Scientific
publications

OBJECTIVE: Smoking represents a major issue for global public health. Owing to methodologic challenges, findings of an association between smoking and risk of knee osteoarthritis (OA) are inconsistent. We sought to assess the relation of onset of smoking cessation to the risk of OA sequelae, i.e., knee replacement, and to perform sub-cohort analysis according to weight change after smoking cessation. DESIGN: Using The Health Improvement Network, we conducted a cohort study to examine the association between smoking cessation and risk of knee replacement among patients with knee OA. Participants who stopped smoking were further grouped into three sub-cohorts: weight gain (body mass index [BMI] increased>1.14 kg/m ), no substantial weight change (absolute value of BMI change<1.14 kg/m ), and weight loss (BMI loss>1.14 kg/m ) after smoking cessation. RESULTS: We identified 108 cases of knee replacement among 1,054 recent quitters (26.7/1,000 person-years) and 1,108 cases among 15,765 current smokers (17.4/1,000 person-years). The rate difference of knee replacement in recent quitter cohort vs current smoker cohort was 10.4 (95% confidence interval [CI]:5.3-15.6)/1,000 person-years and the adjusted hazard ratio (HR) was 1.30 (95%CI:1.05-1.59). Compared with current smokers, risk of knee replacement was higher among quitters with weight gain (HR = 1.42,95%CI:1.01-1.98), but not among those with no substantial weight change (HR = 1.29,95%CI:0.90-1.83) or those with weight loss (HR = 1.11,95%CI:0.71-1.75). CONCLUSIONS: Our large population-based cohort study provides the first evidence that smoking cessation was associated with a higher risk of knee replacement among individuals with knee OA, and such an association was due to weight gain after smoking cessation.

OBJECTIVE: Assess whether statins reduce mortality in the general population aged 60 years and above. DESIGN: Retrospective cohort study. SETTING: Primary care practices contributing to The Health Improvement Network database, England and Wales, 1990-2017. PARTICIPANTS: Cohort who turned age 60 between 1990 and 2000 with no previous cardiovascular disease or statin prescription and followed up until 2017. RESULTS: Current statin prescription was associated with a significant reduction in all-cause mortality from age 65 years onward, with greater reductions seen at older ages. The adjusted HRs of mortality associated with statin prescription at ages 65, 70, 75, 80 and 85 years were 0.76 (95% CI 0.71 to 0.81), 0.71 (95% CI 0.68 to 0.75), 0.68 (95% CI 0.65 to 0.72), 0.63 (95% CI 0.53 to 0.73) and 0.54 (95% CI 0.33 to 0.92), respectively. The adjusted HRs did not vary by sex or cardiac risk. CONCLUSIONS: Using regularly updated clinical information on sequential treatment decisions in older people, mortality predictions were updated every 6 months until age 85 years in a combined primary and secondary prevention population. The consistent mortality reduction of statins from age 65 years onward supports their use where clinically indicated at age 75 and older, where there has been particular uncertainty of the benefits.

AIM: To investigate the effectiveness of premixed insulin for achieving glycaemic outcomes in clinical practice in the UK. MATERIALS AND METHODS: Electronic medical record data from The Health Improvement Network database were captured for adults with type 2 diabetes (T2D) uncontrolled (HbA1c ≥9%) on two or more oral antihyperglycaemic drugs (OADs) initiating premixed insulin. Effectiveness of premixed insulin was assessed by the probability and incidence of achieving glycaemic outcomes (target HbA1c <7.5% [<58 mmol/mol] and a ≥1% or ≥2% HbA1c reduction) over 24 months. RESULTS: Data from 974 participants (mean age 62 years; 56% male; 52% obese or extremely obese; mean HbA1c 11.3% [100 mmol/mol]; hypertension 64%, dyslipidaemia 23% and nephropathy 21%) were analysed. The probability of achieving HbA1c  <7.5% was highest during months 3-6 (18.2%), while the cumulative probability of achieving this target plateaued between months 15-24 (15.7%-16.0%). Incidence of achieving all glycaemic outcomes plateaued after 12 months and differed by baseline HbA1c, but not OAD use. Factors affecting some glycaemic outcomes included a body mass index >40 kg/m and co-morbidities including nephropathy and stroke. CONCLUSIONS: In people with uncontrolled T2D (HbA1c ≥9%), glycaemic outcome achievement on premixed insulin was low at 6 months with little additional clinical benefit beyond 12 months, suggesting a high unmet need for early, timely treatment changes with more effective, simpler therapies.

OBJECTIVE: Diabetes has emerged as an important risk factor for mortality from COVID-19. Metformin, the most commonly prescribed glucose-lowering agent, has been proposed to influence susceptibility to and outcomes of COVID-19 via multiple mechanisms. We investigated whether, in patients with diabetes, metformin is associated with susceptibility to COVID-19 and its outcomes. RESEARCH DESIGN AND METHODS: We performed a propensity score-matched cohort study with active comparators using a large UK primary care dataset. Adults with type 2 diabetes patients and a current prescription for metformin and other glucose-lowering agents (MF+) were compared to those with a current prescription for glucose-lowering agents that did not include metformin (MF-). Outcomes were confirmed COVID-19, suspected/confirmed COVID-19, and associated mortality. A negative control outcome analysis (back pain) was also performed. RESULTS: There were 29 558 and 10 271 patients in the MF+ and MF- groups, respectively, who met the inclusion criteria. In the propensity score-matched analysis, the adjusted hazard ratios for suspected/confirmed COVID-19, confirmed COVID-19, and COVID-19-related mortality were 0.85 (95% CI 0.67, 1.08), 0.80 (95% CI 0.49, 1.30), and 0.87 (95% CI 0.34, 2.20) respectively. The negative outcome control analysis did not suggest unobserved confounding. CONCLUSION: Current prescription of metformin was not associated with the risk of COVID-19 or COVID-19-related mortality. It is safe to continue prescribing metformin to improve glycemic control in patients with.

AIMS: To investigate whether exposure to antipsychotic medications during pregnancy is associated with gestational diabetes mellitus (GDM) in United Kingdom (UK) and Hong Kong (HK) population cohorts. METHODS: Two population-based cohort studies were conducted using data from the UK The Health Improvement Network (THIN) and HK Clinical Data Analysis and Reporting System (CDARS). Nondiabetic women who received any type of antipsychotic medicine before their first pregnancy were included in our cohorts. The exposed group comprised women who continued using antipsychotics from the start of pregnancy to delivery (continuers), while the comparison group included women who were prescribed antipsychotics before the start of pregnancy but stopped during pregnancy (discontinuers). GDM was identified using GDM diagnosis and/or clinicians reported GDM. Odds ratios (ORs) with a 95% confidence interval (CI) were calculated to assess the association between antipsychotic use during pregnancy and GDM. Propensity Score fine-stratification weighting was used to adjust for potential confounding factors. RESULTS: 3114 women with registered first pregnancies (2351 in THIN and 763 in CDARS) were included. 5.49% (2.55% in THIN and 14.55% in CDARS) were diagnosed with GDM. The adjusted OR of GDM in continuers was 0.73 (95% CI: 0.43-1.25) in THIN and 1.16 (95% CI: 0.78-1.73) in CDARS compared with discontinuers. CONCLUSIONS: Our results do not suggest an increased risk of GDM in women who continued using antipsychotics during pregnancy compared to women who stopped. Based on these results, women should not stop their regular antipsychotics prescriptions in pregnancy due to the fear of GDM.

BACKGROUND: Generalised anxiety disorder and symptoms are associated with poor physical, emotional and social functioning and frequent primary and acute care visits. We investigated recent temporal trends in anxiety and related mental illness in UK general practice. AIMS: The aims of this analysis are to examine temporal changes in recording of generalised anxiety in primary care and initial pharmacologic treatments. METHOD: Annual incidence rates of generalised anxiety diagnoses and symptoms were calculated from 795 UK general practices contributing to The Health Improvement Network (THIN) database between 1998 and 2018. Poisson mixed regression was used to account for age, gender and general practitioner practice. Subsequent pharmacologic treatment was examined. RESULTS: Generalised anxiety recording rates increased in both genders aged 18-24 between 2014 and 2018. For women, the increase was from 17.06 to 23.33/1000 person years at risk (PYAR); for men, 8.59 to 11.65/1000 PYAR. Increases persisted for a composite of anxiety and depression (49.74 to 57.81/1000 PYAR for women; 25.41 to 31.45/1000 PYAR for men). Smaller increases in anxiety were seen in both genders age 25-34 and 35-44. Anxiety rates among older patients remained stable, although a composite of anxiety and depression decreased for older women. About half of drug-naïve patients were prescribed anxiety drugs within 1 year following diagnosis. The most common choice was a selective serotonin reuptake inhibitor. Benzodiazepine prescription rate has fallen steadily. CONCLUSIONS: We observed a substantial increase in general practitioner consulting for generalised anxiety and depression recently, concentrated within younger people and in particular women.

PURPOSE: Real-world studies to describe the use of first, second and third line therapies for the management and symptomatic treatment of dementia are lacking. This retrospective cohort study describes the first-, second- and third-line therapies used for the management and symptomatic treatment of dementia, and in particular Alzheimer's Disease. METHODS: Medical records of patients with newly diagnosed dementia between 1997 and 2017 were collected using four databases from the UK, Denmark, Italy and the Netherlands. RESULTS: We identified 191,933 newly diagnosed dementia patients in the four databases between 1997 and 2017 with 39,836 (IPCI (NL): 3281, HSD (IT): 1601, AUH (DK): 4474, THIN (UK): 30,480) fulfilling the inclusion criteria, and of these, 21,131 had received a specific diagnosis of Alzheimer's disease. The most common first line therapy initiated within a year (± 365 days) of diagnosis were Acetylcholinesterase inhibitors, namely rivastigmine in IPCI, donepezil in HSD and the THIN and the N-methyl-D-aspartate blocker memantine in AUH. CONCLUSION: We provide a real-world insight into the heterogeneous management and treatment pathways of newly diagnosed dementia patients and a subset of Alzheimer's Disease patients from across Europe.

BACKGROUND: Umeclidinium bromide (UMEC) and umeclidinium/vilanterol (UMEC/VI) received European approval for maintenance treatment of patients with chronic obstructive pulmonary disease (COPD) in 2014. This study examined prescribing patterns, possible off-label prescribing, potential safety-related outcomes and adherence of these medications in routine clinical practice post-approval. METHODS: This retrospective, multi-database, longitudinal observational study of new users of UMEC, UMEC/VI, or other long-acting bronchodilators (LABD) analyzed data from UK electronic health record databases (primary care cohort), linked to hospital data (linked cohort). Off-label prescribing, safety outcomes (cardiovascular, respiratory, and mortality), treatment patterns, and medication adherence were assessed. RESULTS: In the primary care cohort (new users of UMEC n=3875; UMEC/VI n=2224; other LABD n=32,809), two-thirds of UMEC users were prescribed concomitant inhaled corticosteroids/long-acting β -agonists. Possible off-label prescribing, defined as use in patients without COPD, was similar for UMEC (7.0%) and UMEC/VI (8.8%), but higher for new users of other LABD (18.0%). There were 547 UMEC users and 512 UMEC/VI users in the linked cohort. In both cohorts, incidence rates (IRs) of cardiovascular outcomes were similar for UMEC and UMEC/VI users (myocardial infarction IR per 1000 person-years [95% CIs]: UMEC 6.9 [4.4, 10.2]; UMEC/VI 6.8 [3.5, 11.9]). IRs of pneumonia and acute COPD exacerbations (AECOPD) were slightly higher among UMEC users compared with UMEC/VI users (AECOPD IR per 1000 person-years [95% CIs]: UMEC 979 [931, 1030]; UMEC/VI 746 [687, 811]). Adherence (medication possession ratio ≥80%) was 64% for UMEC and UMEC/VI. CONCLUSION: Most new users of UMEC were receiving multiple-inhaler triple therapy. Off-label prescribing was uncommon for new users of UMEC and UMEC/VI. Incidence of cardiovascular and respiratory outcomes was as expected for these drug classes. This study provides evidence that UMEC and UMEC/VI are being prescribed appropriately and their safety profile remains unchanged.

OBJECTIVE: To investigate the relationship between social deprivation and incident diabetes-related foot disease (DFD) in newly diagnosed patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A population-based open retrospective cohort study using The Health Improvement Network (1 January 2005 to 31 December 2019) was conducted. Patients with type 2 diabetes free of DFD at baseline were stratified by Townsend deprivation index, and risk of developing DFD was calculated. DFD was defined as a composite of foot ulcer (FU), Charcot arthropathy, lower-limb amputation (LLA), peripheral neuropathy (PN), peripheral vascular disease (PVD), and gangrene. RESULTS: A total of 176,359 patients were eligible (56% men; mean age 62.9 [SD 13.1] years). After excluding 26,094 patients with DFD before/within 15 months of type 2 diabetes diagnosis, DFD incidentally developed in 12.1% of the study population over 3.27 years (interquartile range 1.41-5.96). Patients in the most deprived Townsend quintile had increased risk of DFD compared with those in the least deprived (adjusted hazard ratio [aHR] 1.22; 95% CI 1.16-1.29) after adjusting for sex, age at type 2 diabetes diagnosis, ethnicity, smoking, BMI, HbA , cardiovascular disease, hypertension, retinopathy, estimated glomerular filtration rate, insulin, glucose/lipid-lowering medication, and baseline foot risk. Patients in the most deprived Townsend quintile had higher risk of PN (aHR 1.18; 95% CI 1.11-1.25), FU (aHR 1.44; 95% CI 1.17-1.77), PVD (aHR 1.40; 95% CI 1.28-1.53), LLA (aHR 1.75; 95% CI 1.08-2.83), and gangrene (aHR 8.49; 95% CI 1.01-71.58) compared with those in the least. CONCLUSIONS: Social deprivation is an independent risk factor for the development of DFD, PN, FU, PVD, LLA, and gangrene in newly diagnosed patients with type 2 diabetes. Considering the high individual and economic burdens of DFD, strategies targeting patients in socially deprived areas are needed to reduce health inequalities.

The Be Clear on Cancer (BCoC) campaigns have run in England since 2010. They aim to raise awareness of possible cancer symptoms, encouraging people to consult a general practice with these symptoms. Our study provides an overview of the impact of 11 national campaigns, for bowel, lung, bladder and kidney, breast and oesophago-gastric cancers. We synthesised existing results for each campaign covering seven clinical metrics across the patient pathway from primary care attendances to one-year net survival. For each metric, "before" and "after" periods were compared to assess change potentially related to the campaign. Results show that primary care attendances for campaign-related symptoms increased for 9 of 10 campaigns and relevant urgent referrals for suspected cancer increased above general trends for 9 of 11 campaigns. Diagnostic tests increased for 6 of 11 campaigns. For 7 of 11 campaigns, there were increases in cancer diagnoses resulting from an urgent referral for suspected cancer. There were sustained periods where more cancers were diagnosed than expected for 8 of 10 campaigns, with higher than expected proportions diagnosed at an early stage for sustained periods for 4 of 10 campaigns. There was no impact on survival. In summary, there is evidence that the BCoC campaigns impact help-seeking by patients and referral patterns by general practitioners, with some impact on diagnosis (incidence and stage). There was no clear evidence of impact on survival.

INTRODUCTION: Renin-angiotensin system (RAS) inhibitors have been postulated to influence susceptibility to Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). This study investigated whether there is an association between their prescription and the incidence of COVID-19 and all-cause mortality. METHODS: We conducted a propensity-score matched cohort study comparing the incidence of COVID-19 among patients with hypertension prescribed angiotensin-converting enzyme I (ACE) inhibitors or angiotensin II type-1 receptor blockers (ARBs) to those treated with calcium channel blockers (CCBs) in a large UK-based primary care database (The Health Improvement Network). We estimated crude incidence rates for confirmed/suspected COVID-19 in each drug exposure group. We used Cox proportional hazards models to produce adjusted hazard ratios for COVID-19. We assessed all-cause mortality as a secondary outcome. RESULTS: The incidence rate of COVID-19 among users of ACE inhibitors and CCBs was 9.3 per 1000 person-years (83 of 18,895 users [0.44%]) and 9.5 per 1000 person-years (85 of 18,895 [0.45%]), respectively. The adjusted hazard ratio was 0.92 (95% CI 0.68 to 1.26). The incidence rate among users of ARBs was 15.8 per 1000 person-years (79 out of 10,623 users [0.74%]). The adjusted hazard ratio was 1.38 (95% CI 0.98 to 1.95). There were no significant associations between use of RAS inhibitors and all-cause mortality. CONCLUSION: Use of ACE inhibitors was not associated with the risk of COVID-19 whereas use of ARBs was associated with a statistically non-significant increase compared to the use of CCBs. However, no significant associations were observed between prescription of either ACE inhibitors or ARBs and all-cause mortality.

There is a gap in the literature investigating the impact of obstetric complications on subsequent mental ill health outcomes. The aim of this study was to establish the association between post-partum haemorrhage (PPH) and mental ill health. We conducted a retrospective open cohort study utilizing linked primary care (The Health Improvement Network (THIN)) and English secondary care (Hospital Episode Statistics (HES)) databases, from January 1, 1990 to January 31, 2018. A total of 42,327 women were included: 14,109 of them were exposed to PPH during the study period and 28,218 unexposed controls were matched for age and date of delivery. Hazard ratios (HRs) for mental illness among women with and without exposure to PPH were estimated after controlling for covariates. Women who had had PPH were at an increased risk of developing postnatal depression (adjusted HR: 1·10, 95%CI: 1·01-1·21) and post-traumatic stress disorder (PTSD) (adjusted HR: 1·17, 95%CI: 0·73-1·89) compared to women unexposed to PPH. When restricting the follow-up to the first year after childbirth, the adjusted HR for PTSD was 3·44 (95% CI 1·31-9·03). No increase in the overall risk was observed for other mental illnesses, including depression (adjusted HR: 0·94, 95%CI: 0·87-1·01), severe mental illness (adjusted HR: 0·65, 95%CI: 0·40-1·08, p = 0·239) and anxiety (adjusted HR: 0·99, 95%CI: 0·90-1·09). PPH is associated with a significant increase in the risk of developing postnatal depression and PTSD in the first year after delivery. Active monitoring for mental illness should form an integral part of the follow-up in women who suffered a PPH.

AIMS: Oral anticoagulant (OAC) is recommended for preventing stroke in atrial fibrillation (AF). However, the OAC utilisation in AF patients with dementia or cognitive impairment (CI) is limited. This study aimed to examine the prevalence of OAC prescriptions in AF patients with dementia/CI and to identify factors associated with OAC treatment within 180 days after dementia/CI diagnosis. METHODS: Using The Health Improvement Network database, the annual trends of OAC between 2000 and 2015 were calculated. Multivariable logistic regression was performed to identify factors associated with OAC treatment. RESULTS: The prevalence rate of OAC prescriptions increased from 6.1% in 2000 to 45.9% in 2015. Among OAC users, the proportion of direct oral anticoagulants (DOACs) use increased significantly from 0.1% in 2011 to 33.8% in 2015 (P-trend < 0.001), while the proportion of vitamin K antagonist use decreased by 28.6% from 100% in 2000 to 71.4% in 2015 (P-trend < 0.001). In the multivariable analysis, younger age, very old age, female sex, higher Charlson Comorbidity Index, having a HAS-BLED score ≥3, a history of intracranial bleeding, falls and polypharmacy were significantly associated with lower odds of receiving OAC. CONCLUSIONS: In UK primary care, OAC use increased from 2000 to 2015 in AF patients with dementia/CI, with a substantial increase in use of DOACs. Characteristics related to frailty are associated with lower odds of OAC prescription. Given the increasing use of DOACs in patients with dementia/CI, further studies are needed to investigate the safety and effectiveness of DOACs in this important patient group.

OBJECTIVES: To describe the variation in weight gain in people chronically exposed to systemic glucocorticoids in primary care and to identify the risk factors for weight gain. METHODS: Data were analysed from the British database, The Health Improvement Network. Body weight variations of individuals prescribed systemic glucocorticoids for at least 3 months at a mean dose ≥10 mg/day were described. The risk factors associated with weight gain ≥10% of the usual weight were assessed. RESULTS: A total of 31 516 adults prescribed glucocorticoids and 26 967 controls were included in the study. During glucocorticoid exposure, only 12 475 (39.6%) individuals gained >2 kg compared with their usual weight. Younger women were more likely to gain weight (mean weight gain in 18-39-year-old glucocorticoid-exposed women: 3.6 kg (s.d. 8.6) compared with 2 kg (s.d. 7.3) in the control group; the absolute mean difference was 1.6 kg (95% CI 0.9, 2.2; P < 0.001). Weight gain ≥10% of the usual weight was observed in 10.2% (n = 3208) of those chronically exposed to glucocorticoids. Women, younger people, those living in areas of higher deprivation, smokers, those on higher doses of the drug and those previously exposed to glucocorticoids were at higher risk. The risk was lower in people prescribed glucocorticoids for an inflammatory condition when compared with asthma or chronic obstructive pulmonary disease. CONCLUSION: After taking into account usual weight rather than weight just before glucocorticoid initiation and the natural history of weight variation, the amount of weight gain induced by systemic glucocorticoids as prescribed in primary care is less than usually thought. CLINICAL TRIAL REGISTRATION: 18THIN081.

AIMS: The aim of this study was to investigate the initial cardiovascular prescription patterns in patients after their first cardiovascular events, and to identify factors associated with cardiovascular polypharmacy. METHODS: This was a cross-sectional study including patients aged ≥ 45 years with the first record of coronary heart disease (CHD) or stroke between 2007 and 2016 using The Health Improvement Network database. This study investigated the patterns of cardiovascular drugs prescribed during the first 90 days after the first cardiovascular events. Logistic regression was used to examine the association between patients' baseline characteristics and cardiovascular polypharmacy (≥5 cardiovascular drugs). RESULTS: A total of 121,600 (59,843 CHD and 61,757 stroke) patients were included in the study. The mean age was 69.5 ± 11.9 years. The proportion of patients who were prescribed 0-1, 2-3, 4-5 drugs and ≥6 drugs were 11.0%, 29.8%, 38.6% and 20.5%, respectively. Factors associated with cardiovascular polypharmacy were sex (female: OR 0.74, 95% CI 0.72-0.76 vs male), age (75-84 years old: OR 0.50, 0.47-0.53 vs 45-54 years old), smoking status (current smoking: OR 1.29, 1.15-1.24 vs never), body mass index (obesity: OR 1.38, 1.34-1.43 vs normal), deprivation status (most deprived: OR 1.09, 1.04-1.14 vs least deprived) and Charlson comorbidity index (index ≥5: OR 1.25, 1.16-1.35 vs index 0). CONCLUSION: Multiple cardiovascular drugs treatment was common in patients with CVD in the UK. High-risk factors of CVD were also associated with cardiovascular polypharmacy. Further studies are warranted to assess the impact of cardiovascular polypharmacy and its interaction on CVD recurrence and mortality.

INTRODUCTION: The public-private ADVANCE collaboration developed and tested a system to generate evidence on vaccine benefits and risks using European electronic healthcare databases. In the safety of vaccines, background incidence rates are key to allow proper monitoring and assessment. The goals of this study were to compute age-, sex-, and calendar-year stratified incidence rates of nine autoimmune diseases in seven European healthcare databases from four countries and to assess validity by comparing with published data. METHODS: Event rates were calculated for the following outcomes: acute disseminated encephalomyelitis, Bell's palsy, Guillain-Barré syndrome, immune thrombocytopenia purpura, Kawasaki disease, optic neuritis, narcolepsy, systemic lupus erythematosus, and transverse myelitis. Cases were identified by diagnosis codes. Participating organizations/databases originated from Denmark, Italy, Spain, and the UK. The source population comprised all persons registered, with at least 1 year of data prior to the study start, or follow-up from birth. Stratified incidence rates were computed per database over the period 2003 to 2014. RESULTS: Between 2003 and 2014, 148,947 incident cases of nine autoimmune diseases were identified. Crude incidence rates were highest for Bell's palsy [23.8/100,000 person-years (PYs), 95% confidence interval (CI) 23.6-24.1] and lowest for Kawasaki disease (0.7/100,000 PYs, 95% CI 0.6-0.7). Specific patterns were observed by sex, age, calendar time, and data sources. Rates were comparable with published estimates. CONCLUSION: A range of autoimmune events could be identified in the ADVANCE system. Estimation of rates indicated consistency across selected European healthcare databases, as well as consistency with US published data.

Sputum colour may mark bacterial involvement in acute exacerbations of chronic obstructive pulmonary disease (COPD). However, whether colour vision deficiency (CVD) in COPD patients could impact the use of sputum colour charts as part of a guide to antibiotic use in exacerbations is unknown. This study used an exploratory mixed-method approach to establish the likelihood that COPD patients will be colour blind and whether this would result in the sputum colour chart being unusable in the context of the patients' self-management of their condition. CVD is under-reported in primary care and comorbidities in COPD patients increase the risk of acquiring CVD. Participants diagnosed with CVD and risk of acquiring CVD were able to use the sputum colour charts. Colour charts are likely to be usable even in the context of undiagnosed CVD in COPD patients.

PURPOSE: To describe the effect that validation of venous thromboembolism (VTE) coded entries in the health improvement network (THIN) has on incidence rates of VTE among a cohort of rivaroxaban/warfarin users. METHODS: Among 36 701 individuals with a first prescription for rivaroxaban/warfarin between 2012 and 2015, we performed a two-step VTE case identification process followed by a two-step case validation process involving manual review of patient records. A valid case required a coded entry for VTE at some point after their first rivaroxaban/warfarin prescription with evidence of referral/hospitalization either as a coded entry or entered as free text. Positive predictive values (PPVs) with 95% confidence intervals (CIs) were calculated using validated cases as the gold standard. Incidence rates were calculated per 1000 person-years with 95% CIs. RESULTS: We identified 2166 patients with a coded entry of VTE after their initial rivaroxaban/warfarin prescription; incidence rate of 45.31 per 1000 person-years (95% CI: 43.49-47.22). After manual review of patient records including the free text, there were 712 incident VTE cases; incidence rate of 14.90 per 1000 person-years (95% CI: 13.85-16.02). The PPV for coded entries of VTE alone was 32.9%, and the PPV for coded entries of VTE with a coded entry of referral/hospitalization was 39.8%; this increased to 69.6% after manual review of coded clinical entries in patient records. CONCLUSIONS: Among rivaroxaban/warfarin users in THIN, valid VTE case identification requires manual review of patient records including the free text to prevent outcome misclassification and substantial overestimation of VTE incidence rates.

OBJECTIVE: To estimate the test accuracy of faecal calprotectin (FC) for inflammatory bowel disease (IBD) in the primary care setting using routine electronic health records. DESIGN: Retrospective cohort test accuracy study. SETTING: UK primary care. PARTICIPANTS: 5970 patients (≥18 years) without a previous IBD diagnosis and with a first FC test between 1 January 2006 and 31 December 2016. We excluded multiple tests and tests without numeric results in units of µg/g. INTERVENTION: FC testing for the diagnosis of IBD. Disease status was confirmed by a recorded diagnostic code and/or a drug code of an IBD-specific medication at three time points after the FC test date. MAIN OUTCOME MEASURES: Sensitivity, specificity, and positive and negative predictive values for the differential of IBD versus non-IBD and IBD versus irritable bowel syndrome (IBS) at the 50 and 100 µg/g thresholds. RESULTS: 5970 patients met the inclusion criteria and had at least 6 months of follow-up data after FC testing. 1897 had an IBS diagnosis, 208 had an IBD diagnosis, 31 had a colorectal cancer diagnosis, 80 had more than one diagnosis and 3754 had no subsequent diagnosis. Sensitivity, specificity, and positive and negative predictive values were 92.9% (88.6% to 95.6%), 61.5% (60.2% to 62.7%), 8.1% (7.1% to 9.2%) and 99.6% (99.3% to 99.7%), respectively, at the threshold of 50 µg/g. Raising the threshold to 100 µg/g missed less than 7% additional IBD cases. Longer follow-up had no effect on test accuracy. Overall, uncertainty was greater for specificity than sensitivity. General practitioners' (GPs') referral decisions did not follow the anticipated clinical pathways in national guidance. CONCLUSIONS: GPs can be confident in excluding IBD on the basis of a negative FC test in a population with low pretest risk but should interpret a positive test with caution. The applicability of national guidance to general practice needs to be improved.