Biosecurity and the ornamental fish trade: A stakeholder perspective in England

The freshwater and marine ornamental fish industry is a primary route of hazard introduction and emergence, including aquatic animal diseases and non-native species. Prevention measures are key to reducing the risk of hazard incursion and establishment, but there is currently little understanding of the biosecurity practices and hazard responses implemented at post-border stages of the ornamental fish supply chain. This study addresses this knowledge gap, using questionnaires to collate information on actual biosecurity behaviours and hazard responses practised by ornamental fish retailers and hobbyist communities in England. Actual behaviours varied considerably within retailers and hobbyists, suggesting that reliance on preventative practices by individuals in the post-border stages of the ornamental fish supply chain is likely to be ineffective in minimizing the risk of hazard incursion and establishment. Resources should be allocated towards improving and enforcing robust pre- and at-border control measures, such as risk-based surveillance of ornamental fish imports at border controls. In addition, these findings should be used to implement targeted awareness-raising campaigns and help create directed training on biosecurity practices for individuals involved in the post-border stages of the ornamental supply chain

Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

Background Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. Methods In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH,non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2–F3, or F1 with at least oneaccompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpointsfor the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2–F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. Findings Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1–F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2–F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1–F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). Interpretation Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes

Development of risk prediction models combining routine EHR data for use in colorectal cancer screening referral decisions

BACKGROUND: Risk prediction models which incorporate the FOBT with other colorectal cancer risk factors have demonstrated increased sensitivity compared with FOBT alone. EHRs from primary care have a rich level of data and may add a further dimension to risk prediction models. The aim of the study was to determine the availability of GP data for key predictors of colorectal cancer in the screening population and whether we can use this additional information to make more accurate screening referral decisions. METHODS: The Health Improvement Network (THIN) database was used to define a screening population by identifying practices which receive electronic bowel cancer screening programme notifications. A prediction model combining the FOBT with other clinical predictors was developed using Cox Regression and multivariable fractional polynomials with backwards elimination. For internal validation, optimism adjusted performance metrics were determined using boot- strapping and absolute risk predictions were estimated. RESULTS: The screening cohort derived from THIN gave 292,168 patients. The Cox Regression model which included the FOBT result (n=98,303, 1197 colorectal cancer/polyps) had 13 predictors and 2 interactions including; MCV, various symptoms/diagnoses and whether previous polyps had been diagnosed. The optimism adjusted performance metrics gave a; C-statistic of 0.850, c-slope of 0.991, D statistic 2.298 and R 2 of 0.558. A model investigating negative results only (n = 95,792, 587 colorectal cancer/polyps) included a similar pat- tern of variables. Performance metrics included a C-statistic of 0.650, C-Slope of 0.944, D statistic 0.836 and R 2 of 0.144. CONCLUSIONS: This study has shown that a screening cohort can be derived from a primary care database using the electronic bowel cancer screening programme notifications. The prediction models estimate an individual’s absolute risk of colorectal cancer. Additional data could be drawn from primary care onto the Bowel Cancer Screening system using the NHS Spine to contribute to a referral algorith

Risk-adjusted colorectal cancer screening using the FIT and routine screening data : development of a risk prediction model

Background: The faecal immunochemical test (FIT) is replacing the guaiac faecal occult blood test in colorectal cancer screening. Increased uptake and FIT positivity will challenge colonoscopy services. We developed a risk prediction model combining routine screening data with FIT concentration to improve the accuracy of screening referrals. Methods: Multivariate analysis used complete cases of those with a positive FIT (⩾20 μg g−1) and diagnostic outcome (n=1810; 549 cancers and advanced adenomas). Logistic regression was used to develop a risk prediction model using the FIT result and screening data: age, sex and previous screening history. The model was developed further using a feedforward neural network. Model performance was assessed by discrimination and calibration, and test accuracy was investigated using clinical sensitivity, specificity and receiver operating characteristic curves. Results: Discrimination improved from 0.628 with just FIT to 0.659 with the risk-adjusted model (P=0.01). Calibration using the Hosmer–Lemeshow test was 0.90 for the risk-adjusted model. The sensitivity improved from 30.78% to 33.15% at similar specificity (FIT threshold of 160 μg g−1). The neural network further improved model performance and test accuracy. Conclusions: Combining routinely available risk predictors with the FIT improves the clinical sensitivity of the FIT with an increase in the diagnostic yield of high-risk adenomas

Threats to UK freshwaters under climate change: Commonly traded aquatic ornamental species and their potential pathogens and parasites

The aquatic ornamental industry, whilst providing socio-economic benefits, is a known introduction pathway for non-native species, which if invasive, can cause direct impacts to native species and ecosystems and also drive disease emergence by extending the geographic range of associated parasites and pathogens and by facilitating host-switching, spillover and spill-back. Although current UK temperatures are typically below those necessary for the survival and establishment of commonly-traded tropical, and some sub-tropical, non-native ornamental species, the higher water temperatures predicted under climate-change scenarios are likely to increase the probability of survival and establishment. Our study aimed primarily to identify which of the commonly-traded non-native ornamental aquatic species (fish and invertebrates), and their pathogens and parasites, are likely to benefit in terms of survival and establishment in UK waters under predicted future climate conditions. Out of 233 ornamental species identified as traded in the UK, 24 were screened, via literature search, for potential parasites and pathogens (PPPs) due to their increased risk of survival and establishment under climate change. We found a total of 155 PPPs, the majority of which were platyhelminths, viruses and bacteria. While many of the identified PPPs were already known to occur in UK waters, PPPs currently absent from UK waters and with zoonotic potential were also identified. Results are discussed in the context of understanding potential impact, in addition to provision of evidence to inform risk assessment and mitigation approaches

Zoonotic Disease Pathogens in Fish Used for Pedicure

“Doctor” fish might not be such good doctors after all. These fish are used for the increasingly popular spa treatment called fish pedicures. During these sessions, spa patrons immerse their feet in water, allowing the live fish to feed on dead skin, mainly for cosmetic reasons. However, examinations of doctor fish destined for these spas found that they can carry harmful bacteria. Thus, although reports of human infection after fish pedicures are few, there may be some risks. Spa patrons who have underlying medical conditions (such as diabetes, immunosuppression, or even simple breaks in the skin) are already discouraged from taking such treatments. However, spas that offer fish pedicures should also consider using only disease-free fish reared in controlled facilities under high standards of husbandry and welfare