Prescribing of direct oral anticoagulants and warfarin to older people with atrial fibrillation in UK general practice: a cohort study.

BACKGROUND: Anticoagulation for stroke prevention in atrial fibrillation (AF) has, historically, been under-used in older people. The aim of this study was to investigate prescribing of oral anticoagulants (OACs) for people aged ≥ 75 years in the UK before and after direct oral anticoagulants (DOACs) became available. METHODS: A cohort of patients aged ≥ 75 years with a diagnosis of AF was derived from the Clinical Practice Research Datalink (CPRD) between January 1, 2003, and December 27, 2017. Patients were grouped as no OAC, incident OAC (OAC newly prescribed) or prevalent OAC (entered study on OAC). Incidence and point prevalence of OAC prescribing were calculated yearly. The risk of being prescribed an OAC if a co-morbidity was present was calculated; the risk difference (RD) was reported. Kaplan-Meier curves were used to explore persistence with anticoagulation. A Cox regression was used to model persistence with warfarin and DOACs over time. RESULTS: The cohort comprised 165,596 patients (66,859 no OAC; 47,916 incident OAC; 50,821 prevalent OAC). Incidence of OAC prescribing increased from 111 per 1000 person-years in 2003 to 587 per 1000 person-years in 2017. Older patients (≥ 90 years) were 40% less likely to receive an OAC (RD -0.40, 95% CI -0.41 to -0.39) than younger individuals (75-84 years). The likelihood of being prescribed an OAC was lower with a history of dementia (RD -0.34, 95% CI -0.35 to -0.33), falls (RD -0.17, 95% CI -0.18 to -0.16), major bleeds (RD -0.17, 95% CI -0.19 to -0.15) and fractures (RD -0.13, 95% CI -0.14 to -0.12). Persistence with warfarin was higher than DOACs in the first year (0-1 year: HR 1.25, 95% CI 1.17-1.33), but this trend reversed by the third year of therapy (HR 0.75, 95% CI 0.63-0.89). CONCLUSIONS: OAC prescribing for older people with AF has increased; however, substantial disparities persist with age and co-morbidities. Whilst OACs should not be withheld solely due to the risk of falls, these results do not reflect this national guidance. Furthermore, the under-prescribing of OACs for patients with dementia or advancing age may be due to decisions around risk-benefit management. TRIAL REGISTRATION: EUPAS29923 . First registered on: 27/06/2019.

Risk of Osteoarthritis in an Incident Cohort of People With Psoriatic Arthritis: A Population-based Cohort Study.

OBJECTIVE: To determine the risk of a diagnosis of osteoarthritis (OA) in patients with psoriatic arthritis (PsA) compared to patients with psoriasis and a general population cohort. METHODS: Incident PsA patients aged 18-89 years at diagnosis were identified from the United Kingdom Clinical Practice Research Datalink between 1998 and 2014. All patients with PsA were matched to 2 cohorts of patients, both at a 1:4 ratio. The first cohort included patients with psoriasis (and no PsA) and the second was a general population cohort (with no psoriasis or PsA). The baseline prevalence of OA was calculated for each study cohort. The incidence of OA was calculated, and adjusted relative risks (RRadj) were calculated using conditional Poisson regression. RESULTS: We identified 6783 incident PsA patients. The baseline prevalence of OA ranged from 22.1% (95% CI 21.1-23.1) in the PsA cohort to 12.6% (95% CI 12.2-13.0) and 11.0% (95% CI 10.6-11.3) in the psoriasis and general population cohorts, respectively. The incidence of OA was significantly higher in the PsA cohort compared to the psoriasis and general population cohorts after adjusting for BMI (RRadj 1.68, 95% CI 1.46-1.93, and RRadj 1.86, 95% CI 1.62-2.14, respectively). CONCLUSION: An increased risk of OA was observed in patients with PsA compared to patients with psoriasis alone and those in the general population. Further work is needed to determine whether this reflects a true increase in OA risk or misdiagnosed PsA, and the extent to which it can be explained by differences in the opportunity for OA diagnosis between cohorts.

Epidemiology of systemic sclerosis in the UK: an analysis of the Clinical Practice Research Datalink.

OBJECTIVES: We developed and tested a robust case ascertainment strategy within the Clinical Practice Research Datalink (CPRD), with the aim of assessing the incidence, prevalence, mortality and delay in diagnosis of SSc in the UK. METHODS: A two-stage case ascertainment strategy was devised and tested to establish a valid cohort of SSc cases within the CPRD. Incidence, prevalence and mortality statistics were analysed, alongside evaluation of the relationship between primary care codes for RP and SSc to examine diagnostic delay. RESULTS: SSc Read codes were identified in 3123 patients (from a study cohort of >10.1 million individuals). Of these, 1757 cases of SSc were identified using our case ascertainment approach. The overall incidence rate of SSc over the period between 1999 and 2017 was 10.7/million/year (95% CI: 9.9-11.4), being higher in females [17.69/million/year (95% CI: 16.32-19.07)] than in males [3.59/million/year (95% CI: 2.97-4.21)]. The overall prevalence of SSc in adults was 235.5/million (95% CI: 207.2-245.7). The mean rate of mortality was 32/1000 person-years, with an overall standardized mortality ratio of 3.51 (95% CI: 3.19-3.84). Of those with an initial code of RP prior to a Read code of SSc, 191/854 (22.4%) had a lag period of >10 years. CONCLUSION: We have developed and tested a robust case ascertainment strategy to examine the incidence, prevalence, mortality and diagnostic delay of SSc using primary care records of over 10 million UK residents. A significant lag between coding of RP and SSc in many patients suggests diagnostic delay in SSc remains an important unmet need.

The promise, perceptions, and pitfalls of immunoassays for autoantibody testing in myositis.

BACKGROUND: A myositis-specific autoantibody can now be identified in the majority of patients with myositis. They identify homogeneous patient subgroups and are key tools in developing a personalized approach to disease management. There is substantial clinical interest in exploiting myositis autoantibodies as biomarkers, and consequently, a large number of commercial assays have been developed for their detection. These assays are already in widespread clinical use. In order to better understand perceived concerns from the international myositis community in relation to the reliability of these assays and how they are being used, we conducted a survey of international myositis experts, all of whom were members of the International Myositis Assessment and Clinical Studies group. RESULTS: We collected data on the types of assay used, manufacturers, and the nature of the report provided by different laboratories and received 111 complete responses. Respondents also provided information on how they used the different assays, their confidence in the results, and how this influenced their clinical practice. Enzyme immunoassay/ELISA was the most popular assay method used worldwide followed by line blot. Line blot was the most popular method used in Europe. Despite concerns from over 80% of respondents regarding false-positive and false-negative results with the assay used by their laboratory, over 80% reported that the identification of a myositis autoantibody influenced their diagnostic confidence, the information they provided to a patient, and their recommended treatment. CONCLUSIONS: In spite of ongoing concerns from the majority of users regarding the reliability of the results, myositis-specific autoantibody testing, using commercial immunoassays, is being used globally to inform clinical decision-making. These findings highlight the need for urgent guidance on the use of myositis autoantibody testing and on the interpretation of results. Knowledge of the reliability of currently available assays is essential given the importance already placed on myositis-specific autoantibodies as clinical decision-making tools.

Use of oral anticoagulants in older people with atrial fibrillation in UK general practice: protocol for a cohort study using the Clinical Practice Research Datalink (CPRD) database.

INTRODUCTION: Warfarin has frequently been underused in older people for stroke prevention in atrial fibrillation (AF). Direct oral anticoagulants (DOACs) entered the UK market from 2008 and have been recommended as an alternative to warfarin. This study aimed to describe any changes in the prescribing of oral anticoagulants (OACs) to people aged ≥75 years in UK general practice before and after the introduction of DOACs, to examine differences in patient characteristics which may influence prescribers' decisions regarding anticoagulation, to evaluate the time people stay on OACs and switching between OACs. METHODS AND ANALYSIS: A retrospective cohort study design will be used. Patients with a diagnosis of AF will be identified from the Clinical Practice Research Datalink (CPRD). The study period will run from 1 January 2003 to 27 December 2017. Patients enter the cohort at the latest date of the start of the study period, first AF diagnosis, 75th birthday or a year from when they started to contribute research standard data. Follow-up continues until they leave the practice, death, the date the practice stops contributing research standard data or the end of the study period (27 December 2017). Exposure to OACs will be defined as ≥1 prescription issued for an OAC of interest during the study period. Patients issued an OAC in the year preceding study entry will be defined as 'prevalent users'. Patients starting on an OAC during the study period will be defined as 'incident users'. Incidence and prevalence of OAC prescribing, patient demographics and characteristics will be described during three time periods: 2003-2007, 2008-2012 and 2013-2017. Persistence (defined as the time from initiation to discontinuation of medication) with and switching between different OACs will be described. ETHICS AND DISSEMINATION: The protocol for this study was approved by the CPRD Independent Scientific Advisory Committee. The results will be disseminated in a peer-reviewed journal and at conferences. TRIAL REGISTRATION NUMBER: EUPAS29923.

Prescription of antiepileptic medicines including valproate in pregnant women: A study in three European countries.

PURPOSE: To study patterns of antiepileptic drugs (AED) prescribing, particularly valproate, during pregnancy over a 10-year period in the UK, Italy, and France. METHODS: Data on pregnancies conceived after 1 January 2007 with outcomes before 31 December 2016 were extracted from four European electronic health care databases (380 499 in the United Kingdom (UK), 66 681 in France, and 649 918 in Italy [355 767 in Emilia Romagna and 294 151 in Tuscany]). Prevalence of AEDs with an ATC code starting N03A and clobazam (N05BA09) were stratified by country and calendar year. RESULTS: AED prescribing during pregnancy varied from 3.0 (2.8-3.1) per 1000 pregnancies in Emilia Romagna to 7.8 (7.5-8.0) in the UK, 5.9 (5.6-6.1) in Tuscany, and 6.3 (5.7-6.9) in France. Lamotrigine was commonly prescribed in all regions with a third of women exposed to an AED during pregnancy taking lamotrigine in the UK and France. Valproate was prescribed to 28.6% of AED exposed pregnant women in Tuscany, 21.6% in France, 16.7% in Emilia Romagna, and 11.9% in the UK. Over the study period, the prevalence of AED prescribing increased in the UK mainly due to increases in pregabalin and gabapentin, declined in France mainly related to decreases in clonazepam, and remained constant in Italy. Valproate prescriptions declined to a prevalence <1 per 1000 pregnancies in 2015 to 2016 in the UK, France, and Emilia Romagna. CONCLUSIONS: Variations in AED prescribing during pregnancy indicate the potential for further reductions, particularly of valproate. Increases in pregabalin/gabapentin prescribing, for which risks are not well known, are a cause for concern.

Did advice on the prescription of sodium valproate reduce prescriptions to women? An observational study in three European countries between 2007 and 2016.

OBJECTIVES: In November 2014, the CMDh (a regulatory body representing EU Member States) advised doctors not to prescribe sodium valproate for epilepsy or bipolar disorder in preg nant women, in women who can become pregnant, or in girls unless other treatments are ineffective or not tolerated. This study aimed to determine if this warning led to changes in prescription patterns. DESIGN AND SETTING: Cohort of 5.4 million women aged between 10 and 50 years identified in electronic health care data from United Kingdom, France, and Italy (2007-2016). MAIN OUTCOME MEASURES: Anti-epileptic drug (AED) prescriptions. RESULTS: The prevalence of women receiving AED prescriptions in 2016 varied from 12.2 per 1000 to 29 per 1000 in the four regions. The incidence of prescribing any AED (excluding clonazepam, gabapentin, and pregabalin) fell each year on average by 7.5% (95% CI, 7.0%-8.0%; Emilia Romagna), 9.6% (8.3%-11.0%; France), 7.1% (6.7%-7.6%; Tuscany), and 0.4% (0.2%-1.0%; United Kingdom). The relative odds of prescribing sodium valproate rather than any other AED decreased more after 2014 compared with before the end of 2014 in France (OR = 0.77; 95% CI, 0.60-0.98), Tuscany (0.81; 0.76-0.86), Emilia Romagna (0.83; 0.76-0.90), and the United Kingdom (0.92; 0.80-1.06; not statistically significant). CONCLUSIONS: There is evidence that the CMDh warning did lead to changes in prescription patterns of sodium valproate in women of childbearing age. There were considerable differences in prescribing practice amongst regions of Europe.

Faecal immunochemical tests versus colonoscopy for post-polypectomy surveillance: an accuracy, acceptability and economic study.

BACKGROUND: In the UK, patients with one or two adenomas, of which at least one is ≥ 10 mm in size, or three or four small adenomas, are deemed to be at intermediate risk of colorectal cancer (CRC) and referred for surveillance colonoscopy 3 years post polypectomy. However, colonoscopy is costly, can cause discomfort and carries a small risk of complications. OBJECTIVES: To determine whether or not annual faecal immunochemical tests (FITs) are effective, acceptable and cost saving compared with colonoscopy surveillance for detecting CRC and advanced adenomas (AAs). DESIGN: Diagnostic accuracy study with health psychology assessment and economic evaluation. SETTING: Participants were recruited from 30 January 2012 to 30 December 2013 within the Bowel Cancer Screening Programme in England. PARTICIPANTS: Men and women, aged 60-72 years, deemed to be at intermediate risk of CRC following adenoma removal after a positive guaiac faecal occult blood test were invited to participate. Invitees who consented and returned an analysable FIT were included. INTERVENTION: We offered participants quantitative FITs at 1, 2 and 3 years post polypectomy. Participants testing positive with any FIT were referred for colonoscopy and not offered further FITs. Participants testing negative were offered colonoscopy at 3 years post polypectomy. Acceptibility of FIT was assessed using discussion groups, questionnaires and interviews. MAIN OUTCOME MEASURES: The primary outcome was 3-year sensitivity of an annual FIT versus colonoscopy at 3 years for detecting advanced colorectal neoplasia (ACN) (CRC and/or AA). Secondary outcomes included participants' surveillance preferences, and the incremental costs and cost-effectiveness of FIT versus colonoscopy surveillance. RESULTS: Of 8008 invitees, 5946 (74.3%) consented and returned a round 1 FIT. FIT uptake in rounds 2 and 3 was 97.2% and 96.9%, respectively. With a threshold of 40 µg of haemoglobin (Hb)/g faeces (hereafter referred to as µg/g), positivity was 5.8% in round 1, declining to 4.1% in round 3. Over three rounds, 69.2% (18/26) of participants with CRC, 34.3% (152/443) with AAs and 35.6% (165/463) with ACN tested positive at 40 µg/g. Sensitivity for CRC and AAs increased, whereas specificity decreased, with lower thresholds and multiple rounds. At 40 µg/g, sensitivity and specificity of the first FIT for CRC were 30.8% and 93.9%, respectively. The programme sensitivity and specificity of three rounds at 10 µg/g were 84.6% and 70.8%, respectively. Participants' preferred surveillance strategy was 3-yearly colonoscopy plus annual FITs (57.9%), followed by annual FITs with colonoscopy in positive cases (31.5%). FIT with colonoscopy in positive cases was cheaper than 3-yearly colonoscopy (£2,633,382), varying from £485,236 (40 µg/g) to £956,602 (10 µg/g). Over 3 years, FIT surveillance could miss 291 AAs and eight CRCs using a threshold of 40 µg/g, or 189 AAs and four CRCs using a threshold of 10 µg/g. CONCLUSIONS: Annual low-threshold FIT with colonoscopy in positive cases achieved high sensitivity for CRC and would be cost saving compared with 3-yearly colonoscopy. However, at higher thresholds, this strategy could miss 15-30% of CRCs and 40-70% of AAs. Most participants preferred annual FITs plus 3-yearly colonoscopy. Further research is needed to define a clear role for FITs in surveillance. FUTURE WORK: Evaluate the impact of ACN missed by FITs on quality-adjusted life-years. TRIAL REGISTRATION: Current Controlled Trials ISRCTN18040196. FUNDING: National Institute for Health Research (NIHR) Health Technology Assessment programme, NIHR Imperial Biomedical Research Centre and the Bobby Moore Fund for Cancer Research UK. MAST Group Ltd provided FIT kits.

Faecal immunochemical tests (FIT) versus colonoscopy for surveillance after screening and polypectomy: a diagnostic accuracy and cost-effectiveness study.

OBJECTIVE: The English Bowel Cancer Screening Programme (BCSP) recommends 3 yearly colonoscopy surveillance for patients at intermediate risk of colorectal cancer (CRC) postpolypectomy (those with three to four small adenomas or one ≥10 mm). We investigated whether faecal immunochemical tests (FITs) could reduce surveillance burden on patients and endoscopy services. DESIGN: Intermediate-risk patients (60-72 years) recommended 3 yearly surveillance were recruited within the BCSP (January 2012-December 2013). FITs were offered at 1, 2 and 3 years postpolypectomy. Invitees consenting and returning a year 1 FIT were included. Participants testing positive (haemoglobin ≥40 µg/g) at years one or two were offered colonoscopy early; all others were offered colonoscopy at 3 years. Diagnostic accuracy for CRC and advanced adenomas (AAs) was estimated considering multiple tests and thresholds. We calculated incremental costs per additional AA and CRC detected by colonoscopy versus FIT surveillance. RESULTS: 74% (5938/8009) of invitees were included in our study having participated at year 1. Of these, 97% returned FITs at years 2 and 3. Three-year cumulative positivity was 13% at the 40 µg/g haemoglobin threshold and 29% at 10 µg/g. 29 participants were diagnosed with CRC and 446 with AAs. Three-year programme sensitivities for CRC and AAs were, respectively, 59% and 33% at 40 µg/g, and 72% and 57% at 10 µg/g. Incremental costs per additional AA and CRC detected by colonoscopy versus FIT (40 µg/g) surveillance were £7354 and £180 778, respectively. CONCLUSIONS: Replacing 3 yearly colonoscopy surveillance in intermediate-risk patients with annual FIT could reduce colonoscopies by 71%, significantly cut costs but could miss 30%-40% of CRCs and 40%-70% of AAs. TRIAL REGISTRATION NUMBER: ISRCTN18040196; Results.

Risk of type 2 diabetes and cardiovascular disease in an incident cohort of people with psoriatic arthritis: a population-based cohort study.

Objectives: To determine the risk of type 2 diabetes (T2D) and cardiovascular diseases in PsA patients compared with the general population and patients with psoriasis. Methods: Incident PsA patients aged 18-89 years were identified in the UK Clinical Practice Research Datalink between 1998 and 2014 and were matched (1:4 ratio) to a general population cohort and psoriasis cohort. The incidence of T2D, cerebrovascular disease, ischaemic heart disease and peripheral vascular disease (PVD) was calculated for each study cohort. Conditional Poisson regression was used to calculate adjusted relative risks. Results: We identified 6783 incident cases of PsA. The risk of T2D was significantly higher in the PsA cohort than in the general population and the psoriasis cohorts [adjusted relative risk 1.40 (CI95 1.15, 1.70) and adjusted relative risk 1.53 (CI95 1.19, 1.97), respectively]. The incidence of ischaemic heart disease, peripheral vascular disease and the three cardiovascular outcomes combined in the PsA cohort was significantly higher than in the general population. No significant differences in risk were observed between the PsA and psoriasis cohorts for any cardiovascular outcome. Conclusion: The development of T2D in an incident population of PsA is significantly higher than in psoriasis alone or in a general population, whereas the increased risk of cardiovascular disease in PsA and psoriasis is similar.

Risk of uveitis and inflammatory bowel disease in people with psoriatic arthritis: a population-based cohort study.

OBJECTIVES: To determine the risk of uveitis and inflammatory bowel disease (IBD) in patients with psoriatic arthritis (PsA) compared with the general population and patients with psoriasis. METHODS: A cohort study using data from the UK Clinical Practice Research Datalink between 1998 and 2014. Patients with incident PsA aged 18-89 years were identified and matched to a cohort of patients with psoriasis and a general population cohort. The incidence of uveitis, all IBD, Crohn's disease and ulcerative colitis was calculated for each study cohort and adjusted relative risks (RRadj) were calculated using conditional Poisson regression. RESULTS: 6783 incident cases of PsA were identified with a median age of 49 years. The risk of uveitis was significantly higher in the PsA cohort than in the general population and psoriasis cohorts (RRadj 3.55, 95% CI 2.21 to 5.70 and RRadj 2.13, 95% CI 1.40 to 3.24, respectively). A significant increase was observed for Crohn's disease (RRadj 2.96, 95% CI 1.46 to 6.00 and RRadj3.60, 95% CI 1.83 to 7.10) but not for ulcerative colitis (RRadj1.30, 95% CI 0.66 to 2.56 and RRadj0.98, 95% CI 0.50 to 1.92). CONCLUSIONS: In a primary care-based incidence cohort of patients with PsA, there were substantial risks of developing uveitis and/or Crohn's disease, but not ulcerative colitis, when compared with the general population and psoriasis controls.

Interval between onset of psoriasis and psoriatic arthritis comparing the UK Clinical Practice Research Datalink with a hospital-based cohort.

Objectives: To describe the time interval between the onset of psoriasis and PsA in the UK primary care setting and compare with a large, well-classified secondary care cohort. Methods: Patients with PsA and/or psoriasis were identified in the UK Clinical Practice Research Datalink (CPRD). The secondary care cohort comprised patients from the Bath PsA longitudinal observational cohort study. For incident PsA patients in the CPRD who also had a record of psoriasis, the time interval between PsA diagnosis and first psoriasis record was calculated. Comparisons were made with the time interval between diagnoses in the Bath cohort. Results: There were 5272 eligible PsA patients in the CPRD and 815 in the Bath cohort. In both cohorts, the majority of patients (82.3 and 61.3%, respectively) had psoriasis before their PsA diagnosis or within the same calendar year (10.5 and 23.8%), with only a minority receiving their PsA diagnosis first (7.1 and 14.8%). Excluding those who presented with arthritis before psoriasis, the median time between diagnoses was 8 years [interquartile range (IQR) 2-15] in the CPRD and 7 years (IQR 0-20) in the Bath cohort. In the CPRD, 60.1 and 75.1% received their PsA diagnosis within 10 and 15 years of their psoriasis diagnosis, respectively; this was comparable with 57.2 and 67.7% in the Bath cohort. Conclusion: A similar distribution for the time interval between psoriasis and arthritis was observed in the CPRD and secondary care cohort. These data can inform screening strategies and support the validity of data from each cohort.

Reducing the socioeconomic gradient in uptake of the NHS bowel cancer screening Programme using a simplified supplementary information leaflet: a cluster-randomised trial.

BACKGROUND: Uptake of colorectal cancer screening is low in the English NHS Bowel Cancer Screening Programme (BCSP). Participation in screening is strongly associated with socioeconomic status. The aim of this study was to determine whether a supplementary leaflet providing the 'gist' of guaiac-based Faecal Occult Blood test (gFOBt) screening for colorectal cancer could reduce the socioeconomic status (SES) gradient in uptake in the English NHS BCSP. METHODS: The trial was integrated within routine BCSP operations in November 2012. Using a cluster randomised controlled design all adults aged 59-74 years who were being routinely invited to complete the gFOBt were randomised based on day of invitation. The Index of Multiple Deprivation was used to create SES quintiles. The control group received the standard information booklet ('SI'). The intervention group received the SI booklet and the Gist leaflet ('SI + Gist') which had been designed to help people with lower literacy engage with the invitation. Blinding of hubs was not possible and invited subjects were not made aware of a comparator condition. The primary outcome was the gradient in uptake across IMD quintiles. RESULTS: In November 2012, 163,525 individuals were allocated to either the 'SI' intervention (n = 79,104) or the 'SI + Gist' group (n = 84,421). Overall uptake was similar between the intervention and control groups (SI: 57.3% and SI + Gist: 57.6%; OR = 1.02, 95% CI: 0.92-1.13, p = 0.77). Uptake was 42.0% (SI) vs. 43.0% (SI + Gist) in the most deprived quintile and 65.6% vs. 65.8% in the least deprived quintile (interaction p = 0.48). The SES gradient in uptake was similar between the study groups within age, gender, hub and screening round sub-groups. CONCLUSIONS: Providing supplementary simplified information in addition to the standard information booklet did not reduce the SES gradient in uptake in the NHS BCSP. The effectiveness of the Gist leaflet when used alone should be explored in future research. TRIAL REGISTRATION: ISRCTN74121020 , registered: 17/20/2012.

Statins during pregnancy: a cohort study using the General Practice Research Database to investigate pregnancy loss.

PURPOSE: The aim of this study was to determine if there are any differences between the types of pregnancy loss experienced by women who have been prescribed a statin just before or early in pregnancy compared with those who have not. METHODS: A retrospective cohort study using the General Practice Research Database was carried out. Women aged 10-49 years at pregnancy start who received a prescription for a statin in the 3 months before and/or during the first trimester of pregnancy were matched to up to 10 pregnancies on age at start date, diabetes and hypertension status before pregnancy. Pregnancies occurring between 1/1/1992 and 31/3/2009 were included. Pregnancy losses were identified and categorised as spontaneous (including miscarriage), induced for medical, other or unknown reasons. Freetext was used to determine the type of loss where this was not clear from the coded medical records. RESULTS: Two hundred eighty-one pregnancies potentially exposed to statins were identified and matched to 2643 unexposed pregnancies. About 54.45% of pregnancies potentially exposed to a statin resulted in a delivery compared with 62.81% of those not exposed. 25.27% of all pregnancies potentially exposed to a statin resulted in a spontaneous loss compared with 20.81% in those not exposed. Using a time to event analysis with exposure as a time-dependent covariate gave an adjusted hazards ratio of 1.64 (95%CI 1.10 to 2.46) of spontaneous pregnancy loss in the statin exposed group. CONCLUSIONS: This study is the first to report the differences in types of pregnancy loss following the potential exposure to a statin just before or early in pregnancy. Copyright © 2017 John Wiley & Sons, Ltd.

Increased uptake and improved outcomes of bowel cancer screening with a faecal immunochemical test: results from a pilot study within the national screening programme in England.

BACKGROUND: The National Health Service Bowel Cancer Screening Programme (BCSP) in England uses a guaiac-based faecal occult blood test (gFOBt). A quantitative faecal immunochemical test (FIT) for haemoglobin (Hb) has many advantages, including being specific for human blood, detecting Hb at a much lower concentration with a single faecal sample and improved uptake. METHODS: In 2014, a large comparative pilot study was performed within BCSP to establish the acceptability and diagnostic performance of FIT. Over a 6-month period, 40 930 (1 in 28) subjects were sent a FIT (OC-SENSOR) instead of a gFOBt. A bespoke FIT package was used to mail FIT sampling devices to and from FIT subjects. All participants positive with either gFOBt or FIT (cut-off 20 µg Hb/g faeces) were referred for follow-up. Subgroup analysis included cut-off concentrations, age, sex, screening history and deprivation quintile. RESULTS: While overall uptake increased by over 7 percentage points with FIT (66.4% vs 59.3%, OR 1.35, 95% CI 1.33 to 1.38), uptake by previous non-responders almost doubled (FIT 23.9% vs gFOBt 12.5%, OR 2.20, 95% CI 2.10 to 2.29). The increase in overall uptake was significantly higher in men than women and was observed across all deprivation quintiles. With the conventional 20 µg/g cut-off, FIT positivity was 7.8% and ranged from 5.7% in 59-64-year-old women to 11.1% in 70-75-year-old men. Cancer detection increased twofold and that for advanced adenomas nearly fivefold. Detection rates remained higher with FIT for advanced adenomas, even at 180 µg Hb/g. CONCLUSIONS: Markedly improved participation rates were achieved in a mature gFOBt-based national screening programme and disparities between men and women were reduced. High positivity rates, particularly in men and previous non-respondents, challenge the available colonoscopy resource, but improvements in neoplasia detection are still achievable within this limited resource.

A national cluster-randomised controlled trial to examine the effect of enhanced reminders on the socioeconomic gradient in uptake in bowel cancer screening.

BACKGROUND: The NHS Bowel Cancer Screening Programme in England offers biennial guaiac faecal occult blood testing (gFOBt). There is a socioeconomic gradient in participation and socioeconomically disadvantaged groups have worse colorectal cancer survival than more advantaged groups. We compared the effectiveness and cost of an enhanced reminder letter with the usual reminder letter on overall uptake of gFOBt and the socioeconomic gradient in uptake. METHODS: We enhanced the usual reminder by including a heading 'A reminder to you' and a short paragraph restating the offer of screening in simple language. We undertook a cluster-randomised trial of all 168 480 individuals who were due to receive a reminder over 20 days in 2013. Randomisation was based on the day of invitation. Blinding of individuals was not possible, but the possibility of bias was minimal owing to the lack of direct contact with participants. The enhanced reminder was sent to 78 067 individuals and 90 413 received the usual reminder. The primary outcome was the proportion of people adequately screened and its variation by quintile of Index of Multiple Deprivation. Data were analysed by logistic regression with conservative variance estimates to take account of cluster randomisation. RESULTS: There was a small but statistically significant (P=0.001) increase in participation with the enhanced reminder (25.8% vs 25.1%). There was significant (P=0.005) heterogeneity of the effect by socioeconomic status with an 11% increase in the odds of participation in the most deprived quintile (from 13.3 to 14.1%) and no increase in the least deprived. We estimated that implementing the enhanced reminder nationally could result in up to 80 more people with high or intermediate risk colorectal adenomas and up to 30 more cancers detected each year if it were implemented nationally. The intervention incurred a small one-off cost of £78 000 to modify the reminder letter. CONCLUSIONS: The enhanced reminder increases overall uptake and reduces the socioeconomic gradient in bowel cancer screening participation at little additional cost.

Reducing the Social Gradient in Uptake of the NHS Colorectal Cancer Screening Programme Using a Narrative-Based Information Leaflet: A Cluster-Randomised Trial.

Objective. To test the effectiveness of adding a narrative leaflet to the current information material delivered by the NHS English colorectal cancer (CRC) screening programme on reducing socioeconomic inequalities in uptake. Participants. 150,417 adults (59-74 years) routinely invited to complete the guaiac Faecal Occult Blood test (gFOBt) in March 2013. Design. A cluster randomised controlled trial (ISRCTN74121020) to compare uptake between two arms. The control arm received the standard NHS CRC screening information material (SI) and the intervention arm received the standard information plus a supplementary narrative leaflet, which had previously been shown to increase screening intentions (SI + N). Between group comparisons were made for uptake overall and across socioeconomic status (SES). Results. Uptake was 57.7% and did not differ significantly between the two trial arms (SI: 58.5%; SI + N: 56.7%; odds ratio = 0.93; 95% confidence interval: 0.81-1.06; p = 0.27). There was no interaction between group and SES quintile (p = 0.44). Conclusions. Adding a narrative leaflet to existing information materials does not reduce the SES gradient in uptake. Despite the benefits of using a pragmatic trial design, the need to add to, rather than replace, existing information may have limited the true value of an evidence-based intervention on behaviour.

Impact of general practice endorsement on the social gradient in uptake in bowel cancer screening.

BACKGROUND: There is a socioeconomic gradient in the uptake of screening in the English NHS Bowel Cancer Screening Programme (BCSP), potentially leading to inequalities in outcomes. We tested whether endorsement of bowel cancer screening by an individual's general practice (GP endorsement; GPE) reduced this gradient. METHODS: A cluster-randomised controlled trial. Over 20 days, individuals eligible for screening in England from 6480 participating general practices were randomly allocated to receive a GP-endorsed or the standard invitation letter. The primary outcome was the proportion of people adequately screened and its variation by quintile of Index of Multiple Deprivation. RESULTS: We enrolled 265,434 individuals. Uptake was 58.2% in the intervention arm and 57.5% in the control arm. After adjusting for age, sex, hub and screening episode, GPE increased the overall odds of uptake (OR=1.07, 95% CI 1.04-1.10), but did not affect its socioeconomic gradient. We estimated that implementing GPE could result in up to 165 more people with high or intermediate risk colorectal adenomas and 61 cancers detected, and a small one-off cost to modify the standard invitation (£78,000). CONCLUSIONS: Although GPE did not improve its socioeconomic gradient, it offers a low-cost approach to enhancing overall screening uptake within the NHS BCSP.

Factors associated with completion of bowel cancer screening and the potential effects of simplifying the screening test algorithm.

BACKGROUND: The primary colorectal cancer screening test in England is a guaiac faecal occult blood test (gFOBt). The NHS Bowel Cancer Screening Programme (BCSP) interprets tests on six samples on up to three test kits to determine a definitive positive or negative result. However, the test algorithm fails to achieve a definitive result for a significant number of participants because they do not comply with the programme requirements. This study identifies factors associated with failed compliance and modifications to the screening algorithm that will improve the clinical effectiveness of the screening programme. METHODS: The BCSP Southern Hub data for screening episodes started in 2006-2012 were analysed for participants aged 60-69 years. The variables included age, sex, level of deprivation, gFOBt results and clinical outcome. RESULTS: The data set included 1,409,335 screening episodes; 95.08% of participants had a definitively normal result on kit 1 (no positive spots). Among participants asked to complete a second or third gFOBt, 5.10% and 4.65%, respectively, failed to return a valid kit. Among participants referred for follow up, 13.80% did not comply. Older age was associated with compliance at repeat testing, but non-compliance at follow up. Increasing levels of deprivation were associated with non-compliance at repeat testing and follow up. Modelling a reduction in the threshold for immediate referral led to a small increase in completion of the screening pathway. CONCLUSIONS: Reducing the number of positive spots required on the first gFOBt kit for referral for follow-up and targeted measures to improve compliance with follow-up may improve completion of the screening pathway.