Comparison of NICE Guideline CG149 and the Sepsis Risk Calculator for the Management of Early-Onset Sepsis on the Postnatal Ward.

INTRODUCTION: The NICE guideline CG149 has increased the number of well infants receiving antibiotics for suspected early-onset sepsis (EOS). The Kaiser Permanente sepsis risk calculator (SRC) has safely and dramatically reduced investigations and antibiotics for suspected EOS in the USA. This study evaluates the current management of suspected EOS against the NICE guideline CG149 and the SRC. METHODS: This study is a prospective, multicentre, observational study across 13 neonatal units in London. Infants were born between June and August 2019 at ≥34 weeks gestation and commenced on antibiotics for suspected EOS and cared for on postnatal/transitional care wards. Data were prospectively recorded: risk factors, clinical indicators, investigations, and results. Outcome measures included the following: (1) incidence of EOS and (2) proportion of infants recommended for antibiotics by NICE versus theoretical application of SRC. RESULTS: 1,066/8,856 (12%) infants on postnatal/transitional care wards received antibiotics, 7 of whom had a positive blood culture (group B Streptococcus = 6 and Escherichia coli = 1), making the EOS incidence 0.8/1,000 infants. Six hundred one infants had data for SRC analysis, which recommended "antibiotics" or "blood culture" for 130/601 (21.6%) infants using an EOS incidence of 0.5/1,000 versus 527/601 (87.7%) if NICE was applied. CONCLUSIONS: Currently, 12.0% of infants on postnatal/transitional care wards receive antibiotics for suspected EOS. The SRC could dramatically reduce antibiotic use, but further prospective studies are required to evaluate safety of SRC implementation.

Recent advances in diffusion neuroimaging: applications in the developing preterm brain.

Measures obtained from diffusion-weighted imaging provide objective indices of white matter development and injury in the developing preterm brain. To date, diffusion tensor imaging (DTI) has been used widely, highlighting differences in fractional anisotropy (FA) and mean diffusivity (MD) between preterm infants at term and healthy term controls; altered white matter development associated with a number of perinatal risk factors; and correlations between FA values in the white matter in the neonatal period and subsequent neurodevelopmental outcome. Recent developments, including neurite orientation dispersion and density imaging (NODDI) and fixel-based analysis (FBA), enable white matter microstructure to be assessed in detail. Constrained spherical deconvolution (CSD) enables multiple fibre populations in an imaging voxel to be resolved and allows delineation of fibres that traverse regions of fibre-crossings, such as the arcuate fasciculus and cerebellar-cortical pathways. This review summarises DTI findings in the preterm brain and discusses initial findings in this population using CSD, NODDI, and FBA.

Exploring the multiple-hit hypothesis of preterm white matter damage using diffusion MRI.

BACKGROUND: Preterm infants are at high risk of diffuse white matter injury and adverse neurodevelopmental outcome. The multiple hit hypothesis suggests that the risk of white matter injury increases with cumulative exposure to multiple perinatal risk factors. Our aim was to test this hypothesis in a large cohort of preterm infants using diffusion weighted magnetic resonance imaging (dMRI). METHODS: We studied 491 infants (52% male) without focal destructive brain lesions born at < 34 weeks, who underwent structural and dMRI at a specialist Neonatal Imaging Centre. The median (range) gestational age (GA) at birth was 30+ 1 (23+ 2-33+ 5) weeks and median postmenstrual age at scan was 42+ 1 (38-45) weeks. dMRI data were analyzed using tract based spatial statistics and the relationship between dMRI measures in white matter and individual perinatal risk factors was assessed. We tested the hypothesis that increased exposure to perinatal risk factors was associated with lower fractional anisotropy (FA), and higher radial, axial and mean diffusivity (RD, AD, MD) in white matter. Neurodevelopmental performance was investigated using the Bayley Scales of Infant and Toddler Development, Third Edition (BSITD-III) in a subset of 381 infants at 20 months corrected age. We tested the hypothesis that lower FA and higher RD, AD and MD in white matter were associated with poorer neurodevelopmental performance. RESULTS: Identified risk factors for diffuse white matter injury were lower GA at birth, fetal growth restriction, increased number of days requiring ventilation and parenteral nutrition, necrotizing enterocolitis and male sex. Clinical chorioamnionitis and patent ductus arteriosus were not associated with white matter injury. Multivariate analysis demonstrated that fetal growth restriction, increased number of days requiring ventilation and parenteral nutrition were independently associated with lower FA values. Exposure to cumulative risk factors was associated with reduced white matter FA and FA values at term equivalent age were associated with subsequent neurodevelopmental performance. CONCLUSION: This study suggests multiple perinatal risk factors have an independent association with diffuse white matter injury at term equivalent age and exposure to multiple perinatal risk factors exacerbates dMRI defined, clinically significant white matter injury. Our findings support the multiple hit hypothesis for preterm white matter injury.

Maturation of Sensori-Motor Functional Responses in the Preterm Brain.

Preterm birth engenders an increased risk of conditions like cerebral palsy and therefore this time may be crucial for the brain's developing sensori-motor system. However, little is known about how cortical sensori-motor function matures at this time, whether development is influenced by experience, and about its role in spontaneous motor behavior. We aimed to systematically characterize spatial and temporal maturation of sensori-motor functional brain activity across this period using functional MRI and a custom-made robotic stimulation device. We studied 57 infants aged from 30 + 2 to 43 + 2 weeks postmenstrual age. Following both induced and spontaneous right wrist movements, we saw consistent positive blood oxygen level-dependent functional responses in the contralateral (left) primary somatosensory and motor cortices. In addition, we saw a maturational trend toward faster, higher amplitude, and more spatially dispersed functional responses; and increasing integration of the ipsilateral hemisphere and sensori-motor associative areas. We also found that interhemispheric functional connectivity was significantly related to ex-utero exposure, suggesting the influence of experience-dependent mechanisms. At term equivalent age, we saw a decrease in both response amplitude and interhemispheric functional connectivity, and an increase in spatial specificity, culminating in the establishment of a sensori-motor functional response similar to that seen in adults.

Long-Term Outcome of Open Plantar Fascia Release.

BACKGROUND: Plantar fasciitis is thought to be a self-limiting condition best treated by conservative measures, but despite this many patients have a prolonged duration of symptoms and surgery may be indicated. Partial plantar fascial release is reported to have a short-term success rate of up to 80%, but anecdotally this was not thought to represent our local experience. METHODS: An audit of long-term patient-reported outcomes following open partial plantar fascia release was performed. A total of 30 patients (33 feet) were identified over a 10-year period and case notes were reviewed. Patients were contacted by letter and invited to complete 2 validated patient-reported outcome score questionnaires (Visual Analog Scale-Foot and Ankle [VAS-FA] and Manchester Oxford Foot Questionnaire [MOXFQ]). Responses were received from 24 patients (26 feet). The average ages were 42.4 (range 24-61) for male and 46.2 (range 33-60) for female patients, with a female/male ratio of 2.7:1. The average duration of treatment prior to operative intervention was 3.1 years (range 1-5). Preoperatively, our cohort underwent a range of conservative measures. All patients were reviewed postoperatively, and average time from surgery to completion of questionnaires was 80 months (range 14-130). RESULTS: The outcomes were worse in patients who had received preoperative steroid injections and this was found to be statistically significant. The mean MOXFQ score was 33.6 ± 3.9 (0-64). Mean VAS-FA score was 57.8 ± 4.9 (24-100). CONCLUSION: This study found a negative correlation between duration of follow-up and outcome, in both MOXFQ and VAS-FA, showing that patients continued to improve many years postoperatively. The authors also found worse outcomes with preoperative steroid injections, better outcomes in older patients, and a weak gender bias, suggesting results in men were better than those in women. A prolonged recovery period and generally poor outcomes leads the authors to suggest that open plantar fascia release is of questionable clinical value and that patients may improve in the natural course of the disease, in spite of surgery. LEVEL OF EVIDENCE: Level III, comparative study.

The brain derived neurotrophic factor and influences of stress in depression.

Brain derived neurotrophic factor (BDNF) is a member of the neurotrophin family and is widely expressed throughout the central nervous system (CNS). BDNF is involved in proliferation, differentiation, survival and death of neuronal and non-neuronal cells in the developing and adult CNS. The BDNF hypothesis of depression postulates that a reduction in BDNF is directly involved in the pathophysiology of depression, whilst anti-depressant mediated restoration of BDNF is responsible for the alleviation of the depressive state. This hypothesis is drawn from several studies implicating BDNF in depression and has received considerable support, which will be reviewed in this paper. This review will also discuss the implications of the functional Val66Met polymorphism of the gene encoding BDNF, which may reduce BDNF expression particularly when exposed to stress and thus may play a critical role in the pathogenesis of depression.

Discovering new genetic and psychosocial pathways in Major Depressive Disorder: the NewMood project.

The World Health Organisation predicts that Major Depressive Disorder (MDD) will be the second greatest contributor to the global burden of disease by 2020, however, the neurobiological mechanisms behind the disease and the risk factors for it are yet unknown. NewMood (New Molecules for Mood Disorders) was a research project funded by the EU, collaborating work from 10 European countries with the aim of finding new molecular mechanisms behind MDD to develop more effective treatment options. This review explains the aims and objectives of NewMood and how it intends to achieve them with regards to the current literature. It also outlines two of its most recent projects: genome wide association replication study for single nucleotide polymorphisms (SNPs) increasing susceptibility to MDD and stress related pathways in depression using the cortisol awakening response (CAR). Both of these studies had significant results and could further contribute to our current understanding of MDD.