Progression of hepatitis C in the haemophiliac population in Ireland, after 30 years of infection in the pre-DAA treatment era.

INTRODUCTION: Prior to the introduction of viral inactivation of factor concentrates and screening of blood, 225 people with haemophilia became infected with hepatitis C (HCV) in Ireland. AIM: Our aim was to assess liver disease progression and mortality in this population after 30 years of infection. METHODS: Demographic and clinical data were collected from medical records in five hepatology units and one infectious disease unit retrospectively in 2005, and on four subsequent occasions. RESULTS: The participation rate was 73% (165/225). Eighty three percent of patients, who had been tested for RNA (n = 106/128), developed chronic HCV infection. Thirty four percent were co-infected with HIV. All-cause mortality, after approximately 30 years of infection with chronic HCV, was 44% in HIV positive patients and 29% in HIV negative patients. Liver-related mortality was 12.5% and did not vary significantly by HIV status. Thirty seven percent of patients had developed advanced liver disease, including 20% with cirrhosis and 9% with hepatocellular carcinoma. In the pre-interferon-free direct acting antivirals era, 57% (n = 60/106) of patients were treated for HCV, 65% of whom achieved a sustained virological response. Successfully treated patients had few adverse liver outcomes. CONCLUSION: After 30 years of infection, 40% of the patients who had evidence of chronic HCV had developed advanced liver disease, such as cirrhosis and HCC, or had died from liver-related causes. This proportion is high relative to similar international cohorts despite good anti-HCV treatment uptake and responses.

A prolonged outbreak of invasive meningococcal disease in an extended Irish Traveller family across three Health Service Executive (HSE) areas in Ireland, 2010 to 2013.

Between March 2010 and November 2013 eight laboratory-confirmed cases of serogroup B, invasive meningococcal disease (IMD) were identified in an extended Irish Traveller family across three Health Service Executive (HSE) areas of Ireland. Cases were aged between 5 and 46 months, and were either a cousin or sibling of another case. All eight cases survived. Chemoprophylaxis was given to relevant nuclear family members and close contacts on each occasion, but failed to prevent further cases. Neisseria meningitidis isolates from six cases were highly related, belonging to the ST-41/44 clonal complex, and shared the porA designation 7­2,4. In November 2013, the outbreak control team recommended that directly observed ciprofloxacin chemoprophylaxis be administered simultaneously to the extended family, and that the four component meningococcal B (4CMenB) vaccine be administered to family members aged 2 months to 23 years inclusive and relevant close contacts of the eighth case. Subsequently these recommendations were implemented at three regional clinics. Additionally pharyngeal swabs (n=112) were collected to assess carriage rates of N. meningitidis in this extended family. Pharyngeal carriage of N. meningitidis was detected in 15 (13%) family members. From the epidemiological investigation and carriage study overcrowding was the most likely risk factor identified in this outbreak. To date, the combination of directly observed ciprofloxacin chemoprophylaxis and use of 4CMenB vaccine have controlled the outbreak with no further cases diagnosed.

SU-E-T-554: PTV to Skin Proximity for Head and Neck IMRT Treatment Planning.

PURPOSE: The goal of this work was to evaluate measured vs. calculated surface dose as a function of PTV-to-skin proximity and calculation matrix oxel size, determine effects on plan quality, and provide parameters and levels of uncertainty for clinical use. METHODS: A right-sided CTV with the lateral border 5mm from the surface was delineated on the CT data of a head and neck phantom. A 5mm PTV was generated except laterally where distances of 0-5mm were used. A 7-field IMRT plan was generated using the Eclipse TPS. Optimization was performed where 95% of the PTV receives the prescription dose using a matrix size of 2mm3 . Dose calculations were repeated for grid sizes of 1, 3 and 5mm3 . For each plan nine point dose values were obtained just inside the phantom surface, corresponding to a 2cm2 grid near the central target region. Nine ultra-thin TLDs were placed on the phantom surface corresponding to the grid. Measured and calculated dose values were compared. Conformality, homogeneity and target coverage were compared. RESULTS: Surface dose is over-estimated by the TPS by 21 and 8% for 5 and 3mm3 voxels, respectively and accurately predicted for 2mm3 voxels. A voxel size of 1mm3 results in underestimation of 13%. Conformality improves with increasing PTV to skin distance and a CI of unity results for grid sizes of 1-3mm3 between 4 and 4.5mm. Hot spot decreases as the PTV moves away from the surface and falls below 110% at 4mm. Underdosage worsens as the PTV approaches the skin. CONCLUSIONS: For decreasing PTV-to-skin distance with this TPS, isodose conformality decreases, 'hot spot' increases, and target coverage degrades. Surface dose is accurately predicted for a 2mm3 voxel size, while choosing a finer or coarser grid results in underestimation or overestimation, respectively. All of the above appear to hold for VMAT.

Service implications of implementing guidance for oral bowel cleansing agents in colonoscopy.

INTRODUCTION: Bowel preparation has led to serious adverse events. Consequently, regulatory and advisory bodies have issued guidance,including a risk stratification of patients,aiming to minimise this risk. AIMS: To determine the impact of the new guidance on our current practice of Picolax used in colonoscopy with regard to patient stratification,compliance and service implementation. METHODS: Patients listed for day case colonoscopy during October 2009 were audited using data from the hospital and endoscopy databases. A follow-up, structured patient telephone interview evaluated side effects, the assessment process and patient experience. RESULTS: Of the participating 112 patients, 97.4% were clinically reviewed before colonoscopy,98.3% received written instructions and 70% verbal instructions. None had their preparation dispensed by a regulated professional. Although 62% of patients were retrospectively identified as 'at risk' (elderly, with congestive cardiac failure, cirrhosis or chronic kidney disease or on angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, diuretics or non-steroidal anti-inflammatory drugs), none were identified before their procedure. Significant events (postural hypotension, collapse, dizziness, palpitations, faint) were seen in 4.4%, all of whom could potentially be identified as 'at risk' using a stratification of low epidermal growth factor receptor with relevant co-morbidity (congestive cardiac failure or cirrhosis). CONCLUSIONS: Given the difficulties with compliance and the high prevalence of 'at risk' patients, the implementation will be challenging and require significant service redesign.

Surfers' awareness of the preventability of 'surfer's ear' and use of water precautions.

OBJECTIVE: To establish surfers' knowledge of the preventability of external auditory canal exostoses ('surfer's ear'), and their use of water precautions. METHOD: Survey of surfers conducted between December 2009 and March 2010 at beaches in Cornwall, UK. RESULTS: Ninety-two surfers were included (78 males and 14 females, mean age 27 years, standard deviation 7.9 years). Participants were grouped according to their awareness of the preventability of surfer's ear (55 aware, 37 unaware). These groups were comparable in age, surfing history and gender mix (p > 0.05). Surfers aware of the preventability of exostoses (66 per cent) were more likely to use water precautions than those who were not (38 per cent) (p < 0.01). Two surfers used water precautions regularly and 48 used them occasionally. Sixty-one of the 76 surfers who did not use water precautions (ear plugs) suggested they would consider doing so in the future. CONCLUSION: Awareness of the preventability of surfer's ear was associated with greater use of water precautions. Further research should explore reasons for the low uptake of such precautions. Most surfers not already using ear plugs would consider doing so in the future.

Expression of somatostatin receptors in arginine vasopressin hormone-secreting olfactory neuroblastoma--report of two cases.

OBJECTIVE: Arginine vasopressin hormone-secreting olfactory neuroblastomas are extremely rare, with fewer than twenty cases reported in the literature. Two of these cases, both initially presenting with the syndrome of inappropriate antidiuretic hormone, are presented. The second tumour was successfully identified using somatostatin receptor (octreotide) radiographic scintography. METHOD: The pathological specimens from both cases were examined immunohistochemically for somatostatin receptors. RESULTS: Samples from both cases demonstrated positivity for somatostatin receptors. CONCLUSIONS: This report demonstrates the potential use of somatastatin analogues in the investigation, follow-up and treatment of patients with olfactory neuroblastoma.

Adolescent pregnancy and substance use.

The question of just what is the relationship of early pregnancy and childbearing and substance use among adolescents remains unanswered. From a public health perspective, both behaviors are unwanted, and populations that are at risk are often at high risk for both. Perhaps prevention of one behavior may be expected to prevent the other. This, however, may be too simplistic a notion, grounded in misconception of the role of early pregnancy and specific cultural context. Furthermore, several studies have documented a decline of drug use during pregnancy and just after delivery among adolescent mothers. Does this trend continue through the parenting years? If so, for whom? What are the individual maternal, child, and family environmental characteristics that predict a decline in use or continued abstinence after early childbearing? Within the context of poverty, lower educational attainment, minority status, and high prevalence of alcohol and drug use, pregnancy may play a positive role. With a change in role, young women may be less likely than nonparenting peers and less likely than prior to their own pregnancy to become deeply involved in the negative behaviors, such as smoking, drinking, and substance use. Perhaps this is a potential opportunity to intervene. To summarize, the health risk behaviors of substance use and adolescent pregnancy and childbearing appear to be linked. Youths who become pregnant before they complete high school represent a particular group of young women who may be at higher risk than the general population for substance use, at least cigarettes, alcohol, and marijuana. Yet, most pregnant teenagers are not substance users. Among those who are, frequency and amounts of use in most samples were low compared with adult samples of pregnant women. Furthermore, there is evidence that teenagers perceive substance use as a risk to their pregnancies and their unborn children. Among users, there is a decrease in use and increase in quit rates during pregnancy and early childrearing years. Many of these young people are embedded in an environment with very high rates of use among family, partners, and peers. There appears to be strong evidence of covariation of risk behaviors. It is possible that for some youths, pregnancy can be viewed as an opportunity and a chance to intervene to decrease risks for initiating and decrease use among adolescents already using substances. It may be a natural touch point, and pregnancy and parenthood may transition youths out of a high-risk experimentation phase of their adolescence. Further research, especially that of a longitudinal nature, is needed to address the complex issues of adolescent pregnancy and substance use.

Diagnosis of ventilator-associated pneumonia.

The diagnosis of ventilator-associated pneumonia (VAP) is problematic despite numerous attempts at defining acceptable diagnostic criteria and the optimal technique for routine respiratory sampling. Clinical criteria have imperfect diagnostic reliability in ventilated patients, but remain crucial for defining those patients who may require respiratory sampling. Quantitative clinical scoring systems may improve the accuracy of clinical diagnosis in some ventilated patients. Review of published studies suggest that fibreoptic bronchoscopic techniques have greater diagnostic reliability than qualitative endotracheal aspirates, despite inconsistent results when comparing the same techniques in different centres. However, the cost and invasive nature of bronchoscopic methods precludes their use as first-line techniques in VAP. Non-bronchoscopic, non-directed techniques are cheaper, safer and more widely available alternatives to fibreoptic bronchoscopy techniques and have comparable accuracy. Quantitation of respiratory tract cultures is useful in excluding VAP in patients with equivocal signs of pneumonia. The diagnostic threshold of bacterial load that defines the presence of VAP should vary according to the pre-test probability of pneumonia, length of ventilation, antibiotic administration and immunocompetence of the patient.

Isolation of Burkholderia cepacia by enrichment.

Burkholderia cepacia is a recognised cause of respiratory failure in patients with cystic fibrosis. The value of routine use of selective enrichment broth to increase the yield of B cepacia from cystic fibrosis sputa was investigated. Two hundred sputa from 86 adult and paediatric patients were cultured onto B cepacia selective agar and also in enrichment broth. The enrichment broths were subcultured after incubation onto B cepacia selective agar. Fourteen sputa from eight patients yielded B cepacia. In all cases the isolate was recovered from the primary selective agar as well as the enrichment broth subcultures. The routine use of enrichment for cystic fibrosis sputa is of unproven benefit and increases laboratory costs.

A homologue of Drosophila aurora kinase is oncogenic and amplified in human colorectal cancers.

Genetic and biochemical studies in lower eukaryotes have identified several proteins that ensure accurate segregation of chromosomes. These include the Drosophila aurora and yeast Ipl1 kinases that are required for centrosome maturation and chromosome segregation. We have identified two human homologues of these genes, termed aurora1 and aurora2, that encode cell-cycle-regulated serine/threonine kinases. Here we demonstrate that the aurora2 gene maps to chromosome 20q13, a region amplified in a variety of human cancers, including a significant number of colorectal malignancies. We propose that aurora2 may be a target of this amplicon since its DNA is amplified and its RNA overexpressed, in more than 50% of primary colorectal cancers. Furthermore, overexpression of aurora2 transforms rodent fibroblasts. These observations implicate aurora2 as a potential oncogene in many colon, breast and other solid tumors, and identify centrosome-associated proteins as novel targets for cancer therapy.

Hearing aids and glue ear.

This study was designed to determine the acceptance and effectiveness of a hearing aid in the management of children with persistent hearing loss due to glue ear (otitis media with effusion [OME]). Forty-eight children with OME, in whom the main symptom was deafness, were treated with a hearing aid instead of surgery and reviewed at 3-monthly intervals over 6-12 months. Seventy-one per cent reported unequivocal satisfaction with the aid. Sixty-five per cent used the aid continuously throughout the day whilst 35% used it only at specific times of need. Ninety-eight per cent noticed a definite improvement in their hearing whilst using the aid and this was confirmed audiometrically in 100%. Disability was considered in terms of speech development and educational achievement. In 66% there had been a subjective decline in these parameters prior to aid prescription. In all but one child significant improvement was made sufficient to alleviate parental and teachers' concern. No children reported significant symptoms due to OME other than deafness and there were no complications of hearing aid usage. At follow-up, however, 13% of children continued to use a hearing aid in an ear in which the OME had resolved. This study has shown that in this preselected group of children with persistent OME and the predominant symptom of deafness, a hearing aid was an effective treatment for their deafness with high acceptance and compliance.

Tympanic thermometry and minor ear surgery.

Infra-red tympanic thermometry is a relatively new technique for measuring body temperature which requires the minimum of co-operation and is quick and easy to use. It is therefore ideal for use in children. Its use is becoming more widespread and as it is theoretically possible that minor ear surgery may interfere with function its reliability in these patients may be in question. Twenty-two children (mean age 5.3 years) who underwent myringotomy +/- grommet insertion had the tympanic temperature of each ear measured immediately before, and 15 minutes after, surgery on the recovery ward. No difference was found between the pre- and post-operative temperatures (mean difference--0.1 degree C, p > 0.1, paired t-test, hypothesized difference of 0). This thermometer appears to be a reliable way of monitoring body temperature on a paediatric ENT recovery ward in patients who have undergone minor ear surgery.

The occurrence of bacteraemia with skin surgery.

The need for chemoprophylaxis for bacterial endocarditis is partly dependent on the risk of bacteraemia associated with the procedure, which has not been adequately defined for skin surgery. The incidence of postoperative bacteraemia in 149 immunocompetent out-patients with non-infected lesions was 0.7% (95% CI 0.3-3.8%). Procedures included excisions, flaps, grafts and micrographically controlled surgery. Coagulase-negative staphylococcus was the most common skin isolate at the site of surgery, present in 68.5% of patients. The most effective chemoprophylaxis would be intravenous vancomycin, which is inconvenient and has an inherent risk of morbidity. Given the low incidence of bacteraemia and the disadvantages of the optimum chemoprophylaxis, surgery on non-infected lesions does not warrant prophylactic antibiotics to prevent the very low risk of bacterial endocarditis.

Iron-responsive element-binding protein in hemochromatosis liver and intestine.

Iron-responsive element-binding protein (IRE-BP) activity was studied in liver and intestinal samples of hemochromatosis and control patients using a short 32P-IRE-RNA probe on "retardation" nondenaturing polyacrylamide gels. IRE-BP activity was assessed in liver biopsy specimens in 36 patients--16 hemochromatosis homozygotes, 4 hemochromatosis heterozygotes, 6 patients with secondary iron overload, and 10 control patients with normal hepatic iron concentrations. Intestinal IRE-BP activity was assessed in 14 hemochromatosis homozygotes and 16 normal subjects. Endogenous IRE-BP activity was determined from 32P retarded on the gel, and total IRE-BP activity was assessed after reducing tissue samples with 2-mercaptoethanol. Hepatic endogenous IRE-BP activity was inversely related to hepatic iron concentration (r = .59, P < .0002). Mean hepatic endogenous IRE-BP activity in the hemochromatosis homozygotes, 0.25 +/- 0.04 pmol/mg protein, was significantly decreased compared with values in the normal controls, 0.45 +/- 0.06 pmol/mg protein, P < .05. Hepatic total IRE-BP was also significantly decreased in the hemochromatosis patients by gel retardation assay and Western blotting with anti-IRE-BP antibody. Intestinal endogenous IRE-BP activity, total IRE-BP activity, and iron concentration did not significantly differ between hemochromatosis patients and normal control subjects. This suggests that both endogenous IRE-BP activity and the total amount of the protein are downregulated in the liver by tissue iron. Intestinal IRE-BP activity that regulates intestinal transferrin receptor expression is normal in hemochromatosis and appropriate for the intracellular iron concentration.