A potentiometric biosensor for rapid on-site disease diagnostics

Quantitative point-of-care (POC) devices are the next generation for serological disease diagnosis. Whilst pathogen serology is typically performed by centralized laboratories using Enzyme-Linked ImmunoSorbent Assay (ELISA), faster on-site diagnosis would infer improved disease management and treatment decisions. Using the model pathogen Bovine Herpes Virus-1 (BHV-1) this study employs an extended-gate field-effect transistor (FET) for direct potentiometric serological diagnosis. BHV-1 is a major viral pathogen of Bovine Respiratory Disease (BRD), the leading cause of economic loss ($2 billion annually in the US only) to the cattle and dairy industry. To demonstrate the sensor capabilities as a diagnostic tool, BHV-1 viral protein gE was expressed and immobilized on the sensor surface to serve as a capture antigen for a BHV-1-specific antibody (anti-gE), produced in cattle in response to viral infection. The gE-coated immunosensor was shown to be highly sensitive and selective to anti-gE present in commercially available anti-BHV-1 antiserum and in real serum samples from cattle with results being in excellent agreement with Surface Plasmon Resonance (SPR) and ELISA. The FET sensor is significantly faster than ELISA (<10 min), a crucial factor for successful disease intervention. This sensor technology is versatile, amenable to multiplexing, easily integrated to POC devices, and has the potential to impact a wide range of human and animal diseases.

The common vaginal commensal bacterium Ureaplasma parvum is associated with chorioamnionitis in extreme preterm labour

OBJECTIVE: To assess the association of vaginal commensal and low grade pathogenic bacteria including Ureaplasma parvum, Ureaplasma urealyticum, Mycoplasma hominis, Mycoplasma genitalium, Group B Streptococcus (GBS), and Gardnerella vaginalis, in women who delivered preterm at less than 37 weeks gestation in the presence or absence of inflammation of the chorioamnionitic membranes.

METHODS: A case control study involving women who delivered before 37 weeks gestation with and without inflammation of chorioamnionitic membranes. A total of 57 placental samples were histologically examined for polymorphonuclear leukocyte infiltration of placental tissue for evidence of chorioamnionitis, and by type-specific nucleic acid amplification for evidence of infection with one or more of the target bacteria. Demographic data was collected for each mother.

RESULTS: Amongst the 57 placental samples, 42.1% had chorioamnionitis and 24.6% delivered in the second trimester of pregnancy; U. parvum, U. urealyticum, G. vaginalis and GBS were all detected in the study with respective prevalence of 19.3%, 3.5%, 17.5% and 15.8%; M.genitalium and M. hominis were not detected. U. parvum was significantly associated with chorioamnionitis (p value = 0.02; OR 5.0; (95% CI 1.2-21.5) and was more common in women who delivered in the second (35.7%) compared to the third trimester of pregnancy (13.9%). None of the other bacteria were associated with chorioamnionitis or earlier delivery and all G.vaginalis positive women delivered in the third trimester of pregnancy (p value 0.04).

CONCLUSIONS: The detection of U. parvum in placental tissue was significantly associated with acute chorioamnionitis in women presenting in extreme preterm labour.

Efficacy and Long-Term Outcomes of Palivizumab Prophylaxis to Prevent Respiratory Syncytial Virus Infection in Infants with Cystic Fibrosis in Northern Ireland

BACKGROUND: RSV causes considerable morbidity and mortality in children. In cystic fibrosis (CF) viral infections are associated with worsening respiratory symptoms and bacterial colonization. Palivizumab is effective in reducing RSV hospitalization in high risk patient groups. Evidence regarding its effectiveness and safety in CF is inconclusive. CF screening in N. Ireland enabled timely palivizumab prophylaxis, becoming routine in 2002.

OBJECTIVES: To determine the effect of palivizumab on RSV-related hospitalization and compare lung function and bacterial colonization at age 6 years for those born pre- and post-introduction of palivizumab prophylaxis.

METHODS: A retrospective audit was conducted for all patients diagnosed with CF during the period from 1997 to 2007 inclusive. RSV-related hospitalization, time to Pseudomonas aeruginosa (PA) 1st isolate, lung function and growth parameters were recorded. Comparisons were made for outcomes pre- and post-introduction of routine palivizumab administration in 2002. A cost evaluation was also performed.

RESULTS: Ninety-two children were included; 47 pre- and 45 post-palivizumab introduction. The overall RSV-positive hospitalization rate was 13%. The relative risk of RSV infection in palivizumab non-recipients versus recipients was 4.78 (95%CI: 1.1-20.7), P = 0.027. Notably, PA 1st isolate was significantly earlier in the palivizumab recipient cohort versus non-recipient cohort (median 57 vs. 96 months, P < 0.025) with a relative risk of 2.5. Chronic PA infection at 6 years remained low in both groups, with similar lung function and growth parameters. Total costs were calculated at £96,127 ($151,880) for the non-recipient cohort versus £137,954 ($217,967) for the recipient cohort.

CONCLUSION: Palivizumab was effective in reducing RSV-related hospitalization infection in CF patients. Surprisingly, we found a significantly earlier time to 1st isolate of PA in palivizumab recipients which we could not explain by altered or improved diagnostic tests. 

Genomic meningococcal load in the nasopharynx of children with meningococcal disease

This study demonstrates the feasibility of using quantitative real time PCR to measure genomic bacterial load in the nasopharynx of children with invasive meningococcal disease and shows that these loads are exceptionally high (median 6.6 x 105 (Range 1.2 x 105 to 1.1 x 108) genome copies of Neisseria meningitidis per swab).

Night-to-night variation of pulse oximetry in children with sleep-disordered breathing

BACKGROUND: Sleep-disordered breathing is a common and serious feature of many paediatric conditions and is particularly a problem in children with Down syndrome. Overnight pulse oximetry is recommended as an initial screening test, but it is unclear how overnight oximetry results should be interpreted and how many nights should be recorded.

METHODS: This retrospective observational study evaluated night-to-night variation using statistical measures of repeatability for 214 children referred to a paediatric respiratory clinic, who required overnight oximetry measurements. This included 30 children with Down syndrome. We measured length of adequate trace, basal SpO2, number of desaturations (>4% SpO2 drop for >10 s) per hour ('adjusted index') and time with SpO2<90%. We classified oximetry traces into normal or abnormal based on physiology.

RESULTS: 132 out of 214 (62%) children had three technically adequate nights' oximetry, including 13 out of 30 (43%) children with Down syndrome. Intraclass correlation coefficient for adjusted index was 0.54 (95% CI 0.20 to 0.81) among children with Down syndrome and 0.88 (95% CI 0.84 to 0.91) for children with other diagnoses. Negative predictor value of a negative first night predicting two subsequent negative nights was 0.2 in children with Down syndrome and 0.55 in children with other diagnoses.

CONCLUSIONS: There is substantial night-to-night variation in overnight oximetry readings among children in all clinical groups undergoing overnight oximetry. This is a more pronounced problem in children with Down syndrome. Increasing the number of attempted nights' recording from one to three provides useful additional clinical information.

Supporting Mothers Bereaved by Suicide in Northern Ireland:Integrating Research and Practice

Fetal umbilical artery Doppler pulsatility index and childhood neurocognitive outcome at 12 years

OBJECTIVE: To determine whether an elevated fetal umbilical artery Doppler (UAD) pulsatility index (PI) at 28 weeks' gestation, in the absence of fetal growth restriction (FGR) and prematurity, is associated with adverse neurocognitive outcome in children aged 12 years.

METHODS: Prospective cohort study, comparing children with a normal fetal UAD PI (<90th centile) (n=110) and those with an elevated PI (≥90th centile) (n=40). UAD was performed at 28, 32 and 34 weeks gestation. At 12 years of age, all children were assessed under standardised conditions at Queen's University, Belfast, UK to determine cognitive and behavioural outcomes using the British Ability Score-II and Achenbach Child Behavioural Checklist Parent Rated Version under standardised conditions. Regression analysis was performed, controlling for confounders such as gender, socioeconomic status and age at assessment.

RESULTS: The mean age of follow-up was 12.4 years (±0.5 SD) with 44% of children male (n=63). When UAD was assessed at 28 weeks, the elevated fetal UAD group had lower scores in cognitive assessments of information processing and memory. Parameters included (1) recall of objects immediate verbal (p=0.002), (2) delayed verbal (p=0.008) and (3) recall of objects immediate spatial (p=0.0016). There were no significant differences between the Doppler groups at 32 or 34 weeks' gestation.

CONCLUSIONS: An elevated UAD PI at 28 weeks' gestation in the absence of FGR or prematurity is associated with lower scores of declarative memory in children aged 12 years. A potential explanation for this is an element of placental insufficiency in the presence of the appropriately grown fetus, which affects the development of the fetal hippocampus and information processing and memory long-term. These findings, however, had no impact on overall academic ability, mental processing and reasoning or overall behavioural function.

A systematic review of evidence-based assessment practices by allied health practitioners for children with cerebral palsy

AIM: The routine use of psychometrically robust assessment tools is integral to best practice. This systematic review aims to determine the extent to which evidence-based assessment tools were used by allied health practitioners for children with cerebral palsy (CP).

METHOD: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis protocols 2015 was employed. A search strategy applied the free text terms: 'allied health practitioner', 'assessment', and 'cerebral palsy', and related subject headings to seven databases. Included articles reported assessment practices of occupational therapists, physiotherapists, or speech pathologists working with children with CP aged 0 to 18 years, published from the year 2000.

RESULTS: Fourteen articles met the inclusion criteria. Eighty-eight assessment tools were reported, of which 23 were in high use. Of these, three tools focused on gross motor function and had acceptable validity for use with children with CP: Gross Motor Function Measure, Gross Motor Function Classification System, and goniometry. Validated tools to assess other activity components, participation, quality of life, and pain were used infrequently or not at all.

INTERPRETATION: Allied health practitioners used only a few of the available evidence-based assessment tools. Assessment findings in many areas considered important by children and families were rarely documented using validated assessment tools.