Expert opinion on diagnosing, treating and managing patients with cerebrotendinous xanthomatosis (CTX): a modified Delphi study.

BACKGROUND: Cerebrotendinous xanthomatosis (CTX) is a rare, chronic, progressive, neurodegenerative disorder requiring life-long care. Patients with CTX often experience a diagnostic delay. Although early diagnosis and treatment initiation can improve symptoms and prognosis, a standardised approach to diagnosis, treatment and management of patients is not yet established. AIM: To assess expert opinion on best care practices for patients with CTX using a modified Delphi method. METHODS: A multidisciplinary group of healthcare professionals with expertise in CTX responded to a 3-round online questionnaire (n = 10 in Rounds 1 and 2; n = 9 in Round 3), containing questions relating to the diagnosis, treatment, monitoring, multidisciplinary care and prognosis of patients with CTX. Determination of consensus achievement was based on a pre-defined statistical threshold of ≥ 70% Delphi panellists selecting 1-2 (disagreement) or 5-6 (agreement) for 6-point Likert scale questions, or ≥ 70% Delphi panellists choosing the same option for ranking and proportion questions. RESULTS: Of the Round 1 (n = 22), Round 2 (n = 32) and Round 3 (n = 26) questions for which consensus was assessed, 59.1%, 21.9% and 3.8% reached consensus, respectively. Consensus agreement that genetic analyses and/or determination of serum cholestanol levels should be used to diagnose CTX, and dried bloodspot testing should facilitate detection in newborns, was reached. Age at diagnosis and early treatment initiation (at birth, where possible) were considered to have the biggest impact on treatment outcomes. All panellists agreed that chenodeoxycholic acid (CDCA) is a lifetime replacement therapy which, if initiated early, can considerably improve prognosis as it may be capable of reversing the pathophysiological process in CTX. No consensus was reached on the value of cholic acid therapy alone. Monitoring patients through testing plasma cholestanol levels and neurologic examination was recommended, although further research regarding monitoring treatment and progression of the disease is required. Neurologists and paediatricians/metabolic specialists were highlighted as key clinicians that should be included in the multidisciplinary team involved in patients' care. CONCLUSIONS: The results of this study provide a basis for standardisation of care and highlight key areas where further research is needed to inform best practices for the diagnosis, treatment and management of patients with CTX.

Traumatic hyphaema in children: a retrospective and prospective study of outcomes at an Australian paediatric centre.

OBJECTIVE: This study aims to evaluate the presenting characteristics, management, outcomes and complications for paediatric traumatic hyphaema in Western Australia. METHODS AND ANALYSIS: A retrospective review of medical records was conducted for consecutive patients ≤16 years of age admitted for traumatic hyphaema to Princess Margaret Hospital for Children (Perth, Australia) between January 2002 and December 2013 (n=82). From this sample, a cohort whose injury occurred ≥5 years prior attended a prospective ocular examination (n=16). Hospital records were reviewed for patient demographics, injury details, management, visual outcomes and complications. The prospective cohort underwent examination for visual and structural outcomes. RESULTS: Most injuries (72%) resulted from projectile objects. Angle recession was present in 53% and was associated with projectiles (p=0.002). Most eyes (81%) achieved a final visual acuity of 0.3 logarithm of the minimum angle of resolution (logMAR) (20/40) or better. Age ≤5 years and posterior segment injury were significant predictors of final visual acuity poorer than 0.3 logMAR. At ≥5 years post-trauma, injured eyes had greater intraocular pressure (IOP) (p=0.024) and anterior chamber depth (ACD) (p=0.022) compared with sound eyes. IOP asymmetry was associated with angle recession (p=0.008) and ACD asymmetry (p=0.012). CONCLUSION: Poorer visual outcomes are associated with younger age at injury and posterior segment injury. Angle recession and ACD asymmetry are associated with IOP asymmetry 5-12 years after injury.

Paediatric ocular and adnexal injuries requiring hospitalisation in Western Australia.

BACKGROUND: The aim was to investigate the characteristics and outcomes of ocular and adnexal injuries requiring hospitalisation in children in Perth, Western Australia. METHODS: This is a hospital-based retrospective review of children admitted to Princess Margaret Hospital for Children with diagnoses of ocular and/or adnexal trauma from 2002-2013. Hospital charts were reviewed for demographic information, injury and management details, follow-up and visual outcome. Final visual acuity was categorised into three groups: 6/12 or better, from 6/12 to 6/60, worse than 6/60. Ordinal logistic regression was used to compute odds ratios and predicted probabilities for each category of final visual outcome. RESULTS: Over the 12-year time period, 482 children were admitted with ocular or adnexal injuries - an average of 40 admissions per year. The mean age of the cohort was 7.1 years (range 0.09 to 16.47 years) with a male to female ratio of 2.6:1.0. There were 185 closed-globe injuries, 72 open-globe injuries and 293 adnexal injuries. Fourteen per cent of the cohort sustained a combined globe and adnexal injury. Children in the up to five-year age group were most susceptible to injury. Eighty-two per cent of the group had a final visual acuity of 6/12 or better. Factors associated with poor visual outcomes included younger age (p < 0.01), open-globe injury (p < 0.01) and lens injury (p < 0.01). CONCLUSIONS: Based on the outcomes of our review, paediatric ocular and adnexal trauma are significant causes for hospital attendance in childhood. Identifying associated risk factors will help develop injury prevention strategies to promote eye safety for children.

Sports-related eye and adnexal injuries in the Western Australian paediatric population.

PURPOSE: To identify the causes of sports-related eye and adnexal injuries in children in Perth, Western Australia, to determine which sporting activities pose the highest risk of eye and adnexal injury to children. METHODS: We performed a 12-year retrospective review of children admitted to hospital from 2002 to 2013 with sports-related ocular and adnexal eye injuries. The main outcome measures were the cause and type of ocular and adnexal injuries, age and gender risk factors. RESULTS: A total of 93 cases of sports-related ocular and adnexal injury were identified in the 12-year time period. A peak in injuries occurred for 12- to 14-year-olds with a second peak in 6- to 8-year-olds; the median age was 8.82 years (range = 1.59-16.47). Cycling, football (including soccer and Australian Rules Football), tennis, trampolining, fishing and swimming were the sports responsible for the greatest number of injuries, a total of 63%. More than one-third (35%) of injuries resulted from being struck by a blunt object, and more than a quarter (26%) were as a result of contact with a blunt projectile. CONCLUSION: Serious ocular and adnexal injuries have occurred in children as a result of participating in sports, with cycling and football being the largest contributors in the 12-year period we assessed. As we continue to encourage children to spend more time participating in sports and recreational activities, identifying associated risk factors will help us develop injury prevention strategies to promote eye safety for children.

Campylobacter jejuni biofilms contain extracellular DNA and are sensitive to DNase I treatment.

Biofilms make an important contribution to survival and transmission of bacterial pathogens in the food chain. The human pathogen Campylobacter jejuni is known to form biofilms in vitro in food chain-relevant conditions, but the exact roles and composition of the extracellular matrix are still not clear. Extracellular DNA has been found in many bacterial biofilms and can be a major component of the extracellular matrix. Here we show that extracellular DNA is also an important component of the C. jejuni biofilm when attached to stainless steel surfaces, in aerobic conditions and on conditioned surfaces. Degradation of extracellular DNA by exogenous addition of DNase I led to rapid biofilm removal, without loss of C. jejuni viability. Following treatment of a surface with DNase I, C. jejuni was unable to re-establish a biofilm population within 48 h. Similar results were obtained by digesting extracellular DNA with restriction enzymes, suggesting the need for high molecular weight DNA. Addition of C. jejuni genomic DNA containing an antibiotic resistance marker resulted in transfer of the antibiotic resistance marker to susceptible cells in the biofilm, presumably by natural transformation. Taken together, this suggest that eDNA is not only an important component of C. jejuni biofilms and subsequent food chain survival of C. jejuni, but may also contribute to the spread of antimicrobial resistance in C. jejuni. The degradation of extracellular DNA with enzymes such as DNase I is a rapid method to remove C. jejuni biofilms, and is likely to potentiate the activity of antimicrobial treatments and thus synergistically aid disinfection treatments.

Animal-inflicted ocular and adnexal injuries in children: A systematic review.

Eye injury remains the leading cause of monocular blindness in children despite 90% of injuries being potentially preventable. Children interact with animals in a variety of situations, and the associated dangers may be underestimated. Animals are capable of causing ocular and adnexal injuries that are cosmetically and visually devastating. We examine the current literature regarding the nature and severity of animal-inflicted ocular and adnexal injuries in children.

Prevention of biofilm formation and removal of existing biofilms by extracellular DNases of Campylobacter jejuni.

The fastidious nature of the foodborne bacterial pathogen Campylobacter jejuni contrasts with its ability to survive in the food chain. The formation of biofilms, or the integration into existing biofilms by C. jejuni, is thought to contribute to food chain survival. As extracellular DNA (eDNA) has previously been proposed to play a role in C. jejuni biofilms, we have investigated the role of extracellular DNases (eDNases) produced by C. jejuni in biofilm formation. A search of 2791 C. jejuni genomes highlighted that almost half of C. jejuni genomes contains at least one eDNase gene, but only a minority of isolates contains two or three of these eDNase genes, such as C. jejuni strain RM1221 which contains the cje0256, cje0566 and cje1441 eDNase genes. Strain RM1221 did not form biofilms, whereas the eDNase-negative strains NCTC 11168 and 81116 did. Incubation of pre-formed biofilms of NCTC 11168 with live C. jejuni RM1221 or with spent medium from a RM1221 culture resulted in removal of the biofilm. Inactivation of the cje1441 eDNase gene in strain RM1221 restored biofilm formation, and made the mutant unable to degrade biofilms of strain NCTC 11168. Finally, C. jejuni strain RM1221 was able to degrade genomic DNA from C. jejuni NCTC 11168, 81116 and RM1221, whereas strain NCTC 11168 and the RM1221 cje1441 mutant were unable to do so. This was mirrored by an absence of eDNA in overnight cultures of C. jejuni RM1221. This suggests that the activity of eDNases in C. jejuni affects biofilm formation and is not conducive to a biofilm lifestyle. These eDNases do however have a potential role in controlling biofilm formation by C. jejuni strains in food chain relevant environments.