Outcomes in patients treated with loop diuretics without a diagnosis of heart failure: a retrospective cohort study.

BACKGROUND: Loop diuretics are commonly prescribed in the community, not always to patients with a recorded diagnosis of heart failure (HF). The rate of HF events in patients prescribed loop diuretics without a diagnosis of HF is unknown. METHODS: This was a propensity-matched cohort study using data from the Clinical Practice Research Datalink, Hospital Episode Statistics and Office of National Statistics in the UK. Patients prescribed a loop diuretic without a diagnosis of HF (loop diuretic group) between 1 January 2010 and 31 December 2015 were compared with patients with HF (HF group)-analysis A, and patients with risk factors for HF (either ischaemic heart disease, or diabetes and hypertension-at-risk group)-analysis B. The primary endpoint was an HF event (a composite of presentation with HF symptoms, HF hospitalisation, HF diagnosis (analysis B only) and all-cause mortality). RESULTS: From a total population of 180 384 patients (78 968 in the loop diuretic group, 28 177 in the HF group and 73 239 in the at-risk group), there were 59 694 patients, 22 352 patients and 57 219 patients in the loop diuretic, HF and at-risk groups, respectively, after exclusion criteria were applied. After propensity matching for age, sex and comorbidities, patients in the loop diuretic group had a similar rate of HF events as those in the HF group (71.9% vs 72.1%; HR=0.92 (95% CI 0.90 to 0.94); p<0.001), and twice as those in the at-risk group (59.2% vs 35.7%; HR=2.04 (95% CI 2.00 to 2.08); p<0.001). CONCLUSIONS: Patients prescribed a loop diuretic without a recorded diagnosis of HF experience HF events at a rate comparable with that of patients with a recorded diagnosis of HF; many of these patients may have undiagnosed HF.

Ethics guidelines for environmental epidemiologists: 2023 revision.

Recognition of the importance to environmental epidemiology of ethical and philosophical deliberation led, in 1996, to the establishment of Ethics Guidelines for the profession. In 1999, these guidelines were adopted by the International Society for Environmental Epidemiology. The guidelines were revised in 2012 and again in 2023 to ensure continued relevance to the major issues facing the field. Comprising normative standards of professional conduct, the guidelines are structured into four subsections: (1) obligations to individuals and communities who participate in research; (2) obligations to society; (3) obligations regarding funders/sponsors and employers; and (4) obligations to colleagues. Through the 2023 revision of the Ethics Guidelines, the International Society for Environmental Epidemiology seeks to ensure the highest possible standards of transparency and accountability for the ethical conduct of environmental epidemiologists engaged in research and public health practice.

Online Interest for Electronic Cigarettes Using Google Trends in the UK: A Correlation Analysis.

BACKGROUND: Google Trends provides an easily accessible and cost-effective method of providing real-time insight into user interest. OBJECTIVE: to address the gap in UK prevalence data for e-cigarettes by analyzing Google Trends to identify correlations with official data from Action on Smoking and Health. The study further evaluates Google Trend's sensitivity to real-time events and the ability for predictive models to forecast future data based on Google Trends. METHODS: UK Google Trends data from 2012 to 2021 was analyzed to assess (a) the most popular electronic nicotine device terminology; (b) statistically significant points in time; (c) correlations between Relative Search Volumes and official reports on electronic cigarette use and (d) whether Google Trends could predict future patterns in data. These were achieved using Locally Weighted Scatterplot Smoothing regression, Pruned Exact Linear Time Method, cross correlation, and Autoregressive Integrated Moving Average algorithms respectively. RESULTS: "Vape" was revealed to be the most popular electronic nicotine device terminology with a correlation coefficient greater than +0.9 when compared to official electronic cigarette consumption data within a one-year timescale (lag 0). Results from ARIMA modeling were varied with the algorithms forecasted trends line occasionally lying outside of a 95% prediction interval. CONCLUSION: Google Trends may correspond to population-based prevalence of electronic cigarette use. The changing trends coincide with changing policy decisions. Google Trends based prediction for online interest in electronic cigarettes requires further validation so should currently be used in conjunction with other traditional methods of data collections.

Breathlessness limiting exertion in very old adults: findings from the Newcastle 85+ study.

INTRODUCTION: Long-term breathlessness is more common with age. However, in the oldest old (>85 years), little is known about the prevalence, or impact of breathlessness. We estimated breathlessness limiting exertion prevalence and explored (i) associated characteristics; and (ii) whether breathlessness limiting exertion explains clinical and social/functional outcomes. METHODS: Health and socio-demographic characteristics were extracted from the Newcastle 85+ Study cohort. Phase 1 (baseline) and follow-up data (18 months, Phase 2; 36 months, Phase 3; 60 months, Phase 4 after baseline) were examined using descriptive statistics and cross-sectional regression models. RESULTS: Eight hundred seventeen participants provided baseline breathlessness data (38.2% men; mean 84.5 years; SD 0.4). The proportions with any limitation of exertion, or severe limitation by breathlessness were 23% (95% confidence intervals (CIs) 20-25%) and 9% (95%CIs 7-11%) at baseline; 20% (16-25%) and 5% (3-8%) at Phase 4. Having more co-morbidities (odds ratio (OR) 1.34, 1.18-1.54; P < 0.001), or self-reported respiratory (OR 1.88, 1.25-2.82; P = 0.003) or cardiovascular disease (OR 2.38, 1.58-3.58; P < 0.001) were associated with breathlessness limiting exertion. Breathlessness severely limiting exertion was associated with poorer self-rated health (OR 0.50, 029-0.86; P = 0.012), depression (beta-coefficient 0.11, P = 0.001), increased primary care contacts (beta-co-efficient 0.13, P = 0.001) and number of nights in hospital (OR 1.81; 1.02-3.20; P = 0.042). CONCLUSIONS: Breathlessness limiting exertion appears to become less prevalent over time due to death or withdrawal of participants with cardio-respiratory illness. Breathlessness severely limiting exertion had a wide range of service utilisation and wellbeing impacts.

Effectiveness of educational interventions on hypertensive patients' self-management behaviours: an umbrella review protocol.

BACKGROUND: Although different educational interventions have been widely used to manage and treat hypertension, alone or in combination with other interventions, there is a significant variation in their claimed effectiveness. REVIEW QUESTION/OBJECTIVE: The objective of this umbrella review is to determine the effectiveness of educational interventions, alone or in combination with other interventions, for improving blood pressure control and self-management practices among hypertensive patients. The review question is: Do educational interventions, alone or in combination with other interventions, improve self-management practices among patients with hypertension? METHODS: We will conduct a review of systematic reviews involving studies that implemented educational interventions, alone or in combination with other interventions, designed to change self-care practices among hypertensive patients who are 18 years and above, regardless of their sex and ethnicity. Following the guidelines set forth in the Preferred Reporting Items for Systematic Review and Meta-Analysis statement, a comprehensive literature search will be conducted from September to December 2023 on six electronic databases: MEDLINE, Embase, PsycINFO, CINAHL, Web of Science Core Collection and Google Scholar. Search terms will be developed using database-specific indexed terms and text words derived from the review aim. We will present the effects of the educational interventions, alone or in combination with other interventions, on hypertension self-management practices. We will report the outcome data with 95% CIs for each study. Relative risk, mean differences or ORs will be used, depending on the measuring indices in each study. ETHICS AND DISSEMINATION: Ethical approval is not required as this study will use aggregated data from previously published systematic reviews. However, we have registered the protocol in PROSPERO. We confirm that all methods will be performed following the guidelines of the Declaration of Helsinki. The findings from this study will be disseminated through presentations at academic conferences and publication in peer-reviewed international journals. PROSPERO REGISTRATION NUMBER: CRD42022375581.

The effect of geographical variation in income measures on measles-mumps-rubella uptake and coverage in England; a protocol for an ecological study.

Measles is a vaccine-preventable disease whose vaccine was introduced in England in 1988, however, Measles outbreaks have still been occurring in the country. Consequently, the World Health Organization (WHO) removed the elimination status of Measles in 2019 from England and the whole United Kingdom. Noticeably, MMR vaccination coverage in England is below the recommended threshold with geographical variations across local authorities (LA). The research into the effect of income disparities on MMR vaccine coverage was insufficiently examined. Therefore, an ecological study will be conducted aiming at determining whether there is a relationship between income deprivation measures and MMR vaccine coverage in upper-tier local authorities in England. This study will be using 2019 publicly available vaccination data for children who were eligible for the MMR vaccine by their second and fifth birthday in 2018/2019. The effect of spatial clustering of income level on vaccination coverage will also be assessed. Vaccination coverage data will be obtained from "Cover of Vaccination Evaluated Rapidly (COVER)". Income deprivation score, Deprivation gap, and Income Deprivation Affecting Children Index will be obtained from Office for National Statistics and Moran's Index will be generated using RStudio. Rural/urban LA classification and mothers' education will be included as possible confounding factors. Additionally, the live births rate per mothers' age group will be included as a proxy for the mothers' age variation in different LA. Multiple linear regression will be used after testing the relevant assumptions, using SPSS software. Moran's I together with income deprivation score will be analysed through regression and mediation analysis. This study will help in determining whether income level is a determinant of MMR vaccination uptake and coverage in LA in England which would help policymakers in designing targeted campaigns, thus preventing measles outbreaks in the future.

Hormone Replacement Therapy and Risk of Severe Asthma Exacerbation in Perimenopausal and Postmenopausal Women: 17-Year National Cohort Study.

BACKGROUND: The impact of hormone replacement therapy (HRT) on clinical outcomes in menopausal women is uncertain. OBJECTIVE: To investigate the association between use of HRT and severe asthma exacerbation in perimenopausal and postmenopausal women with asthma. METHODS: We used the Optimum Patient Care Research Database, a population-based longitudinal primary care database in the United Kingdom, to construct a 17-year (January 1, 2000, to December 31, 2016) cohort of perimenopausal and postmenopausal (46-70 years, N = 31,656) women. We defined use of HRT, its subtypes, and duration of HRT use. Severe asthma exacerbation was defined as an asthma-related hospitalization, emergency department visits due to asthma, and/or prescription of oral corticosteroids. Analyses were undertaken using multilevel mixed-effects Poisson regression. RESULTS: At baseline, 22% of women were using any HRT, 11% combined HRT, and 11% estrogen-only HRT. Previous, but not current, use of any (incidence rate ratio [IRR]: 1.24, 95% confidence interval [CI]: 1.22-1.26), combined (IRR: 1.28, 95% CI: 1.25-1.31), and estrogen-only HRT (IRR: 1.18, 95% CI: 1.14-1.21), and longer duration (1-2 years: IRR: 1.16, 95% CI: 1.13-1.19; 3-4 years: IRR: 1.43, 95% CI: 1.38-1.48; 5+ years: IRR: 1.32, 95% CI: 1.28-1.36) of HRT use were associated with increased risk of severe asthma exacerbation compared with nonuse. The risk estimates were greater among lean women (body mass index [BMI] <25 kg/m2) than among heavier women (BMI 25-29.9 kg/m2 and ≥30 kg/m2) and higher among smokers than nonsmokers. CONCLUSION: Use of HRT and subtypes, particularly previous, but not current, use and use for more than 2 years, is associated with an increased risk of severe asthma exacerbation in perimenopausal/postmenopausal women with established asthma. Lean women and smokers are at greater risk than heavier women and nonsmokers, respectively.

Hormone replacement therapy and asthma onset in menopausal women: National cohort study.

BACKGROUND: There is uncertainty about the role of hormonal replacement therapy (HRT) in the development of asthma. OBJECTIVE: We investigated whether use of HRT and duration of use was associated with risk of development of asthma in perimenopausal and postmenopausal women. METHODS: We constructed a 17-year (from January 1, 2000, to December 31, 2016) open cohort of 353,173 women (aged 46-70 years) from the Optimum Patient Care Database, a longitudinal primary care database from across the United Kingdom. HRT use, subtypes, and duration of use; confounding variables; and asthma onset were defined by using the Read Clinical Classification System. We fitted multilevel Cox regression models to estimate hazard ratios (HRs) with 95% CIs. RESULTS: During the 17-year follow-up (1,340,423 person years), 7,614 new asthma cases occurred, giving an incidence rate of 5.7 (95% CI = 5.5-5.8) per 1,000 person years. Compared with nonuse of HRT, previous use of any (HR = 0.83; 95% CI = 0.76-0.88), estrogen-only (HR = 0.89; 95% CI = 0.84-0.95), or combined estrogen and progestogen (HR = 0.82; 95% CI = 0.76-0.88) HRT was associated with a reduced risk of asthma onset. This was also the case with current use of any (HR = 0.79; 95% CI = 0.74-0.85), estrogen-only (HR = 0.80; 95% CI = 0.73-0.87), and combined estrogen and progestogen (HR = 0.78; 95% CI = 0.70-0.87) HRT. Longer duration of HRT use (1-2 years [HR = 0.93; 95% CI = 0.87-0.99]; 3-4 years [HR = 0.77; 95% CI = 0.70-0.84]; and ≥5 years [HR = 0.71; 95% CI = 0.64-0.78]) was associated with a dose-response reduced risk of asthma onset. CONCLUSION: We found that HRT was associated with a reduced risk of development of late onset asthma in menopausal women. Further cohort studies are needed to confirm these findings.

Hormonal contraception and the risk of severe asthma exacerbation: 17-year population-based cohort study.

BACKGROUND: Longitudinal studies investigating impact of exogenous sex steroids on clinical outcomes of asthma in women are lacking. We investigated the association between use of hormonal contraceptives and risk of severe asthma exacerbation in reproductive-age women with asthma. METHODS: We used the Optimum Patient Care Research Database, a population-based, longitudinal, anonymised primary care database in the UK, to construct a 17-year (1 January 2000-31 December 2016) retrospective cohort of reproductive-age (16-45 years, n=83 084) women with asthma. Using Read codes, we defined use, subtypes and duration of use of hormonal contraceptives. Severe asthma exacerbation was defined according to recommendations of the European Respiratory Society/American Thoracic Society as asthma-related hospitalisation, accident and emergency department visits due to asthma and/or oral corticosteroid prescriptions. Analyses were done using multilevel mixed-effects Poisson regression with QR decomposition. RESULTS: The 17-year follow-up resulted in 456 803 person-years of follow-up time. At baseline, 34% of women were using any hormonal contraceptives, 25% combined (oestrogen/progestogen) and 9% progestogen-only contraceptives. Previous (incidence rate ratio (IRR) 0.94, 95% CI 0.92 to 0.97) and current (IRR 0.96, 95% CI 0.94 to 0.98) use of any, previous (IRR 0.92, 95% CI 0.87 to 0.97) and current use of combined (IRR 0.93, 95% CI 0.91 to 0.96) and longer duration of use (3-4 years: IRR 0.94, 95% CI 0.92 to 0.97; 5+ years: IRR 0.91, 95% CI 0.89 to 0.93) of hormonal contraceptives, but not progestogen-only contraceptives, were associated with reduced risk of severe asthma exacerbation compared with non-use. CONCLUSIONS: Use of hormonal contraceptives may reduce the risk of severe asthma exacerbation in reproductive-age women. Mechanistic studies investigating the biological basis for the influence of hormonal contraceptives on clinical outcomes of asthma in women are required. PROTOCOL REGISTRATION NUMBER: European Union electronic Register of Post-Authorisation Studies (EUPAS22967).

Hormonal contraceptives and onset of asthma in reproductive-age women: Population-based cohort study.

BACKGROUND: Despite well-described sex differences in asthma incidence, there remains uncertainty about the role of female sex hormones in the development of asthma. OBJECTIVE: We sought to investigate whether hormonal contraceptive use, its subtypes, and duration of use were associated with new-onset asthma in reproductive-age women. METHODS: Using the Optimum Patient Care Research Database, a UK national primary care database, we constructed an open cohort of 16- to 45-year-old women (N = 564,896) followed for up to 17 years (ie, January 1, 2000, to December 31, 2016). We fitted multilevel Cox regression models to analyze the data. RESULTS: At baseline, 26% of women were using any hormonal contraceptives. During follow-up (3,597,146 person-years), 25,288 women developed asthma, an incidence rate of 7.0 (95% CI, 6.9-7.1) per 1000 person-years. Compared with nonuse, previous use of any hormonal contraceptives (hazard ratio [HR], 0.70; 95% CI, 0.68-0.72), combined (HR, 0.70; 95% CI, 0.68-0.72), and progestogen-only therapy (HR, 0.70; 95% CI, 0.67-0.74) was associated with reduced risk of new-onset asthma. For current use, the estimates were as follows: any (HR, 0.63; 95% CI, 0.61-0.65), combined (HR, 0.65; 95% CI, 0.62-0.67), and progestogen-only therapy (HR, 0.59; 95% CI, 0.56-0.62). Longer duration of use (1-2 years: HR, 0.83; 95% CI, 0.81-0.86; 3-4 years: HR, 0.64; 95% CI, 0.61-0.67; 5+ years: HR, 0.46; 95% CI, 0.44-0.49) was associated with a lower risk of asthma onset than nonuse. CONCLUSIONS: Hormonal contraceptive use was associated with reduced risk of new-onset asthma in women of reproductive age. Mechanistic investigations to uncover the biological processes for these observations are required. Clinical trials investigating the safety and effectiveness of hormonal contraceptives for primary prevention of asthma will be helpful to confirm these results.

High health gain patients with asthma: a cross-sectional study analysing national Scottish data sets.

Studies have shown that a small proportion of patients have particularly high needs and are responsible for disproportionally high disease burden. Estimates suggest that 2-5% of patients are high users of healthcare for their health gain. Such patients in Scotland are referred to as high health gain (HHG) patients. We wanted to investigate if there were HHG individuals with asthma in Scotland. We analysed data from the Scottish Health Survey (2010-11), and primary and National Health Survey (NHS) secondary healthcare and administrative data sets (2011-12). In all, 1,379,690 (26.0%) and 836,135 (15.8%) people reported to have ever had and currently have symptoms suggestive of asthma, respectively; 369,868 (7.0%) people reported current symptomatic clinician-diagnosed asthma. 310,050 (5.6%) people had clinician-reported-diagnosed asthma; there were 289,120 nurse consultations, 215,610 GP consultations, 9235 accident and emergency visits (0.2% people), 8263 ambulance conveyances (0.2% people), 7744 inpatient episodes (0.1% people), 3600 disability allowance claims (0.1% people), 187 intensive care unit (ICU) episodes and 94 deaths from asthma. From our study a maximum of about 9.4% of asthma patients (n = 29,145), which is 0.5% of the Scottish population, and from the National Review of Asthma Deaths' estimate (10% hospitalised), a minimum of nine people had severe asthma attacks that needed acute hospital attendance/admission. We found that although a high proportion of the Scottish population had symptoms suggestive of asthma and clinician diagnosed asthma, only a small proportion of asthma patients experienced exacerbations that were severe enough to warrant hospital attendance/admission in any given year. Developing risk prediction models to identify these HHG patients has the potential to both improve health outcomes while substantially reducing healthcare expenditure.

Exogenous sex steroid hormones and asthma in females: protocol for a population-based retrospective cohort study using a UK primary care database.

INTRODUCTION: Female sex steroid hormones have been implicated in sex-related differences in the development and clinical outcomes of asthma. The role of exogenous sex steroids, however, remains unclear. Our recent systematic review highlighted the lack of high-quality population-based studies investigating this subject. We aim to investigate whether the use of hormonal contraception and hormone replacement therapy (HRT), subtypes and route of administration are associated with asthma onset and clinical outcomes in reproductive age and perimenopausal/postmenopausal females. METHODS AND ANALYSIS: Using the Optimum Patient Care Research Database (OPCRD), a national primary care database in the UK, we will construct a retrospective longitudinal cohort of reproductive age (16-45 years) and perimenopausal/postmenopausal (46-70 years) females. We will estimate the risk of new-onset asthma using Cox regression and multilevel modelling for repeated asthma outcomes, such as asthma attacks. We will adjust for confounding factors in all analyses. We will evaluate interactions between the use of exogenous sex hormones and body mass index and smoking by calculating the relative excess risk due to interaction and the attributable proportion due to interaction. With 90% power, we need 23 700 reproductive age females to detect a 20% reduction (risk ratio 0.8) in asthma attacks for use of any hormonal contraception and 6000 perimenopausal/postmenopausal females to detect a 40% (risk ratio 1.40) increased risk of asthma attacks for use of any HRT. ETHICS AND DISSEMINATION: We have obtained approval (ADEPT1317) from the Anonymised Data Ethics and Protocol Transparency Committee which grants project-specific ethics approvals for the use of OPCRD data. Optimum Patient Care has an existing NHS Health Research Authority ethics approval for the use of OPCRD data for research (15/EM/150). We will present our findings at national and international scientific meetings and publish the results in international peer-reviewed journals. TRIAL REGISTRATION NUMBER: EUPAS22967.

Improving predictive asthma algorithms with modelled environment data for Scotland: an observational cohort study protocol.

INTRODUCTION: Asthma has a considerable, but potentially, avoidable burden on many populations globally. Scotland has some of the poorest health outcomes from asthma. Although ambient pollution, weather changes and sociodemographic factors have been associated with asthma attacks, it remains unclear whether modelled environment data and geospatial information can improve population-based asthma predictive algorithms. We aim to create the afferent loop of a national learning health system for asthma in Scotland. We will investigate the associations between ambient pollution, meteorological, geospatial and sociodemographic factors and asthma attacks. METHODS AND ANALYSIS: We will develop and implement a secured data governance and linkage framework to incorporate primary care health data, modelled environment data, geospatial population and sociodemographic data. Data from 75 recruited primary care practices (n=500 000 patients) in Scotland will be used. Modelled environment data on key air pollutants at a horizontal resolution of 5 km×5 km at hourly time steps will be generated using the EMEP4UK atmospheric chemistry transport modelling system for the datazones of the primary care practices' populations. Scottish population census and education databases will be incorporated into the linkage framework for analysis. We will then undertake a longitudinal retrospective observational analysis. Asthma outcomes include asthma hospitalisations and oral steroid prescriptions. Using a nested case-control study design, associations between all covariates will be measured using conditional logistic regression to account for the matched design and to identify suitable predictors and potential candidate algorithms for an asthma learning health system in Scotland.Findings from this study will contribute to the development of predictive algorithms for asthma outcomes and be used to form the basis for our learning health system prototype. ETHICS AND DISSEMINATION: The study received National Health Service Research Ethics Committee approval (16/SS/0130) and also obtained permissions via the Public Benefit and Privacy Panel for Health and Social Care in Scotland to access, collate and use the following data sets: population and housing census for Scotland; Scottish education data via the Scottish Exchange of Data and primary care data from general practice Data Custodians. Analytic code will be made available in the open source GitHub website. The results of this study will be published in international peer reviewed journals.

Poor glycaemic control and its metabolic and demographic risk factors in a Malaysian community-based study.

OBJECTIVES: The lack of population-based evidence on the risk factors for poor glycaemic control in diabetics, particularly in resource-poor settings, is a challenge for the prevention of long-term complications. This study aimed to identify the metabolic and demographic risk factors for poor glycaemic control among diabetics in a rural community in Malaysia. METHODS: A total of 1844 (780 males and 1064 females) known diabetics aged ≥ 35 years were identified from the South East Asia Community Observatory (SEACO) health and demographic surveillance site database. RESULTS: 41.3% of the sample had poor glycaemic control. Poor glycaemic control was associated with age and ethnicity, with older participants (65+) better controlled than younger adults (45-54), and Malaysian Indians most poorly controlled, followed by Malay and then Chinese participants. Metabolic risk factors were also highly associated with poor glycaemic control. CONCLUSIONS: There is a critical need for evidence for a better understanding of the mechanisms of the associations between risk factors and glycaemic control.

Smoke-free legislation and paediatric hospitalisations for acute respiratory tract infections: national quasi-experimental study with unexpected findings and important methodological implications.

OBJECTIVES: We investigated whether Scottish implementation of smoke-free legislation was associated with a reduction in unplanned hospitalisations or deaths ('events') due to respiratory tract infections (RTIs) among children. DESIGN: Interrupted time series (ITS). SETTING/PARTICIPANTS: Children aged 0-12 years living in Scotland during 1996-2012. INTERVENTION: National comprehensive smoke-free legislation (March 2006). MAIN OUTCOME MEASURE: Acute RTI events in the Scottish Morbidity Record-01 and/or National Records of Scotland Death Records. RESULTS: 135 134 RTI events were observed over 155 million patient-months. In our prespecified negative binomial regression model accounting for underlying temporal trends, seasonality, sex, age group, region, urbanisation level, socioeconomic status and seven-valent pneumococcal vaccination status, smoke-free legislation was associated with an immediate rise in RTI events (incidence rate ratio (IRR)=1.24, 95% CI 1.20 to 1.28) and an additional gradual increase (IRR=1.05/year, 95% CI 1.05 to 1.06). Given this unanticipated finding, we conducted a number of post hoc exploratory analyses. Among these, automatic break point detection indicated that the rise in RTI events actually preceded the smoke-free law by 16 months. When accounting for this break point, smoke-free legislation was associated with a gradual decrease in acute RTI events: IRR=0.91/year, 95% CI 0.87 to 0.96. CONCLUSIONS: Our prespecified ITS approach suggested that implementation of smoke-free legislation in Scotland was associated with an increase in paediatric RTI events. We were concerned that this result, which contradicted published evidence, was spurious. The association was indeed reversed when accounting for an unanticipated antecedent break point in the temporal trend, suggesting that the legislation may in fact be protective. ITS analyses should be subjected to comprehensive robustness checks to assess consistency.

Land cover and air pollution are associated with asthma hospitalisations: A cross-sectional study.

BACKGROUND: There is increasing policy interest in the potential for vegetation in urban areas to mitigate harmful effects of air pollution on respiratory health. We aimed to quantify relationships between tree and green space density and asthma-related hospitalisations, and explore how these varied with exposure to background air pollution concentrations. METHODS: Population standardised asthma hospitalisation rates (1997-2012) for 26,455 urban residential areas of England were merged with area-level data on vegetation and background air pollutant concentrations. We fitted negative binomial regression models using maximum likelihood estimation to obtain estimates of asthma-vegetation relationships at different levels of pollutant exposure. RESULTS: Green space and gardens were associated with reductions in asthma hospitalisation when pollutant exposures were lower but had no significant association when pollutant exposures were higher. In contrast, tree density was associated with reduced asthma hospitalisation when pollutant exposures were higher but had no significant association when pollutant exposures were lower. CONCLUSIONS: We found differential effects of natural environments at high and low background pollutant concentrations. These findings can provide evidence for urban planning decisions which aim to leverage health co-benefits from environmental improvements.