Blood tests in primary care: A qualitative study of communication and decision-making between doctors and patients.

OBJECTIVE: Blood tests are commonly used in primary care as a tool to aid diagnosis, and to offer reassurance and validation for patients. If doctors and patients do not have a shared understanding of the reasons for testing and the meaning of results, these aims may not be fulfilled. Shared decision-making is widely advocated; yet, most research focusses on treatment decisions rather than diagnostic decisions. The aim of this study was to explore communication and decision-making around diagnostic blood tests in primary care. METHODS: Qualitative interviews were undertaken with patients and clinicians in UK primary care. Patients were interviewed at the time of blood testing, with a follow-up interview after they received test results. Interviews with clinicians who requested the tests provided paired data to compare clinicians' and patients' expectations, experiences and understandings of tests. Interviews were analysed thematically using inductive and deductive coding. RESULTS: A total of 80 interviews with 28 patients and 19 doctors were completed. We identified a mismatch in expectations and understanding of tests, which led to downstream consequences including frustration, anxiety and uncertainty for patients. There was no evidence of shared decision-making in consultations preceding the decision to test. Doctors adopted a paternalistic approach, believing that they were protecting patients from anxiety. CONCLUSION: Patients were not able to develop informed preferences and did not perceive that choice is possible in decisions about testing, because they did not have sufficient information and a shared understanding of tests. A lack of shared understanding at the point of decision-making led to downstream consequences when test results did not fulfil patients' expectations. Although shared decision-making is recommended as best practice, it does not reflect the reality of doctors' and patients' accounts of testing; a broader model of shared understanding seems to be more relevant to the complexity of primary care diagnosis. PATIENT OR PUBLIC CONTRIBUTION: A patient and public involvement group comprising five participants with lived experience of blood testing in primary care met regularly during the study. They contributed to the development of the research objectives, planning recruitment methods, reviewing patient information leaflets and topic guides and also contributed to discussion of emerging themes at an early stage in the analysis process.

Influenza vaccination reduced myocardial infarctions in United Kingdom older adults: a prior event rate ratio study.

OBJECTIVES: We aimed to estimate the real-world effectiveness of the influenza vaccine against myocardial infarction (MI) and influenza in the decade since adults aged ≥ 65 years were first recommended the vaccine. STUDY DESIGN AND SETTING: We identified annual cohorts, 1997 to 2011, of adults aged ≥ 65 years, without previous influenza vaccination, from UK general practices, registered with the Clinical Practice Research Datalink. Using a quasi-experimental study design to control for confounding bias, we estimated influenza vaccine effectiveness on hospitalization for MI, influenza, and antibiotic prescriptions for lower respiratory tract infections. RESULTS: Vaccination was moderately effective against influenza, the prior event rate ratio-adjusted hazard ratios ranging from 0.70 in 1999 to 0.99 in 2001. Prior event rate ratio-adjusted hazard ratios demonstrated a protective effect against MIs, varying between 0.40 in 2010 and 0.89 in 2001. Aggregated across the cohorts, influenza vaccination reduced the risk of MIs by 39% (95% confidence interval: 34%, 44%). CONCLUSION: Effectiveness of the flu vaccine in preventing MIs in older UK adults is consistent with the limited evidence from clinical trials. Similar trends in effectiveness against influenza and against MIs suggest the risk of influenza mediates the effectiveness against MIs, although divergence in some years implies the mechanism may be complex.

'I guess I'll wait to hear'- communication of blood test results in primary care a qualitative study.

BACKGROUND: Rates of blood testing in primary care are rising. Communicating blood test results generates significant workload for patients, GPs, and practice staff. AIM: To explore GPs' and patients' experience of systems of blood test communication. DESIGN AND SETTING: Qualitative interviews with patients and GPs in UK primary care in both urban and rural practices in the West of England. METHOD: A total of 28 patients and 19 GPs from six practices were recruited, with a range of socioeconomic and demographic characteristics. Patients were interviewed at two time points: a) at or soon after their blood test and b) after they had received their test results. The GPs who requested the tests were also interviewed (they could complete a maximum of two interviews about different patients). Eighty qualitative interviews were undertaken; 54 patient interviews and 26 GP interviews. RESULTS: Methods of test result communication varied between doctors and were based on habits, unwritten heuristics, and personal preferences rather than protocols. Doctors expected patients to know how to access their test results. In contrast, patients were often uncertain and used guesswork to decide when and how to access their tests. Patients and doctors generally assumed that the other party would make contact, with potential implications for patient safety. Text messaging and online methods of communication have benefits, but were perceived by some patients as 'flippant' or 'confusing'. Delays and difficulties obtaining and interpreting test results can lead to anxiety and frustration for patients. CONCLUSION: Current systems of test result communication are complex and confusing, and mostly based on habits and routines rather than clear protocols. This has important implications for patient-centred care and patient safety.

Diagnoses after newly recorded abdominal pain in primary care: observational cohort study.

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.

Intra-abdominal cancer risk with abdominal pain: a prospective cohort primary care study.

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.

Recognizing sinonasal cancer in primary care: a matched case-control study using electronic records.

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.

Sinonasal cancer occurs in the back of the nose or in the sinuses. It is rare in the United Kingdom, with most cases being diagnosed at an advanced stage. Delayed presentation and non-specific symptoms often lead to diagnosis at a later stage, with consequently poorer survival outcomes. Currently, there is no research describing the symptoms presented by these patients to their general practitioner (GP), nor referral guidelines for primary healthcare professionals. The aim of this study was to detect the symptoms of patients aged ≥40 years, diagnosed with sinonasal cancer in primary care. Three symptoms in the year before their diagnosis were linked with sinonasal cancer: nosebleeds, runny nose, and sinusitis. These symptoms may help GPs to identify possible sinonasal cancer patients earlier, though each symptom was low-risk on its own.

A prospective cohort evaluation of the sensitivity and specificity of the chest X-ray for the detection of lung cancer in symptomatic adults.

BACKGROUND: The accuracy of the chest x-ray (CXR) in the identification of lung cancer amongst symptomatic individuals is uncertain. PURPOSE: To determine the diagnostic accuracy of the CXR for the detection of non-small cell carcinomas (NSCLC) and all primary intrathoracic malignancies. METHODS: A prospective cohort study of consecutive CXR reports obtained within a primary care open access initiative. Eligibility criteria were symptoms specified by National Institute for Clinical Excellence as indicative of possible lung cancer and age over 50-yrs. A positive test was a CXR which led directly or indirectly to investigation with CT. The reference standards were malignancies observed within a one- or two-year post-test period. RESULTS: 8,948 CXR outcomes were evaluated. 496 positive studies led to a diagnosis of 101 patients with primary intrathoracic malignancy including 80 with NSCLC. Within two-years, a cumulative total of 168 patients with primary intrathoracic malignancies including 133 NSCLC were observed. The sensitivity and specificity for NSCLC were 76% (95 %CI 68-84) and 95% (95 %CI 95-96) within 1-year and 60% (95 %CI 52-69) and 95% (95 %CI 95-96) within 2-years. The 2-yr positive and negative likelihood ratios were 12.8 and 0.4. The results did not differ for NSCLC compared to all primary malignancies. Within this symptomatic population a negative test reduced the 2-year risk of lung cancer to 0.8%. CONCLUSIONS: A positive test strongly increases the probability of malignancy whereas a negative test does not conclusively exclude the disease. The findings allow the risk of malignancy following a negative test to be estimated.

Targeted encouragement of GP consultations for possible cancer symptoms: a randomised controlled trial.

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.

Chest X-ray sensitivity and lung cancer outcomes: a retrospective observational study.

BACKGROUND: Chest X-ray (CXR) is the first-line investigation for lung cancer in many healthcare systems. An understanding of the consequences of false-negative CXRs on time to diagnosis, stage, and survival is limited. AIM: To determine the sensitivity of CXR for lung cancer and to compare stage at diagnosis, time to diagnosis, and survival between those with CXR that detected, or did not detect, lung cancer. DESIGN AND SETTING: Retrospective observational study using routinely collected healthcare data. METHOD: All patients diagnosed with lung cancer in Leeds Teaching Hospitals NHS Trust during 2008-2015 who had a GP-requested CXR in the year before diagnosis were categorised based on the result of the earliest CXR performed in that period. The sensitivity of CXR was calculated and analyses were performed with respect to time to diagnosis, survival, and stage at diagnosis. RESULTS: CXR was negative for 17.7% of patients (n = 376/2129). Median time from initial CXR to diagnosis was 43 days for those with a positive CXR and 204 days for those with a negative CXR. Of those with a positive CXR, 29.8% (95% confidence interval [CI] = 27.9% to 31.8%) were diagnosed at stage I or II, compared with 33.5% (95% CI = 28.8% to 38.6%) with a negative CXR. CONCLUSION: GPs should consider lung cancer in patients with persistent symptoms even when CXR is negative. Despite longer duration to diagnosis for those with false-negative CXRs, there was no evidence of an adverse impact on stage at diagnosis or survival; however, this comparison is likely to be affected by confounding variables.

Quantifying the impact of pre-existing conditions on the stage of oesophagogastric cancer at diagnosis: a primary care cohort study using electronic medical records.

BACKGROUND: Pre-existing conditions interfere with cancer diagnosis by offering diagnostic alternatives, competing for clinical attention or through patient surveillance. OBJECTIVE: To investigate associations between oesophagogastric cancer stage and pre-existing conditions. METHODS: Retrospective cohort study using Clinical Practice Research Datalink (CPRD) data, with English cancer registry linkage. Participants aged ≥40 years had consulted primary care in the year before their incident diagnosis of oesophagogastric cancer in 01/01/2010-31/12/2015. CPRD records pre-diagnosis were searched for codes denoting clinical features of oesophagogastric cancer and for pre-existing conditions, including those providing plausible diagnostic alternatives for those features. Logistic regression analysed associations between stage and multimorbidity (≥2 conditions; reference category: no multimorbidity) and having 'diagnostic alternative(s)', controlling for age, sex, deprivation and cancer site. RESULTS: Of 2444 participants provided, 695 (28%) were excluded for missing stage, leaving 1749 for analysis (1265/1749, 72.3% had advanced-stage disease). Multimorbidity was associated with stage [odds ratio 0.63, 95% confidence interval (CI) 0.47-0.85, P = 0.002], with moderate evidence of an interaction term with sex (1.76, 1.08-2.86, P = 0.024). There was no association between alternative explanations and stage (odds ratio 1.18, 95% CI 0.87-1.60, P = 0.278). CONCLUSIONS: In men, multimorbidity is associated with a reduced chance of advanced-stage oesophagogastric cancer, to levels seen collectively for women.

Diagnosing cancer is complicated by existing medical conditions. Diagnosis may be delayed if conditions explain cancer symptoms, or dominate appointments. Diagnosis may be quicker if conditions increase doctor­patient contact. We studied the association between existing illness and stage (early or advanced) of diagnosis with cancer of the stomach or gullet. We studied the primary-care records of patients aged ≥40 years, diagnosed in 01/01/2010­31/12/2015, and got stage from English cancer registry data. We searched the primary-care records for cancer symptoms (e.g. difficulty swallowing), and for 27 conditions that were common or explained cancer symptoms (e.g. difficulty swallowing following a stroke). We analysed cancer stage, looking at age, sex, multimorbidity (two or more conditions) and explanations for symptoms. We studied 1749 patients, of whom 1265 (72.3%) had advanced-stage cancer. The chance of advanced stage was similar in women with (71%, 95% CI 66­75%) or without (69%, 62­76%) multimorbidity. It was lower for men with (70%, 67­74%) than without (79%, 75­83%) multimorbidity. Stage of cancer was not affected by having explanations for cancer symptoms. In summary, for men, multimorbidity is associated with a reduced chance of advanced-stage cancer of the stomach or gullet to levels seen collectively for women.

Estimating lung cancer risk from chest X-ray and symptoms: a prospective cohort study.

BACKGROUND: Chest X-ray (CXR) is the first-line investigation for lung cancer in many countries but previous research has suggested that the disease is not detected by CXR in approximately 20% of patients. The risk of lung cancer, with particular symptoms, following a negative CXR is not known. AIM: To establish the sensitivity and specificity of CXR requested by patients who are symptomatic; determine the positive predictive values (PPVs) of each presenting symptom of lung cancer following a negative CXR; and determine whether symptoms associated with lung cancer are different in those who had a positive CXR result compared with those who had a negative CXR result. DESIGN AND SETTING: A prospective cohort study was conducted in Leeds, UK, based on routinely collected data from a service that allowed patients with symptoms of lung cancer to request CXR. METHOD: Symptom data were combined with a diagnostic category (positive or negative) for each CXR, and the sensitivity and specificity of CXR for lung cancer were calculated. The PPV of lung cancer associated with each symptom or combination of symptoms was estimated for those patients with a negative CXR. RESULTS: In total, 114 (1.3%) of 8996 patients who requested a CXR were diagnosed with lung cancer within 1 year. Sensitivity was 75.4% and specificity was 90.2%. The PPV of all symptoms for a diagnosis of lung cancer within 1 year of CXR was <1% for all individual symptoms except for haemoptysis, which had a PPV of 2.9%. PPVs for a diagnosis of lung cancer within 2 years of CXR was <1.5% for all single symptoms except for haemoptysis, which had a PPV of 3.9%. CONCLUSION: CXR has limited sensitivity; however, in a population with a low prevalence of lung cancer, its high specificity and negative predictive value means that lung cancer is very unlikely to be present following a negative result. Findings also support guidance that unexplained haemoptysis warrants urgent referral, regardless of CXR result.

Microcytosis as a risk marker of cancer in primary care: a cohort study using electronic patient records.

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.

Sensitivity of chest X-ray for detecting lung cancer in people presenting with symptoms: a systematic review.

BACKGROUND: Despite increasing use of computed tomography (CT), chest X-ray remains the first-line investigation for suspected lung cancer in primary care in the UK. No systematic review evidence exists as to the sensitivity of chest X-ray for detecting lung cancer in people presenting with symptoms. AIM: To estimate the sensitivity of chest X-ray for detecting lung cancer in symptomatic people. DESIGN AND SETTING: A systematic review was conducted to determine the sensitivity of chest X-ray for the detection of lung cancer. METHOD: Databases including MEDLINE, EMBASE, and the Cochrane Library were searched; a grey literature search was also performed. RESULTS: A total of 21 studies met the eligibility criteria. Almost all were of poor quality. Only one study had the diagnostic accuracy of chest X-ray as its primary objective. Most articles were case studies with a high risk of bias. Several were drawn from non-representative groups, for example, specific presentations, histological subtypes, or comorbidities. Only three studies had a low risk of bias. Two primary care studies reported sensitivities of 76.8% (95% confidence interval [CI] = 64.5 to 84.2%) and 79.3% (95% CI = 67.6 to 91.0%). One secondary care study reported a sensitivity of 79.7% (95% CI = 72.7 to 86.8%). CONCLUSION: Though there is a paucity of evidence, the highest-quality studies suggest that the sensitivity of chest X-ray for symptomatic lung cancer is only 77% to 80%. GPs should consider if further investigation is necessary in high-risk patients who have had a negative chest X-ray.

Recognising laryngeal cancer in primary care: a large case-control study using electronic records.

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.

Sex and BMI Alter the Benefits and Risks of Sulfonylureas and Thiazolidinediones in Type 2 Diabetes: A Framework for Evaluating Stratification Using Routine Clinical and Individual Trial Data.

OBJECTIVE: The choice of therapy for type 2 diabetes after metformin is guided by overall estimates of glycemic response and side effects seen in large cohorts. A stratified approach to therapy would aim to improve on this by identifying subgroups of patients whose glycemic response or risk of side effects differs markedly. We assessed whether simple clinical characteristics could identify patients with differing glycemic response and side effects with sulfonylureas and thiazolidinediones. RESEARCH DESIGN AND METHODS: We studied 22,379 patients starting sulfonylurea or thiazolidinedione therapy in the U.K. Clinical Practice Research Datalink (CPRD) to identify features associated with increased 1-year HbA1c fall with one therapy class and reduced fall with the second. We then assessed whether prespecified patient subgroups defined by the differential clinical factors showed differing 5-year glycemic response and side effects with sulfonylureas and thiazolidinediones using individual randomized trial data from ADOPT (A Diabetes Outcome Progression Trial) (first-line therapy, n = 2,725) and RECORD (Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycemia in Diabetes) (second-line therapy, n = 2,222). Further replication was conducted using routine clinical data from GoDARTS (Genetics of Diabetes Audit and Research in Tayside Scotland) (n = 1,977). RESULTS: In CPRD, male sex and lower BMI were associated with greater glycemic response with sulfonylureas and a lesser response with thiazolidinediones (both P < 0.001). In ADOPT and RECORD, nonobese males had a greater overall HbA1c reduction with sulfonylureas than with thiazolidinediones (P < 0.001); in contrast, obese females had a greater HbA1c reduction with thiazolidinediones than with sulfonylureas (P < 0.001). Weight gain and edema risk with thiazolidinediones were greatest in obese females; however, hypoglycemia risk with sulfonylureas was similar across all subgroups. CONCLUSIONS: Patient subgroups defined by sex and BMI have different patterns of benefits and risks on thiazolidinedione and sulfonylurea therapy. Subgroup-specific estimates can inform discussion about the choice of therapy after metformin for an individual patient. Our approach using routine and shared trial data provides a framework for future stratification research in type 2 diabetes.

Selection of men for investigation of possible testicular cancer in primary care: a large case-control study using electronic patient records.

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.

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.

Is omission of free text records a possible source of data loss and bias in Clinical Practice Research Datalink studies? A case-control study.

OBJECTIVES: To estimate data loss and bias in studies of Clinical Practice Research Datalink (CPRD) data that restrict analyses to Read codes, omitting anything recorded as text. DESIGN: Matched case-control study. SETTING: Patients contributing data to the CPRD. PARTICIPANTS: 4915 bladder and 3635 pancreatic, cancer cases diagnosed between 1 January 2000 and 31 December 2009, matched on age, sex and general practitioner practice to up to 5 controls (bladder: n=21 718; pancreas: n=16 459). The analysis period was the year before cancer diagnosis. PRIMARY AND SECONDARY OUTCOME MEASURES: Frequency of haematuria, jaundice and abdominal pain, grouped by recording style: Read code or text-only (ie, hidden text). The association between recording style and case-control status (χ(2) test). For each feature, the odds ratio (OR; conditional logistic regression) and positive predictive value (PPV; Bayes' theorem) for cancer, before and after addition of hidden text records. RESULTS: Of the 20 958 total records of the features, 7951 (38%) were recorded in hidden text. Hidden text recording was more strongly associated with controls than with cases for haematuria (140/336=42% vs 556/3147=18%) in bladder cancer (χ(2) test, p<0.001), and for jaundice (21/31=67% vs 463/1565=30%, p<0.0001) and abdominal pain (323/1126=29% vs 397/1789=22%, p<0.001) in pancreatic cancer. Adding hidden text records corrected PPVs of haematuria for bladder cancer from 4.0% (95% CI 3.5% to 4.6%) to 2.9% (2.6% to 3.2%), and of jaundice for pancreatic cancer from 12.8% (7.3% to 21.6%) to 6.3% (4.5% to 8.7%). Adding hidden text records did not alter the PPV of abdominal pain for bladder (codes: 0.14%, 0.13% to 0.16% vs codes plus hidden text: 0.14%, 0.13% to 0.15%) or pancreatic (0.23%, 0.21% to 0.25% vs 0.21%, 0.20% to 0.22%) cancer. CONCLUSIONS: Omission of text records from CPRD studies introduces bias that inflates outcome measures for recognised alarm symptoms. This potentially reinforces clinicians' views of the known importance of these symptoms, marginalising the significance of 'low-risk but not no-risk' symptoms.

Quantifying the risk of non-Hodgkin lymphoma in symptomatic primary care patients aged ≥40 years: a large case-control study using electronic records.

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.