Methodologic limitations of prescription opioid safety research and recommendations for improving the evidence base

Purpose: The ongoing opioid epidemic has claimed more than a quarter million Americans' lives over the past 15 years. The epidemic began with an escalation of prescription opioid deaths and has now evolved to include secondary waves of illicit heroin and fentanyl deaths, while the deaths due to prescription opioid overdoses are still increasing. In response, the Centers for Disease Control and Prevention (CDC) moved to limit opioid prescribing with the release of opioid prescribing guidelines for chronic noncancer pain in March 2016. The guidelines represent a logical and timely federal response to this growing crisis. However, CDC acknowledged that the evidence base linking opioid prescribing to opioid use disorders and overdose was grades 3 and 4. Methods: Motivated by the need to strengthen the evidence base, this review details limitations of the opioid safety studies cited in the CDC guidelines with a focus on methodological limitations related to internal and external validity. Results: Internal validity concerns were related to poor confounding control, variable misclassification, selection bias, competing risks, and potential competing interventions. External validity concerns arose from the use of limited source populations, historical data (in a fast-changing epidemic), and issues with handling of cancer and acute pain patients' data. We provide a nonexhaustive list of 7 recommendations to address these limitations in future opioid safety studies. Conclusion: Strengthening the opioid safety evidence base will aid any future revisions of the CDC guidelines and enhance their prevention impact

Trends in unintentional polysubstance overdose deaths and individual and community correlates of polysubstance overdose, North Carolina, 2009-2018

Background: Polysubstance involvement is increasing among fatal drug overdoses. However, little is known about the epidemiology of polysubstance drug overdoses. This paper describes emerging trends in unintentional polysubstance overdose deaths in North Carolina (NC) and examines associations with individual and community factors. Methods: Using 2009–2018 NC death certificate data, we identified unintentional drug overdose deaths and commonly involved substances (opioids, stimulants, benzodiazepines, alcohol, and antiepileptics). We examined polysubstance combinations, comparing opioid and non-opioid involved deaths. We examined individual level correlates from death certificate data and community level correlates from the American Community Survey and Robert Wood Johnson Foundation County Health Rankings to quantify associations. Results: From 2009–2018, 53 % of opioid and 19 % of non-opioid overdose deaths involved multiple substances. During this period, polysubstance overdose death increased dramatically, from 2.9 to 12.1 per 100,000 persons, with the greatest increases among drug combinations involving stimulants. The most common polysubstance combinations were: opioids and stimulants (12.1 % of overdose deaths); opioids and benzodiazepines (9.0 %); opioids and alcohol (5.1 %); opioids, stimulants, and benzodiazepines (3.1 %); and opioids, benzodiazepines, and antiepileptics (2.2 %). Compared to overdoses involving opioids alone, overdoses involving combinations of opioids, stimulants, and benzodiazepines involved younger individuals (53.7 % in 15−34 years of age vs. 40.7 %). Men comprised two-thirds of overdoses involving opioids alone, however, overdoses involving opioids, benzodiazepines, and antiepileptics were predominantly among women (60.6 %). Conclusions: Polysubstance involvement has increased among overdose deaths in NC. These findings can be used to inform public health interventions addressing polysubstance deaths and associated individual and community level factors

Sustained impacts of North Carolina prison therapeutic diversion units on behavioral outcomes, mental health, self-injury, and restrictive housing readmission

Therapeutic Diversion Units (TDUs) in North Carolina prisons are intended to reduce cycling of individuals with mental health conditions through restrictive housing (i.e., solitary confinement). This paper investigates if previously identified benefits of TDU are sustained when individuals return to the general prison population. Using administrative data on 3170 people, we compare individuals placed in TDUs to TDU-eligible individuals (i.e., individuals with mental health needs) placed in restrictive housing. We use survival analysis methods to estimate hazard ratios (HRs) with confidence intervals (CIs), controlling for confounders. Compared to restrictive housing placement, TDU placement reduced the hazard of infractions (HR: 0.66; 95% CI: 0.52, 0.84) and subsequent restrictive housing placement (HR: 0.64; 95% CI: 0.55, 0.73) but increased the hazard of self-harm (HR: 2.67; 95% CI: 1.66, 4.29) upon program release to the general prison population. These findings suggest a need for additional investments and research on restrictive housing diversion programming, including post-diversion program supports

Trajectories of child protective services contact among Alaska Native/American Indian and non-Native children

Background: Contact with child protective services (CPS) functions as an independent marker of child vulnerability. Alaska children are an important population for understanding patterns of CPS contact given high rates of contact overall and among specific demographic groups. Objective: We aimed to identify longitudinal trajectory classes of CPS contact among Alaska Native/American Indian (AN/AI) and non-Native children and examine preconception and prenatal risk factors associated with identified classes. Participants and setting: We used data from the Alaska Longitudinal Child Abuse and Neglect Linkage (ALCANLink) project, a linkage of 2009–2011 Alaska Pregnancy Risk Assessment Monitoring System (PRAMS) births with administrative data including CPS records. Methods: We conducted growth mixture modeling to identify trajectory classes of CPS contact from birth to age five years. We used Vermunt's three-step approach to examine associations with preconception and prenatal risk factors. Results: Among AN/AI children, we identified three classes: 1) no/low CPS contact (75.4%); 2) continuous CPS contact (19.6%), and 3) early, decreasing CPS contact (5.0%). Among non-Native children, we identified four classes: 1) no CPS contact (81.3%); 2) low, increasing CPS contact (9.5%); 3) early, rapid decline CPS contact (5.8%); and 4) high, decreasing CPS contact (3.3%). Maternal substance use had the largest impact on probabilities of class membership, increasing the probability of membership in classes characterized by CPS contact, among both AN/AI and non-Native children. Conclusions: Results reveal heterogeneity in longitudinal patterns CPS contact across early childhood among Alaska children and identify maternal substance use as an important target for primary prevention

Impact of a community-based naloxone distribution program on opioid overdose death rates

Background: In August 2013, a naloxone distribution program was implemented in North Carolina (NC). This study evaluated that program by quantifying the association between the program and county-level opioid overdose death (OOD) rates and conducting a cost-benefit analysis. Methods: One-group pre-post design. Data included annual county-level counts of naloxone kits distributed from 2013 to 2016 and mortality data from 2000-2016. We used generalized estimating equations to estimate the association between cumulative rates of naloxone kits distributed and annual OOD rates. Costs included naloxone kit purchases and distribution costs; benefits were quantified as OODs avoided and monetized using a conservative value of a life. Results: The rate of OOD in counties with 1–100 cumulative naloxone kits distributed per 100,000 population was 0.90 times (95% CI: 0.78, 1.04) that of counties that had not received kits. In counties that received >100 cumulative kits per 100,000 population, the OOD rate was 0.88 times (95% CI: 0.76, 1.02) that of counties that had not received kits. By December 2016, an estimated 352 NC deaths were avoided by naloxone distribution (95% CI: 189, 580). On average, for every dollar spent on the program, there was $2742 of benefit due to OODs avoided (95$1,237, $4882). Conclusions: Our estimates suggest that community-based naloxone distribution is associated with lower OOD rates. The program generated substantial societal benefits due to averted OODs. States and communities should continue to support efforts to increase naloxone access, which may include reducing legal, financial, and normative barriers

Measurement of the polarisation of W bosons produced with large transverse momentum in pp collisions at sqrt(s) = 7 TeV with the ATLAS experiment

This paper describes an analysis of the angular distribution of W->enu and W->munu decays, using data from pp collisions at sqrt(s) = 7 TeV recorded with the ATLAS detector at the LHC in 2010, corresponding to an integrated luminosity of about 35 pb^-1. Using the decay lepton transverse momentum and the missing transverse energy, the W decay angular distribution projected onto the transverse plane is obtained and analysed in terms of helicity fractions f0, fL and fR over two ranges of W transverse momentum (ptw): 35 < ptw < 50 GeV and ptw > 50 GeV. Good agreement is found with theoretical predictions. For ptw > 50 GeV, the values of f0 and fL-fR, averaged over charge and lepton flavour, are measured to be : f0 = 0.127 +/- 0.030 +/- 0.108 and fL-fR = 0.252 +/- 0.017 +/- 0.030, where the first uncertainties are statistical, and the second include all systematic effects.Comment: 19 pages plus author list (34 pages total), 9 figures, 11 tables, revised author list, matches European Journal of Physics C versio

Observation of a new chi_b state in radiative transitions to Upsilon(1S) and Upsilon(2S) at ATLAS

The chi_b(nP) quarkonium states are produced in proton-proton collisions at the Large Hadron Collider (LHC) at sqrt(s) = 7 TeV and recorded by the ATLAS detector. Using a data sample corresponding to an integrated luminosity of 4.4 fb^-1, these states are reconstructed through their radiative decays to Upsilon(1S,2S) with Upsilon->mu+mu-. In addition to the mass peaks corresponding to the decay modes chi_b(1P,2P)->Upsilon(1S)gamma, a new structure centered at a mass of 10.530+/-0.005 (stat.)+/-0.009 (syst.) GeV is also observed, in both the Upsilon(1S)gamma and Upsilon(2S)gamma decay modes. This is interpreted as the chi_b(3P) system.Comment: 5 pages plus author list (18 pages total), 2 figures, 1 table, corrected author list, matches final version in Physical Review Letter

Search for displaced vertices arising from decays of new heavy particles in 7 TeV pp collisions at ATLAS

We present the results of a search for new, heavy particles that decay at a significant distance from their production point into a final state containing charged hadrons in association with a high-momentum muon. The search is conducted in a pp-collision data sample with a center-of-mass energy of 7 TeV and an integrated luminosity of 33 pb^-1 collected in 2010 by the ATLAS detector operating at the Large Hadron Collider. Production of such particles is expected in various scenarios of physics beyond the standard model. We observe no signal and place limits on the production cross-section of supersymmetric particles in an R-parity-violating scenario as a function of the neutralino lifetime. Limits are presented for different squark and neutralino masses, enabling extension of the limits to a variety of other models.Comment: 8 pages plus author list (20 pages total), 8 figures, 1 table, final version to appear in Physics Letters