Lung cancer screening - gaining consensus on next steps - proceedings of a closed workshop in the UK.

Lung cancer is the most common cause of cancer death in the UK, and survival from the disease is persistently poor. Efforts to improve outcomes for patients have focused on ways of reducing late diagnosis of the disease, and access to optimal treatment. Research on lung cancer screening has so far provided some evidence of an impact on lung cancer mortality, but there is some debate about whether implementation of a national screening programme should await further trial data, principally that from the NELSON trial. The ongoing poor outcomes and the belief amongst some clinicians that there is sufficient evidence has prompted several local projects testing out lung screening in their communities, sometimes referred to as lung health checks or proactive approaches to high-risk individuals. Funding from NHS England has been forthcoming to support this. Acknowledging roll-out of such activities, which effectively constitute local lung screening in the absence of a NSC recommendation, it was timely to bring key national stakeholders together with academic and clinical experts, to agree a way forward. Cancer Research UK therefore convened a closed workshop in March 2018, involving national and international expertise. This paper outlines the proceedings, key discussion points, highlighted research gaps, and areas of consensus and next steps.

Routes to diagnosis for cancer - determining the patient journey using multiple routine data sets.

BACKGROUND: Cancer survival in England is lower than the European average, which has been at least partly attributed to later stage at diagnosis in English patients. There are substantial regional and demographic variations in cancer survival across England. The majority of patients are diagnosed following symptomatic or incidental presentation. This study defines a methodology by which the route the patient follows to the point of diagnosis can be categorised to examine demographic, organisational, service and personal reasons for delayed diagnosis. METHODS: Administrative Hospital Episode Statistics data are linked with Cancer Waiting Times data, data from the cancer screening programmes and cancer registration data. Using these data sets, every case of cancer registered in England, which was diagnosed in 2006-2008, is categorised into one of eight 'Routes to Diagnosis'. RESULTS: Different cancer types show substantial differences between the proportion of cases that present by each route, in reasonable agreement with previous clinical studies. Patients presenting via Emergency routes have substantially lower 1-year relative survival. CONCLUSION: Linked cancer registration and administrative data can be used to robustly categorise the route to a cancer diagnosis for all patients. These categories can be used to enhance understanding of and explore possible reasons for delayed diagnosis.

The Aarhus statement: improving design and reporting of studies on early cancer diagnosis.

Early diagnosis is a key factor in improving the outcomes of cancer patients. A greater understanding of the pre-diagnostic patient pathways is vital yet, at present, research in this field lacks consistent definitions and methods. As a consequence much early diagnosis research is difficult to interpret. A consensus group was formed with the aim of producing guidance and a checklist for early cancer-diagnosis researchers. A consensus conference approach combined with nominal group techniques was used. The work was supported by a systematic review of early diagnosis literature, focussing on existing instruments used to measure time points and intervals in early cancer-diagnosis research. A series of recommendations for definitions and methodological approaches is presented. This is complemented by a checklist that early diagnosis researchers can use when designing and conducting studies in this field. The Aarhus checklist is a resource for early cancer-diagnosis research that should promote greater precision and transparency in both definitions and methods. Further work will examine whether the checklist can be readily adopted by researchers, and feedback on the guidance will be used in future updates.

Development of a measurement tool to assess public awareness of cancer.

OBJECTIVE: We aimed to develop and validate a measurement tool to assess cancer awareness in the general population: the cancer awareness measure (CAM). METHODS: Items assessing awareness of cancer warning signs, risk factors, incidence, screening programmes and attitudes towards help seeking were extracted from the literature or generated by expert groups. To determine reliability, the CAM was administered to a university participant panel (n=148), with a sub-sample (n=94) completing it again 2 weeks later. To establish construct validity, CAM scores of cancer experts (n=12) were compared with those of non-medical academics (n=21). Finally, university students (n=49) were randomly assigned to read either a cancer information leaflet or a leaflet with control information before completing the measure, to ensure the CAM was sensitive to change. RESULTS: Cognitive interviewing indicated that the CAM was being interpreted as intended. Internal reliability (Cronbach's alpha=0.77) and test-retest reliability (r=0.81) were high. Scores for cancer experts were significantly higher than those for non-medical academics (t(31)=6.8, P<0.001). CAM scores were higher among students who received an intervention leaflet than the control leaflet (t(47)=4.8, P<0.001). CONCLUSIONS: These studies show the psychometric properties of the CAM and support its validity as a measure of cancer awareness in the general population.

Public awareness of cancer in Britain: a population-based survey of adults.

OBJECTIVE: To assess public awareness of cancer warning signs, anticipated delay and perceived barriers to seeking medical advice in the British population. METHODS: We carried out a population-based survey using face-to-face, computer-assisted interviews to administer the cancer awareness measure (CAM), a newly developed, validated measure of cancer awareness. The sample included 2216 adults (970 males and 1246 females) recruited as part of the Office for National Statistics Opinions Survey using stratified probability sampling. RESULTS: Awareness of cancer warning signs was low when open-ended (recall) questions were used and higher with closed (recognition) questions; but on either measure, awareness was lower in those who were male, younger, and from lower socio-economic status (SES) groups or ethnic minorities. The most commonly endorsed barriers to help seeking were difficulty making an appointment, worry about wasting the doctor's time and worry about what would be found. Emotional barriers were more prominent in lower SES groups and practical barriers (e.g. too busy) more prominent in higher SES groups. Anticipated delay was lower in ethnic minority and lower SES groups. In multivariate analysis, higher symptom awareness was associated with lower anticipated delay, and more barriers with greater anticipated delay. CONCLUSIONS: A combination of public education about symptoms and empowerment to seek medical advice, as well as support at primary care level, could enhance early presentation and improve cancer outcomes.

Awareness of cancer symptoms and anticipated help seeking among ethnic minority groups in England.

OBJECTIVE: Little is known about ethnic differences in awareness of cancer-warning signs or help-seeking behaviour in Britain. As part of the National Awareness and Early Diagnosis Initiative (NAEDI), this study aimed to explore these factors as possible contributors to delay in cancer diagnosis. METHODS: We used quota sampling to recruit 1500 men and women from the six largest minority ethnic groups in England (Indian, Pakistani, Bangladeshi, Caribbean, African and Chinese). In face-to-face interviews, participants completed the newly developed cancer awareness measure (CAM), which includes questions about warning signs for cancer, speed of consultation for possible cancer symptoms and barriers to help seeking. RESULTS: Awareness of warning signs was low across all ethnic groups, especially using the open-ended (recall) question format, with lowest awareness in the African group. Women identified more emotional barriers and men more practical barriers to help seeking, with considerable ethnic variation. Anticipated delay in help seeking was higher in individuals who identified fewer warning signs and more barriers. CONCLUSIONS: The study suggests the need for culturally sensitive, community-based interventions to raise awareness and encourage early presentation.

Evaluation of alcohol wipes used during aseptic manufacturing.

AIM: During aseptic manufacturing and specifically during the transfer of items into an isolator, disinfection of surfaces is essential for reducing the risk of final product contamination. Surface disinfection can be carried out by a variety of methods, however the most accepted current practice is a combination of spraying with 70% alcohol and wiping. The aim of this study was to evaluate the effectiveness of two wipe systems by determining their ability to remove, kill and transfer bacterial contaminants from standardized surfaces. METHODS AND RESULTS: The protocol used to achieve these objectives was based on a newly published method specifically designed to test wipes. Alcohol impregnated wipes performed better at reducing microbial bioburden than the alcohol spray/dry wipe applications. Impregnated wipes drastically reduced (1-2 log(10) reduction) a small bioburden (approx. 2 log(10)) of spores of Bacillus subtilis and methicillin-resistant Staphylococcus aureus from the surface, but failed to remove (<0.2 log(10) reduction) Staphylococcus epidermidis. The alcohol spray/dry wipes did not manage to remove (<0.2 log(10) reduction) spore or bacterial bioburden from surfaces and was able to transfer some viable micro-organisms to other surfaces. Both wipe types showed poor antimicrobial efficacy (<1 log(10) reduction) against the test bacteria and spores. CONCLUSIONS: As far as the authors are aware this is the first time that such a practical study has been reported and our results suggest that the best wipes for surface disinfection in aseptic units are the alcohol (IPA) impregnated wipes when compared with the dry wipes sprayed with alcohol. SIGNIFICANCE AND IMPACT OF THE STUDY: The impregnated wipes performed better than the dry wipes sprayed with alcohol and should be used for surface disinfection in aseptic units.

Evaluation of the effectiveness of commercially available contact plates for monitoring microbial environments.

AIM: The aim of this study was to measure the efficiency of contact plates to recover microbial contaminants from stainless steel surface. MATERIALS AND METHODS: Three commercially available contact plates were used to recover two biological indicators from stainless steel sheets. The method used was standardised and validated to provide robust results. Parameters such as wetness, fertility and loss of water were also investigated for possible correlation with recovery efficiency. RESULTS: The percentage of recovery from the contact plates was low and differences in recovery efficiency between brands depended upon the test organism. The poor recovery was probably due to the inability of the dried micro-organism to transfer to the plate, rather than the inability of the plate to grow the micro-organism. Wetness might help in improving recovery. CONCLUSIONS: The use of a validated protocol allowed robust investigations into the recovery efficiency of contact plates. SIGNIFICANCE AND IMPACT OF THE STUDY: The poor and variable recovery rates are of concern as they cast doubt on the comparability and reliability of environmental monitoring results where different commercial contact plates have been used.

Benchmarking the current dispensing rate of Welsh hospital pharmacies.

BACKGROUND: There is a need to develop capacity measures for pharmacy services for strategic purposes, to provide guidance on safe working limits and to contribute to the target 40% reduction in serious medication errors by 2005. Attempts have been made to quantify workloads in the form of items/person/hour (i/p/h). However, much of these data are anecdotal, small scale or associated with vague methodology. OBJECTIVE: We estimate national average dispensing rates by collecting accurate data from secondary care dispensaries across Wales. METHOD: Seventeen sites collected hourly data relating to staff time and items dispensed over a 3-day period. The result showed a Welsh national average for non-specialist hospital pharmacy dispensing rates of 9.9 items/person/h (95% CI = 0.9, n = 17). There was a significant positive association between hospital size and telephone interruptions (r(s) = 0.83, P < 0.001) but no correlation between hospital size and dispensing rates (r(s) = 0.06, P = 0.822).

SunSmart? Skin cancer knowledge and preventive behaviour in a British population representative sample.

The incidence of skin cancer has risen rapidly in the UK over the last 20 years, prompting public health organizations to try and raise awareness of the dangers of sun exposure and the need to practice sun-safe behaviour. This study aimed to assess baseline levels of sun-safe knowledge and behaviour in a British population-representative sample, prior to the launch of Cancer Research UK's 'SunSmart' campaign. A face-to-face survey was conducted through the Office for National Statistics as part of their Omnibus survey. In total, 1848 men and women aged 18 and over were interviewed. Knowledge of what to do to reduce skin cancer risk was modest. Two-thirds mentioned avoiding the sun by seeking shade, 50% mentioned covering up and only 43% said to use high factor sunscreen. Practice of sun-safe behaviours was also poor, with only one-third saying they sought shade, covered up or used high factor sunscreen to protect themselves from the sun. Men and those from lower socioeconomic groups were least informed and least likely to report using sun-protective behaviours. Increases in both knowledge and use of appropriate sun-protective behaviours are needed if skin cancer incidence rates are to decrease.

A survey of rotational use of biocides in hospital pharmacy aseptic units.

A postal survey of biocide rotation in UK hospital pharmacy aseptic units was carried out. Seventy per cent of respondents stated that biocides were rotated, most frequently in areas outside critical work zones. High-level disinfection was employed when 'aseptic' conditions were required. Decisions on frequency of rotation were most often based on in-house validation or consultation with colleagues. Toxicity and corrosiveness were the criteria rated most important in a rotation policy. Microbiological monitoring was carried out most frequently in critical work zones but less often for handwashing. Most QC hospital pharmacists supported rotation and would prefer a standard period for all applications (monthly). Guidelines need to be clarified to assist staff in decisions regarding biocide rotation.

Resistance to antibiotics and biocides among non-fermenting Gram-negative bacteria.

OBJECTIVE: To investigate the antibiotic and biocide susceptibilities of clinical isolates of rarely encountered Gram-negative, non-fermenting bacteria. METHODS: Thirty Gram-negative non-fermenting bacterial strains were isolated from blood cultures of oncology patients. These were studied for their resistance to 11 antibiotics. Their susceptibilities to seven biocides used in hospitals were also examined. RESULTS: Isolates of Stenotrophomonas maltophilia and Ochrobactrum anthropi were generally resistant to at least five of the antibiotics, whereas isolates of Comamonas acidivorans, Flavobacterium oryzihabitans, Aeromonas hydrophila, Sphingobacterium spiritivorum, Acinetobacter junii and Acinetobacter lwoffi were generally sensitive to at least nine of the antibiotics. Trovafloxacin and trimethoprim-sulfamethoxazole were the most effective antibacterial agents tested, with 0% and 7%, respectively, of isolates being resistant, whereas 63% of isolates were resistant to aztreonam. Some isolates, sensitive to meropenem and/or ceftazidime in vitro, possessed very high MBC/MIC ratios for these beta-lactams. Two out of three biocides used in hospital pharmacies showed lethal activity towards all strains tested when used at less than one-third of their recommended in-use concentration. Proceine 40 failed to give a 5 log reduction in bacterial cell number for the isolates tested when used at its "in-use" concentration. A concentration of > 500 mg/L chlorhexidine was required to achieve a 5 log reduction for the same isolates. CONCLUSIONS: We have examined the antibiotic susceptibilities of non-fermenting Gram-negative bacterial strains isolated from immunocompromised patients. Despite being sensitive to certain antibiotics in vitro, some isolates were still able to cause serious bacteremia. We have also reported for the first time the susceptibilities of non-fermenting Gram-negative bacteria to common biocides used in hospital infection control, and have shown that some strains are able to persist at the "in-use" concentration of particular biocides. It is therefore important to study further this particular group of organisms, and, in particular, to examine whether there exists a link between resistance to antibiotics and resistance to biocides.

Bulleidia extructa gen. nov., sp. nov., isolated from the oral cavity.

Five strains of anaerobic non-sporing Gram-positive bacilli isolated from advanced periodontitis (four strains) and a dentoalveolar abscess (one strain) that did not correspond to existing species were subjected to phenotypic and genetic characterization. Following 16S rDNA sequence analysis, they were found to constitute a novel branch of the low G+C Gram-positive division of the phylogenetic tree related to Erysipelothrix rhusiopathiae and Holdemania filiformis. A new genus Bulleidia, and the species Bulleidia extructa, are proposed. Growth of B. extructa in broth media was poor but was enhanced by the addition of fructose, glucose or maltose together with Tween 80. Glucose and maltose were fermented and arginine was hydrolysed. Acetate, lactate and trace amounts of succinate were the end products of glucose fermentation. The G+C content of the DNA of the type strain is 38 mol%. The type strain of Bulleidia extructa is DSM 13220T.

The family Coriobacteriaceae: reclassification of Eubacterium exiguum (Poco et al. 1996) and Peptostreptococcus heliotrinreducens (Lanigan 1976) as Slackia exigua gen. nov., comb. nov. and Slackia heliotrinireducens gen. nov., comb. nov., and Eubacterium lentum (Prevot 1938) as Eggerthella lenta gen. nov., comb. nov.

16S rRNA gene sequences were determined for Eubacterium exiguum and Peptostreptococcus heliotrinreducens. These species were found to be closely related and, together with Eubacterium lentum, to constitute a branch of the Coriobacteriaceae. Two new genera are proposed on the basis of phenotypic characteristics and 16S rRNA gene sequence comparisons: Slackia to include the bile-sensitive species Eubacterium exiguum and P. heliotrinreducens, and Eggerthella to include the bile-resistant Eubacterium lentum. It is proposed that Eubacterium exiguum and Peptostreptococcus heliotrinreducens are transferred to the genus Slackia gen. nov. as Slackia exigua gen. nov., comb. nov. (type strain ATCC 700122T) and Slackia heliotrinireducens gen. nov., comb. nov. (type strain NTCC 11029T), respectively, and Eubacterium lentum is transferred to the genus Eggerthella gen. nov. as Eggerthella lenta gen. nov., comb. nov. with Eggerthella lenta as the type species.

Design and evaluation of useful bacterium-specific PCR primers that amplify genes coding for bacterial 16S rRNA.

We report the design and evaluation of PCR primers 63f and 1387r for amplification of 16S rRNA genes from bacteria. Their specificity and efficacy were tested systematically with a bacterial species and environmental samples. They were found to be more useful for 16S rRNA gene amplification in ecological and systematic studies than PCR amplimers that are currently more generally used.

Phylogeny of oral asaccharolytic Eubacterium species determined by 16S ribosomal DNA sequence comparison and proposal of Eubacterium infirmum sp. nov. and Eubacterium tardum sp. nov.

16S rRNA gene sequences of Eubacterium brachy, Eubacterium nodatum, Eubacterium saphenum, Eubacterium timidum, and two previously unnamed taxa were determined. The results of a phylogenetic analysis indicated that all of the strains sequenced belonged to a deep branch of the low-G+C-content gram-positive group. The levels of 16S ribosomal DNA sequence similarity between species were low, suggesting that a number of genera may be represented in this group. The representatives of the two unnamed taxa, which were isolated from patients with periodontitis, were clearly distinct from the previously described species, and, therefore, the following two new species are proposed: Eubacterium infirmum (type strain, NCTC 12940) and Eubacterium tardum (type strain, NCTC 12941).

Identification and discrimination of oral asaccharolytic Eubacterium spp. by pyrolysis mass spectrometry and artificial neural networks.

Curie-point pyrolysis mass spectra were obtained from 29 oral asaccharolytic Eubacterium strains and 6 abscess isolates previously identified as Peptostreptococcus heliotrinreducens. Pyrolysis mass spectrometry (PyMS) with cluster analysis was able to clarify the taxonomic position of this group of organisms. Artificial neural networks (ANNS) were then trained by supervised learning (with the back-propagation algorithm) to recognize the strains from their pyrolysis mass spectra; all Eubacterium strains were correctly identified, and the abscess isolates were identified as un-named Eubacterium taxon C2 and were distinct from the type strain of P. heliotrinreducens. These results demonstrate that the combination of PyMS and ANNs provides a rapid and accurate identification technique.