Chapter 11 An International Perspective on the Regulation of Rodenticides

In the late 1940s, anticoagulant active ingredients were introduced into the global rodenticide market. They were rapidly favored over existing rodenticides, such as red squill, zinc phosphide, strychnine and inorganic compounds, because they were comparatively inexpensive and did not appear to have any unpalatable taste, odor or cause any immediate post-ingestive reaction that could lead to bait shyness in rodents (Wardrop and Keeling 2008). The number of products registered in the United States (US) under Section 3 of the Federal Fungicide, Insecticide and Rodenticide Act (FIFRA), which was passed in 1947 and was the first US law to require product registration, illustrates the rapid dominance of anticoagulants in the US rodenticide market (Fig. 11.1). It is striking that the number of anticoagulant-based rodenticide products (ARs) registered under FIFRA was more than two times greater than the other categories of rodenticide active ingredients 40 years after the enactment of FIFRA. The greatest number of rodenticide products registered in a single year under Section 3 of FIFRA (750) was in 1985, and ARs accounted for 547 (73%) o

Patient understanding of moles and skin cancer, and factors influencing presentation in primary care: a qualitative study.

BACKGROUND: Melanoma incidence in the UK has doubled over two decades, yet there is conflicting evidence about factors which prompt or delay patients seeking advice. AIM: To explore patient understanding of pigmented skin lesions (moles) and skin cancer, and factors which influence seeking help in primary care. METHOD: Semi-structured interviews with forty MoleMate Trial participants, analysed using the theoretical framework of the Safer-Andersen model of Total Patient Delay. RESULTS: Patient understanding and awareness was influenced by personal, family and friends' experiences of moles, skin cancer and other cancers, knowledge of risk factors, and the lay media. The route to consulting was complex and often iterative. For lesions that people could see, detecting and appraising change was influenced by comparisons with a normal mole on themselves, a family member, friend or image. Inferring illness came about with recognition of changes (particularly size) as serious, and associated 'internal' symptoms such as pain. For lesions that people could not see, family, friends and health professionals detected and appraised changes. Deciding to seek help was often prompted by another person or triggered by rapid or multiple changes in a mole. Three of four people subsequently diagnosed with melanoma did not seek help; instead, their GP opportunistically noticed the lesion. CONCLUSIONS: Changing moles are often perceived as trivial and not signifying possible skin cancer. This study contributes to current national strategies to improve patient awareness and earlier diagnosis of cancer by highlighting factors that can trigger or act as barriers to seeking help.(ISRCTN79932379).RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Informed consent in randomised controlled trials:further development and evaluation of the participatory and informed consent (PIC) measure

Background: Informed consent is an accepted ethical and legal prerequisite for trial participation, yet there is no standardised method of assessing patient understanding for informed consent. The participatory and informed consent (PIC) measure was developed for application to recruitment discussions to evaluate recruiter information provision and evidence of patient understanding. Preliminary evaluation of the PIC indicated the need to improve inter-rater and intra-rater reliability ratings and conduct further psychometric evaluation. This paper describes the assessment, revision and evaluation of the PIC within the context of OPTiMISE, a pragmatic primary care-based trial. Methods: This study used multiple methods across two phases. In phase one, one researcher applied the existing PIC measure to 18 audio-recorded recruitment discussions from the OPTiMISE study and made detailed observational notes about any uncertainties in application. Appointments were sampled to be maximally diverse for patient gender, study centre, recruiter and before and after an intervention to optimise information provision. Application uncertainties were reviewed by the study team, revisions made and a coding manual developed and agreed. In phase two, the coding manual was used to develop tailored guidelines for applying the PIC to appointments within the OPTiMISE trial. Two researchers then assessed 27 further appointments, purposively sampled as above, to evaluate inter-rater and intra-rater reliability, content validity and feasibility. Results: Application of the PIC to 18 audio-recorded OPTiMISE recruitment discussions resulted in harmonisation of the scales rating recruiter information provision and evidence of patient understanding, minor amendments to clarify wording and the development of detailed generic coding guidelines for applying the measure within any trial. Application of the revised measure using these guidelines to 27 further recruitment discussions showed good feasibility (time to complete), content validity (completion rate) and reliability (inter- and intra-rater) of the measure. Conclusion: The PIC provides a means to evaluate the content of information provided by recruiters, patient participation in recruitment discussions and, to some extent, evidence of patient understanding. Future work will use the measure to evaluate recruiter information provision and evidence of patient understanding both across and within trials

Phylogenetic analysis of human Chlamydia pneumoniae strains reveals a distinct Australian indigenous clade that predates European exploration of the continent

© 2015 Roulis et al. Background: The obligate intracellular bacterium Chlamydia pneumoniae is a common respiratory pathogen, which has been found in a range of hosts including humans, marsupials and amphibians. Whole genome comparisons of human C. pneumoniae have previously highlighted a highly conserved nucleotide sequence, with minor but key polymorphisms and additional coding capacity when human and animal strains are compared. Results: In this study, we sequenced three Australian human C. pneumoniae strains, two of which were isolated from patients in remote indigenous communities, and compared them to all available C. pneumoniae genomes. Our study demonstrated a phylogenetically distinct human C. pneumoniae clade containing the two indigenous Australian strains, with estimates that the most recent common ancestor of these strains predates the arrival of European settlers to Australia. We describe several polymorphisms characteristic to these strains, some of which are similar in sequence to animal C. pneumoniae strains, as well as evidence to suggest that several recombination events have shaped these distinct strains. Conclusions: Our study reveals a greater sequence diversity amongst both human and animal C. pneumoniae strains, and suggests that a wider range of strains may be circulating in the human population than current sampling indicates

Patient symptom experience prior to a diagnosis of oesophageal or gastric cancer: a multi-methods study.

BACKGROUND: Late stage diagnosis of oesophageal and gastric cancer is common, which limits treatment options and contributes to poor survival. AIM: To explore patients' understanding, experience and presentation of symptoms before a diagnosis of oesophageal or gastric cancer. DESIGN & SETTING: Between May 2016 and October 2017, all patients newly diagnosed with oesophageal or gastric cancer were identified at weekly multidisciplinary team meetings at two large hospitals in England. A total of 321 patients were invited to participate in a survey and secondary care medical record review; 127 (40%) participants responded (102 patients had oesophageal cancer and 25 had gastric cancer). Of these, 26 participated in an additional face-to-face interview. METHOD: Survey and medical record data were analysed descriptively. Interviews were analysed using thematic analysis, informed by the Model of Pathways to Treatment. RESULTS: Participants experienced multiple symptoms before diagnosis. The most common symptom associated with oesophageal cancer was dysphagia (n = 66, 65%); for gastric cancer, fatigue or tiredness (n = 20, 80%) was the most common symptom. Understanding of heartburn, reflux and indigestion, and associated symptoms differed between participants and often contrasted with clinical perspectives. Bodily changes attributed to personal and/or lifestyle factors were self-managed, with presentation to primary care prompted when symptoms persisted, worsened, or impacted daily life, or were notably severe or unusual. Participants rarely presented all symptoms at the initial consultation. CONCLUSION: The patient interval may be lengthened by misinterpretation of key terms, such as heartburn, or misattribution or non-recognition of important bodily changes. Clearly defined symptom awareness messages may encourage earlier help-seeking, while eliciting symptom experience and meanings in primary care consultations could prompt earlier referral and diagnosis.This research was funded by the Medical Research Council and the Raymond and Beverly Sackler Fund as part of EH’s PhD. FMW was supported by an NIHR Clinician Scientist award. JDE was supported by an NHMRC Practitioner Fellowship. JB was supported by the National Institute for Health Research School for Primary Care Research

Characterizing human lung tissue microbiota and its relationship to epidemiological and clinical features

Background: The human lung tissue microbiota remains largely uncharacterized, although a number of studies based on airway samples suggest the existence of a viable human lung microbiota. Here we characterized the taxonomic and derived functional profiles of lung microbiota in 165 non-malignant lung tissue samples from cancer patients. Results: We show that the lung microbiota is distinct from the microbial communities in oral, nasal, stool, skin, and vagina, with Proteobacteria as the dominant phylum (60 %). Microbiota taxonomic alpha diversity increases with environmental exposures, such as air particulates, residence in low to high population density areas, and pack-years of tobacco smoking and decreases in subjects with history of chronic bronchitis. Genus Thermus is more abundant in tissue from advanced stage (IIIB, IV) patients, while Legionella is higher in patients who develop metastases. Moreover, the non-malignant lung tissues have higher microbiota alpha diversity than the paired tumors. Conclusions: Our results provide insights into the human lung microbiota composition and function and their link to human lifestyle and clinical outcomes. Studies among subjects without lung cancer are needed to confirm our findings

Microbial Biomarkers of Intestinal Barrier Maturation in Preterm Infants

Intestinal barrier immaturity, or “leaky gut,” is the proximate cause of susceptibility to necrotizing enterocolitis in preterm neonates. However, the impact of intestinal microbiota development on intestinal mucosal barrier maturation has not been evaluated in this population. In this study, we investigated a longitudinally sampled cohort of 38 preterm infants < 33 weeks gestation monitored for intestinal permeability (IP) and fecal microbiota during the first 2 weeks of life. Rapid decrease in IP indicating intestinal barrier function maturation correlated with significant increase in community diversity. In particular, members of the Clostridiales and Bifidobacterium were highly transcriptionally active, and progressively increasing abundance in Clostridiales was significantly associated with decreased intestinal permeability. Further, neonatal factors previously identified to promote intestinal barrier maturation, including early exclusive breastmilk feeding and shorter duration antibiotic exposure, associate with the early colonization of the intestinal microbiota by members of the Clostridiales, which altogether are associated with improved intestinal barrier function in preterm infants

Protocol for the MoleMate UK Trial: a randomised controlled trial of the MoleMate system in the management of pigmented skin lesions in primary care [ISRCTN 79932379].

BACKGROUND: Suspicious pigmented lesions are a common presenting problem in general practice consultations; while the majority are benign a small minority are melanomas. Differentiating melanomas from other pigmented lesions in primary care is challenging: currently, 95% of all lesions referred to a UK specialist are benign. The MoleMate system is a new diagnostic aid, incorporating a hand-held SIAscopy scanner with a primary care diagnostic algorithm. This trial tests the hypothesis that adding the MoleMate system to current best primary care practice will increase the proportion of appropriate referrals of suspicious pigmented lesions to secondary care compared with current best practice alone. METHODS/DESIGN: The MoleMate UK Trial is a primary care based multi-centre randomised controlled trial, with randomisation at patient level using a validated block randomisation method for two age groups (45 years and under; 46 years and over). We aim to recruit adult patients seen in general practice with a pigmented skin lesion that cannot immediately be diagnosed as benign and the patient reassured. The trial has a 'two parallel groups' design, comparing 'best practice' with 'best practice' plus the MoleMate system in the intervention group. The primary outcome is the positive predictive value (PPV) of referral defined as the proportion of referred lesions seen by secondary care experts that are considered 'clinically significant' (i.e. biopsied or monitored). Secondary outcomes include: the sensitivity, specificity and negative predictive value (NPV) of the decision not to refer; clinical outcomes (melanoma thickness, 5 year melanoma incidence and mortality); clinician outcomes (Index of Suspicion, confidence, learning effects); patient outcomes (satisfaction, general and cancer-specific worry), and cost-utility. DISCUSSION: The MoleMate UK Trial tests a new technology designed to improve the management of suspicious pigmented lesions in primary care. If effective, the MoleMate system could reduce the burden on skin cancer clinics of patients with benign pigmented skin lesions, and improve patient care in general practice.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are