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J Ayres

Publications and source records attributed to J Ayres.

At least 19 recordsLinked to original sources
PubMed2006

The clinical effectiveness and cost-effectiveness of computed tomography screening for lung cancer: systematic reviews.

OBJECTIVES: The aim of this review is to examine the clinical and cost-effectiveness of screening for lung cancer using computed tomography (CT) to assist policy making and to clarify research needs. DATA SOURCES: Electronic databases and Internet resources. REVIEW METHODS: A systematic review was undertaken and selected studies were assessed using the checklists and methods described in NHS Centre for Reviews and Dissemination (CRD) Report 4. Separate narrative summaries were performed for clinical effectiveness and cost-effectiveness. Cost-effectiveness analysis resulting in a cost per quality-adjusted life-year was not feasible, therefore the main elements of such an appraisal were summarised and the key issues relating to the existing evidence base were discussed. RESULTS: Twelve studies of CT screening for lung cancer were identified, including two randomised controlled trials (RCTs) and ten studies of screening without comparator groups. The quality of reporting of these studies was variable, but the overall quality was adequate. The two RCTs were of short duration (1 year) and therefore there was currently no evidence that screening improves survival or reduces mortality. The proportion of people with abnormal CT findings varied widely between studies (5-51%). The prevalence of lung cancer detected was between 0.4% and 3.2% (number need to screen to detect one lung cancer = 31-249). Incidence rates of lung cancer were lower (0.1-1% per year). Detection of stage I and resectable tumours was high, 100% in some studies. Adverse events, as a result of investigation or surgery, or the screening process per se were poorly reported. Incidental findings of other abnormalities requiring medical follow-up were reported to be as high as 49%. Six full economic evaluations of population CT screening programmes for lung cancer were included in the review. The magnitude of cost-effectiveness ratios reported varied widely. None was set in the UK and generalisation was complicated by wide variation in the data used in different countries and a paucity of UK data for comparison. All six made the fundamental assumption that screening with CT for lung cancer reduced mortality. At the current time, there is no evidence to support that assumption. In the absence of evidence of health gains from screening for lung cancer, in terms of either quantity or quality of life, and faced with a range of uncertainties, from the frequency of abnormal screening findings within a population to the natural history of screening detected lung cancers, it is not feasible at the current time to develop accurately and meaningfully an economic argument for CT screening for lung cancer in the UK. For subgroups, in particular certain occupational groups, there is evidence of increased risk of lung cancer, but the role of screening has not been demonstrated by the current studies. CONCLUSIONS: The accepted National Screening Committee criteria are not currently met, with no RCTs, no evidence to support clinical effectiveness and no evidence of cost-effectiveness. RCTs are needed to examine the effect of CT screening on mortality, either with whole-population screening or for particular subgroups; to determine the rate of positive screening and detected lung cancers. Research is also needed to understand better the natural history and epidemiology of screening-detected lung cancers, particularly small, well-differentiated adenocarcinomas; as well as the impacts on quality of life. Increased collection is needed of UK health service data regarding resource use and safety data for lung cancer management and services. Research is also needed into the feasibility and logistics of tracing people who have in the past worked in industry where there was exposure to lung carcinogens.

Adult↗
PubMed2005

Immune response genes in the post-Q-fever fatigue syndrome, Q fever endocarditis and uncomplicated acute primary Q fever.

BACKGROUND: The influence of immune response gene variations on the development of chronic complications of Q fever is presently unclear. AIM: To compare the frequencies of allelic polymorphisms in immune response genes in different Q fever patient groups. DESIGN: Genetic association study. METHODS: We measured the frequencies of immune response gene variants in: (i) an expanded group of 31 post-Q-fever fatigue patients (QFS); (ii) 22 Q fever endocarditis patients (QFE); and (iii) 22 patients who made an uncomplicated recovery from their initial attack of primary acute Q fever, comparing them with various standard control panels from the general population. RESULTS: There were significant differences between the three Q fever groups. QFS patients differed from both QFE and uncomplicated patients and controls in the frequency of carriage of HLA-DRB1*11 and of the 2/2 genotype of the interferon-gamma intron1 microsatellite. Carriage of the HLA DRB1*11 allele was associated with reduced interferon-gamma and IL-2 responses from PBMC stimulated with ligand in short-term culture. QFE showed differences in the IL-10 promoter microsatellites R and G and had higher frequencies of the TNF-alpha receptor II 196R polymorphism. Q fever patients who had made an uncomplicated recovery differed from those with QFS or QFE, but were not significantly different in allelic frequencies to the control panels. DISCUSSION: These immunogenetic differences support the concept of different immune states in chronic Q fever, determined by genetic variations in host immune responses, rather than by solely properties of Coxiella burnetii.

Coxiella burnetii↗
PubMed2005

Benefits of omalizumab as add-on therapy in patients with severe persistent asthma who are inadequately controlled despite best available therapy (GINA 2002 step 4 treatment): INNOVATE.

BACKGROUND: Patients with severe persistent asthma who are inadequately controlled despite Global Initiative for Asthma (GINA) 2002 step 4 therapy are a challenging population with significant unmet medical need. We determined the effect of omalizumab on clinically significant asthma exacerbations (requiring systemic corticosteroids) in the first omalizumab study to exclusively enrol patients from this difficult-to-treat patient population. METHODS: Following a run-in phase, patients (12-75 years) inadequately controlled despite therapy with high-dose inhaled corticosteroids (ICS) and long-acting beta(2)-agonists (LABA) with reduced lung function and a recent history of clinically significant exacerbations were randomized to receive omalizumab or placebo for 28 weeks in a double-blind, parallel-group, multicentre study. RESULTS: A total of 419 patients were included in the efficacy analyses. The clinically significant asthma exacerbation rate (primary efficacy variable), adjusted for an observed relevant imbalance in history of clinically significant asthma exacerbations, was 0.68 with omalizumab and 0.91 with placebo (26% reduction) during the 28-week treatment phase (P = 0.042). Without adjustment, a similar magnitude of effect was seen (19% reduction), but this did not reach statistical significance. Omalizumab significantly reduced severe asthma exacerbation rate (0.24 vs 0.48, P = 0.002) and emergency visit rate (0.24 vs 0.43, P = 0.038). Omalizumab significantly improved asthma-related quality of life, morning peak expiratory flow and asthma symptom scores. The incidence of adverse events was similar between treatment groups. CONCLUSIONS: In patients with inadequately controlled severe persistent asthma, despite high-dose ICS and LABA therapy, and often additional therapy, omalizumab significantly reduced the rate of clinically significant asthma exacerbations, severe exacerbations and emergency visits. Omalizumab is effective and should be considered as add-on therapy for patients with inadequately controlled severe persistent asthma who have a significant unmet need despite best available therapy.

Administration, Inhalation↗
PubMed2004

The longer term outcome of children born to mothers with epilepsy.

OBJECTIVES: To determine the prevalence of cognitive delay and possible associated dysmorphic features in children exposed to antiepileptic drugs (AEDs) in utero. DESIGN: Retrospective study of children born to mothers with epilepsy. SETTING: Regional epilepsy clinics in Liverpool and Manchester, UK. PARTICIPANTS: Children aged between 6 months and 16 years born to mothers with epilepsy. MAIN OUTCOME MEASURES: Structured interviews, hospital records, clinical examination, and psychometric tests (Wechsler) were used to assess exposure and intelligence quotient (IQ). Blinded assessment of photographs was used to score children with characteristic dysmorphic features. RESULTS: A total of 249 children aged 6 and over were studied: 41 were exposed to sodium valproate, 52 to carbamazepine, 21 to phenytoin, 49 to polytherapy, and 80 were unexposed. Mean verbal IQ was significantly lower in the valproate group compared to unexposed and other monotherapy groups. Multiple regression analysis showed that both valproate exposure and frequent tonic-clonic seizures in pregnancy were significantly associated with a lower verbal IQ despite adjusting for other confounding factors. There was a significant negative correlation between dysmorphic features and verbal IQ in children exposed to valproate. CONCLUSIONS: This study identifies valproate as a drug carrying potential risks for developmental delay and cognitive impairment and is the first to suggest that frequent tonic-clonic seizures have a similar effect. Our results need to be interpreted with caution given their retrospective nature. Women with epilepsy need careful counselling about individual risk benefit of AED treatment before pregnancy.

Abnormalities, Drug-Induced↗
PubMed2002

Formoterol in patients with chronic obstructive pulmonary disease: a randomized, controlled, 3-month trial.

The aim of this study was to investigate formoterol, an inhaled long-acting beta2-agonist, in patients with chronic obstructive pulmonary disease (COPD). Six-hundred and ninety-two COPD patients, mean baseline forced expiratory volume in one second (FEV1) 54%, FEV1/forced vital capacity 75% of predicted, reversibility 6.4% pred, were treated with formoterol (4.5, 9 or 18 microg b.i.d.) or placebo via Turbuhaler for 12 weeks. Symptoms were recorded daily. Spirometry and the incremental shuttle walking test (SWT) were performed at clinic visits. Compared with placebo, 18 microg b.i.d. formoterol reduced the mean total symptom score by 13% and increased the percentage of nights without awakenings by 15%. Formoterol (9 and 18 microg b.i.d.) significantly reduced symptom scores for breathlessness (-7% and -9%, respectively) and chest tightness (-11% and -8%, respectively), reduced the need for rescue medication (-25% and -18%, respectively), and increased symptom-free days (71% and 86%, respectively). FEV1 improved significantly after all three doses of formoterol (versus placebo). No differences were found between groups in SWT walking distance. No unexpected adverse events were seen. In conclusion, 9 and 18 microg b.i.d. formoterol reduced symptoms and increased the number of symptom-free days in a dose-dependent manner in chronic obstructive pulmonary disease patients. Formoterol improved lung function at a dose of 4.5 microg b.i.d. and higher.

Administration, Inhalation↗
PubMed2001

Acute effects of particulate air pollution on respiratory admissions: results from APHEA 2 project. Air Pollution and Health: a European Approach.

The APHEA 2 project investigated short-term health effects of particles in eight European cities. In each city associations between particles with an aerodynamic diameter of less than 10 microm (PM(10)) and black smoke and daily counts of emergency hospital admissions for asthma (0-14 and 15-64 yr), chronic obstructive pulmonary disease (COPD), and all-respiratory disease (65+ yr) controlling for environmental factors and temporal patterns were investigated. Summary PM(10) effect estimates (percentage change in mean number of daily admissions per 10 microg/m(3) increase) were asthma (0-14 yr) 1.2% (95% CI: 0.2, 2.3), asthma (15-64 yr) 1.1% (0.3, 1.8), and COPD plus asthma and all-respiratory (65+ yr) 1.0% (0.4, 1.5) and 0.9% (0.6, 1.3). The combined estimates for Black Smoke tended to be smaller and less precisely estimated than for PM(10). Variability in the sizes of the PM(10) effect estimates between cities was also investigated. In the 65+ groups PM(10) estimates were positively associated with annual mean concentrations of ozone in the cities. For asthma admissions (0-14 yr) a number of city-specific factors, including smoking prevalence, explained some of their variability. This study confirms that particle concentrations in European cities are positively associated with increased numbers of admissions for respiratory diseases and that some of the variation in PM(10) effect estimates between cities can be explained by city characteristics.

Acute Disease↗
PubMed1998

Randomised placebo-controlled crossover trial on effect of inactivated influenza vaccine on pulmonary function in asthma.

BACKGROUND: Despite current recommendations, many people with asthma do not receive annual vaccination against influenza, partly because of concern that vaccine may trigger exacerbations. Colds can trigger exacerbations, which may be mistaken for vaccine-related adverse events. We undertook a double-blind placebo-controlled multicentre crossover study to assess the safety of influenza vaccine in patients with asthma, with allowance for the occurrence of colds. METHODS: We studied 262 patients, aged 18-75 years, who recorded daily peak expiratory flow (PEF), respiratory symptoms, medication, medical consultations, and hospital admissions for 2 weeks before the first injection and until 2 weeks after the second injection. Order of injection (vaccine and placebo) was assigned randomly. There was an interval of 2 weeks between injections. The main outcome measure was an exacerbation of asthma within 72 h of injection (defined as a fall in PEF of >20%). FINDINGS: Among 255 participants with paired data, 11 recorded a fall in PEF of more than 20% after vaccine compared with three after placebo (McNemar's test p=0.06); a fall of more than 30% was recorded by eight after vaccine compared with none after placebo (binomial test p=0.008). However, when participants with colds were excluded, there was no significant difference in the numbers with falls of more than 20% between vaccine and placebo (six vs three; binomial test p=0.51), although the difference for PEF decreases of more than 30% approached significance (five vs none; binomial test, p=0.06). This association was confined to first-time vaccinees. INTERPRETATION: Our findings indicate that pulmonary-function abnormalities may occur as a complication of influenza vaccination. However, the risk of pulmonary complications is very small and outweighed by the benefits of vaccination.

Adult↗
PubMed1995

Atopic status in patients with brittle and non-brittle asthma: a case-control study.

BACKGROUND: Sensitization to inhaled and ingested allergens is an important process in determining the subsequent clinical expression of asthma. Allergen exposure has also been reported to be associated with admission to hospital with acute severe asthma. Patients with brittle asthma, characterized by widely variable peak expiratory flow are at increased risk of life-threatening episodes but the role of atopy in these patients is unknown. OBJECTIVE: To determine the atopic status of patients with brittle asthma using a case-control design. METHODS: We have assessed the atopic status by skin-prick tests to 19 common allergens, and total and specific immunoglobulin E (IgE) in 29 patients with well characterized brittle asthma and an age, sex and treatment-matched control group without brittle asthma. RESULTS: Mean weal diameters were higher in brittle compared to non-brittle asthma for grass pollen (4.64 vs 2.17; P = 0.01), horse hair (6.28 vs 2.64; P = 0.02), feathers (2.96 vs 1.52; P = 0.01), wheat (1.48 vs 0.66; P = 0.001) and chocolate (1.09 vs 0.41; P = 0.05). Mean radioallergosorbent (RAST) scores to house dust mite were also greater in brittle asthma patients (19.3 vs 7.65; P = 0.05). Patients with brittle asthma also exhibited a significantly greater degree of atopy when weal diameters to all 19 allergens were summated to produce an atopy score (brittle 44.35 vs non-brittle 23.72; P = 0.04). There were no significant differences between the two groups in either the number of positive skin tests (using a 4 mm definition of skin-test positivity), total IgE or RASTs (using a weak +ve score to define positivity). However, the use of differing definitions of atopy (1, 2, 3, 4 and 5 mm skin test weal diameters) resulted in marked intra-group variation in atopic status in both brittle and non-brittle asthma patients. CONCLUSIONS: The greater degree of atopy seen may be an important factor in patients with brittle asthma. The varying interpretations of the classification of what constitutes the presence or absence of atopy, based on mean weal diameters of skin-prick tests, or from IgE or RAST positivity shows that there is considerable potential variation in the degree of difference between the two groups depending on what criteria are used. Although internationally agreed definitions of atopic status have been devised a more rigorous application, or review of these guidelines needs to accompany future epidemiological studies of allergic sensitization.

Animals↗
PubMed1995

Hospital admission rates for asthma and respiratory disease in the West Midlands: their relationship to air pollution levels.

BACKGROUND: A study was undertaken to determine the relationship between hospital admissions for asthma and all respiratory conditions in electoral wards in the West Midlands and ambient levels of smoke, sulphur dioxide, and nitrogen dioxide, and to establish whether the relationship is independent of social deprivation and ethnicity, and is different for young children and older individuals. METHODS: Data on hospital admissions for acute respiratory conditions were obtained by electoral ward from the West Midlands Regional Health Authority Information Department Körner inpatient data including asthma (ICD 493) and all acute respiratory disease (466, 480-486, 490-496) for the period April 1988 to March 1990. The population for each electoral ward, percentage of ward population that was from non-white ethnic groups, and Townsend deprivation score were all calculated from 1991 census information. Data on smoke and sulphur dioxide (SO2) levels were obtained for 24 wards in Birmingham, Coventry, Wolverhampton, Dudley, Stafford, and Burton-on-Trent, and on nitrogen dioxide (NO2) levels from 39 wards in the same local authority areas. All were background urban sites and most participated in the Warren Spring national quality control programme for SO2 and smoke monitoring. Indirect age-sex standardised hospitalisation rates (SHR) for all respiratory conditions and asthma were calculated using the 1991 rates for the West Midlands RHA as the standard. Multivariate regression models were used to assess the relationship between individual pollutants and the SHR. The Townsend score and percentage of the population from non-white ethnic groups were included in all models to adjust for ethnicity and socioeconomic deprivation. RESULTS: The SHR for asthma varied almost fourfold across the region, and all respiratory SHR showed more than three fold variation. Bivariate regression revealed both Townsend score and percentage of non-white individuals to be associated with SHR for asthma and all respiratory conditions at all ages, but not for children under 5 years. NO2 was associated with hospital admission rates for all ages including children under 5. SO2 and smoke were not associated with hospital admissions. Multivariate analysis including Townsend score and percentage of non-white subjects in the model revealed that NO2 was associated with hospital admission rates for all respiratory conditions only for children under 5. The Townsend score was associated with SHR for all respiratory conditions, and both the Townsend score and percentage of non-white subjects were associated with SHR for asthma in children under 5 in two of three models. The association between SHR for asthma and percentage of non-white subjects was negative. CONCLUSIONS: Socioeconomic deprivation, as measured by the Townsend score, is a significant predictor of hospital admission rates for respiratory disease in older individuals, and both the percentage of non-white subjects and the Townsend score are significant predictors of hospital admission rates for asthma in children. After correction for socioeconomic deprivation and ethnicity, background urban NO2 levels in the ward of residence are significantly associated with standardised hospital admission rates for all respiratory disease in children under 5. This may represent a causal effect of NO2 on the respiratory health of children, or the effect of confounding factors not corrected by use of the Townsend score.

Acute Disease↗