Assessing the risk of endogeneity bias in health and mortality inequalities research using composite measures of multiple deprivation which include health-related indicators: A case study using the Scottish Index of Multiple Deprivation and population health and mortality data.

The inclusion of health-related indicators in composite measures of multiple deprivation introduces a risk of endogeneity bias when using the latter in health inequalities research. This bias may ultimately result in the inappropriate allocation of healthcare resources and maintenance of preventable health inequalities. Mitigation strategies to avoid this bias include removing the health-related indicators or using single constituent domains (such as income or employment class) in isolation. These strategies have not been widely validated. This study used population-level health and mortality data with a contemporary composite measure of multiple deprivation (Scottish Index of Multiple Deprivation; SIMD) to assess these mitigation strategies. The differences between deprivation methods (original, health excluded, and income domain) were negligible. The results of quantitative research on health inequalities are unlikely to be affected by endogeneity bias.

Economic Evaluation of the Protecting Teeth @ 3 Randomized Controlled Trial.

INTRODUCTION: An economic evaluation (EE) was conducted alongside a randomized controlled trial (the Protecting Teeth @ 3 Study [PT@3]), exploring the additional preventive value of fluoride varnish (FV) application at 6-monthly intervals in nursery schools compared to treatment as usual (TAU) in the same nurseries. TAU represented a multicomponent national child oral health improvement intervention, the Childsmile program, apart from nursery FV. METHODS: The EE was a within-trial cost-utility analysis (CUA) comparing the FV and TAU groups. The CUA was conducted from a National Health Service perspective and followed relevant methods guidance. Within-trial costs included intervention costs and health care resource use costs. Health outcomes were expressed in quality-adjusted life years (QALYs) accrued over the 2-y follow-up period. The Child Health Utility 9 Dimensions questionnaire was used to obtain utility scores. National reference costs were used, a discount rate of 1.5% for public health interventions was adopted, multiple imputation methods for missing data were employed, sensitivity analyses were conducted, and incremental cost-utility ratios were calculated. RESULTS: Data from 534 participants from the 2014-2015 PT@3 intake were used in the EE analyses, n = 265 (50%) in the FV arm and n = 269 (50%) in the TAU arm. Mean incremental cost per child in the FV arm was £68.37 (P = 0.382; 95% confidence interval [CI], -£18.04 to £143.82). Mean incremental QALY was -0.004 (P = 0.636; 95% CI, -0.016 to 0.007). The probability that the FV intervention was cost-effective at the UK £20,000 threshold was 11.3%. CONCLUSION: The results indicate that applying FV in nurseries in addition to TAU (all other components of Childsmile, apart from nursery FV) would not be deemed cost-effective given current UK thresholds. In view of previously proven clinical effectiveness and economic worthiness of the universal nursery toothbrushing component of Childsmile, continuation of the additional, targeted nursery FV component in its pre-COVID-19 form should be reviewed given its low probability of cost-effectiveness. KNOWLEDGE TRANSFER STATEMENT: The results of this study can be used by child oral health policy makers and dental public health professionals. They can form part of the evidence to inform the Scottish, UK, and international guidance on community-based child oral health promotion programs.

Is detecting oral cancer in general dental practices a realistic expectation? A population-based study using population linked data in Scotland.

Aims: To examine, for the first time on a population-basis via data linkage, whether early detection by general dental practices (GDP) is a realistic expectation by i) estimating the number of OC cases/year a dentist in Scotland may encounter over time, accounting for the deprivation level of practice location and dental registration/attendance rates, and ii) assessing whether patients attended GDPs two years pre-diagnosis. Materials and methods: Scottish Cancer Registry data on all OC cases (2010-2012), published NHS Scotland dental workforce and registration/participation statistics, and individual patient data linked with NHS dental service activity were analysed. Results: Dentists were estimated to potentially encounter one case of OC every 10 years, OCC every 16.7 years, and OPC every 25 years. However, 53.7% of OC patients had made no dental contact two years pre-diagnosis. Conclusion: Strategies for early detection must consider the rarity of OC incidence and poor dental attendance patterns. These results highlight the importance of improving access and uptake of dental services among those at highest risk to increase the opportunities for early detection.

Presenting symptoms and long-term survival in head and neck cancer.

OBJECTIVES: To assess how type and number of symptoms are related to survival in patients with head and neck cancer. DESIGN: Patients were followed up for over 10 years from the Scottish Audit of Head and Neck Cancer (national cohort of head and neck cancer patients in Scotland 1999-2001). September 2013, cohort was linked to national mortality data. First, second and third presenting symptoms were recorded at diagnosis. SETTING: National prospective audit-Scotland. PARTICIPANTS: A subset of 1589 patients, from the original cohort of 1895, who had cancer arising from one of the four main subsites; larynx, oropharynx, oral cavity and hypopharynx. MAIN OUTCOME MEASURES: Median survival in relation to patients' presenting symptoms. RESULTS: A total of 1146 (72%) males and 443 (28%) females, mean age at diagnosis 64 years (13-95). There was a significant difference in survival in relation to the number of the patient's presenting symptoms; one symptom had a median survival of 5.3 years compared with 1.1 years for three symptoms. Patients who presented with weight loss had a median survival of 0.8 years, compared to 4.2 years if they did not (P < .001). Patients who presented with hoarseness had a median survival of 5.9 years compared to 2.6 years without (P < .001). There was no significant difference in long-term survival for patients who presented with an ulcer, compared to those that did not (P = .105). CONCLUSIONS: This study highlights the importance of patients' presenting symptoms, giving valuable information in highlighting appropriate "red flag" symptoms and subsequent treatment planning and prognosis.

Linking routinely collected social work, education and health data to enable monitoring of the health and health care of school-aged children in state care ('looked after children') in Scotland: a national demonstration project.

BACKGROUND AND OBJECTIVES: Children in state care ('looked after children') have poorer health than children who are not looked after. Recent developments in Scotland and elsewhere have aimed to improve services and outcomes for looked after children. Routine monitoring of the health outcomes of looked after children compared to those of their non-looked after peers is currently lacking. Developing capacity for comparative monitoring of population-based outcomes based on linkage of routinely collected administrative data has been identified as a priority. To our knowledge there are no existing population-based data linkage studies providing data on the health of looked after and non-looked after children at national level. Smaller scale studies that are available generally provide very limited information on linkage methods and hence do not allow scrutiny of bias that may be introduced through the linkage process. STUDY DESIGN AND METHODS: National demonstration project testing the feasibility of linking routinely collected looked after children, education and health data. PARTICIPANTS: All children in publicly funded school in Scotland in 2011/12. RESULTS: Linkage between looked after children data and the national pupil census classified 10,009 (1.5%) and 1757 (0.3%) of 670,952 children as, respectively, currently and previously looked after. Recording of the unique pupil identifier (Scottish Candidate Number, SCN) on looked after children returns is incomplete, with 66% of looked after records for 2011/12 for children of possible school age containing a valid SCN. This will have resulted in some under-ascertainment of currently and, particularly, previously looked after children within the general pupil population. Further linkage of the pupil census to the National Health Service Scotland master patient index demonstrated that a safe link to the child's unique health service (Community Health Index) number could be obtained for a very high proportion of children in each group (94%, 95% and 95% of children classified as currently, previously, and non-looked after, respectively). In general, linkage rates were higher for older children and those living in more affluent areas. Within the looked after group, linkage rates were highest for children with the fewest placements and for those in permanent fostering. CONCLUSIONS: This novel data linkage demonstrates the feasibility of monitoring population-based health outcomes of school-aged looked after and non-looked after children using linked routine administrative data. Improved recording of the unique pupil identifier number on looked after data returns would be beneficial. Extending the range of personal identifiers on looked after children returns would enable linkage to health data for looked after children who are not in publicly funded schooling (i.e. those who are preschool or postschool, home schooled or in independent schooling).

Traumatic dental injury and social deprivation in five-year-old children in Scotland 1993-2007.

OBJECTIVE: To describe the pattern and time trends of dental injury and its sociodemographic determinants among five-year-old children in Scotland. DESIGN AND METHODS: A retrospective analysis of Scottish Health Boards' Dental Epidemiological Programme (SHBDEP) and National Dental Inspection Programme (NDIP) records for the period 1993-2007. Annual incidences were calculated by age, gender, health board and deprivation categories (DEPCAT). RESULTS: Out of 68,354 children examined only 405 (0.6%) had suffered dental injury with an overall incidence of 5.9/1000 population. There was a remarkable decrease in incidence over time. Virtually the same rates were recorded for the two genders (M:F = 1.13:1.0). The incidence varied significantly between health boards' areas (p <0.001); the highest incidence being reported in Dumfries (14.2/1,000 population), which was 11 times greater than that in Ayrshire (1.3/1,000 population). There was no significant association between risk of dental injury and increasing deprivation (p = 0.956); in DEPCAT 1 (most affluent) the incidence was 6.4/1,000 population, while in DEPCAT 7 (most deprived) the incidence was 5.7/1,000 population. CONCLUSION: The incidence of dental injury is varied among health boards, though it had significantly decreased since 1993. Gender and deprivation level had no effect on incidence of dental injury.

Primary-care observational database study of the efficacy of GLP-1 receptor agonists and insulin in the UK.

AIMS: We investigated use and efficacy of glucagon-like peptide-1 (GLP-1) receptor agonists in UK practice. METHODS: People starting a GLP-1 receptor agonist (exenatide, liraglutide) or insulin (glargine, detemir, NPH) after a regimen of two or three oral glucose-lowering agents were identified from The Health Information Network observational primary care database (2007-2011). Mean change in HbA1c and body weight were compared at 1 year between cohorts, adjusting for baseline characteristics. RESULTS: Baseline characteristics of GLP-1 receptor agonist (n = 1123) vs. insulin (n = 1842) users were HbA1c 78 vs. 84 mmol/mol (9.3 vs. 9.8%) and BMI 38.2 vs. 30.9 kg/m². The GLP-1 receptor agonist cohort was younger, had shorter diabetes duration and follow-up, less microvascular disease and heart failure, higher estimated glomerular filtration rate and more use of oral glucose-lowering agents. Lower HbA1c reduction on GLP-1 receptor agonist [7 vs. 13 mmol/mol (0.6 vs. 1.2%) (n = 366 vs. 892)] was not statistically significant [adjusted mean difference -1.4 (95% CI -4.1, 1.2) mmol/mol], except in the highest HbA1c quintile [>96 mmol/mol (>10.9%); adjusted mean difference -17.8 (-28.6, -7.0) mmol/mol]. GLP-1 receptor agonist users lost weight [-4.5 vs. +1.5 kg; adjusted mean difference 4.7 (3.7, 5.8) kg; n = 335 vs. 634]. A UK 6-month target reduction for GLP-1 receptor agonists of 11 mmol/mol (1.0%) HbA1c and 3% weight was reached by 24.9% of those continuing treatment. CONCLUSIONS: Those starting GLP-1 receptor agonists are heavier with better glycaemic control than those starting basal insulin. Subsequently, they have improved weight change, with similar HbA1c reduction unless baseline HbA1c is very high. The UK 6-month GLP-1 receptor agonist target is usually not reached.

National supervised toothbrushing program and dental decay in Scotland.

We aimed to assess the association between the roll-out of the national nursery toothbrushing program and a reduction in dental decay in five-year-old children in a Scotland-wide population study. The intervention was supervised toothbrushing in nurseries and distribution of fluoride toothpaste and toothbrushes for home use, measured as the percentage of nurseries participating in each health service administrative board area. The endpoint was mean d(3)mft in 99,071 five-year-old children, covering 7% to 25% of the relevant population (in various years), who participated in multiple cross-sectional dental epidemiology surveys in 1987 to 2009. The slope of the uptake in toothbrushing was correlated with the slope in the reduction of d(3)mft. The mean d(3)mft in Years -2 to 0 (relative to that in start-up Year 0) was 3.06, reducing to 2.07 in Years 10 to 12 (difference = -0.99; 95% CI -1.08, -0.90; p < 0.001). The uptake of toothbrushing correlated with the decline in d(3)mft (correlation = -0.64; -0.86, -0.16; p = 0.011). The result improved when one outlying Health Board was excluded (correlation = -0.90; -0.97, -0.70; p < 0.0001). An improvement in the dental health of five-year-olds was detected and is associated with the uptake of nursery toothbrushing.

Socioeconomic deprivation and NHS orthodontic treatment delivery in Scotland.

OBJECTIVE: The purpose of this observational study was to investigate the relationship between deprivation and the delivery of primary care NHS orthodontic services across Scotland. METHOD: Deprivation was measured using the Scottish Index of Multiple Deprivation (SIMD). The Information Services Division, NHS National Services Scotland, supplied data on all claims for orthodontic treatments in Scotland for the years 2008 and 2009. Each claim was assigned to a SIMD quintile (SIMD 1 being the most deprived, and SIMD 5 the least deprived), and odds ratios were calculated. RESULTS: Uptake of orthodontic services is highest in the least deprived areas. Patients from the least deprived areas are nearly twice as likely to receive orthodontic treatment as those from the most deprived areas (odds ratio of 1.90 with a 95% confidence interval (CI) 1.86 to 1.94). CONCLUSION: Patients from more the most deprived backgrounds are less likely to receive orthodontic treatment than those from more affluent backgrounds, which does not necessarily reflect need.

Early prognostic indicators and outcome prediction model for replanted avulsed teeth.

AIM: To identify early clinical variables that are most predictive of treatment outcome and to develop a model that will allow prediction of treatment outcomes based on these variables. STUDY DESIGN AND METHODS: A dental trauma database was used to randomly identify patients who had received treatment for avulsed teeth between 1998 and 2007. A data extraction form was designed and completed for each tooth. Demographic, diagnostic and treatment information recorded in the patient's records, in addition to radiographs, were viewed retrospectively. STATISTICS: The significance and the predictive power for each early clinical variable were assessed using a univariate logistic regression model. Only significant variables (p<0.05) were considered eligible for the prediction model and a c-index was then constructed for their respective predictive power (0.5 = no predictive power, 1.0 = perfect prediction). RESULTS: Of the original sample of 213 patients who had received treatment for avulsed teeth between 1998-2007 only 105 fulfilled the criteria for evaluation. Two models ('At first visit' and 'at initial treatment visits') were produced with a total of five variables that were significant and holding the greatest predictive power (high c-index): patient age (p=0.001, c=0.80); stage of root formation (p=0.001, c=0.76); storage medium (p=0.047, c=0.58); tooth mobility after dressing (p=0.001, c=0.70); and tooth mobility after splinting (p=0.003, c=0.70). These variables underwent multi-variate analysis and the final models had good predictive abilities (c-index of 0.80 and 0.74). CONCLUSION: These predictive models based on patient age, stage of root formation, storage medium, tooth mobility after dressing and tooth mobility after splinting were shown to have high predictive value and will enable a clinician to estimate the long term prognosis of avulsed and replanted teeth. It will enable planning for further treatment with a realistic view of outcome at an early stage.

A comparison of duration of first prescribed insulin therapy in uncontrolled type 2 diabetes.

AIMS: We investigated whether differences in duration of first insulin use in type 2 diabetes remain after adjustment for potential confounders, and what factors are associated with longer use. METHODS: People prescribed a first insulin (2000-2007) after 2-3 non-insulin glucose lowering treatments (OGLD) were identified from the THIN UK primary care database and grouped by insulin, detemir (n=165), glargine (n=1011) or NPH (n=420). Time from beginning insulin to the prescription of another insulin type or a glucagon-like peptide was compared between insulins in a Cox model adjusting for: demographics, HbA1c, history of vascular complications and cardiovascular risk factors. The strength of association between duration of use and these variables was investigated. RESULTS: The adjusted hazard ratios compared to glargine for treatment change were 1.58 (95% CI 1.25, 2.00) for detemir and 1.49 (1.25, 1.78) for NPH. Lower mean treatment HbA(1c) correlated with longer time to a different insulin regimen (Spearman rank correlation -0.30, p<0.01) as were continuing OGLDs, older age, longer time from diagnosis, lower body mass index, lower HbA(1c), and no heart failure at baseline. CONCLUSIONS: People who began treatment with glargine and those with better on-treatment HbA(1c) remained on their first insulin for longer than those who began detemir or NPH.

Changes and predictors for change to thiazolidinedione prescribing in UK primary care following the rosiglitazone safety warning.

OBJECTIVE: To investigate switching from thiazolidinediones, and predictors for switching treatment, after publication of a meta-analysis reporting an increased risk of myocardial infarction associated with rosiglitazone use. RESEARCH DESIGN AND METHODS: Using the Health Information Network (THIN) UK primary care database, the number of people with type 2 diabetes prescribed either thiazolidinedione, rosiglitazone (n = 10,062) or pioglitazone (n = 4454), and the rate of switching from thiazolidinediones (n = 3301 and 1106, respectively), were computed for each month, May 2006 to January 2008. The probability of switching post-publication, May 2007 to January 2008, was modelled by logistic regression in a forward stepwise model. Variables included demographics, history of ischaemic heart disease (IHD), heart failure (HF) or stroke, risk factors for IHD, glucose-lowering and cardiovascular drug use, HbA(1c) and diabetes duration. RESULTS: There was a sharp increase in switching from both thiazolidinediones in summer 2007; rosiglitazone prescription numbers then decreased while pioglitazone prescribing increased. Switching from rosiglitazone was associated with IHD [adjusted odds ratio (OR) 1.72; 95% confidence intervals (CI) 1.47-2.00], insulin treatment (OR 5.10; 95% CI 3.21-8.10), HF (OR 2.26; 95% CI 1.62-3.18), a recent sulphonylurea prescription (OR 1.33; 95% CI 1.17-1.51) gender (OR men vs. women 0.79; 95% CI 0.70, 0.90) and duration of therapy. Switching from pioglitazone was associated with HF (OR 3.05; 95% CI 1.77-5.26), duration of therapy, and number of glucose-lowering treatments. CONCLUSIONS: Prescribing habits for both thiazolidinediones changed immediately following the safety warning. IHD was associated with switching from rosiglitazone; otherwise reasons for change appear to be complex, not directly related to the findings of the meta-analysis.

The dental health of three-year-old children in Greater Glasgow, Scotland.

OBJECTIVE: To report on the dental health of three-year-old children in Greater Glasgow, and to examine the amount of dental caries associated with deprivation in this young age group. DESIGN: Dental inspections in nursery schools. SUBJECTS AND METHODS: The national inspection programme using BASCD criteria was extended to include an additional group of nursery attending three-year-olds in Greater Glasgow in 2006/7 and 2007/8. Caries experience was analysed by logistic regression models and ROC plots. RESULTS: Fourteen percent of this population was sampled in 2006/7 and 19% in 2007/8 (usable data n = 1,711 in 2006/7, 2,428 in 2007/8). Mean d(3)mft was 1.1 in 2006/7 and 1.0 in 2007/8. The prevalence of caries experience was 26% in 2006/7 and 25% in 2007/8 (33% and 32%, respectively, for children in deprived areas). The adjusted odds-ratio for caries experience for children living in the most deprived areas was 2.90 (2.31, 3.64), p <0.001. There was a high rate of caries in the upper anterior teeth. CONCLUSION: It was feasible to conduct large scale caries surveys of three-year-olds in a nursery setting. Poor dental health and inequality commence early in life. Caries prevention should be targeted toward deprived families from birth.

Life course social mobility and risk of upper aerodigestive tract cancer in men.

The aim of this study was to explore associations between social mobility and tumours of the upper aero-digestive tract (UADT), focussing on life-course transitions in social prestige (SP) based on occupational history. 1,796 cases diagnosed between 1993 and 2005 in ten European countries were compared with 1585 controls. SP was classified by the Standard International Occupational Prestige Scale (SIOPS) based on job histories. SIOPS was categorised in high (H), medium (M) and low (L). Time weighted average achieved and transitions between SP with nine trajectories: H --> H, H --> M, H --> L, M --> H, M --> M, M --> L, L --> H, L --> M and L --> L were analysed. Odds ratios (ORs) and 95%-confidence intervals [95%-CIs] were estimated with logistic regression models including age, consumption of fruits/vegetables, study centre, smoking and alcohol consumption. The adjusted OR for the lowest versus the highest of three categories (time weighted average of SP) was 1.28 [1.04-1.56]. The distance of SP widened between cases and controls during working life. The downward trajectory H --> L gave an OR of 1.71 [0.75-3.87] as compared to H --> H. Subjects with M --> M and L --> L trajectories ORs were also elevated relative to subjects with H --> H trajectories. The association between SP and UADT is not fully explained by confounding factors. Downward social trajectory during the life course may be an independent risk factor for UADT cancers.

Socioeconomic factors associated with risk of upper aerodigestive tract cancer in Europe.

INTRODUCTION: In the European Union, there are 180,000 new cases of upper aerodigestive tract (UADT) cancer cases per year--more than half of whom will die of the disease. Socioeconomic inequalities in UADT cancer incidence are recognised across Europe. We aimed to assess the components of socioeconomic risk both independently and through their influence on the known behavioural risk factors of smoking, alcohol consumption and diet. PATIENTS AND METHODS: A multicentre case-control study with 2198 cases of UADT cancer and 2141 controls from hospital and population sources was undertaken involving 14 centres from 10 countries. Personal interviews collected information on demographics, lifetime occupation history, smoking, alcohol consumption and diet. Socioeconomic status was measured by education, occupational social class and unemployment. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed using unconditional logistic regression. RESULTS: When controlling for age, sex and centre significantly increased risks for UADT cancer were observed for those with low versus high educational attainment OR=1.98 (95% CI 1.67, 2.36). Similarly, for occupational socioeconomic indicators--comparing the lowest versus highest International Socio-Economic Index (ISEI) quartile for the longest occupation gave OR=1.60 (1.28, 2.00); and for unemployment OR=1.64 (1.24, 2.17). Statistical significance remained for low education when adjusting for smoking, alcohol and diet behaviours OR=1.29 (1.06, 1.57) in the multivariate analysis. Inequalities were observed only among men but not among women and were greater among those in the British Isles and Eastern European countries than in Southern and Central/Northern European countries. Associations were broadly consistent for subsite and source of controls (hospital and community). CONCLUSION: Socioeconomic inequalities for UADT cancers are only observed among men and are not totally explained by smoking, alcohol drinking and diet.

Effect of improved home ventilation on asthma control and house dust mite allergen levels.

BACKGROUND: The warm, humid environment in modern homes favours the dust mite population, but the effect of improved home ventilation on asthma control has not been established. We tested the hypothesis that a domestic mechanical heat recovery ventilation system (MHRV), in addition to allergen avoidance measures, can improve asthma control by attenuating re-colonization rates. METHODS: We conducted a randomized double-blind placebo-controlled parallel group trial of the installation of MHRV activated in half the homes of 120 adults with asthma, allergic to Dermatophagoides pteronyssinus. All homes had carpets steam cleaned and new bedding and mattress covers at baseline. The primary outcome was morning peak expiratory flow (PEF) at 12 months. RESULTS: At 12 months, the primary end-point; change in mean morning PEF as compared with baseline, did not differ between the MHRV group and the control group (mean difference 13.5 l/min, 95% CI: -2.6 to 29.8, P = 0.10). However, a secondary end-point; evening mean PEF, was significantly improved in the MHRV group (mean difference 24.5 l/min, 95% CI: 8.9-40.1, P = 0.002). Indoor relative humidity was reduced in MHRV homes, but there was no difference between the groups in Der p 1 levels, compared with baseline. CONCLUSIONS: The addition of MHRV to house dust mite eradication strategies did not achieve a reduction in mite allergen levels, but did improve evening PEF.

Effects of atorvastatin added to inhaled corticosteroids on lung function and sputum cell counts in atopic asthma.

BACKGROUND: Statins have anti-inflammatory properties that may be beneficial in the treatment of asthma. A study was undertaken to test the hypothesis that atorvastatin added to inhaled corticosteroids improves lung function and airway inflammation in atopic adults with asthma. METHODS: 54 adults with atopic asthma were recruited to a double-blind randomised controlled crossover trial comparing the effect of oral atorvastatin 40 mg daily with that of a matched placebo on asthma control and airway inflammation. Each treatment was administered for 8 weeks separated by a 6-week washout period. The primary outcome was morning peak expiratory flow (PEF). Secondary outcomes included forced expiratory volume in 1 s, asthma control questionnaire score, airway hyper-responsiveness to methacholine, induced sputum cytology and inflammatory biomarkers. RESULTS: At 8 weeks the change in mean morning PEF compared with baseline did not differ substantially between the atorvastatin and placebo treatment periods (mean difference -0.5 l/min, 95% CI -10.6 to 9.6, p = 0.921). Values for other clinical outcomes were similar between the atorvastatin and placebo treatment periods. The absolute sputum macrophage count was reduced after atorvastatin compared with placebo (mean difference -45.0 x 10(4) cells, 95% CI -80.1 to -9.7, p = 0.029), as was the sputum fluid leucotriene B4 (mean difference -88.1 pg/ml, 95% CI -156.4 to -19.9, p = 0.014). CONCLUSION: The addition of atorvastatin to inhaled corticosteroids results in no short-term improvement in asthma control but reduces sputum macrophage counts in mild to moderate atopic asthma. The change in sputum macrophage count suggests potential areas for investigation of statins in other chronic lung diseases.

Triple therapy in early active rheumatoid arthritis: a randomized, single-blind, controlled trial comparing step-up and parallel treatment strategies.

OBJECTIVE: The Tight Control of Rheumatoid Arthritis study previously demonstrated that an intensive step-up disease-modifying antirheumatic drug (DMARD) treatment strategy targeting persistent disease activity was superior to routine care in the management of early rheumatoid arthritis (RA). We undertook this study to test the hypothesis that early parallel triple therapy achieves better outcomes than step-up therapy within an intensive disease management regimen. METHODS: Ninety-six patients with early RA (mean disease duration 11.5 months) were randomized to receive step-up therapy (sulfasalazine [SSZ] monotherapy, then after 3 months, methotrexate [MTX] was added, and when the maximum tolerated dosage of MTX was reached, hydroxychloroquine [HCQ] was added) or parallel triple therapy (SSZ/MTX/HCQ). All patients were assessed monthly for 12 months. If their disease activity score in 28 joints (DAS28) was > or =3.2, the dosage of DMARDs was increased according to protocol, and swollen joints were injected with triamcinolone acetonide (maximum dosage 80 mg per month). A metrologist who was blinded to the treatment allocation performed assessments every 3 months. The primary outcome measure was the mean decrease in the DAS28 score at 12 months. RESULTS: Both groups showed substantial improvements in disease activity and functional outcome. At 12 months, the mean decrease in the DAS28 score was -4.0 (step-up therapy group) versus -3.3 (parallel therapy group) (P = 0.163). No significant differences in the percentages of patients with DAS28 remission (step-up therapy group 45% versus parallel triple therapy group 33%), DAS28 good response (60% versus 41%, respectively), or American College of Rheumatology criteria for 20% improvement (ACR20) (77% versus 76%, respectively), ACR50 (60% versus 51%, respectively), or ACR70 (30% versus 20%, respectively) responses were seen. Radiologic progression was similar in both groups. CONCLUSION: This study confirms that highly effective control of disease activity can be achieved using conventional DMARDs as part of an intensive disease management strategy. Within this setting, step-up therapy is at least as effective as parallel triple therapy.

Widening socio-economic inequalities in oral cancer incidence in Scotland, 1976-2002.

Oral cancer incidence was investigated among 10 857 individuals using Scottish Cancer Registry data. Since 1980 the incidence of oral cancer among males in Scotland has significantly increased, the rise occurring almost entirely in the most deprived areas of residence.

Systemic sensitivity to corticosteroids in smokers with asthma.

Cigarette smokers with asthma are insensitive to the therapeutic effects of corticosteroids. It is not known whether this insensitivity to corticosteroids in smokers affects tissue sites beyond the airways. A total of 75 asthmatic subjects (39 smokers) and 78 healthy controls (30 smokers) were recruited to an observational study. The cutaneous and peripheral blood lymphocyte responses to corticosteroids were measured. The cutaneous vasoconstrictor response to topical beclometasone was measured by applying different concentrations of beclometasone solutions to the skin in a random double-blind manner. The degree of blanching at each concentration was graded after 18 h. The sensitivity of peripheral blood lymphocytes to corticosteroids was assessed by measuring the suppressive effect of dexamethasone on lymphocyte proliferation stimulated by phytohaemagglutinin (PHA). Total mean+/-sd cutaneous vasoconstrictor response score to beclometasone was reduced in smokers with asthma to 5.39+/-3.58 versus 7.26+/-3.05 in never-smokers with asthma; and in all smokers to 6.47+/-3.33 versus 7.86+/-2.81 in all never-smokers. The sensitivity to corticosteroids of lymphocytes stimulated by PHA was similar between groups. In conclusion, smokers with asthma have an impaired cutaneous vasoconstrictor response to topical corticosteroids compared with never-smokers with asthma. This finding suggests that the insensitivity to corticosteroids in smokers with asthma affects tissue sites other than the airways.