Developing an Improved Statistical Approach for Survival Estimation in Bone Metastases Management: The Bone Metastases Ensemble Trees for Survival (BMETS) Model.

PURPOSE: To determine whether a machine learning approach optimizes survival estimation for patients with symptomatic bone metastases (SBM), we developed the Bone Metastases Ensemble Trees for Survival (BMETS) to predict survival using 27 prognostic covariates. To establish its relative clinical utility, we compared BMETS with 2 simpler Cox regression models used in this setting. METHODS AND MATERIALS: For 492 bone sites in 397 patients evaluated for palliative radiation therapy (RT) for SBM from January 2007 to January 2013, data for 27 clinical variables were collected. These covariates and the primary outcome of time from consultation to death were used to build BMETS using random survival forests. We then performed Cox regressions as per 2 validated models: Chow's 3-item (C-3) and Westhoff's 2-item (W-2) tools. Model performance was assessed using cross-validation procedures and measured by time-dependent area under the curve (tAUC) for all 3 models. For temporal validation, a separate data set comprised of 104 bone sites treated in 85 patients in 2018 was used to estimate tAUC from BMETS. RESULTS: Median survival was 6.4 months. Variable importance was greatest for performance status, blood cell counts, recent systemic therapy type, and receipt of concurrent nonbone palliative RT. tAUC at 3, 6, and 12 months was 0.83, 0.81, and 0.81, respectively, suggesting excellent discrimination of BMETS across postconsultation time points. BMETS outperformed simpler models at each time, with respective tAUC at each time of 0.78, 0.76, and 0.74 for the C-3 model and 0.80, 0.78, and 0.77 for the W-2 model. For the temporal validation set, respective tAUC was similarly high at 0.86, 0.82, and 0.78. CONCLUSIONS: For patients with SBM, BMETS improved survival predictions versus simpler traditional models. Model performance was maintained when applied to a temporal validation set. To facilitate clinical use, we developed a web platform for data entry and display of BMETS-predicted survival probabilities.

Who is 'Molly'? MDMA adulterants by product name and the impact of harm-reduction services at raves.

Methylenedioxymethamphetamine (MDMA), often sold as 'Ecstasy' or 'Molly', is commonly used at music festivals and reported to be responsible for an increase in deaths over the last decade. Ecstasy is often adulterated and contains compounds that increase morbidity and mortality. While users and clinicians commonly assume that products sold as Molly are less-adulterated MDMA products, this has not been tested. Additionally, while pill-testing services are sometimes available at raves, the assumption that these services decrease risky drug use has not been studied. This study analyzed data collected by the pill-testing organization, DanceSafe, from events across the United States from 2010 to 2015. Colorimetric reagent assays identified MDMA in only 60% of the 529 samples collected. No significant difference in the percentage of samples testing positive for MDMA was determined between Ecstasy and Molly. Individuals were significantly less likely to report intent to use a product if testing did not identify MDMA (relative risk (RR) = 0.56, p = 0.01). Results suggest that Molly is not a less-adulterated substance, and that pill-testing services are a legitimate harm-reduction service that decreases intent to consume potentially dangerous substances and may warrant consideration by legislators for legal protection. Future research should further examine the direct effects of pill-testing services and include more extensive pill-testing methods.

A Comparative Study of Peripheral Immune Responses to Taenia solium in Individuals with Parenchymal and Subarachnoid Neurocysticercosis.

BACKGROUND: The ability of Taenia solium to modulate the immune system likely contributes to their longevity in the human host. We tested the hypothesis that the nature of the immune response is related to the location of parasite and clinical manifestations of infection. METHODOLOGY: Peripheral blood mononuclear cells (PBMC) were obtained from untreated patients with neurocysticercosis (NCC), categorized as having parenchymal or subarachnoid infection by the presence of cysts exclusively within the parenchyma or in subarachnoid spaces of the brain, and from uninfected (control) individuals matched by age and gender to each patient. Using multiplex detection technology, sera from NCC patients and controls and cytokine production by PBMC after T. solium antigen (TsAg) stimulation were assayed for levels of inflammatory and regulatory cytokines. PBMC were phenotyped by flow cytometry ex vivo and following in vitro stimulation with TsAg. PRINCIPAL FINDINGS: Sera from patients with parenchymal NCC demonstrated significantly higher Th1 (IFN-γ/IL-12) and Th2 (IL-4/IL-13) cytokine responses and trends towards higher levels of IL-1ß/IL-8/IL-5 than those obtained from patients with subarachnoid NCC. Also higher in vitro antigen-driven TNF-ß secretion was detected in PBMC supernatants from parenchymal than in subarachnoid NCC. In contrast, there was a significantly higher IL-10 response to TsAg stimulation in patients with subarachnoid NCC compared to parenchymal NCC. Although no differences in regulatory T cells (Tregs) frequencies were found ex vivo, there was a trend towards greater expansion of Tregs upon TsAg stimulation in subarachnoid than in parenchymal NCC when data were normalized for the corresponding controls. CONCLUSIONS/SIGNIFICANCE: T. solium infection of the subarachnoid space is associated with an enhanced regulatory immune response compared to infection in the parenchyma. The resulting anti-inflammatory milieu may represent a parasite strategy to maintain a permissive environment in the host or diminish inflammatory damage from the host immune response in the central nervous system.