Individuals with filaggrin-related eczema and asthma have increased long-term medication and hospital admission costs.

BACKGROUND: Eczema and asthma are chronic diseases with onset usually before the age of 5 years. More than 50% of individuals with eczema will develop asthma and/or other allergic diseases. Several loss-of-function mutations in filaggrin (FLG) have been identified in patients with eczema. However, the association of FLG with healthcare use is unknown. OBJECTIVES: To determine whether FLG mutations are associated with increased prescribing for eczema and asthma and whether increased prescribing is associated with increased healthcare costs. METHODS: A secondary analysis of BREATHE, a cross-sectional study of gene-environment associations with asthma severity, was undertaken. BREATHE data was collected for 1100 participants with asthma, in Tayside and Fife, Scotland during the period 2003-2005. Through collaboration with the Health Informatics Centre in Dundee, BREATHE was linked to accident and emergency, community prescribing and Scottish morbidity records. The data linkage allowed longitudinal exploration of associations between genetic variation and prescribing. RESULTS: An association was found between FLG mutations and increased prescribing for mild and moderate eczema, asthma-reliever medicine and asthma exacerbations. A strong association was found between FLG mutations and prescribing of emollients [incidence rate ratio (IRR) 2·19, 95% confidence interval (CI) 1·36-3·52], treatment for severe eczema (IRR 2·18, 95% CI 1·22-3·91) and a combination of a long-acting ß2 -agonist and corticosteroids (IRR 3·29, 95% CI 1·68-6·43). CONCLUSIONS: The presence of FLG mutations in this cohort is associated with increased prescribing for eczema and asthma. Randomized controlled trials are required to determine if these individuals could benefit from management strategies to reduce morbidity and treatment costs.

Deriving a clinical prediction rule to target sexual healthcare to women attending British General Practices.

Some women attending General Practices (GPs) are at higher risk of unintended pregnancy (RUIP) and sexually transmitted infections (STI) than others. A clinical prediction rule (CPR) may help target resources using psychosocial questions as an acceptable, effective means of assessment. The aim was to derive a CPR that discriminates women who would benefit from sexual health discussion and intervention. Participants were recruited to a cross-sectional survey from six GPs in a city in South-East England in 2016. On arrival, female patients aged 16-44 years were invited to complete a questionnaire that addressed psychosocial factors, and the following self-reported outcomes: 2+ sexual partners in the last year (2PP) and RUIP. For each sexual risk, psychosocial questions were retained from logistic regression modelling which best discriminated women at risk using the C-statistic. Sensitivity and specificity were established in consultation with GP staff. The final sample comprised N = 1238 women. 2PP was predicted by 11 questions including age, binge-drinking weekly, ever having a partner who insulted you often, current smoking, and not cohabiting (C-statistic = 0.83, sensitivity = 73% and specificity = 77%). RUIP was predicted by 5 questions including sexual debut <16 years, and emergency contraception use in the last 6 months (C-statistic = 0.70, sensitivity = 69% and specificity = 57%). 2PP was better discriminated than RUIP but neither to a clinically-useful degree. The finding that different psychosocial factors predicted each outcome has implications for prevention strategies. Further research should investigate causal links between psychosocial factors and sexual risk.

Randomized clinical trial of sacral versus percutaneous tibial nerve stimulation in patients with faecal incontinence.

BACKGROUND: Sacral nerve stimulation (SNS) is a well established therapy for faecal incontinence (FI). Percutaneous tibial nerve stimulation (PTNS) is a newer, less invasive, treatment. The effectiveness and acceptability of these treatments have not been compared systematically. METHODS: An investigator-blinded randomized pilot trial of PTNS versus SNS with a parallel qualitative study was performed. Quantitative clinical outcomes and qualitative data from patient interviews were collected for both interventions. RESULTS: Forty patients (39 women; mean age 59 years) met the eligibility criteria; 23 were randomized to receive SNS and 17 to PTNS. Fifteen patients progressed to permanent SNS implantation and 16 received a full course of PTNS. Within-group effect sizes were marginally greater for SNS than for PTNS on available-case analysis. Mean(s.d.) FI episodes per week at baseline, and 3 and 6 months of follow-up were: 11·4(12·0), 4·0(4·0) and 4·9(6·9) respectively for SNS compared with 10·6(11·2), 5·8(6·9) and 6·3(6·9) for PTNS. Mean(s.d.) Cleveland Clinic Incontinence Score values at baseline, and 3 and 6 months were: 16·2(3·0), 11·1(5·2) and 10·4(5·6) for SNS versus 15·1(2·7), 11·7(4·4) and 12·1(5·2) for PTNS. Improvement of at least 50 per cent in FI episodes per week at 6 months was seen in 11 of 18 patients in the SNS group compared with seven of 15 in the PTNS group. Effect estimates for SNS with chronic implanted stimulation were larger (10 of 15 patients at 6 months). Disease-specific and generic quality-of-life improvements complemented clinical outcome data. Qualitative analysis of interview data suggested that both treatments had high acceptability amongst patients. CONCLUSION: In the short term, both SNS and PTNS provide some clinical benefit to patients with FI. Registration numbers: 2010-018728-15 and 10479 (http://public.ukcrn.org.uk/search/StudyDetail.aspx?StudyID=10479).

Association between Gc genotype and susceptibility to TB is dependent on vitamin D status.

Group-specific component (Gc) variants of vitamin D binding protein differ in their affinity for vitamin D metabolites that modulate antimycobacterial immunity. We conducted studies to determine whether Gc genotype associates with susceptibility to tuberculosis (TB). The following subjects were recruited into case-control studies: in the UK, 123 adult TB patients and 140 controls, all of Gujarati Asian ethnic origin; in Brazil, 130 adult TB patients and 78 controls; and in South Africa, 281 children with TB and 182 controls. Gc genotypes were determined and their frequency was compared between cases versus controls. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were obtained retrospectively for 139 Gujarati Asians, and case-control analysis was stratified by vitamin D status. Interferon (IFN)-gamma release assays were also performed on 36 Gujarati Asian TB contacts. The Gc2/2 genotype was strongly associated with susceptibility to active TB in Gujarati Asians, compared with Gc1/1 genotype (OR 2.81, 95% CI 1.19-6.66; p = 0.009). This association was preserved if serum 25(OH)D was <20 nmol.L(-1) (p = 0.01) but not if serum 25(OH)D was > or =20 nmol.L(-1) (p = 0.36). Carriage of the Gc2 allele was associated with increased PPD of tuberculin-stimulated IFN-gamma release in Gujarati Asian TB contacts (p = 0.02). No association between Gc genotype and susceptibility to TB was observed in other ethnic groups studied.

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.

Association between ambient air pollution and birth weight in São Paulo, Brazil.

OBJECTIVES: Previous studies have implicated air pollution in increased mortality and morbidity, especially in the elderly population and children. More recently, associations with mortality in infants and with some reproductive outcomes have also been reported. The aim of this study is to explore the association between exposure to outdoor air pollution during pregnancy and birth weight. DESIGN: Cross sectional study using data on all singleton full term live births during a one year period. For each individual birth, information on gestational age, type of delivery, birth weight, sex, maternal education, maternal age, place of residence, and parity was available. Daily mean levels of PM(10), sulphur dioxide, nitrogen dioxide, carbon monoxide, and ozone were also gathered. The association between birth weight and air pollution was assessed in regression models with exposure averaged over each trimester of pregnancy. SETTING: São Paulo city, Brazil. RESULTS: Birth weight was shown to be associated with length of gestation, maternal age and instruction, infant gender, number of antenatal care visits, parity, and type of delivery. On adjusting for these variables negative effects of exposure to PM(10) and carbon monoxide during the first trimester were observed. This effect seemed to be more robust for carbon monoxide. For a 1 ppm increase in mean exposure to carbon monoxide during the first trimester a reduction of 23 g in birth weight was estimated. CONCLUSIONS: The results are consistent in revealing that exposure to air pollution during pregnancy may interfere with weight gain in the fetus. Given the poorer outlook for low birthweight babies on a number of health outcomes, this finding is important from the public health perspective.

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.

Short-term associations between emergency hospital admissions for respiratory and cardiovascular disease and outdoor air pollution in London.

There are concerns about the possible short-term effects of outdoor air pollution on health in the United Kingdom. In a study conducted during the time period between 1987 and 1992, investigators determined that ozone had small, but significant effects on emergency respiratory admissions. In the current study, the authors investigated associations between emergency admissions and outdoor air pollution for the time period from 1992 to 1994, inclusive, and compared the results with those obtained in the earlier study. The authors also examined particulate matter less than 10 microm in diameter (PM10) and carbon monoxide in the current study. Appropriate confounding factors, such as seasonal patterns, temperature, and humidity, were controlled for, and the authors used Poisson regression to estimate the association between daily emergency admissions for respiratory and cardiovascular diseases and ozone, nitrogen dioxide, sulfur dioxide, carbon monoxide, particles measured as Black Smoke, and PM10. Significant positive associations were found between emergency hospital admissions for respiratory disease and PM10 and sulfur dioxide, but such an association did not exist for ozone. The results were not significantly different from earlier results from London and were comparable with those determined in North America and Europe. Cardiovascular disease was associated with carbon monoxide and Black Smoke, but weaker associations existed with the other pollutants studied.

Exercise for depression in care home residents: a randomised controlled trial with cost-effectiveness analysis (OPERA).

BACKGROUND: Many older people living in care homes (long term residential care or nursing homes) are depressed. Exercise is a promising non-drug intervention for preventing and treating depression in this population. OBJECTIVE: To evaluate the impact of a 'whole-home' intervention, consisting of training for residential and nursing home staff backed up with a twice-weekly, physiotherapist-led exercise class on depressive symptoms in care home residents. DESIGN: A cluster randomised controlled trial with a cost-effectiveness analysis to compare (1) the prevalence of depression in intervention homes with that in control homes in all residents contributing data 12 months after homes were randomised (cross-sectional analysis); (2) the number of depressive symptoms at 6 months between intervention and control homes in residents who were depressed at pre-randomisation baseline assessment (depressed cohort comparison); and (3) the number of depressive symptoms at 12 months between intervention and control homes in all residents who were present at pre-randomisation baseline assessment (cohort comparison). SETTING: Seventy-eight care homes in Coventry and Warwickshire and north-east London. PARTICIPANTS: Care home residents aged ≥ 65 years. INTERVENTIONS: Control intervention: Depression awareness training programme for care home staff. Active intervention: A 'whole-home' exercise intervention, consisting of training for care home staff backed up with a twice-weekly, physiotherapist-led exercise group. MAIN OUTCOME MEASURES: Geriatric Depression Scale-15, proxy European Quality of Life-5 Dimensions (EQ-5D), cost-effectiveness from an National Health Service perspective, peripheral fractures and death. RESULTS: We recruited a total of 1054 participants. Cross-sectional analysis: We obtained 595 Geriatric Depression Scale-15 scores and 724 proxy EQ-5D scores. For the cohort analyses we obtained 765 baseline Geriatric Depression Scale-15 scores and 776 proxy EQ-5D scores. Of the 781 who we assessed prior to randomisation, 765 provided a Geriatric Depression Scale-15 score. Of these 374 (49%) were depressed and constitute our depressed cohort. Resource-use and quality-adjusted life-year data, based on proxy EQ-5D, were available for 798 residents recruited prior to randomisation. We delivered 3191 group exercise sessions with 31,705 person attendances and an average group size of 10 (5.3 study participants and 4.6 non-study participants). On average, our participants attended around half of the possible sessions. No serious adverse events occurred during the group exercise sessions. In the cross-sectional analysis the odds for being depressed were 0.76 [95% confidence interval (CI) 0.53 to 1.09] lower in the intervention group at 12 months. The point estimates for benefit for both the cohort analysis (0.13, 95% CI -0.33 to 0.60) and depressed cohort (0.22, 95% CI -0.52 to 0.95) favoured the control intervention. There was no evidence of differences in fracture rates or mortality (odds ratio 1.07, 95% CI 0.79 to 1.48) between the two groups. There was no evidence of differences in the other outcomes between the two groups. Economic analysis: The additional National Health Service cost of the OPERA intervention was £374 per participant (95% CI -£655 to £1404); the mean difference in quality-adjusted life-year was -0.0014 (95% CI -0.0728 to 0.0699). The active intervention was thus dominated by the control intervention, which was more effective and less costly. CONCLUSION: The results do not support the use of a whole-home physical activity and moderate-intensity exercise programme to reduce depression in care home residents. TRIAL REGISTRATION: Current Controlled Trials ISRCTN43769277. FUNDING: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 18. See the Health Technology Assessment programme website for further project information.

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.

Timing of routine immunisations and subsequent hay fever risk.

BACKGROUND: Suggestions that immunisation influences allergic disease risk, either positively (pertussis) or negatively (BCG) are of concern for vaccination policy. AIMS: To determine whether DTP, MMR, and BCG vaccination in infancy influenced hay fever risk. METHODS: Case-control study of 7098 hay fever cases and controls, within two primary care databases. One control per case was matched for practice, age, and sex. Odds ratios (OR) were derived using conditional logistic regression. RESULTS: Compared to those completing in month 5 (base group) (39.3%), DTP unvaccinated children (4.3%) had a similar risk of hay fever (OR = 0.94, 95% CI 0.73 to 1.23). However, those completing after 12 months (4.2%) had a reduced risk (OR = 0.60, 95% CI 0.45 to 0.76) compared to the base group. Compared to those vaccinated in month 14 (base group) (29.5%), MMR unvaccinated children (2.3%) had an OR of 0.79 (95% CI 0.58 to 1.08). Completion of MMR after two years was associated with reduced hay fever risk (OR = 0.62, 95% CI 0.48 to 0.80) compared to the base group. The effects of late immunisation with DTP and MMR were independent. Those vaccinated with BCG by age 2 (2.4%) had an odds ratio of 1.28 (95% CI 0.96 to 1.70). Adjustment for consulting behaviour, social factors, or sibship size did not alter these associations. CONCLUSIONS: Immunisation against DTP or MMR does not increase the risk of hay fever. The lower confidence limit for BCG vaccination contradicts the hypothesised protective effect. The reduced risk of hay fever among children immunised late may be explained by a third factor causing both postponement and reduced risk such as intercurrent febrile illnesses.

Particulate air pollution and hospital admissions for cardiorespiratory diseases: are the elderly at greater risk?

A systematic literature review suggests that particulate air pollution is associated with daily admissions for both respiratory and cardiac diseases in people aged > 65 yrs. A model of acute effects is proposed which shows how admissions can be brought forward by a relatively short period of time as well as events being added that would not have happened at all except for air pollution. A model of the effects of air pollution on chronic disease is proposed that provides the background of long-term vulnerability upon which the increased short-term vulnerability is superimposed. A study of daily hospital admissions in London shows that for respiratory disease the relative risks of admission associated with particles reduce with increasing age, while for cardiac disease, there is no trend. When the attributable risk is estimated using baseline admission rates for respiratory disease, it is children who have the highest attributable risk, followed by the elderly. For cardiac disease there is a steep increase in attributable risk with age, reflecting the dominant influence of baseline risks. The attributable risk for cardiovascular disease in the elderly is considerably greater than for respiratory disease, due to higher baseline admission rates.

Particulate matter and daily mortality and hospital admissions in the west midlands conurbation of the United Kingdom: associations with fine and coarse particles, black smoke and sulphate.

OBJECTIVES: There is considerable evidence linking ambient particles measured as particulate matter with aerodynamic diameter <10 microm (PM(10)) to daily mortality and hospital admissions but it is not clear which physical or chemical components of the particle mixture are responsible. The relative effects of fine particles (PM(2.5)), coarse particles (PM(2.5-10)), black smoke (mainly fine particles of primary origin) and sulphate (mainly fine particles of secondary origin) were investigated, together with ozone, SO(2), NO(2), and CO, on daily mortality and hospital admissions in the west Midlands conurbation of the United Kingdom. METHODS: Time series of health outcome and environmental data were obtained for the period 1994-6. The relative risk of death or hospital admission was estimated with regression techniques, controlling for long term time trends, seasonal patterns, influenza epidemics, effects of day of the week, and temperature and humidity. Models were adjusted for any remaining residual serial correlation and overdispersion. The sensitivities of the estimates for the effects of pollution to the inclusion of a second pollutant and seasonal interactions (warm or cool) were also examined. RESULTS: Daily all cause mortality was not associated with any gaseous or particulate air pollutant in the all year analysis, although all measures of particles apart from PM(2.5-10) showed significant positive effects of the warm season. Neither respiratory nor cardiovascular admissions (all ages) were associated with any air pollutant, and there were no important seasonal interactions. However, analysis of admissions by age found evidence for various associations-notably between PM(10), PM(2.5), black smoke, SO(2,) and ozone (negative) and respiratory admissions in the 0-14 age group. The coarse fraction, PM(2.5-10) differed from PM(2.5) in having smaller and less consistent associations (including several large significant negative associations) and a different lag distribution. The results for black smoke, an indicator of fine primary carbonaceous particles, were very similar to those for PM(2.5), and tended to be more robust in two pollutant models. The effects of sulphate, an indicator of secondary particles, also showed some similarities to those of PM(2.5). CONCLUSIONS: Clear effects of air pollution on mortality and hospital admissions were difficult to discern except in certain age or diagnostic subgroups and seasonal analyses. It was also difficult to distinguish between different measures of particles. Within these limitations the results suggest that the active component of PM(10) resides mostly in the fine fraction and that this is due mainly to primary particles from combustion (mainly vehicle) sources with a contribution from secondary particles. Effects of the coarse fraction cannot be excluded.

Evolution of statin prescribing 1994-2001: a case of agism but not of sexism?

OBJECTIVE: To study trends in the use of lipid lowering drugs in the UK, and to assess which patient factors influence prescribing. METHODS: Routinely collected computerised medical data were analysed from 142 general practices across England and Wales that provide data for the Doctors' Independent Network database. Subjects included were people aged 35 years or more with treated ischaemic heart disease, averaging annually over 30,000. The temporal trend from 1994 to 2001 in prescription of lipid lowering drugs and daily statin dose and the odds ratios (ORs) for receiving a statin prescription in 1998 were examined. RESULTS: Lipid lowering drug prescribing increased greatly over time, entirely because of statins, so that in 2001 56.3% of men and 41.1% of women with ischaemic heart disease received lipid lowering drugs. However, 33% of these patients were on a < 20 mg simvastatin daily equivalent. In 1998 the OR for receiving a statin fell from 1 at age 55-64 to 0.64 at 65-74 and 0.16 at 75-84 years. The age effect was similar in those without major comorbidity. Revascularised patients were much more likely to receive a statin than those with angina (OR 3.92, 95% confidence interval (CI) 3.57 to 4.31). Men were more likely to receive a statin than women (OR 1.62, 95% CI 1.54 to 1.71) but this difference disappeared after adjustment for age and severity of disease (OR 1.06). Geographical region had little effect but there was a very weak socioeconomic gradient. CONCLUSIONS: Although prescribing has increased, many patients who may benefit from lipid lowering drugs either do not receive it or are undertreated, possibly because of lack of awareness of the relative potency of the different statins. Patients with angina and the elderly are less likely to receive treatment that may prevent a coronary event.

Association between air pollution and daily consultations with general practitioners for allergic rhinitis in London, United Kingdom.

Few published studies have looked at the health effects of air pollution in the primary care setting, and most have concentrated on lower rather than upper respiratory diseases. The authors investigated the association of daily consultations with general practitioners for allergic rhinitis with air pollution in London, United Kingdom. Generalized additive models were used to regress time series of daily numbers of patients consulting for allergic rhinitis against 1992--1994 measures of air pollution, after control for possible confounders and adjustment for overdispersion and serial correlation. In children, a 10th--90th percentile increase in sulfur dioxide (SO(2)) levels 4 days prior to consultation (13-31 microg/m(3)) was associated with a 24.5% increase in consultations (95% confidence interval: 14.6, 35.2; p < 0.00001); a 10th--90th percentile increase in averaged ozone (O(3)) concentrations on the day of consultation and the preceding 3 days (6--29 parts per billion) was associated with a 37.6% rise (95% confidence interval: 23.3, 53.5; p < 0.00001). For adults, smaller effect sizes were observed for SO(2) and O(3). The association with SO(2) remained highly significant in the presence of other pollutants. This study suggests that air pollution worsens allergic rhinitis symptoms, leading to substantial increases in consultations. SO(2) and O(3) seem particularly responsible, and both seem to contribute independently.

Acute effects of winter air pollution on respiratory function in schoolchildren in southern England.

AIM: To investigate the acute health effects of winter outdoor air pollution (nitrogen dioxide (NO(2)), ozone (O(3)), sulphur dioxide (SO(2)), sulphate (SO(4)(2-)),and particles (PM(10))) on schoolchildren in an area of southern England where levels of SO(2) had been reported to be high. METHODS: A total of 179 children, aged 7-13, from three schools (two urban and one rural location), were included. Peak expiratory flow rate (PEFR) and presence or absence of upper respiratory infections were recorded on 63 school days from 1 November 1996 to 14 February 1997. Air pollution and meteorological data were taken from monitors at each school site. The analysis regressed daily PEFR on pollutant level adjusting for confounders and serial correlation and calculated a weighted pooled estimate of effect overall for each pollutant. In addition, large decrements in PEFR were analysed as a binary outcome. Same day, lag 1, lag 2, and a five day average of pollutant levels were used. RESULTS: There were no clear effects of any pollutant on mean PEFR. In addition, we analysed large PEFR decrements (a binary outcome), observing consistent negative associations with NO(2), SO(4)(2-), and PM(10), although few lag/pollutant combinations were significant: odds ratios (95% CI) for five day average effect: NO(2) 24 h average 1.043 (1.000 to 1.089), SO(4)(2-) 1.090 (0.898 to 1.322), PM(10) 1.037 (0.992 to 1.084). The observed effects of PM(10) (only) were stronger in wheezy children (1.114 (1.057 to 1.174)). There were no consistent negative associations between large decrements and ozone or SO(2). CONCLUSIONS: There is no strong evidence for acute effects of winter outdoor air pollution on mean PEFR overall in this area, but there is evidence for negative effects on large PEFR decrements.

Short-term associations between outdoor air pollution and mortality in London 1992-4.

OBJECTIVES: A previous study of the short term effects of air pollution in London from April 1987 to March 1992 found associations between all cause mortality and black smoke and ozone, but no clear evidence of specificity for cardiorespiratory deaths. London data from 1992 to 1994 were analysed to examine the consistency of results over time and to include particles with a mean aerodynamic diameter of 10 microns (PM10) and carbon monoxide. METHODS: Poisson regression was used of daily mortality counts grouped by age and diagnosis, adjusting for trend, seasonality, calendar effects, deaths from influenza, meteorology, and serial correlation. The pollutants examined were particles (PM10 and black smoke), nitrogen dioxide, ozone, sulphur dioxide, and carbon monoxide with single and cumulative lags up to 3 days. RESULTS: No significant associations were found between any pollutant and all cause mortality, but, with the exception of ozone, all estimates were positive. Each pollutant apart from ozone was significantly associated with respiratory mortality; PM10 showed the largest effect (4% increase in deaths of all ages for a 10th-90th percentile increment). The pollutants significantly associated with cardiovascular deaths were nitrogen dioxide, ozone, and black smoke but there was no evidence of an association with PM10. In two pollutant models of respiratory deaths, the effect of black smoke, which in London indicates fine particles of diesel origin, was independent of that of PM10, but not vice versa. CONCLUSION: These results from a new data set confirm a previous report that there are associations between various air pollutants and daily mortality in London. This new study found greater specificity for associations with respiratory and cardiovascular deaths, and this increases the plausibility of a causal explanation. However, the effects of ozone found in the earlier study were not replicated. The fraction of PM10 which comprises black smoke accounted for much of the effect of PM10.

Short-term associations between outdoor air pollution and visits to accident and emergency departments in London for respiratory complaints.

Many epidemiological studies have shown positive short-term associations between health and current levels of outdoor air pollution. The aim of this study was to investigate the association between air pollution and the number of visits to accident and emergency (A&E) departments in London for respiratory complaints. A&E visits include the less severe cases of acute respiratory disease and are unrestricted by bed availability. Daily counts of visits to 12 London A&E departments for asthma, other respiratory complaints, and both combined for a number of age groups were constructed from manual registers of visits for the period 1992-1994. A Poisson regression allowing for seasonal patterns, meteorological conditions and influenza epidemics was used to assess the associations between the number of visits and six pollutants: nitrogen dioxide, ozone, sulphur dioxide, carbon monoxide, and particles measured as black smoke (BS) and particles with a median aerodynamic diameter of <10 microm (PM10). After making an allowance for the multiplicity of tests, there remained strong associations between visits for all respiratory complaints and increases in SO2: a 2.8% (95% confidence interval (CI) 0.7-4.9) increase in the number of visits for a 18 microg x (-3) increase (10th-90th percentile range) and a 3.0% (95% CI 0.8-5.2) increase for a 31 microg x m(-3) increase in PM10. There were also significant associations between visits for asthma and SO2, NO2 and PM10. No significant associations between O3 and any of the respiratory complaints investigated were found. Because of the strong correlation between pollutants, it was difficult to identify a single pollutant responsible for the associations found in the analyses. This study suggests that the levels of air pollution currently experienced in London are linked to short-term increases in the number of people visiting accident and emergency departments with respiratory complaints.

Early-life exposure to antibacterials and the subsequent development of hayfever in childhood in the UK: case-control studies using the General Practice Research Database and the Doctors' Independent Network.

BACKGROUND: Theoretically, antibacterial agents in early life might influence allergic sensitization in two ways: (i) as an indicator of infectious illness, they might be expected to protect against allergy; (ii) alternatively they might increase the risk through effects on the commensal bowel flora. Epidemiological evidence linking the prescription of antibacterial agents in early life to the subsequent development of hayfever is conflicting. OBJECTIVE: To establish definitively whether an association exists between early-life antibacterial exposure and childhood hayfever diagnosis. METHODS: Nested case-control studies were based on birth cohorts of children identified within two large UK general practice databases of electronic patient records. One hundred and sixteen thousand and four hundred and ninety-three children from 605 general practices were identified as being continuously registered from birth to at least age 5 years. Seven thousand and ninety-eight cases were diagnosed with hayfever after the age of 2 years. One control per case was matched for practice, birth month, sex and still being registered on case diagnosis date. Odds ratios were derived from conditional logistic regressions within each database followed by pooling using a fixed-effect model. RESULTS: The pooled odds ratio for hayfever was 1.11, 95% CI (1.03-1.20) if exposed to antibacterials in the first year of life, 1.35 (1.25-1.46) in year 2 and 1.47 (1.37-1.59) in year 3. Adjusting for consultation frequency reduced these odds ratios to 0.92, 1.05 and 1.10, respectively. There was no evidence that broader spectrum antibacterials, exposure in any specific month of year 1 or in the grass pollen season influenced the risk of hayfever. CONCLUSION: These data exclude any important effect of antibacterial exposure in infancy on subsequent hayfever risk. Associations reported in earlier studies have likely been exaggerated through publication bias and by lack of control for the tendency of some families to consult frequently for a range of conditions.