Comparison of the management recommendations of the Kaiser Permanente neonatal early-onset sepsis risk calculator (SRC) with NICE guideline CG149 in infants ≥34 weeks' gestation who developed early-onset sepsis.

OBJECTIVE: To compare the management recommendations of the Kaiser Permanente neonatal early-onset sepsis risk calculator (SRC) with National Institute for Health and Care Excellence (NICE) guideline CG149 in infants ≥34 weeks' gestation who developed early-onset sepsis (EOS). DESIGN: Retrospective multicentre study. SETTING: Five maternity services in South West of England and Wales. PATIENTS: 70 infants with EOS (<72 hours) confirmed on blood or cerebrospinal fluid culture. METHODS: Retrospective virtual application of NICE and SRC through review of maternal and neonatal notes. MAIN OUTCOME MEASURE: The number of infants recommended antibiotics by 4 hours of birth. RESULTS: The incidence of EOS ≥34 weeks was 0.5/1000 live births. Within 4 hours of birth, antibiotics were recommended for 39 infants (55.7%) with NICE, compared with 27 (38.6%) with SRC. The 12 infants advised early treatment by NICE but not SRC remained well, only one showing transient mild symptoms after 4 hours. Another four babies received antibiotics by 4 hours outside NICE and SRC guidance. The remaining 27 infants (38.6%) received antibiotics when symptomatic after 4 hours. Only one infant who was unwell from birth, died. Eighty-one per cent of all EOS infants were treated for clinical reasons rather than for risk factors alone. CONCLUSION: While both tools were poor in identifying EOS within 4 hours, NICE was superior to SRC in identifying asymptomatic cases. Currently, four out of five EOS have symptoms at first identification, the majority of whom present within 24 hours of birth. Antibiotic stewardship programmes using SRC should include enhanced observation for infants currently treated within NICE guidance.

Accumulation of α-synuclein in the bowel of patients in the pre-clinical phase of Parkinson's disease.

Parkinson's disease primarily affects the central nervous system, but autopsy and small patient studies have revealed autonomic nervous system pathology in most cases. We looked for α-synuclein pathology in routinely acquired biopsies from patients and matched controls. Immunocytochemistry was performed and assessed blind to the clinical diagnoses. One hundred and seventeen gastrointestinal tissue samples from 62 patients, and 161 samples from 161 controls, were examined. Twelve biopsies from seven patients showed accumulation of α-synuclein within mucosal and submucosal nerve fibres, and ganglia, which was more extensive with an antibody to phosphorylated, than with an antibody to non-phosphorylated, α-synuclein. These included gastric, duodenal and colonic biopsies, and were taken up to 8 years prior to the onset of motor symptoms. All patients with positive biopsies had early autonomic symptoms and all controls were negative. This large scale study demonstrates that accumulation of α-synuclein in the gastrointestinal tract is a highly specific finding that could be used to confirm a clinical diagnosis of Parkinson's disease. We have shown that α-synuclein accumulation occurs prior to the onset of motor symptoms in the upper, as well as the lower gastrointestinal tract, remains present in serial biopsies until the onset of motor symptoms and is predominantly composed of phosphorylated α-synuclein. Accumulation of α-synuclein in the bowel therefore offers an accessible biomarker which allows further study of the early stages of the disease and could be of value in the assessment of disease modifying treatments.