Traffic pollution and the incidence of cardiorespiratory outcomes in an adult cohort in London.

OBJECTIVES: The epidemiological evidence for adverse health effects of long-term exposure to air and noise pollution from traffic is not coherent. Further, the relative roles of background versus near traffic pollution concentrations in this process are unclear. We investigated relationships between modelled concentrations of air and noise pollution from traffic and incident cardiorespiratory disease in London. METHODS: Among 211 016 adults aged 40-79 years registered in 75 Greater London practices between 2005 and 2011, the first diagnosis for a range of cardiovascular and respiratory outcomes were identified from primary care and hospital records. Annual baseline concentrations for nitrogen oxide (NOx), particulate matter with a median aerodynamic diameter <2.5 µm (PM2.5) attributable to exhaust and non-exhaust sources, traffic intensity and noise were estimated at 20 m2 resolution from dispersion models, linked to clinical data via residential postcode. HRs were adjusted for confounders including smoking and area deprivation. RESULTS: The largest observed associations were between traffic-related air pollution and heart failure (HR=1.10 for 20 µg/m3 change in NOx, 95% CI 1.01 to 1.21). However, no other outcomes were consistently associated with any of the pollution indicators, including noise. The greater variations in modelled air pollution from traffic between practices, versus within, hampered meaningful fine spatial scale analyses. CONCLUSIONS: The associations observed with heart failure may suggest exacerbatory effects rather than underlying chronic disease. However, the overall failure to observe wider associations with traffic pollution may reflect that exposure estimates based on residence inadequately represent the relevant pattern of personal exposure, and future studies must address this issue.

Long-term exposure to outdoor air pollution and the incidence of chronic obstructive pulmonary disease in a national English cohort.

OBJECTIVES: The role of outdoor air pollution in the incidence of chronic obstructive pulmonary disease (COPD) remains unclear. We investigated this question using a large, nationally representative cohort based on primary care records linked to hospital admissions. METHODS: A cohort of 812 063 patients aged 40-89 years registered with 205 English general practices in 2002 without a COPD diagnosis was followed from 2003 to 2007. First COPD diagnoses recorded either by a general practitioner (GP) or on admission to hospital were identified. Annual average concentrations in 2002 for particulate matter with an aerodynamic diameter <10 µm (PM10) and <2.5 µm (PM2.5), nitrogen dioxide (NO2), ozone and sulfur dioxide (SO2) at 1 km(2) resolution were estimated from emission-based dispersion models. Hazard ratios (HRs) per interquartile range change were estimated from Cox models adjusting for age, sex, smoking, body mass index and area-level deprivation. RESULTS: 16 034 participants (1.92%) received a COPD diagnosis from their GP and 2910 participants (0.35%) were admitted to hospital for COPD. After adjustment, HRs for GP recorded COPD and PM10, PM2.5 and NO2 were close to unity, positive for SO2 (HR=1.07 (95% CI 1.03 to 1.11) per 2.2 µg/m(3)) and negative for ozone (HR=0.94 (0.89 to 1.00) per 3 µg/m(3)). For admissions HRs for PM2.5 and NO2 remained positive (HRs=1.05 (0.98 to 1.13) and 1.06 (0.98 to 1.15) per 1.9 µg/m(3) and 10.7 µg/m(3), respectively). CONCLUSIONS: This large population-based cohort study found limited, inconclusive evidence for associations between air pollution and COPD incidence. Further work, utilising improved estimates of air pollution over time and enhanced socioeconomic indicators, is required to clarify the association between air pollution and COPD incidence.

Statin use after first myocardial infarction in UK men and women from 1997 to 2006: Who started and who continued treatment?

BACKGROUND AND AIMS: To examine trends in initiation and continuation of statin treatment after myocardial infarction (MI) and their determinants, during a period of increasing usage. METHODS AND RESULTS: 9367 patients aged 30-84 with a first Myocardial Infarction (MI) in 1997-2006 were identified in DIN-LINK, an anonymised, UK primary care database. We assessed statin initiation (prescription within 6 months of MI) and continued therapy (% covered by a prescription on a given day of those prescribed a statin within 6 months). The influences of co-morbidities and socio-economic deprivation (Index of Multiple Deprivation) were examined. Statin initiation increased from 37% for MIs in 1997 to 92% in 2006. Continuation at 1 year remained stable over successive cohorts at approximately 80%, settling to about 76% in patients with 5-10 years follow up. Younger age, affluence, revascularisation in 6 months after MI, and absence of congestive heart failure, predicted higher initiation and continuation; a diagnosis of hypertension or diabetes predicted higher initiation, while smoking was associated with poorer continuation. Men had higher initiation and continued therapy, but these effects were largely explained by their younger age. Type of statin initially prescribed did not influence continued usage. CONCLUSION: Statin use after MI increased markedly between 1997 and 2006, whilst continued therapy remained high and stable. Importantly, first choice of statin had no effect on continuation. Whilst the high current levels of initiation may have reached a ceiling, increasing continuation rates among smokers, older patients and those from lower socio-economic groups, should remain a priority.

Antipsychotic prescribing to older people living in care homes and the community in England and Wales.

OBJECTIVE: Excessive use of antipsychotic medication by older people is an international concern, but there is limited comparative information on their use in different residential settings. This paper describes and compares antipsychotic prescribing to older people in care homes and the community in England and Wales. METHOD: Analysis of a primary care database (THIN) with 403 259 community and 10 387 care home residents aged 65-104 years in 2008-9. RESULTS: 3677 (0.9%) patients in the community and 2173 (20.9%) in care homes (20.5% in residential homes, 21.7% in nursing homes) received an antipsychotic medication prescription in the last 90 days. Most patients had received prescriptions for more than three months and 60% of prescriptions were for atypical antipsychotics. In patients without severe mental illness, 2367 (0.6%) patients in the community and 1765 (18.2%) in care homes received antipsychotic medication; such prescribing was common for patients with recorded dementia (30.2% in care home, 10.1% in the community). In care homes, younger age and living in the North of England predicted prescribing, but care home type did not. In the community, female gender, increasing age, living in a deprived area and the North predicted prescribing. CONCLUSIONS: Despite safety concerns, antipsychotic prescribing is markedly higher in care homes than in the community, and strongly associated with dementia in both settings. In England and Wales, we estimate that 54 000 older care home patients and 50 000 community patients receive antipsychotic medication without a diagnosis of severe mental illness with important implications for health and social services.

Infections presenting for clinical care in early life and later risk of hay fever in two UK birth cohorts.

BACKGROUND: The 'hygiene hypothesis' proposes that infections in infancy protect against hay fever (HF). We investigated infections during infancy in relation to HF, including rarer ones not previously researched in this context, while examining the role of potential confounding variables. METHODS: From birth cohorts derived within the General Practice Research Database (GPRD) and Doctors Independent Network (DIN) database of computerized patient records from UK general practice, we selected 3549 case-control pairs, matched for practice, age, sex and control follow-up to case diagnosis. Conditional logistic regressions were fitted for each of 30 infections; behavioural problems (BP) acted as a control condition unrelated to HF. Odds ratios (OR), adjusted for consultation frequency were pooled across the databases using fixed effect models. We also adjusted for sibship size in GPRD and a socioeconomic marker in DIN. RESULTS: Upper respiratory tract infections, diarrhoea and vomiting and acute otitis media in infancy were each related with a moderately increased risk of HF in both databases, as were BP. These associations were lost on adjustment for consultation frequency. Only bronchiolitis was significantly associated with a reduced pooled risk of HF after adjustment for consultations (OR = 0.8). Adjustment for sibship size in GPRD and a socioeconomic marker in DIN had little impact on the OR. CONCLUSIONS: Of 30 infectious illnesses investigated, none had strong or consistent associations with HF after adjustment for consultation frequency. Except for bronchiolitis, possibly a chance finding, none of the clinically apparent infections considered appear to have an important role in allergy prevention.

The epidemiology of medical treatment for glaucoma and ocular hypertension in the United Kingdom: 1994 to 2003.

AIMS: To study trends in the prevalence of being treated for glaucoma and ocular hypertension from 1994 to 2003, and to examine factors determining treatment in 2002. METHODS: Computerised data (the DIN-LINK database) from 131 general practices across the United Kingdom, in which half a million patients aged 40 years or more were registered annually, were used. On average 10 000 patients were treated for glaucoma and ocular hypertension annually. RESULTS: Prevalence of being treated for glaucoma and ocular hypertension increased from 1.7% in 1994 to 2.3% in 2003. Those aged 85 years or more were 13 times (95% CI 12.2 to 13.8) more likely to be treated than those aged 40-64 years. Men were more likely to be treated than women (OR 1.24, 95% CI 1.19 to 1.28). Subjects "hard pressed" were less likely to be treated than "wealthy achievers" (OR 0.92, 95% CI 0.86 to 0.99). While use of topical beta blocker only medications has declined since 1995, use of topical prostaglandins and combination therapies has increased. In 2003, use of prostaglandins overtook beta blocker only medications. CONCLUSION: Prevalence of being treated for glaucoma has increased over time, and rises with age. Differences in treatment by sex and social status could be explained by use of or access to health care or by underlying prevalence of disease. Trends in treated glaucoma emphasise the shift from use of topical beta blockers to newer therapies.

C-reactive protein concentration in children: relationship to adiposity and other cardiovascular risk factors.

Whether or not C-reactive protein (CRP) predicts heart disease in adults because it is a marker of damage or atherosclerosis is difficult to assess. In children, there is no confounding with coronary disease or active smoking. We measured CRP in 699 children aged 10-11 years. CRP levels were 47% higher in girls than boys, and rose with age by 15%/year. CRP levels were 270% (95% CI, 155-439%) higher in the top fifth than the bottom fifth of Ponderal index (weight/height(3)). After adjustment, CRP levels remained 104% (95% CI, 23-236%) higher in the 56 children of South Asian origin. CRP was unrelated to: birth weight, height, social class, Helicobacter pylori infection or passive smoke exposure. CRP was correlated with several cardiovascular risk factors, but only fibrinogen (r = 0.33, P = 0.0001), HDL-cholesterol (r = -0.13, P = 0.0006), heart rate (r = 0.12, P = 0.002) and systolic blood pressure (r = 0.08, P = 0.02) remained statistically significant after adjustment. We conclude that adiposity is the major determinant of CRP levels in children while physical fitness has a small independent effect. The strong relationships with fibrinogen and HDL-cholesterol suggest a role for inflammation throughout life in the development of atherosclerosis and cardiovascular disease. Longitudinal studies are needed to determine whether these associations reflect long term elevations of these risk factors in some individuals, or short term fluctuations in different individuals.

Protection against vertical transmission in bovine neosporosis.

In this study we were interested to determine whether infection of cattle prior to pregnancy would afford any protection to the foetus if the dams were challenged with Neospora caninum at mid-gestation. The experiment comprised four groups of cattle: group 1, uninfected controls; group 2, inoculated with N. caninum tachyzoites 6 weeks prior to mating and then challenged with N. caninum at mid-gestation; group 3, naive cattle challenged with N. caninum at mid-gestation and group 4 were infected with N. caninum prior to mating and left unchallenged throughout pregnancy. Positive cell-mediated and humoral immune responses to N. caninum were recorded in groups 2 and 4 prior to pregnancy and in groups 2, 3 and 4 following challenge at mid-gestation. However there was a marked down regulation of the cell-mediated immune response in all groups around mid-gestation. There was a significant increase in rectal temperature response in animals in group 3 compared to group 2 following challenge but no other clinical symptoms of disease were recorded and all cattle proceeded to calving. At calving, pre-colostral blood samples were negative for antibodies to N. caninum in all the calves born to dams in groups 1, 2 and 4. In contrast, all the calves born to dams in group 3 had high levels of specific antibody to N. caninum indicating that they had been exposed to the parasite in utero. At post-mortem N. caninum DNA was detected in CNS, thymus and placental cotyledon samples in calves from group 3. All tissue samples from calves in the other 3 groups were negative for N. caninum DNA with the exception of one calf from group 2 where specific DNA was detected in a sample of spinal cord. These results suggest that the immune response generated in the dams in group 2 prior to pregnancy had protected against vertical transmission of the parasite following challenge at mid-gestation.

Maternal cotinine level during pregnancy and birthweight for gestational age.

BACKGROUND: Recent studies have found that cotinine is a better predictor of birthweight than the number of cigarettes smoked in pregnancy. In this paper we test this hypothesis and use cotinine to explore the effect of environmental tobacco smoke (ETS) on birthweight. METHODS: In all, 1254 white women were interviewed at booking, 28 and 36 weeks about the number and brand of cigarette smoked. Cotinine was assayed from blood samples taken on the day of interview. The outcome was birthweight for gestational age. RESULTS: There was good agreement between self-reported smoker/non-smoker status and maternal cotinine with 1.3% women mis-reported as non-smokers at booking, 0.6% and 1.8% mis-reported at 28 and 36 weeks respectively. Among smokers, cotinine was more closely related to birthweight than the number of cigarettes smoked at all three time points (r = -0.25 versus r = -0.16 at booking). A reduction in cotinine between booking and 28 weeks was associated with increased birthweight but the effect was not statistically significant. Among non-smokers the association between birthweight and cotinine was not statistically significant after adjusting for maternal height, parity, sex and gestational age. Difference in mean birthweight between non-smokers in the lower and upper quintiles of cotinine was 0.2% (95% CI: -2.4, 2.8). Pooling the results of 10 studies plus our own gave an estimated difference in mean birthweight between women unexposed and exposed to passive smoke of 31 g (95% CI: 19, 44). CONCLUSIONS: Cotinine is a better predictor of birthweight than the reported number of cigarettes smoked. If biochemical analysis is impossible, then self-reported smoking habit should be obtained prospectively using a structured approach. Any effect on birthweight of maternal passive smoking during pregnancy is small compared with the effects of maternal active smoking.

Do children who become autistic consult more often after MMR vaccination?

A close temporal association has been reported between the measles, mumps, and rubella (MMR) vaccination and dramatic behavioural decline in children subsequently diagnosed as autistic. We hypothesised that such a decline would be reflected in increased consultations with the child's general practitioner. The Doctor's Independent Network database was used to examine whether children subsequently diagnosed as autistic consulted more frequently than controls after MMR vaccination. No difference in consulting behaviour was seen in the six months post MMR. Any dramatic effect of MMR on behaviour seems unlikely.

A comparison of the recording of 30 common childhood conditions in the Doctor's Independent Network and General Practice Research Databases.

In this article we compare the recording of 30 common childhood conditions in two general practice databases of anonymised computerised medical records based on fundamentally different systems--the Doctor's Independent Network (DIN) database (Torex system) and the General Practice Research Database (GPRD) (In Practice Systems). Analysing the records of all children born 1990-1993 and followed for 5 years we found comparable results for most conditions, but differences between the hierarchical structures of the diagnostic coding systems (Read in DIN, OXMIS in GPRD) led to some differences between the databases. Practice variation was marked, but comparable between databases. Variation was greatest in conditions that are poorly defined clinically.

Home environment and severe asthma in adolescence: a population based case-control study.

OBJECTIVE: To investigate the effects of the home environment on the risk of severe asthma during adolescence. DESIGN: A questionnaire based case-control study drawn from a cross sectional survey of allergic diseases among secondary school pupils in Sheffield in 1991. SUBJECTS: 763 children whose parents had reported that over the previous 12 months they had suffered either 12 or more wheezing attacks or a speech limiting attack of wheeze. A further 763 children were frequency matched for age and school class to act as controls. Analysis was restricted to 486 affected children and 475 others born between 1975 and 1980 who had lived at their present address for more than three years. RESULTS: Independent associations with severe wheeze were seen for non-feather bedding, especially foam pillows (odds ratio 2.78; 95% confidence interval 1.89 to 4.17), and the ownership of furry pets now (1.51; 1.04 to 2.20) and at birth (1.70; 1.20 to 2.40). These estimates were derived from subjects whose parents denied making changes in the bedroom or avoiding having a pet because of allergy. Parental smoking, use of gas for cooking, age of mattress, and mould growth in the child's bedroom were not significantly associated with wheezing. CONCLUSIONS: Either our study questionnaire failed to detect the avoidance or removal of feather bedding by allergic families or there is some undetermined hazard related to foam pillows. Synthetic bedding and furry pets were both widespread in this population and may represent remediable causes of childhood asthma.

Relation of caffeine intake and blood caffeine concentrations during pregnancy to fetal growth: prospective population based study.

OBJECTIVES: To examine the association of plasma caffeine concentrations during pregnancy with fetal growth and to compare this with relations with reported caffeine intake. DESIGN: Prospective population based study. SETTING: District general hospital, inner London. SUBJECTS: Women booking for delivery between 1982 and 1984. Stored plasma was available for 1,500 women who had provided a blood sample on at least one occasion and for 640 women who had provided a sample on all three occasions (at booking, 28 weeks, and 36 weeks). MAIN OUTCOME MEASURE: Birth weight adjusted for gestational age, maternal height, parity, and sex of infant. The exposures of interest were reported caffeine consumption and blood caffeine concentration. Cigarette smoking was assessed by blood cotinine concentration. RESULTS: Caffeine intake showed no changes during pregnancy, but blood caffeine concentrations rose by 75%. Although caffeine intake increased steadily with increasing cotinine concentration above 15 ng/ml, blood caffeine concentrations fell. Caffeine consumption was inversely related to adjusted birth weight, the estimated effect being a 1.3% fall in birth weight for a 1,000 mg per week increase in intake (95% confidence interval 0.5% to 2.1%). The apparent caffeine effect was confined to cigarette smokers, among whom the estimated effect was-1.6%/1000 mg a week (-2.9% to -0.2%) after adjustment for cotinine and -1.3% (-2.7% to 0.1%) after further adjustment for social class and alcohol intake. Adjusted birth weight was unrelated to blood caffeine concentrations overall (P = 0.09, but a positive coefficient), after adjustment for cotinine (P = 0.73), or among current smokers (P = 0.45). CONCLUSIONS: Smokers consume more caffeine than non-smokers. Blood caffeine concentrations during pregnancy are not related to fetal growth, but caffeine intake is negatively associated with birth weight, with this effect being apparent only in smokers. The effect remains of borderline significance after adjustment for other factors. Prudent advice for pregnant women would be to reduce caffeine intake in conjunction with stopping smoking.

Blood pressure recording bias during a period when the Quality and Outcomes Framework was introduced.

The 2004 UK Quality and Outcomes Framework (QOF) remunerates general practitioners for achieving a target blood pressure (BP) of 150 mm Hg in 2000-2001, and only 19% in 2004-2005. However, there was a trend towards recording systolic values just below, rather than just above the 150 cut-off. In 2000-2001, 2.3% of patients had 148-149 recorded and 1.8% had 151-152. In 2004-2005, the figures were 4.2 and 1.3%, respectively. By smoothing the distribution we estimate that the true percentage of patients with SBP>150 mm Hg in 2004-2005 was 23%, rather than the 19% recorded. Moreover, patients with a recorded SBP=148-149 were more likely to have a recorded diastolic BP

Persistency with medical treatment for glaucoma and ocular hypertension in the United Kingdom: 1994-2005.

PURPOSE: To examine trends and demographic factors affecting persistence with ocular hypotensive therapy, from a period before prostaglandins were available to when they were the most common therapy. METHODS: Computerised patient records from 94 general practices across the United Kingdom, identified 5670 registered patients newly prescribed an ocular hypotensive drug (1993-2005). Persistence was defined as continuing therapy without a 90-day gap in prescription for (i) any ocular hypotensive and (ii) initial monotherapy. Time to failure with the treatment was compared using proportional hazard analyses, adjusted for age, gender, practice, year of initial treatment, and a sociodemographic indicator. Study findings were set in the context of a review of the literature. RESULTS: Percentage persistent at 1-year rose after 1997 when prostaglandins were introduced; from 61% in 1994-1996 to 70% in 2002-2004. Persistence with any treatment did not differ between those initiated on beta-blockers compared to prostaglandins (1.05, 95% CI 0.93-1.17). However, 20% of subjects initiated on beta-blockers received a prostaglandin by 1 year. Conversely, 8% of those initiated on prostaglandins received a beta-blocker. When failure with initial therapy was considered, beta-blockers appeared worse (1.35, 95% CI 1.21-1.50); this was consistent with findings from six studies in the review (1.40, 95% CI 1.34-1.46). Neither gender nor social factors were associated with persistence, but younger subjects (35-64 years) were significantly more likely to fail as were those over 85 years. CONCLUSIONS: Introduction of prostaglandins may explain an improvement in persistence over a decade. However, whether the higher cost of initiating patients on prostaglandins is justified remains questionable unless clinically indicated.

Trends in secondary prevention of ischaemic heart disease in the UK 1994 2005: use of individual and combination treatment.

BACKGROUND: Statins, antiplatelet drugs, beta-blockers and ACE inhibitors may produce marked benefits in secondary prevention of ischaemic heart disease (IHD), especially in combination. OBJECTIVE: To examine trends in treatment and factors associated with treatment using a population-based general practice database. DESIGN: Analysis of routinely collected computerised data from 201 general practices using iSOFT software contributing to the DIN-LINK database. SETTING AND PATIENTS: Subjects aged >or=35 years and registered with the practices; on average, 30 000 men and 21 000 women with IHD each year. MAIN OUTCOME MEASURE: Percentage of subjects with IHD receiving individual drugs and combined treatment in any given year. RESULTS: Between 1994 and 2005 use of drugs for secondary prevention increased markedly. By 2005, 80% of men and 70% of women were receiving a statin, 75% and 74% were receiving antiplatelet drugs, 55% and 48% were receiving beta-blockers and 57% and 51% were receiving an ACE inhibitor; 55% of men and 46% of women were receiving a statin, antiplatelet drug and either beta-blocker or ACE inhibitor, of whom just under half were receiving all four classes of drug. Gender differences were largely explained by more severe disease in men. In 2005, subjects less likely to receive combination therapy were older, had not had a myocardial infarction or revascularisation, and lacked comorbidities such as diabetes or hypertension. CONCLUSIONS: Despite high levels of statin and antiplatelet prescribing, opportunities exist for increasing the benefits of secondary prevention, especially through the wider use of combined treatments. Future targets could usefully include combination therapy.

Vaccinations, infections and antibacterials in the first grass pollen season of life and risk of later hayfever.

BACKGROUND: It has been hypothesized that early-life exposure to vaccinations, infections or antibacterials influence allergic disease development. Concurrent exposure to grass pollens may alter any effect. OBJECTIVE: To test the hypothesis that exposure to antibacterials, vaccinations (DTP or MMR) or specific infections during the first grass pollen seasons of life influences the risk of hayfever more than at any other time of the year. METHODS: Nested case-control studies were based on birth cohorts within two large databases of computerized patient records from UK general practices: the General Practice Research Database (GPRD) and Doctors' Independent Network (DIN). Seven thousand ninety-eight hayfever cases, diagnosed after age 2, were matched to controls for practice, age, sex and follow-up of control to case ascertainment date. Conditional logistic regression was used to compare exposure by age 1 (age 2 for MMR) inside vs. outside the grass pollen season (May, June, July). Odds ratios (ORs) were pooled across databases. RESULTS: There were no associations in either database between MMR during vs. outside the grass pollen season and later hayfever. Of 23 infections studied, none were statistically significant; although analyses for the less common conditions were limited by low statistical power. The pooled OR for hayfever comparing exposure to antibacterials only in the grass pollen season with only outside it was 1.20 (95% CI 0.98-1.47) and for DTP was 0.84 (95% CI 0.72-0.98). CONCLUSION: Although an interaction between early exposure to microbial agents and concurrent grass pollen exposure on hayfever risk seemed plausible, there was little evidence to support it across a range of analyses. However, the effect of DTP though weak deserves further study.