Dendritic cells inclusion and cell-subset assessment improve flow-cytometry-based proliferation test in non-immediate drug hypersensitivity reactions.

BACKGROUND: Lymphocyte transformation test (LTT) has been widely used to evaluate non-immediate drug hypersensitivity reactions (NIDHRs). However, the lack of standardization and the low sensitivity have limited its routine diagnostic use. The drug presentation by dendritic cells (DCs) and the assessment of proliferation on effector cells have shown promising results. Flow-cytometry-based methods can help apply these improvements. We aimed to assess the added value of using drug-primed-DCs and the determination of the proliferative response of different lymphocyte subpopulations in NIDHRs. METHODS: Patients with confirmed NIDHR were evaluated by both conventional (C-LTT) and with drug-primed-DCs LTT (dDC-LTT)analysing the proliferative response in T cells and other effector cell subpopulations by using the fluorescent molecule, carboxyfluorescein diacetate succinimidyl ester (CFSE). RESULTS: The C-LTT showed a significantly lower sensitivity (29.4%) compared with dDC-LTT (61.8%), which was confirmed analysing each particular clinical entity: SJS-TEN (62.5% vs 87.5%), MPE (15% vs 47.4%) and AGEP (33% vs 80%). When including the effector cell subpopulations involved in each clinical entity, CD3+ +CD4+ Th 1 or CD3+ +NK cells in SJS-TEN, CD3+ +CD4+ Th 1+NK cells in MPE and CD3+ +NK cells in AGEP, we could significantly increase the sensitivity of the in vitro test to 100%, 68.4% and 100%, respectively, with an overall sensitivity of 87% and 85% of specificity in NIDHR. CONCLUSIONS: The use of a flow-cytometry-based test, DCs as drug presenting cells, and focusing on effector cell subpopulations for each clinical entity significantly improved the drug-specific proliferative response in NIDHRs with a unique cellular in vitro test.

Stress reactions following acute situations involving moral challenges among health care professionals.

Many health care professionals have to make morally difficult decisions during acute, stressful situations. The aim was to explore the applicability of an existing qualitatively developed model of individual reactions among professional first responders following such situations using a quantitative approach. According to the model, the interaction of antecedent individual and contextual characteristics affect the immediate emotional reactions to acute, stressful events involving a moral dilemma. Continuous coping efforts and the quality of social support will also affect the long-term positive and negative reactions to the event. The participants (n = 204, about 50% response rate) represented three Swedish health care professions stationed at a university hospital and a regional hospital: Physicians (n = 50), nurses (n = 94) and "others" (n =60, mainly social welfare officers and assistant nurses). Except for the personality dimension emotional stability which was measured using an established instrument, all measurement scales were operationalizations of codes and categories from the qualitative study (ten scales altogether). Four multiple regression analyses were performed with long-term positive and negative reactions in everyday acute and morally extremely taxing situations respectively as dependent variables. The outcome showed that long-term positive reactions covaried with much use of the coping strategies Emotional distancing and Constructive emotional confrontation and a perception of a well-functioning Formal social support. Regarding long-term negative reactions, higher age and little use of Emotional distancing accounted for much of the variance. Immediate emotional reactions also contributed significantly. CONCLUSION: the results largely supported the model concepts and their assumed relationships.