Completeness, agreement, and representativeness of ethnicity recording in the United Kingdom's Clinical Practice Research Datalink (CPRD) and linked Hospital Episode Statistics (HES).

BACKGROUND: This descriptive study assessed the completeness, agreement, and representativeness of ethnicity recording in the United Kingdom (UK) Clinical Practice Research Datalink (CPRD) primary care databases alone and, for those patients registered with a GP in England, when linked to secondary care data from Hospital Episode Statistics (HES). METHODS: Ethnicity records were assessed for all patients in the May 2021 builds of the CPRD GOLD and CPRD Aurum databases for all UK patients. In analyses of the UK, English data was from combined CPRD-HES, whereas data from Northern Ireland, Scotland, and Wales drew from CPRD only. The agreement of ethnicity records per patient was assessed within each dataset (CPRD GOLD, CPRD Aurum, and HES datasets) and between datasets at the highest level ethnicity categorisation ('Asian', 'black', 'mixed', 'white', 'other'). Representativeness was assessed by comparing the ethnic distributions at the highest-level categorisation of CPRD-HES to those from the Census 2011 across the UK's devolved administrations. Additionally, CPRD-HES was compared to the experimental ethnic distributions for England and Wales from the Office for National Statistics in 2019 (ONS2019) and the English ethnic distribution from May 2021 from NHS Digital's General Practice Extraction Service Data for Pandemic Planning and Research with HES data linkage (GDPPR-HES). RESULTS: In CPRD-HES, 81.7% of currently registered patients in the UK had ethnicity recorded in primary care. For patients with multiple ethnicity records, mismatched ethnicity within individual primary and secondary care datasets was < 10%. Of English patients with ethnicity recorded in both CPRD and HES, 93.3% of records matched at the highest-level categorisation; however, the level of agreement was markedly lower in the 'mixed' and 'other' ethnic groups. CPRD-HES was less proportionately 'white' compared to the UK Census 2011 (80.3% vs. 87.2%) and experimental ONS2019 data (80.4% vs. 84.3%). CPRD-HES was aligned with the ethnic distribution from GDPPR-HES ('white' 80.4% vs. 80.7%); however, with a smaller proportion classified as 'other' (1.1% vs. 2.8%). CONCLUSIONS: CPRD-HES has suitable representation of all ethnic categories with some overrepresentation of minority ethnic groups and a smaller proportion classified as 'other' compared to the UK general population from other data sources. CPRD-HES data is useful for studying health risks and outcomes in typically underrepresented groups.

Temporal trends and demographic risk factors for hospital admissions due to carbon monoxide poisoning in England.

Unintentional non-fire related (UNFR) carbon monoxide (CO) poisoning is a preventable cause of morbidity and mortality. Epidemiological data on UNFR CO poisoning can help monitor changes in the magnitude of this burden, particularly through comparisons of multiple countries, and to identify vulnerable sub-groups of the population which may be more at risk. Here, we collected data on age- and sex- specific number of hospital admissions with a primary diagnosis of UNFR CO poisoning in England (2002-2016), aggregated to small areas, alongside area-level characteristics (i.e. deprivation, rurality and ethnicity). We analysed temporal trends using piecewise log-linear models and compared them to analogous data obtained for Canada, France, Spain and the US. We estimated age-standardized rates per 100,000 inhabitants by area-level characteristics using the WHO standard population (2000-2025). We then fitted the Besag York Mollie (BYM) model, a Bayesian hierarchical spatial model, to assess the independent effect of each area-level characteristic on the standardized risk of hospitalization. Temporal trends showed significant decreases after 2010. Decreasing trends were also observed across all countries studied, yet France had a 5-fold higher risk. Based on 3399 UNFR CO poisoning hospitalizations, we found an increased risk in areas classified as rural (0.69, 95% CrI: 0.67; 0.80), highly deprived (1.77, 95% CrI: 1.66; 2.10) or with the largest proportion of Asian (1.15, 95% CrI: 1.03; 1.49) or Black population (1.35, 95% CrI: 1.20; 1.80). Our multivariate approach provides strong evidence for the identification of vulnerable populations which can inform prevention policies and targeted interventions.

Approach to record linkage of primary care data from Clinical Practice Research Datalink to other health-related patient data: overview and implications.

Record linkage is increasingly used to expand the information available for public health research. An understanding of record linkage methods and the relevant strengths and limitations is important for robust analysis and interpretation of linked data. Here, we describe the approach used by Clinical Practice Research Datalink (CPRD) to link primary care data to other patient level datasets, and the potential implications of this approach for CPRD data analysis. General practice electronic health record software providers separately submit de-identified data to CPRD and patient identifiers to NHS Digital, excluding patients who have opted-out from contributing data. Data custodians for external datasets also send patient identifiers to NHS Digital. NHS Digital uses identifiers to link the datasets using an 8-stage deterministic methodology. CPRD subsequently receives a de-identified linked cohort file and provides researchers with anonymised linked data and metadata detailing the linkage process. This methodology has been used to generate routine primary care linked datasets, including data from Hospital Episode Statistics, Office for National Statistics and National Cancer Registration and Analysis Service. 10.6 million (M) patients from 411 English general practices were included in record linkage in June 2018. 9.1M (86%) patients were of research quality, of which 8.0M (88%) had a valid NHS number and were eligible for linkage in the CPRD standard linked dataset release. Linking CPRD data to other sources improves the range and validity of research studies. This manuscript, together with metadata generated on match strength and linkage eligibility, can be used to inform study design and explore potential linkage-related selection and misclassification biases.

Estimating Particulate Exposure from Modern Municipal Waste Incinerators in Great Britain.

Municipal Waste Incineration (MWI) is regulated through the European Union Directive on Industrial Emissions (IED), but there is ongoing public concern regarding potential hazards to health. Using dispersion modeling, we estimated spatial variability in PM10 concentrations arising from MWIs at postcodes (average 12 households) within 10 km of MWIs in Great Britain (GB) in 2003-2010. We also investigated change points in PM10 emissions in relation to introduction of EU Waste Incineration Directive (EU-WID) (subsequently transposed into IED) and correlations of PM10 with SO2, NOx, heavy metals, polychlorinated dibenzo-p-dioxins/furan (PCDD/F), polycyclic aromatic hydrocarbon (PAH) and polychlorinated biphenyl (PCB) emissions. Yearly average modeled PM10 concentrations were 1.00 × 10-5 to 5.53 × 10-2 µg m-3, a small contribution to ambient background levels which were typically 6.59-2.68 × 101 µg m-3, 3-5 orders of magnitude higher. While low, concentration surfaces are likely to represent a spatial proxy of other relevant pollutants. There were statistically significant correlations between PM10 and heavy metal compounds (other heavy metals (r = 0.43, p = <0.001)), PAHs (r = 0.20, p = 0.050), and PCBs (r = 0.19, p = 0.022). No clear change points were detected following EU-WID implementation, possibly as incinerators were operating to EU-WID standards before the implementation date. Results will be used in an epidemiological analysis examining potential associations between MWIs and health outcomes.

Historic air pollution exposure and long-term mortality risks in England and Wales: prospective longitudinal cohort study.

INTRODUCTION: Long-term air pollution exposure contributes to mortality but there are few studies examining effects of very long-term (>25 years) exposures. METHODS: This study investigated modelled air pollution concentrations at residence for 1971, 1981, 1991 (black smoke (BS) and SO2) and 2001 (PM10) in relation to mortality up to 2009 in 367,658 members of the longitudinal survey, a 1% sample of the English Census. Outcomes were all-cause (excluding accidents), cardiovascular (CV) and respiratory mortality. RESULTS: BS and SO2 exposures remained associated with mortality decades after exposure-BS exposure in 1971 was significantly associated with all-cause (OR 1.02 (95% CI 1.01 to 1.04)) and respiratory (OR 1.05 (95% CI 1.01 to 1.09)) mortality in 2002-2009 (ORs expressed per 10 µg/m(3)). Largest effect sizes were seen for more recent exposures and for respiratory disease. PM10 exposure in 2001 was associated with all outcomes in 2002-2009 with stronger associations for respiratory (OR 1.22 (95% CI 1.04 to 1.44)) than CV mortality (OR 1.12 (95% CI 1.01 to 1.25)). Adjusting PM10 for past BS and SO2 exposures in 1971, 1981 and 1991 reduced the all-cause OR to 1.16 (95% CI 1.07 to 1.26) while CV and respiratory associations lost significance, suggesting confounding by past air pollution exposure, but there was no evidence for effect modification. Limitations include limited information on confounding by smoking and exposure misclassification of historic exposures. CONCLUSIONS: This large national study suggests that air pollution exposure has long-term effects on mortality that persist decades after exposure, and that historic air pollution exposures influence current estimates of associations between air pollution and mortality.

Analysis of hospital admissions due to accidental non-fire-related carbon monoxide poisoning in England, between 2001 and 2010.

BACKGROUND: Accidental non-fire-related (ANFR) carbon monoxide (CO) poisoning is a cause of fatalities and hospital admissions. This is the first study that describes the characteristics of ANFR CO hospital admissions in England. METHODS: Hospital Episode Statistics (HES) inpatient data for England between 2001 and 2010 were used. ANFR CO poisoning admissions were defined as any mention of ICD-10 code T58: toxic effect of CO and X47: accidental poisoning by gases or vapours, excluding ICD-10 codes potentially related to fires (X00-X09, T20-T32 and Y26). RESULTS: There were 2463 ANFR CO admissions over the 10-year period (annual rate: 0.49/100 000); these comprised just under half (48.7%) of all non-fire-related (accidental and non-accidental) CO admissions. There was seasonal variability, with more admissions in colder winter months. Higher admission rates were observed in the north of England. Just over half (53%) of ANFR admissions were male, and the highest rates of ANFR admissions were in those aged >80 years. CONCLUSION: The burden of ANFR CO poisoning is preventable. The results of this study suggest an appreciable burden of CO and highlight differences that may aid targeting of public health interventions.

Human leukocyte antigen class II variants and adult-onset asthma: does occupational allergen exposure play a role?

Recently, a locus centred on rs9273349 in the HLA-DQ region emerged from genome-wide association studies of adult-onset asthma. We aimed to further investigate the role of human leukocyte antigen (HLA) class II in adult-onset asthma and a possible interaction with occupational exposures. We imputed classical HLA-II alleles from 7579 single-nucleotide polymorphisms in 6025 subjects (1202 with adult-onset asthma) from European cohorts: ECRHS, SAPALDIA, EGEA and B58C, and from surveys of bakers and agricultural workers. Based on an asthma-specific job-exposure matrix, 2629 subjects had ever been exposed to high molecular weight (HMW) allergens. We explored associations between 23 common HLA-II alleles and adult-onset asthma, and tested for gene-environment interaction with occupational exposure to HMW allergens. Interaction was also tested for rs9273349. Marginal associations of classical HLA-II alleles and adult-onset asthma were not statistically significant. Interaction was detected between the DPB1*03:01 allele and exposure to HMW allergens (p = 0.009), in particular to latex (p = 0.01). In the unexposed group, the DPB1*03:01 allele was associated with adult-onset asthma (OR 0.67, 95%CI 0.53-0.86). HMW allergen exposures did not modify the association of rs9273349 with adult-onset asthma. Common classical HLA-II alleles were not marginally associated with adult-onset asthma. The association of latex exposure and adult-onset asthma may be modified by DPB1*03:01.

Asthma and occupation in the 1958 birth cohort.

OBJECTIVE: To examine the association of adult onset asthma with lifetime exposure to occupations and occupational exposures. METHODS: We generated lifetime occupational histories for 9488 members of the British 1958 birth cohort up to age 42 years. Blind to asthma status, jobs were coded to the International Standard Classification of Occupations 1988 and an Asthma Specific Job Exposure Matrix (ASJEM) with an expert re-evaluation step. Associations of jobs and ASJEM exposures with adult onset asthma were assessed in logistic regression models adjusting for sex, smoking, social class at birth and childhood hay fever. RESULTS: Of the 7406 cohort members with no asthma or wheezy bronchitis in childhood, 639 (9%) reported asthma by age 42 years. Adult onset asthma was associated with 18 occupations, many previously identified as risks for asthma (eg, farmers: OR 4.26, 95% CI 2.06 to 8.80; hairdressers: OR 1.88, 95% CI 1.24 to 2.85; printing workers: OR 3.04, 95% CI 1.49 to 6.18). Four were cleaning occupations and a further three occupations were likely to use cleaning agents. Adult onset asthma was associated with five of the 18 high-risk specific ASJEM exposures (flour exposure: OR 2.12, 95% CI 1.17 to 3.85; enzyme exposure: OR 2.32, 95% CI 1.22 to 4.42; cleaning/disinfecting products: OR 1.67, 95% CI 1.26 to 2.22; metal and metal fumes: OR 1.45, 95% CI 1.02 to 2.07; textile production: OR 1.71, 95% CI 1.12 to 2.61). Approximately 16% (95% CI 3.8% to 27.1%) of adult onset asthma was associated with known asthmagenic occupational exposures. CONCLUSIONS: This study suggests that about 16% of adult onset asthma in British adults born in the late 1950s could be due to occupational exposures, mainly recognised high-risk exposures.

Valsartan, Losartan and Irbesartan use in the USA, UK, Canada and Denmark after the nitrosamine recalls: a descriptive cohort study.

OBJECTIVES: To examine valsartan, losartan and irbesartan usage and switching patterns in the USA, UK, Canada and Denmark before and after July 2018, when the first Angiotensin-Receptor-Blocker (ARB) (valsartan) was recalled. DESIGN: Retrospective cohort study. SETTING: USA, Canadian administrative healthcare data, Danish National Prescription Registry and UK primary care electronic health records. PARTICIPANTS: Patients aged 18 years and older between January 2014 and December 2020. INTERVENTION: Valsartan, losartan and irbesartan. MAIN OUTCOME: Monthly percentages of individual ARB episodes, new users and switches to another ARB, ACE inhibitors (ACEI) or calcium channel blockers containing products. RESULTS: We identified 10.8, 3.2, 1.8 and 1.2 million ARB users in the USA, UK, Canada and Denmark, respectively. Overall proportions of valsartan, losartan and irbesartan use were 18.4%, 67.9% and 5.2% in the USA; 3.1%, 48.3% and 10.2% in the UK, 16.3%, 11.4% and 18.3% in Canada, 1%, 93.5% and 0.6% in Denmark. In July 2018, we observed an immediate steep decline in the proportion of valsartan use in the USA and Canada. A similar trend was observed in Denmark; however, the decline was only minimal. We observed no change in trends of ARB use in the UK. Accompanying the valsartan decline was an increase in switching to other ARBs in the USA, Canada and Denmark. There was a small increase in switching to ACEI relative to the valsartan-to-other-ARBs switch. We also observed increased switching from other affected ARBs, losartan and irbesartan, to other ARBs throughout 2019, in the USA and Canada, although the usage trends in the USA remained unchanged. CONCLUSION: The first recall notice for valsartan resulted in substantial decline in usage due to increased switching to other ARBs. Subsequent notices for losartan and irbesartan were also associated with increased switching around the time of the recall, however, overall usage trends remained unchanged.

Completeness and representativeness of small area socioeconomic data linked with the UK Clinical Practice Research Datalink (CPRD).

BACKGROUND: The Clinical Practice Research Datalink (CPRD) holds primary care electronic healthcare records for 25% of the UK population. CPRD data can be linked via practice postcode in the UK, and additionally via patient postcode in England, to area-level socioeconomic status (SES) data including the Index of Multiple Deprivation (IMD), the Carstairs Index and the Townsend Deprivation Index; as well as rural-urban classification (RUC). This study aims to describe the completeness and representativeness of CPRD-linked SES and RUC data. METHODS: Patients currently registered at general practices contributing data to the May 2021 snapshots of CPRD GOLD (n=445 587) and CPRD Aurum (n=13 278 825) were used to assess the completeness and representativeness of CPRD-linked SES and RUC data against the UK general population. RESULTS: All currently registered patients had complete SES and RUC data at practice level across the UK. Most English patients in CPRD GOLD (78%), CPRD Aurum (94%) and combined (93%) had SES and RUC data at patient level. Patient-level SES data in CPRD for England were comparable to England's general population (average IMD decile in CPRD 5.52±0.00 vs 5.50±0.02). CPRD UK practices were on average in more deprived areas than the UK general population (6.06±0.07 vs 5.50±0.02). A slightly higher proportion of CPRD patients and practices were from urban areas (85%) as compared with the UK general population (82%). CONCLUSION: Completeness of CPRD-linked SES and RUC data is high. The CPRD populations were broadly representative of the general populations in the UK in terms of SES and RUC.

Systematic approach to outcome assessment from coded electronic healthcare records in the DaRe2THINK NHS-embedded randomized trial.

Aims: Improving the efficiency of clinical trials is key to their continued importance in directing evidence-based patient care. Digital innovations, in particular the use of electronic healthcare records (EHRs), allow for large-scale screening and follow up of participants. However, it is critical these developments are accompanied by robust and transparent methods that can support high-quality and high clinical value research. Methods and results: The DaRe2THINK trial includes a series of novel processes, including nationwide pseudonymized pre screening of the primary-care EHR across England, digital enrolment, remote e-consent, and 'no-visit' follow up by linking all primary- and secondary-care health data with patient-reported outcomes. DaRe2THINK is a pragmatic, healthcare-embedded randomized trial testing whether earlier use of direct oral anticoagulants in patients with prior or current atrial fibrillation can prevent thromboembolic events and cognitive decline (www.birmingham.ac.uk/dare2think). This study outlines the systematic approach and methodology employed to define patient information and outcome events. This includes transparency on all medical code lists and phenotypes used in the trial across a variety of national data sources, including Clinical Practice Research Datalink Aurum (primary care), Hospital Episode Statistics (secondary care), and the Office for National Statistics (mortality). Conclusion: Co-designed by a patient and public involvement team, DaRe2THINK presents an opportunity to transform the approach to randomized trials in the setting of routine healthcare, providing high-quality evidence generation in populations representative of the community at risk.

The feasibility of pragmatic influenza vaccine randomized controlled real-world trials in Denmark and England.

We estimated the frequency of non-specific influenza-associated clinical endpoints to inform the feasibility of pragmatic randomized controlled trials (RCT) assessing relative vaccine effectiveness (rVE). Hospitalization rates of respiratory, cardiovascular and diabetic events were estimated from Denmark and England's electronic databases and stratified by age, comorbidity and influenza vaccination status. We included a seasonal average of 4.5 million Danish and 7.2 million English individuals, 17 and 32% with comorbidities. Annually, approximately 1% of Danish and 0.5% of English individuals were hospitalized for selected events, ~50% of them respiratory. Hospitalization rates were 40-50-fold and 2-10-fold higher in those >50 years and with comorbidities, respectively. Our findings suggest that a pragmatic RCT using non-specific endpoints is feasible. However, for outcomes with rates <2.5%, it would require randomization of ~100,000 participants to have the power to detect a rVE difference of ~13%. Targeting selected groups (older adults, those with comorbidities) where frequency of events is high would improve trial efficiency.

Job choice and the influence of prior asthma and hay fever.

OBJECTIVES: To investigate whether prior symptoms of allergic disease influence first job undertaken on leaving school. METHODS: The study included 5020 members of the 1958 British birth cohort who provided a job history (including start dates) at age 33 and for whom information on allergic disease in childhood and adolescence was reported by parents at ages 7, 11 and 16. Occupational group (high risk, low risk, reference) was based on first job and its probable asthma risk. RESULTS: With occupational group defined using only job title, the RR of taking a high risk over a reference level job was an estimated 30% (RR ratio (RRR) 0.70; 95% CI 0.56 to 0.88) lower among those with than without prior reported symptoms of hay fever/allergic rhinitis but an estimated 60% (RRR 1.60; 1.17 to 2.19) higher among those with symptoms of asthma/wheezy bronchitis in adolescence compared to those with no history of asthma/wheezy bronchitis. With occupational group defined using an asthma specific job exposure matrix, a similar association was observed for prior hay fever/allergic rhinitis (RRR 0.77; 0.62 to 0.96) but not for asthma/wheezy bronchitis (RRR 1.18; 0.85 to 1.64). There was no evidence of an association between prior eczema and occupational group of first job. CONCLUSION: Whether our findings indicate avoidance or residual confounding, it would be prudent for future studies of occupation and the incidence or recurrence of asthma in adult life to adjust for any previous history of hay fever/allergic rhinitis.

The Utilization and Safety of Umeclidinium and Umeclidinium/Vilanterol in UK Primary Care: A Retrospective Cohort Study.

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 ß2-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.

Risk of congenital anomalies near municipal waste incinerators in England and Scotland: Retrospective population-based cohort study.

BACKGROUND: Few studies have investigated congenital anomalies in relation to municipal waste incinerators (MWIs) and results are inconclusive. OBJECTIVES: To conduct a national investigation into the risk of congenital anomalies in babies born to mothers living within 10 km of an MWI associated with: i) modelled concentrations of PM10 as a proxy for MWI emissions more generally and; ii) proximity of residential postcode to nearest MWI, in areas in England and Scotland that are covered by a congenital anomaly register. METHODS: Retrospective population-based cohort study within 10 km of 10 MWIs in England and Scotland operating between 2003 and 2010. Exposure was proximity to MWI and log of daily mean modelled ground-level particulate matter ≤10 µm diameter (PM10) concentrations. RESULTS: Analysis included 219,486 births, stillbirths and terminations of pregnancy for fetal anomaly of which 5154 were cases of congenital anomalies. Fully adjusted odds ratio (OR) per doubling in PM10 was: 1·00 (95% CI 0·98-1·02) for all congenital anomalies; 0·99 (0·97-1·01) for all congenital anomalies excluding chromosomal anomalies. For every 1 km closer to an MWI adjusted OR was: 1·02 (1·00-1·04) for all congenital anomalies combined; 1·02 (1·00-1·04) for all congenital anomalies excluding chromosomal anomalies; and, for specific anomaly groups, 1·04 (1·01-1·08) for congenital heart defect sand 1·07 (1·02-1·12) for genital anomalies. DISCUSSION: We found no increased risk of congenital anomalies in relation to modelled PM10 emissions, but there were small excess risks associated with congenital heart defects and genital anomalies in proximity to MWIs. These latter findings may well reflect incomplete control for confounding, but a possible causal effect cannot be excluded.

Birth weight centiles and small for gestational age by sex and ethnicity for England and Wales.

OBJECTIVES: To construct UK ethnicity birth weight centiles (UK-EBWC) for gestational age and cut-offs for small for gestational age (SGA) for England and Wales and to evaluate the SGA misclassification using the UK centiles. DESIGN: Analysis of national birth data. PARTICIPANTS: All live singleton births in England and Wales in 2006-2012, as recorded by the Office for National Statistics and birth registrations, linked with National Health Service into numbers for babies. MAIN OUTCOME MEASURES: Both sex-specific and ethnicity-sex-specific birth weight centiles for gestational age, and ethnicity-sex-specific SGA cut-offs. Centiles were computed using the generalised additive model for location, scale and shape. RESULTS: Our sex-specific centiles performed well and showed an agreement between the expected and observed number of births below the centiles. The ethnicity-sex-specific centiles for Black and Asian presented lower values compared with the White centiles. Comparisons of sex-specific and ethnicity-sex-specific centiles shows that use of sex-specific centiles increases the SGA diagnosed cases by 50% for Asian, 30% for South Asian (Indian, Pakistani and Bangladeshi) and 20% for Black ethnicity. CONCLUSIONS: The centiles show important differences between ethnic groups, in particular the 10th centile used to define SGA. To account for these differences and to minimise misclassification of SGA, we recommend the use of customised birth weight centiles.

How Clinical Practice Research Datalink data are used to support pharmacovigilance.

Pharmacovigilance can be defined as the science of monitoring medicines and vaccines after license for use, the purpose of which is to quantify and characterise the safety profile of a medicine, identify previously unknown adverse reactions, inform risk-benefit assessment, and support the development of actions that can be taken to reduce risks, optimise benefits and monitor their effectiveness. This review discusses the Clinical Practice Research Datalink (CPRD), which is the source of the largest research database in the UK with longitudinal, representative primary care data linked to data from other healthcare settings. CPRD supports international pharmacovigilance by providing a large, anonymised representative general population database with comprehensive capture of patient risk factors and outcomes to researchers within academic, regulatory and pharmaceutical organisations. The specific advantages of CPRD data are discussed in the context of the 'six Vs of big data' including volume, velocity, variety, veracity, validity and value. Examples of where CPRD data have been used for pharmacovigilance research and how these have fed into guidelines and policy are discussed.

Treatment Patterns of New Users of Fluticasone Furoate/Vilanterol in Asthma and COPD in UK Primary Care: Retrospective Cohort Study.

INTRODUCTION: This retrospective database study explored treatment patterns and potential off-label prescribing among patients newly prescribed fluticasone furoate/vilanterol (FF/VI) in a UK primary care setting. METHODS: In Europe, FF/VI is approved in two strengths: 100/25 µg for adults with chronic obstructive pulmonary disease (COPD) and 100/25 µg or 200/25 µg for treatment of asthma in patients aged 12 or older. Using electronic health records from the Clinical Practice Research Datalink, new users of FF/VI or other inhaled corticosteroid/long-acting beta-agonist fixed-dose combination products were identified and classified into one of three groups: COPD diagnosis, asthma diagnosis, and other diagnosis (not COPD or asthma). RESULTS: During 2014-2015, 4373 patients initiated FF/VI: 3380 on FF/VI 100/25 (65% in the COPD diagnosis group) and 993 on FF/VI 200/25 (51% in the asthma diagnosis group). During up to 12 months of follow-up, the median number (interquartile range) of prescriptions of the index strength issued per patient was 7 (2-8) for FF/VI 100/25 and 5 (2-8) for FF/VI 200/25; most new users did not change from the index strength prescribed (93.0% COPD; 89.7% asthma, of all patients initiating treatment with FF/VI). Potential off-label FF/VI prescribing in children < 12 years old was rare (< 0.29% in the combined asthma and other diagnosis groups), and up to one in five new users of FF/VI with COPD were potentially prescribed FF/VI 200/25 off-label during the study period. Much of the potential off-label prescribing in COPD occurred in patients with a history of asthma, those presenting with greater disease severity, and/or prior treatment with high-dose steroids. CONCLUSIONS: The prescription of FF/VI is rare in children under 12 years of age in the UK, according to our findings, but up to one in five COPD patients in the UK may have been prescribed FF/VI 200/25, some of which may have been off-label. FUNDING: This study was funded by GlaxoSmithKline plc (study 205052). STUDY REGISTRATION: GlaxoSmithKline plc Clinical Trial Registry study number 205052.

Fetal growth, stillbirth, infant mortality and other birth outcomes near UK municipal waste incinerators; retrospective population based cohort and case-control study.

BACKGROUND: Some studies have reported associations between municipal waste incinerator (MWI) exposures and adverse birth outcomes but there are few studies of modern MWIs operating to current European Union (EU) Industrial Emissions Directive standards. METHODS: Associations between modelled ground-level particulate matter ≤10 µm in diameter (PM10) from MWI emissions (as a proxy for MWI emissions) within 10 km of each MWI, and selected birth and infant mortality outcomes were examined for all 22 MWIs operating in Great Britain 2003-10. We also investigated associations with proximity of residence to a MWI. Outcomes used were term birth weight, small for gestational age (SGA) at term, stillbirth, neonatal, post-neonatal and infant mortality, multiple births, sex ratio and preterm delivery sourced from national registration data from the Office for National Statistics. Analyses were adjusted for relevant confounders including year of birth, sex, season of birth, maternal age, deprivation, ethnicity and area characteristics and random effect terms were included in the models to allow for differences in baseline rates between areas and in incinerator feedstock. RESULTS: Analyses included 1,025,064 births and 18,694 infant deaths. There was no excess risk in relation to any of the outcomes investigated during pregnancy or early life of either mean modelled MWI PM10 or proximity to an MWI. CONCLUSIONS: We found no evidence that exposure to PM10 from, or living near to, an MWI operating to current EU standards was associated with harm for any of the outcomes investigated. Results should be generalisable to other MWIs operating to similar standards.

Birth weight trends in England and Wales (1986-2012): babies are getting heavier.

INTRODUCTION: Birth weight is a strong predictor of infant mortality, morbidity and later disease risk. Previous work from the 1980s indicated a shift in the UK towards heavier births; this descriptive analysis looks at more recent trends. METHODS: Office for National Statistics (ONS) registration data on 17.2 million live, single births from 1986 to 2012 were investigated for temporal trends in mean birth weight, potential years of birth weight change and changes in the proportions of very low (<1500 g), low (<2500 g) and high (≥4000 g) birth weight. Analysis used multiple linear and logistic regression adjusted for maternal age, marital status, area-level deprivation and ethnicity. Additional analyses used the ONS NHS Numbers for Babies data set for 2006-2012, which has information on individual ethnicity and gestational age. RESULTS: Over 27 years there was an increase in birth weight of 43 g (95% CI 42 to 44) in females and 44 g (95% CI 43 to 45) in males, driven by birth weight increases between 1986-1990 and 2007-2012. There was a concurrent decreased risk of having low birth weight but an 8% increased risk in males and 10% increased risk in females of having high birth weight. For 2006-2012 the birth weight increase was greater in preterm as compared with term births. CONCLUSIONS: Since 1986 the birth weight distribution of live, single births in England and Wales has shifted towards heavier births, partly explained by increases in maternal age and non-white ethnicity, as well as changes in deprivation levels. Other potential influences include increases in maternal obesity and reductions in smoking prevalence particularly following the introduction of legislation restricting smoking in public places in 2007.