Attitudes towards faecal immunochemical testing in patients at increased risk of colorectal cancer: an online survey of GPs in England

Background: There is increasing interest in using a quantitative faecal immunochemical test (FIT) to rule out colorectal cancer (CRC) in patients with high-risk symptoms in primary care.  Aim: This study aimed to investigate GPs’ attitudes and willingness to use a FIT over an urgent 2-week wait (2WW) referral.  Design and setting: A cross-sectional online survey involving 1024 GPs working across England.  Method: Logistic regression models were used to explore the likelihood of GPs using a FIT instead of a 2WW referral, and reported using odds ratios (ORs) and 95% confidence intervals (95% CIs).  Results: Just over one-third of GPs (n = 365) preferred to use a FIT as a rule-out test over a 2WW referral. GPs were more willing if they were: aged 36–45 years (OR 1.59 [95% CI = 1.04 to 2.44]); 46–55 years (OR 1.99 [95% CI = 1.14 to 3.47]); thought a FIT was highly accurate (OR 1.63 [95% CI = 1.16 to 2.29]); thought patients would benefit compared with having a colonoscopy (OR 2.02 [95% CI = 1.46 to 2.79]); and were highly confident about discussing the benefits of a FIT (OR 2.14 [95% CI = 1.46 to 3.16]). GPs were less willing if they had had >10 urgent referrals in the past year (OR 0.62 [95% CI = 0.40 to 0.94]) and thought that longer consultations would be needed (OR 0.61 [95% CI = 0.44 to 0.83]).  Conclusion: The study findings suggest that the acceptability of using a FIT as a rule-out test in primary care is currently low, with less than half of GPs who perceived the test to be accurate preferring it over colonoscopy. Any potential guideline changes recommending a FIT in patients with high-risk symptoms, instead of urgent referral to rule out CRC, are likely to require intensive supporting educational outreach to increase GP confidence in the accuracy and application of a FIT in this context

Faecal immunochemical testing for haemoglobin in detecting bowel polyps in symptomatic patients: multicentre prospective cohort study

BACKGROUND: Measurement of faecal haemoglobin using faecal immunochemistry testing is recommended in patients presenting with symptoms suspicious for colorectal cancer, to aid in triage and prioritization of definitive investigations. While its role in colorectal cancer has been extensively investigated, the ability of faecal immunochemistry testing to detect adenomas in symptomatic patients is unclear. METHODS: A multicentre prospective observational study was conducted between April 2017 and March 2019, recruiting adults from 24 hospitals across England and 59 general practices in London who had been urgently referred with suspected colorectal cancer symptoms. Each patient provided a stool sample for faecal immunochemistry testing, in parallel with definitive investigation. A final diagnosis for each patient was recorded, including the presence, size, histology, and risk type of colonic polyps. The outcome of interest was the sensitivity of faecal immunochemistry testing in detecting the presence of adenomas. RESULTS: Of 3496 patients included in the analysis, 553 (15.8 per cent) had polyps diagnosed. Sensitivity of faecal immunochemistry testing for polyp detection was low across all ranges; with a cut-off for faecal haemoglobin of 4 µg/g or lower, sensitivity was 34.9 per cent and 46.8 per cent for all polyp types and high-risk polyps respectively. The area under the receiver operating characteristic curve in detection probability was relatively low for both intermediate-risk (0.63) and high-risk polyps (0.63). CONCLUSION: While faecal immunochemistry testing may be useful in prioritizing investigations to diagnose colorectal cancer, if used as a sole test, the majority of polyps would be missed and the opportunity to prevent progression to colorectal cancer may be lost

Overlapping Genetic Background of Coronary Artery and Carotid/Femoral Atherosclerotic Calcification

Background and objectives: Multivessel atherosclerosis and its genetic background are under-investigated, although atherosclerosis is seldom local and still causes high mortality. Alternative methods to assess coronary calcification (CAC) might incorporate genetic links between different arteries’ atherosclerotic involvement, however, co-occurrences of coronary calcification have not been investigated in twins yet. Materials and Methods: We assessed the heritability of radio morphologically distinct atherosclerotic plaque types in coronary (non-enhanced CT, Agatston score), carotid, and femoral arteries (B-mode ultrasound) in 190 twin subjects (60 monozygotic, 35 dizygotic pairs). Four-segment scores were derived in order to assess the dissemination of the distinct plaque types in the carotid and femoral arteries taking bilaterality into account. We calculated the genetic correlation between phenotypically correlating plaque types in these arteries. Results: CAC and dissemination of calcified plaques in the carotid and femoral arteries (4S_hyper) were moderately heritable (0.67 [95% CI: 0.37–1] and 0.69 [95% CI: 0.38–1], respectively) when adjusted for age and sex. Hypoechoic plaques in the carotid and femoral arteries showed no heritability, while mixed plaques showed intermediate heritability (0.50 [95% CI: 0–0.76]). Age and sex-adjusted phenotypic correlation between CAC and 4segm_hyper was 0.48 [95% CI: 0.30–0.63] and the underlying genetic correlation was 0.86 [95% CI: 0.42–1]. Conclusions: Calcification of atherosclerotic plaques is moderately heritable in all investigated arteries and significant overlapping genetic factors can be attributed to the phenotypical resemblance of coronary and carotid or femoral atherosclerotic calcification. Our findings support the idea of screening extracoronary arteries in asymptomatic individuals. We also propose a hypothesis about primarily carotid-coronary and femoral-coronary atherosclerosis as two distinct genetic predispositions to co-localization

Assessing the Effects of Climate on Host-Parasite Interactions: A Comparative Study of European Birds and Their Parasites

[Background] Climate change potentially has important effects on distribution, abundance, transmission and virulence of parasites in wild populations of animals. [Methodology/Principal Finding] Here we analyzed paired information on 89 parasite populations for 24 species of bird hosts some years ago and again in 2010 with an average interval of 10 years. The parasite taxa included protozoa, feather parasites, diptera, ticks, mites and fleas. We investigated whether change in abundance and prevalence of parasites was related to change in body condition, reproduction and population size of hosts. We conducted analyses based on the entire dataset, but also on a restricted dataset with intervals between study years being 5–15 years. Parasite abundance increased over time when restricting the analyses to datasets with an interval of 5–15 years, with no significant effect of changes in temperature at the time of breeding among study sites. Changes in host body condition and clutch size were related to change in temperature between first and second study year. In addition, changes in clutch size, brood size and body condition of hosts were correlated with change in abundance of parasites. Finally, changes in population size of hosts were not significantly related to changes in abundance of parasites or their prevalence. [Conclusions/Significance] Climate change is associated with a general increase in parasite abundance. Variation in laying date depended on locality and was associated with latitude while body condition of hosts was associated with a change in temperature. Because clutch size, brood size and body condition were associated with change in parasitism, these results suggest that parasites, perhaps mediated through the indirect effects of temperature, may affect fecundity and condition of their hosts. The conclusions were particularly in accordance with predictions when the restricted dataset with intervals of 5–15 years was used, suggesting that short intervals may bias findings.The Academy of Finland is acknowledged for a grant to TE (project 8119367) and EK (project 250709). PLP was supported by a research grant (TE_291/2010) offered by the Romanian Ministry of Education and Science. T. Szép received funding from OTKA K69068 and JT from OTKA 75618. JMP was supported by a JAE grant from Consejo Superior de Investigaciones Científicas. SM-JM, FdL-AM, JF, JJS and FV were respectively supported by projects CGL2009-09439, CGL2012-36665, CGL2009- 11445, CGL2010-19233-C03-01 and CGL2008-00562 by the Spanish Ministry of Science and Innovation and FEDER and project EVITAR by the Spanish Ministry of Health. FV was also supported by the European Regional Development Fund. MACT was funded by a predoctoral FPU grant from the Spanish Ministry of Education (AP20043713). PM was supported by grant from the Polish Ministry of Science and Higher Education (project 2P04F07030), and the Foundation for Polish Science

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

The transmission of vibration through gloves: effects of push force, vibration magnitude and inter-subject variability

The extent to which a glove modifies the risks from hand-transmitted vibration is quantified in ISO 10819:1996 by a measure of glove transmissibility determined with one vibration magnitude, one contact force with a handle and only three subjects. This study was designed to investigate systematically the vibration transmissibility of four ‘anti-vibration’ gloves over the frequency range 16–1600 Hz with 12 subjects, at six magnitudes of vibration (0.25–8.0 ms?2 r.m.s.) and with six push forces (5 N to 80 N). The four gloves showed different transmissibility characteristics that were not greatly affected by vibration magnitude but highly dependent on push force. In all conditions, the variability in transmissibility between subjects was as great as the variability between gloves. It is concluded that a standardised test of glove dynamic performance should include a wide range of hands and a range of forces representative of those occurring in work with vibratory tools.Statement of Relevance: The transmission of vibration through anti-vibration gloves is highly dependent on the push force between the hand and a handle and also highly dependent on the hand that is inside the glove. The influence of neither factor is well reflected in ISO 10819:1996, the current standard for anti-vibration gloves.<br/

Reproductive Outcomes Associated with Noise Exposure — A Systematic Review of the Literature

Introduction: High noise exposure during critical periods in gestation is a potential stressor that may result in increased risk of implantation failure, dysregulation of placentation or decrease of uterine blood flow. This paper systematically reviews published evidence on associations between reproductive outcomes and occupational and environmental noise exposure. Methods: The Web of Science, PubMed and Embase electronic databases were searched for papers published between 1970 to June 2014 and via colleagues. We included 14 epidemiological studies related to occupational noise exposure and nine epidemiological studies related to environmental noise exposure. There was some evidence for associations between occupational noise exposure and low birthweight, preterm birth and small for gestational age, either independently or together with other occupational risk factors. Five of six epidemiologic studies, including the two largest studies, found significant associations between lower birthweight and higher noise exposure. There were few studies on other outcomes and study design issues may have led to bias in assessments in some studies. Conclusions: There is evidence for associations between noise exposure and adverse reproductive outcomes from animal studies. Few studies in have been conducted in humans but there is some suggestive evidence of adverse associations with environmental noise from both occupational and epidemiological studies, especially for low birthweight

Strong Genetic Effects on Bone Mineral Density in Multiple Locations with Two Different Techniques: Results from a Cross-Sectional Twin Study

Background and Objectives: Previous studies have demonstrated that risk of hip fracture is at least partly heritable. The aim of this study was to determine the magnitude of the genetic component of bone mineral density (BMD), using both X-ray and ultrasound assessment at multiple sites. Materials and Methods: 216 adult, healthy Hungarian twins (124 monozygotic, MZ, 92 dizygotic, DZ; mean age 54.2 ± 14.3 years), recruited from the Hungarian Twin Registry with no history of oncologic disease underwent cross-sectional BMD studies. We measured BMD, T- and Z-scores with dual energy X-ray absorptiometry (DEXA) at multiple sites (lumbar spine, femoral neck, total hip and radius). Quantitative bone ultrasound (QUS) was also performed, resulting in a calculated value of estimated bone mineral density (eBMD) in the heel bone. Heritability was calculated using the univariate ACE model. Results: Bone density had a strong genetic component at all sites with estimates of heritability ranging from 0.613 to 0.838 in the total sample. Lumbar BMD and calcaneus eBMD had major genetic components with estimates of 0.828 and 0.838 respectively, and least heritable (0.653) at the total hip. BMD of the radius had also a strong genetic component with an estimate of 0.806. No common environmental effect was found. The remaining variance was influenced by unique environment (0.162 to 0.387). In females only, slightly higher additive genetic estimates were found, especially in the case of the femoral neck and total hip. Conclusion: Bone mineral density is strongly heritable, especially in females at all locations using both DEXA and QUS, which may explain the importance of family history as a risk factor for bone fractures. Unshared environmental effects account for the rest of the variance with slight differences in magnitude across various bone regions, supporting the role of lifestyle in preventing osteoporotic fractures with various efficacy in different bone regions

The Relationship between Atherosclerosis and Gut Microbiome in Patients with Obstructive Sleep Apnoea

Background: Obstructive sleep apnoea (OSA) and gut dysbiosis are known risk factors for atherosclerosis. However, only very few studies have been focused on the relationship between OSA, atherosclerosis, and the intestinal microbiome, all in animal models. Methods: Twenty-two patients with OSA, 16 with and 6 without carotid atherosclerosis were involved in the study. After a diagnostic sleep examination, the intima media thickness (IMT) was measured and plaques were found using carotid ultrasound. Blood was also drawn for metabolic profile, and a stool sample was provided for 16S ribosomal RNA microbiome investigation. Results: An increased maximal common carotid artery (CCA) IMT was significantly associated with decreased phylum-level diversity. The level of Peptostreptococcaceae was significantly lower in atherosclerotic subjects. Some other candidate microbes appeared in the two groups at the genus level as well: Bilophila, Romboutsia, Slackia, and Veillonella in the non-atherosclerotic group; and Escherichia-Shigella, Prevotella, and Ruminococcaceae in the atherosclerotic group. Conclusions: This is the first pilot research to analyze the association between the gut microbiome and atherosclerosis in adult patients with OSA with and without carotid atherosclerosis. Dysbiosis and individual bacteria may contribute to the development of carotid atherosclerosis in patients with OSA. Further investigations are necessary to reveal a more precise background in a larger sample

Cardiovascular effects of the combined exposure to noise and outdoor air pollution: a review

The combination of noise with other environmental stressors, particularly traffic-related air pollution, has been of growing interest in recent years. Cardiovascular effects are among the most evidence-based physical health outcomes. Moreover, the European Network on Noise and Health (ENNAH), which helped to establish collaboration between researchers on noise and researchers on air quality, identified gaps in the evidence of noise related health research and concluded that one of the most important topics to focus on was noise and co-exposures. Therefore, the objective of this paper is to summarize current knowledge on the association of noise and air pollutant exposure on related cardiovascular health effects and to look at whether the evidence suggests that noise and air pollution confound or interact with each other. This review comprised a literature search for the period 2005 to 2012. It also aims to identify gaps which could help to shape future research directions. The results suggest that noise and air pollution exert independent effects on cardiovascular health, but the evidence for any interactive effects is still limited and has to be further investigated.JRC.I.1-Chemical Assessment and Testin