Paediatric meningitis in the conjugate vaccine era and a novel clinical decision model to predict bacterial aetiology.

OBJECTIVES: The aims of this study were to assess aetiology and clinical characteristics in childhood meningitis, and develop clinical decision rules to distinguish bacterial meningitis from other similar clinical syndromes. METHODS: Children aged <16 years hospitalised with suspected meningitis/encephalitis were included, and prospectively recruited at 31 UK hospitals. Meningitis was defined as identification of bacteria/viruses from cerebrospinal fluid (CSF) and/or a raised CSF white blood cell count. New clinical decision rules were developed to distinguish bacterial from viral meningitis and those of alternative aetiology. RESULTS: The cohort included 3002 children (median age 2·4 months); 1101/3002 (36·7%) had meningitis, including 180 bacterial, 423 viral and 280 with no pathogen identified. Enterovirus was the most common pathogen in those aged <6 months and 10-16 years, with Neisseria meningitidis and/or Streptococcus pneumoniae commonest at age 6 months to 9 years. The Bacterial Meningitis Score had a negative predictive value of 95·3%. We developed two clinical decision rules, that could be used either before (sensitivity 82%, specificity 71%) or after lumbar puncture (sensitivity 84%, specificity 93%), to determine risk of bacterial meningitis. CONCLUSIONS: Bacterial meningitis comprised 6% of children with suspected meningitis/encephalitis. Our clinical decision rules provide potential novel approaches to assist with identifying children with bacterial meningitis. FUNDING: This study was funded by the Meningitis Research Foundation, Pfizer and the NIHR Programme Grants for Applied Research.

Characterizing the burden of invasive Pseudomonas infection on neonatal units in the UK between 2005 and 2011.

Concern about Pseudomonas infection in neonatal units has focused on outbreaks. This study analysed cases of invasive Pseudomonas infection in 18 UK neonatal units participating in the NeonIN Neonatal Infection Surveillance Network from January 2005 to December 2011. Forty-two cases were reported. The majority (35/42, 93%) of cases were late-onset (median 14 days, range 2-262 days), the highest incidence was seen in extremely-low-birthweight infants and all cases were sporadic. One-third of cases were known to be colonized prior to invasive disease. Attributable mortality was 18%. Opportunities for preventing invasive disease due to this important pathogen should be prioritized.

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.

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

UNLABELLED: 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. CONCLUSION: The early diagnosis and treatment of cCMV may prevent a small proportion of late SNHL. In the absence of any screening programme, we provide evidence that clinically targeted screening through the NHSP is a potential option in the UK, enhancing the diagnostic pathway and enabling appropriate early treatment to reduce long-term morbidity.

Clinical course and visual outcome in patients with diabetes mellitus and uveitis.

PURPOSE: We report the clinical course and visual outcome of patients with diabetes mellitus (DM) who subsequently developed uveitis from any cause. METHODS: Longitudinal, retrospective case note review. RESULTS: A total of 36 patients (M/F: 18/18, 58 eyes) were included, Of the 36 patients, 35 had Type 2 DM and one had Type 1 DM. Mean age of onset of DM was 49 years and uveitis 55 years. The uveitis was bilateral in 22 (61%) patients. There were 19 patients with anterior uveitis, 12 with panuveitis and 5 with intermediate uveitis. Mean follow up was 4.4 years (range 1-18). Mean number of uveitis recurrences was 3 (range 1-7). Causes of vision of 6/18 or worse appeared related to the uveitis in 9 eyes and diabetes in 4 eyes. Cataract occurred in 22 eyes, glaucoma in 17 eyes, and cystoid macular oedema in 10 eyes. Diabetic retinopathy was detected in 38 (65.5%) eyes (29 non-proliferative including 6 with clinically significant macular oedema, and 9 proliferative). Progression of diabetic retinopathy to proliferative stage occurred in 7 eyes of 4 patients over a mean duration of 4.4 years. In 10 patients with active uveitis the mean HbA1c was 80 mmol/mol [9.5%], (range 49-137 [6.6-14.7]), and 67 mmol/mol [8.3%] (range 46-105 [6.4-11.8]) when the uveitis was quiescent, p = 0.01. Better glycaemic control was required in 10 patients during episodes of uveitis. CONCLUSIONS: Patients with DM who develop uveitis may have a high complication rate, reduced vision and poor glycaemic control. Checking blood glucose during episodes of uveitis is important.

The dominant human conjunctival epithelial CD8αß+ T cell population is maintained with age but the number of CD4+ T cells increases.

The conjunctiva is a highly specialized ocular mucosal surface that, like other mucosa, houses a number of leukocyte populations. These leukocytes have been implicated in age-related inflammatory diseases such as dry-eye, but their phenotypic characteristics remain largely undetermined. Existing literature provides rudimentary data from predominantly immunohistochemical analyses of tissue sections, prohibiting detailed and longitudinal examination of these cells in health and disease. Using recovered cells from ocular surface impression cytology and flow cytometry, we examined the frequency of leukocyte subsets in human conjunctival epithelium and how this alters with age. Of the total CD45+ leukocyte population within the conjunctival epithelium, 87% [32-99] (median) [range] comprised lymphocytes, with 69% [47-90] identified as CD3 + CD56- T cells. In contrast to peripheral blood, the dominant conjunctival epithelial population was TCRαß + CD8αß + (80% [37-100]) with only 10% [0-56%] CD4+ cells. Whilst a significant increase in the CD4+ population was seen with age (r = 0.5; p < 0.01) the CD8+ population remained unchanged, resulting in an increase in the CD4:CD8 ratio (r = 0.5;p < 0.01). IFNγ expression was detectable in 18% [14-48] of conjunctival CD4+ T cells and this was significantly higher among older individuals (<35 years, 7[4-39] vs. >65 years, 43[20-145]; p < 0.05). The elevation of CD4+ cells highlights a potentially important age-related alteration in the conjunctival intra-epithelial leukocyte population, which may account for the vulnerability of the aging ocular surface to disease.

Evidence based management guidelines for the detection and treatment of congenital CMV.

CMV is the most common congenital infection in newborns worldwide. Congenital CMV causes sensorineural hearing loss in a significant proportion of infected newborns, while the majority of newborns are asymptomatic. In the last three years there have been significant advances in the diagnosis and treatment of congenital CMV. We have developed practical evidence based guidelines for the management of congenital CMV.

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 unit's 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.

Clinical features of patients with diabetes mellitus presenting with their first episode of uveitis.

PURPOSE: Little is known about uveitis in patients with diabetes mellitus (DM). The authors studied diabetic patients with their first episode of uveitis. METHODS: Cross-sectional, case note study documenting the uveitis, underlying cause/syndrome, treatment, type of DM and treatment, and any diabetic retinopathy. RESULTS: There were 34 patients (M/F: 17/17, 48 eyes) with their first uveitis episode (33 had type 2 DM). Mean age of onset of DM 49 years and uveitis 56 years. Uveitis was bilateral in 14 (45%), with most having idiopathic anterior uveitis. Visual acuity 6/18-6/60 in 15 eyes, and worse than 6/60 in 11 eyes. There was 3-4+ flare in 16 eyes, 3-4+ anterior chamber cells in 13 eyes. Diabetic retinopathy was seen in 20 (42%) eyes, and mean blood glucose was 13.64 mmol/L in 11 patients. CONCLUSIONS: Diabetic patients presenting with uveitis, whatever the aetiology, may have severe inflammation, reduced vision, and poor glycaemic control.

Manic-depressive psychosis in a mentally handicapped person: diagnosis and management.

The diagnosis of manic-depressive psychosis in mentally handicapped people can be easily overlooked, partly because its presentation differs from that in people with normal intelligence. This report illustrates some of the difficulties involved in making the diagnosis of manic-depressive psychosis in a mentally handicapped person and in planning for her future care.

Family structure and birth order of patients with anorexia nervosa.

A retrospective case-notes study of 252 patients was undertaken, to focus on their birth order, and other aspects of their sibships. There is little evidence of a relationship to birth order using an established measure (Slater, 1962). Previous researchers have found a preponderance of female siblings in the families of patients with anorexia nervosa. We have not found this, neither is our sample characterised by older or younger siblings of any one sex. This is true for both female and male anorexics. These results are discussed in terms of experimental and family theories concerning the development of anorexia nervosa.