General Practice and Primary Care - Research Publications

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    Barrett's oESophagus trial 3 (BEST3): study protocol for a randomised controlled trial comparing the Cytosponge-TFF3 test with usual care to facilitate the diagnosis of oesophageal pre-cancer in primary care patients with chronic acid reflux
    Offman, J ; Muldrew, B ; O'Donovan, M ; Debiram-Beecham, I ; Pesola, F ; Kaimi, I ; Smith, SG ; Wilson, A ; Khan, Z ; Lao-Sirieix, P ; Aigret, B ; Walter, FM ; Rubin, G ; Morris, S ; Jackson, C ; Sasieni, P ; Fitzgerald, RC (BMC, 2018-08-03)
    BACKGROUND: Early detection of oesophageal cancer improves outcomes; however, the optimal strategy for identifying patients at increased risk from the pre-cancerous lesion Barrett's oesophagus (BE) is not clear. The Cytosponge, a novel non-endoscopic sponge device, combined with the biomarker Trefoil Factor 3 (TFF3) has been tested in four clinical studies. It was found to be safe, accurate and acceptable to patients. The aim of the BEST3 trial is to evaluate if the offer of a Cytosponge-TFF3 test in primary care for patients on long term acid suppressants leads to an increase in the number of patients diagnosed with BE. METHODS: The BEST3 trial is a pragmatic multi-site cluster-randomised controlled trial set in primary care in England. Approximately 120 practices will be randomised 1:1 to either the intervention arm, invitation to a Cytosponge-TFF3 test, or the control arm usual care. Inclusion criteria are men and women aged 50 or over with records of at least 6 months of prescriptions for acid-suppressants in the last year. Patients in the intervention arm will receive an invitation to have a Cytosponge-TFF3 test in their general practice. Patients with a positive TFF3 test will receive an invitation for an upper gastro-intestinal endoscopy at their local hospital-based endoscopy clinic to test for BE. The primary objective is to compare histologically confirmed BE diagnosis between the intervention and control arms to determine whether the offer of the Cytosponge-TFF3 test in primary care results in an increase in BE diagnosis within 12 months of study entry. DISCUSSION: The BEST3 trial is a well-powered pragmatic trial testing the use of the Cytosponge-TFF3 test in the same population that we envisage it being used in clinical practice. The data generated from this trial will enable NICE and other clinical bodies to decide whether this test is suitable for routine clinical use. TRIAL REGISTRATION: This trial was prospectively registered with the ISRCTN Registry on 19/01/2017, trial number ISRCTN68382401 .
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    Associations between diagnostic activity and measures of patient experience in primary care: a cross-sectional ecological study of English general practices
    Lyratzopoulos, G ; Mendonca, SC ; Gildea, C ; McPhail, S ; Peake, MD ; Rubin, G ; Singh, H ; Hamilton, W ; Walter, FM ; Roland, M ; Abel, GA (ROYAL COLL GENERAL PRACTITIONERS, 2018-01)
    BACKGROUND: Lower use of endoscopies and urgent referrals for suspected cancer has been linked to poorer outcomes for patients with cancer; it is important to examine potential predictors of variable use. AIM: To examine the associations between general practice measures of patient experience and practice use of endoscopies or urgent referrals for suspected cancer. DESIGN AND SETTING: Cross-sectional ecological analysis in English general practices. METHOD: Data were taken from the GP Patient Survey and the Cancer Services Public Health Profiles. After adjustment for practice population characteristics, practice-level associations were examined between the use of endoscopy and urgent referrals for suspected cancer, and the ability to book an appointment (used as proxy for ease of access), the ability to see a preferred doctor (used as proxy for relational continuity), and doctor/nurse communication skills. RESULTS: Taking into account practice scores for the ability to book an appointment, practices rated higher for the proxy measure of relational continuity used urgent referrals and endoscopies less often (for example, 30% lower urgent referral and 15% lower gastroscopy rates between practices in the 90th/10th centiles, respectively). In contrast, practices rated higher for doctor communication skills used urgent referrals and endoscopies more often (for example, 26% higher urgent referral and 17% higher gastroscopy rates between practices in the 90th/10th centiles, respectively). Patients with cancer in practices that were rated higher for doctor communication skills were less likely to be diagnosed as emergencies (1.7% lower between practices in the 90th than in the 10th centile). CONCLUSION: Practices where patients rated doctor communication highly were more likely to investigate and refer patients urgently but, in contrast, practices where patients could see their preferred doctor more readily were less likely to do so. This article discusses the possible implications of these findings for clinical practice.
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    Factors associated with intentional and unintentional non-adherence to adjuvant endocrine therapy following breast cancer
    Brett, J ; Fenlon, D ; Boulton, M ; Hulbert-Williams, NJ ; Walter, FM ; Donnelly, P ; Lavery, B ; Morgan, A ; Morris, C ; Watson, E (WILEY, 2018-01)
    Adherence to adjuvant endocrine therapy (AET) following breast cancer is known to be suboptimal despite its known efficacy in reducing recurrence and mortality. This study aims to investigate factors associated with non-adherence and inform the development of interventions to support women and promote adherence. A questionnaire survey to measure level of adherence, side effects experienced, beliefs about medicine, support received and socio-demographic details was sent to 292 women 2-4 years post breast cancer diagnosis. Differences between non-adherers and adherers to AET were explored, and factors associated with intentional and unintentional non-adherence are reported. Approximately one quarter of respondents, 46 (22%), were non-adherers, comprising 29 (14%) intentional non-adherers and 17 (8%) unintentional non-adherers. Factors significantly associated with intentional non-adherence were the presence of side effects (p < .03), greater concerns about AET (p < .001) and a lower perceived necessity to take AET (p < .001). Half of the sample (105/211) reported that side effects had a moderate or high impact on their quality of life. Factors associated with unintentional non-adherence were younger age (<65) (p < .001), post-secondary education (p = .046) and paid employment (p = .031). There are distinct differences between intentional non-adherence and unintentional non-adherence. Differentiation between the two types of non-adherence may help tailor support and advice interventions.
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    The Improving Rural Cancer Outcomes Trial: a cluster-randomised controlled trial of a complex intervention to reduce time to diagnosis in rural cancer patients in Western Australia (vol 117, pg 1459, 2017)
    Emery, JD ; Gray, V ; Walter, FM ; Cheetham, S ; Croager, EJ ; Slevin, T ; Saunders, C ; Threlfall, T ; Auret, K ; Nowak, AK ; Geelhoed, E ; Bulsara, M ; Holman, CDJ (NATURE PUBLISHING GROUP, 2018-03-20)
    This corrects the article DOI: 10.1038/bjc.2017.310.
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    The Aarhus statement on cancer diagnostic research: turning recommendations into new survey instruments
    Coxon, D ; Campbell, C ; Walter, FM ; Scott, SE ; Neal, RD ; Vedsted, P ; Emery, J ; Rubin, G ; Hamilton, W ; Weller, D (BMC, 2018-09-03)
    BACKGROUND: Over recent years there has been a growth in cancer early diagnosis (ED) research, which requires valid measurement of routes to diagnosis and diagnostic intervals. The Aarhus Statement, published in 2012, provided methodological guidance to generate valid data on these key pre-diagnostic measures. However, there is still a wide variety of measuring instruments of varying quality in published research. In this paper we test comprehension of self-completion ED questionnaire items, based on Aarhus Statement guidance, and seek input from patients, GPs and ED researchers to refine these questions. METHODS: We used personal interviews and consensus approaches to generate draft ED questionnaire items, then a combination of focus groups and telephone interviews to test comprehension and obtain feedback. A framework analysis approach was used, to identify themes and potential refinements to the items. RESULTS: We found that many of the questionnaire items still prompted uncertainty in respondents, in both routes to diagnosis and diagnostic interval measurement. Uncertainty was greatest in the context of multiple or vague symptoms, and potentially ambiguous time-points (such as 'date of referral'). CONCLUSIONS: There are limits on the validity of self-completion questionnaire responses, and refinements to the wording of questions may not be able to completely overcome these limitations. It's important that ED researchers use the best identifiable measuring instruments, but accommodate inevitable uncertainty in the interpretation of their results. Every effort should be made to increase clarity of questions and responses, and use of two or more data sources should be considered.
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    The LEAD study protocol: a mixed-method cohort study evaluating the lung cancer diagnostic and pre-treatment pathways of patients from Culturally and Linguistically Diverse (CALD) backgrounds compared to patients from Anglo-Australian backgrounds
    Mazza, D ; Lin, X ; Walter, FM ; Young, JM ; Barnes, DJ ; Mitchell, P ; Brijnath, B ; Martin, A ; Emery, JD (BMC, 2018-07-21)
    BACKGROUND: Lung cancer is the leading cause of cancer mortality worldwide. Early diagnosis and treatment is a key factor in reducing mortality and improving patient outcomes. To achieve this, it is important to understand the diagnostic pathways of cancer patients. Patients from Culturally and Linguistically Diverse (CALD) are a vulnerable group for lung cancer with higher mortality rates than Caucasian patients. The aim of this study is to explore differences in the lung cancer diagnostic pathways between CALD and Anglo-Australian patients and factors underlying these differences. METHODS: This is a prospective, observational cohort study using a mixed-method approach. Quantitative data regarding time intervals in the lung cancer diagnostic pathways will be gathered via patient surveys, General practitioner (GP) review of general practice records, and case-note analysis of hospital records. Qualitative data will be gathered via structured interviews with lung cancer patients, GPs, and hospital specialists. The study will be conducted in five study sites across three states in Australia. Anglo-Australian patients and patients from five CALD groups (i.e., Arabic, Chinese, Greek, Italian and Vietnamese communities) will mainly be identified through the list of new cases presented at lung multidisciplinary team meetings. For the quantitative component, it is anticipated that 724 patients (362 Anglo-Australian and 362 CALD patients) will be recruited to obtain a final sample of 290 (145 per group) assuming a 50% patient survey completion rate and a 80% GP record review completion rate. For the qualitative component, 60 interviews with lung cancer patients (10 Anglo-Australian and 10 patients per CALD group), 20 interviews with GPs, and 20 interviews with specialists will be conducted. DISCUSSION: This is the first Australian study to compare the time intervals along the lung cancer diagnostic pathway between CALD and Anglo-Australian patients. The study will also explore the underlying patient, healthcare provider, and health system factors that influence the time intervals in the two groups. This information will improve our understanding of the effect of ethnicity on health outcomes among lung cancer patients and will inform future interventions aimed at early diagnosis and treatment for lung cancer, particularly patients from CALD backgrounds. TRIAL REGISTRATION: The project was retrospectively registered with Australian New Zealand Clinical Trials Registry (registration number: ACTRN12617000957392 , date registered: 4th July 2017).
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    Reasons why people do not attend NHS Health Checks: a systematic review and qualitative synthesis
    Harte, E ; MacLure, C ; Martin, A ; Saunders, CL ; Meads, C ; Walter, FM ; Griffin, SJ ; Mant, J ; Usher-Smith, JA (ROYAL COLL GENERAL PRACTITIONERS, 2018-01)
    BACKGROUND: The NHS Health Check programme is a prevention initiative offering cardiovascular risk assessment and management advice to adults aged 40-74 years across England. Its effectiveness depends on uptake. When it was introduced in 2009, it was anticipated that all those eligible would be invited over a 5-year cycle and 75% of those invited would attend. So far in the current cycle from 2013 to 2018, 33.8% of those eligible have attended, which is equal to 48.5% of those invited to attend. Understanding the reasons why some people do not attend is important to maximise the impact of the programmes. AIM: To review why people do not attend NHS Health Checks. DESIGN AND SETTING: A systematic review and thematic synthesis of qualitative studies. METHOD: An electronic literature search was carried out of MEDLINE, Embase, Health Management Information Consortium, Cumulative Index to Nursing and Allied Health Literature, Global Health, PsycINFO, Web of Science, OpenGrey, the Cochrane Library, NHS Evidence, Google Scholar, Google, ClinicalTrials.gov, and the ISRCTN registry from 1 January 1996 to 9 November 2016, and the reference lists of all included papers were also screened manually. Inclusion criteria were primary research studies that reported the views of people who were eligible for but had not attended an NHS Health Check. RESULTS: Nine studies met the inclusion criteria. Reasons for not attending included lack of awareness or knowledge, misunderstanding the purpose of the NHS Health Check, aversion to preventive medicine, time constraints, difficulties with access to general practices, and doubts regarding pharmacies as appropriate settings. CONCLUSION: The findings particularly highlight the need for improved communication and publicity around the purpose of the NHS Health Check programme and the personal health benefits of risk factor detection.
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    Symptom Signatures and Diagnostic Timeliness in Cancer Patients: A Review of Current Evidence
    Koo, MM ; Hamilton, W ; Walter, FM ; Rubin, GP ; Lyratzopoulos, G (ELSEVIER SCIENCE INC, 2018-02)
    Early diagnosis is an important aspect of contemporary cancer prevention and control strategies, as the majority of patients are diagnosed following symptomatic presentation. The nature of presenting symptoms can critically influence the length of the diagnostic intervals from symptom onset to presentation (the patient interval), and from first presentation to specialist referral (the primary care interval). Understanding which symptoms are associated with longer diagnostic intervals to help the targeting of early diagnosis initiatives is an area of emerging research. In this Review, we consider the methodological challenges in studying the presenting symptoms and intervals to diagnosis of cancer patients, and summarize current evidence on presenting symptoms associated with a range of common and rarer cancer sites. We propose a taxonomy of cancer sites considering their symptom signature and the predictive value of common presenting symptoms. Finally, we consider evidence on associations between symptomatic presentations and intervals to diagnosis before discussing implications for the design, implementation, and evaluation of public health or health system interventions to achieve the earlier detection of cancer.
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    Variation in 'fast-track' referrals for suspected cancer by patient characteristic and cancer diagnosis: evidence from 670 000 patients with cancers of 35 different sites
    Zhou, Y ; Mendonca, SC ; Abel, GA ; Hamilton, W ; Walter, FM ; Johnson, S ; Shelton, J ; Elliss-Brookes, L ; McPhail, S ; Lyratzopoulos, G (NATURE PUBLISHING GROUP, 2018-01-09)
    BACKGROUND: In England, 'fast-track' (also known as 'two-week wait') general practitioner referrals for suspected cancer in symptomatic patients are used to shorten diagnostic intervals and are supported by clinical guidelines. However, the use of the fast-track pathway may vary for different patient groups. METHODS: We examined data from 669 220 patients with 35 cancers diagnosed in 2006-2010 following either fast-track or 'routine' primary-to-secondary care referrals using 'Routes to Diagnosis' data. We estimated the proportion of fast-track referrals by sociodemographic characteristic and cancer site and used logistic regression to estimate respective crude and adjusted odds ratios. We additionally explored whether sociodemographic associations varied by cancer. RESULTS: There were large variations in the odds of fast-track referral by cancer (P<0.001). Patients with testicular and breast cancer were most likely to have been diagnosed after a fast-track referral (adjusted odds ratios 2.73 and 2.35, respectively, using rectal cancer as reference); whereas patients with brain cancer and leukaemias least likely (adjusted odds ratios 0.05 and 0.09, respectively, for brain cancer and acute myeloid leukaemia). There were sex, age and deprivation differences in the odds of fast-track referral (P<0.013) that varied in their size and direction for patients with different cancers (P<0.001). For example, fast-track referrals were least likely in younger women with endometrial cancer and in older men with testicular cancer. CONCLUSIONS: Fast-track referrals are less likely for cancers characterised by nonspecific presenting symptoms and patients belonging to low cancer incidence demographic groups. Interventions beyond clinical guidelines for 'alarm' symptoms are needed to improve diagnostic timeliness.
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    pedigreejs: a web-based graphical pedigree editor
    Carver, T ; Cunningham, AP ; de Villiers, CB ; Lee, A ; Hartley, S ; Tischkowitz, M ; Walter, FM ; Easton, DF ; Antoniou, AC ; Stegle, O (OXFORD UNIV PRESS, 2018-03-15)
    MOTIVATION: The collection, management and visualization of clinical pedigree (family history) data is a core activity in clinical genetics centres. However, clinical pedigree datasets can be difficult to manage, as they are time consuming to capture, and can be difficult to build, manipulate and visualize graphically. Several standalone graphical pedigree editors and drawing applications exist but there are no freely available lightweight graphical pedigree editors that can be easily configured and incorporated into web applications. RESULTS: We developed 'pedigreejs', an interactive graphical pedigree editor written in JavaScript, which uses standard pedigree nomenclature. Pedigreejs provides an easily configurable, extensible and lightweight pedigree editor. It makes use of an open-source Javascript library to define a hierarchical layout and to produce images in scalable vector graphics (SVG) format that can be viewed and edited in web browsers. AVAILABILITY AND IMPLEMENTATION: The software is freely available under GPL licence (https://ccge-boadicea.github.io/pedigreejs/). CONTACT: tjc29@cam.ac.uk. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.