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

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/

General practitioners' awareness of the recommendations for faecal immunochemical tests (FITs) for suspected lower gastrointestinal cancers:a national survey

OBJECTIVES: In July 2017, UK National Institute for Health and Care Excellence (NICE) published a diagnostic guidance (DG30) recommending the use of faecal immunochemical tests (FITs) for symptomatic patients who do not meet the urgent referral pathway for suspected colorectal cancer (CRC). We assessed general practitioners' (GP) awareness of DG30 in primary care 6 months after its publication. DESIGN AND SETTING: Cross-sectional online survey of GPs hosted by an English panel of Primary health care professionals. PARTICIPANTS: In December 2017, 1024 GPs registered on an online panel (M3) based in England took part in an online survey. OUTCOMES AND VARIABLES: We investigated a number of factors including previous experience of using FIT and guaiac faecal occult blood tests (FOBTs), the number of urgent referrals for CRC that GPs have made in the last year and their sociodemographic and professional characteristics that could be associated with their self-reported awareness of the FIT diagnostic guidance. RESULTS: Of the 1024 GPs who completed the survey, 432 (42.2%) were aware of the current recommendation but only 102 (10%) had used it to guide their referrals. Awareness was lowest in North West England compared with London (30.5% vs 44.9%; adjusted OR: 0.55, 95% CI 0.33 to 0.92). Awareness of the FIT guidance was positively associated with test usage after the NICE update (adjusted OR: 13.00, 95% CI 6.87 to 24.61) and having specialist training (adjusted OR: 1.48, 95% CI 1.05 to 2.08). The number of urgent referrals, the previous use of FOBt, GPs' age and gender, work experience and practice size (both in terms of the number of GPs or patients at the practice) were not associated with awareness. CONCLUSIONS: Less than half of GPs in this survey recognised the current guidance on the use of FIT. Self-reported awareness was not systematically related to demographic of professional characteristics

Daytime and night-time aircraft noise and cardiovascular disease near Heathrow airport in London

ABSTRACT Background. Few studies have investigated associations of aircraft noise with cardiovascular health. We investigated this in areas exposed to noise from London Heathrow airport. Methods. A small area study was conducted in 12,110 census output areas covering 3.6 million residents. Risks for hospital admissions and mortality in 2001-05 were assessed in relation to aircraft noise in 2001, adjusted for relevant confounders. Night (L night ) and daytime (L Aeq,16h ) aircraft noise were assessed separately. Results. Higher aircraft noise was associated with higher relative risks for hospital admissions and mortality from stroke, coronary heart disease (CHD) and cardiovascular disease. Risk estimates were higher for night-time than daytime noise. Adjusted risks were highest for stroke, with RR 1.29 [95% CI 1.14 to 1.46] for L night and RR 1.08 [95% CI 1.02 to 1.14] for L Aeq,16h for &gt;55dB vs. &lt;50dB. All linear dose-response relationships were statistically significant for hospital admissions but not for mortality, except for CHD and L Aeq,16h . Discussion. This research attracted a high level of policy interest. However, the impact of this and other recent papers on policy decisions such as increased airport capacity in England is currently unclear. Priority areas for follow-up health research into aircraft noise need to be considered

Daytime and night-time aircraft noise and cardiovascular disease near Heathrow airport in London

ABSTRACT Background. Few studies have investigated associations of aircraft noise with cardiovascular health. We investigated this in areas exposed to noise from London Heathrow airport. Methods. A small area study was conducted in 12,110 census output areas covering 3.6 million residents. Risks for hospital admissions and mortality in 2001-05 were assessed in relation to aircraft noise in 2001, adjusted for relevant confounders. Night (L night ) and daytime (L Aeq,16h ) aircraft noise were assessed separately. Results. Higher aircraft noise was associated with higher relative risks for hospital admissions and mortality from stroke, coronary heart disease (CHD) and cardiovascular disease. Risk estimates were higher for night-time than daytime noise. Adjusted risks were highest for stroke, with RR 1.29 [95% CI 1.14 to 1.46] for L night and RR 1.08 [95% CI 1.02 to 1.14] for L Aeq,16h for &gt;55dB vs. &lt;50dB. All linear dose-response relationships were statistically significant for hospital admissions but not for mortality, except for CHD and L Aeq,16h . Discussion. This research attracted a high level of policy interest. However, the impact of this and other recent papers on policy decisions such as increased airport capacity in England is currently unclear. Priority areas for follow-up health research into aircraft noise need to be considered

Genetic analysis of candidate genes modifying the age-at-onset in Huntington's disease.

The expansion of a polymorphic CAG repeat in the HD gene encoding huntingtin has been identified as the major cause of Huntington's disease (HD) and determines 42-73% of the variance in the age-at-onset of the disease. Polymorphisms in huntingtin interacting or associated genes are thought to modify the course of the disease. To identify genetic modifiers influencing the age at disease onset, we searched for polymorphic markers in the GRIK2, TBP, BDNF, HIP1 and ZDHHC17 genes and analysed seven of them by association studies in 980 independent European HD patients. Screening for unknown sequence variations we found besides several silent variations three polymorphisms in the ZDHHC17 gene. These and polymorphisms in the GRIK2, TBP and BDNF genes were analysed with respect to their association with the HD age-at-onset. Although some of the factors have been defined as genetic modifier factors in previous studies, none of the genes encoding GRIK2, TBP, BDNF and ZDHHC17 could be identified as a genetic modifier for HD.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe