Morbidity and measures of the diagnostic process in primary care for patients subsequently diagnosed with cancer.

BACKGROUND: There is uncertainty regarding how pre-existing conditions (morbidities) may influence the primary care investigation and management of individuals subsequently diagnosed with cancer. METHODS: We identified morbidities using information from both primary and secondary care records among 11,716 patients included in the English National Cancer Diagnosis Audit (NCDA) 2014. We examined variation in 5 measures of the diagnostic process (the primary care interval, diagnostic interval, number of pre-referral consultations, use of primary care-led investigations, and referral type) by both primary care- and hospital records-derived measures of morbidity. RESULTS: Morbidity prevalence recorded before cancer diagnosis was almost threefold greater using the primary care (75%) vs secondary care-derived measure (28%). After adjustment, there was limited variation in the primary care interval and the number of pre-referral consultations by either definition of morbidity. Patients with more severe morbidities were less likely to have had a primary care-led investigation before cancer diagnosis compared with those without any morbidity (adjusted odds ratio, OR [95% confidence interval]: 0.72 [0.60-0.86] for Charlson score 3+ vs 0; joint P < 0.001). Patients with multiple primary care-recorded conditions or a Charlson score of 3+ were more likely to have diagnostic intervals exceeding 60 days (aOR: 1.26 [1.10-1.45] and 1.19 [>1.00-1.41], respectively), and more likely to receive an emergency referral (aOR: 1.60 [1.26-2.02] and 1.61 [1.26-2.06], respectively). CONCLUSION: Among cancer cases with up to 2 morbidities, there was no evidence of differences in diagnostic processes and intervals in primary care but higher morbidity burden was associated with longer time to diagnosis and higher likelihood of emergency referral.

Individuals with pre-existing long-term conditions (morbidities) may have a different pathways leading to their cancer diagnosis compared with those without such conditions but detailed evidence is limited. We aimed to investigate how morbidities were associated with a range of measures of the diagnostic process in primary care. We examined morbidity in 2 ways, using information from a primary care audit and hospital records. We found that three-quarters of patients were living with 1 or more conditions according to primary care-based information, while the prevalence was almost threefold lower when estimated using hospital records. There was little difference in the time from first primary care appointment to specialist referral and the number of appointments before specialist referral by morbidity, particularly when comparing patients with 1 or 2 conditions vs those without. However, patients with multiple conditions or more serious diseases experienced lower likelihood of investigation, greater likelihood of being sent to the hospital as an emergency, and longer time to diagnosis. We did not find evidence of substantial differences in primary care-based diagnostic processes by morbidity. However, once an initial referral has been made, multiple or more severe conditions appear to influence the time taken to reach a diagnosis.

Presenting symptoms of cancer and stage at diagnosis: evidence from a cross-sectional, population-based study.

BACKGROUND: Early diagnosis interventions such as symptom awareness campaigns increasingly form part of global cancer control strategies. However, these strategies will have little impact in improving cancer outcomes if the targeted symptoms represent advanced stage of disease. Therefore, we aimed to examine associations between common presenting symptoms of cancer and stage at diagnosis. METHODS: In this cross-sectional study, we analysed population-level data from the English National Cancer Diagnosis Audit 2014 for patients aged 25 years and older with one of 12 types of solid tumours (bladder, breast, colon, endometrial, laryngeal, lung, melanoma, oral or oropharyngeal, ovarian, prostate, rectal, and renal cancer). We considered 20 common presenting symptoms and examined their associations with stage at diagnosis (TNM stage IV vs stage I-III) using logistic regression. For each symptom, we estimated these associations when reported as a single presenting symptom and when reported together with other symptoms. FINDINGS: We analysed data for 7997 patients. The proportion of patients diagnosed with stage IV cancer varied substantially by presenting symptom, from 1% (95% CI 1-3; eight of 584 patients) for abnormal mole to 80% (71-87; 84 of 105 patients) for neck lump. Three of the examined symptoms (neck lump, chest pain, and back pain) were consistently associated with increased odds of stage IV cancer, whether reported alone or with other symptoms, whereas the opposite was true for abnormal mole, breast lump, postmenopausal bleeding, and rectal bleeding. For 13 of the 20 symptoms (abnormal mole, breast lump, post-menopausal bleeding, rectal bleeding, lower urinary tract symptoms, haematuria, change in bowel habit, hoarseness, fatigue, abdominal pain, lower abdominal pain, weight loss, and the "any other symptom" category), more than 50% of patients were diagnosed at stages other than stage IV; for 19 of the 20 studied symptoms (all except for neck lump), more than a third of patients were diagnosed at stages other than stage IV. INTERPRETATION: Despite specific presenting symptoms being more strongly associated with advanced stage at diagnosis than others, for most symptoms, large proportions of patients are diagnosed at stages other than stage IV. These findings provide support for early diagnosis interventions targeting common cancer symptoms, countering concerns that they might be simply expediting the detection of advanced stage disease. FUNDING: UK Department of Health's Policy Research Unit in Cancer Awareness, Screening and Early Diagnosis; and Cancer Research UK.

The nature and frequency of abdominal symptoms in cancer patients and their associations with time to help-seeking: evidence from a national audit of cancer diagnosis.

Background: Raising awareness of possible cancer symptoms is important for timely help-seeking; recent campaigns have focused on symptom groups (such as abdominal symptoms) rather than individual alarm symptoms associated with particular cancer sites. The evidence base supporting such initiatives is still emerging however; understanding the frequency and nature of presenting abdominal symptoms among cancer patients could inform the design and evaluation of public health awareness campaigns. Methods: We examined eight presenting abdominal symptoms (abdominal pain, change in bowel habit, bloating/distension, dyspepsia, rectal bleeding, dysphagia, reflux and nausea/vomiting) among 15 956 patients subsequently diagnosed with cancer in England. We investigated the cancer site case-mix and variation in the patient interval (symptom-onset-to-presentation) by abdominal symptom. Results: Almost a quarter (23%) of cancer patients presented with abdominal symptoms before being diagnosed with one of 27 common and rarer cancers. The patient interval varied substantially by abdominal symptom: median (IQR) intervals ranged from 7 (0-28) days for abdominal pain to 30 (4-73) days for dysphagia. This variation persisted after adjusting for age, sex and ethnicity (P < 0.001). Conclusions: Abdominal symptoms are common at presentation among cancer patients, while time to presentation varies by symptom. The need for awareness campaigns may be greater for symptoms associated with longer intervals to help-seeking.

Symptoms and patient factors associated with longer time to diagnosis for colorectal cancer: results from a prospective cohort study.

BACKGROUND: The objective of this study is to investigate symptoms, clinical factors and socio-demographic factors associated with colorectal cancer (CRC) diagnosis and time to diagnosis. METHODS: Prospective cohort study of participants referred for suspicion of CRC in two English regions. Data were collected using a patient questionnaire, primary care and hospital records. Descriptive and regression analyses examined associations between symptoms and patient factors with total diagnostic interval (TDI), patient interval (PI), health system interval (HSI) and stage. RESULTS: A total of 2677 (22%) participants responded; after exclusions, 2507 remained. Participants were diagnosed with CRC (6.1%, 56% late stage), other cancers (2.0%) or no cancer (91.9%). Half the cohort had a solitary first symptom (1332, 53.1%); multiple first symptoms were common. In this referred population, rectal bleeding was the only initial symptom more frequent among cancer than non-cancer cases (34.2% vs 23.9%, P=0.004). There was no evidence of differences in TDI, PI or HSI for those with cancer vs non-cancer diagnoses (median TDI CRC 124 vs non-cancer 138 days, P=0.142). First symptoms associated with shorter TDIs were rectal bleeding, change in bowel habit, 'feeling different' and fatigue/tiredness. Anxiety, depression and gastro-intestinal co-morbidities were associated with longer HSIs and TDIs. Symptom duration-dependent effects were found for rectal bleeding and change in bowel habit. CONCLUSIONS: Doctors and patients respond less promptly to some symptoms of CRC than others. Healthcare professionals should be vigilant to the possibility of CRC in patients with relevant symptoms and mental health or gastro-intestinal comorbidities.

Attitudes and beliefs of non-participants in a population-based screening programme for colorectal cancer.

BACKGROUND: Uptake of colorectal cancer screening programmes needs to be improved or at least maintained in order to achieve projected reductions in mortality and morbidity. Understanding the origins of non-participation in screening is therefore important. OBJECTIVE: To explore the beliefs and experiences of individuals who had not responded either to their screening invitation or reminder. DESIGN: A qualitative study using in-depth interviews with non-participants from England's population-based colorectal cancer screening programme. Data collection and analysis were carried out using a grounded theory approach, with an emphasis on the constant comparison method, and continued until saturation (27 interviews). FINDINGS: The interviews provided an in-depth understanding of a range of reasons and circumstances surrounding non-participation in screening, including contextual and environmental influences as well as factors specific to the screening test. Non-participation in screening was not necessarily associated with negative attitudes towards screening or a decision to not return a kit. Reasons for non-participation in screening included not feeling that participation is personally necessary, avoiding or delaying decision making, and having some degree of intention to take part but failing to do so because of practicalities, conflicting priorities or external circumstances. Beliefs, awareness and intention change over time. DISCUSSION AND CONCLUSIONS: A range of approaches may be required to improve screening uptake. Some non-participants may already have a degree of intention to take part in screening in the future, and this group may be more responsive to interventions based on professional endorsement, repeat invitations, reminders and aids to making the test more practical.

Pre-Referral Primary Care Blood Tests and Symptom Presentation before Cancer Diagnosis: National Cancer Diagnosis Audit Data.

BACKGROUND: Blood tests can support the diagnostic process in primary care. Understanding how symptomatic presentations are associated with blood test use in patients subsequently diagnosed with cancer can help to benchmark current practices and guide interventions. METHODS: English National Cancer Diagnosis Audit data on 39,751 patients with incident cancer in 2018 were analysed. The frequency of four generic (full blood count, urea and electrolytes, liver function tests, and inflammatory markers) and five organ-specific (cancer biomarkers (PSA or CA125), serum protein electrophoresis, ferritin, bone profile, and amylase) blood tests was described for a total of 83 presenting symptoms. The adjusted analysis explored variation in blood test use by the symptom-positive predictive value (PPV) group. RESULTS: There was a large variation in generic blood test use by presenting symptoms, being higher in patients subsequently diagnosed with cancer who presented with nonspecific symptoms (e.g., fatigue 81% or loss of appetite 79%), and lower in those who presented with alarm symptoms (e.g., breast lump 3% or skin lesion 1%). Serum protein electrophoresis (reflecting suspicion of multiple myeloma) was most frequently used in cancer patients who presented with back pain (18%), and amylase measurement (reflecting suspicion of pancreatic cancer) was used in those who presented with upper abdominal pain (14%). Prostate-specific antigen (PSA) use was greatest in men with cancer who presented with lower urinary tract symptoms (88%), and CA125 in women with cancer who presented with abdominal distention (53%). Symptoms with PPV values between 2.00-2.99% were associated with greater test use (64%) compared with 52% and 51% in symptoms with PPVs in the 0.01-0.99 or 1.00-1.99% range and compared with 42% and 31% in symptoms with PPVs in either the 3.00-4.99 or ≥5% range (p < 0.001). CONCLUSIONS: Generic blood test use reflects the PPV of presenting symptoms, and the use of organ-specific tests is greater in patients with symptomatic presentations with known associations with certain cancer sites. There are opportunities for greater blood test use in patients presenting with symptoms that do not meet referral thresholds (i.e., <3% PPV for cancer) where information gain to support referral decisions is likely greatest. The findings benchmark blood test use in cancer patients, highlighting opportunities for increasing use.

Primary care blood tests before cancer diagnosis: National Cancer Diagnosis Audit data.

BACKGROUND: Blood tests can support the diagnostic process in patients with cancer but how often they are used is unclear. AIM: To explore use of common blood tests before cancer diagnosis in primary care. DESIGN AND SETTING: English National Cancer Diagnosis Audit data on 39 752 patients with cancer diagnosed in 2018. METHOD: Common blood test use (full blood count [FBC], urea and electrolytes [U&E], and liver function tests [LFTs]), variation by patient and symptom group, and associations with the primary care interval and the diagnostic interval were assessed. RESULTS: At least one common blood test was used in 41% (n = 16 427/39 752) of patients subsequently diagnosed with cancer. Among tested patients, (n = 16 427), FBC was used in 95% (n = 15 540), U&E in 89% (n = 14 555), and LFTs in 76% (n = 12 414). Blood testing was less common in females (adjusted odds ratio versus males: 0.92, 95% confidence interval [CI] = 0.87 to 0.98) and Black and minority ethnic patients (0.89, 95% CI = 0.82 to 0.97 versus White), and more common in older patients (1.12, 95% CI = 1.06 to 1.18 for ≥70 years versus 50-69 years). Test use varied greatly by cancer site (melanoma 2% [ n = 55/2297]; leukaemia 84% [ n = 552/661]). Fewer patients presenting with alarm symptoms alone were tested (24% [ n = 3341/13 778]) than those with non-alarm symptoms alone (50% [ n = 8223/16 487]). Median primary care interval and diagnostic interval were longer in tested than non-tested patients (primary care interval: 10 versus 0 days; diagnostic interval: 49 versus 32 days, respectively, P<0.001 for both), including among tested patients with alarm symptoms (primary care interval: 4 versus 0 days; diagnostic interval: 41 versus 22 days). CONCLUSION: Two-fifths of patients subsequently diagnosed with cancer have primary care blood tests as part of their diagnostic process. Given variable test use, research is needed on the clinical context in which blood tests are ordered.

Development of a community-based model for respiratory care services.

BACKGROUND: Chronic respiratory diseases are a major cause of mortality and morbidity, and represent a high chronic disease burden, which is expected to rise between now and 2020. Care for chronic diseases is increasingly located in community settings for reasons of efficiency and patient preference, though what services should be offered and where is contested. Our aim was to identify the key characteristics of a community-based service for chronic respiratory disease to help inform NHS commissioning decisions. METHODS: We used the Delphi method of consensus development. We derived components from Wagner's Chronic Care Model (CCM), an evidence-based, multi-dimensional framework for improving chronic illness care. We used the linked Assessment of Chronic Illness Care to derive standards for each component.We established a purposeful panel of experts to form the Delphi group. This was multidisciplinary and included national and international experts in the field, as well as local health professionals involved in the delivery of respiratory services. Consensus was defined in terms of medians and means. Participants were able to propose new components in round one. RESULTS: Twenty-one experts were invited to participate, and 18 agreed to take part (85.7% response). Sixteen responded to the first round (88.9%), 14 to the second round (77.8%) and 13 to the third round (72.2%). The panel rated twelve of the original fifteen components of the CCM to be a high priority for community-based respiratory care model, with varying levels of consensus. Where consensus was achieved, there was agreement that the component should be delivered to an advanced standard. Four additional components were identified, all of which would be categorised as part of delivery system design. CONCLUSIONS: This consensus development process confirmed the validity of the CCM as a basis for a community-based respiratory care service and identified a small number of additional components. Our approach has the potential to be applied to service redesign for other chronic conditions.

Recruitment to a large scale randomised controlled clinical trial in primary care: the Helicobacter Eradication Aspirin Trial (HEAT).

BACKGROUND: The Helicobacter Eradication Aspirin Trial (HEAT) is a multicentre, double blind, randomised controlled trial investigating whether Helicobacter (H.) pylori eradication reduces hospitalisation for peptic ulcer bleeding. Recruited participants were aged 60 and over and taking aspirin (≤325 mg daily) for at least four months prior to consent. Based on results of a pilot study, a sample size calculation predicted 6600 H. pylori-positive randomised participants would be required, from 33,000 volunteers, recruited from 170,000 invited patients. Methodology was therefore designed for recruitment of large numbers of patients from primary care using a novel electronic search tool, automated mail-out and electronic follow-up. Recruitment started in 2012 and completed in 2017. METHODS: All participants were recruited from GP practices, with assistance from the UK Clinical Research Network (UKCRN). H. pylori-positive participants were randomised to one week of eradication treatment or placebo. Recruitment was managed using a bespoke web-based database that communicated directly with a programmed search tool downloaded at participating practices. The primary endpoint is hospitalisation due to peptic ulcer bleeding. The trial will end when 87 adjudicated events have occurred, identified from searches of GP databases, review of secondary care admission data and mortality data, and reported events from randomised participants and GPs. RESULTS: HEAT has recruited participants from 1208 GP practices across the UK. Of the 188,875 invitation letters sent, 38,771 returned expressions of interest. Of these, 30,166 patients were consented to the trial, of whom 5355 H. pylori-positive participants (17.8% of those consented) were randomised. Mean age at consent was 73.1 ± 6.9 (SD) years and 72.2% of participants were male. Of the randomised (H. pylori-positive) participants, 531 have died (as of 17 Sep 2020); none of the deaths was due to trial treatment. CONCLUSION: The HEAT trial methodology has demonstrated that recruitment of large numbers of patients from primary care is attainable, with the assistance of the UKCRN, and could be applied to other clinical outcomes studies. TRIAL REGISTRATION: ClinicalTrials.gov ; registration number NCT01506986 . Registered on 10 Jan 2012.

Conceptual Framework to Guide Early Diagnosis Programs for Symptomatic Cancer as Part of Global Cancer Control.

Diagnosing cancer earlier can enable timely treatment and optimize outcomes. Worldwide, national cancer control plans increasingly encompass early diagnosis programs for symptomatic patients, commonly comprising awareness campaigns to encourage prompt help-seeking for possible cancer symptoms and health system policies to support prompt diagnostic assessment and access to treatment. By their nature, early diagnosis programs involve complex public health interventions aiming to address unmet health needs by acting on patient, clinical, and system factors. However, there is uncertainty regarding how to optimize the design and evaluation of such interventions. We propose that decisions about early diagnosis programs should consider four interrelated components: first, the conduct of a needs assessment (based on cancer-site-specific statistics) to identify the cancers that may benefit most from early diagnosis in the target population; second, the consideration of symptom epidemiology to inform prioritization within an intervention; third, the identification of factors influencing prompt help-seeking at individual and system level to support the design and evaluation of interventions; and finally, the evaluation of factors influencing the health systems' capacity to promptly assess patients. This conceptual framework can be used by public health researchers and policy makers to identify the greatest evidence gaps and guide the design and evaluation of local early diagnosis programs as part of broader cancer control strategies.

The prevalence of chronic conditions in patients diagnosed with one of 29 common and rarer cancers: A cross-sectional study using primary care data.

BACKGROUND: Pre-existing chronic conditions (morbidities) influence the diagnosis and management of cancer. The prevalence of specific morbidities in patients diagnosed with common and rarer cancers is inadequately described. METHODS: Using data from the English National Cancer Diagnosis Audit 2014, we studied 11 pre-existing morbidities recorded as yes/no items by participating general practitioners based on information included in primary care records. We examined the number and type of morbidities across socio-demographic and cancer site strata, and subsequently estimated observed and age/sex standardised prevalence of each morbidity by cancer. RESULTS: Over three-quarters (77 %; 11,429/14,774) of non-screen-detected patients had at least one chronic condition before diagnosis, while nearly half (47 %) had two or more. Hypertension (39 %) and physical disability (2%) were the most and least common conditions. Male, older and more socio-economically deprived patients were more likely to have at least one morbidity (p < 0.001 for all between variable group comparisons). For most morbidities, the standardised prevalence was similar across different cancers with a few exceptions, including respiratory disease prevalence being greatest among lung cancer patients and diabetes prevalence being greatest among liver, pancreatic, and endometrial cancer patients. CONCLUSIONS: Most cancer patients have at least one morbidity, while almost one in two have two or more. The findings highlight the need to take certain morbidity- and cancer-site combinations into account when examining associations between morbidity and cancer outcomes.

Symptom Signatures and Diagnostic Timeliness in Cancer Patients: A Review of Current Evidence.

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.

Typical and atypical presenting symptoms of breast cancer and their associations with diagnostic intervals: Evidence from a national audit of cancer diagnosis.

INTRODUCTION: Most symptomatic women with breast cancer have relatively short diagnostic intervals but a substantial minority experience prolonged journeys to diagnosis. Atypical presentations (with symptoms other than breast lump) may be responsible. METHODS: We examined the presenting symptoms of breast cancer in women using data from a national audit initiative (n=2316). Symptoms were categorised topographically. We investigated variation in the length of the patient interval (time from symptom onset to presentation) and the primary care interval (time from presentation to specialist referral) across symptom groups using descriptive analyses and quantile regression. RESULTS: A total of 56 presenting symptoms were described: breast lump was the most frequent (83%) followed by non-lump breast symptoms, (e.g. nipple abnormalities (7%) and breast pain (6%)); and non-breast symptoms (e.g. back pain (1%) and weight loss (0.3%)). Greater proportions of women with 'non-lump only' and 'both lump and non-lump' symptoms waited 90days or longer before seeking help compared to those with 'breast lump only' (15% and 20% vs. 7% respectively). Quantile regression indicated that the differences in the patient interval persisted after adjusting for age and ethnicity, but there was little variation in primary care interval for the majority of women. CONCLUSIONS: About 1 in 6 women with breast cancer present with a large spectrum of symptoms other than breast lump. Women who present with non-lump breast symptoms tend to delay seeking help. Further emphasis of breast symptoms other than breast lump in symptom awareness campaigns is warranted.

Clinical features of bowel disease in patients aged <50 years in primary care: a large case-control study.

BACKGROUND: Incidences of colorectal cancer (CRC) and inflammatory bowel disease (IBD) are increasing in those aged <50 years. AIM: To identify and quantify clinical features in primary care of CRC/IBD in those aged <50 years. This study considered the two conditions together and aimed to determine which younger patients, presenting in primary care with symptoms, would benefit from investigation for potentially serious colorectal disease. DESIGN AND SETTING: Matched case-control study using primary care records from the Clinical Practice Research Datalink, UK. METHOD: Incident cases (aged <50 years) of CRC (n = 1661) and IBD (n = 9578) diagnosed between 2000 and 2013 were each matched with up to three controls (n = 3979 CRC; n = 22 947 IBD). Odds ratios (OR) and positive predictive values (PPV) were estimated for features of CRC/IBD in the year before diagnosis. RESULTS: Ten features were independently associated with CRC/IBD (all P<0.001): rectal bleeding, change in bowel habit, diarrhoea, raised inflammatory markers, thrombocytosis, abdominal pain, low mean cell volume (MCV), low haemoglobin, raised white cell count, and raised hepatic enzymes. PPVs were >3% for rectal bleeding with diarrhoea, thrombocytosis, low MCV, low haemoglobin or raised inflammatory markers; for change in bowel habit with low MCV, thrombocytosis or low haemoglobin; and for diarrhoea with thrombocytosis. CONCLUSION: This study quantified the risk of serious bowel disease in symptomatic patients aged <50 years in primary care. Rectal bleeding and change in bowel habit are strongly predictive of CRC/IBD when combined with abnormal haematology. The present findings help prioritise patients for colonoscopy where the diagnosis is not immediately apparent.

Understanding symptom appraisal and help-seeking in people with symptoms suggestive of pancreatic cancer: a qualitative study.

OBJECTIVE: Pancreatic cancer has poor survival rates due to non-specific symptoms leading to later diagnosis. Understanding how patients interpret their symptoms could inform approaches to earlier diagnosis. This study sought to explore symptom appraisal and help-seeking among patients referred to secondary care for symptoms suggestive of pancreatic cancer. DESIGN: Qualitative analysis of semistructured in-depth interviews. Data were analysed iteratively and thematically, informed by the Model of Pathways to Treatment. PARTICIPANTS AND SETTING: Pancreatic cancer occurs rarely in younger adults, therefore patients aged ≥40 years were recruited from nine hospitals after being referred to hospital with symptoms suggestive of pancreatic cancer; all were participants in a cohort study. Interviews were conducted soon after referral, and where possible, before diagnosis. RESULTS: Twenty-six interviews were conducted (cancer n=13 (pancreas n=9, other intra-abdominal n=4), non-cancer conditions n=13; age range 48-84 years; 14 women). Time from first symptoms to first presentation to healthcare ranged from 1 day to 270 days, median 21 days. We identified three main themes. Initial symptom appraisal usually began with intermittent, non-specific symptoms such as tiredness or appetite changes, attributed to diet and lifestyle, existing gastrointestinal conditions or side effects of medication. Responses to initial symptom appraisal included changes in meal type or frequency, or self-medication. Symptom changes such as alterations in appetite and enjoyment of food or weight loss usually prompted further appraisal. Triggers to seek help included a change or worsening of symptoms, particularly pain, which was often a 'tipping point'. Help-seeking was often encouraged by others. We found no differences in symptom appraisal and help-seeking between people diagnosed with cancer and those with other conditions. CONCLUSIONS: Greater public and healthcare professional awareness of the combinations of subtle and intermittent symptoms, and their evolving nature, is needed to prompt timelier help-seeking and investigation among people with symptoms of pancreatic cancer.

Symptoms and patient factors associated with diagnostic intervals for pancreatic cancer (SYMPTOM pancreatic study): a prospective cohort study.

BACKGROUND: Pancreatic cancer is the tenth most common cancer in the UK; however, outcomes are poor, in part due to late diagnosis. We aimed to identify symptoms and other clinical and sociodemographic factors associated with pancreatic cancer diagnosis and diagnostic intervals. METHODS: We did this prospective cohort study at seven hospitals in two regions in England. We recruited participants aged 40 years or older who were referred for suspicion of pancreatic cancer. Data were collected by use of a patient questionnaire and primary care and hospital records. Descriptive and regression analyses were done to examine associations between symptoms and patient factors with the total diagnostic interval (time from onset of the first symptom to the date of diagnosis), comprising patient interval (time from first symptom to first presentation) and health system interval (time from first presentation to diagnosis). FINDINGS: We recruited 391 participants between Jan 1, 2011, and Dec 31, 2014 (24% response rate). 119 (30%) participants were diagnosed with pancreatic cancer (41 [34%] had metastatic disease), 47 (12%) with other cancers, and 225 (58%) with no cancer. 212 (54%) patients had multiple first symptoms whereas 161 (41%) patients had a solitary first symptom. In this referred population, no initial symptoms were reported more frequently by patients with cancer than by those with no cancer. Several subsequent symptoms predicted pancreatic cancer: jaundice (51 [49%] of 105 patients with pancreatic cancer vs 25 [12%] of 211 patients with no cancer; p<0·0001), fatigue (48/95 [51%] vs 40/155 [26%]; p=0·0001), change in bowel habit (36/87 [41%] vs 28/175 [16%]; p<0·0001), weight loss (55/100 [55%] vs 41/184 [22%]; p<0·0001), and decreased appetite (41/86 [48%] vs 41/156 [26%]; p=0·0011). There was no difference in any interval between patients with pancreatic cancer and those with no cancer (total diagnostic interval: median 117 days [IQR 57-234] vs 131 days [IQR 66-284]; p=0·32; patient interval 18 days [0-37] vs 15 days [1-62]; p=0·22; health system interval 76 days [28-161] vs 79 days [30-156]; p=0·68). Total diagnostic intervals were shorter when jaundice (hazard ratio [HR] 1·38, 95% CI 1·07-1·78; p=0·013) and decreased appetite (1·42, 1·11-1·82; p=0·0058) were reported as symptoms, and longer in patients presenting with indigestion (0·71, 0·56-0·89; p=0·0033), back pain (0·77, 0·59-0·99; p=0·040), diabetes (0·71, 0·52-0·97; p=0·029), and self-reported anxiety or depression, or both (0·67, 0·49-0·91; p=0·011). Health system intervals were likewise longer with indigestion (0·74, 0·58-0·95; p=0·0018), back pain (0·76, 0·58-0·99; p=0·044), diabetes (0·63, 0·45-0·89; p=0·0082), and self-reported anxiety or depression, or both (0·63, 0·46-0·88; p=0·0064), but were shorter with male sex (1·41, 1·1-1·81; p=0·0072) and decreased appetite (1·56, 1·19-2·06; p=0·0015). Weight loss was associated with longer patient intervals (HR 0·69, 95% CI 0·54-0·89; p=0·0047). INTERPRETATION: Although we identified no initial symptoms that differentiated people diagnosed with pancreatic cancer from those without pancreatic cancer, key additional symptoms might signal the disease. Health-care professionals should be vigilant to the possibility of pancreatic cancer in patients with evolving gastrointestinal and systemic symptoms, particularly in those with diabetes or mental health comorbidities. FUNDING: National Institute for Health Research and Pancreatic Cancer Action.

The Helicobacter Eradication Aspirin Trial (HEAT): A Large Simple Randomised Controlled Trial Using Novel Methodology in Primary Care.

BACKGROUND: Clinical trials measuring the effect of an intervention on clinical outcomes are more influential than those investigating surrogate measures but are costly. We developed methods to reduce costs substantially by using existing data in primary care systems, to ask whether Helicobacter pylori eradication would reduce the incidence of hospitalisation for ulcer bleeding in aspirin users. METHODS: The Helicobacter Eradication Aspirin Trial (HEAT) is a National Institute of Health Research-funded, double-blind placebo controlled randomised trial of the effects of H. pylori eradication on subsequent ulcer bleeding in infected individuals taking aspirin daily, conducted in practices across the whole of England, Wales and Northern Ireland. A bespoke web-based trial management system developed for the trial (and housed within the secure NHS Data Network) communicates directly with the HEAT Toolkit software downloaded at participating practices, which issues queries searching entry criteria (≥ 60 years, on chronic aspirin ≤ 325 mg daily, not on anti-ulcer therapy or non-steroidal anti-inflammatory drugs) for GP review of eligibility. Trial participation is invited using a highly secure automated online mail management system. Interested patients are seen once for consent and breath testing. Those with a positive test are randomised to eradication treatment (lansoprazole, clarithromycin, metronidazole) or placebo, with drug sent by post. Events are tracked by upload of accumulating information in the GP database, patient contact, review of National Hospital Episode Statistics and Office of National Statistics data. RESULTS: HEAT is the largest Clinical Research Network-supported drug trial, with 115,660 invitation letters sent from 850 practices, 22,922 volunteers, and 3038 H. pylori positive patients randomised to active or placebo treatment after 2.5 years of recruitment. 178 practices have performed their first follow-up data search to identify 21 potential endpoints to date. DISCUSSION: HEAT is important medically, because aspirin is so widely used, and methodologically, as a successful trial would show that large-scale studies of important clinical outcomes can be conducted at a fraction of the cost of those conducted by industry, which in turn will help to ensure that trials of primarily medical rather than commercial interest can be conducted successfully in the UK.

The utility of an online diagnostic decision support system (Isabel) in general practice: a process evaluation.

OBJECTIVES: To evaluate the utility of Isabel, an online diagnostic decision support system developed by Isabel Healthcare primarily for secondary medical care, in the general practice setting. DESIGN: Focus groups were conducted with clinicians to understand why and how they used the system. A modified online post-use survey asked practitioners about its impact on their decision-making. Normalization process theory (NPT) was used as a theoretical framework to determine whether the system could be incorporated into routine clinical practice. SETTING: The system was introduced by NHS County Durham and Darlington in the UK in selected general practices as a three-month pilot. PARTICIPANTS: General practitioners and nurse practitioners who had access to Isabel as part of the Primary Care Trust's pilot. MAIN OUTCOME MEASURES: General practitioners' views, experiences and usage of the system. RESULTS: Seven general practices agreed to pilot Isabel. Two practices did not subsequently use it. The remaining five practices conducted searches on 16 patients. Post-use surveys (n = 10) indicated that Isabel had little impact on diagnostic decision-making. Focus group participants stated that, although the diagnoses produced by Isabel in general did not have an impact on their decision-making, they would find the tool useful if it were better tailored to the primary care setting. Our analysis concluded that normalization was not likely to occur in its current form. CONCLUSIONS: Isabel was of limited utility in this short pilot study and may need further modification for use in general practice.