An exploration of the professional identity of clinical academics using repertory grid technique.

BACKGROUND: Clinicians who divide their time between clinical work and research have contributed to some of the most fundamental breakthroughs in medicine in recent history, yet their role is not always well-understood or valued. Understanding the factors which contribute to career success for clinical academics is critical for supporting this workforce. Social Cognitive Career Theory (SCCT) provides a conceptual framework for career success, incorporating personal and environmental factors. PURPOSE: The aim of this study is to explore clinical academics' construal of successful clinical academic practice and to contribute to a holistic view of the professional identity of the clinical academic. METHODOLOGY: Using a constructivist technique, repertory grid, the authors interviewed ten clinical academics at different career stages in one-to-one structured interviews conducted virtually between November 2020 and April 2021. Data from the interviews were analysed qualitatively and quantitatively. Common themes were identified, analysed, and ranked according to importance with respect to successful clinical academic practice. Using SCCT as a framework, constructs were categorised as personal factors, organisational factors, competencies and person-environment fit. A differential analysis between established/trainee and female/male participants was carried out. SUMMARY OF RESULTS: One hundred and thirty-three constructs were elicited and categorised into 20 themes (constructs). There was consensus among participants that 6 were of high importance with respect to successful clinical academic practice, 8 of intermediate and 4 of low importance, with no consensus on 2 constructs. Personal factors of high importance include innovation and integrity. Competencies including research and teaching skills are highly important, and ability to collaborate is also considered central to successful clinical academic practice. Female participants expressed greater concerns about the impact of familial responsibilities on career progression. DISCUSSION AND CONCLUSIONS: This study highlights the importance of interactions between the person and environment, and characterises the important attributes of successful clinical academics including personal factors such as integrity and innovation.

St Johns wort increases expression of P-glycoprotein: implications for drug interactions.

AIMS: St John's Wort (SJW) is widely used in the treatment of depression but concerns have been raised about its potential to interact with other drugs. Co-administration with SJW has resulted in significant reductions in trough plasma concentrations of indinavir and cyclosporin [1, 2]. Induction of cytochrome P450 3A4 (CYP3A4) has been implicated as the most likely interaction mechanism. However, the magnitude of the interaction seen in clinical practice is greater than that predicted by in vitro studies suggesting additional interaction mechanisms may exist. As indinavir and cyclosporin are substrates for both CYP3A4 and the multi drug transporter P-glycoprotein we hypothesized that modulation of P-glycoprotein expression and function by SJW may contribute to the development of potentially harmful drug-drug interactions. METHODS: Healthy volunteers were randomized to either SJW (0.15%) 600 mg three times daily for 16 days (n = 15) or placebo (n = 7). Blood samples were obtained for P-glycoprotein expression and function at baseline, 16 and 32 days post treatment. Peripheral blood lymphocytes (PBMCs) were isolated by Ficoll density gradient centrifugation, fixed and permeabilized. Cells were stained with a P-glycoprotein specific antibody, quantified by flow cytometry and median fluorescence intensity (MFI) values obtained. Vimentin and IE (nonsense antibody) were used as controls. The presence of the MDR 1 gene product was confirmed by RT-PCR. P-glycoprotein mediated drug efflux was determined as a function of rhodamine efflux in the absence and presence of ritonavir. Data are expressed as mean +/- s.d. and were subjected to nonparametric analysis. RESULTS: P-glycoprotein expression increased 4.2 fold from baseline in subjects treated with SJW (7.0 +/- 1.9 vs 29.5 +/- 14.3 (MFI); P < 0.05). There was no effect with placebo (5.1 +/- 1.3 vs 6.0 +/- 1.9 MFI). SJW increased P-glycoprotein mediated rhodamine efflux (reduced ratio) compared with baseline (0.12 +/- 0.04 vs 0.24 +/- 0.18 P < 0.05). There was no change with placebo. Ritonavir (5 microm) inhibited P-glycoprotein mediated efflux in both groups producing greater intracellular accumulation of rhodamine. However, this effect was attenuated following treatment with SJW (23.9 +/- 15.3% vs 75.4 +/- 16.4% P < 0.05). CONCLUSIONS: SJW increased expression and enhanced the drug efflux function of the multi drug transporter P-glycoprotein in PBMCs of healthy volunteers. This may represent a second mechanism for the drug-herb interactions seen in clinical practice and account for the discrepancies between in vitro and in vivo data. Since P-glycoprotein and CYP3A4 have distinct though overlapping substrates, patients receiving drugs, which are P-glycoprotein substrates should be warned against self-medication with SJW as clinically significant drug interactions may occur.