Publications

BACKGROUND

Due to rising rates of opioid addiction and overdose among individuals on chronic opioid therapy, aberrant drug-related behaviors (ADRBs) are an important and challenging issue. Our objective was to qualitatively investigate the documentation of ADRBs in the medical record.

METHODS

Manually abstracted provider notes from an HIV primary care clinic were analyzed using content analysis methods.

RESULTS

Categories of ADRBs identified included patients requesting opioids, obtaining nonprescribed opioids, and becoming emotional about opioids. We also identified several types of provider language used when documenting ADRBs, including purely descriptive language and emotional language such as labeling, frustration, and concern, and responses such as setting conditions for opioid prescription and action-oriented language.

CONCLUSIONS

The impact of including emotional language in the medical record is unknown. Development of instruments that can be used to facilitate ADRB documentation, as well as evidence-based approaches to addressing ADRBs, is needed.

T-cell antigen receptor (TCR) signaling is essential for activation, proliferation, and effector function of T cells. Modulation of both intensity and duration of TCR signaling can regulate these events. However, it remains unclear how individual T cells integrate such signals over time to make critical cell-fate decisions. We have previously developed an engineered mutant allele of the critical T-cell kinase zeta-chain-associated protein kinase 70 kDa (Zap70) that is catalytically inhibited by a small molecule inhibitor, thereby blocking TCR signaling specifically and efficiently. We have also characterized a fluorescent reporter Nur77-eGFP transgenic mouse line in which T cells up-regulate GFP uniquely in response to TCR stimulation. The combination of these technologies unmasked a sharp TCR signaling threshold for commitment to cell division both in vitro and in vivo. Further, we demonstrate that this threshold is independent of both the magnitude of the TCR stimulus and Interleukin 2. Similarly, we identify a temporal threshold of TCR signaling that is required for commitment to proliferation, after which T cells are able to proliferate in a Zap70 kinase-independent manner. Taken together, our studies reveal a sharp threshold for the magnitude and duration of TCR signaling required for commitment of T cells to proliferation. These results have important implications for understanding T-cell responses to infection and optimizing strategies for immunomodulatory drug delivery.