Interleukin 6 (IL-6) plays a central role in the immunopathogenesis of rheumatoid arthritis (RA) and tocilizumab [TCZ] (an anti-IL-6 receptor antibody) has been shown to be effective in the treatment of the condition. As up-regulation of IL-6 reduces the activity of cytochrome P450 (CYP) enzymes, blockade of this cytokine may enhance CYP function. This may lead to reduced bioavailability of CYP-metabolized drugs. Due to the increasing use of TCZ, we undertook a systematic literature review to explore such interactions. Our search was conducted in MEDLINE, EMBASE, Web of Science, FDA and EMEA websites for in vitro and in vivo studies, clinical trials and reviews mentioning TCZ and CYP on the basis of the title and abstract. Appropriate articles were further screened based on full-text review to select only those reporting IL-6, TCZ and their potential interaction with CYP-metabolized drugs. Two in vitro studies showed that TCZ-reversed IL-6 induced reduction of CYP isozymes. CYP3A4 mRNA expression was most reduced by IL-6 followed by CYP2C9 and CYP2C19. This change was prevented with TCZ. Three clinical studies investigated the interaction showing simvastatin (CYP3A4 substrate) bioavailability reduced by TCZ and omeprazole bioavailability was decreased by TCZ-induced CYP2C19 activity. The bioavailability of dextromethorphan (CYP2D6 and CYP3A4 substrates) was shown to be unaffected by TCZ treatment. The observed increase in CYP isozyme activity by TCZ is of clinical relevance as the bioavailability of the CYP isozyme substrates were decreased in vivo. As CYP3A4 is the isozyme responsible for the largest proportion of drug metabolism, it is probable that the bioavailability of other drugs may be reduced by TCZ. Thus, clinicians should exercise caution when co-prescribing TCZ and CYP-metabolized drugs. More studies are required to investigate this interaction further.

e18232 Background: Cancer patients are at increased risk of developing diabetes mellitus (DM) or having worsening control of their pre-existent DM. The causes of this are multifactorial but the use of steroids, either in the palliative setting or short-term whilst on chemotherapy, is a significant contributor. An audit carried out at a district general hospital demonstrated that 5% of all oncology admissions were secondary to DM complications. A study was conducted to evaluate the prevalence of impaired blood glucose (BG) control and to assess the value of routine HbA1c testing in this population. Methods: Patients having routine chemotherapy blood tests were also tested for HbA1c over a 10 day period in December 2016. HbA1c diagnostic criteria was used as per NICE guidelines. Information on previous diabetic status, primary tumour type, chemotherapy status (number of cycles and treatment intent) was recorded. Results: 134 patients were tested for HbA1c; 28 (21%) had a HbA1c diagnostic of DM and 32 (24%) were at high risk of DM. The mean HbA1c of those in the DM group was 67.3 mmol/mol (range 48-120). Of the 28 with a HbA1C diagnostic of DM, 13 (46%) were already known to have DM with 15 (54%) being newly diagnosed from this study. 11 (73%) of those with a new diagnosis of DM were receiving a short course of steroids with chemotherapy. 12 patients in the DM group were having chemotherapy with curative intent; 6 of whom were newly diagnosed. Conclusions: 11% of the study cohort met criteria for a new diagnosis of DM with 73% of this group receiving steroids. NICE advises on monitoring of BG for all diabetics receiving steroids. Monitoring of BG and using anti-diabetic medications could prevent DM related complications. This highlights the need to involve local diabetic services and primary care providers for diabetic management. 43% of patients in DM group were receiving chemotherapy with curative intent. This has large implications on cancer survivorship and it is vital that these patients receive appropriate DM treatment. This will not only improve quality of care and patient satisfaction but also lead to significant cost savings from reduced admissions and length of stay in hospital. We therefore recommend a routine HbA1c test for all cancer patients having chemotherapy.

Acute bacterial meningitis (ABM) carries a 20–50% mortality rate with significant morbidity in survivors. Appropriate investigations and expeditious treatment (particularly antibiotics and often steroids) significantly improve outcomes. The National Institute for Clinical and Health Excellence (NICE) has not published guidance directing management in adults despite robust evidence informing treatment. We aimed to evaluate the investigation and initial management of suspected ABM against a European guideline1 in five East Anglian hospitals. We subsequently explored whether the results reflected insufficient knowledge by inviting all doctors in these emergency and acute medical departments to complete a survey. Audit Clinical coding searches over 12 months at 5 hospitals for any type of meningitis identified 32 patients with proven ABM (bacteria in cerebrospinal fluid or typical composition) or those treated as ABM if lumbar puncture (LP) was omitted. 28 patients (88%) survived to discharge. Blood culture collection preceded antibiotics in 28 patients (88%). LP was attempted in 26 patients (81%), all undergoing prior head imaging; 19 patients (73%) merited this scan suggesting that LP (and subsequent antibiotics) were unnecessarily delayed in 7 patients (27%). LP was performed within the recommended 4 hours in 17 patients (65%); the median time to LP was 218 minutes (range: 5–1235). Median time to antibiotic administration from first documented suspicion of ABM was 72 minutes (range: 0–4740); 9 patients (28%) were treated within the recommended 30 minutes. 29 patients (94%) were treated according to local antibiotic policy (or had valid reasoning for deviation). High dose corticosteroids, recommended for non–meningococcal ABM before or with the first antibiotic dose, were given to 11 patients (34%); the remainder had no documented contraindication although 2 patients (6%) later cultured meningococcus. Median time to steroid administration was 17 hours, 16 hours after antibiotics. 25 patients (78%) had seizures or reduced conscious level at presentation; 12 of these (48%) received acyclovir. Survey: 101 doctors (22 consultants, 41 registrars and 38 junior doctors; response rate 62%) completed an online questionnaire addressing ABM management in adults against European guidance.1 18 doctors (18%) correctly identified the indications for head imaging before LP; 1% identified all contraindications to LP. 32% selected the correct indications and 1% the correct contraindications to high–dose corticosteroids. 62% referred to (non–existent) NICE guidelines; none were aware of the European guidelines.1 The majority felt their undergraduate and postgraduate training in managing ABM sufficient and reported a median confidence of 7/10 (where 10=fully confident) in it's management. Conclusions Unjustified variance from European guidelines occurred in one or more aspect of every patient's management. Significant deficits in knowledge, particularly regarding expeditious antibiotic and steroid therapy, appear to be contributory ...