Higher Risk of Ischemic Stroke After an Intracerebral Hemorrhage Than in General Population: A Cohort Study From the United Kingdom.

[Figure: see text].

Trends in the use of oral anticoagulants, antiplatelets and statins in four European countries: a population-based study.

PURPOSE: To evaluate time trends in the prevalence of antithrombotic and statin use in four European countries. METHODS: Using population-based data from the United Kingdom, Denmark, Spain and Italy between 2010 and 2018, we calculated standardized annual prevalence proportions of antithrombotics and statin use, and changes in prevalence proportions (2018 vs. 2010). RESULTS: Prevalence proportion of statins increased from 24.8% to 24.6% (UK), 21.0% to 22.3% (Region of Southern Denmark [RSD]), 12.9% to 14.3% (Udine, Italy), and 20.3% to 23.2% (Spain). Prevalence proportions of antithrombotics declined in all four countries: 18.7% to 15.9% (UK; - 2.8% points), 18.9% to 18.1% (RSD; - 0.8% points), 17.7% to 16.6% (Udine; - 1.1% points) and 15.0% to 13.6% (Spain; - 1.4% points). These declines were driven by reductions in low-dose aspirin use: 15.3% to 8.9% (UK; - 6.4% points), 16.3% to 9.5% (RSD; - 6.8% points), 13.5% to 11.6% (Udine; - 1.9% points), and 10.2% to 8.8% (Spain; - 1.4% points). In the UK, low-dose aspirin use declined from 9.1% to 4.3% (- 4.8% points) for primary CVD prevention, and from 49.6% to 36.9% (- 12.7% points) for secondary prevention. Oral anticoagulant use gradually increased but did not fully account for the decrease in low-dose aspirin use. CONCLUSIONS: Antithrombotic use in the UK, RSD, Udine and Spain declined between 2010 and 2018, driven by a reduction in use of low-dose aspirin that is not completely explained by a gradual increase in OAC use. Use of statins remained constant in the UK, and increased gradually in the RSD, Udine and Spain.

Pre- and post-stroke oral antithrombotics and mortality in patients with ischaemic stroke.

BACKGROUND: Reducing stroke occurrence requires the effective management of cardiovascular and other stroke risk factors. PURPOSE: To describe pre- and post-stroke medication use, focusing on antithrombotic therapy and mortality risk, in individuals hospitalised for ischaemic stroke (IS) in the United Kingdom. METHOD: Using primary care electronic health records from the United Kingdom, we identified patients hospitalised for IS (July 2016-September 2019) and classed them into three groups: atrial fibrillation (AF) diagnosed pre-stroke, AF diagnosed post-stroke, and non-AF stroke (no AF diagnosed pre-/post-stroke). We determined use of cardiovascular medications in the 90 days pre- and post-stroke and calculated mortality rates. RESULTS: There were 3201 hospitalised IS cases: 76.2% non-AF stroke, 15.7% AF pre-stroke, and 8.1% AF post-stroke. Oral anticoagulant (OAC) use increased between the pre- and post-stroke periods as follows: 54.3%-78.7% (AF pre-stroke group), 2.3%-84.8% (AF post-stroke group), and 3.4%-7.3% (non-AF stroke group). Corresponding increases in antiplatelet use were 30.8%-35.4% (AF pre-stroke group) 38.5%-47.5% (AF post-stroke group), and 37.5%-87.3% (non-AF stroke group). Among all IS cases, antihypertensive use increased from 66.8% pre-stroke to 78.8% post-stroke; statin use increased from 49.6%-85.2%. Mortality rates per 100 person-years (95% CI) were 17.30 (14.70-20.35) in the AF pre-stroke group and 9.65 (8.81-10.56) among all other stroke cases. CONCLUSION: Our findings identify areas for improvement in clinical practice, including optimising the level of OAC prescribing to patients with known AF, which could potentially help reduce the future burden of stroke.

Validation of venous thromboembolism diagnoses in patients receiving rivaroxaban or warfarin in The Health Improvement Network.

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.

Use of non-vitamin K antagonist oral anticoagulants in Colombia: A descriptive study using a national administrative healthcare database.

PURPOSE: We aimed to describe time-trends in the use of NOACs among a group of ambulatory patients with nonvalvular atrial fibrillation (NVAF) in Colombia and to describe treatment patterns and user characteristics. METHODS: Using the Audifarma S.A administrative healthcare database in Colombia, we identified 10 528 patients with NVAF aged at least 18 years between July 2009 and June 2017 with a first prescription (index date) for apixaban, dabigatran or rivaroxaban (index NOAC) and followed them for at least year (max, 8.0 years, mean 2.2 years). We described patient characteristics, NOAC use over time, and the dose of the first NOAC prescription. RESULTS: A total of 2153 (20.5%) patients started on apixaban, 3089 (29.3%) on dabigatran and 5286 (50.2%) on rivaroxaban. The incidence of new users of apixaban and rivaroxaban increased over study years while for dabigatran it decreased. Mean age at the index date was: 78.5 years (apixaban), 76.5 years (dabigatran), 76.0 years (rivaroxaban). The percentage of patients started NOAC therapy on the standard dose was: apixaban 38.0%, dabigatran 30.9%, rivaroxaban 56.9%. The percentage still prescribed their index NOAC at 6 months was apixaban 44.6%, dabigatran 51.4%, rivaroxaban 52.7%. Hypertension was the most common comorbidity (>80% in each NOAC cohort). CONCLUSION: During the last decade, the incidence of NOAC use in patients with NVAF affiliated with a private healthcare regime in Colombia has markedly increased. Future studies should evaluate whether the large number of patients with NVAF starting NOAC treatment on a reduced dose are done so appropriately.

Low-dose aspirin and risk of gastric and oesophageal cancer: A population-based study in the United Kingdom using The Health Improvement Network.

There is increasing interest regarding potential protective effects of low-dose aspirin against various gastrointestinal cancers. We aimed to quantify the association between use of low-dose aspirin and risk of gastric/oesophageal cancer using a population-based primary care database in the UK. Between January 2005 and December 2015, we identified a cohort of 223 640 new users of low-dose aspirin (75-300 mg/day) and a matched cohort of nonusers at the start of follow-up from The Health Improvement Network. Cohorts were followed to identify incident cases of gastric/oesophageal cancer. Nested case-control analyses were conducted and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for current vs nonuse of low-dose aspirin using logistic regression. Current use was defined as when low-dose aspirin lasted 0 to 90 days before the index date (event date for cases, random date for controls) and previous duration was ≥1 year. We identified 727 incident cases of gastric cancer and 1394 incident cases of oesophageal cancer. ORs (95% CIs) were 0.46 (0.38-0.57) for gastric cancer and 0.59 (0.51-0.69) for oesophageal cancer. The effect remained consistent with no clear change seen between previous duration of low-dose aspirin use of 1-3, 3-5 or >5 years. The reduced risks was seen with 75 mg/day, and effects were consistent in lag-time analyses. In conclusion, our results indicate that use of low-dose aspirin is associated with a 54% reduced risk of gastric cancer and a 41% reduced risk of oesophageal cancer as supported by mechanistic data.

Ethoscopes: An open platform for high-throughput ethomics.

Here, we present the use of ethoscopes, which are machines for high-throughput analysis of behavior in Drosophila and other animals. Ethoscopes provide a software and hardware solution that is reproducible and easily scalable. They perform, in real-time, tracking and profiling of behavior by using a supervised machine learning algorithm, are able to deliver behaviorally triggered stimuli to flies in a feedback-loop mode, and are highly customizable and open source. Ethoscopes can be built easily by using 3D printing technology and rely on Raspberry Pi microcomputers and Arduino boards to provide affordable and flexible hardware. All software and construction specifications are available at http://lab.gilest.ro/ethoscope.

No association between use of phosphodiesterase 5 inhibitors and colorectal cancer in men with erectile dysfunction.

PURPOSE: There is an increase interest on the potential chemoprotective effect of selective phosphodiesterase 5 (PDE5) inhibitors. Several authors have shown in vivo the immune-mediated anti-tumor effect of these inhibitors on tumors arising from the digestive tract. OBJECTIVES: To test the potential effect of selective PDE5 inhibitors against colorectal cancer (CRC) onset previously observed. METHODS: We used data from The Health Improvement Network database and identified an established cohort of 200 000 new users of low-dose aspirin and a matched comparison cohort aged 40-84 years between 1 January 2000 and 31 December 2011. A follow-up to identify CRC cases was performed within an extensive validation exercise. Nested case-control analyses compared PDE5 inhibitors vs non-use on CRC risk were performed. RESULTS: Restricting to males (59.3% controls and 59.5% cases), no association was observed among current users of PDE5 inhibitors (1.05 [95% CI: 0.69-1.60]) and neither among recent (1.36 [95% CI: 0.81-2.28]) or past users (1.06 [95% CI: 0.72-1.58]). No duration response effect was found. CONCLUSIONS: Our results do not support an increased risk of CRC associated with the use of PDE5 inhibitors among men with erectile dysfunction.

Feasibility study to identify women of childbearing age at risk of pregnancy not using any contraception in The Health Improvement Network (THIN) database.

BACKGROUND: Worldwide the rate of unplanned pregnancies is more than 40%. Identifying women at risk of pregnancy can help prevent negative outcomes and also reduce healthcare costs of potential complications. It can also allow the investigation of the natural history of pregnancy outcomes, such as ectopic pregnancies or miscarriages. The use of medical records databases has been a crucial development in the field of pharmacoepidemiology - e.g. The Health Improvement Network (THIN) database is a validated database representative of the UK population. This project aimed to test the feasibility of identifying a population of women of childbearing age who are at risk of pregnancy not using any contraception in THIN database. METHODS: First a cohort of women of childbearing age (15-45yo) was identified. By applying a computer-based algorithm, containing codes for contraception methods or other suggestion of contraception, the risk of pregnancy was then ascertained. Next, two validation steps were implemented: 1) Revision of medical records/free text and 2) Questionnaires were sent to primary care practitioners (PCP) of women whose medical records had been reviewed. Positive predicted values (PPV) were calculated. RESULTS: A total of 266,433 women were identified in THIN. For the first validation step, 123 records were reviewed, with a PPV of 99.2% (95%CI: 95.5-99.9). For the questionnaires step, the PPV was of 82.3% (95%CI: 70-91.1). Information on sexual behaviour and attitudes towards conception was not captured by THIN. CONCLUSION: This study shows that by applying a comprehensive computer-based algorithm, THIN can be used to identify women at risk of pregnancy.

Clopidogrel and Low-Dose Aspirin, Alone or Together, Reduce Risk of Colorectal Cancer.

BACKGROUND & AIMS: The antiplatelet effect of low-dose aspirin, via inhibition of cyclooxygenase-1, might contribute to its ability to reduce the risk of colorectal cancer (CRC). Antiplatelet agents with a different mechanism, such as clopidogrel, might have the same effects. We aimed to quantify the effects of low-dose aspirin and clopidogrel on the risk of CRC in a Mediterranean population. METHODS: We performed a nested case-control study using a primary care database (Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria) in Spain. We collected data, from 2001 through 2014, on 15,491 incident cases of CRC and 60,000 randomly selected individuals (controls), frequency-matched to cases by age, sex, and year. To estimate the association between exposure to different antiplatelet agents and the risk of colorectal cancer, we built multiple logistic regression models and computed the adjusted-odds ratios (AORs) and their respective 95% CIs. RESULTS: Use of low-dose aspirin was associated with a reduced risk of CRC overall (AOR, 0.83; 95% CI, 0.78-0.89) and in patients receiving treatment for more than 1 year (AOR, 0.79; 95% CI, 0.73-0.85). Use of clopidogrel was associated with a decreased risk of CRC overall (AOR, 0.8; 95% CI, 0.69-0.93) and in patients receiving treatment for more than 1 year (AOR, 0.65; 95% CI, 0.55-0.78). Dual antiplatelet therapy had the same effect as either drug taken as monotherapy. No modification by sex or age was observed. CONCLUSIONS: In a nested case-control study of a primary care database in Spain, we found clopidogrel use, alone or in combination with low-dose aspirin, to reduce the risk of CRC by 20% to 30%, a magnitude similar to that of low-dose aspirin alone. These data support the concept that inhibiting platelets is an effective strategy for prevention of CRC.

Incidence of Upper and Lower Gastrointestinal Bleeding in New Users of Low-Dose Aspirin.

BACKGROUND & AIMS: There are few data on the incidence of upper and lower gastrointestinal bleeding (UGIB and LGIB) from observational studies of low-dose aspirin users. We aimed to estimate incidence rates of UGIB and LGIB in a large cohort of new users of low-dose aspirin in the United Kingdom, with subanalyses of hospitalization status and fatalities. METHODS: We performed a population-based study of 199,079 new users of low-dose aspirin (median age, 64.0 years) identified from the Health Improvement Network primary care database (2000-2012). Individuals were followed for a median 5.4 years (maximum, 14 years) to identify new cases of UGIB and LGIB. Following multistep validation, we calculated overall and age- and sex-specific incidence rates; we performed subanalyses for health care use and death within 30 days of GIB. We also estimated rates within a matched (1:1) cohort of nonusers of low-dose aspirin at the start of the follow-up period. RESULTS: The low-dose aspirin users had 1115 UGIB events and 1936 LGIB events; most subjects with UGIB events (58.9%) were hospitalized, whereas most subjects with LGIB events were referred to secondary care (72.8%). Crude incidence rates of GIB per 1000 person-years were 0.97 for subjects with UGIB (95% CI, 0.91-1.02) and 1.68 for subjects with LGIB (95% CI, 1.60-1.75). Incidence rates per 1000 person-years for patients hospitalized for GIB were 0.57 for UGIB (95% CI, 0.53-0.61) and 0.45 for LGIB (95% CI, 0.42-0.49); for referred (but not hospitalized) cases, these values were 0.39 for UGIB (95% CI, 0.36-0.43) and 1.22 for LGIB (1.16-1.29). Incidence rates per 1000 person-years were 0.06 for fatal UGIB (95% CI, 0.04-0.07), 0.01 for fatal LGIB (95% CI, 0.01-0.02), 0.91 for nonfatal UGIB (95% CI, 0.86-0.97), and 1.66 for nonfatal LGIB (95% CI, 1.59-1.74). Among nonusers of low-dose aspirin, incidence rates per 1000 person-years were 0.67 (95% CI, 0.63-0.75) for UGIB and 0.76 (95% CI, 0.72-0.82) for LGIB. CONCLUSION: In a population-based study of low-dose aspirin users, the incidence of LGIB was higher than the incidence of UGIB. However, incidence rates of hospitalized GI bleeds and 30-day mortality rates were lower for LGIB than for UGIB. These estimates are valuable for benefit-risk assessments of low-dose aspirin for cardiovascular and colorectal cancer prevention.

Feasibility and validity of The Health Improvement Network database of primary care electronic health records to identify and characterise patients with small cell lung cancer in the United Kingdom.

BACKGROUND: Epidemiological research on small cell lung cancer (SCLC) is limited and based on cancer registry data. We evaluated the feasibility and validity of using primary care electronic health records (The Health Improvement Network [THIN]) in the UK to identify and characterise SCLC. METHODS: We searched THIN records of individuals aged 18-89 years between 2000 and 2014 for a first diagnostic code suggestive of lung cancer (group 1) or small cell cancer (SCC; group 2) and for text strings among free text comments to identify and characterise incident SCLC cases. We validated our case identification strategy by manual review of patient EHRs, including free text comments, for a random sample of 400 individuals initially detected with a diagnostic code (300 from group 1 and 100 from group 2). RESULTS: Twenty five thousand two hundred fourty one individuals had a code for lung cancer (n = 24,508 [97.1%]) or SCC (733 [2.9%]). Following free-text searches, there were 3530 incident SCLC cases (2956 from group 1; 574 from group 2) corresponding to an incidence rate of 1.01 per 10,000 person-years. In the validation exercise, SCLC confirmation rates were 99% (group 1) and 85% (group 2). Mean age at diagnosis among confirmed cases was 68.5 years; staging information was present in 63.5% of cases of whom 17.8% had limited disease and 82.2% had extensive disease. The majority (84.5%) had a recorded symptom suggestive of lung cancer; chest infection was the most common (18%) followed by cough (15.8%) and chest/abdominal/back pain (15.2%). The first year crude mortality rates was 9.9 per 100 person-months (95% confidence interval [CI] 9.5-10.4), was higher among men and those aged 80 years and above. A total of 144 (37.8%) confirmed cases had metastases recorded. Median survival among the whole study cohort was 7.37 months. CONCLUSIONS: Our SCLC case identification method appears to be valid and could potentially be adapted to identify other cancer types. However, complete characterisation of staging requires information from additional data sources including cancer registries.

Ascertainment and validation of major bleeding events in a primary care database.

PURPOSE: The purpose of the study is to evaluate the impact of validation on the identification of major bleeding events in The Health Improvement Network (THIN) database in patients receiving anticoagulant therapy. METHODS: Patients aged 2 to 89 years with a first prescription for an anticoagulant (rivaroxaban or warfarin) between 2012 and 2015 were identified in THIN. Major bleeding events, defined as bleeding events necessitating hospitalization or referral to accident and emergency services or a specialist clinic, were identified using a 2-step ascertainment process based on read codes only, and then validated using a 2-step process requiring manual review of patients' records. RESULTS: The positive predictive value for the ascertainment of major intracranial (IC) bleeds using only read codes was 96.9%, compared with 70.4% for gastrointestinal (GI) bleeds and 64.1% for urogenital (UG) bleeds. The incidence rate of major IC bleeding events was therefore similar when it was calculated before and after validation (0.32 per 100 person-years and 0.31 per 100 person-years, respectively). The incidence rate of major GI bleeds identified using read codes alone was reduced following validation from 2.05 to 0.94 per 100 person-years, and that of major UG bleeds decreased from 2.45 to 1.11 per 100 person-years. CONCLUSIONS: Major GI and UG bleeding events ascertained from THIN using read codes require validation using additional information to prevent outcome misclassification. The absence of validation may lead to overestimated incidence rates of major bleeding for GI and UG bleeds.

Validation study of colorectal cancer diagnosis in the Spanish primary care database, BIFAP.

PURPOSE: To define and validate a case-finding algorithm to identify incident colorectal cancer (CRC) in the Spanish primary care database BIFAP. METHODS: All potential incident CRC cases recorded during the study period 2001 to 2014 among patients 20 to 89 years old were identified using a defined case-finding algorithm tailored to BIFAP database characteristics and based on codes plus text mining strategies. Potential CRC cases identified by the algorithm were classified into eight homogeneous groups according to recording characteristics. Random samples of 100 cases per group were obtained, and electronic medical records were manually reviewed by two independent researchers. Positive predictive values (PPVs) were estimated per each group and for the whole sample taking into account the stratified sampling. Standardized incidence rate (SIR) of CRC was estimated and compared with that reported by the National Cancer Registry. Negative predictive value (NPV) was also estimated in a random sample of 100 non-CRC patients by the algorithm. RESULTS: A total of 17 008 potential CRC cases were identified. Most of them (14793; 87%) were recorded as incident diagnosis with linked clinical notes as free text, having this group a PPV of 92.1% (95%CI: 87.1%-95.3%). The overall PPV including all groups was 87.3% (95%CI: 83.3%-90.4%). SIR of CRC was 55.5 per 100.000 person-years. SIR increased with age and was higher in men as compared with women (77.7 vs 38.1 per 100.000 py, respectively) which were in line with those reported by the Network of Cancer Registries in Spain. NPV was of 100% (96.3%-100%). CONCLUSIONS: This study shows a high validity of the CRC cases identified by the algorithm and a high level of CRC recording in BIFAP database and supports its appropriateness to validly identify incident CRC cases in BIFAP.

Lack of Association Between Proton Pump Inhibitor Use and Cognitive Decline.

BACKGROUND & AIMS: Studies of association between use of proton pump inhibitors (PPI) and dementia have yielded conflicting results. We investigated the effects of PPIs on cognitive decline in a study of middle-aged and elderly twins in Denmark. METHODS: In a prospective study, we collected data from surveys of middle-aged individuals (46-67 years old; the Middle Aged Danish Twin study) and older individuals (the Longitudinal Study of Aging Danish Twins) who underwent cognitive assessments (a 5-component test battery) over a 10-year period (middle-age study, n = 2346) or a 2-year period (longitudinal study of aging: n = 2475). We determined cumulative use of PPIs 2 years prior study enrollment and during follow up, in defined daily doses (DDDs) of PPIs, using data from a nationwide prescription register. Multi-variable linear regression models were used to examine associations between cumulative PPI use and a composite score of cognitive function at baseline and decreases in scores during the follow-up periods. RESULTS: Use of PPIs before study enrollment was associated with a slightly lower mean cognitive score at baseline in the middle age study. The adjusted difference in mean score of individuals with high consumption of PPIs (≥400 DDD) was lower than that of non-users in the middle-age study (mean crude score for high PPI use, 43.4 ± 13.1 vs for non-use, 46.8 ± 10.2; adjusted difference of 0.69 points; 95% CI, -4.98 to 3.61). In the longitudinal study of aging twins, individuals with high consumption of PPI had higher adjusted scores than non-users (mean crude score for high PPI use, 35.2 ± 10.8 vs for non-use, 36.2 ± 11.1; adjusted difference of 0.95 points; 95% CI, -1.88 to 3.79). In analyses of cognitive decline, among individuals with high consumption of PPIs in the longitudinal study of aging, the adjusted mean difference between baseline score and follow-up score was lower than that of non-users (mean crude score for high PPI use at baseline, 36.6 ± 10.1 and at follow up, 34.3 ± 12.3 vs for non-use at baseline, 38.1 ± 10.5 and at follow up, 37.6 ± 11.3; adjusted difference of -1.22 points; 95% CI, -3.73 to 1.29). In the middle-age study, users with the highest consumption of PPIs (≥1600 DDD) had slightly less cognitive decline than non-users (baseline mean crude score for high PPI use, 43.4 ± 10.1 and follow-up mean crude score, 41.3 ± 9.7 vs baseline score of 49.1 ± 10.2 for non-users and follow-up score of 46.3 ± 9.9 for non-users; adjusted difference of 0.94 points; 95% CI, -1.63 to 3.50). No stated differences in scores between PPI users and non-users were significant. CONCLUSIONS: In analyzing data from 2 large population-based studies of twins in Denmark, we found no association between PPI use and cognitive decline.

Challenges of evaluating chronic heart failure and acute heart failure events in research studies using large health care databases.

Epidemiological studies on heart failure (HF) using large health care databases are becoming increasingly frequent, as they represent an invaluable opportunity to characterize the importance and risk factors of HF from a population perspective. Nevertheless, because of its complex diagnosis and natural history, the heterogeneous use of the relevant terminology in routine clinical practice, and the limitations of some disease coding systems, HF can be a challenging condition to assess using large health care databases as the main source of information. In this narrative review, we discuss some of the challenges that researchers may face, with a special focus on the identification and validation of chronic HF cases and acute HF decompensations. For each of these challenges, we present some potential solutions inspired by the literature and/or based on our research experience, aimed at increasing the internal validity of research and at informing its interpretation. We also discuss future directions on the field, presenting constructive recommendations aimed at facilitating the conduct of valid epidemiological studies on HF in the coming years.

Trends in the contemporary incidence of colorectal cancer and patient characteristics in the United Kingdom: a population-based cohort study using The Health Improvement Network.

BACKGROUND: Cancer registry data show that survival of colorectal cancer (CRC) in the United Kingdom is poor compared with other European countries and the United States, yet these data sources lack information on patient comorbidities and medication use, which could help explain these differences. METHODS: Among individuals aged 40-89 years in The Health Improvement Network (2000-2014), we identified first ever cases of CRC and calculated incidence rates with 95% confidence intervals (CIs). For CRC cases and non-cases in two separate calendar years (2002 and 2014), we evaluated patient demographics, lifestyle factors, comorbidities and medication use and bowel screening. RESULTS: The incidence of CRC remained relatively constant across the study period; incidence rates per 10,000 person-years (95% CIs) were 9.27 (8.59-1.01) in 2000, 10.65 (10.15-11.18) in 2007 and 8.37 (7.93-8.83) in 2014. Incidence rates per 10,000 person-years were higher in men than women at 11.44 (95% CI: 10.35-12.66) vs. 7.40 (95% CI: 6.59-8.32) in 2000, and 9.39 (95% CI: 8.74-10.10) vs. 7.38 (95% CI: 6.81-8.00) in 2014. An increase was seen in the proportion of CRC cases diagnosed at age < 60 years. In 2002, 3.5% of CRC cases were diagnosed at age 40-49 compared with 5.1% in 2014 (p = 0.064). Similarly, in 2002, 12.5% were diagnosed at age 50-59 years compared with 16.2% in 2014 (p = 0.002). Between 2002 and 2014, previous bowel screening increased in both CRC cases (+ 10.6%) and non-cases (+ 9.7%)(p < 0.001 for both groups). Greater rises in the following were seen among CRC cases compared with non-cases: diabetes (+ 9.3% vs. + 3.3%; p < 0.001 for both), obesity (+ 14.5% vs. + 10.1%; p < 0.001 for both), hypertension (+ 8.3% vs. + 3.6%; p < 0.001 for both), atrial fibrillation (+ 2.6% [p < 0.01] vs. + 0.3% [p < 0.001]), and use of proton pump inhibitors (+ 11.5% vs. + 9.0%), anti-hypertensives (+ 9.9% vs. + 1.4%) and warfarin (+ 3.2% vs. + 0.4%); p < 0.001 for CRC cases and non-cases with respect to each medication. CONCLUSIONS: CRC incidence has remained relatively stable in the UK over the last decade. The increased prevalence of some comorbidities and medications among CRC cases should be considered when evaluating patterns in CRC survival.

Safety of non-insulin glucose-lowering drugs in pregnant women with pre-gestational diabetes: A cohort study.

AIMS: To evaluate the association between use of non-insulin antidiabetics in early pregnancy and the risk of miscarriages, stillbirths and major structural malformations. MATERIALS AND METHODS: A cohort of 1511 pregnant women with pre-gestational diabetes linked to live births was identified using electronic medical records from The Health Improvement Network (THIN) for the period 1995 to 2012. Information on prescriptions, foetal outcomes and potential confounders was ascertained from both codes and free text in the THIN database. Odds ratios (OR) and 95% confidence intervals (CI) of adverse foetal outcomes in women treated with non-insulin antidiabetics during the first trimester compared to those on insulin were estimated using logistic regression to adjust for type of diabetes, glycaemic control and other maternal characteristics. RESULTS: Among 311 pregnant women on non-insulin antidiabetics, 21.9% had a miscarriage and 1.6% a stillbirth; 1.9% of live births had major malformations. The corresponding frequencies for the 883 women on insulin were 13.3%, 1.7% and 9.6%. Insulin users more often had type 1 diabetes and poor glycaemic control. Compared to women with type 1 diabetes, those with type 2 diabetes had a higher risk of miscarriages (20.5% vs 12.8%) but a lower prevalence of malformations (4.0% vs 9.2%). Compared to women with HbA1c ≤7%, those with HbA1c >7% had a higher prevalence of malformations (12.6% vs 2.7%). After adjustment for diabetes type and glycaemic control, compared to insulin, non-insulin antidiabetic patients were associated with an OR for miscarriage of 1.19 (95% CI, 0.75-1.89), for stillbirths of 0.65 (95% CI, 0.16-2.58), and for major malformations of 0.25 (95% CI, 0.08-0.84). CONCLUSION: Among women with diabetes, use of non-insulin antidiabetics early in pregnancy was not associated with greater risks of foetal losses or major malformations than was insulin.

Hormonal contraception is not associated with increased risk for seizures in the general population: results from a cohort study using The Health Improvement Network.

PURPOSE: Endogenous human gonadal steroids and especially female sex hormones modulate the risk of developing epileptic seizures. In most circumstances, estrogens increase excitability, while progesterone bears substantial anticonvulsive properties. We questioned whether exogenous gonadal steroids used as hormonal contraception are associated with risk of seizures. METHODS: In a dynamic cohort ascertained within The Health Improvement Network database, we identified 2201 female patients aged 20-44 years with seizures during follow-up. In a nested case-control analysis, we matched these cases to 10,143 controls. Using logistic regression, we calculated the risk of seizure associated with use of contraceptives and adjusted for potential confounders. We performed same analyses among women with no prior hormonal contraception use ("new user" analyses) and in patients with a history of epilepsy. RESULTS: Unadjusted data suggested a lower risk for seizures in patients taking exogenous gonadal steroids irrespective of type of contraception used. After adjustment for potential confounders, neither use of combined oral contraceptives nor progestin-only oral contraceptives was associated with the risk for seizures overall. Analyses of "new users" of oral contraceptives produced similar risk estimates. CONCLUSIONS: We found no evidence supporting an effect of oral exogenous gonadal steroids used for hormonal contraception on the risk of seizures in the general female population.