Incorporating epilepsy genetics into clinical practice:A 360° evaluation

AbstractWe evaluated a new epilepsy genetic diagnostic and counseling service covering a UK population of 3.5 million. We calculated diagnostic yield, estimated clinical impact, and surveyed referring clinicians and families. We costed alternative investigational pathways for neonatal onset epilepsy. Patients with epilepsy of unknown aetiology onset &lt; 2 years; treatment resistant epilepsy; or familial epilepsy were referred for counseling and testing. We developed NGS panels, performing clinical interpretation with a multidisciplinary team. We held an educational workshop for paediatricians and nurses. We sent questionnaires to referring paediatricians and families. We analysed investigation costs for 16 neonatal epilepsy patients. Of 96 patients, a genetic diagnosis was made in 34% of patients with seizure onset &lt; 2 years, and 4% &gt; 2 years, with turnaround time of 21 days. Pathogenic variants were seen in SCN8A, SCN2A, SCN1A, KCNQ2, HNRNPU, GRIN2A, SYNGAP1, STXBP1, STX1B, CDKL5, CHRNA4, PCDH19 and PIGT. Clinician prediction was poor. Clinicians and families rated the service highly. In neonates, the cost of investigations could be reduced from £9362 to £2838 by performing gene panel earlier and the median diagnostic delay of 3.43 years reduced to 21 days. Panel testing for epilepsy has a high yield among children with onset &lt; 2 years, and an appreciable clinical and financial impact. Parallel gene testing supersedes single gene testing in most early onset cases that do not show a clear genotype-phenotype correlation. Clinical interpretation of laboratory results, and in-depth discussion of implications for patients and their families, necessitate multidisciplinary input and skilled genetic counseling.</jats:p

Comparison of diagnoses of early-onset sepsis associated with use of Sepsis Risk Calculator versus NICE CG149: a prospective, population-wide cohort study in London, UK, 2020–2021

Objective We sought to compare the incidence of early-onset sepsis (EOS) in infants ≥34 weeks’ gestation identified &gt;24 hours after birth, in hospitals using the Kaiser Permanente Sepsis Risk Calculator (SRC) with hospitals using the National Institute for Health and Care Excellence (NICE) guidance.Design and setting Prospective observational population-wide cohort study involving all 26 hospitals with neonatal units colocated with maternity services across London (10 using SRC, 16 using NICE).Participants All live births ≥34 weeks’ gestation between September 2020 and August 2021.Outcome measures EOS was defined as isolation of a bacterial pathogen in the blood or cerebrospinal fluid (CSF) culture from birth to 7 days of age. We evaluated the incidence of EOS identified by culture obtained &gt;24 hours to 7 days after birth. We also evaluated the rate empiric antibiotics were commenced &gt;24 hours to 7 days after birth, for a duration of ≥5 days, with negative blood or CSF cultures.Results Of 99 683 live births, 42 952 (43%) were born in SRC hospitals and 56 731 (57%) in NICE hospitals. The overall incidence of EOS (&lt;72 hours) was 0.64/1000 live births. The incidence of EOS identified &gt;24 hours was 2.3/100 000 (n=1) for SRC vs 7.1/100 000 (n=4) for NICE (OR 0.5, 95% CI (0.1 to 2.7)). This corresponded to (1/20) 5% (SRC) vs (4/45) 8.9% (NICE) of EOS cases (χ=0.3, p=0.59). Empiric antibiotics were commenced &gt;24 hours to 7 days after birth in 4.4/1000 (n=187) for SRC vs 2.9/1000 (n=158) for NICE (OR 1.5, 95% CI (1.2 to 1.9)). 3111 (7%) infants received antibiotics in the first 24 hours in SRC hospitals vs 8428 (15%) in NICE hospitals.Conclusion There was no significant difference in the incidence of EOS identified &gt;24 hours after birth between SRC and NICE hospitals. SRC use was associated with 50% fewer infants receiving antibiotics in the first 24 hours of life