia in 19% (95% CI 12%-28%; p  less then  0.001)). Conclusions 177Lu-EDTMP seems to have comparable efficacy and safety profile as that of the frequently administered radiopharmaceuticals for bone palliation. Therefore, this agent can be a good option for bone pain palliative purposes, in case of limited access to other bone palliative radiopharmaceuticals.Purpose This clinical focus article is a companion to the work of Erdman et al. (2019), in which we described the rationale, development, and implementation of the standard-of-care protocol used in the Tinnitus Retraining Therapy Trial (TRTT), a multicenter, placebo-controlled, randomized, definitive efficacy trial of tinnitus retraining therapy (TRT). We now describe the historical background, development, and standardized implementation and delivery of the TRT counseling protocol (tinnitus counseling [TC]) used in the TRTT. TC is conjectured to be the key component in the TRT protocol for initiating the habituation process that reduces the response to the tinnitus signal and, ultimately, reduces its impact. In the TRTT, participants assigned to receive TC achieved &gt; 30% reduction in the impact of tinnitus. Method and Results The design and implementation of standardized treatments in multisite randomized controlled trials presents many challenges for investigators. Here, subsequent to presenting the background, rationale, and the TRT protocol model, we describe the development, refinement, and training/certification for standardized delivery of TC in the TRTT. The primary challenges encountered while distilling and streamlining TC for standardized delivery across multiple clinicians and their replacements at six participating military treatment centers in the TRTT are considered, and the resulting counseling protocol is detailed. Conclusions The standardized and streamlined TC used in the TRTT was successful for treating debilitating tinnitus among persons with functionally adequate unaided hearing sensitivity. The structured TC protocol described here appears to be the main determinant of the significant and sizable TRT treatment effects measured in the TRTT, thus bolstering the merits of this standardized counseling approach as one model for the clinical implementation of TRT for the treatment of primary tinnitus.Atherosclerosis (AS) is a chronic inflammatory disease accompanied by complex pathological changes, such as endothelial dysfunction, foam cell formation, and vascular smooth muscle cell proliferation. Many approaches, including regulating AS-related gene expression in the transcriptional or post-transcriptional level, contribute to alleviating AS development. The DNA methylation is a crucial epigenetic modification in regulating cell function by silencing the relative gene expression. The microRNA (miRNA) is a type of noncoding RNA that plays an important role in gene post-transcriptional regulation and disease development. The DNA methylation and the miRNA are important epigenetic factors in AS. However, recent studies have found a mutual regulation between these two factors in AS development. In this study, recent insights into the roles of miRNA and DNA methylation and their interaction in the AS progression are reviewed.Purpose Traditional clinical measures of cochlear implant (CI) recipient performance may not fully evaluate the benefit of bimodal listening (hearing aid contralateral to a CI). The clinical assessment of spatial release from masking (SRM) may be a sensitive measure of the benefit of listening with bimodal stimulation. This study compared the SRM of pediatric bimodal and bilateral CI listeners using a clinically feasible method, and investigated variables that may contribute to speech recognition performance with spatially separated maskers. Method Forty pediatric bimodal (N = 20) and bilateral CI (N = 20) participants were assessed in their best aided listening condition on sentence recognition in a four-talker masker. Testing was completed with target and masker colocated at 0° azimuth, and with the masker directed at 90° to either ear. SRM was calculated as the difference in performance between the colocated and each 90° condition. A two-way mixed-methods analysis of variance was used to compare performance between groups in the three masker conditions. Multiple regression analyses were conducted to investigate potential predictors for SRM asymmetry including hearing history, unaided thresholds, word recognition, duration of device use, and acoustic bandwidth. Results Both groups demonstrated SRM, with significantly better recognition in each 90° condition as compared to the colocated condition. The groups did not differ significantly in SRM. The multiple regression analyses did not reveal any significant predictors of SRM asymmetry. Conclusions Bimodal and bilateral CI listeners demonstrated similar amounts of SRM. While no specific variables predicted SRM asymmetry in bimodal listeners, pediatric bimodal and bilateral CI recipients should expect similar amounts of SRM regardless of the side of the masker. SRM asymmetry in pediatric bimodal listeners may signal a need for consideration of a second CI.