Search

Interaction between arterial stiffness and hypertension plays an important role in the development of cardiovascular disease. Accordingly, assessment of arterial stiffness may provide a tool for estimating cardiovascular risk and monitoring therapy in hypertensive patients. Radiofrequency-based vascular ultrasound allows accurate noninvasive assessment of local mechanical properties of large arteries, but for its use in clinical practice, reference values according to age and sex are mandatory for each vascular site. To provide reference values for common carotid artery stiffness as assessed by an echo-tracking imaging system Hitachi-Aloka, we pooled measurements collected in 1847 healthy subjects aged 3–74 years (1008 males and 839 females) recruited in 14 European centers in the E-tracking International Collaboration (ETIC). Statistical models were developed to describe relationships of different stiffness indices with age and to calculate median values and Z-scores corresponding to ± 1 and ± 2 standard deviations. In our apparently healthy population, age accounted for 53% of variability in the elastic modulus (epsilon), 39% in arterial compliance, 47% in stiffness index (β), and 56% in local pulse wave velocity; on average, blood pressure accounted for a further 7.5% of variability. Dependence on age was not linear; changes in mean values increased at older ages, especially for epsilon and β. There was an interaction between age and gender for arterial compliance, which was higher in males. We present nomograms and a software that can be used for the automated calculation of Z-scores for local carotid stiffness in individual patients. These tools can be used to establish prognostic indicators or surrogate targets for treatment monitoring.

IntroductionEarly infant diet might influence the risk of subsequent allergic disease.MethodsThe Merthyr Allergy Prevention Study (MAPS) was a randomised controlled trial in infants at high risk of allergic disease. The trial determined whether a cow’s milk exclusion diet for the first 4 months of life decreased the risk of allergic disease including asthma compared with a normal diet. A soya milk preparation was offered to those in the intervention group. A standardised questionnaire for allergic disease was completed at ages 1, 7, 15 and 23 years, with clinical assessment at 1, 7 and 23 years. The effect of the intervention on the risk of atopy, asthma and wheeze at age 23 years was determined.Findings487 subjects entered the study; at age 23 years 299 completed the questionnaire, of which 119 attended clinical assessment. Subjects randomised to the intervention group had a significantly increased risk of atopy (adjusted OR 2.97, 95% CI 1.30 to 6.80; p=0.01) and asthma (OR 2.07, 95%CI 1.09 to 3.91; p=0.03) at age 23 years, but not wheeze (OR 1.43, 95%CI 0.87 to 2.37; p=0.16). Earlier exposure to cow’s milk was associated with a decreased risk of wheeze and asthma at age 23 years, while earlier exposure to soya milk was associated with an increased risk of atopy and asthma.InterpretationIn infants at high risk of allergic disease, either cow’s milk exclusion or early soya milk introduction for the first 4 months of life increases the risk of atopy, wheeze and asthma in adulthood.

Objective Examine the health and economic impact of extending screening intervals in people with Type 2 diabetes (T2DM) and Type 1 diabetes (T1DM) without diabetes-related retinopathy (DR). Setting Diabetic Eye Screening Wales (DESW). Study design Retrospective observational study with cost-utility analysis (CUA) and Decremental Cost-Effectiveness Ratios (DCER) study. Intervention Biennial screening versus usual care (annual screening). Inputs Anonymised data from DESW were linked to primary care data for people with two prior screening events with no DR. Transition probabilities for progression to DR were estimated based on a subset of 26,812 and 1232 people with T2DM and T1DM, respectively. DCER above £20,000 per QALY was considered cost-effective. Results The base case analysis DCER results of £71,243 and £23,446 per QALY for T2DM and T1DM respectively at a 3.5% discount rate and £56,822 and £14,221 respectively when discounted at 1.5%. Diabetes management represented by the mean HbA1c was 7.5% for those with T2DM and 8.7% for T1DM. Sensitivity analysis Extending screening to biennial based on HbA1c, being the strongest predictor of progression of DR, at three levels of HbA1c 6.5%, 8.0% and 9.5% lost one QALY saving the NHS £106,075; £58,653 and £31,626 respectively for T2DM and £94,696, £37,646 and £11,089 respectively for T1DM. In addition, extending screening to biennial based on the duration of diabetes > 6 years for T2DM per QALY lost, saving the NHS £54,106 and for 6-12 and > 12 years for T1DM saving £83,856, £23,446 and £13,340 respectively. Conclusions Base case and sensitivity analyses indicate biennial screening to be cost-effective for T2DM irrespective of HbA1c and duration of diabetes. However, the uncertainty around the DCER indicates that annual screening should be maintained for those with T1DM especially when the HbA1c exceeds 80 mmol/mol (9.5%) and duration of diabetes is greater than 12 years.

Background and objective\ud \ud Health status in childhood is correlated with educational outcomes. Emergency hospital admissions during childhood are common but it is not known how these unplanned breaks from schooling impact on education outcomes. We hypothesised that children who had emergency hospital admissions had an increased risk of lower educational attainment, in addition to the increased risks associated with other health, social and school factors.\ud \ud \ud Methods\ud \ud This record-linked electronic birth cohort, included children born in Wales between 1 January 1998 and 31 August 2001. We fitted multilevel logistic regression models grouped by schools, to determine whether emergency hospital inpatient admission before age 7 years was associated with the educational outcome of not attaining the expected level in a teacher-based assessment at age 7 years (KS1). We adjusted for pregnancy, perinatal, socio-economic, neighbourhood, pupil mobility and school-level factors.\ud \ud \ud Results\ud \ud The cohort comprised 64 934 children. Overall, 4680 (7.2%) did not attain the expected educational level. Emergency admission to hospital was associated with poor educational attainment (OR 1.12 95% Credible Interval (CI) 1.05, 1.20 for all causes during childhood, OR 1.19 95%CI 1.07, 1.32 for injuries and external causes and OR 1.31 95%CI 1.04, 1.22 for admissions during infancy), after adjusting for known determinants of education outcomes such as extreme prematurity, being small for gestational age and socio-economic indicators, such as eligibility for free school meals.\ud \ud \ud Conclusion\ud \ud Emergency inpatient hospital admission during childhood, particularly during infancy or for injuries and external causes was associated with an increased risk of lower education attainment at age 7 years, in addition to the effects of pregnancy factors (gestational age, birthweight) and social deprivation. These findings support the need for injury prevention measures and additional support in school for affected children to help them to achieve their potential.

Background: There are conflicting findings regarding the impact of residential mobility on immunisationstatus. Our aim was to determine whether there was any association between residential mobility andtake up of immunisations and whether they were delayed in administration.\ud \ud Methods: We carried out a cohort analysis of children born in Wales, UK. Uptake and time of immunisationwere collected electronically. We defined frequent movers as those who had moved: 2 or more times inthe period prior to the final scheduled on-time date (4 months) for 5 in 1 vaccinations; and 3 or moretimes in the period prior to the final scheduled on-time date (12 months) for MMR, pneumococcal andmeningitis C vaccinations. We defined immunisations due at 2–4 months delayed if they had not beengiven by age 1; and those due at 12–13 months as delayed if they had not been given by age 2.\ud \ud Results: Uptake rates of routine immunisations and whether they were given within the specified time-frame were high for both groups. There was no increased risk (odds ratios (95% confidence intervals)between frequent movers compared to non-movers for the uptake of: primary MMR 1.08 (0.88–1.32);booster Meningitis C 1.65 (0.93–2.92); booster pneumococcal 1.60 (0.59–4.31); primary 5 in 1 1.28(0.92–1.78); and timeliness: primary MMR 0.92 (0.79–1.07); booster Meningitis C 1.26 (0.77–2.07);booster pneumococcal 1.69 (0.23–12.14); and primary 5 in 1 1.04 (0.88–1.23).\ud \ud Discussion: Findings suggest that children who move home frequently are not adversely affected in termsof the uptake of immunisations and whether they were given within a specified timeframe. Both werehigh and may reflect proactive behaviour in the primary healthcare setting to meet Government coveragerates for immunisation.

Aims Determine the prevalence and severity of diabetic retinopathy (DR) and risk factors in a large community based screening programme, in order to accurately estimate the future burden of this specific and debilitating complication of diabetes. Methods A cross-sectional analysis of 91 393 persons with diabetes, 5003 type 1 diabetes and 86 390 type 2 diabetes, at their first screening by the community based National Diabetic Retinopathy Screening Service for Wales from 2005 to 2009. Image capture used 2×45° digital images per eye following mydriasis, classified by qualified retinal graders with final grading based on the worst eye. Results The prevalence of any DR and sightthreatening DR in those with type 1 diabetes was 56.0% and 11.2%, respectively, and in type 2 diabetes was 30.3% and 2.9%, respectively. The presence of DR, non-sight-threatening and sight-threatening, was strongly associated with increasing duration of diabetes for either type 1 or type 2 diabetes and also associated with insulin therapy in those with type 2 diabetes. Conclusions Prevalence of DR within the largest reported community-based, quality assured, DR screening programme, was higher in persons with type 1 diabetes; however, the major burden is represented by type 2 diabetes which is 94% of the screened population.

OBJECTIVE: To investigate the risk of emergency respiratory hospital admission during childhood associated with gestational age at birth and growth restriction in utero. METHODS: The study included a total population electronic birth cohort with anonymized record-linkage of multiple health and administrative data sets. Participants were 318 613 children born in Wales, United Kingdom, between May 1, 1998, and December 31, 2008. The main outcome measure was emergency respiratory hospital admissions. RESULTS: The rate of admission in the first year of life ranged from 41.5 per 100 child-years for infants born before 33 weeks’ gestation to 9.8 per 100 child-years for infants born at 40 to 42 weeks’ gestation. The risk of any emergency respiratory admission up to age 5 years increased as gestational age decreased to CONCLUSIONS: The risk of emergency respiratory admission up to age 5 years decreased with each successive week in gestation up to 40 to 42 weeks. Although the magnitude of increased risk associated with moderate and late preterm births is small, the number of infants affected is large and therefore presents a significant impact on health care services.

Background Eczema is common in infancy; however, there is little evidence about its natural history to adulthood. Objectives To study the natural history of eczema from birth to young adult life with particular reference to its relation to atopy. Methods A birth cohort of children with atopic family histories was followed for 23 years. Clinical examinations were conducted until the age of 7 years, skin-prick tests and serum total IgE were recorded in infancy and at ages 7 and 23 years, and questionnaires about eczema symptoms were completed at 15 and 23 years. Results Information was obtained on 497 subjects at birth, 482 at 1 year, 440 at 7 years, 363 at 15 years and 304 at 23 years. Eczema usually remitted from age 1 to 7 years but became more persistent from the age of 15 years, especially in those who were atopic. The prevalence of eczema rose in women from age 15 to 23 years but declined in men. Adults with eczema had higher IgE than those without at 3 months (geometric mean 3·0 vs. 1·7 kU L-1; P = 0·01), 7 years (107·9 vs. 45·2 kU L-1; P = 0·01) and 23 years (123·4 vs. 42·3 kU L-1; P = 0·01), and were more likely to have had positive skin-prick tests at 1 year of age. Current eczema was associated with raised IgE in infancy and adulthood but not in childhood. Conclusions Predisposed infants and children with eczema usually grow out of the disease, but in adolescence it is more likely to persist. Adult eczema is related to atopy from the age of 3 months. What's already known about this topic? Eczema is associated with atopy, asthma and rhinoconjunctivitis. Eczema in infancy usually remits but is more likely to persist if the child is atopic. After puberty eczema often persists to adult life. What does this study add? Adult eczema is associated with atopy from the age of 3 months. Atopy increases the likelihood of persistence after adolescence.

OBJECTIVES:To investigate the association between moving home in the first year of life and subsequent emergency admissions for potentially preventable hospitalizations.METHODS:We undertook a cohort analysis of linked anonymized data on 237 842 children in the Welsh Electronic Cohort for Children. We included children born in Wales between April 1, 1999 and December 31, 2008. The exposure was the number of residential moves from birth up to 1 year. The main outcome was emergency admissions for potentially preventable hospitalizations (PPH) between the age of 1 and 5 years.RESULTS:After adjustment for confounders, we identified that moving home frequently in the first year of life was associated with an increased risk of emergency PPH between the ages of 1 and 5 when compared with not moving. We found significant differences associated with ≥2 moves for the following: ear, nose, and throat infections (incidence risk ratio [IRR], 1.44; 95% confidence interval [CI], 1.29–1.61); convulsions/epilepsy (IRR, 1.58; 95% CI, 1.23–2.04); injuries (IRR, 1.33; 95% CI, 1.18–1.51); dehydration/gastroenteritis (IRR, 1.51; 95% CI, 1.21–1.88); asthma (IRR, 1.61; 95% CI, 1.19–2.16); influenza/pneumonia (IRR, 1.15; 95% CI, 1.00–1.32); and dental conditions (IRR, 1.30; 95% CI, 1.03–1.64) for ≥1 moves.CONCLUSIONS:Children who move home in the first year of life are at substantially increased risk of emergency admissions for PPH in early childhood. Additional research that focuses on enhancing health and social support services for highly mobile families, educating parents about safety risks, and improving housing quality is warranted.

BackgroundExcess alcohol consumption has serious adverse effects on health and results in violence-related harm.ObjectiveThis study investigated the impact of change in community alcohol availability on alcohol consumption and alcohol-related harms to health, assessing the effect of population migration and small-area deprivation.DesignA natural experiment of change in alcohol outlet density between 2006 and 2011 measured at census Lower Layer Super Output Area level using observational record-linked data.SettingWales, UK; population of 2.5 million aged ≥ 16 years.Outcome measuresAlcohol consumption, alcohol-related hospital admissions, accident and emergency (A&E) department attendances from midnight to 06.00 and violent crime against the person.Data sourcesLicensing Act 2003 [Great Britain.Licensing Act 2003. London: The Stationery Office; 2003. URL:www.legislation.gov.uk/ukpga/2003/17/contents(accessed 8 June 2015)] data on alcohol outlets held by the 22 local authorities in Wales, alcohol consumption data from annual Welsh Health Surveys 2008–12, hospital admission data 2006–11 from the Patient Episode Database for Wales (PEDW) and A&E attendance data 2009–11 were anonymously record linked to the Welsh Demographic Service age–sex register within the Secure Anonymised Information Linkage Databank. A final data source was recorded crime 2008–11 from the four police forces in Wales.MethodsOutlet density was estimated (1) as the number of outlets per capita for the 2006 static population and the per quarterly updated population to assess the impact of population migration and (2) using new methods of network analysis of distances between each household and alcohol outlets within 10 minutes of walking and driving. Alcohol availability was measured by three variables: (1) the previous quarterly value; (2) positive and negative change over the preceding five quarters; and (3) volatility, a measure of absolute quarterly changes during the preceding five quarters. Longitudinal statistical analysis used multilevel Poisson models of consumption and Geographically Weighted Regression (GWR) spatial models of binge drinking, Cox regression models of hospital admissions and A&E attendance and GWR models of violent crime against the person, each as a function of alcohol availability adjusting for confounding variables. The impact on health inequalities was investigated by stratifying models within quintiles of the Welsh Index of Multiple Deprivation.ResultsThe main finding was that change in walking outlet density was associated with alcohol-related harms: consumption, hospital admissions and violent crime against the person each tracked the quarterly changes in outlet density. Alcohol-related A&E attendances were not clinically coded and the association was less conclusive. In general, social deprivation was strongly associated with the outcome measures but did not substantially modify the associations between the outcomes and alcohol availability. We found no evidence for an important effect of population migration.LimitationsLimitations included the absence of any standardised methods of alcohol outlet data collation, processing and validation, and incomplete data on on-sales and off-sales. We were dependent on the quality of clinical coding and administrative records and could not identify alcohol-related attendances in the A&E data set.ConclusionThis complex interdisciplinary study found that important alcohol-related harms were associated with change in alcohol outlet density. Future work recommendations include defining a research standard for recording outlet data and classification of outlet type, the methodological development of residence-based density measures and a health economic analysis of model-predicted harms.FundingThe National Institute for Health Research Public Health Research programme. Additional technical and computing support was provided by the Farr Institute at Swansea University, made possible by the following grant:Centre for the Improvement of Population Health through E-records Research (CIPHER) and Farr Institute capital enhancement. CIPHER and the Farr Institute are funded by Arthritis Research UK, the British Heart Foundation, Cancer Research UK, the Chief Scientist Office (Scottish Government Health Directorates), the Economic and Social Research Council, the Engineering and Physical Sciences Research Council, the Medical Research Council, the National Institute for Health Research, the National Institute for Social Care and Health Research (Welsh Government) and the Wellcome Trust (grant reference MR/K006525/1).

Background Aortic dilatation is the main therapeutic target in patients with Marfan syndrome. Standard treatment with a β-blocker may not lower central pulse pressure – the major objective – because it does not do so in hypertension, unlike angiotensin-converting enzyme inhibitors and calcium-channel blockers. We therefore performed a prospective, randomised, double-blind, crossover trial to compare the effects of these three agents on large artery function and central aortic pressure in patients with Marfan syndrome. Methods and Results Eighteen patients had applanation tonometry, pulse wave analysis and echocardiography, before and after atenolol 75 mg, perindopril 4 mg and verapamil 240 mg, each given for 4 weeks, in a random order, with 2 weeks between medications. Fourteen patients completed the study. Within-drug comparisons demonstrated that perindopril (−10·3 mmHg, P = 0·002), verapamil (−9·2 mmHg, P = 0·003) and atenolol (−7·1 mmHg, P = 0·01) all reduced central systolic pressure and brachial pressure; central changes were least, and peripheral changes greatest with atenolol but between-drug comparisons (analysis of covariance) were not significant. There was a trend for augmentation to be reduced by perindopril (−6·3%, P = 0·05), verapamil (−5·5%, P = 0·07) and atenolol (−3·2%, P = 0·09). Only atenolol reduced heart rate (by 16%) and delayed expansion in the arch and abdominal aorta (by 8% and 11%) (P < 0·001, P < 0·01 and P < 0·05, respectively, for between-drug comparisons). Conclusions Perindopril, verapamil and atenolol all reduced peripheral and central systolic pressure. As atenolol slowed heart rate and delayed aortic wave travel, β-blockade may have a continuing role in the treatment of patients with Marfan syndrome.

Rationale: Few studies have investigated childhood respiratory outcomes of intrauterine growth retardation (IUGR), and it is unclear if catch-up growth in these children influences lung function. Objectives: We determined if lung function differed in 8- to 9-year-old children born at term with or without growth retardation, and, in the growth-retarded group, if lung function differed between those who did and those who did not show weight catch up. Methods: Caucasian singleton births of 37 weeks or longer gestation from the Avon Longitudinal Study of Parents and Children (n = 14,062) who had lung spirometry at 8–9 years of age were included (n = 5,770). Measurements and Main Results: Infants with gestation-appropriate birthweight (n = 3,462) had significantly better lung function at 8–9 years of age than those with IUGR (i.e., birthweight

BACKGROUND:Coronary heart disease (CHD) mortality in England fell by 36% between 2000 and 2007 and it is estimated that approximately 50% of the fall was due to improved treatment uptake. Marked socio-economic inequalities in CHD mortality in the United Kingdom (UK) remain, with higher age-adjusted rates in more deprived groups. Inequalities in the persistence of medication for primary and secondary prevention of CHD may contribute to the observed social gradient and we investigated this possibility in the population of Wales (UK). METHODS AND FINDINGS:An electronic cohort of individuals aged over 20 (n = 1,199,342) in Wales (UK) was formed using linked data from primary and secondary care and followed for six years (2004-2010). We identified indications for medication (statins, aspirin, ACE inhibitors, clopidogrel) recommended in UK National Institute for Clinical Excellence (NICE) guidance for CHD (high risk, stable angina, stable angina plus diabetes, unstable angina, and myocardial infarction) and measured the persistence of indicated medication (time from initiation to discontinuation) across quintiles of the Welsh Index of Multiple Deprivation, an area-based measure of socio-economic inequality, using Cox regression frailty models. In models adjusted for demographic factors, CHD risk and comorbidities across 15 comparisons for persistence of the medications, none favoured the least deprived quintile, two favoured the most deprived quintile and 13 showed no significant differences. CONCLUSIONS:During our study period (2004-2010) we found no significant evidence of socio-economic inequality in the persistence of recommended medication for primary and secondary prevention of CHD.

Objective— Hemostasis and inflammation have been implicated in dementia. This study investigates the role of specific hemostatic and inflammatory pathways with incident vascular and nonvascular dementia. Methods and Results— This was a prospective study of a population sample of men aged 65 to 84 years, with baseline assessment of hemostatic and inflammatory factors and cognition measured 17 years later. The sample included 865 men (59 had dementia and 112 had cognitive impairment, not dementia), free of vascular disease at baseline and for whom hemostatic and inflammatory marker data were available and cognitive status was known. A total of 15 hemostatic and 6 inflammatory markers were assessed. Factor analysis was used to identify hemostatic subsystems. The National Institute of Neurological Disorders and Stroke–Association Internationale pour la Recherche et l’Enseignement en Neurologie criteria were used to identify vascular dementia. By using standardized ( z ) scores for hemostatic and inflammatory markers, and after adjustment for age and risk factors, vascular dementia was associated with fibrinogen (hazard ratio [HR], 1.68; 95% confidence interval [CI], 1.02–2.76), factor VIII (HR, 1.79; 95% CI, 1.09–3.00), and plasminogen activator inhibitor 1 (HR, 3.13; 95% CI, 1.73–5.70). For vascular dementia, the HR risk from high levels of all three hemostatic variables (fibrinogen, factor VIII, and plasminogen activator inhibitor 1) was 2.97 ( P Conclusion— The associations of these hemostatic markers with vascular dementia may implicate clot formation as the primary mechanism and are consistent with a microinfarct model of vascular dementia.

Background Studies have found that health checking in primary care led to the identification of previously unrecognized morbidity among adults with intellectual disabilities. The aim here was to evaluate whether health checking stimulated increased consultation with the general practitioner or another member of the primary care team, increased health promotion actions undertaken outside the health check or increased contact with specialists. Method Data on the above three categories of activity were abstracted from the medical records of 77 adult participants with intellectual disabilities for eight 6-month periods before and seven 6 month periods after they had undergone a health check. Comparisons of access to care before and after the health check were made using non-parametric statistics. Results On average, participants had 5.4 and 1.8 primary care and specialist consultations per year respectively. There were no significant differences in either rate before and after the health check. The frequency of health promotion actions increased significantly after the health check from a mean of 1.2 to 2.2/year. Conclusions Comparison of the primary care and specialist consultations rates of people with intellectual disabilities with those for the general population might suggest that the former have greater access to these services. However, comparison to the general practitioner consultation rates of patients with other chronic conditions would seem to indicate that contact with primary care may not be commensurate with need. Attention to health promotion is inadequate. Further research is required to substantiate whether health checking increases health promotion and how increased health promotion activity would affect the health of this population.

Background An earlier study (Baxter et al. 2006) found that a structured health check conducted in primary care identified clinically significant previously unrecognized morbidity among adults with intellectual disabilities. The aim here was to examine whether follow-up health checks would identify equally significant newly identified morbidity and to investigate this as a function of the interval between health checks. Method Adults with intellectual disabilities who had had an initial health check (n = 108) participated: group 1 (n = 39) had a repeat health check an average of 28 months later, group 2 (n = 36) had a repeat health check an average of 44 months later and group 3 (n = 33) did not have a subsequent health check. Thirty participants in group 1 had a second repeat health check an average of 14 months after the first repeat. An audit of the results of the health check established whether morbidity was newly identified. Information was collected on each participant’s age, gender, place of residence, skills, challenging behaviour, social abilities, psychiatric status and perceived health. Comparisons within groups over time or between groups at a point in time were made using non-parametric statistics. Results A similar number of newly identified health problems were found at the repeat health check compared to the initial check. The nature of needs identified was also similar. There was no association between the number of new needs identified at the repeat health check and the interval between it and the initial check. The perceived health of participants receiving health checks tended to decline. Conclusions As the level of new need revealed by repeated checks at even the shortest interval since the previous check studied here (mean = 14 months) was as high as that found by the initial check, annual health checking could be a justifiable intervention for this population. Decline in perceived health may represent more accurate assessment by carers following feedback from the health checks.

BackgroundThe relationship between the Mental Illness Needs Index (MINI) and the common mental disorders is not known.AimsTo investigate associations between the small-area MINI score and common mental disorder at individual level.MethodMental health status was measured using the Mental Health Inventory of the Short Form 36 instrument (SF-36). Data from the Caerphilly Health and Social Needs population survey were analysed in multilevel models of 10 653 individuals aged 18–74 years nested within the 2001 UK census geographies of 110 lower super output areas and 33 wards.ResultsThe MINI score was significantly associated with common mental disorder after adjusting for individual risk factors. This association was stronger at the smaller spatial scale of the lower super output area and for individuals who were permanently sick or disabled.ConclusionsThe MINI is potentially useful for small-area needs assessment and service planning for common mental disorder in community settings.

Background: A study was undertaken to see whether the prevalence of asthma has changed since a survey was conducted in 1988, using the same methods that showed an increase during the previous 15 years. Methods: A survey of 12 year old children was conducted in schools in South Wales where surveys had taken place in 1973 and 1988. The survey comprised a parentally completed questionnaire and an exercise challenge test, performed when no bronchodilator had been recently used. Results: In 1973, 1988, and 2003, questionnaires were obtained for 817, 965 and 1148 children, respectively; the exercise test was performed by 812, 960 and 1019 children, respectively. The prevalence of reported wheeze in the last year rose during each 15 year period (9.8%, 15.2%, 19.7%), with an even steeper rise in reported asthma ever (5.5%, 12.0%, 27.3%). There was a continued increase in wheeze attributed to running, in terms of all children (5.8%, 10.5%, 16.0%) and also as the proportion of those with a history of wheeze (34.1%, 47.0%, 57.3%). The use of inhaled corticosteroids (not available in 1973) increased fourfold between 1988 and 2003. The prevalence of exercise induced bronchoconstriction rose between 1973 and 1988 but had declined by 2003. Conclusions: The rise in the prevalence of asthmatic symptoms has continued since 1988. This appears to conflict with a reported recent decline, unless asthma prevalence peaked in the 1990s. The decline in exercise induced bronchoconstriction is probably attributable to better control of the disease as more children are now using inhaled corticosteroids as preventive treatment.

Two successive randomized trials examined the effect of an increased intake of fatty fish, or the use of fish oil supplements, in reducing mortality in men with heart disease. The Diet and Reinfarction Trial (DART) was conducted in 2033 men who were recovering from acute myocardial infarction (MI). Those who were advised to eat fatty fish (or who opted to take fish oil capsules instead) had a 29% reduction in all-cause mortality over the following two years compared with those not so advised. The effect appeared in the first few months of the trial. The Diet and Angina Randomized Trial (DART 2) involved 3114 men with stable angina. Advice to eat fatty fish did not reduce mortality, and taking fish oil capsules was associated with a higher risk of cardiac and sudden death. The adverse effects of fish or fish oil were restricted to men not taking beta-blockers or dihydropyridine calcium-channel blockers, and were greater in those taking digoxin. Evidence from other sources strongly suggests an anti-arrhythmic action of fish oil, particularly after MI or in the presence of acute ischemia. The apparently conflicting results of the two trials may reflect different actions of n-3 fatty acids in acute and chronic conditions, together with different effects of eating fish and taking fish oil capsules. A mechanism is proposed that could account for these findings.

In all temperate countries campylobacter infection in humans follows a striking seasonal pattern, but little attention has been given to exploring the epidemiological explanations. In order to better characterize the seasonal patterns, data from nine European countries and New Zealand have been examined. Several European countries with weekly data available showed remarkably consistent seasonal patterns from year to year, with peaks in week 22 in Wales, week 26 in Scotland, week 32 in Denmark, week 30 in Finland and week 33 in Sweden. In Europe, the seasonal peak was most prominent in Finland and least prominent in Scotland and Austria. In New Zealand the seasonality was less consistent since the peak was more prolonged. Possible explanations for the seasonal peaks are discussed. Research into the causes of campylobacter seasonality should help considerably in elucidating the sources of human infection.

Preterm birth, low birth weight and poor foetal nutrition have been linked to cardiovascular disease, but the underlying mechanisms remain unclear. We explored prematurity and vascular function by studying a UK cohort of 14 049 children and conducting a systematic review.Systolic blood pressure was higher in subjects born preterm than term, but there were no differences in endothelial dysfunction or arterial stiffness. The systematic review revealed no clear association between prematurity and vascular function.

STUDY QUESTION Are arterial stiffness, carotid intima-media thickness and diastolic dysfunction increased in young women with polycystic ovary syndrome (PCOS) independently of the effects of obesity? SUMMARY ANSWER Insulin resistance and central obesity are associated with subclinical cardiovascular dysfunction in young women, but a diagnosis of PCOS does not appear to confer additional risk at this age. WHAT IS KNOWN ALREADY Some studies have shown that young women with PCOS may have increased measures of cardiovascular risk, including arterial stiffness, carotid intima-media thickness and myocardial dysfunction. However, it is difficult to establish how much of this risk is due to PCOS per se and how much is due to obesity and insulin resistance, which are common in PCOS and themselves associated with greater vascular risk. STUDY DESIGN, SIZE, DURATION This cross-sectional study comprised 84 women with PCOS and 95 healthy volunteers, aged 16–45 years. PARTICIPANTS/MATERIALS, SETTING, METHODS The study was conducted in a university hospital. Subjects underwent a comprehensive assessment of body composition (including computed tomography (CT) assessment of visceral fat; VF), measurements of arterial stiffness (aortic pulse wave velocity; aPWV), common carotid intima-media thickness (ccIMT), diastolic function (longitudinal tissue velocity; e′:a′) and endocrinological measures. A sample size of 80 in each group gave 80% power for detecting a difference of 0.45 m/s in aPWV or a difference of 0.25 in e′:a′. MAIN RESULTS AND THE ROLE OF CHANCE After adjustment for age and body mass index (BMI), PCOS subjects had a greater insulin response (insulin area under the curve—IAUC) following glucose challenge (adjusted difference [AD] 35 900 pmol min/l, P < 0.001) and higher testosterone (AD 0.57 nmol/l, P < 0.001) and high molecular weight adiponectin than controls (AD 3.01 µg/ml, P = 0.02), but no significant differences in aPWV (AD −0.13 m/s, P = 0.33), ccIMT (AD −0.01 mm, P = 0.13), or e′:a′ (AD −0.01, P = 0.86) were observed. After adjustment for age, height and central pulse pressure, e′:a′ and aPWV were associated with logVF and IAUC. ccIMT was not related to logVF. The relationships between e′:a′ or aPWV and insulin resistance were only partly attenuated by adjusting for logVF. There was no significant relationship between aPWV or e′:a′ and either testosterone or adiponectin. LIMITATIONS, REASONS FOR CAUTION The study recruited young women meeting the Rotterdam criteria for PCOS diagnosis; hence our findings may not be generalizable to older patients or those meeting other definitions of the syndrome. Biochemical hyperandrogenism was based solely on measurement of total testosterone. Cases and controls were not matched in advance for age and BMI, although the influence of these variables on the cardiovascular outcome measures was adjusted for. WIDER IMPLICATIONS OF THE FINDINGS This study shows that central arterial stiffness and diastolic dysfunction are not increased in young women with PCOS, whereas they are associated with both insulin resistance and central obesity. Obesity thus represents the greatest modifiable risk factor for cardiovascular disease in young women with PCOS and lifestyle measures which target weight reduction are critical. STUDY FUNDING/COMPETING INTEREST(S) This study received no specific grant support from any funding body. The authors have no conflicts of interest to declare.

Background\ud Improvement in ultrasound imaging has led to the identification of subtle non-structural markers during the 18 – 20 week fetal anomaly scan, such as echogenic bowel, mild cerebral ventriculomegaly, renal pelvicalyceal dilatation, and nuchal thickening. These markers are estimated to occur in between 0.6% and 4.3% of pregnancies. Their clinical significance, for pregnancy outcomes or childhood morbidity, is largely unknown. The aim of this study is to estimate the prevalence of seven markers in the general obstetric population and establish a cohort of children for longer terms follow-up to assess the clinical significance of these markers. \ud \ud Methods/Design\ud All women receiving antenatal care within six of seven Welsh Health Boards who had an 18 to 20 week ultrasound scan in Welsh NHS Trusts between July 2008 and March 2011 were eligible for inclusion. Data were collected on seven markers (echogenic bowel, cerebral ventriculomegaly, renal pelvicalyceal dilatation, nuchal thickening, cardiac echogenic foci, choroid plexus cysts, and short femur) at the time of 18 – 20 week fetal anomaly scan. Ultrasound records were linked to routinely collected data on pregnancy outcomes (work completed during 2012 and 2013). Images were stored and reviewed by an expert panel. \ud \ud The prevalence of each marker (reported and validated) will be estimated. A projected sample size of 23,000 will allow the prevalence of each marker to be estimated with the following precision: a marker with 0.50% prevalence to within 0.10%; a marker with 1.00% prevalence to within 0.13%; and a marker with 4.50% prevalence to within 0.27%. The relative risk of major congenital abnormalities, stillbirths, pre-term birth and small for gestational age, given the presence of a validated marker, will be reported. \ud \ud Discussion\ud This is a large, prospective study designed to estimate the prevalence of markers in a population-based cohort of pregnant women and to investigate associations with adverse pregnancy outcomes. The study will also establish a cohort of children that can be followed-up to explore associations between specific markers and longer-term health and social outcomes.

AIMS To investigate the relation between social deprivation and causes of stillbirth and infant mortality. METHODS Stillbirths and infant deaths in 6347 enumeration districts in Wales were linked with the Townsend score of social deprivation. In 1993–98 there were 211 072 live births, 1147 stillbirths, and 1223 infant deaths. Poisson regression analysis was used to estimate the magnitude of effect for associations between the Townsend score and categories of death by age and the causes of death. The relative risk of death between most and least deprived enumeration districts was derived. RESULTS Relative risk of combined stillbirth and infant death was 1.53 (95% CI 1.35 to 1.74) in the most deprived compared with the least deprived enumeration districts. The early neonatal mortality rate was not significantly associated with deprivation. Sudden infant death syndrome showed a 307% (95% CI 197% to 456%) increase in mortality across the range of deprivation. Deaths caused by specific conditions and infection were also associated with deprivation, but there was no evidence of a significant association with deaths caused by placental abruption, intrapartum asphyxia, and prematurity. CONCLUSIONS Collaborative public health action at national and local level to target resources in deprived communities and reduce these inequalities in child health is required. Early neonatal mortality rates and deaths from intrapartum asphyxia and prematurity are not significantly associated with deprivation and may be more appropriate quality of clinical care indicators than stillbirth, perinatal, and neonatal mortality rates.

The efficiency of a screening programme for Down's syndrome is usually expressed in terms of the detection rate for a given false positive rate. Two programmes with approximately equal detection rates and false positive rates would then be regarded as being broadly equivalent. While this might be the case at a population level, we show in this paper that it may be far from true at the individual patient level. Different algorithms, or even different implementations of the same algorithm can lead to calculation of very different individual risks and can result in different decisions for individual patients. Even though two programmes might lead to the same number of referrals, they could be referring quite different women. We consider the effect of using different parameter values within an algorithm, different algorithms and alternative ways of estimating the gestational age-dependent medians of the marker values. We show that the combined effects of these factors could explain much of the range of risks reported in the UK National External Quality Assessment Scheme for Down's syndrome screening.

To evaluate the role of tacrolimus in the treatment of Chronic Graft Nephropathy (CGN), a pilot cross-sectional study was performed on 14 patients with deteriorating renal function and biopsy-proven CGN. Maintenance therapy was switched from cyclosporin to tacrolimus, and results of conversion on allograft function were assessed by estimated glomerular filtration rate (GFR) and clinical outcome. Minimum follow-up was 15 months. Two distinctive response patterns emerged: (i) continuing deterioration of renal function with no apparent benefit over the projected trend of GFR (nine patients), and (ii) unequivocal change in the GFR trend line equation with reduced rate of deterioration in one patient and sustained improvement of GFR in four patients (reversal of downward trend). Five out of 14 patients (36 %) benefited from replacing Neoral with Prograf. All five patients exceeded their estimated time of return to dialysis by a median of 41 weeks (range: 29-52) and their grafts continue to function.

Active support, a package of procedures which includes activity planning, support planning and training on providing effective assistance, was introduced in five community residences serving 19 adults with severe intellectual disability following a multiple baseline design. The residents were directly observed to ascertain the level of assistance they received from staff and their engagement in activity. The introduction of active support increased the levels of assistance residents received, their engagement in domestic activities and their total engagement in activity. The intervention did not affect the level of social engagement. Across individuals, increases in assistance and engagement in activity were significantly and positively correlated. Both were significantly inversely related to resident adaptive behaviour. At baseline, staff gave more attention and assistance to people who were behaviourally more able. After the introduction of active support, receipt of attention was unrelated to adaptive behaviour and the behaviourally less able received more assistance. The disparity in activity between the more and less able was reduced. Gains were maintained in the majority of houses.

Background Intensification chemotherapy improves the prognosis for children with acute lymphoblastic leukemia (ALL), but results in considerable morbidity, primarily due to myelosuppression with resultant neutropenia. Recombinant granulocyte colony-stimulating factor (G-CSF) shortens neutropenia following intensive chemotherapy, but potential benefits in the therapy of ALL remain inadequately explored. Accordingly, a randomized, crossover study was undertaken to clarify this issue. Procedure Seventeen children with acute lymphoblastic leukemia or T-cell non-Hodgkin lymphoma and treated on standard protocols were randomized to receive G-CSF following either the first or second intensification blocks of chemotherapy. G-CSF was administered as a single daily subcutaneous injection of 5 mcg/kg from day 9 following the start of intensification therapy, and continued until the neutrophil count exceeded 0.5 × 109/l for 3 days. Study endpoints were days of neutropenia (neutrophils

OBJECTIVE: To determine the day-to-day intraindividual variability of fasting plasma glucose (FPG) in newly diagnosed Caucasian type 2 diabetic subjects. RESEARCH DESIGN AND METHODS: A total of 193 newly diagnosed, previously untreated, Caucasian type 2 diabetic subjects (135 men, 58 women) had FPG measured on two consecutive days (FPG1, FPG2). Ethical approval and subjects' full informed consent were obtained. Subjects fasted for 12 h before each study day and rested for at least 30 min before blood was taken. Plasma glucose was analyzed by a glucose oxidase method with intra- and interassay coefficients of variation (CVs) < 2%. Variability of FPG was assessed by comparison of percentage differences (PDs): PD = 100 (FPG2 - FPG1)/FPG1, with averaged FPG (FPGaver = [FPG1 + FPG2]/2). Biological and analytical variability were determined by use of SD2total = SD2biological + SD2analytical, where SD2analytical approximately equal to 2 x (CVglucose measurement)2. Given normally distributed data with zero mean, 95% of daily percentage differences will be expected to fall within a range of +/- 2 SDtotal. RESULTS: Subjects were age 54 +/- 10 years (mean +/- SD) and had BMI of 29.3 +/- 5.3 kg/m2. FPG values for both days were 12.2 +/- 3.4 mmol/l (FPG1) and 12.1 +/- 3.3 mmol/l (FPG2), with a mean paired difference (95% CI) of 0.1 (0.0 to 0.3) mmol/l. The variance of these differences increased with increasing FPGaver. The PDs did not exhibit this effect and were normally distributed (mean -0.6% [-1.7 to 0.4]; SD 7.4% [6.8 to 8.3]), giving a 95% variability (2 SD) of 14.8%. Biological variability (2 SDbiological) was 13.7%. No significant difference in PD was found between men and women (mean difference 1.3% [-1.0 to 3.6]; SDmale 7.4%, SDfemale 7.3%; P = 0.62). CONCLUSIONS: A total of 95% of the FPG values for this group of newly diagnosed type 2 diabetic subjects varied within approximately +/- 15% on a daily basis, with approximately 14% caused by biological variability. As these results are expressed in percentage terms, subjects in the group with higher FPG values are likely to experience larger changes in FPG values measured from day to day. This variability should be considered when using FPG for the diagnosis and/or monitoring of response to treatment in patients with type 2 diabetes.

We compared digital retinal images and 35 mm colour transparencies taken with the Canon CR5 retinal camera for the detection and grading of diabetic retinopathy in a clinical setting, in a randomized, blinded study of diabetic patients with a spectrum of severity of diabetic retinopathy. Forty patients were photographed, giving a total of 75 eyes including non-diabetic eyes as controls. Images were graded according to the validated European guidelines. There was exact agreement between grades obtained from both the 2 field 45 degrees 35 mm colour transparencies and digital images in 93.3% (70/75) of eyes, with Cohen's Kappa statistic for the comparison being 0.92. Overall, when grading from the digital images 5.3% (4/75) eyes were undergraded with three cases of sight threatening diabetic retinopathy (STDR) graded as non-sight threatening (NSTDR) (3/48, 6.3%). One eye was overgraded (1/75, 1.3%). Two of the three cases of STDR undergraded as NSTDR had small numbers of intra-retinal microvascular abnormalities (IRMA) discernible on the colour transparencies but which were not visible from the digital image. The third had multiple small cotton wool spots graded as laser photocoagulation scars from the digital images. In conclusion there is good to excellent agreement between retinopathy grades using the Canon CR5 digital retinal imaging system compared to 35 mm colour transparencies.

Various studies have suggested that there may be an environmental factor in schizophrenia acting before or at birth but with delayed effects. Evidence that the risk of developing schizophrenia varies randomly with the year of birth would help confirm the existence of such a factor. Data from the Scottish Health Service Information and Statistics Division, comprising all first admissions for ICD-9 schizophrenia in the years 1963-91, were used to estimate the lifetime risk of developing schizophrenia for each year of birth from 1900 to 1969. In the period after 1928 the lifetime risk steadily declined. The rate of decline was greater in females. The random fluctuations in the risks in females did not change systematically, but there was a significant decline in the variability of these fluctuations in males. These random fluctuations suggest a possible role for randomly varying environmental influences around the time of birth. Our findings suggest a possible diminution in the role of such environmental influences in schizophrenia among males in Scotland in the years 1929 to 1969.

Retinal photography is an adjunct to ophthalmoscopy in screening for diabetic retinopathy (DR). Digital retinal cameras allow a retinal image to be displayed immediately on a high resolution video display monitor. We conducted a pilot study to investigate the agreement in retinopathy grading from digitized images in comparison to original colour transparencies as 35 mm slides. One hundred and fifty macula-centred, 45 degree, non-stereoscopic retinal images were digitized onto CD ROM by Kodak at base resolution of 768 x 512 pixels. The anonymized images were displayed on a 17" monitor running Windows at 800 x 600 resolution in 64,000 colours (PC images) and graded in random order. Alternatively the transparencies were graded on a Slidex viewer. A quality control set were also graded with exact agreement in 93% of cases (91% (73/80) of PC images and 94% (75/80) of slide images). Compared to colour transparencies, 95% (84/88) of sight threatening diabetic retinopathy (STDR) and 100% (62/62) of non-STDR cases were diagnosed using the PC. One case of pre-proliferative DR and three cases of non-proliferative DR were graded as non-STDR from the PC. There was good agreement between PC displayed digitized retinal images and 35 mm colour transparencies.

BACKGROUND: It is uncertain as to what extent the development of allergic disease in childhood is predictable during early infancy. A number of environmental factors have been suspected of increasing the risk of acquiring allergy, but the evidence is conflicting. OBJECTIVE: To observe the development of atopy and allergic disease in a cohort of high-risk children so as to determine the importance of certain environmental factors and to study the relationship between early and later manifestations. METHODS: A cohort of infants, all at high risk of allergy, was followed up from birth to the age of 7 years. In half, selected at random, cow's milk protein was avoided for 4 months. Skin-prick tests were performed and serum IgE measured in infancy and at 7 years, when an AlaTOP test was also performed. RESULTS: Skin sensitivity to egg in the first year of life was strongly associated with eczema, asthma, mite sensitivity and serum IgE at the age of 7 years, when mother's atopic history was associated with AlaTOP status, father's atopic history with skin sensitivity, and male sex with both. Maternal smoking during pregnancy was associated positively with IgE at 3 months and negatively with skin sensitivity at 7 years. The development of allergy was unrelated to infant feeding method or number of older siblings. CONCLUSION: Allergic disease in childhood is to a large degree determined before birth or during infancy.

The prevalence of osteopenia in children with inflammatory bowel disease (IBD) is unknown. The effect of nutritional state, disease activity, and steroid therapy on bone mineral content (BMC) of whole body, lumbar spine, and left femoral neck measured by dual energy x ray absorptiometry in 32 children with IBD was assessed by comparison with 58 healthy local school children. Using the control data, a predicted BMC was calculated taking into account bone area, age, height, weight, and pubertal stage. The measured BMC in children with IBD was expressed as a percentage of this predicted value (% BMC). Mean (SD) % BMC was significantly reduced for the whole body and left femoral neck in the children with IBD (97.0 (4.5)% and 93.1 (12.0)% respectively, p < 0.05). Of the children with IBD, 41% had a % BMC less than 1 SD below the mean for the whole body and 47% at the femoral neck. Reduction in % BMC was associated with steroid usage but not with the magnitude of steroid dose, disease activity, or biochemical markers of bone metabolism. In conclusion, osteopenia is relatively common in childhood IBD and may be partly related to the previous use of steroids.

Recently published standards for body mass index (BMI) based on population studies of height and weight in healthy British children allow an easy but indirect assessment of adiposity in healthy children. However, assessment of adiposity based on standards derived from reference populations may not be appropriate for use in subjects with disease states associated with abnormalities of growth and body composition. This hypothesis was tested by comparison between BMI standard deviation scores (SDS) and more direct measures of body fat derived from dual-energy X-ray absorptiometry (DEXA) and skinfold thickness in groups of children, receiving growth hormone, with inflammatory bowel disease, previously treated for malignancy, and healthy controls. Excess adiposity was defined as a body fat greater than the 85th percentile and was compared to a BMI SDS of +1.0. Overall the sensitivity and specificity for a BMI SDS of +1.0 to correctly identify individuals as having excess adiposity was 66% and 94%, respectively, when body fat was measured by DEXA, and 50% and 100% when estimated from skinfold measurements, respectively. There were no significant differences in these statistics whether applied to the individual disease groups or to healthy controls. These findings suggest that BMI under-predicts the prevalence of excess adiposity in children with disease states but surprisingly to no greater degree than that seen in healthy subjects.

Background Increasing evidence suggests that preterm birth affects later lung function. We systematically reviewed the literature to determine whether percentage predicted forced expiratory volume in 1 s (%FEV1) is lower in later life in preterm-born subjects, with or without bronchopulmonary dysplasia (BPD), compared with term-born controls. Methods Studies reporting %FEV1, with or without a term-born control group, in later life for preterm-born subjects (

OBJECTIVES: To examine the incidence of Campylobacter and Salmonella infection in patients prescribed proton pump inhibitors (PPIs) compared with controls. METHODS: Retrospective cohort study using anonymous general practitioner (GP) data. Anonymised individual-level records from the Secure Anonymised Information Linkage (SAIL) system between 1990 and 2010 in Wales were selected. Data were available from 1,913,925 individuals including 358,938 prescribed a PPI. The main outcome measures examined included incidence of Campylobacter or Salmonella infection following a prescription for PPI. RESULTS: The rate of Campylobacter and Salmonella infections was already at 3.1–6.9 times that of non-PPI patients even before PPI prescription. The PPI group had an increased hazard rate of infection (after prescription for PPI) of 1.46 for Campylobacter and 1.2 for Salmonella, compared with baseline. However, the non-PPI patients also had an increased hazard ratio with time. In fact, the ratio of events in the PPI group compared with the non-PPI group using the prior event rate ratio was 1.17 (95% CI 0.74–1.61) for Campylobacter and 1.00 (0.5–1.5) for Salmonella. CONCLUSIONS: People who go on to be prescribed PPIs have a greater underlying risk of gastrointestinal (GI) infection beforehand and they have a higher prevalence of risk factors before PPI prescription. The rate of diagnosis of infection is increasing with time regardless of PPI use, and there is no evidence that PPI is associated with an increase in diagnosed GI infection. It is likely that factors associated with the demographic profile of the patient are the main contributors to increased rate of GI infection for patients prescribed PPIs.

In Down's syndrome screening using biochemical markers, the marker concentrations are adjusted for the gestational age of the fetus, since they are known to change with gestational age. This adjustment is performed by referring to the population median of each marker for the appropriate gestational age group. The measurement of gestational age is subject to error, whatever method is used, and the population median used is actually the median of a mixture of distributions for different true gestational ages. We show how the proportions in this mixture can be estimated and how the true median corresponding to a given true gestational age can be estimated. For simplicity, we consider the case of using a single marker, namely maternal serum α-fetoprotein, and show that the usual estimation method has considerable bias. The effect of this mixture on the calculation of patient-specific risks is discussed and we show that detection rates can be improved by allowing for this error in the dating process. The overall detection rate is increased by about 1%. The increase in detection rate is age-dependent and for some maternal ages the increase is of the order of 5%. The comparative effects of different methods for dating are discussed.

Background Little is known on the longitudinal relationship between alcohol availability and the risk of admission to hospital for an alcohol-related injury. We aimed to quantify this relationship using observational record-linked data in a total adult population cohort in Wales, UK; population 2.5 million aged 16 years and over. Methods Data sources included licensed outlets held by the 22 local authorities in Wales under The Licensing Act 2003 for each quarter between 2006 and 2011. Alcohol outlet density was estimated for Census geography small areas (n = 1896 divided into quintiles of equal counts) based on the mean network walking distances between each household and alcohol outlet within a 10 minute walk. Hospital admissions 2006–2011 from the Patient Episode Database for Wales (PEDW) for wholly alcohol-related conditions were anonymously record-linked to the Welsh Demographic Service age-sex register within the Secure Anonymised Information Linkage Databank. Injury admissions were defined by ICD-10 codes S00-99 and T00-19 linked to an alcohol code. Longitudinal statistical analysis used Cox regression models of hospital admissions as a function of outlet density at baseline, adjusting for confounding variables of age, sex and small area deprivation and settlement type, and censoring for death, migration and other cause admission. Results Alcohol outlet density at baseline was significantly associated with emergency hospital admission; the hazard ratio (HR) of an alcohol-related admission (n = 25,722) for living in the highest compared with the lowest quintile of outlet density was 1.17 (95% CI: 1.11, 1.23). The risk was higher for alcohol-related admissions with injury (n = 4,308; HR 1.27, 95% CI: 1.13, 1.42). Conclusions Higher alcohol outlet availability was associated with more emergency hospital admissions for alcohol-related injury. This suggests that restricting the density of alcohol outlets within walking distance from home may improve population health.

Objectives To determine the association between area and individual measures of social disadvantage and infant health in the UK. Design Systematic review and meta-analyses. Data sources 26 databases and websites, reference lists, experts in the field and hand-searching. Study selection 36 prospective and retrospective observational studies with socioeconomic data and health outcomes for infants in the UK, published from 1994 to May 2011. Data extraction and synthesis 2 independent reviewers assessed the methodological quality of the studies and abstracted data. Where possible, study outcomes were reported as ORs for the highest versus the lowest deprivation quintile. Results In relation to the highest versus lowest area deprivation quintiles, the odds of adverse birth outcomes were 1.81 (95% CI 1.71 to 1.92) for low birth weight, 1.67 (95% CI 1.42 to 1.96) for premature birth and 1.54 (95% CI 1.39 to 1.72) for stillbirth. For infant mortality rates, the ORs were 1.72 (95% CI 1.37 to 2.15) overall, 1.61 (95% CI 1.08 to 2.39) for neonatal and 2.31 (95% CI 2.03 to 2.64) for post-neonatal mortality. For lowest versus highest social class, the odds were 1.79 (95% CI 1.43 to 2.24) for low birth weight, 1.52 (95% CI 1.44 to 1.61) for overall infant mortality, 1.42 (95% CI 1.33 to1.51) for neonatal and 1.69 (95% CI 1.53 to 1.87) for post-neonatal mortality. There are similar patterns for other infant health outcomes with the possible exception of failure to thrive, where there is no clear association. Conclusions This review quantifies the influence of social disadvantage on infant outcomes in the UK. The magnitude of effect is similar across a range of area and individual deprivation measures and birth and mortality outcomes. Further research should explore the factors that are more proximal to mothers and infants, to help throw light on the most appropriate times to provide support and the form(s) that this support should take., Article summary Article focus To determine the association between area and individual measures of social disadvantage and infant health in the UK. Key messages It is possible to be reasonably confident of the magnitude of effect of social disadvantage on health outcomes for UK infants, in particular the effects of area or individual deprivation on birth outcomes and infant mortality. The magnitude of effect, of a range of measures of social disadvantage on infant health outcomes, is broadly similar and has remained so over the past 30 years. Future research should concentrate on the more proximal determinants of infant health outcomes (such as individual maternal and infant factors) and the impact of any interventions employed to mitigate these determinants. Strengths and limitations of this study A rigorous systematic review and accompanying meta-analyses provide confidence in the findings. Specific relevance to the UK. A risk of publication bias (missing studies) cannot be ruled out though, given the large size of many included studies, the likely effect is minimal. The review concentrates on health outcomes only.

Objective: To examine the association of anxiety with incident dementia and cognitive impairment not dementia (CIND). Methods: We conducted a prospective study of men aged 48 to 67 years at baseline anxiety assessment; we measured cognition 17 years later. We studied 1481 men who were either eligible for examination or were known to have dementia. Trait Anxiety was assessed using the Spielberger State Trait Anxiety Inventory. Psychological distress was assessed using the 30-item general health questionnaire. Cognitive screening was followed by a clinical examination. Medical notes and death certificates of those not seen were also examined. Outcomes were CIND and Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) dementia. Results: Of 1160 men who were cognitively screened, 174 cases of CIND and 69 cases of dementia were identified. A further 21 cases of dementia were identified from medical records. After adjustment for age, vascular risk factors and premorbid cognitive function associations with higher anxiety (31st–95th centile) were for CIND odds ratio (OR) 2.31 (95% Confidence Interval (CI) = 1.20–4.44) and for dementia OR 2.37 (95% CI = 0.98–5.71). These associations were slightly stronger for nonvascular (OR = 2.45; 95% CI = 1.28–4.68) than for vascular impairment (OR = 1.94; 95% CI = 0.77–4.89). Analyses of change in cognitive performance, assessed by the Cambridge Cognitive Examination of the Elderly subscales found some evidence for decline in learning memory with higher anxiety score (bage adj = −0.291 (−0.551, −0.032), but not for any other subscale. Conclusions: Anxiety is a risk factor for CIND and dementia. The extent to which the association is independent of depression and whether or not it is causal requires further study.

Aims Whilst epistaxis is a frequent and trivial finding in most children, it is rare in those aged less than 2 years. Epistaxis has been observed amongst intentionally asphyxiated infants using covert surveillance, although the precise relationship between epistaxis and asphyxia has subsequently been called into question. This systematic review aims to determine the probability of asphyxia amongst young children presenting with epistaxis, and define the clinical characteristics of such children. Methods An all-language search of published and grey literature across 10 databases from 1900–2014 was conducted with 76 key terms. Searches were supplemented with ‘snowballing’ techniques including hand searching non-indexed journals, checking articles’ references, and correspondence with authors for clarification. Inclusion criteria: high quality studies involving children with epistaxis aged less than 2 years; alive or dead on presentation; adequate confirmation or exclusion of intentional or unintentional asphyxia (upper airway obstruction), using an explicit rank of confirmation of asphyxia and non-asphyxia. Studies of traumatic or pathological epistaxis were excluded. All studies were independently critically appraised and data extracted by two trained reviewers. The probability of asphyxiation in a young child with epistaxis was estimated in a meta-analysis using a random-effects model and is reported as a proportion with 95% Confidence Intervals (CI). Results Of 2549 studies identified, 100 underwent full review, resulting in six included studies, representing 30 children with asphyxia-related epistaxis and 74 non-asphyxia related epistaxis. Meta-analysis was feasible for 4 studies yielding a probability of asphyxiation of 20% (95% CI = 13–29%). Children with asphyxia-related epistaxis were aged 30–684 days and described by 2 comparative cross-sectional studies, 1 case-control study, and 3 case series (1 of which was comparative). Live asphyxiated children tended to present unwell with altered skin colour, respiratory difficulty, and chest X-ray abnormalities. There were no associated features described among those dead on arrival. Conclusion This systematic review defines the probability that epistaxis, in the absence of trauma or medical explanation, may indicate asphyxia in children aged less than 2 years, thus reiterating the importance of full investigation of these children who may be at considerable risk of death.

Background/Aims: The prevalence of dementia and cognitive impairment not dementia was investigated in the Caerphilly Prospective Study cohort (men currently aged 65–84 years). Methods: Of 1,633 men eligible for cognitive screening, 1,225 (75%) were seen, with those failing the screening criteria (CAMCOG 9) being neurologically examined. Results: For dementia, diagnosed by DSM-IV criteria, the population prevalence was 5.2% rising to 6.1% in the screened population. For cognitive impairment not dementia, the prevalence in the screened population was 15.6% giving an overall prevalence of cognitive impairment of 21.8%. Prevalence rose fivefold between ages of 65 and 84 years to reach over 50%. Conclusion: These figures are likely to underestimate actual prevalence in this population, and developing effective interventions should be a public health priority.

Objectives: We do not know how representative reported levels of resistance to antibiotics in urinary tract infections (UTIs) are as there is wide variation in the rate of urine specimens submitted to microbiology laboratories by general practices. We used a questionnaire to investigate variation in sampling for patients with suspected UTI to explore any systematic bias that may influence interpretation of surveillance data based on routine data. Methods: We sent a questionnaire to a stratified random sample of general practitioners (GPs) in Wales for self-completion. The GPs were presented with six clinical scenarios and asked about their proposed clinical management. Results: We found that nearly all of the GPs indicated they would request a specimen for scenarios representing a probable UTI in a female child and a probable asymptomatic UTI in pregnancy. There was some variation between the GPs about sampling in a situation of treatment failure in an older woman and recurrent UTI in a male diabetic, with 90% and 81%, respectively, indicating they would request a specimen for these scenarios. The greatest variation was in relation to scenarios concerning the management of a probable uncomplicated UTI, and early patient symptoms with pressure to prescribe, with 56% and 33% of GPs, respectively, indicating they would request a urine specimen for laboratory analysis. Conclusions: In the light of this reported sampling behaviour, it is likely that there is a systematic bias in surveillance data based on routinely collected data, with samples from cases of uncomplicated UTI being under represented, potentially leading to an overestimation of true resistance rates.

Background. Gulf War veterans have a number of health complaints. We therefore decided to carry out a systematic review to identify and summarize the findings from studies that have assessed multi-symptom conditions in Gulf War veterans and in an unexposed comparison group.Method. Studies published between January 1990 and May 2004 were identified by searching a large number of electronic databases. Reference lists and websites were also searched and key researchers were contacted. Studies were included if they compared the prevalence of chronic fatigue syndrome, multiple chemical sensitivity, CDC-defined chronic multi-symptom illness, fibromyalgia, or symptoms of either fatigue or numbness and tingling in Gulf War veterans and non-Gulf veterans. A total of 2401 abstracts were independently reviewed by two authors.Results. Twenty-three publications fulfilled the inclusion criteria. Gulf deployment was most strongly associated with chronic fatigue syndrome (OR 3·8, 95% CI 2·2–6·7). Gulf War veterans were also approximately three and a half times more likely than non-Gulf veterans to report multiple chemical sensitivity or chronic multi-symptom illness as defined by CDC. The methodological quality of the studies varied but the later and larger studies were of a high methodological standard with robust sampling strategies, adequate response rates and good adjustment for confounders.Conclusions. The results support the hypothesis that deployment to the Gulf War is associated with greater reporting of multi-symptom conditions.

Background Veterans of the Persian Gulf War of 1991 have reported a range of adverse health symptoms. This systematic review aims to identify all studies that have compared the prevalence of symptoms of pain in veterans of the Gulf War to that in a non-Gulf military comparison group, and to determine whether Gulf War veterans are at increased risk of reporting pain. Methods Studies published between January 1990 and May 2004 were identified by searching a large number of electronic databases. Reference lists and websites were also searched and key researchers were contacted. Studies were included if they reported the prevalence of any symptom or condition that included the word "pain" in Gulf War veterans and in a comparison group of non-Gulf veterans. 2401 abstracts were independently reviewed by two authors. Results Twenty studies fulfilled the inclusion criteria. Five main sites of pain were identified (muscle, joint, chest/heart, back and abdominal pain) and separate meta-analyses were performed to summarise the results related to each site. A greater proportion of Gulf veterans reported symptoms at each site of pain when compared to a non-Gulf military group. Gulf deployment was most strongly associated with abdominal pain, with Gulf veterans being more than three times more likely to report such pain than a comparison group (OR 3.23; 95%CI 2.31–4.51). Statistical heterogeneity between study estimates was significant, probably due to variation in measured periods of prevalence and symptom measurement methods. Conclusion A higher proportion of veterans of the Persian Gulf War of 1991 reported symptoms of pain than military comparison groups. This is consistent with previously demonstrated increased reporting of more general symptoms (fatigue, multiple chemical sensitivity, post traumatic stress disorder) in these veterans compared with non-Gulf military groups. However, the primary studies were heterogeneous and varied greatly in quality.

Measuring the prevalence of malocclusion and treatment need in a population is useful for the planning of orthodontic services. In addition, knowledge concerning the attitudes of patients to malocclusion is becoming increasingly important in orthodontics. Without a satisfactory estimate of the need and demand for treatment it is difficult to develop and organize a meaningful service. The aims of this investigation were to estimate the need for orthodontic treatment in 12–13?year?old school children in urban and rural schools in Latvia. Five hundred and four school children aged 12–13 years were examined using the Index of Complexity, Outcome and Need (ICON). The children were invited to complete a questionnaire about treatment need and their appearance. The survey was carried out in four urban and five rural school settings. There were no statistically significant differences in treatment need between rural and urban settings or between boys and girls. However, there was a difference in ICON scores between Riga and Daugavpils, with a greater need for treatment in Daugavpils. Individual responses to questionnaires illustrated a correlation between individuals who expressed dissatisfaction with the arrangement of their teeth and treatment need according to the ICON score. The overall prevalence of individuals needing orthodontic treatment in Latvia was 35.3 per cent, but this figure masked considerable variation between schools. For example, a greater need was found in Daugavpils than in Riga. This difference is not fully explained but could be due to genetics, the individuals in Daugavpils being mainly of Russian origin. The individuals' perception of the arrangement of teeth and the need for treatment correlated significantly with the ICON score.

Background Many maternal serum markers show concentration changes in Down's syndrome pregnancies but the magnitude of the change in median marker levels varies with gestation. To date these changes have not been accurately specified. Methods The trends in marker median levels between 6 and 20 weeks of gestation were examined for alphafetoprotein (AFP), free β human chorionic gonadotrophin (F β-hCG), total human chorionic gonadotrophin (ThCG) and pregnancy-associated plasma protein A (PAPP-A) by a meta-analysis of data obtained from our collaborative studies and routine screening programmes for Down's syndrome over a 10-year period. Data were available from between 709 and 1082 Down's syndrome pregnancies and from between 14 607 and 153 909 unaffected pregnancies for each marker. The median multiple of the median (MoM) and mean log10MoM for each marker at each completed week of gestation were estimated and the trend with gestation smoothed using a weighted least squares regression model. Results The gestational ages at which maximum separation of marker levels occurred, comparing affected and unaffected pregnancies, and the respective regressed median MoMs and mean log10MoMs, were: for AFP at 16 weeks, 0·72 MoM, 0·14288 log10MoM; for F β-hCG at 15 weeks, 2·24 MoM, 0·35034 log10MoM; for ThCG at 16 weeks, 1·93 MoM, 0·28548 log10MoM, as well as before 8 weeks (< 0·65 MoM, 0·18853 log10MoM); and for PAPP-A before 8 weeks, < 0·33 MoM, 0·47727 log10MoM. Conclusion There is significant temporal variation in mean log10MoM values for the screening markers investigated. Screening algorithms, modified to take account of this variation, should allow more accurate gestation-specific risks to be calculated in individual pregnancies.