Identification of genes expressed by immune cells of the colon that are regulated by colorectal cancer-associated variants.

A locus on human chromosome 11q23 tagged by marker rs3802842 was associated with colorectal cancer (CRC) in a genome-wide association study; this finding has been replicated in case-control studies worldwide. In order to identify biologic factors at this locus that are related to the etiopathology of CRC, we used microarray-based target selection methods, coupled to next-generation sequencing, to study 103 kb at the 11q23 locus. We genotyped 369 putative variants from 1,030 patients with CRC (cases) and 1,061 individuals without CRC (controls) from the Ontario Familial Colorectal Cancer Registry. Two previously uncharacterized genes, COLCA1 and COLCA2, were found to be co-regulated genes that are transcribed from opposite strands. Expression levels of COLCA1 and COLCA2 transcripts correlate with rs3802842 genotypes. In colon tissues, COLCA1 co-localizes with crystalloid granules of eosinophils and granular organelles of mast cells, neutrophils, macrophages, dendritic cells and differentiated myeloid-derived cell lines. COLCA2 is present in the cytoplasm of normal epithelial, immune and other cell lineages, as well as tumor cells. Tissue microarray analysis demonstrates the association of rs3802842 with lymphocyte density in the lamina propria (p = 0.014) and levels of COLCA1 in the lamina propria (p = 0.00016) and COLCA2 (tumor cells, p = 0.0041 and lamina propria, p = 6 × 10(-5)). In conclusion, genetic, expression and immunohistochemical data implicate COLCA1 and COLCA2 in the pathogenesis of colon cancer. Histologic analyses indicate the involvement of immune pathways

Global data for ecology and epidemiology: a novel algorithm for temporal Fourier processing MODIS data

Background. Remotely-sensed environmental data from earth-orbiting satellites are increasingly used to model the distribution and abundance of both plant and animal species, especially those of economic or conservation importance. Time series of data from the MODerate-resolution Imaging Spectroradiometer (MODIS) sensors on-board NASA's Terra and Aqua satellites offer the potential to capture environmental thermal and vegetation seasonality, through temporal Fourier analysis, more accurately than was previously possible using the NOAA Advanced Very High Resolution Radiometer (AVHRR) sensor data. MODIS data are composited over 8- or 16-day time intervals that pose unique problems for temporal Fourier analysis. Applying standard techniques to MODIS data can introduce errors of up to 30% in the estimation of the amplitudes and phases of the Fourier harmonics. Methodology/Principal Findings. We present a novel spline-based algorithm that overcomes the processing problems of composited MODIS data. The algorithm is tested on artificial data generated using randomly selected values of both amplitudes and phases, and provides an accurate estimate of the input variables under all conditions. The algorithm was then applied to produce layers that capture the seasonality in MODIS data for the period from 2001 to 2005. Conclusions/Significance. Global temporal Fourier processed images of 1 km MODIS data for Middle Infrared Reflectance, day- and night-time Land Surface Temperature (LST), Normalised Difference Vegetation Index (NDVI), and Enhanced Vegetation Index (EVI) are presented for ecological and epidemiological applications. The finer spatial and temporal resolution, combined with the greater geolocational and spectral accuracy of the MODIS instruments, compared with previous multi-temporal data sets, mean that these data may be used with greater confidence in species' distribution modelling

British Society of Gastroenterology Best Practice Guidance: outpatient management of cirrhosis - part 3: special circumstances

\ua9 2023 BMJ Publishing Group. All rights reserved.The prevalence of cirrhosis has risen significantly over recent decades and is predicted to rise further. Widespread use of non-invasive testing means cirrhosis is increasingly diagnosed at an earlier stage. Despite this, there are significant variations in outcomes in patients with cirrhosis across the UK, and patients in areas with higher levels of deprivation are more likely to die from their liver disease. This three-part best practice guidance aims to address outpatient management of cirrhosis, in order to standardise care and to reduce the risk of progression, decompensation and mortality from liver disease. Part 1 addresses outpatient management of compensated cirrhosis: screening for hepatocellular cancer, varices and osteoporosis, vaccination and lifestyle measures. Part 2 concentrates on outpatient management of decompensated disease including management of ascites, encephalopathy, varices, nutrition as well as liver transplantation and palliative care. In this, the third part of the guidance, we focus on special circumstances encountered in managing people with cirrhosis, namely surgery, pregnancy, travel, managing bleeding risk for invasive procedures and portal vein thrombosis

British Society of Gastroenterology Best Practice Guidance: outpatient management of cirrhosis - part 1: compensated cirrhosis

\ua9 2023 BMJ Publishing Group. All rights reserved.The prevalence of cirrhosis has risen significantly over recent decades and is predicted to rise further. Widespread use of non-invasive testing means cirrhosis is increasingly diagnosed at an earlier stage. Despite this, there are significant variations in outcomes in patients with cirrhosis across the UK, and patients in areas with higher levels of deprivation are more likely to die from their liver disease. This three-part best practice guidance aims to address outpatient management of cirrhosis, in order to standardise care and to reduce the risk of progression, decompensation and mortality from liver disease. Here, in part one, we focus on outpatient management of compensated cirrhosis, encompassing hepatocellular cancer surveillance, screening for varices and osteoporosis, vaccination and lifestyle measures. We also introduce a compensated cirrhosis care bundle for use in the outpatient setting. Part two concentrates on outpatient management of decompensated disease including management of ascites, encephalopathy, varices, nutrition as well as liver transplantation and palliative care. The third part of the guidance covers special circumstances encountered in managing people with cirrhosis: surgery, pregnancy, travel, managing bleeding risk for invasive procedures and portal vein thrombosis

The association between family and community social capital and health risk behaviours in young people: an integrative review

Background: Health risk behaviours known to result in poorer outcomes in adulthood are generally established in late childhood and adolescence. These ‘risky’ behaviours include smoking, alcohol and illicit drug use and sexual risk taking. While the role of social capital in the establishment of health risk behaviours in young people has been explored, to date, no attempt has been made to consolidate the evidence in the form of a review. Thus, this integrative review was undertaken to identify and synthesise research findings on the role and impact of family and community social capital on health risk behaviours in young people and provide a consolidated evidence base to inform multi-sectorial policy and practice.<p></p> Methods: Key electronic databases were searched (i.e. ASSIA, CINAHL, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, Embase, Medline, PsycINFO, Sociological Abstracts) for relevant studies and this was complemented by hand searching. Inclusion/exclusion criteria were applied and data was extracted from the included studies. Heterogeneity in study design and the outcomes assessed precluded meta-analysis/meta-synthesis; the results are therefore presented in narrative form.<p></p> Results: Thirty-four papers satisfied the review inclusion criteria; most were cross-sectional surveys. The majority of the studies were conducted in North America (n=25), with three being conducted in the UK. Sample sizes ranged from 61 to 98,340. The synthesised evidence demonstrates that social capital is an important construct for understanding the establishment of health risk behaviours in young people. The different elements of family and community social capital varied in terms of their saliency within each behavioural domain, with positive parent–child relations, parental monitoring, religiosity and school quality being particularly important in reducing risk.<p></p> Conclusions: This review is the first to systematically synthesise research findings about the association between social capital and health risk behaviours in young people. While providing evidence that may inform the development of interventions framed around social capital, the review also highlights key areas where further research is required to provide a fuller account of the nature and role of social capital in influencing the uptake of health risk behaviours.<p></p&gt

A descriptive study of UK cancer genetics services: an emerging clinical response to the new genetics

The objective was to describe NHS cancer genetic counselling services and compare UK regions. The study design was a cross-sectional study over 4 weeks and attendee survey. The setting was 22 of the 24 regional cancer genetics services in the UK NHS. Participants were individuals aged over 18 attending clinics at these services. Outcome measures were staff levels, referral rates, consultation rates, follow-up plans, waiting time. There were only 11 dedicated cancer geneticists across the 22 centres. Referrals were mainly concerned with breast (63%), bowel (18%) and ovarian (12%) cancers. Only 7% of referrals were for men and 3% were for individuals from ethnic minorities. Referral rates varied from 76 to 410 per million per annum across the regions. Median waiting time for an initial appointment was 19 weeks, ranging across regions from 4 to 53 weeks. Individuals at population-level genetic risk accounted for 27% of consultations (range 0%, 58%). Shortfalls in cancer genetics staff and in the provision of genetic testing and cancer surveillance have resulted in large regional variations in access to care. Initiatives to disseminate referral and management guidelines to cancer units and primary care should be adequately resourced so that clinical genetics teams can focus on the genetic testing and management of high-risk families. © 2001 Cancer Research Campaign http://www.bjcancer.co

Use of low-dose oral theophylline as an adjunct to inhaled corticosteroids in preventing exacerbations of chronic obstructive pulmonary disease: study protocol for a randomised controlled trial.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with high morbidity, mortality, and health-care costs. An incomplete response to the anti-inflammatory effects of inhaled corticosteroids is present in COPD. Preclinical work indicates that 'low dose' theophylline improves steroid responsiveness. The Theophylline With Inhaled Corticosteroids (TWICS) trial investigates whether the addition of 'low dose' theophylline to inhaled corticosteroids has clinical and cost-effective benefits in COPD. METHOD/DESIGN: TWICS is a randomised double-blind placebo-controlled trial conducted in primary and secondary care sites in the UK. The inclusion criteria are the following: an established predominant respiratory diagnosis of COPD (post-bronchodilator forced expiratory volume in first second/forced vital capacity [FEV1/FVC] of less than 0.7), age of at least 40 years, smoking history of at least 10 pack-years, current inhaled corticosteroid use, and history of at least two exacerbations requiring treatment with antibiotics or oral corticosteroids in the previous year. A computerised randomisation system will stratify 1424 participants by region and recruitment setting (primary and secondary) and then randomly assign with equal probability to intervention or control arms. Participants will receive either 'low dose' theophylline (Uniphyllin MR 200 mg tablets) or placebo for 52 weeks. Dosing is based on pharmacokinetic modelling to achieve a steady-state serum theophylline of 1-5 mg/l. A dose of theophylline MR 200 mg once daily (or placebo once daily) will be taken by participants who do not smoke or participants who smoke but have an ideal body weight (IBW) of not more than 60 kg. A dose of theophylline MR 200 mg twice daily (or placebo twice daily) will be taken by participants who smoke and have an IBW of more than 60 kg. Participants will be reviewed at recruitment and after 6 and 12 months. The primary outcome is the total number of participant-reported COPD exacerbations requiring oral corticosteroids or antibiotics during the 52-week treatment period. DISCUSSION: The demonstration that 'low dose' theophylline increases the efficacy of inhaled corticosteroids in COPD by reducing the incidence of exacerbations is relevant not only to patients and clinicians but also to health-care providers, both in the UK and globally. TRIAL REGISTRATION: Current Controlled Trials ISRCTN27066620 was registered on Sept. 19, 2013, and the first subject was randomly assigned on Feb. 6, 2014

Variability of adenoidectomy/tonsillectomy rates among children of the Veneto Region, Italy

<p>Abstract</p> <p>Background</p> <p>Despite national guidelines in 2003 aimed at limiting the recourse to tonsillectomy and/or adenoidectomy (A/T), the latter are among the most frequent pediatric surgeries performed in Italy. Aim of the study is to investigate variability of A/T rates among children of the Veneto Region, Italy.</p> <p>Methods</p> <p>All discharges of Veneto residents with Diagnosis-Related Groups 57–60 and ICD9-CM intervention codes 28.2 (tonsillectomy), 28.3 (adenotonsillectomy), 28.6 (adenoidectomy) were selected in the period 2000–2006 for a descriptive analysis. A multilevel Poisson regression model was applied to estimate Incidence Rate Ratios (IRR) with 95% Confidence Intervals (CI) for A/T surgery among children aged 2–9 years in 2004–2006, while taking into account clustering of interventions within the 21 Local Health Units.</p> <p>Results</p> <p>Through 2000–2006, the overall number of A/T surgeries decreased (-8%); there was a decline of adenoidectomies (-20%) and tonsillectomies (-8%), whereas adenotonsillectomies raised (+18%). Analyses on children aged 2–9 resulted in an overall rate of 14.4 surgeries per 1000 person-years (16.1 among males and 12.5 among females), with a wide heterogeneity across Local Health Units (range 8.1–27.6). At random intercept Poisson regression, while adjusting for sex and age, intervention rates were markedly lower among foreign than among Italian children (IRR = 0.57, CI 0.53–0.61). A/T rates in the 10–40 age group (mainly tonsillectomies) computed for each Local Health Unit and introduced in the regression model accounted for 40% of the variance at Local Health Unit level of pediatric rates (mainly adenoidectomies and adenotonsillectomies).</p> <p>Conclusion</p> <p>A/T rates in the Veneto Region, especially adenoidectomies among children aged 2–9 years, remain high notwithstanding a decrease through 2000–2006. A wide heterogeneity according to nationality and Local Health Units is evident. The propensity to A/T surgery of each Local Health Unit is similar in different age groups and for different surgical indications.</p

Pneumonia care and the nursing home: a qualitative descriptive study of resident and family member perspectives

BACKGROUND: Nursing home residents are frequently sent to hospital for diagnostic tests or to receive acute health care services. These transfers are both costly and for some, associated with increased risks. Although improved technology allows long-term care facilities to deliver more complex health care on site, if this is to become a trend then residents and family members must see the value of such care. This qualitative study examined resident and family member perspectives on in situ care for pneumonia. METHODS: A qualitative descriptive study design was used. Participants were residents and family members of residents treated for pneumonia drawn from a larger randomized controlled trial of a clinical pathway to manage nursing home-acquired pneumonia on-site. A total of 14 in-depth interviews were conducted. Interview data were analyzed using the editing style, described by Miller and Crabtree, to identify key themes. RESULTS: Both residents and family members preferred that pneumonia be treated in the nursing home, where possible. They both felt that caring and attention are key aspects of care which are more easily accessible in the nursing home setting. However, residents felt that staff or doctors should make the decision whether to hospitalize them, whereas family members wanted to be consulted or involved in the decision-making process. CONCLUSION: These findings suggest that interventions to reduce hospitalization of nursing home residents with pneumonia are consistent with resident and family member preferences