Veterans Health Administration. (PROSPERO: CRD42015020347).

U.S. Department of Veterans Affairs. (PROSPERO: CRD42016033623).

Little is known about patients prescribed high doses of opioids to treat chronic non-cancer pain, though these patients may be at higher risk for medication-related complications. We describe the prevalence of high-dose opioid use and associated demographic and clinical characteristics among veterans treated in a VA regional healthcare network. Veterans with chronic non-cancer pain prescribed high doses of opioids (>=180 mg/day morphine equivalent; n=478) for 90+ consecutive days were compared to two groups with chronic pain: Traditional-dose (5-179 mg/day; n=500) or no opioid (n=500). High-dose opioid use occurred in 2.4% of all chronic pain patients and in 3.4% of all chronic pain patients prescribed opioids long-term. The average dose in the high-dose group was 324.9 (SD=285.1) mg/day. The only significant demographic difference among groups was race (p=0.03) with black veterans less likely to receive high doses. High-dose patients were more likely to have four or more pain diagnoses and the highest rates of medical, psychiatric, and substance use disorders. After controlling for demographic factors and VA facility, neuropathy, low back pain, and nicotine dependence diagnoses were associated with increased likelihood of high-dose prescriptions. High-dose patients frequently did not receive care consistent with treatment guidelines: there was frequent use of short-acting opioids, urine drug screens were administered to only 40.8% of patients in the prior year, and 32.0% received concurrent benzodiazepine prescriptions, which may increase risk for overdose and death. Further study is needed to identify better predictors of high-dose usage, as well as the efficacy and safety of such dosing.

The relationships between immune and neural function are an increasingly important area of study for neuropsychiatric disorders, in particular depression. This is exemplified by the growing number of publications on cytokines and depression during the last 10 years, as compared to earlier decades. This review summarizes the current theories and novel treatment strategies for depression, with a focus on cytokine-induced depression. Neuroimmune mechanisms are now viewed as central to the development of depressive symptoms and emerging evidence is beginning to identify the neural circuits involved in cytokine-induced depression. The current diagnostic categories for depression, as defined by the Diagnostic and Statistical Manual of Mental Disorders, however, are not etiologically or biologically derived, and it has been proposed that "depression", likely reflects multiple pathogeneses leading to varying symptom constellations. As we move toward a better biological understanding of depression-related symptom constellations or syndromes, the term "depression" may prove inadequately broad, and an integration of interdisciplinary literatures will increase in importance. Future research should aim to characterize these depression-related symptom constellations or syndromes better with the goal of optimizing treatment strategies.

The cre(2C) hairpin is a cis-acting replication element in poliovirus RNA and serves as a template for the synthesis of VPgpUpU. We investigated the role of the cre(2C) hairpin on VPgpUpU synthesis and viral RNA replication in preinitiation RNA replication complexes isolated from HeLa S10 translation-RNA replication reactions. cre(2C) hairpin mutations that block VPgpUpU synthesis in reconstituted assays with purified VPg and poliovirus polymerase were also found to completely inhibit VPgpUpU synthesis in preinitiation replication complexes. Surprisingly, blocking VPgpUpU synthesis by mutating the cre(2C) hairpin had no significant effect on negative-strand synthesis but completely inhibited positive-strand synthesis. Negative-strand RNA synthesized in these reactions immunoprecipitated with anti-VPg antibody and demonstrated that it was covalently linked to VPg. This indicated that VPg was used to initiate negative-strand RNA synthesis, although the cre(2C)-dependent synthesis of VPgpUpU was inhibited. Based on these results, we concluded that the cre(2C)-dependent synthesis of VPgpUpU was required for positive-but not negative-strand RNA synthesis. These findings suggest a replication model in which negative-strand synthesis initiates with VPg uridylylated in the 3 poly(A) tail in virion RNA and positive-strand synthesis initiates with VPgpUpU synthesized on the cre(2C) hairpin. The pool of excess VPgpUpU synthesized on the cre(2C) hairpin should support high levels of positive-strand synthesis and thereby promote the asymmetric replication of poliovirus RNA.Poliovirus is a prototypic positive-strand RNA virus with a single-stranded genome that contains a 3Ј-terminal poly(A) tail and a 5Ј-terminal covalently linked protein, VPg (1,15,27). Once released into the cytoplasm of infected cells, poliovirion RNA serves as an mRNA for translation and then as a template for negative-strand synthesis. Multiple rounds of positivestrand synthesis on each molecule of negative-strand RNA result in the synthesis of excess genomic RNA. Overall, the ratio of positive-to negative-strand synthesis is greater than 30:1 (10, 24), which is essential for the production of high yields of virion RNA and progeny virus in infected cells.cis-active replication sequences that are present at the 3Ј and 5Ј ends of poliovirion RNA play an important role in regulating poliovirus RNA replication. The 3Ј nontranslated region (NTR) and the associated poly(A) tail are important cis-active determinants that are required for efficient negative-strand RNA synthesis (14,21,22,28,30,36). The 5Ј-terminal cloverleaf structure in poliovirus RNA is a multifunctional element that is required in cis for negative-strand synthesis, RNA stability, and VPg uridylylation in membrane replication complexes (8,14,17,23,34). A new cis-acting replication element (cre) was recently identified in the genomes of several picornaviruses (9,11,16,18,20). The cre was originally identified in the P1 capsid coding region of HRV14 [cre(VP1)] (19). Mutational analysis of the cr...

The measurement of posttraumatic stress disorder (PTSD) is critically important for the identification and treatment of this disorder. The PTSD Checklist (PCL; F. W. Weathers and J. Ford, 1996) is a self-report measure that is increasingly used. In this study, the authors investigated the factorial validity of the PCL with data from 236 cancer survivors who received a bone marrow or stem cell transplantation. The authors examined the fit of these data with the clinical model of 3 symptom clusters for PTSD, as proposed in the Diagnostic and Statistical Manual of Mental Disorders, and alternative models tested in prior research. By using confirmatory factor analysis the authors found that a 4-first-order-factor model of PTSD provided the best fit. The relations of PTSD symptoms with sociodemographic and medical variables were also explored.

A lifetime diagnosis of pathologic gambling is associated with several medical disorders and increased medical utilization, perhaps leading to a burden on healthcare costs in the United States.

Objectives Little is known about how opioid prescriptions for chronic pain are initiated. We sought to describe patterns of prescription opioid initiation, identify correlates of opioid initiation, and examine correlates of receipt of chronic opioid therapy (COT) among veterans with persistent non-cancer pain. Methods Using Veterans Affairs (VA) administrative data, we identified 5,961 veterans from the Pacific Northwest with persistent elevated pain intensity scores who had not been prescribed opioids in the prior 12 months. We compared veterans not prescribed opioids over the subsequent 12 months to those prescribed any opioid and to those prescribed COT (≥90 consecutive days). Results During the study year, 34% of the sample received an opioid prescription, and 5% received COT. Most first opioid prescriptions were written by primary care clinicians. Veterans prescribed COT were younger, had greater pain intensity, and high rates of psychiatric and substance use disorders (SUDs) compared to veterans in the other two groups. Among patients receiving COT, 29% were prescribed long-acting opioids, 37% received one or more urine drug screens, and 24% were prescribed benzodiazepines. Adjusting for age, sex, and baseline pain intensity, major depression (OR 1.24 [1.10–1.39]; 1.48 [1.14–1.93]) and nicotine dependence (1.34 [1.17–1.53]; 2.02 [1.53–2.67]) were associated with receiving any opioid prescription and with COT, respectively. Discussion Opioid initiations are common among veterans with persistent pain, but most veterans are not prescribed opioids long-term. Psychiatric disorders and SUDs are associated with receiving COT. Many Veterans receiving COT are concurrently prescribed benzodiazepines and many do not receive urine drug screening; additional study regarding practices that optimize safety of COT in this population is indicated.