Opioid use does not limit potent low-dose HIV-1 latency reversal agent boosting.

The combined effects of the HIV-1 and opioid epidemics on virus reservoir dynamics are less well characterized. To assess the impact of opioid use on HIV-1 latency reversal, we studied forty-seven suppressed participants with HIV-1 and observed that lower concentrations of combination latency reversal agents (LRA) led to synergistic virus reactivation ex vivo, regardless of opioid use. The use of a Smac mimetic or low-dose protein kinase C agonist, compounds that did not reverse latency alone, in combination with low-dose histone deacetylase inhibitors generated significantly more HIV-1 transcription than phorbol 12-myristate 13-acetate (PMA) with ionomycin, the maximal known HIV-1 reactivator. This LRA boosting did not differ by sex or race and associated with greater histone acetylation in CD4+ T cells and modulation of T cell phenotype. Virion production and the frequency of multiply spliced HIV-1 transcripts did not increase, suggesting a post-transcriptional block still limits potent HIV-1 LRA boosting.

An analysis of police transport in an Eastern Association for the Surgery of Trauma multicenter trial examining prehospital procedures in penetrating trauma patients.

BACKGROUND: Police transport (PT) of penetrating trauma patients in urban locations has become routine in certain metropolitan areas; however, whether it results in improved outcomes over prehospital Advanced life support (ALS) transport has not been determined in a multicenter study. We hypothesized that PT would not result in improved outcomes. METHODS: This was a multicenter, prospective, observational study of adults (18+ years) with penetrating trauma to the torso and/or proximal extremity presenting at 25 urban trauma centers. Police transport and ALS patients were allocated via nearest neighbor, propensity matching. Transport mode also examined by Cox regression. RESULTS: Of 1,618 total patients, 294 (18.2%) had PT and 1,324 (81.8%) were by ALS. After matching, 588 (294/cohort) remained. The patients were primarily Black (n = 497, 84.5%), males (n = 525, 89.3%, injured by gunshot wound (n = 494, 84.0%) with 34.5% (n = 203) having Injury Severity Score of 16 or higher. Overall mortality by propensity matching was not different between cohorts (15.6% ALS vs. 15.0% PT, p = 0.82). In severely injured patients (Injury Severity Score ≥16), mortality did not differ between PT and ALS transport (38.8% vs. 36.0%, respectively; p = 0.68). Cox regression analysis controlled for relevant factors revealed no association with a mortality benefit in patients transported by ALS. CONCLUSION: Police transport of penetrating trauma patients in urban locations results in similar outcomes compared with ALS. Immediate transport to definitive trauma care should be emphasized in this patient population. LEVEL OF EVIDENCE: Prognostic and Epidemiologic; Level III.

An Eastern Association for the Surgery of Trauma multicenter trial examining prehospital procedures in penetrating trauma patients.

BACKGROUND: Prehospital procedures (PHP) by emergency medical services (EMS) are performed regularly in penetrating trauma patients despite previous studies demonstrating no benefit. We sought to examine the influence of PHPs on outcomes in penetrating trauma patients in urban locations where transport to trauma center is not prolonged. We hypothesized that patients without PHPs would have better outcomes than those undergoing PHP. METHODS: This was an Eastern Association for the Surgery of Trauma-sponsored, multicenter, prospective, observational trial of adults (18+ years) with penetrating trauma to the torso and/or proximal extremity presenting at 25 urban trauma centers. The impact of PHPs and transport mechanism on in-hospital mortality were examined. RESULTS: Of 2,284 patients included, 1,386 (60.7%) underwent PHP. The patients were primarily Black (n = 1,527, 66.9%) males (n = 1,986, 87.5%) injured by gunshot wound (n = 1,510, 66.0%) with 34.1% (n = 726) having New Injury Severity Score of ≥16. A total of 1,427 patients (62.5%) were transported by Advanced Life Support EMS, 17.2% (n = 392) by private vehicle, 13.7% (n = 312) by police, and 6.7% (n = 153) by Basic Life Support EMS. Of the PHP patients, 69.1% received PHP on scene, 59.9% received PHP in route, and 29.0% received PHP both on scene and in route. Initial scene vitals differed between groups, but initial emergency department vitals did not. Receipt of ≥1 PHP increased mortality odds (odds ratio [OR], 1.36; 95% confidence interval [CI], 1.01-1.83; p = 0.04). Logistic regression showed increased mortality with each PHP, whether on scene or during transport. Subset analysis of specific PHP revealed that intubation (OR, 10.76; 95% CI, 4.02-28.78; p < 0.001), C-spine immobilization (OR, 5.80; 95% CI, 1.85-18.26; p < 0.01), and pleural decompression (OR, 3.70; 95% CI, 1.33-10.28; p = 0.01) had the highest odds of mortality after adjusting for multiple variables. CONCLUSION: Prehospital procedures in penetrating trauma patients impart no survival advantage and may be harmful in urban settings, even when performed during transport. Therefore, PHP should be forgone in lieu of immediate transport to improve patient outcomes. LEVEL OF EVIDENCE: Prognostic, level III.

Balancing Patient Autonomy, Surrogate Decision Making, and Physician Non-Maleficence When Considering Do-Not-Resuscitate Orders: An Ethics Case Analysis.

[Full article available at http://rimed.org/rimedicaljournal-2017-10.asp].