BackgroundFentanyl-detected illicit drug overdose deaths in British Columbia (BC) recently increased dramatically from 13 deaths in 2012 to 90 deaths in 2014, signaling an emerging public health concern. Illicit fentanyl is sold as pills or powders, often mixed with other substances like heroin or oxycodone; reports from coroners suggested that fentanyl was frequently taken unknowingly by people who use drugs. This study aimed to assess the prevalence and characteristics of fentanyl use among clients accessing harm reduction (HR) services in BC.MethodsParticipants attending HR services at 17 sites across BC were invited to complete an anonymous questionnaire describing drugs they have used within the last 3 days and provide a urine sample to test for fentanyl. Data from eligible participants were analyzed using descriptive, bivariate, and multivariate statistical methods.ResultsSurveys from 17 HR sites were received, resulting in analysis of responses from 242 eligible participants. Most participants used multiple substances (median = 3), with crystal meth (59 %) and heroin (52 %) use most frequently reported. Seventy participants (29 %) tested positive for fentanyl, 73 % of whom did not report using fentanyl. Controlling for age, gender, and health authority, reported use of fentanyl (odds ratio (OR) = 6.13, 95 % confidence interval (CI) = [2.52, 15.78], p < 0.001) and crystal methamphetamine (OR = 3.82, 95 % CI = [1.79, 8.63], p < 0.001) use were significantly associated with fentanyl detection.ConclusionsThe proportion of those testing positive who did not report knowingly using fentanyl represents a considerable public health concern. The risk of overdose among this vulnerable population highlights the need for targeted HR strategies, such as increased accessibility to naloxone, overdose education, and urine screens.

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Intellectual disability affects about 3% of individuals globally, withB50% idiopathic. We designed an exonic-resolution array targeting all known submicroscopic chromosomal intellectual disability syndrome loci, causative genes for intellectual disability, and potential candidate genes, all genes encoding glutamate receptors and epigenetic regulators. Using this platform, we performed chromosomal microarray analysis on 165 intellectual disability trios (affected child and both normal parents). We identified and independently validated 36 de novo copy-number changes in 32 trios. In all, 67% of the validated events were intragenic, involving only exon 1 (which includes the promoter sequence according to our design), exon 1 and adjacent exons, or one or more exons excluding exon 1. Seventeen of the 36 copy-number variants involve genes known to cause intellectual disability. Eleven of these, including seven intragenic variants, are clearly pathogenic (involving STXBP1, SHANK3 (3 patients), IL1RAPL1, UBE2A, NRXN1, MEF2C, CHD7, 15q24 and 9p24 microdeletion), two are likely pathogenic (PI4KA, DCX), two are unlikely to be pathogenic (GRIK2, FREM2), and two are unclear (ARID1B, 15q22 microdeletion). Twelve individuals with genomic imbalances identified by our array were tested with a clinical microarray, and six had a normal result. We identified de novo copynumber variants within genes not previously implicated in intellectual disability and uncovered pathogenic variation of known intellectual disability genes below the detection limit of standard clinical diagnostic chromosomal microarray analysis.

Purpose: RNA-sequencing–based subtyping of pancreatic ductal adenocarcinoma (PDAC) has been reported by multiple research groups, each using different methodologies and patient cohorts. “Classical” and “basal-like” PDAC subtypes are associated with survival differences, with basal-like tumors associated with worse prognosis. We amalgamated various PDAC subtyping tools to evaluate the potential of such tools to be reliable in clinical practice. Experimental Design: Sequencing data for 574 PDAC tumors was obtained from prospective trials and retrospective public databases. Six published PDAC subtyping strategies (Moffitt regression tools, clustering-based Moffitt, Collisson, Bailey, and Karasinska subtypes) were used on each sample, and results were tested for subtype call consistency and association with survival. Results: Basal-like and classical subtype calls were concordant in 88% of patient samples, and survival outcomes were significantly different (P &lt; 0.05) between prognostic subtypes. Twelve percent of tumors had subtype-discordant calls across the different methods, showing intermediate survival in univariate and multivariate survival analyses. Transcriptional profiles compatible with that of a hybrid subtype signature were observed for subtype-discordant tumors, in which classical and basal-like genes were concomitantly expressed. Subtype-discordant tumors showed intermediate molecular characteristics, including subtyping gene expression (P &lt; 0.0001) and mutant KRAS allelic imbalance (P &lt; 0.001). Conclusions: Nearly 1 in 6 patients with PDAC have tumors that fail to reliably fall into the classical or basal-like PDAC subtype categories, based on two regression tools aimed toward clinical practice. Rather, these patient tumors show intermediate prognostic and molecular traits. We propose close consideration of the non-binary nature of PDAC subtypes for future incorporation of subtyping into clinical practice.

Background: Nutrition monitoring in the context of critical care presents unique challenges. Traditionally used anthropometric and biochemical markers may be difficult to obtain or confounded by factors such as fluid status and the inflammatory response. A previous survey identified 15 parameters in common use, all of which have confounding influences during critical illness. Materials and Methods: A literature search was conducted to assess current use of commonly used nutrition-monitoring parameters and to explore other possible methods that might be more useful. More than 1000 journal articles were reviewed to identify indicators of nutrition status or nutrition progress that have been used in ICU studies. The most recent 200 articles were examined to quantify the number of occurrences for each indicator. Each parameter was rated for availability and feasibility in the ICU. Results: There were 53 parameters found, including the 15 already identified as commonly used; 27 were used in ࣙ3 recent studies. Less-wellestablished nutrition indicators with potential for use in the ICU (moderate or high feasibility and availability) included ultrasound measurement of arm or leg muscle thickness, fatigue scoring with the Chalder scale, urinary creatinine assay, and serum insulin-like growth factor 1 level. None of these was among the commonly used indicators in recent studies. Conclusion: This study identifies commonly used nutrition-monitoring parameters and discusses their feasibility and availability in the critical care setting. Further investigation of nutrition indicators in ICU is needed, ideally as part of a randomized trial to reduce the effect of the many possible confounding factors. (Nutr Clin Pract. 2018;33:133-146)