Evidence arising from primary care electronic health records can help to assess the risk of symptomatic-but-as-yet-undiagnosed cancer. Existing evidence and methodological innovations in this field ...of study hold further promise for improving the diagnostic process and achieving earlier diagnosis in cancer patients.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The management of adults presenting with fatigue presents a diagnostic challenge, particularly regarding possible underlying cancer.
Using electronic health records, we examined cancer risk in ...patients presenting to primary care with new-onset fatigue in England during 2007-2013, compared to general population estimates. We examined variation by age, sex, deprivation, and time following presentation.
Of 250,606 patients presenting with fatigue, 12-month cancer risk exceeded 3% in men aged 65 and over and women aged 80 and over, and 6% in men aged 80 and over. Nearly half (47%) of cancers were diagnosed within 3 months from first fatigue presentation. Site-specific cancer risk was higher than the general population for most cancers studied, with greatest relative increases for leukaemia, pancreatic and brain cancers.
In older patients, new-onset fatigue is associated with cancer risk exceeding current thresholds for urgent specialist referral. Future research should consider how risk is modified by the presence or absence of other signs and symptoms. Excess cancer risk wanes rapidly after 3 months, which could inform the duration of a 'safety-netting' period. Fatigue presentation is not strongly predictive of any single cancer, although certain cancers are over-represented; this knowledge can help prioritise diagnostic strategies.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Cancer patients often have pre-existing comorbidities, which can influence timeliness of cancer diagnosis. We examined symptoms, investigations and emergency presentation (EP) risk among colorectal ...cancer (CRC) patients by comorbidity status.
Using linked cancer registration, primary care and hospital records of 4836 CRC patients (2011-2015), and multivariate quantile and logistic regression, we examined variations in specialist investigations, diagnostic intervals and EP risk.
Among colon cancer patients, 46% had at least one pre-existing hospital-recorded comorbidity, most frequently cardiovascular disease (CVD, 18%). Comorbid versus non-comorbid cancer patients more frequently had records of anaemia (43% vs 38%), less frequently rectal bleeding/change in bowel habit (20% vs 27%), and longer intervals from symptom-to-first relevant test (median 136 vs 74 days). Comorbid patients were less likely investigated with colonoscopy/sigmoidoscopy, independently of symptoms (adjusted OR = 0.70.6, 0.9 for Charlson comorbidity score 1-2 and OR = 0.5 0.4-0.7 for score 3+ versus 0. EP risk increased with comorbidity score 0, 1, 2, 3+: 23%, 35%, 33%, 47%; adjusted OR = 1.8 1.4, 2.2; 1.7 1.3, 2.3; 3.0 2.3, 4.0) and for patients with CVD (adjusted OR = 2.0 1.5, 2.5).
Comorbid individuals with as-yet-undiagnosed CRC often present with general rather than localising symptoms and are less likely promptly investigated with colonoscopy/sigmoidoscopy. Comorbidity is a risk factor for diagnostic delay and has potential, additionally to symptoms, as risk-stratifier for prioritising patients needing prompt assessment to reduce EP.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Summary The nature of cancer control is changing, with an increasing emphasis, fuelled by public and political demand, on prevention, early diagnosis, and patient experience during and after ...treatment. At the same time, primary care is increasingly promoted, by governments and health funders worldwide, as the preferred setting for most health care for reasons of increasing need, to stabilise health-care costs, and to accommodate patient preference for care close to home. It is timely, then, to consider how this expanding role for primary care can work for cancer control, which has long been dominated by highly technical interventions centred on treatment, and in which the contribution of primary care has been largely perceived as marginal. In this Commission, expert opinion from primary care and public health professionals with academic and clinical cancer expertise—from epidemiologists, psychologists, policy makers, and cancer specialists—has contributed to a detailed consideration of the evidence for cancer control provided in primary care and community care settings. Ranging from primary prevention to end-of-life care, the scope for new models of care is explored, and the actions needed to effect change are outlined. The strengths of primary care—its continuous, coordinated, and comprehensive care for individuals and families—are particularly evident in prevention and diagnosis, in shared follow-up and survivorship care, and in end-of-life care. A strong theme of integration of care runs throughout, and its elements (clinical, vertical, and functional) and the tools needed for integrated working are described in detail. All of this change, as it evolves, will need to be underpinned by new research and by continuing and shared multiprofessional development.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Summary Background Information from patient surveys can help to identify patient groups and cancers with the greatest potential for improvement in the experience and timeliness of cancer diagnosis. ...We aimed to examine variation in the number of pre-referral consultations with a general practitioner between patients with different cancers and sociodemographic characteristics. Methods We analysed data from 41 299 patients with 24 different cancers who took part in the 2010 National Cancer Patient Experience Survey in England. We examined variation in the number of general practitioner consultations with cancer symptoms before hospital referral to diagnose cancer. Logistic regression was used to identify independent predictors of three or more pre-referral consultations, adjusting for cancer type, age, sex, deprivation quintile, and ethnic group. Findings We identified wide variation between cancer types in the proportion of patients who had visited their general practitioner three or more times before hospital referral (7·4% 625 of 8408 for breast cancer and 10·1% 113 of 1124 for melanoma; 41·3% 193 of 467 for pancreatic cancer and 50·6% 939 of 1854 for multiple myeloma). In multivariable analysis, with patients with rectal cancer as the reference group, those with subsequent diagnosis of multiple myeloma (odds ratio OR 3·42, 95% CI 3·01–3·90), pancreatic cancer (2·35, 1·91–2·88), stomach cancer (1·96, 1·65–2·34), and lung cancer (1·68, 1·48–1·90) were more likely to have had three or more pre-referral consultations; conversely patients with subsequent diagnosis of breast cancer (0·19; 0·17–0·22), melanoma (0·34, 0·27–0·43), testicular cancer (0·47, 0·33–0·67), and endometrial cancer (0·59, 0·49–0·71) were more likely to have been referred to hospital after only one or two consultations. The probability of three or more pre-referral consultations was greater in young patients (OR for patients aged 16–24 years vs 65–74 years 2·12, 95% CI 1·63–2·75; p<0·0001), those from ethnic minorities (OR for Asian vs white 1·73, 1·45–2·08; p<0·0001; OR for black vs white 1·83, 1·51–2·23; p<0·0001), and women (OR for women vs men 1·28, 1·21–1·36; p<0·0001). We identified strong evidence of interactions between cancer type and age group and sex (p<0·0001 for both), and between age and ethnicity (p=0·0013). The model including these interactions showed a particularly strong sex effect for bladder cancer (OR for women vs men 2·31, 95% CI 1·98–2·69) and no apparent ethnic group differences in young patients aged 16–24 years, whilst the only cancers without an apparent age gradient were testicular cancer and mesothelioma. Interpretation Our findings could help to prioritise and stratify early diagnosis initiatives and research, focusing on patients with cancers and sociodemographic characteristics with the largest potential for improvement. Funding None.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
One in three colon cancers are diagnosed as an emergency, which is associated with worse cancer outcomes. Chronic conditions (comorbidities) affect large proportions of adults and they might ...influence the risk of emergency presentations (EP).
We aimed to evaluate the effect of specific pre-existing comorbidities on the risk of colon cancer being diagnosed following an EP rather than through non-emergency routes. The cohort study included 5745 colon cancer patients diagnosed in England 2005-2010, with individually-linked cancer registry, primary and secondary care data. In addition to multivariable analyses we also used potential-outcomes methods.
Colon cancer patients with comorbidities consulted their GP more frequently with cancer symptoms during the pre-diagnostic year, compared with non-comorbid cancer patients. EP occurred more frequently in patients with 'serious' or complex comorbidities (diabetes, cardiac and respiratory diseases) diagnosed/treated in hospital during the years pre-cancer diagnosis (43% EP in comorbid versus 27% in non-comorbid individuals; multivariable analysis Odds Ratio (OR), controlling for socio-demographic factors and symptoms: men OR = 2.40; 95% CI 2.0-2.9 and women OR = 1.98; 95% CI 1.6-2.4. Among women younger than 60, gynaecological (OR = 3.41; 95% CI 1.2-9.9) or recent onset gastro-intestinal conditions (OR = 2.84; 95% CI 1.1-7.7) increased the risk of EP. In contrast, primary care visits for hypertension monitoring decreased EPs for both genders.
Patients with comorbidities have a greater risk of being diagnosed with cancer as an emergency, although they consult more frequently with cancer symptoms during the year pre-cancer diagnosis. This suggests that comorbidities may interfere with diagnostic reasoning or investigations due to 'competing demands' or because they provide 'alternative explanations'. In contrast, the management of chronic risk factors such as hypertension may offer opportunities for earlier diagnosis. Interventions are needed to support the diagnostic process in comorbid patients. Appropriate guidelines and diagnostic services to support the evaluation of new or changing symptoms in comorbid patients may be useful.
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CEKLJ, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective
Younger people, minority ethnic groups, sexual minorities and people of lower socioeconomic status report poorer experiences of primary care. In light of NHS ambitions to reduce unwarranted ...variations in care, we aimed to investigate whether inequalities in patient experience of primary care changed between 2011 and 2017, using data from the General Practice Patient Survey in England.
Methods
We considered inequalities in relation to age, sex, deprivation, ethnicity, sexual orientation and geographical region across five dimensions of patient experience: overall experience, doctor communication, nurse communication, access and continuity of care. We used linear regression to explore whether the magnitude of inequalities changed between 2011 and 2017, using mixed models to assess changes within practices and models without accounting for practice to assess national trends.
Results
We included 5,241,408 responses over 11 survey waves from 2011–2017. There was evidence that inequalities changed over time (p < 0.05 for 27/30 models), but the direction and magnitude of changes varied. Changes in gaps in experience ranged from a 1.6 percentage point increase for experience of access among sexual minorities, to a 5.6 percentage point decrease for continuity, where experience worsened for older ages. Inequalities in access in relation to socio-economic status remained reasonably stable for individuals attending the same GP practice; nationally inequalities in access increased 2.1 percentage points (p < 0.0001) between respondents living in more/less deprived areas, suggesting access is declining fastest in practices in more deprived areas.
Conclusions
There have been few substantial changes in inequalities in patient experience of primary care between 2011 and 2017.
Immunodeficiency syndromes (acquired/congenital/iatrogenic) are known to increase Hodgkin lymphoma (HL) risk, but the effects of allergic immune dysregulation and corticosteroids are poorly ...understood.
We sought to assess the risk of HL associated with allergic disease (asthma, eczema, and allergic rhinitis) and corticosteroid use.
We conducted a case-control study using the United Kingdom Clinical Practice Research Datalink (CPRD) linked to hospital data. Multivariable logistic regression investigated associations between allergic diseases and HL after adjusting for established risk factors. Potential confounding or effect modification by steroid treatment were examined.
One thousand two hundred thirty-six patients with HL were matched to 7416 control subjects. Immunosuppression was associated with 6-fold greater odds of HL (adjusted odds ratio aOR, 6.18; 95% CI, 3.04-12.57), with minimal change after adjusting for steroids. Any prior allergic disease or eczema alone was associated with 1.4-fold increased odds of HL (aOR, 1.41 95% CI, 1.24-1.60 and 1.41 95% CI, 1.20-1.65, respectively). These associations decreased but remained significant after adjustment for steroids (aOR, 1.25 95% CI, 1.09-1.43 and 1.27 95% CI, 1.08-1.49, respectively). There was no effect modification by steroid use. Previous steroid treatment was associated with 1.4-fold greater HL odds (aOR, 1.38; 95% CI, 1.20-1.59).
In addition to established risk factors (immunosuppression and infectious mononucleosis), allergic disease and eczema are risk factors for HL. This association is only partially explained by steroids, which are associated with increased HL risk. These findings add to the growing evidence that immune system malfunction after allergic disease or immunosuppression is central to HL development.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The diagnostic assessment of abdominal symptoms in primary care presents a challenge. Evidence is needed about the positive predictive values (PPVs) of abdominal symptoms for different cancers and ...inflammatory bowel disease (IBD).
Using data from The Health Improvement Network (THIN) in the United Kingdom (2000-2017), we estimated the PPVs for diagnosis of (i) cancer (overall and for different cancer sites); (ii) IBD; and (iii) either cancer or IBD in the year post-consultation with each of 6 abdominal symptoms: dysphagia (n = 86,193 patients), abdominal bloating/distension (n = 100,856), change in bowel habit (n = 106,715), rectal bleeding (n = 235,094), dyspepsia (n = 517,326), and abdominal pain (n = 890,490). The median age ranged from 54 (abdominal pain) to 63 years (dysphagia and change in bowel habit); the ratio of women/men ranged from 50%:50% (rectal bleeding) to 73%:27% (abdominal bloating/distension). Across all studied symptoms, the risk of diagnosis of cancer and the risk of diagnosis of IBD were of similar magnitude, particularly in women, and younger men. Estimated PPVs were greatest for change in bowel habit in men (4.64% cancer and 2.82% IBD) and for rectal bleeding in women (2.39% cancer and 2.57% IBD) and lowest for dyspepsia (for cancer: 1.41% men and 1.03% women; for IBD: 0.89% men and 1.00% women). Considering PPVs for specific cancers, change in bowel habit and rectal bleeding had the highest PPVs for colon and rectal cancer; dysphagia for esophageal cancer; and abdominal bloating/distension (in women) for ovarian cancer. The highest PPVs of abdominal pain (either sex) and abdominal bloating/distension (men only) were for non-abdominal cancer sites. For the composite outcome of diagnosis of either cancer or IBD, PPVs of rectal bleeding exceeded the National Institute of Health and Care Excellence (NICE)-recommended specialist referral threshold of 3% in all age-sex strata, as did PPVs of abdominal pain, change in bowel habit, and dyspepsia, in those aged 60 years and over. Study limitations include reliance on accuracy and completeness of coding of symptoms and disease outcomes.
Based on evidence from more than 1.9 million patients presenting in primary care, the findings provide estimated PPVs that could be used to guide specialist referral decisions, considering the PPVs of common abdominal symptoms for cancer alongside that for IBD and their composite outcome (cancer or IBD), taking into account the variable PPVs of different abdominal symptoms for different cancers sites. Jointly assessing the risk of cancer or IBD can better support decision-making and prompt diagnosis of both conditions, optimising specialist referrals or investigations, particularly in women.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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