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Background: Non-acute abdominal pain in primary care is diagnostically challenging.Aim: To quantify the 1-year cumulative incidence of 35 non-malignant diagnoses and nine cancers in adults after newly recorded abdominal pain in primary care.Design and Setting: Observational cohort study of 125 793 Clinical Practice Research Datalink GOLD records.Method: Participants, aged ≥40 years, had newly recorded abdominal pain between 1 January 2009 and 31 December 2013. Age- and sex-stratified 1-year cumulative incidence by diagnosis is reported.Results: Most (>70%) participants had no pre-specified diagnoses after newly recorded abdominal pain. Non-malignant diagnoses were most common: upper gastrointestinal problems (gastro-oesophageal reflux disease, hiatus hernia, gastritis, oesophagitis, and gastric/duodenal ulcer) in males and urinary tract infection in females. The incidence of upper gastrointestinal problems plateaued at age ≥60 years (aged 40-59 years: males 4.9%, 95% confidence interval [CI] = 4.6 to 5.1, females 4.0%, 95% CI = 3.8 to 4.2; aged 60-69 years: males 5.8%, 95% CI = 5.4 to 6.2, females 5.4%, 95% CI = 5.1 to 5.8). Urinary tract infection incidence increased with age (aged 40-59 years: females 5.1%, 95% CI = 4.8 to 5.3, males 1.1%, 95% CI = 1.0 to 1.2; aged ≥70 years: females 8.0%, 95% CI = 7.6 to 8.4, males 3.3%, 95% CI = 3.0 to 3.6%). Diverticular disease incidence rose with age, plateauing at 4.2% (95% CI = 3.9 to 4.6) in males aged ≥60 years, increasing to 6.1% (95% CI = 5.8 to 6.4) in females aged ≥70 years. Irritable bowel syndrome incidence was higher in females (aged 40-59 years: 2.9%, 95% CI = 2.7 to 3.1) than males (aged 40-59 years: 2.1%, 95% CI = 1.9 to 2.3), decreasing with age to 1.3% (95% CI = 1.2 to 1.5) in females and 0.6% (95% CI = 0.5 to 0.8) in males aged ≥70 years.Conclusion: Although abdominal pain commonly remains unexplained, non-malignant diagnosis are more likely than cancer. [ABSTRACT FROM AUTHOR]

Background: Cancers of the nasopharynx, nasal cavity, and accessory sinuses ("sinonasal") are rare in England, with around 750 patients diagnosed annually. There are no specific National Institute for Health and Care Excellence (NICE) referral guidelines for these cancers and no primary care research published.Objective: To identify and quantify clinical features of sinonasal cancer in UK primary care patients.Methods: This matched case-control study used UK Clinical Practice Research Datalink (CPRD) data. Patients were aged ≥40 years with a diagnosis of sinonasal cancer between January 1, 2000 and December 31, 2009 and had consulted their GP in the year before diagnosis. Clinical features of sinonasal cancer were analysed using conditional logistic regression. Positive predictive values (PPVs) for single and combined features were calculated.Results: In total, 155 cases and 697 controls were studied. Nine symptoms and one abnormal investigation were significantly associated with the cancer: nasal mass; odds ratio, 95 (95% confidence interval 7.0, 1315, P = 0.001); head and neck lumps, 68 (12, 387, P < 0.001); epistaxis, 17 (3.9, 70, P < 0.001); rhinorrhoea, 14 (4.6, 44, P < 0.001); visual disturbance, 12 (2.2, 67, P = 0.004); sinusitis, 7.3 (2.2, 25, P = 0.001); sore throat, 6.0 (2.0, 18, P = 0.001); otalgia, 5.4 (1.6, 18, P = 0.007); headache, 3.6 (1.4, 9.5, P = 0.01); raised white cell count, 8.5 (2.8, 27, P < 0.001). Combined PPVs for epistaxis/rhinorrhoea, epistaxis/sinusitis, and rhinorrhoea/sinusitis were 0.62%.Conclusion: This is the first primary care study identifying epistaxis, sinusitis, and rhinorrhoea as part of the clinical prodrome of sinonasal cancer. Although no PPVs meet the 3% NICE referral threshold, these results may help clinicians identify who warrants safety-netting and possible specialist referral, potentially reducing the number of advanced-stage diagnoses of sinonasal cancer. [ABSTRACT FROM AUTHOR]

Background: Quantifying cancer risk in primary care patients with abdominal pain informs diagnostic strategies. Aim: To quantify oesophagogastric, colorectal, liver, pancreatic, ovarian, uterine, kidney, and bladder cancer risks associated with newly reported abdominal pain with or without other symptoms, signs, or abnormal blood tests (that is, features) indicative of possible cancer. Design and setting: This was an observational prospective cohort study using Clinical Practice Research Datalink records with English cancer registry linkage. Method: The authors studied 125 793 patients aged ≥40 years with newly reported abdominal pain in primary care between 1 January 2009 and 31 December 2013. The 1-year cumulative incidence of cancer, and the composite 1-year cumulative incidence of cancers with shared additional features, stratified by age and sex are reported. Results: With abdominal pain, overall risk was greater in men and increased with age, reaching 3.4% (95% confidence interval [CI] = 3.0 to 3.7, predominantly colorectal cancer 1.9%, 95% CI = 1.6 to 2.1) in men ≥70 years, compared with their expected incidence of 0.88% (95% CI = 0.87 to 0.89). Additional features increased cancer risk; for example, for men, colorectal or pancreatic cancer risk with abdominal pain plus diarrhoea at 60–69 years of age was 3.1% (95% CI = 1.9 to 4.9) predominantly colorectal cancer (2.2%, 95% CI = 1.2 to 3.8). Conclusion: Abdominal pain increases intra-abdominal cancer risk nearly fourfold in men aged ≥70 years, exceeding the 3% threshold warranting investigation. This threshold is surpassed for the >60 years age group only with additional features. These results will help direct appropriate referral and testing strategies for patients based on their demographic profile and reporting features. The authors suggest non-invasive strategies first, such as faecal immunochemical testing, with safety-netting in a shared decision-making framework. [ABSTRACT FROM AUTHOR]

Background: For some common cancers, survival is lower in the UK than in comparable high-income countries.Aim: To assess the effectiveness of a targeted postal intervention (to promote awareness of cancer symptoms and earlier help seeking) on patient consultation rates.Design and Setting: A two-arm randomised controlled trial was carried out on patients aged 50-84 years registered at 23 general practices in rural and urban areas of Greater London, Greater Manchester, and the North East of England.Method: Patients who had not had a consultation at their general practice in the previous 12 months and had at least two other risk factors for late presentation with cancer were randomised to intervention and control arms. The intervention consisted of a posted letter and leaflet. Primary outcome was the number of consultations at the practice with patients randomised to each arm in the 6 months subsequent to posting the intervention. All patients with outcome data were included in the intention-to-treat analyses.Results: In total, 1513 patients were individually randomised to the intervention (n = 783) and control (n = 730) arms between Nov 2016 - May 2017; outcome data were available for 749 and 705 patients, respectively, with a statistically significantly higher rate of consultation in the intervention arm compared with the control arm: 436 versus 335 consultations (relative risk 1.40, 95% confidence interval = 1.11 to 1.77, P = 0.004). There was, however, no difference in the numbers of patients consulting.Conclusion: Targeted interventions of this nature can change behaviour; there is a need to develop interventions that can be more effective at engaging patients with primary care. This study demonstrates that targeted interventions promoting both awareness of possible cancer symptoms and earlier health seeking, can change behaviour. There is a need to develop and test interventions that can be more effective at engaging the most at-risk patients. [ABSTRACT FROM AUTHOR]

Background: Microcytosis (smaller than normal red blood cells) has previously been identified as a possible early risk marker for some cancers. However, the role of microcytosis across all cancers has not been fully investigated.Aim: To examine cancer incidence in a cohort of patients with microcytosis, with and without accompanying anaemia.Design and Setting: Cohort study of patients aged ≥40 years using UK primary care electronic patient records.Method: The 1-year cancer incidence was compared between cohorts of patients with a mean red cell volume of <85 femtolitres (fL) (low) or 85-101 fL (normal). Further analyses examined sex, age group, cancer site, and haemoglobin values.Results: Of 12 289 patients with microcytosis, 497 had a new cancer diagnosis within 1 year (4.0%, 95% confidence interval [CI] = 3.7 to 4.4), compared with 1465 of 73 150 without microcytosis (2.0%, CI = 1.9 to 2.1). In males, 298 out of 4800 with microcytosis were diagnosed with cancer (6.2%, CI = 5.5 to 6.9), compared with 940 out of 34 653 without (2.7%, CI = 2.5 to 2.9). In females with microcytosis, 199 out of 7489 were diagnosed with cancer (2.7%, CI = 2.3 to 3.1), compared with 525 out of 38 497 without (1.4%, CI = 1.3 to 1.5). In patients with microcytosis but normal haemoglobin, 86 out of 2637 males (3.3%, CI = 2.6 to 4.0) and 101 out of 5055 females (2.0%, CI = 1.6 to 2.4) were diagnosed with cancer.Conclusion: Microcytosis is a predictor of underlying cancer even if haemoglobin is normal. Although a benign explanation is more likely, clinicians in primary care should consider simple testing for cancer on encountering unexplained microcytosis, particularly in males. [ABSTRACT FROM AUTHOR]

Background: Over 1700 people are diagnosed with laryngeal cancer annually in England. Current National Institute for Health and Care Excellence (NICE) guidelines on referral for suspected laryngeal cancer were based on clinical consensus, in the absence of primary care studies.Aim: To identify and quantify the primary care features of laryngeal cancer.Design and Setting: Matched case-control study of patients aged ≥40 years using data from the UK's Clinical Practice Research Datalink.Method: Clinical features of laryngeal cancer with which patients had presented to their GP in the year before diagnosis were identified and their association with cancer was assessed using conditional logistic regression. Positive predictive values (PPVs) for each clinical feature were calculated for the consulting population aged >60 years.Results: In total, 806 patients diagnosed with laryngeal cancer between 2000 and 2009 were studied, together with 3559 age-, sex-, and practice-matched controls. Ten features were significantly associated with laryngeal cancer: hoarseness odds ratio [OR] 904 (95% confidence interval [CI] = 277 to 2945); sore throat, first attendance OR 6.2 (95% CI = 3.7 to 10); sore throat, re-attendance OR 7.7 (95% CI = 2.6 to 23); dysphagia OR 6.5 (95% CI = 2.7 to 16); otalgia OR 5.0 (95% CI = 1.9 to 13); dyspnoea, re-attendance OR 4.7 (95% CI = 1.9 to 12); mouth symptoms OR 4.7 (95% CI = 1.8 to 12); recurrent chest infection OR 4.5 (95% CI = 2.4 to 8.5); insomnia OR 2.7 (95% CI = 1.3 to 5.6); and raised inflammatory markers OR 2.5 (95% CI = 1.5 to 4.1). All P-values were <0.01. Hoarseness had the highest individual PPV of 2.7%. Symptom combinations currently not included in NICE guidance were sore throat plus either dysphagia, dyspnoea, or otalgia, for which PPVs were >5%.Conclusion: These results expand current NICE guidance by identifying new symptom combinations that are associated with laryngeal cancer; they may help GPs to select more appropriate patients for referral. [ABSTRACT FROM AUTHOR]

Background: Testicular cancer incidence has risen over the last two decades and is expected to continue to rise. There are no primary care studies on the clinical features of testicular cancer, with recent National Institute for Health and Care Excellence (NICE) guidance based solely upon clinical consensus.Aim: To identify clinical features of testicular cancer and to quantify their risk in primary care patients, with the aim of improving the selection of patients for investigation.Design and Setting: A matched case-control study in males aged ≥17 years, using Clinical Practice Research Datalink records.Method: Putative clinical features of testicular cancer were identified and analysed using conditional logistic regression. Positive predictive values (PPVs) were calculated for those aged <50 years.Results: In all, 1398 cases were available, diagnosed between 2000 and 2012, with 4956 age-, sex-, and practice-matched controls. Nine features were independently associated with testicular cancer, the top three being testicular swelling (odds ratio [OR] 280, 95% confidence interval [CI] = 110 to 690), testicular lump (OR 270, 95% CI = 100 to 740), and scrotal swelling (OR 170, 95% CI = 35 to 800). The highest PPV for 17-49-year-olds was testicular lump, at 2.5% (95% CI = 1.1 to 5.6). Combining testicular lump with testicular swelling or testicular pain produced PPVs of 17% and 10%, respectively.Conclusion: Testicular enlargement carries a risk of cancer of 2.5% - close to the current 3% threshold in UK referral guidance. Contrary to traditional teaching, painful testicular enlargement may signify cancer. Some initial hydrocele diagnoses appear to be wrong, with missed cancers, suggesting an ultrasound may be useful when a hydrocele diagnosis is uncertain. These results support the existing NICE guidelines, and help to characterise when an ultrasound should be considered in symptomatic men. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background In the UK, approximately five people are diagnosed with Hodgkin lymphoma (HL) daily. One-tenth of diagnoses are in those aged >75 years. Aim To establish a symptom profile of HL and quantify their risk in primary care patients aged ≥40 years. Design and setting Matched case-control study using Clinical Practice Research Datalink patient records. Method Putative clinical features of HL were identified in the year before diagnosis. Results were analysed using conditional logistic regression and positive predictive values (PPVs) calculated for the consulting population. Results Two-hundred and eighty-three patients aged ≥40 years, diagnosed with HL between 2000 and 2009, and 1237 age, sex, and general practice-matched participants were studied. Six features were independently associated with HL: lymphadenopathy (OR 280, 95% confidence interval [CI] = 25 to 3100), head and neck mass not described as lymphadenopathy (OR 260, 95% CI = 21 to 3200), other mass (OR 12, 95% CI = 4.4 to 35), thrombocytosis (OR 6.0, 95% CI = 2.6 to 14), raised inflammatory markers (OR 5.2, 95% CI = 3.0 to 9.0), and low full blood count (OR 2.8, 95% CI = 1.6 to 4.8). Lymphadenopathy per se has a positive predictive value (PPV) of 5.6% for HL in patients aged ≥60 years. Conclusion Consistent with secondary care findings, lymphadenopathy is the clinical feature with the highest risk of HL in primary care and warrants urgent investigation. [ABSTRACT FROM AUTHOR]

Background Non-Hodgkin lymphoma (NHL) is the sixth most common cancer in the UK; approximately 35 people are diagnosed and 13 die from the disease daily. Aim To identify the primary care clinical features of NHL and quantify their risk in symptomatic patients. Design and setting Matched case-control study using Clinical Practice Research Datalink patient records. Method Putative clinical features of NHL were identified in the year before diagnosis. Results were analysed using conditional logistic regression and positive predictive values (PPVs). Results A total of 4362 patients aged ≥ 40 years, diagnosed with NHL between 2000 and 2009, and 19 468 age, sex, and general practice-matched controls were studied. Twenty features were independently associated with NHL. The five highest risk symptoms were lymphadenopathy, odds ratio (OR) 263 (95% CI = 133 to 519), head and neck mass not described as lymphadenopathy OR 49 (95% CI = 32 to 74), other mass OR 12 (95% CI = 10 to 16), weight loss OR 3.2 (95% CI = 2.3 to 4.4), and abdominal pain OR 2.5 (95% CI = 2.1 to 2.9). Lymphadenopathy has a PPV of 13% for NHL in patients ≥60 years. Weight loss in conjunction with repeated back pain or raised gamma globulin had PPVs >2%. Conclusion Unexplained lymphadenopathy in patients aged ≥60 years produces a very high risk of NHL in primary care. These patients warrant urgent investigation, potentially sooner than 6 weeks from initial presentation where the GP is particularly concerned. [ABSTRACT FROM AUTHOR]

Background Diagnosis of bladder cancer relies on investigation of symptoms presented to primary care, notably visible haematuria. The importance of non-visible haematuria has never been estimated. Aim To estimate the risk of bladder cancer with nonvisible haematuria. Design and setting A case-control study using UK electronic primary care medical records, including uncoded data to supplement coded records. Method A total of 4915 patients (aged ⩾40 years) diagnosed with bladder cancer between January 2000 and December 2009 were selected from the Clinical Practice Research Datalink and matched to 21 718 controls for age, sex, and practice. Variables for visible and non-visible haematuria were derived from coded and uncoded data. Analyses used multivariable conditional logistic regression, followed by estimation of positive predictive values (PPVs) for bladder cancer using Bayes' theorem. Results Non-visible haematuria (coded/uncoded data) was independently associated with bladder cancer: odds ratio (OR) 20 (95% confidence interval [CI] =12 to 33). The PPV of non-visible haematuria was 1.6% (95% CI = 1.2 to 2.1) in those aged ⩾60 years and 0.8% (95% CI = 0.1 to 5.6) in 40-59-year-olds. The PPV of visible haematuria was 2.8% (95% CI = 2.5 to 3.1) and 1.2% (95% CI = 0.6 to 2.3) for the same age groups respectively, lower than those calculated using coded data alone. The proportion of records of visible haematuria in coded, rather than uncoded, format was higher in cases than in controls (P<0.002, χ2 test). There was no evidence for such differential recording of non-visible haematuria by case/control status (P = 0.78), although, overall, the uncoded format was preferred (P<0.001). Conclusion Both non-visible and visible haematuria are associated with bladder cancer, although the visible form confers nearly twice the risk of cancer compared with the non-visible form. GPs' style of record keeping varies by symptom and possible diagnosis. [ABSTRACT FROM AUTHOR]

Background: Kidney cancer accounts for over 4000 UK deaths annually, and is one of the cancer sites with a poor mortality record compared with Europe. Aim: To identify and quantify all clinical features of kidney cancer in primary care. Design: Case-control study, using General Practice Research Database records. Method: A total of 3149 patients aged =40 years, diagnosed with kidney cancer between 2000 and 2009, and 14 091 age, sex and practicematched controls, were selected. Clinical features associated with kidney cancer were identified, and analysed using conditional logistic regression. Positive predictive values for features of kidney cancer were estimated. Results: Cases consulted more frequently than controls in the year before diagnosis: median 16 consultations (interquartile range 10-25) versus 8 (4-15): P<0.001. Fifteen features were independently associated with kidney cancer: visible haematuria, odds ratio 37 (95% confidence interval [CI] = 28 to 49), abdominal pain 2.8 (95% CI = 2.4 to 3.4), microcytosis 2.6 (95% CI = 1.9 to 3.4), raised inflammatory markers 2.4 (95% CI = 2.1 to 2.8), thrombocytosis 2.2 (95% CI = 1.7 to 2.7), low haemoglobin 1.9 (95% CI = 1.6 to 2.2), urinary tract infection 1.8 (95% CI = 1.5 to 2.1), nausea 1.8 (95% CI = 1.4 to 2.3), raised creatinine 1.7 (95% CI = 1.5 to 2.0), leukocytosis 1.5 (95% CI = 1.2 to 1.9), fatigue 1.5 (95% CI = 1.2 to 1.9), constipation 1.4 (95% CI = 1.1 to 1.7), back pain 1.4 (95% CI = 1.2 to 1.7), abnormal liver function 1.3 (95% CI = 1.2 to 1.5), and raised blood sugar 1.2 (95% CI = 1.1 to 1.4). The positive predictive value for visible haematuria in patients aged =60 years was 1.0% (95% CI = 0.8 to 1.3). Conclusion: Visible haematuria is the commonest and most powerful single predictor of kidney cancer, and the risk rises when additional symptoms are present. When considered alongside the risk of bladder cancer, the overall risk of urinary tract cancer from haematuria warrants referral. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article on inflammatory markers of acute pancreatitis and acute appendicitis.