Operational definition of precipitated opioid withdrawal

Background Opioid withdrawal can be expressed as both a spontaneous and precipitated syndrome. Although spontaneous withdrawal is well-characterized, there is no operational definition of precipitated opioid withdrawal.MethodsPeople (N = 106) with opioid use disorder maintained on morphine received 0.4 mg intramuscular naloxone and completed self-report (Subjective Opiate Withdrawal Scale, SOWS), visual analog scale (VAS), Bad Effects and Sick, and observer ratings (Clinical Opiate Withdrawal Scale, COWS). Time to peak severity and minimal clinically important difference (MCID) in withdrawal severity were calculated. Principal component analysis (PCA) during peak severity were conducted and analyzed with repeated measures analyses of variance (ANOVA).ResultsWithin 60 min, 89% of people reported peak SOWS ratings and 90% of people had peak COWS scores as made by raters. Self-reported signs of eyes tearing, yawning, nose running, perspiring, hot flashes, and observed changes in pupil diameter and rhinorrhea/lacrimation were uniquely associated with precipitated withdrawal. VAS ratings of Bad Effect and Sick served as statistically significant severity categories (0, 1–40, 41–80, and 81–100) for MCID evaluations and revealed participants' identification with an increase of 10 [SOWS; 15% maximum percent effect (MPE)] and 6 (COWS; 12% MPE) points as meaningful shifts in withdrawal severity indicative of precipitated withdrawal.ConclusionData suggested that a change of 10 (15% MPE) and 6 (12% MPE) points on the SOWS and COWS, respectively, that occurred within 60 min of antagonist administration was identified by participants as a clinically meaningful increase in symptom severity. These data provide a method to begin examining precipitated opioid withdrawal

Single-cell multi-omics analysis of the immune response in COVID-19

Funder: Lister Institute of Preventive Medicine; doi: https://doi.org/10.13039/501100001255Funder: University College London, Birkbeck MRC Doctoral Training ProgrammeFunder: The Jikei University School of MedicineFunder: Action Medical Research (GN2779)Funder: NIHR Clinical Lectureship (CL-2017-01-004)Funder: NIHR (ACF-2018-01-004) and the BMA FoundationFunder: Chan Zuckerberg Initiative (grant 2017-174169) and from Wellcome (WT211276/Z/18/Z and Sanger core grant WT206194)Funder: UKRI Innovation/Rutherford Fund Fellowship allocated by the MRC and the UK Regenerative Medicine Platform (MR/5005579/1 to M.Z.N.). M.Z.N. and K.B.M. have been funded by the Rosetrees Trust (M944)Funder: Barbour FoundationFunder: ERC Consolidator and EU MRG-Grammar awardsFunder: Versus Arthritis Cure Challenge Research Grant (21777), and an NIHR Research Professorship (RP-2017-08-ST2-002)Funder: European Molecular Biology Laboratory (EMBL)Abstract: Analysis of human blood immune cells provides insights into the coordinated response to viral infections such as severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19). We performed single-cell transcriptome, surface proteome and T and B lymphocyte antigen receptor analyses of over 780,000 peripheral blood mononuclear cells from a cross-sectional cohort of 130 patients with varying severities of COVID-19. We identified expansion of nonclassical monocytes expressing complement transcripts (CD16+C1QA/B/C+) that sequester platelets and were predicted to replenish the alveolar macrophage pool in COVID-19. Early, uncommitted CD34+ hematopoietic stem/progenitor cells were primed toward megakaryopoiesis, accompanied by expanded megakaryocyte-committed progenitors and increased platelet activation. Clonally expanded CD8+ T cells and an increased ratio of CD8+ effector T cells to effector memory T cells characterized severe disease, while circulating follicular helper T cells accompanied mild disease. We observed a relative loss of IgA2 in symptomatic disease despite an overall expansion of plasmablasts and plasma cells. Our study highlights the coordinated immune response that contributes to COVID-19 pathogenesis and reveals discrete cellular components that can be targeted for therapy

SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion

Abstract: The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era

The relationship between treatment accessibility and preference amongst out-of-treatment individuals who engage in non-medical prescription opioid use

BackgroundRelatively little is known regarding the perception of medication-assisted treatments (MATs) and other treatment options amongst individuals that engage in non-medical prescription opioid use. This study surveyed out-of-treatment individuals that misuse opioids to better understand how perceived access to treatment shapes treatment preference.MethodsParticipants (n=357) were out-of-treatment adults registered as workers on the Amazon Mechanical Turk platform who reported current non-medical prescription opioid use. Participants were surveyed regarding demographics, insurance status, attitudes toward opioid use disorder (OUD) treatments, and self-reported symptoms of OUD.ResultsParticipants who were male, did not have health insurance, and knew that counseling-type services were locally available were most likely to first attempt counseling/detox treatments (χ2(6)=30.19, p<0.001). Participants who met criteria for severe OUD, used heroin in the last 30days, knew their insurance covered MAT, and knew of locally available MAT providers were most likely to first attempt MAT (χ2(4)=26.85, p<0.001). Participants with insurance and who knew of locally available physicians were most likely to attempt physician visits without the expressed purpose of MAT (χ2(3)=24.75, p<0.001).ConclusionOut-of-treatment opioid users were particularly interested in counseling-based services and medical care that could be attained from a primary-care physician. Results suggest that insurance coverage and perceived access to OUD treatment modalities influences where out-of-treatment opioid users might first seek treatment; understanding the factors that shape treatment preference is critical in designing early interventions to effectively reach this population

Substance Use in the Performing Artist with Chronic Pain.

ObjectivesTo evaluate how performing artists (PAs) with chronic pain may differ on measures of substance use compared to non-PA controls.Methods157 participants reporting chronic pain (89 PAs, 68 non-PA controls) completed an online cross-sectional survey. Participants were assessed for self-reported current pain severity using the Brief Pain Inventory Short-Form, opioid misuse risk using the Screener and Opioid Assessment for Patients with Pain-Revised, opioid withdrawal using the Subjective Opiate Withdrawal Scale, and symptoms of opioid use disorder (OUD) using a modified version of the DSM-V checklist.ResultsPAs had lower pain severity (p <0.05, t=2.196, df=155) and lower pain interference (p <0.05, t=2.194) than non-PA controls. 24% of PAs and 13% of controls reported using opioids within the past month. Among PAs, the number of days using opioids in the past month was positively associated with hours spent practicing per week (r=0.508, p <0.05). PAs (66%) were more likely to endorse current alcohol use than controls (44.1%, t= -2.136, X2=7.72, p <0.01). Importantly, PAs (19%) were more likely than controls (3%) to endorse symptoms of at least mild OUD (X2(3)=11.3, p <0.01) and higher ratings of opioid misuse risk (t=-2.166, p <0.05). Past month opioid withdrawal was also greater in PAs than controls (t=-2.136, p <0.05), and 5.6% of PAs and 1.5% of controls reported at least one prior incidence incident of opioid overdose in their lifetime (X2 =1.80, NS).ConclusionsAmong persons with chronic pain, PAs may have higher risk for opioid-related consequences, including OUD, and should be screened during health care encounters

Recovery Goals and Long-term Treatment Preference in Persons Who Engage in Nonmedical Opioid Use

BackgroundWhile most opioid use disorder (OUD) treatment providers consider opioid abstinence to be the preferred outcome, little is known about the treatment preferences of the larger population of individuals who engage in nonmedical opioid use and have not yet sought treatment. This study sought to descriptively quantify the proportion of out-of-treatment individuals with nonmedical opioid use that have abstinent and nonabstinent recovery goals.MethodsParticipants (N = 235) who engage in nonmedical opioid use and met self-reported criteria for OUD were recruited online and participated in a cross-sectional survey on recovery goals and treatment perceptions. Participants were dichotomized as having either abstinent (70.6%) or nonabstinent (29.4%) recovery goals. Participants were presented with 13 treatment options and asked which treatment they would "try first" and which treatment they thought would be the best option for long-term recovery.ResultsPersons in the nonabstinent group were more likely to want to continue use of prescription opioids as prescribed by a physician compared with the abstinent group (χ[1] = 9.71, P = 0.002). There were no group differences regarding preference for individual OUD treatments. The most frequently endorsed treatments that participants would "try first" were physician visits (23.4%), one-on-one counseling (18.7%), and 12-step groups (13.2%), whereas the most frequently endorsed treatments for long-term recovery were one-on-one counseling (17.4%), residential treatment (16.7%), and buprenorphine (15.3%).ConclusionPublic health initiatives to engage out-of-treatment individuals should take into account recovery goals and treatment preferences to maximize treatment initiation and retention

A hidden aspect of the U.S. opioid crisis: Rise in first-time treatment admissions for older adults with opioid use disorder

BackgroundOlder adults with opioid use disorder (OUD) are a medically complex population. The current study evaluated trends in older adults seeking treatment for OUD, with a focus on primary heroin versus prescription opioid use. This study also compared older adults with OUD to the younger OUD population on demographics and drug use behaviors.MethodsPublicly available data from state-certified addiction treatment centers were collected via the Treatment Episode Data Set - Admissions (TEDS-A) between 2004-2015. This study utilized Joinpoint Regression to conduct a cross-sectional, longitudinal analysis of trends in first-time treatment admissions for OUD in adults 55 and older (older adults; n = 400,421) versus adults under the age of 55 (n = 7,795,839). Given the rapid increase in older adults seeking treatment for OUD between 2013-2015, secondary outcomes include changes in demographics and drug use between 2012 (as a baseline year) and 2015.ResultsThe proportion of older adults seeking treatment for OUD rose steadily between 2004-2013 (41.2% increase; p-trend = 0.046), then rapidly between 2013-2015 (53.5% increase; p-trend = 0.009). The proportion of older adults with primary heroin use more than doubled between 2012-2015 (p < 0.001); these individuals were increasingly male (p < 0.001), African American (p < 0.001), and using via the intranasal route of administration (p < 0.001).ConclusionsThere has been a recent surge in older adults seeking treatment for OUD, particularly those with primary heroin use. Specialized treatment options for this population are critically needed, and capacity for tailored elder care OUD treatments will need to increase if these trends continue