Risk of respiratory depression with opioids and concomitant gabapentinoids.

Introduction:The combination of opioids and central nervous system depressants such as benzodiazepines and barbiturates has an additive effect on the frequency of oversedation and respiratory depression requiring naloxone use in hospitalized patients. Gabapentinoids (gabapentin and pregabalin) are frequently prescribed with opioids for their opioid-sparing and adjuvant analgesic effects. There is limited literature on the risk of respiratory depression due to the combination of opioids and gabapentinoids requiring naloxone administration. Methods:This retrospective study evaluated patients who were prescribed opioids and at least one dose of naloxone between March 1, 2014 and September 30, 2016. The primary objective of this study was to compare the frequency of respiratory depression among patients who received naloxone and opioids (non-gabapentinoid group) with those who received naloxone, opioids, and gabapentinoids (gabapentinoid group). Secondary objectives included comparing the association of oversedation, using the Pasero Opioid-induced Sedation Scale, and various risk factors with those in the gabapentinoid group. Results:A total of 153 patient episodes of naloxone administration (102 in the non-gabapentinoid and 51 in the gabapentinoid groups) in 125 unique patients were included in the study. For the primary objective, there were 33 episodes of respiratory depression associated with the non-gabapentinoid group (33/102=32.4%) versus 17 episodes of respiratory depression with the gabapentinoid group (17/51=33.3%) (p=0.128). Secondary objectives showed a significant association between respiratory depression and surgery in the previous 24 hours (p=0.036) as well as respiratory depression and age >65 years (p=0.031) for patients in the non-gabapentinoid group compared to the gabapentinoid group. Conclusion:There was no significant association of respiratory depression in the gabapentinoid group versus the non-gabapentinoid group. There was an increased risk of respiratory depression in the gabapentinoid group, specifically in patients who had surgery within the previous 24 hours

GCAM v5.1: representing the linkages between energy, water, land, climate, and economic systems

This paper describes GCAM v5.1, an open source model that represents the linkages between energy, water, land, climate, and economic systems. GCAM is a market equilibrium model, is global in scope, and operates from 1990 to 2100 in 5-year time steps. It can be used to examine, for example, how changes in population, income, or technology cost might alter crop production, energy demand, or water withdrawals, or how changes in one region's demand for energy affect energy, water, and land in other regions. This paper describes the model, including its assumptions, inputs, and outputs. We then use 11 scenarios, varying the socioeconomic and climate policy assumptions, to illustrate the results from the model. The resulting scenarios demonstrate a wide range of potential future energy, water, and land uses. We compare the results from GCAM v5.1 to historical data and to future scenario simulations from earlier versions of GCAM and from other models. Finally, we provide information on how to obtain the model.</p

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

A Multi-Centered Case Series Highlighting the Clinical Use and Dosing of Lidocaine and Mexiletine for Refractory Cancer Pain

Lidocaine infusion for pain control has been used for years. While some centers transition from continuous infusion lidocaine to oral mexiletine, there are no published studies to guide this conversion in pain and palliative care settings. This is a retrospective case series of 10 cancer patients across four institutions, with attention to dosing of both agents, and subsequent decrease in morphine-equivalent daily dosing (MEDD). The mean age was 55 years (range 34-78). The mean bolus dose of lidocaine was 1.6 mg/kg, infused over an average of 24 minutes, followed by a mean continuous infusion rate of 1.1 mg/kg/hr, and the infusion was continued for an average of 14.1 hours (range of 0.2 - 28 hours). The mean starting daily mexiletine dose was 400 mg (in 2-3 divided doses) and final dosing averaged 500 mg/day. The mean MEDD prior to starting lidocaine was 1118 mg/24 hours, which, by the time of final mexiletine dosing, was 882 mg/24 hours, a 21% MEDD reduction. The average hospital length of stay was 14 days. There was no lidocaine-induced toxicity and no lidocaine levels were obtained. Two of the 10 patients stopped mexiletine early, one from confusion four days after initiation of mexiletine, and the other after six weeks due to dizziness and visual changes. For cancer patients with suboptimal pain control on large doses of opioid, lidocaine infusion followed by oral mexiletine was well tolerated and effective

Variable Patterns of Continuous Morphine Infusions at End of Life

BackgroundContinuous morphine infusions (CMIs) treat pain and dyspnea at the end of life (EOL). CMIs may be initiated at an empiric rate and/or are rapidly escalated without proper titration.ObjectiveThe study objective was to evaluate CMI patterns at the EOL.MethodsThis single-center, retrospective chart review evaluated adult patients who died while receiving CMI at EOL. Patient demographics and opioid dosing information were extracted from an electronic medical record. Twenty-four hour IV morphine equivalent was calculated prior to CMI initiation and at the time of death.ResultsOf the 190 patient charts, 63.2% (n=120) received no bolus doses prior to CMI initiation. Mean 24-hour IV morphine equivalent prior to CMI initiation was 49.3 mg (range: 0-1200 mg, SD 384.9) and at time of death was 267.1 mg (12.0-5193.2 mg, SD 442.2), representing an increase of +442%. Mean CMI starting rate was 3.3 mg/hour (0.4-30.0 mg/hour, SD 3.6) with titration at time of death to a mean of 7.7 mg/hour (0.4-70.0 mg/hour, SD 9.4), representing an increase of +130%. Mean number of CMI rate adjustments was 2.5 (0-5, SD 3.3); and number of bolus doses administered between titrations was 4.2 (0-27, SD 4.8). Mean time from CMI initiation to death was 15.5 hours (0.05-126.9 hours, SD 21.7). There was a negative association between rate of infusion increase per hour and total number of hours on CMI (r=-0.2, p=0.0062).ConclusionsHospitalized patients at EOL had a much higher 24-hour IV morphine equivalents and CMI rates at time of death compared to CMI initiation. Variability was observed in the number of CMI rate adjustments and the number of bolus doses administered

Risk of respiratory depression with opioids and concomitant gabapentinoids.

IntroductionThe combination of opioids and central nervous system depressants such as benzodiazepines and barbiturates has an additive effect on the frequency of oversedation and respiratory depression requiring naloxone use in hospitalized patients. Gabapentinoids (gabapentin and pregabalin) are frequently prescribed with opioids for their opioid-sparing and adjuvant analgesic effects. There is limited literature on the risk of respiratory depression due to the combination of opioids and gabapentinoids requiring naloxone administration.MethodsThis retrospective study evaluated patients who were prescribed opioids and at least one dose of naloxone between March 1, 2014 and September 30, 2016. The primary objective of this study was to compare the frequency of respiratory depression among patients who received naloxone and opioids (non-gabapentinoid group) with those who received naloxone, opioids, and gabapentinoids (gabapentinoid group). Secondary objectives included comparing the association of oversedation, using the Pasero Opioid-induced Sedation Scale, and various risk factors with those in the gabapentinoid group.ResultsA total of 153 patient episodes of naloxone administration (102 in the non-gabapentinoid and 51 in the gabapentinoid groups) in 125 unique patients were included in the study. For the primary objective, there were 33 episodes of respiratory depression associated with the non-gabapentinoid group (33/102=32.4%) versus 17 episodes of respiratory depression with the gabapentinoid group (17/51=33.3%) (p=0.128). Secondary objectives showed a significant association between respiratory depression and surgery in the previous 24 hours (p=0.036) as well as respiratory depression and age &gt;65 years (p=0.031) for patients in the non-gabapentinoid group compared to the gabapentinoid group.ConclusionThere was no significant association of respiratory depression in the gabapentinoid group versus the non-gabapentinoid group. There was an increased risk of respiratory depression in the gabapentinoid group, specifically in patients who had surgery within the previous 24 hours