The role of the aryl hydrocarbon receptor (AhR) in modulating intestinal ILC3s to optimise gut pathogen resistance in lupus and benefits of nutritional AhR ligands.

BACKGROUND AND AIMS: Dysbiosis is emerging as a potential trigger of systemic lupus erythematosus (SLE). Group 3 innate lymphoid cells (ILC3s) are recognised as key regulators of intestinal homeostasis. The aryl hydrocarbon receptor (AhR) is critical to intestinal ILC3 development and function. This mechanistic review aimed to investigate whether AhR activation of gut ILC3s facilitates IL-22-mediated antimicrobial peptide (AMP) production to enhance colonisation resistance and ameliorate SLE pathology associated with intestinal dysbiosis. Furthermore, nutritional AhR ligand potential to enhance pathogen resistance was explored. METHODOLOGY: This mechanistic review involved a three-tranche systematic literature search (review, mechanism, intervention) using PubMed with critical appraisal. Data was synthesised into themes and summarised in a narrative analysis. RESULTS: Preclinical mechanistic data indicate that AhR modulation of intestinal ILC3s optimises pathogen resistance via IL-22-derived AMPs. Pre-clinical research is required to validate this mechanism in SLE. Data on systemic immune consequences of AhR modulation in lupus suggest UVB-activated ligands induce aberrant AhR signalling while many dietary ligands exert beneficial effects. Data on xenobiotic-origin ligands is varied, although considerable evidence has demonstrated negative effects on Th17 to Treg balance. Limited human evidence supports the role of nutritional AhR ligands in modulating SLE pathology. Preclinical and clinical data support anti-inflammatory effects of dietary AhR ligands. CONCLUSION: Current evidence is insufficient to fully validate the hypothesis that AhR modulation of intestinal ILC3s can enhance pathogen resistance to ameliorate lupus pathology driven by dysbiosis. However, anti-inflammatory effects of dietary AhR ligands suggest a promising role as a therapeutic intervention for SLE.

Identification of risks associated with the prescribing and dispensing of oral anticancer medicines in Ireland.

BACKGROUND: Oral anticancer medicines (OAM) facilitate transfer of cancer care into the community, where safeguards developed in hospitals that control their prescribing, dispensing and administration may not exist. OBJECTIVE: To determine if the systems of prescribing and dispensing OAM in Ireland facilitate clinical verification of the prescription, thereby ensuring treatment is tailored and appropriate for the patient. SETTING: Randomly selected community pharmacies in Ireland and all Irish hospitals with cancer services. METHOD: A questionnaire was sent to a random selection of Irish community pharmacists. A different questionnaire was sent to all Irish hospitals treating cancer patients. One hundred OAM prescriptions were retrospectively reviewed, to assess the information presented and the potential barriers to a community pharmacist performing a clinical verification of the prescription. MAIN OUTCOME MEASURE: Community pharmacist survey: problems experienced when dispensing OAM and risk factors identified with the current system. Hospital pharmacist survey: proportion of hospitals that clinically verify prescriptions for parenteral versus oral anticancer medicines and associated policies. OAM prescription review: proportion of OAM prescriptions that contained sufficient information for a community pharmacist to clinically verify the prescription and safely dispense the medication. RESULTS: Sixty-four percent of community pharmacist respondents felt they did not have enough information available to them to safely dispense these prescriptions, and 74 % felt that patients are at risk with the current Irish system of prescribing and dispensing OAM. Irish hospitals do not have systems to ensure that all OAM prescriptions are clinically verified by a pharmacist. Seventeen different agents were prescribed on the prescriptions reviewed. The information provided to the community pharmacist would have allowed them to clinically verify 7 % of the OAM prescriptions. CONCLUSION: Prescriptions for OAM reach the community pharmacist with little chance that they have been clinically verified in the hospital and the medicine reaches the patient with little chance that the community pharmacist has been able to clinically verify it. Healthcare risks are increased when inadequate information about patients and their medicines are available. Appropriate specialist practitioners should be provided nationally to clinically oversee each stage of the OAM use process.