No abstract

Resting CD4+ T cells infected with HIV persist in the presence of suppressive anti-viral therapy (ART) and are barriers to a cure. One potential curative approach, therapeutic vaccination, is fueled by recognition of the ability of a subset of elite controllers (EC) to control virus without therapy due to robust anti-HIV immune responses. Controllers have low levels of integrated HIV DNA and low levels of replication competent virus, suggesting a small reservoir. As our recent data indicates some reservoir cells can produce HIV proteins (termed GPR cells for Gag-positive reservoir cells), we hypothesized that a fraction of HIV-expressing resting CD4+ T cells could be efficiently targeted and cleared in individuals who control HIV via anti-HIV cytotoxic T lymphocytes (CTL). To test this we examined if superinfected resting CD4+ T cells from EC express HIV Gag without producing infectious virus and the susceptibility of these cells to CTL. We found that resting CD4+ T cells expressed HIV Gag and were cleared by autologous CD8+ T cells from EC. Importantly, we found the extent of CTL clearance in our in vitro assay correlates with in vivo reservoir size and that a population of Gag expressing resting CD4+ T cells exists in vivo in patients well controlled on therapy.

ICD-9 code 427.5 is sensitive and specific for identifying ED patients who suffer OHCA with a positive predictive value of 92%.

Objectives To describe the frequency and risk of return visit to the emergency department (ED) by older adults after prescription of any of four potentially inappropriate medication (PIM) classes included in the 2015 Beers Criteria commonly used for the relief of acute pain in the ED. Design Retrospective cohort study. Setting Large urban academic ED from January 1, 2013, to December 31, 2015. Participants Patients age 65 and older discharged from the ED with an initial pain score of 1 or higher (11 822 visits). Measurements Prescriptions for PIM classes were collected from the medical record: nonsteroidal anti‐inflammatory drugs (NSAIDs), benzodiazepines, skeletal muscle relaxants, and opioids. The proportion of patients with ED returns within 9 days were compared by medication class and pain severity (mild, moderate, or severe). Multivariable logistic regression was performed for each pain category to determine adjusted odds ratios (aORs) of ED return. Results Of 11 822 included patients, PIMs were prescribed in 3392 (28.7%): 2550 (21.6%) opioids, 826 (7.0%) NSAIDs, 277 (2.3%) benzodiazepines, and 68 (0.6%) nonbenzodiazepine skeletal muscle relaxants. Total 9‐day ED returns were 1125 (9.5%): mild 7.0%, moderate 8.3%, and severe pain 11.7%. Opioids were not associated with more frequent ED returns for mild or moderate pain, and they were associated with less frequent ED returns for severe pain (9.2% vs 12.7%; p < .001; aOR 0.69; 95% confidence interval [CI] = 0.54‐0.87). Benzodiazepines were associated with more frequent ED returns for patients with moderate pain (15.5% vs 8.2%; p < .01; aOR = 2.01; 95%CI = 1.10‐3.70). Conclusions These results are consistent with recommendations to limit benzodiazepine prescriptions for older adults and that among older adults with severe pain, opioid prescribing is associated with less frequent ED visits within 9 days of discharge. However, this study was not designed to evaluate safety, adverse events, or other important patient‐centered outcomes. J Am Geriatr Soc 67:719–725, 2019.