Tuberous sclerosis complex: clinical features, diagnosis, and prevalence within Northern Ireland

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutations in the TSC1 and TSC2 genes on chromosomes 9 and 16 respectively. Diagnosis is based on clinical features but can be difficult as a result of variable phenotypic expression. With the advantage of mutation analysis in making a diagnosis of TSC, and improved identification of the associated clinical features, there have been few new data on its prevalence and on the proportion of cases due to new mutations. We have performed a retrospective epidemiological study on the prevalence of TSC, the clinical features attributed to it, and the availability of mutational analysis. We identified 73 known patients with TSC (5 deceased): 39 were female and 34 male. Ages ranged from 10 months to 69 years, with a mean age of 27 years 11 months (SD 16y 10mo). The point prevalence of TSC in our study was estimated at I out of 24 956 on the prevalence day (30 April 2004). The majority of patients (42.5%) were diagnosed at less than 15 months of age; 25% were not given a diagnosis on first developing symptoms. In all, 93.2% had epilepsy and 71.2% had a learning disability.* A mutation was identified in 95.8% of those tested (26% TSC1 and 74% TSC2). TSC2 mutations were correlated with a more severe phenotype. The new mutation rate was calculated at 64%. We conclude that the prevalence of TSC is higher than previously calculated. We recommend that all children with epilepsy be assessed for features of TSC. Larger studies will be required to assess the prevalence of mutations in each gene, and genotype-phenotype correlation.

A point prevalence survey of antibiotic prescriptions: benchmarking and patterns of use

center dot Inappropriate antimicrobial use has been associated with increased morbidity and hospital costs.

Changes in the prevalence of badger persecution in Northern Ireland.

Animal populations generally increase after release from hunting pressure and/or cessation of illegal persecution. Implementation of full legislative protection of the Eurasian badger Meles meles in Great Britain is thought to have led to increases in badger abundance due to reduced levels of persecution. Conversely, prevalence of badger persecution in Northern Ireland was historically much higher than in Great Britain, and badger abundance remained stable over time despite similar legislative protection. We examined temporal changes in the prevalence of badger sett disturbance in Northern Ireland from 1990/1993 to 2007/2008 in relation to population status. A total of 56 (12.6%) of 445 setts surveyed during 1990/1993 had been disturbed compared to 29 (4.4%) of 653 setts during 2007/2008. This was a significant decline (-65%) in the incidence of sett disturbance over the 14–18-year period. Most notably, the incidence of digging at badger setts, indicative of local badger baiting activity, declined from 50% to 3.5% of disturbed setts. Signs of recent disturbance were significantly more frequent at disused setts suggesting that once disturbed, badgers may vacate a sett. The number of badger social groups in Northern Ireland did not differ between the two study periods, suggesting that previously high levels of badger persecution did not limit the number of badger social groups. The stability of the badger population in Northern Ireland compared to the growing population in Great Britain cannot be attributed to changes in the prevalence of persecution. Differences in the trajectories of both populations could be due to a range of factors including climate, habitat composition and structure, farming practices or food availability. More work is needed to determine how such factors influence badger population dynamics.

Antimicrobial prescribing in Nursing Homes in Northern Ireland: Results of Two Point-Prevalence Surveys

BACKGROUND: In 2005, the European Commission recommended that all member states should establish or strengthen surveillance systems for monitoring the use of antimicrobial agents. There is no evidence in the literature of any surveillance studies having been specifically conducted in nursing homes (NHs) in Northern Ireland (NI).

OBJECTIVE: The aim of this study was to determine the prevalence of antimicrobial prescribing and its relationship with certain factors (e.g. indwelling urinary catheterization, urinary incontinence, disorientation, etc.) in NH residents in NI.

METHODS: This project was carried out in NI as part of a wider European study under the protocols of the European Surveillance of Antimicrobial Consumption group. Two point-prevalence surveys (PPSs) were conducted in 30 NHs in April and November 2009. Data were obtained from nursing notes, medication administration records and staff in relation to antimicrobial prescribing, facility and resident characteristics and were analysed descriptively.

RESULTS: The point prevalence of antimicrobial prescribing was 13.2% in April 2009 and 10.7% in November 2009, with a 10-fold difference existing between the NHs with the highest and lowest antimicrobial prescribing prevalence during both PPSs. The same NH had the highest rate of antimicrobial prescribing during both April (30.6%) and November (26.0%). The group of antimicrobials most commonly prescribed was the penicillins (April 28.6%, November 27.5%) whilst the most prevalent individual antimicrobial prescribed was trimethoprim (April 21.3%, November 24.3%). The majority of antimicrobials were prescribed for the purpose of preventing urinary tract infections (UTIs) in both April (37.8%) and in November (46.7%), with 5% of all participating residents being prescribed an antimicrobial for this reason. Some (20%) antimicrobials were prescribed at inappropriate doses, particularly those which were used for the purpose of preventing UTIs. Indwelling urinary catheterization and wounds were significant risk factors for antimicrobial use in April [odds ratio {OR} (95% CI) 2.0 (1.1, 3.5) and 1.8 (1.1, 3.0), respectively] but not in November 2009 [OR (95% CI) 1.6 (0.8, 3.2) and 1.2 (0.7, 2.2), respectively]. Other resident factors, e.g. disorientation, immobility and incontinence, were not associated with antimicrobial use. Furthermore, none of the NH characteristics investigated (e.g. number of beds, hospitalization episodes, number of general practitioners, etc.) were found to be associated with antimicrobial use in either April or November 2009.

CONCLUSIONS: This study has identified a high overall rate of antimicrobial use in NHs in NI, with variability evident both within and between homes. More research is needed to understand which factors influence antimicrobial use and to determine the appropriateness of antimicrobial prescribing in this population in general and more specifically in the management of recurrent UTIs.

The prevalence of alpha-1 antitrypsin deficiency in Ireland

Background: Alpha-1 antitrypsin deficiency (AATD) results from mutations in the SERPINA1 gene and classically presents with early-onset emphysema and liver disease. The most common mutation presenting with clinical evidence is the Z mutation, while the S mutation is associated with a milder plasma deficiency. AATD is an under-diagnosed condition and the World Health Organisation recommends targeted detection programmes for AATD in patients with chronic obstructive pulmonary disease (COPD), non-responsive asthma, cryptogenic liver disease and first degree relatives of known AATD patients.

Mutation altering the miR-184 seed region causes keratoconus with cataract

MicroRNAs (miRNAs) bind to complementary sequences within the 3? untranslated region (UTR) of mRNAs from hundreds of target genes, leading either to mRNA degradation or suppression of translation. We found that a mutation in the seed region of miR-184 (MIR184) is responsible for familial severe keratoconus combined with early-onset anterior polar cataract, by deep sequencing of a linkage region known to contain the mutation. The mutant form fails to compete with miR-205 (MIR205) for overlapping target sites on the 3? UTRs of INPPL1 and ITGB4. Although these target genes and miR-205 are expressed widely, the phenotype is restricted to the cornea and lens because of the very high expression of miR-184 in these tissues. Our finding highlights the tissue-specificity of a gene network regulated by a miRNA. Awareness of the important function of miRNAs may aid identification of susceptibility genes and new therapeutic targets for treatment of both rare and common diseases.