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, 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.

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.

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.

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 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.

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.

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.

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.

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.

Impact of London's road traffic air and noise pollution on birth weight: retrospective population based cohort study.

Objective To investigate the relation between exposure to both air and noise pollution from road traffic and birth weight outcomes.Design Retrospective population based cohort study.Setting Greater London and surrounding counties up to the M25 motorway (2317 km2), UK, from 2006 to 2010.Participants 540 365 singleton term live births.Main outcome measures Term low birth weight (LBW), small for gestational age (SGA) at term, and term birth weight.Results Average air pollutant exposures across pregnancy were 41 µg/m3 nitrogen dioxide (NO2), 73 µg/m3 nitrogen oxides (NOx), 14 µg/m3 particulate matter with aerodynamic diameter <2.5 µm (PM2.5), 23 µg/m3 particulate matter with aerodynamic diameter <10 µm (PM10), and 32 µg/m3 ozone (O3). Average daytime (LAeq,16hr) and night-time (Lnight) road traffic A-weighted noise levels were 58 dB and 53 dB respectively. Interquartile range increases in NO2, NOx, PM2.5, PM10, and source specific PM2.5 from traffic exhaust (PM2.5 traffic exhaust) and traffic non-exhaust (brake or tyre wear and resuspension) (PM2.5 traffic non-exhaust) were associated with 2% to 6% increased odds of term LBW, and 1% to 3% increased odds of term SGA. Air pollutant associations were robust to adjustment for road traffic noise. Trends of decreasing birth weight across increasing road traffic noise categories were observed, but were strongly attenuated when adjusted for primary traffic related air pollutants. Only PM2.5 traffic exhaust and PM2.5 were consistently associated with increased risk of term LBW after adjustment for each of the other air pollutants. It was estimated that 3% of term LBW cases in London are directly attributable to residential exposure to PM2.5>13.8 µg/m3during pregnancy.Conclusions The findings suggest that air pollution from road traffic in London is adversely affecting fetal growth. The results suggest little evidence for an independent exposure-response effect of traffic related noise on birth weight outcomes.

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.

Routinely collected English birth data sets: comparisons and recommendations for reproductive epidemiology.

BACKGROUND: In England there are four national routinely collected data sets on births: Office for National Statistics (ONS) births based on birth registrations; Hospital Episode Statistics (HES) deliveries (mothers' information); HES births (babies' information); and NHS Numbers for Babies (NN4B) based on ONS births plus gestational age and ethnicity information. This study describes and compares these data, with the aim of recommending the most appropriate data set(s) for use in epidemiological research and surveillance. METHODS: We assessed the completeness and quality of the data sets in relation to use in epidemiological research and surveillance and produced detailed descriptive statistics on common reproductive outcomes for each data set including temporal and spatial trends. RESULTS: ONS births is a high quality complete data set but lacks interpretive and clinical information. HES deliveries showed good agreement with ONS births but HES births showed larger amounts of missing or unavailable data. Both HES data sets had improved quality from 2003 onwards, but showed some local spatial variability. NN4B showed excellent agreement with ONS and HES deliveries for the years available (2006-2010). Annual number of births increased by 17.6% comparing 2002 with 2010 (ONS births). Approximately 6% of births were of low birth weight (2.6% term low birth weight) and 0.5% were stillbirths. CONCLUSIONS: Routinely collected data on births provide a valuable resource for researchers. ONS and NN4B offer the most complete and accurate record of births. Where more detailed clinical information is required, HES deliveries offers a high quality data set that captures the majority of English births.

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.

Is long-term exposure to traffic pollution associated with mortality? A small-area study in London.

Long-term exposure to primary traffic pollutants may be harmful for health but few studies have investigated effects on mortality. We examined associations for six primary traffic pollutants with all-cause and cause-specific mortality in 2003-2010 at small-area level using linear and piecewise linear Poisson regression models. In linear models most pollutants showed negative or null association with all-cause, cardiovascular or respiratory mortality. In the piecewise models we observed positive associations in the lowest exposure range (e.g. relative risk (RR) for all-cause mortality 1.07 (95% credible interval (CI) = 1.00-1.15) per 0.15 µg/m(3) increase in exhaust related primary particulate matter ≤2.5 µm (PM2.5)) whereas associations in the highest exposure range were negative (corresponding RR 0.93, 95% CI: 0.91-0.96). Overall, there was only weak evidence of positive associations with mortality. That we found the strongest positive associations in the lowest exposure group may reflect residual confounding by unmeasured confounders that varies by exposure group.