Publications by authors named "Andrew Roberts"

361 Publications

Intact TP53 function is essential for sustaining durable responses to BH3-mimetic drugs in leukemias.

Blood 2021 Apr 6. Epub 2021 Apr 6.

Monash University, Australia.

Selective targeting of BCL2 with the BH3-mimetic venetoclax is proving transformative for patients with various leukemias. TP53 controls apoptosis upstream from where BCL2 and its pro-survival relatives, such as MCL1, act. Therefore, targeting these pro-survival proteins could trigger apoptosis across diverse blood cancers, irrespective of TP53 mutation status. Indeed, targeting BCL2 has produced clinically relevant responses in blood cancers with aberrant TP53. However, we show that TP53 mutated or deficient myeloid and lymphoid leukemias outcompete isogenic controls with intact TP53, unless sufficient concentrations of BH3-mimetics targeting BCL2 or MCL1 are applied. Strikingly, tumor cells with TP53 dysfunction escape and thrive over time if inhibition of BCL2 or MCL1 is sub-lethal, in part because of an increased threshold for BAX/BAK activation in these cells. Our study reveals the key role of TP53 in shaping long-term responses to BH3-mimetic drugs and reconciles the disparate pattern of initial clinical response to venetoclax, followed by subsequent treatment failure among patients with TP53-mutant chronic lymphocytic leukemia (CLL) or acute myeloid leukemia (AML). In contrast to BH3-mimetics targeting just BCL2 or MCL1 at doses which are individually sub-lethal, we find that a combined BH3-mimetic approach targeting both pro-survival proteins enhances lethality and durably suppresses leukemic burden, regardless of TP53 mutation status. Our findings highlight the importance of employing sufficiently lethal treatment strategies to maximize outcomes for patients with TP53-mutant disease. In addition, our findings caution against use of sub-lethal BH3-mimetic drug regimens, which may enhance the risk of disease progression driven by emergent TP53 mutant clones.
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http://dx.doi.org/10.1182/blood.2020010167DOI Listing
April 2021

COVID-19: pivoting from in-person to virtual orthopedic surgical evaluation.

Can J Surg 2021 02 18;64(1):E101-E102. Epub 2021 Feb 18.

From the Faculty of Medicine, University of British Columbia, Vancouver, BC (Roberts, Johnston, Landells).

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http://dx.doi.org/10.1503/cjs.022520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955834PMC
February 2021

A machine learning algorithm for predicting maternal readmission for hypertensive disorders of pregnancy.

Am J Obstet Gynecol MFM 2021 01 6;3(1):100250. Epub 2020 Oct 6.

Cerner Intelligence, Cerner Corporation, Kansas City, MO.

Background: Maternal postpartum hypertensive emergency is a major cause of maternal mortality and maternal readmission, yet prediction of women who require readmission is limited with false negatives and false positives.

Objective: This study aimed to develop and validate a predictive algorithm for maternal postpartum readmission from complications of hypertensive disorders of pregnancy using machine learning.

Study Design: We performed a cohort study of pregnant women delivering at a single institution using prospectively collected clinical information available from the electronic medical record at the time of discharge. Our primary outcome was readmission within 42 days of delivery for complications of hypertensive disorders of pregnancy. The data set was divided into a derivation and a separate validation cohort. In the derivation cohort, 10 independent data sets were created by randomly suppressing 10% of the population, and then clinical features predictive of complications of hypertensive disorders of pregnancy were analyzed using machine learning to optimize the area under the curve. Once an optimal model was determined, this model was then validated using a second independent validation cohort.

Results: A total of 20,032 delivering women with 238 readmissions for complications of hypertensive disorders of pregnancy (1.2%) were included in the derivation cohort. The validation cohort consisted of 5823 women with 82 readmissions for complications of hypertensive disorders of pregnancy (1.4%). The demographics were similar between the 2 populations as was the test performance characteristics (area under the curve, 0.85 in the derivation cohort vs 0.81 in the validation cohort). Both the derivation and validation algorithms used 31 clinical features that were found to be comparably predictive in both models.

Conclusion: In this evaluation of a machine learning algorithm, readmission for complications of hypertensive disorders of pregnancy can be predicted with reasonable accuracy using clinical data at the time of discharge. Validation of this model in other care settings is necessary to validate its utility.
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http://dx.doi.org/10.1016/j.ajogmf.2020.100250DOI Listing
January 2021

Medicaid prescription limits and their implications for naloxone accessibility.

Drug Alcohol Depend 2021 01 17;218:108355. Epub 2020 Oct 17.

Division of Pharmaceutical Outcomes and Policy, UNC Eshelman School of Pharmacy, One University Heights, CB# 2125, Asheville, NC 28804, USA. Electronic address:

Background: Expanding access to and utilization of naloxone is a vitally important harm reduction strategy for preventing opioid overdose deaths, particularly in vulnerable populations like Medicaid beneficiaries. The objective of this study was to characterize the landscape of monthly prescription fill limit policies in Medicaid programs and their potential implications for expanding naloxone use for opioid overdose harm reduction.

Methods: A cross-sectional, multi-modal online and telephonic data collection strategy was used to identify and describe the presence and characteristics of monthly prescription fill limit policies across state Medicaid programs. Contextual characteristics were described regarding each state's Medicaid enrollment, opioid prescribing rates, and overdose death rates. Data collection and analysis occurred between February and May 2020.

Results: Medicaid-covered naloxone fills are currently subject to monthly prescription fill limit policies in 10 state Medicaid programs, which cover 20 % of the Medicaid population nationwide. Seven of these programs are located in states ranking in the top 10 highest per-capita opioid prescribing rates in the country. However, 8 of these programs are located in states with opioid overdose death rates below the national average.

Conclusions: Medicaid beneficiaries at high risk of opioid overdose living in states with monthly prescription fill limits may experience significant barriers to obtaining naloxone. Exempting naloxone from Medicaid prescription limit restrictions may help spur broader adoption of naloxone for opioid overdose mortality prevention, especially in states with high opioid prescribing rates. Achieving unfettered naloxone coverage in Medicaid is critical as opioid overdoses and Medicaid enrollment increase amid the COVID-19 pandemic.
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http://dx.doi.org/10.1016/j.drugalcdep.2020.108355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7568500PMC
January 2021

Therapeutic development and current uses of BCL-2 inhibition.

Authors:
Andrew W Roberts

Hematology Am Soc Hematol Educ Program 2020 12;2020(1):1-9

Blood Cells and Blood Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; Department of Clinical Haematology, The Royal Melbourne Hospital and Peter MacCallum Cancer Centre, Melbourne, Australia; Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, Australia; and Victorian Comprehensive Cancer Centre, Melbourne, Australia.

B-cell lymphoma 2 (BCL2) is a key protein regulator of apoptosis. It is variably highly expressed in many hematological malignancies, providing protection from cell death induced by oncogenic and external stresses. Venetoclax is the first selective BCL2 inhibitor, and the first of a new class of anticancer drug (BH3-mimetics) to be approved for routine clinical practice, currently in chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML). To help understand the potential and limitations of this therapy, this brief review will touch on the history of development of venetoclax, dissect its mechanism of action, and summarize critical evidence for its approved use in the management of patients with CLL and AML. It will also consider recent data on mechanisms of resistance and explore concepts pertinent to its future development based on key lessons learned to date.
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http://dx.doi.org/10.1182/hematology.2020000154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7727569PMC
December 2020

Should Sea-Ice Modeling Tools Designed for Climate Research Be Used for Short-Term Forecasting?

Curr Clim Change Rep 2020 26;6(4):121-136. Epub 2020 Sep 26.

Polar Science Center, University of Washington, Seattle, WA USA.

In theory, the same sea-ice models could be used for both research and operations, but in practice, differences in scientific and software requirements and computational and human resources complicate the matter. Although sea-ice modeling tools developed for climate studies and other research applications produce output of interest to operational forecast users, such as ice motion, convergence, and internal ice pressure, the relevant spatial and temporal scales may not be sufficiently resolved. For instance, sea-ice research codes are typically run with horizontal resolution of more than 3 km, while mariners need information on scales less than 300 m. Certain sea-ice processes and coupled feedbacks that are critical to simulating the Earth system may not be relevant on these scales; and therefore, the most important model upgrades for improving sea-ice predictions might be made in the atmosphere and ocean components of coupled models or in their coupling mechanisms, rather than in the sea-ice model itself. This paper discusses some of the challenges in applying sea-ice modeling tools developed for research purposes for operational forecasting on short time scales, and highlights promising new directions in sea-ice modeling.
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http://dx.doi.org/10.1007/s40641-020-00162-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683458PMC
September 2020

A consideration of factors affecting palliative oral appliance effectiveness for obstructive sleep apnea: a scoping review.

J Clin Sleep Med 2021 Apr;17(4):833-848

Department of Physiology, School of Medicine, University of Louisville, Louisville, Kentucky.

Study Objectives: This scoping review allows physicians, researchers, and others interested in obstructive sleep apnea to consider effectiveness of oral appliances (OAs). The intent is to improve understanding of OA effectiveness by considering morphologic interaction in patients with obstructive sleep apnea.

Methods: Morphologic and biomechanical criteria for positional alterations of the mandible assessed success rates of OA appliances. Searches of databases (Medline, PubMed, The Cochrane Library, EBSCO) using terms: OA treatment effectiveness and positive and/or negative outcome predictors. Craniofacial predictors of OAs and obstructive sleep apnea biomechanical factors of anatomical traits associated with OA effectiveness were included. Databases searched radiographic cephalometric imaging for morphology/phenotypes and apnea-hypopnea index responses. Articles were excluded if title or abstract was not relevant or a case report. If the analysis did not report mean or standard deviation for apnea-hypoxia index, it was excluded. No language, age, or sex restrictions were applied.

Results: Analysis of 135 articles included in searched literature indicated alterations in musculature and pharyngeal airway structure through OA use. These alterations were individually unpredictable with wide variability 61.81% ± 12.29 (apnea-hypoxia index mean ± standard deviation). Morphologic variations as predictors were typically weak and idiosyncratic. Biomechanical factors and wide variations in the metrics of appliance application were unclear, identifying gaps in knowledge and practice of OAs.

Conclusions: An integrated basis to identify morphologic and biomechanical elements of phenotypic expressions of sleep-disordered breathing in the design and application of OAs is needed. Current knowledge is heterogeneous and shows high variability. Identification of subgroups of patients with obstructive sleep apnea responding to OAs is needed.
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http://dx.doi.org/10.5664/jcsm.9018DOI Listing
April 2021

Runs of homozygosity and analysis of inbreeding depression.

J Anim Sci 2020 Dec;98(12)

Department of Animal and Dairy Science, University of Georgia, Athens, GA.

Pedigree information was traditionally used to assess inbreeding. The availability of high-density marker panels provides an alternative to assess inbreeding, particularly in the presence of incomplete and error-prone pedigrees. Assessment of autozygosity across chromosomal segments using runs of homozygosity (ROH) has emerged as a valuable tool to estimate inbreeding due to its general flexibility and ability to quantify the chromosomal contribution to genome-wide inbreeding. Unfortunately, the identification of ROH segments is sensitive to the parameters used during the search process. These parameters are heuristically set, leading to significant variation in the results. The minimum length required to identify an ROH segment has major effects on the estimation of inbreeding and inbreeding depression, yet it is arbitrarily set. To overcome this limitation, a search algorithm to approximate mutation enrichment was developed to determine the minimum length of ROH segments. It consists of finding genome segments with significant effect differences in trait means between animals with high and low burdens of autozygous intervals with a specific length. The minimum length could be determined heuristically as the smallest interval at which a significant signal is detected. The proposed method was tested in an inbred Hereford cattle population genotyped for 30,220 SNPs. Phenotypes recorded for six traits were used for the approximation of mutation loads. The estimated minimum length was around 1 Mb for yearling weight (YW) and average daily gain (ADG) and 4 Mb for birth weight and weaning weight. These trait-specific thresholds estimated using the proposed method could be attributed to a trait-dependent effect of homozygosity. The detection of significant inbreeding effects was well aligned with the estimated thresholds, especially for YW and ADG. Although highly deleterious alleles are expected to be more frequent in recent inbreeding (long ROH), short ROH segments (<5 Mb) could contain a large number of less deleterious mutations with substantial joint effects on some traits (YW and ADG). Our results highlight the importance of accurate estimation of the ROH-based inbreeding and the necessity to consider a trait-specific minimum length threshold for the identification of ROH segments in inbreeding depression analyses. These thresholds could be determined using the proposed method provided the availability of phenotypic information.
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http://dx.doi.org/10.1093/jas/skaa361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846130PMC
December 2020

Expanding magnetic organelle biogenesis in the domain Bacteria.

Microbiome 2020 10 30;8(1):152. Epub 2020 Oct 30.

Key Laboratory of Earth and Planetary Physics, Institute of Geology and Geophysics, Chinese Academy of Sciences, Beijing, 100029, China.

Background: The discovery of membrane-enclosed, metabolically functional organelles in Bacteria has transformed our understanding of the subcellular complexity of prokaryotic cells. Biomineralization of magnetic nanoparticles within magnetosomes by magnetotactic bacteria (MTB) is a fascinating example of prokaryotic organelles. Magnetosomes, as nano-sized magnetic sensors in MTB, facilitate cell navigation along the local geomagnetic field, a behaviour referred to as magnetotaxis or microbial magnetoreception. Recent discovery of novel MTB outside the traditionally recognized taxonomic lineages suggests that MTB diversity across the domain Bacteria are considerably underestimated, which limits understanding of the taxonomic distribution and evolutionary origin of magnetosome organelle biogenesis.

Results: Here, we perform the most comprehensive metagenomic analysis available of MTB communities and reconstruct metagenome-assembled MTB genomes from diverse ecosystems. Discovery of MTB in acidic peatland soils suggests widespread MTB occurrence in waterlogged soils in addition to subaqueous sediments and water bodies. A total of 168 MTB draft genomes have been reconstructed, which represent nearly a 3-fold increase over the number currently available and more than double the known MTB species at the genome level. Phylogenomic analysis reveals that these genomes belong to 13 Bacterial phyla, six of which were previously not known to include MTB. These findings indicate a much wider taxonomic distribution of magnetosome organelle biogenesis across the domain Bacteria than previously thought. Comparative genome analysis reveals a vast diversity of magnetosome gene clusters involved in magnetosomal biogenesis in terms of gene content and synteny residing in distinct taxonomic lineages. Phylogenetic analyses of core magnetosome proteins in this largest available and taxonomically diverse dataset support an unexpectedly early evolutionary origin of magnetosome biomineralization, likely ancestral to the origin of the domain Bacteria.

Conclusions: These findings expand the taxonomic and phylogenetic diversity of MTB across the domain Bacteria and shed new light on the origin and evolution of microbial magnetoreception. Potential biogenesis of the magnetosome organelle in the close descendants of the last bacterial common ancestor has important implications for our understanding of the evolutionary history of bacterial cellular complexity and emphasizes the biological significance of the magnetosome organelle. Video Abstract.
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http://dx.doi.org/10.1186/s40168-020-00931-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602337PMC
October 2020

Orbital climate variability on the northeastern Tibetan Plateau across the Eocene-Oligocene transition.

Nat Commun 2020 10 16;11(1):5249. Epub 2020 Oct 16.

State Key Laboratory of Loess and Quaternary Geology, Institute of Earth Environment, Chinese Academy of Sciences, Xi'an, China.

The first major build-up of Antarctic glaciation occurred in two consecutive stages across the Eocene-Oligocene transition (EOT): the EOT-1 cooling event at ~34.1-33.9 Ma and the Oi-1 glaciation event at ~33.8-33.6 Ma. Detailed orbital-scale terrestrial environmental responses to these events remain poorly known. Here we present magnetic and geochemical climate records from the northeastern Tibetan Plateau margin that are dated precisely from ~35.5 to 31 Ma by combined magneto- and astro-chronology. These records suggest a hydroclimate transition at ~33.7 Ma from eccentricity dominated cycles to oscillations paced by a combination of eccentricity, obliquity, and precession, and confirm that major Asian aridification and cooling occurred at Oi-1. We conclude that this terrestrial orbital response transition coincided with a similar transition in the marine benthic δO record for global ice volume and deep-sea temperature variations. The dramatic reorganization of the Asian climate system coincident with Oi-1 was, thus, a response to coeval atmospheric CO decline and continental-scale Antarctic glaciation.
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http://dx.doi.org/10.1038/s41467-020-18824-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567875PMC
October 2020

Immune recovery in patients with mantle cell lymphoma receiving long-term ibrutinib and venetoclax combination therapy.

Blood Adv 2020 10;4(19):4849-4859

ACRF Translational Research Laboratory, Royal Melbourne Hospital, Melbourne, VIC, Australia.

Combination venetoclax plus ibrutinib for the treatment of mantle cell lymphoma (MCL) has demonstrated efficacy in the relapsed or refractory setting; however, the long-term impact on patient immunology is unknown. In this study, changes in immune subsets of MCL patients treated with combination venetoclax and ibrutinib were assessed over a 4-year period. Multiparameter flow cytometry of peripheral blood mononuclear cells showed that ≥12 months of treatment resulted in alterations in the proportions of multiple immune subsets, most notably CD4+ and CD8+ effector and central memory T cells and natural killer cells, and normalization of T-cell cytokine production in response to T-cell receptor stimulation. Gene expression analysis identified upregulation of multiple myeloid genes (including S100 and cathepsin family members) and inflammatory pathways over 12 months. Four patients with deep responses stopped study drugs, resulting in restoration of normal immune subsets for all study parameters except myeloid gene/pathway expression, suggesting long-term combination venetoclax and ibrutinib irreversibly affects this population. Our findings demonstrate that long-term combination therapy is associated with immune recovery in MCL, which may allow responses to subsequent immunotherapies and suggests that this targeted therapy results in beneficial impacts on immunological recovery. This trial was registered at www.clinicaltrials.gov as #NCT02471391.
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http://dx.doi.org/10.1182/bloodadvances.2020002810DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556128PMC
October 2020

Diverse phylogeny and morphology of magnetite biomineralized by magnetotactic cocci.

Environ Microbiol 2021 Feb 10;23(2):1115-1129. Epub 2020 Oct 10.

Key Laboratory of Earth and Planetary Physics, Institute of Geology and Geophysics, Innovation Academy for Earth Science, Chinese Academy of Sciences, Beijing, China.

Magnetotactic bacteria (MTB) are diverse prokaryotes that produce magnetic nanocrystals within intracellular membranes (magnetosomes). Here, we present a large-scale analysis of diversity and magnetosome biomineralization in modern magnetotactic cocci, which are the most abundant MTB morphotypes in nature. Nineteen novel magnetotactic cocci species are identified phylogenetically and structurally at the single-cell level. Phylogenetic analysis demonstrates that the cocci cluster into an independent branch from other Alphaproteobacteria MTB, that is, within the Etaproteobacteria class in the Proteobacteria phylum. Statistical analysis reveals species-specific biomineralization of magnetosomal magnetite morphologies. This further confirms that magnetosome biomineralization is controlled strictly by the MTB cell and differs among species or strains. The post-mortem remains of MTB are often preserved as magnetofossils within sediments or sedimentary rocks, yet paleobiological and geological interpretation of their fossil record remains challenging. Our results indicate that magnetofossil morphology could be a promising proxy for retrieving paleobiological information about ancient MTB.
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http://dx.doi.org/10.1111/1462-2920.15254DOI Listing
February 2021

Response to Strassels and Durham.

J Natl Cancer Inst 2020 12;112(12):1280

Department of Population Health and Department of Anesthesiology, University of Kansas Medical Center (KUMC), Kansas City, KS, USA.

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http://dx.doi.org/10.1093/jnci/djaa146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7735774PMC
December 2020

Association of Current Opioid Use With Serious Adverse Events Among Older Adult Survivors of Breast Cancer.

JAMA Netw Open 2020 09 1;3(9):e2016858. Epub 2020 Sep 1.

Department of Population Health, University of Kansas Medical Center, Kansas City.

Importance: National efforts to improve safe opioid prescribing focus on preventing misuse, overdose, and opioid use disorder. This approach overlooks opportunities to better prevent other serious opioid-related harms in complex populations, such as older adult survivors of cancer. Little is known about the rates and risk factors for comprehensive opioid-related harms in this population.

Objective: To determine rates of multiple opioid-related adverse drug events among older adults who survived breast cancer and estimate the risk of these events associated with opioid use in the year after completing cancer treatment.

Design, Setting, And Participants: This retrospective cohort study used 2007 to 2016 Surveillance, Epidemiology and End Results-Medicare data from fee-for-service Medicare beneficiaries with first cancer diagnosis of stage 0 to III breast cancer at age 66 to 90 years from January 1, 2008, through December 31, 2015, who completed active breast cancer treatment. Data were analyzed from October 31, 2019, to June 10, 2020.

Exposures: Repeated daily measure indicating possession of any prescription opioid supply in Medicare Part D prescription claims.

Main Outcomes And Measures: Adjusted risk ratios (aRRs), estimated using modified Poisson generalized estimating equation models, for adverse drug events related to substance misuse (ie, diagnosed opioid abuse, dependence, or poisoning), other adverse drug events associated with opioid use (ie, gastrointestinal events, infections, falls and fractures, or cardiovascular events), and all-cause hospitalization associated with opioid supply the prior day, controlling for patient characteristics.

Results: Among 38 310 women included in the study (mean [SD] age, 74.3 [6.3] years), there were 0.010 (95% CI, 0.008-0.011) adverse drug events related to substance misuse per 1000 person-days, 0.237 (95% CI, 0.229-0.245) other adverse drug events associated with opioid use per 1000 person-days, and 0.675 (95% CI, 0.662-0.689) all-cause hospitalizations per 1000 person-days. Opioid use was associated with increased risk of adverse drug events related to substance misuse (aRR, 14.62; 95% CI, 9.69-22.05; P < .001), other adverse drug events related to opioid use (aRR, 2.50; 95% CI, 2.11-2.96; P < .001), and all-cause hospitalization (aRR, 2.77; 95% CI, 2.55-3.02; P < .001). In a dose-response effect, individuals with high daily opioid doses had consistently higher risks of all study outcomes compared with individuals who had low opioid doses. Compared with days with no opioid exposure, the risk of any adverse drug event related to substance misuse was 3.4-fold higher for individuals with a current opioid supply ≥50 mg morphine equivalent dose per day (aRR, 3.40; 95% CI, 2.47-4.68; P < .001), while the risk was 2.3-fold higher for individuals with 1 to 49 mg morphine equivalent dose per day (aRR, 2.29; 95% CI, 1.89-2.77; P < .001).

Conclusions And Relevance: These findings suggest that among older adults who survived breast cancer, continued prescription opioid use in the year after completing active cancer treatment was associated with an immediate increased risk of a broad range of serious adverse drug events related to substance misuse and other adverse drug events associated with opioid use. Clinicians should consider the comprehensive risks of managing cancer pain with long-term opioid therapy.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.16858DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7492912PMC
September 2020

Magnetic Vortex States in Toroidal Iron Oxide Nanoparticles: Combining Micromagnetics with Tomography.

Nano Lett 2020 Oct 22;20(10):7405-7412. Epub 2020 Sep 22.

Department of Materials Science and Metallurgy, University of Cambridge, Cambridge CB3 0FS, United Kingdom.

Iron oxide nanorings have great promise for biomedical applications because of their magnetic vortex state, which endows them with a low remanent magnetization while retaining a large saturation magnetization. Here we use micromagnetic simulations to predict the exact shapes that can sustain magnetic vortices, using a toroidal model geometry with variable diameter, ring thickness, and ring eccentricity. Our model phase diagram is then compared with simulations of experimental geometries obtained by electron tomography. High axial eccentricity and low ring thickness are found to be key factors for forming vortex states and avoiding net-magnetized metastable states. We also find that while defects from a perfect toroidal geometry increase the stray field associated with the vortex state, they can also make the vortex state more energetically accessible. These results constitute an important step toward optimizing the magnetic behavior of toroidal iron oxide nanoparticles.
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http://dx.doi.org/10.1021/acs.nanolett.0c02795DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7587137PMC
October 2020

Impact of On-site Compared to Send-away Testing for SARS-CoV-2 on Duration of Isolation and Resource Utilization.

Infect Control Hosp Epidemiol 2020 Aug 24:1-15. Epub 2020 Aug 24.

Monash Infectious Diseases, Monash Health, Clayton, Victoria, Australia.

Rapid detection and isolation of COVID-19 patients is the only means of reducing hospital transmission. We describe the impact of implementation of on-site SARS-CoV-2 RT-PCR testing on reduction in result turnaround time, isolation duration, pathology test ordering and antibiotic use in patients who do not have COVID-19.
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http://dx.doi.org/10.1017/ice.2020.433DOI Listing
August 2020

Opioid Use Disorder and Overdose in Older Adults With Breast, Colorectal, or Prostate Cancer.

J Natl Cancer Inst 2021 Apr;113(4):425-433

Department of Population Health Sciences, Duke University School of Medicine; Duke Cancer Institute, Durham, NC, USA.

Background: Despite high rates of opioid therapy, evidence about the risk of preventable opioid harms among cancer survivors is underdeveloped. Our objective was to estimate the odds of opioid use disorder (OUD) and overdose following breast, colorectal, or prostate cancer diagnosis among Medicare beneficiaries.

Methods: We conducted a retrospective cohort study using 2007-2014 Surveillance, Epidemiology, and End Results-Medicare data for cancer survivors with a first cancer diagnosis of stage 0-III breast, colorectal, or prostate cancer at age 66-89 years between 2008 and 2013. Cancer survivors were matched to up to 2 noncancer controls on age, sex, and Surveillance, Epidemiology, and End Results region. Using Firth logistic regression, we estimated adjusted 1-year odds of OUD or nonfatal opioid overdose associated with a cancer diagnosis. We also estimated adjusted odds of OUD and overdose separately and by cancer stage, prior opioid use, and follow-up time.

Results: Among 69 889 cancer survivors and 125 007 controls, the unadjusted rates of OUD or nonfatal overdose were 25.2, 27.1, 38.9, and 12.4 events per 10 000 patients in the noncancer, breast, colorectal, and prostate samples, respectively. There was no association between cancer and OUD. Colorectal survivors had 2.3 times higher odds of opioid overdose compared with matched controls (adjusted odds ratio = 2.33, 95% confidence interval  = 1.49 to 3.67). Additionally, overdose risk was greater in those with more advanced disease, no prior opioid use, and preexisting mental health conditions.

Conclusions: Opioid overdose was a rare, but statistically significant, outcome following stage II-III colorectal cancer diagnosis, particularly among previously opioid-naïve patients. These patients may require heightened screening and intervention to prevent inadvertent adverse opioid harms.
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http://dx.doi.org/10.1093/jnci/djaa122DOI Listing
April 2021

Zanubrutinib for the treatment of patients with Waldenström macroglobulinemia: 3 years of follow-up.

Blood 2020 10;136(18):2027-2037

Haematology Department, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, VIC, Australia.

Inhibitors of Bruton's tyrosine kinase (BTK) have established therapeutic activity in patients with Waldenström macroglobulinemia (WM). Zanubrutinib, a potent and selective BTK inhibitor, was evaluated in a phase 1/2 study in patients with WM who were either treatment-naïve (TN) or had relapsed/refractory (R/R) disease. Patients had disease requiring treatment per International Workshop on Waldenström Macroglobulinemia (IWWM) criteria. Treatment was 160 mg of oral zanubrutinib twice daily (n = 50) or 320 mg once daily (n = 23). Efficacy endpoints included overall response rate (ORR) and very good partial response/complete response (VGPR/CR) rates per IWWM-6 criteria (with modification of VGPR definition published previously). Between September 2014 and March 2018, 77 patients (24 TN and 53 R/R) began treatment. At a median follow-up of 36.0 months for patients with R/R disease and 23.5 months for TN, 72.7% remained on treatment. Reasons for treatment discontinuation included any adverse events in 13.0% of patients (1 treatment related), disease progression (10.4%), and other (3.9%). The ORR was 95.9%, and the VGPR/CR rate was 45.2%, which increased over time: 20.5% at 6 months, 32.9% at 12 months, and 43.8% at 24 months. Estimated 3-year progression-free survival rate was 80.5%, and overall survival rate was 84.8%. Adverse events of interest included contusion (32.5%, all grade 1), neutropenia (18.2%), major hemorrhage (3.9%), atrial fibrillation/flutter (5.2%), and grade 3 diarrhea (2.6%). Long-term treatment with single-agent zanubrutinib resulted in deep and durable responses in some patients with WM. The safety profile of long-term zanubrutinib therapy in these patients was acceptable. This trial was registered at www.clinicaltrials.gov as #NCT02343120.
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http://dx.doi.org/10.1182/blood.2020006449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596846PMC
October 2020

Design, synthesis and characterization of structurally dynamic cyclic N,S-acetals.

Chem Commun (Camb) 2020 Aug 22;56(64):9118-9121. Epub 2020 Jul 22.

Department of Chemistry, University of Utah, 315 South 1400 East, Salt Lake City, Utah 84112, USA.

We report the synthesis, characterization and comparison of a series of electronically perturbed, cyclic N,S-acetals. Inspired by electrophilic auxiliaries utilized for amine capture and concomitant peptide ligation, we studied these N,S-acetal systems and evaluated their propensity to generate zwitterionic intermediates in situ. Certain N,S-acetals in this study exhibit structurally dynamic properties through a solvent and pH-dependent ability to ring-open and ring-close via C1-S bond ionization at room temperature.
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http://dx.doi.org/10.1039/d0cc03503cDOI Listing
August 2020

Chemotherapy and Venetoclax in Elderly Acute Myeloid Leukemia Trial (CAVEAT): A Phase Ib Dose-Escalation Study of Venetoclax Combined With Modified Intensive Chemotherapy.

J Clin Oncol 2020 10 20;38(30):3506-3517. Epub 2020 Jul 20.

Department of Haematology, The Alfred Hospital, Melbourne, Victoria, Australia.

Purpose: The B-cell lymphoma 2 (BCL-2) inhibitor venetoclax has an emerging role in acute myeloid leukemia (AML), with promising response rates in combination with hypomethylating agents or low-dose cytarabine in older patients. The tolerability and efficacy of venetoclax in combination with intensive chemotherapy in AML is unknown.

Patients And Methods: Patients with AML who were ≥ 65 years (≥ 60 years if monosomal karyotype) and fit for intensive chemotherapy were allocated to venetoclax dose-escalation cohorts (range, 50-600 mg). Venetoclax was administered orally for 14 days each cycle. During induction, a 7-day prephase/dose ramp-up (days -6 to 0) was followed by an additional 7 days of venetoclax combined with infusional cytarabine 100 mg/m on days 1-5 and idarubicin 12 mg/m intravenously on days 2-3 (ie, 5 + 2). Consolidation (4 cycles) included 14 days of venetoclax (days -6 to 7) combined with cytarabine (days 1-2) and idarubicin (day 1). Maintenance venetoclax was permitted (7 cycles). The primary objective was to assess the optimal dose schedule of venetoclax with 5 + 2.

Results: Fifty-one patients with a median age of 72 years (range, 63-80 years) were included. The maximum tolerated dose was not reached with venetoclax 600 mg/day. The main grade ≥ 3 nonhematologic toxicities during induction were febrile neutropenia (55%) and sepsis (35%). In contrast to induction, platelet recovery was notably delayed during consolidation cycles. The overall response rate (complete remission [CR]/CR with incomplete count recovery) was 72%; it was 97% in de novo AML and was 43% in secondary AML. During the venetoclax prephase, marrow blast reductions (≥ 50%) were noted in -, -, and -mutant AML.

Conclusion: Venetoclax combined with 5 + 2 induction chemotherapy was safe and tolerable in fit older patients with AML. Although the optimal postremission therapy remains to be determined, the high remission rate in de novo AML warrants additional investigation (ANZ Clinical Trial Registry No. ACTRN12616000445471).
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http://dx.doi.org/10.1200/JCO.20.00572DOI Listing
October 2020

Ni-Catalyzed Iterative Alkyl Transfer from Nitrogen Enabled by the In Situ Methylation of Tertiary Amines.

J Org Chem 2020 08 30;85(15):9979-9992. Epub 2020 Jul 30.

Department of Chemistry, University of Utah, 315 South 1400 East, Salt Lake City, Utah 84112, United States.

Current methods to achieve transition-metal-catalyzed alkyl carbon-nitrogen (C-N) bond cleavage require the preformation of ammonium, pyridinium, or sulfonamide derivatives from the corresponding alkyl amines. These activated substrates permit C-N bond cleavage, and their resultant intermediates can be intercepted to affect carbon-carbon bond-forming transforms. Here, we report the combination of in situ amine methylation and Ni-catalyzed benzalkyl C-N bond cleavage under reductive conditions. This method permits iterative alkyl group transfer from tertiary amines and demonstrates a deaminative strategy for the construction of Csp-Csp bonds. We demonstrate PO(OMe) (trimethylphosphate) to be a Ni-compatible methylation reagent for the in situ conversion of trialkyl amines into tetraalkylammonium salts. Single, double, and triple benzalkyl group transfers can all be achieved from the appropriately substituted tertiary amines. Transformations developed herein proceed via recurring events: the in situ methylation of tertiary amines by PO(OMe), Ni-catalyzed C-N bond cleavage, and concurrent Csp-Csp bond formation.
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http://dx.doi.org/10.1021/acs.joc.0c01274DOI Listing
August 2020

Palliative Care's Role Managing Cancer Pain During the Opioid Crisis: A Qualitative Study of Patients, Caregivers, and Clinicians.

J Pain Symptom Manage 2020 12 6;60(6):1127-1135.e2. Epub 2020 Jul 6.

Division of Palliative Medicine, Department of Internal Medicine, University of Kansas School of Medicine, Kansas City, Kansas, USA; Department of History and Philosophy of Medicine, University of Kansas School of Medicine, Kansas City, Kansas, USA.

Context: Patients with cancer face symptoms because of disease and treatment, and pain is common and complex. The opioid crisis may complicate patients' and clinicians' experiences of managing pain in cancer care.

Objectives: In our study of perceptions and experiences with palliative care (PC) at an outpatient cancer center, we examined communication around symptom management throughout cancer care, and pain and its management emerged as particularly salient. The objective of this article is to describe, from the perspectives of patients, caregivers, and oncology health care professionals, the role of PC in navigating the complicated dynamics of pain management amidst the opioid crisis.

Methods: A qualitative descriptive study with grounded theory components was designed to investigate experiences with and perceptions of specialist PC and symptom management, including pain. Interviews were audiorecorded and transcribed, and focused coding identified themes related to pain and pain management from all three perspectives.

Results: About 44 patients, caregivers, and non-PC health care professionals completed interviews. Patients with cancer and their caregivers had many concerns about pain management and were specifically concerned about opioid use and stigma. For patients, PC improved pain management and helped to destigmatize appropriate pain management. Oncology clinicians reported that partnering with PC facilitated complex pain management and also provided moral support around difficult opioid recommendations for patients.

Conclusion: PC offers the potential to uniquely support both patients and other oncology professionals in optimally navigating the complexity around pain management for cancer care in the midst of the opioid crisis.
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http://dx.doi.org/10.1016/j.jpainsymman.2020.06.039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680449PMC
December 2020

Sublethal Endpoints in Non-target Organism Testing for Insect-Active GE Crops.

Front Bioeng Biotechnol 2020 9;8:556. Epub 2020 Jun 9.

USDA, Corn Insects and Crop Genetics Research Unit, Ames, IA, United States.

Historically, genetically engineered (GE) plants that have incorporated genes conferring insect protection have primarily used Cry proteins derived from () to achieve their insecticidal phenotype. As a result, regulators have developed a level of familiarity and confidence in reviewing plants incorporating these insecticidal proteins. However, new technologies have been developed that produce GE plants that incorporate pest protection by triggering an RNA interference (RNAi) response or proteins other than Cry proteins. These technologies have new modes of action. Although the overall assessment paradigm for GE plants is robust, there are ongoing discussions about the appropriate tests and measurement endpoints needed to inform non-target arthropod assessment for technologies that have a different mode of action than the Cry proteins. As a result, increasing attention is being paid to the use of sublethal endpoints and their value for environmental risk assessment (ERA). This review focuses on the current status and history of sublethal endpoint use in insect-active GE crops, and evaluates the future use of sublethal endpoints for new and emerging technologies. It builds upon presentations made at the Workshop on Sublethal Endpoints for Non-target Organism Testing for Non- GE Crops (Washington DC, USA, 4-5 March 2019), and the discussions of government, academic and industry scientists convened for the purpose of reviewing the progress and status of sublethal endpoint testing in non-target organisms.
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http://dx.doi.org/10.3389/fbioe.2020.00556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295912PMC
June 2020

Cotargeting BCL-2 and MCL-1 in high-risk B-ALL.

Blood Adv 2020 06;4(12):2762-2767

Centre for Cancer Research, University of Melbourne, Parkville, Melbourne, Australia.

Improving survival outcomes in adult B-cell acute lymphoblastic leukemia (B-ALL) remains a clinical challenge. Relapsed disease has a poor prognosis despite the use of tyrosine kinase inhibitors (TKIs) for Philadelphia chromosome positive (Ph+ ALL) cases and immunotherapeutic approaches, including blinatumomab and chimeric antigen receptor T cells. Targeting aberrant cell survival pathways with selective small molecule BH3-mimetic inhibitors of BCL-2 (venetoclax, S55746), BCL-XL (A1331852), or MCL1 (S63845) is an emerging therapeutic option. We report that combined targeting of BCL-2 and MCL1 is synergistic in B-ALL in vitro. The combination demonstrated greater efficacy than standard chemotherapeutics and TKIs in primary samples from adult B-ALL with Ph+ ALL, Ph-like ALL, and other B-ALL. Moreover, combined BCL-2 or MCL1 inhibition with dasatinib showed potent killing in primary Ph+ B-ALL cases, but the BH3-mimetic combination appeared superior in vitro in a variety of Ph-like ALL samples. In PDX models, combined BCL-2 and MCL1 targeting eradicated ALL from Ph- and Ph+ B-ALL cases, although fatal tumor lysis was observed in some instances of high tumor burden. We conclude that a dual BH3-mimetic approach is highly effective in diverse models of high-risk human B-ALL and warrants assessment in clinical trials that incorporate tumor lysis precautions.
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http://dx.doi.org/10.1182/bloodadvances.2019001416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7322969PMC
June 2020

Genetic Biocontrol for Invasive Species.

Front Bioeng Biotechnol 2020 25;8:452. Epub 2020 May 25.

ILSI Research Foundation, Washington, DC, United States.

Invasive species are increasingly affecting agriculture, food, fisheries, and forestry resources throughout the world. As a result of global trade, invasive species are often introduced into new environments where they become established and cause harm to human health, agriculture, and the environment. Prevention of new introductions is a high priority for addressing the harm caused by invasive species, but unfortunately efforts to prevent new introductions do not address the economic harm that is presently manifested where invasive species have already become established. Genetic biocontrol can be defined as the release of organisms with genetic methods designed to disrupt the reproduction of invasive populations. While these methods offer the potential to control or even eradicate invasive species, there is a need to ensure that genetic biocontrol methods can be deployed in a way that minimizes potential harm to the environment. This review provides an overview of the state of genetic biocontrol, focusing on several approaches that were the subject of presentations at the Genetic Biocontrol for Invasive Species Workshop in Tarragona, Spain, March 31st, 2019, a workshop sponsored by the OECD's Co-operative Research Program on Biological Resource Management for Sustainable Agricultural Systems. The review considers four different approaches to genetic biocontrol for invasive species; sterile-release, YY Males, Trojan Female Technique, and gene drive. The different approaches will be compared with respect to the efficiency each affords as a genetic biocontrol tool, the practical utility and cost/benefits associated with implementation of the approach, and the regulatory considerations that will need to be addressed for each. The opinions expressed and arguments employed in this publication are the sole responsibility of the authors and do not necessarily reflect those of the OECD or of the governments of its Member countries.
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http://dx.doi.org/10.3389/fbioe.2020.00452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261935PMC
May 2020

Safety and tolerability of subcutaneous methotrexate in routine clinical practice.

Arthritis Care Res (Hoboken) 2020 May 31. Epub 2020 May 31.

Translational and Clinical Research Institute, Newcastle University, Newcastle Upon Tyne, United Kingdom.

Objectives: To show safety and efficacy of subcutaneous (sc) methotrexate (MTX) compared to oral MTX, alternative disease-modifying anti-rheumatic drugs (DMARD) monotherapy, and combinations (biologic monotherapy, conventional and biologic combination groups) in routine clinical practice.

Methods: Clinical and laboratory data were retrospectively analysed for rheumatology clinic attendances at a large North-East England hospital trust between January 2014-January 2018. Adverse and stop event rates (transaminitis [serum alanine aminotransferase >80U/l] or neutropenia [neutrophils <2.0x10 /l]) were calculated, adjusted for duration of DMARD exposure.

Results: 8394 patients received DMARDs: 2093 oral MTX; 949 sc MTX. Median (Interquartile range - IQR) oral MTX dose was 15 (10-20) mg, and sc MTX was 20 (15-25) mg (p<0.0001). Continuation rates were higher for sc MTX when adjusted for follow-up duration (RR=1.54, 95% CI: 1.40-1.70; p<0.0001). 2382 patients experienced 4358 adverse events (1711 transaminitis, 2647 neutropenia). Significantly fewer adverse events were observed for sc MTX monotherapy versus biologic and combination DMARD therapies (p<0.01). Compared to oral MTX, sc MTX was associated with a non-significant trend to lower rates of neutropenia, but only slightly higher rate of transaminitis (RR=1.26, 95% CI: 1.07-1.48; p=0.006) despite significantly higher doses.

Conclusions: Subcutaneous MTX is safe in routine practice. This is the largest study yet reported and provides observational data that sc MTX is continued longer and better tolerated compared to other therapy groups, especially oral MTX.
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http://dx.doi.org/10.1002/acr.24334DOI Listing
May 2020

Changes in Opioid Prescribing Patterns Among Generalists and Oncologists for Medicare Part D Beneficiaries From 2013 to 2017.

JAMA Oncol 2020 08;6(8):1271-1274

Department of Radiation Oncology, University of North Carolina at Chapel Hill.

Importance: In response to the opioid epidemic, policies aiming to reduce opioid prescribing, misuse, and abuse may have the unintended consequence of restricting access to necessary opioid therapy for cancer-related pain. It is unknown how opioid prescribing patterns have changed among generalists and oncologists during this era.

Objective: To examine trends in opioid prescription rates for Medicare Part D beneficiaries from 2013 to 2017 among oncologists and generalists.

Design, Setting, And Participants: This repeated cross-sectional study of generalist physicians (internal medicine, family medicine, geriatric medicine, general practice) and oncology specialists (medical oncology, hematology-oncology, and radiation oncology) analyzed the Medicare Provider Utilization and Payment Data: Part D prescriber files from 2013 to 2017.

Exposures: Generalist vs oncology specialty.

Main Outcomes And Measures: Outcomes included physician-level rates of both opioid and long-acting opioid prescriptions per 100 Medicare Part D beneficiaries. Poisson regression was used to estimate annual predicted outcome rates and incidence rate ratios, adjusting for prescriber characteristics and state fixed effects.

Results: We analyzed the prescribing patterns of 251 820 generalists and 14 210 oncologists. From 2013 to 2017, the annual adjusted predicted mean rate of opioid prescriptions per 100 Medicare beneficiaries decreased from 68.2 to 49.7 among generalists (adjusted incidence rate ratio [aIRR] = 0.73; 95% CI, 0.73-0.73) and from 77.8 to 58.8 among oncologists (aIRR = 0.76; 95% CI, 0.74-0.77). The rate of long-acting opioid prescriptions per 100 Medicare beneficiaries also decreased from 8.0 to 5.4 for generalists (aIRR = 0.67; 95% CI, 0.66-0.68) and from 18.6 to 13.3 for oncologists (aIRR = 0.72; 95% CI, 0.69-0.74).

Conclusions And Relevance: We found large declines in opioid prescription rates for Medicare beneficiaries by generalists and oncologists from 2013 to 2017. Opioid policy and advocacy appear to have been effective in reducing the extent of opioid prescribing in the Medicare population. Similar declines between generalists and oncologists raise concern that access to cancer pain management may have been inadvertently restricted. How much of the decrease in prescribing by oncologists is appropriate vs inappropriate deserves further investigation.
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http://dx.doi.org/10.1001/jamaoncol.2020.2211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7260690PMC
August 2020

Naloxone Prescribing Among Frequent Opioid Prescribers in Medicare Part D from 2013 to 2017: a Retrospective Study.

Authors:
Andrew W Roberts

J Gen Intern Med 2021 Feb 6;36(2):543-545. Epub 2020 May 6.

Department of Population Health, Department of Anesthesiology, University of Kansas Medical Center, Kansas City, KS, USA.

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http://dx.doi.org/10.1007/s11606-020-05872-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878639PMC
February 2021

BTK inhibitor therapy is effective in patients with CLL resistant to venetoclax.

Blood 2020 06;135(25):2266-2270

Department of Clinical Haematology, Royal Melbourne Hospital and Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

Highly active BTK inhibitors (BTKis) and the BCL2 inhibitor venetoclax have transformed the therapeutic landscape for chronic lymphocytic leukemia (CLL). Results of prospective clinical trials demonstrate the efficacy of venetoclax to salvage patients with disease progression on BTKis, but data on BTKi therapy after disease progression on venetoclax are limited, especially regarding durability of benefit. We retrospectively evaluated the records of 23 consecutive patients with relapsed/refractory CLL who received a BTKi (ibrutinib, n = 21; zanubrutinib, n = 2) after stopping venetoclax because of progressive disease. Median progression-free survival (PFS) and median overall survival after BTKi initiation were 34 months (range, <1 to 49) and 42 months (range, 2-49), respectively. Prior remission duration ≥24 months and attainment of complete remission or undetectable measurable residual disease on venetoclax were associated with longer PFS after BTKi salvage (P = .044 and P = .029, respectively). BTKi therapy achieved durable benefit for patients with the BCL2 Gly101Val venetoclax resistance mutation (estimated 24-month PFS, 69%). At a median survivor follow-up of 33 months (range, 2-53), 11 patients remained on BTKi and 12 had stopped therapy because of disease progression (n = 8) or toxicity (n = 4). Our findings indicate that BTKi therapy can provide durable CLL control after disease progression on venetoclax.
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http://dx.doi.org/10.1182/blood.2020004782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7316215PMC
June 2020

Cancer survivorship and its association with perioperative opioid use for minor non-cancer surgery.

Support Care Cancer 2020 Dec 25;28(12):5763-5770. Epub 2020 Mar 25.

Department of Anesthesiology, University of Kansas Medical Center, Kansas City, KS, USA.

Purpose: Reducing high-risk prescription opioid use after surgery has become a key strategy in mitigating the opioid crisis. Yet, despite their vulnerabilities, we know little about how cancer survivors use opioids for non-cancer perioperative pain compared to those with no history of cancer. The purpose was to examine the association of cancer survivorship with the likelihood of receiving perioperative opioid therapy for non-cancer minor surgery.

Methods: Using 2007-2014 SEER-Medicare data for breast, colorectal, prostate, and non-cancer populations, we conducted retrospective cohort study of opioid-naïve Medicare beneficiaries who underwent one of six common minor non-cancer surgeries. Modified Poisson regression estimated the relative risk of receiving a perioperative opioid prescription associated with cancer survivorship compared to no history of cancer. Stabilized inverse probability of treatment weights were used to balance measurable covariates between cohorts.

Results: We included 1486 opioid-naïve older adult cancer survivors and 3682 opioid-naïve non-cancer controls. Cancer survivorship was associated with a 5% lower risk of receiving a perioperative opioid prescription (95% confidence interval: 0.89, 1.00; p = 0.06) compared to no history of cancer. Cancer survivorship was not associated with the extent of perioperative opioid exposure.

Conclusion: Cancer survivors were slightly less likely to receive opioid therapy for non-cancer perioperative pain than those without a history of cancer. It is unclear if this reflects a reduced risk of opioid-related harms for cancer survivors or avoidance of appropriate perioperative pain therapy. Further examination of cancer survivors' experiences with and attitudes about opioids may inform improvements to non-cancer pain management for cancer survivors.
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http://dx.doi.org/10.1007/s00520-020-05420-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529663PMC
December 2020