Seilesh Kadambari

First estimates of the potential cost and cost saving of protecting childhood hearing from damage caused by congenital CMV infection

Background Congenital cytomegalovirus (cCMV) is an important cause of childhood deafness, which is modifiable if diagnosed within the first month of life. Targeted screening of infants who do not pass their newborn hearing screening tests in England is a feasible approach to identify and treat cases to improve hearing outcome. Aims To conduct a cost analysis of targeted screening and subsequent treatment for cCMV-related sensorineural hearing loss (SNHL) in an, otherwise, asymptomatic infant, from the perspective of the UK National Health Service (NHS). Methods Using data from the newborn hearing screening programme (NHSP) in England and a recent study of targeted screening for cCMV using salivary swabs within the NHSP, we estimate the cost (in UK pounds (£)) to the NHS. The cost of screening (time, swabs and PCR), assessing, treating and following up cases is calculated. The cost per case of preventing hearing deterioration secondary to cCMV with targeted screening is calculated. Results The cost of identifying, assessing and treating a case of cCMV-related SNHL through targeted cCMV screening is estimated to be £6683. The cost of improving hearing outcome for an infant with cCMV-related SNHL through targeted screening and treatment is estimated at £14 202. Conclusions The costs of targeted screening for cCMV using salivary swabs integrated within NHSP resulted in an estimate of cost per case that compares favourably with other screening programmes. This could be used in future studies to estimate the full economic value in terms of incremental costs and incremental health benefits.

Variation in gentamicin and vancomycin dosage and monitoring in UK neonatal units

BACKGROUND Gentamicin and vancomycin are commonly used in neonatal units for the treatment of life-threatening infections. This study aimed to describe the dosage regimen and the approach to therapeutic drug monitoring (TDM) for both antibiotics in units that participate in a UK neonatal network. METHODS Questionnaires were sent to all units across the Extended Neonatal Network, requesting details of each units dosing regimen and TDM practice. RESULTS A total of 43 (of 114) units replied to the gentamicin questionnaire and 29 to the vancomycin questionnaire. Ten different gentamicin dosing regimens were used, depending on gestational age and weight. Most units (79%) followed British National Formulary for Children dosing guidance regarding vancomycin, but there were nine variations in TDM practice. CONCLUSIONS There is significant variation in gentamicin and vancomycin dosing regimens and TDM guidance across a UK network of neonatal units. The development of standardized, evidence-based protocols should be prioritized.

Feasibility and acceptability of targeted screening for congenital CMV-related hearing loss

Background Congenital cytomegalovirus (cCMV) is the most common non-genetic cause of sensorineural hearing loss (SNHL) in children. Ganciclovir has been shown to prevent the continued deterioration in hearing of children with symptomatic cCMV, but some children with cCMV-related SNHL are unidentified in the neonatal treatment period. Neonatal cCMV screening provides an opportunity to identify infants with cCMV-related SNHL who might benefit from early treatment. Objectives To assess the feasibility (ability to take samples before 3 weeks of age and clinical assessment by 30 days of age) and acceptability (maternal anxiety) of targeted CMV testing of infants who are ‘referred’ for further audiological testing after routine newborn hearing screening programme (NHSP). Methods Parents of infants who have ‘no clear responses’ on routine NHSP before 22 days of life in London and North East England were approached. Salivary and urine samples were tested by CMV PCR. At recruitment and 3 months, the short form Spielberger State-Trait Anxiety Inventory measured maternal anxiety. Results 411 infants were recruited. 99% (407/411) returned a sample; 98% (404/411) successfully yielded a CMV result, 6 had cCMV, all diagnosed on salivary samples taken <22 days of age (1.5%; 95% CI 0.6% to 3.2%). Only 50% returned urine samples compared with 99% returning salivary samples (p<0.001). Using saliva swabs 98% were successfully screened for CMV within 3 weeks. All positive screening CMV results were known by day 23, and 5/6 infants with cCMV were assessed within 31 days. Anxiety was not increased in mothers of infants screened for cCMV. Conclusions Targeted salivary screening for cCMV within the NHSP is feasible, acceptable and detects infants with cCMV-related SNHL who could benefit from early treatment.

A patient's journey.

Dr Joanne Curry of the School of Computing, Engineering and Mathematics together with Dr Kathy Tannous of the School of Business and Professor Anneke Fitzgerald of Griffith University are using innovative modelling and management techniques to improve the coordination of patient care for people with osteoarthritis in various healthcare settings, including hospitals. This research has been funded by Hunter New England Local Health Network.

Childhood meningitis in the conjugate vaccine era: a prospective cohort study

Bacterial conjugate vaccines have dramatically changed the epidemiology of childhood meningitis; viral causes are increasingly predominant, but the current UK epidemiology is unknown. This prospective study recruited children under 16 years of age admitted to 3 UK hospitals with suspected meningitis. 70/388 children had meningitis—13 bacterial, 26 viral and 29 with no pathogen identified. Group B Streptococcus was the most common bacterial pathogen. Infants under 3 months of age with bacterial meningitis were more likely to have a reduced Glasgow Coma Score and respiratory distress than those with viral meningitis or other infections. There were no discriminatory clinical features in older children. Cerebrospinal fluid (CSF) white blood cell count and plasma C-reactive protein at all ages, and CSF protein in infants <3 months of age, distinguished between bacterial meningitis and viral meningitis or other infections. Improved diagnosis of non-bacterial meningitis is urgently needed to reduce antibiotic use and hospital stay.

Enterovirus infections in England and Wales, 2000–2011: the impact of increased molecular diagnostics

There have recently been significant changes in diagnostic practices for detecting enterovirus (EV) infections across England and Wales. Reports of laboratory-confirmed EV infections submitted by National Health Service (NHS) hospital laboratories to Public Health England (PHE) over a 12-year period (2000-2011) were analysed. Additionally, the PHE Virus Reference Department (VRD) electronic database containing molecular typing data from 2004 onwards was interrogated. Of the 13,901 reports, there was a decline from a peak of 2254 in 2001 to 589 in 2006, and then an increase year-on-year to 1634 in 2011. This increase coincided with increasing PCR-based laboratory diagnosis, which accounted for 36% of reported cases in 2000 and 92% in 2011. The estimated annual incidence in 2011 was 3.9/100,000 overall and 238/100,000 in those aged <3 months, who accounted for almost one-quarter of reported cases (n = 2993, 23%). During 2004-2011, 2770 strains were submitted for molecular typing to the VRD, who found no evidence for a predominance of any particular strain. Thus, the recent increase in reported cases closely reflects the increase in PCR testing by NHS hospitals, but is associated with a lower proportion of samples being submitted for molecular typing. The high EV rate in young infants merits further investigation to inform evidence-based management guidance.

Seven-fold increase in viral meningo-encephalitis reports in England and Wales during 2004–2013

OBJECTIVES In highly immunised populations viruses contribute to a substantially higher proportion of meningo-encephalitis cases. This national study aimed to describe population trends in laboratory-confirmed, viral meningo-encephalitis reports in England and Wales over a ten-year period. METHODS Laboratory-confirmed, viral meningo-encephalitis cases submitted by National Health Service hospitals in England and Wales during 2004-13 were analysed. RESULTS There were 9941 laboratory-confirmed reports of viral meningo-encephalitis in England and Wales over the 10-year period. Number of reports increased across all age-groups and for all viruses from 311 (incidence, 0.6/100,000) in 2004 to 2168 in 2013 (incidence, 3.9/100,000). Median age at diagnosis was 30.6 (IQR, 1.3-51.5) years, with a third of cases diagnosed in children. In 2013, infants aged <3 months accounted for 27% (588/2168) of cases, but had the highest incidence (329/100,000). Enteroviruses were responsible for 52% (5133/9941) of all cases and 92% (1952/2121) in <3 month-olds (incidence, 313/100,000 in 2013, equivalent to 77/100,000 live-births) followed by herpes simplex (2885/9941; 29%) and varicella zoster (1342/9941; 13%), mainly among ≥45 year-olds. CONCLUSION Increasing use of molecular testing has led to a 7-fold increase in laboratory-confirmed, viral meningo-encephalitis reports. Large clinical-observational studies are necessary to determine the burden of viral meningo-encephalitis, especially in infants.

Clinically targeted screening for congenital CMV – potential for integration into the National Hearing Screening Programme

Screening for a condition should only be undertaken if certain strict criteria are met. Congenital CMV (cCMV) is a leading cause of sensorineuronal hearing loss (SNHL) and meets many of these criteria, but is not currently screened for in the UK. Ganciclovir reduces CMV‐induced progressive SNHL if treatment is begun in the first month of life. The Newborn Hearing Screening Programme (NHSP) has been shown to identify SNHL at the earliest possible age. The potential of integrating screening for cCMV into the NHSP is discussed to consolidate the link between screening, early diagnosis and management.

Fifteen-minute consultation: diagnosis and management of congenital CMV

Congenital cytomegalovirus (cCMV) infection can result in permanent neurological problems and is a potentially preventable cause of sensorineural hearing loss in the UK. There is an urgency to diagnose and assess cCMV as antiviral treatment and has only been shown to be effective if started in the first 4 weeks of life. A recent randomised controlled trial of 6 months of treatment using oral valganciclovir has shown modest benefit in preventing hearing deterioration and in improving some neurodevelopmental outcomes. Parents and clinicians need to make a timely and informed choice regarding antiviral treatment and ensure that relevant non-pharmaceutical interventions are considered. This paper brings together the current evidence regarding the diagnosis and treatment of cCMV, consensus from two paediatric infectious diseases centres and outlines research priorities.

Integrating rapid diagnostic testing for congenital CMV into the Newborn Hearing Screening Programme: the audiovestibular physician's perspective.

Congenital cytomegalovirus (cCMV) affects 0.3% of all babies born in the UK and accounts for 20% of all childhood sensorineural hearing loss.1 Samples need to be taken in the first 3 weeks of life to confirm congenital infection. Treatment using oral valganciclovir has been shown in a recent randomised controlled trial to prevent hearing deterioration and improve neurocognitive outcomes when started in the first month of life.2 In the absence of a screening programme, the great majority of affected infants are detected in early childhood when no randomised studies have yet shown treatment to be effective. A multicentre cohort study showed that testing for cCMV in …