Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Naloxone availability and dispensing in Indiana pharmacies 2 years after the implementation of a statewide standing order

Objectives: This study examined changes in rates of pharmacy naloxone stocking and dispensing in Indiana between 2016 and 2018 and explored supplemental variables and factors that may have affected observed differences. Methods: Researchers used data from 2 existing datasets that were collected from managing pharmacists who responded to statewide pharmacy censuses in 2016 and 2018. After identifying all cases in which a pharmacy's managing pharmacist responded in both 2016 and 2018 censuses, researchers conducted a nonparametric statistical comparison of naloxone stocking and dispensing rates in 107 Indiana pharmacies. Additional descriptive data regarding naloxone-related pharmacy policies and educational programs during those years were collected in 2019 from pharmacy corporations operating food stores or chain pharmacies in Indiana and from the Indiana Pharmacists Association. Results: Pharmacy stocking and dispensing in Indiana increased from 2016 to 2018. In 2016, 57% of pharmacies reported stocking naloxone compared with 92.5% in 2018 (P < 0.001). Similarly, 23.4% of pharmacies reported dispensing naloxone in 2016 compared with 76.6% of pharmacies in 2018 (P < 0.001). All responding pharmacy corporations and the state pharmacy association reported offering self-directed volunteer-training programs regarding naloxone since 2016. In addition, they reported that company policy and procedures regarding naloxone were put into place in response to the 2016 statewide standing order. Conclusion: Pharmacy naloxone stocking and dispensing increased in the 2 years after the statewide standing order was issued. The effect of the order itself was likely moderated or mediated by corporate responses to the law. Research examining the impact of naloxone-availability policies on pharmacy practice and patient incomes should longitudinally examine data after policy implementation and with covariates that include type of pharmacy (e.g., chain or independent), location, and opioid overdose-associated mortality rates. (C) 2020 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.12 month embargo; available online 06 January 2020This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Relationship Between Substance Use and the Onset of Spinal Cord Injuries: A Medical Chart Review

Background: Opioid misuse is a leading health care concern within the United States. In many cases, opioid misuse and opioid use disorder are associated with pain, a secondary health condition affecting individuals with spinal cord injury (SCI). Further, substance use is a known risk factor for SCI, resulting in the potential for a substance-related risk trajectory running from pre- to post-SCI. However, little research has examined substance use prior to SCI since the opioid epidemic began, and so the relative risk of opioids to patients with SCI is unclear. Objective: To determine whether individuals with SCI tested positive for substance use at the time of injury and identify the primary substances used at the time of injury. Methods: This study retrospectively reviewed all medical charts of individuals ages 18 and older who had sustained an SCI during an identified 18-month period and received medical care at a selected level 1 trauma center in the Midwest. Results: Data revealed an 80% combined positive toxicology and/or self-report of substance use immediately prior to the onset of the SCI. Twenty-five percent of males were positive for more than one substance at time of injury. Substances used prior to injury, listed most to least prevalent, were opioids (37.5%), alcohol (25%), marijuana (25%), methamphetamines (12.5%), benzodiazepines (12.5%), followed by cocaine (6.25%) and synthetic cathinone (6.25%). Conclusion: Although opioids were the most common substance used prior to SCI, none of the individuals positive for opioids at the time of injury were identified by the reviewing medical professional as having pain as a secondary health condition either prior to or after injury. However, pain is commonly listed as the primary health concern among individuals living with SCI, and the possibility of opioid use prior to injury likely warrants pain management planning that includes careful pharmacological and nonpharmacological interventions

I could take the judgment if you could just provide the service: non-prescription syringe purchase experience at Arizona pharmacies, 2018

Background: Community pharmacies are important for health access by rural populations and those who do not have optimum access to the health system, because they provide myriad health services and are found in most communities. This includes the sale of non-prescription syringes, a practice that is legal in the USA in all but two states. However, people who inject drugs (PWID) face significant barriers accessing sterile syringes, particularly in states without laws allowing syringe services programming. To our knowledge, no recent studies of pharmacy-based syringe purchase experience have been conducted in communities that are both rural and urban, and none in the Southwestern US. This study seeks to understand the experience of retail pharmacy syringe purchase in Arizona by PWID. Methods: An interview study was conducted between August and December 2018 with 37 people living in 3 rural and 2 urban Arizona counties who identified as current or former users of injection drugs. Coding was both a priori and emergent, focusing on syringe access through pharmacies, pharmacy experiences generally, experiences of stigma, and recommendations for harm reduction services delivered by pharmacies. Results: All participants reported being refused syringe purchase at pharmacies. Six themes emerged about syringe purchase: (1) experience of stigma and judgment by pharmacy staff, (2) feelings of internalized stigma, (3) inconsistent sales outcomes at the same pharmacy or pharmacy chain, (4) pharmacies as last resort for syringes, (5) fear of arrest for syringe possession, and (6) health risks resulting from syringe refusal. Conclusions: Non-prescription syringe sales in community pharmacies are a missed opportunity to improve the health of PWID by reducing syringe sharing and reuse. Yet, current pharmacy syringe sales refusal and stigmatization by staff suggest that pharmacy-level interventions will be necessary to impact pharmacy practice. Lack of access to sterile syringes reinforces health risk behaviors among PWID. Retail syringe sales at pharmacies remain an important, yet barrier-laden, element of a comprehensive public health response to reduce HIV and hepatitis C among PWID. Future studies should test multilevel evidence-based interventions to decrease staff discrimination and stigma and increase syringe sales.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Sex differences in oncogenic mutational processes

Funder: Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada (NSERC Canadian Network for Research and Innovation in Machining Technology); doi: https://doi.org/10.13039/501100002790Funder: Genome Canada (Génome Canada); doi: https://doi.org/10.13039/100008762Funder: Canada Foundation for Innovation (Fondation canadienne pour l'innovation); doi: https://doi.org/10.13039/501100000196Funder: Terry Fox Research Institute (Institut de Recherche Terry Fox); doi: https://doi.org/10.13039/501100004376Abstract: Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Sex differences in oncogenic mutational processes

Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research.Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research.Peer reviewe