Antinuclear antibodies (ANA) in chronic hepatitis C virus infection: correlates of positivity and clinical relevance.

We examined correlates of antinuclear antibody (ANA) positivity (ANA+) in individuals with chronic hepatitis C virus (HCV) infection and the effect of positivity on clinical outcome of HCV. Pretreatment sera from 645 patients from three centres in Sweden (n = 225), the UK (n = 207) and Italy (n = 213) were evaluated by indirect immunofluorescence on Hep-2 cells for ANA pattern and titre by a single laboratory. Liver biopsies were all scored by one pathologist. A total of 258 patients were subsequently treated with interferon monotherapy. There was a significant difference in the prevalence of ANA (1:40) by geographic location: Lund 4.4%, London 8.7%, Padova 10.3% [odds ratio (OR) = 0.66; 95% CI: 0.46-0.94; P = 0.023]. Duration of HCV infection, age at infection, current age, route of infection, viral genotype, alcohol consumption, fibrosis stage and inflammatory score were not correlated with ANA+ or ANA pattern. Female gender was correlated with ANA+ and this association persisted in multivariable analyses (OR = 3.0; P = 0.002). Increased plasma cells were observed in the liver biopsies of ANA-positive individuals compared with ANA-negative individuals, while a trend towards decreased lymphoid aggregates was observed [hazard ratio (HR) = 9.0, P = 0.037; HR = 0.291, P = 0.118, respectively]. No correlations were observed between ANA positivity and nonresponse to therapy (OR = 1.4; P = 0.513), although ANA+ was correlated with faster rates of liver fibrosis, this was not statistically significant (OR = 1.8; P = 0.1452). Low titre ANA+ should not be a contraindication for interferon treatment. Our observation of increased plasma cells in ANA+ biopsies might suggest B-cell polyclonal activity with a secondary clinical manifestation of increased serum immunoglobulins

Delirium: assessment and treatment of patients with cancer PART 2

Delirium at the end of life may present significant ethical dilemmas in clinical practice: whether to simply treat it in order to maximise symptom relief, with the resulting side effect being palliative sedation, or to attempt to reverse delirium and risk prolonging suffering. Determining whether the delirium can be reversed involves comprehensive assessment using established tools, which may or may not provide the answer to the question posed. This article examines the evidence surrounding several assessment tools that have been suggested as effective in identifying delirium, and the consequences of various approaches to the management of delirium in a patient with a cancer diagnosis. It also considers the impact delirium may have on the health professional and those close to the patient.N/

Self-hypnosis for anxiety associated with severe asthma: a case report

BACKGROUND: Management of asthma can be complicated by both medical and psychiatric conditions, such as gastroesophageal reflux, chronic sinusitis, and anxiety. When symptoms of asthma are interpreted without regard to such conditions treatment may yield a suboptimal outcome. For example, anxiety-associated dyspnea, tachypnea, and chest tightness can be mistakenly interpreted as resulting from an exacerbation of asthma. Medical treatment directed only for asthma may thus lead to overuse of asthma medications and increased hospitalizations. CASE PRESENTATION: The described case illustrates how a systemic steroid-dependent patient with asthma benefited from receiving care from a pediatric pulmonologist who also was well versed in the diagnosis and treatment of anxiety. By using self-hypnosis, the patient was able to reduce her dependence on bronchodilators. Following modification of her medical therapy under supervision of the pulmonologist, and regular use of hypnosis, the patient ultimately was weaned off her systemic steroid therapy. CONCLUSIONS: This report emphasizes that anxiety must be considered as a comorbid condition in the treatment of asthma. Self-hypnosis can be a useful skill in the treatment of a patient with anxiety and asthma

Parents’ experiences of health visiting for children with Down syndrome

© MA Healthcare Limited.Children with Down syndrome have an increased likelihoodof experiencing serious health conditions. Health visitors canhave an important role in monitoring and promoting healthand development for young children with Down syndrome.This study aimed to explore parents’ experiences of healthvisiting services for children with Down syndrome. Twentyfour parents of children with Down syndrome aged 0–5 yearscompleted a brief questionnaire about the number and natureof visits from health visitors in the previous 12 months andtheir support needs. Some parents commented that otherprofessionals met the needs of their child, whereas others saidthat they would like more advice and support from healthvisitors. A further exploration of broader health serviceprovision, including health visiting, for young children withDown syndrome is needed.Peer reviewedFinal Accepted Versio

Preliminary results of a feasibility study of the use of information technology for identification of suspected colorectal cancer in primary care: the CREDIBLE study

This is the final version of the article. Available from Cancer Research UK/Nature Publishing Group via the DOI in this record.BACKGROUND: We report the findings of a feasibility study using information technology to search electronic primary care records and to identify patients with possible colorectal cancer. METHODS: An algorithm to flag up patients meeting National Institute for Health and Care Excellence (NICE) urgent referral criteria for suspected colorectal cancer was developed and incorporated into clinical audit software. This periodically flagged up such patients aged 60 to 79 years. General practitioners (GPs) reviewed flagged-up patients and decided on further clinical management. We report the numbers of patients identified and the numbers that GPs judged to need further review, investigations or referral to secondary care and the final diagnoses. RESULTS: Between January 2012 and March 2014, 19,580 records of patients aged 60 to 79 years were searched in 20 UK general practices, flagging up 809 patients who met urgent referral criteria. The majority of the patients had microcytic anaemia (236 (29%)) or rectal bleeding (205 (25%)). A total of 274 (34%) patients needed further clinical review of their records; 199 (73%) of these were invited for GP consultation, and 116 attended, of whom 42 were referred to secondary care. Colon cancer was diagnosed in 10 out of 809 (1.2%) flagged-up patients and polyps in a further 28 out of 809 (3.5%). CONCLUSIONS: It is technically possible to identify patients with colorectal cancer by searching electronic patient records.We acknowledge the General Practitioners, practice nurses, practice managers and administrative staff who supported this study, our trial co-ordinator Marie Crook, Anthony Ingold who was one of our patient representatives and MSDi for their support in developing the software algorithm. We also acknowledge the support of the National Institute for Health Research Clinical Research Network. This study was funded by the National Awareness and Early Diagnosis Initiative (NAEDI). TM is partly funded by the National Institute for Health Research (NIHR) through the Collaborations for Leadership in Applied Health Research and Care for the West Midlands (CLAHRC-WM) programme

Solubility evaluation of murine hybridoma antibodies

The successful development of antibody therapeutics depends on the molecules having properties that are suitable for manufacturing, as well as use by patients. Because high solubility is a desirable property for antibodies, screening for solubility has become an essential step during the early candidate selection process. In considering the screening process, we formed a hypothesis that hybridoma antibodies are filtered by nature to possess high solubility and tested this hypothesis using a large number of murine hybridoma-derived antibodies. Using the cross-interaction chromatography (CIC) method, we screened the solubility of 92 murine hybridoma-derived monoclonal antibodies and found that all of these molecules exhibited CIC profiles that are indicative of high solubility (>100mg/mL). Further investigations revealed that variable region N-linked glycosylation or isoelectric parameters are unlikely to contribute to the high solubility of these antibodies. These results support the general hypothesis that hybridoma monoclonal antibodies are highly soluble

Assessing the Health of Richibucto Estuary with the Latent Health Factor Index

The ability to quantitatively assess the health of an ecosystem is often of great interest to those tasked with monitoring and conserving ecosystems. For decades, research in this area has relied upon multimetric indices of various forms. Although indices may be numbers, many are constructed based on procedures that are highly qualitative in nature, thus limiting the quantitative rigour of the practical interpretations made from these indices. The statistical modelling approach to construct the latent health factor index (LHFI) was recently developed to express ecological data, collected to construct conventional multimetric health indices, in a rigorous quantitative model that integrates qualitative features of ecosystem health and preconceived ecological relationships among such features. This hierarchical modelling approach allows (a) statistical inference of health for observed sites and (b) prediction of health for unobserved sites, all accompanied by formal uncertainty statements. Thus far, the LHFI approach has been demonstrated and validated on freshwater ecosystems. The goal of this paper is to adapt this approach to modelling estuarine ecosystem health, particularly that of the previously unassessed system in Richibucto in New Brunswick, Canada. Field data correspond to biotic health metrics that constitute the AZTI marine biotic index (AMBI) and abiotic predictors preconceived to influence biota. We also briefly discuss related LHFI research involving additional metrics that form the infaunal trophic index (ITI). Our paper is the first to construct a scientifically sensible model to rigorously identify the collective explanatory capacity of salinity, distance downstream, channel depth, and silt-clay content --- all regarded a priori as qualitatively important abiotic drivers --- towards site health in the Richibucto ecosystem.Comment: On 2013-05-01, a revised version of this article was accepted for publication in PLoS One. See Journal reference and DOI belo

Composite Dirac Neutrinos

We present a mechanism that naturally produces light Dirac neutrinos. The basic idea is that the right-handed neutrinos are composite. Any realistic composite model must involve `hidden flavor' chiral symmetries. In general some of these symmetries may survive confinement, and in particular, one of them manifests itself at low energy as an exact $B-L$ symmetry. Dirac neutrinos are therefore produced. The neutrinos are naturally light due to compositeness. In general, sterile states are present in the model, some of them can naturally be warm dark matter candidates.Comment: 12 pages; Sec. IIC updated; minor corrections; published versio

Reverberation Mapping and the Physics of Active Galactic Nuclei

Reverberation-mapping campaigns have revolutionized our understanding of AGN. They have allowed the direct determination of the broad-line region size, enabled mapping of the gas distribution around the central black hole, and are starting to resolve the continuum source structure. This review describes the recent and successful campaigns of the International AGN Watch consortium, outlines the theoretical background of reverberation mapping and the calculation of transfer functions, and addresses the fundamental difficulties of such experiments. It shows that such large-scale experiments have resulted in a ``new BLR'' which is considerably different from the one we knew just ten years ago. We discuss in some detail the more important new results, including the luminosity-size-mass relationship for AGN, and suggest ways to proceed in the near future.Comment: Review article to appear in Astronomical Time Series, Proceedings of the Wise Observatory 25th Ann. Symposium. 24 pages including 7 figure