AimTo determine the frequency and spectrum of mutations causing Familial Hypercholesterolaemia (FH) in patients attending a single UK specialist hospital lipid clinic in Oxford and to identify characteristics contributing to a high mutation detection rate.Methods289 patients (272 probands) were screened sequentially over a 2-year period for mutations in LDLR, APOB and PCSK9 using standard molecular genetic techniques. The Simon Broome (SB) clinical diagnostic criteria were used to classify patients and a separate cohort of 409 FH patients was used for replication.ResultsAn FH-causing mutation was found in 101 unrelated patients (LDLR = 54 different mutations, APOB p.(Arg3527Gln) = 10, PCSK9 p.(Asp374Tyr) = 0). In the 60 SB Definite FH patients the mutation detection rate was 73% while in the 142 with Possible FH the rate was significantly lower (27%, p < 0.0001), but similar (14%, p = 0.06) to the 70 in whom there was insufficient data to make a clinical diagnosis. The mutation detection rate varied significantly (p = 9.83 × 10−5) by untreated total cholesterol (TC) levels (25% in those <8.1 mmol/l and 74% in those >10.0 mmol/l), and by triglyceride levels (20% in those >2.16 mmol/l and 60% in those <1.0 mmol/l (p = 0.0005)), with both effects confirmed in the replication sample (p for trend = 0.0001 and p = 1.8 × 10−6 respectively). There was no difference in the specificity or sensitivity of the SB criteria versus the Dutch Lipid Clinic Network score in identifying mutation carriers (AROC respectively 0.73 and 0.72, p = 0.68).ConclusionsIn this genetically heterogeneous cohort of FH patients the mutation detection rate was significantly dependent on pre-treatment TC and triglyceride levels.

Introduction: According to the American Stroke Association’s “Guidelines for Acute Ischemic Stroke (2018),” it is a Class IIb recommendation that hospitals set a goal of achieving Door to Needle (DTN) times within 45 minutes in > 50% of ischemic stroke patients who are treated with IV alteplase (tPA). Furthermore, a new Class I recommendation states that “multidisciplinary teams with access to neurological expertise [be utilized] to safely increase IV thrombolytic treatment.” Review of the literature shows that there is still limited research in this area, and the potential exists to discover more about the utility of the pharmacist role in the acute stroke patient. Methods: A retrospective, single-center study of patients who received alteplase for acute ischemic stroke in the Emergency Department, based on the initial “Code Stroke” activation, between January 1, 2019 and July 1, 2020 was conducted. The purpose was to investigate the difference in DTN treatment times when a pharmacist is involved compared with times when a pharmacist is not available. The primary outcome was the median DTN administration time, with secondary outcome of achievement of DTN time < 45 minutes. Results: The patients who had a pharmacist involved in their care (n=30) showed a median DTN time of 42.5 minutes, compared to 58 minutes in the group without pharmacy involvement (n=22). Patients in the pharmacy group achieved a DTN time of < 45 minutes in 57% of cases, versus 32% of cases in the non-pharmacy group. Conclusion: Our current practice in the ED regarding availability of a pharmacist varies, given variable patient volume and limitation of resources in our community-based, Primary Stroke Center. Our data suggests that expanding the number of hours covered by a dedicated pharmacist might help improve DTN times. Though our standard practice is still to provide scheduled, regular training on alteplase to ED nursing staff, the unique expertise and additional benefits provided by a pharmacist may serve to complement and enhance the treatment effectiveness of the entire team.