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1.  Maternal Plasma Phosphatidylcholine Fatty Acids and Atopy and Wheeze in the Offspring at Age of 6 Years 
Variation in exposure to polyunsaturated fatty acids (PUFAs) might influence the development of atopy, asthma, and wheeze. This study aimed to determine whether differences in PUFA concentrations in maternal plasma phosphatidylcholine are associated with the risk of childhood wheeze or atopy. For 865 term-born children, we measured phosphatidylcholine fatty acid composition in maternal plasma collected at 34 weeks' gestation. Wheezing was classified using questionnaires at 6, 12, 24, and 36 months and 6 years. At age of 6 years, the children underwent skin prick testing, fractional exhaled nitric oxide (FENO) measurement, and spirometry. Maternal n-6 fatty acids and the ratio of n-3 to n-6 fatty acids were not associated with childhood wheeze. However, higher maternal eicosapentaenoic acid, docosahexaenoic acid, and total n-3 fatty acids were associated with reduced risk of non-atopic persistent/late wheeze (RR 0.57, 0.67 and 0.69, resp. P = 0.01, 0.015, and 0.021, resp.). Maternal arachidonic acid was positively associated with FENO (P = 0.024). A higher ratio of linoleic acid to its unsaturated metabolic products was associated with reduced risk of skin sensitisation (RR 0.82, P = 0.013). These associations provide some support for the hypothesis that variation in exposure to n-6 and n-3 fatty acids during pregnancy influences the risk of childhood wheeze and atopy.
PMCID: PMC3463812  PMID: 23049600
2.  A new look at the pathogenesis of asthma 
Asthma is an inflammatory disorder of the conducting airways that has strong association with allergic sensitization. The disease is characterized by a polarized Th-2 (T-helper-2)-type T-cell response, but in general targeting this component of the disease with selective therapies has been disappointing and most therapy still relies on bronchodilators and corticosteroids rather than treating underlying disease mechanisms. With the disappointing outcomes of targeting individual Th-2 cytokines or manipulating T-cells, the time has come to re-evaluate the direction of research in this disease. A case is made that asthma has its origins in the airways themselves involving defective structural and functional behaviour of the epithelium in relation to environmental insults. Specifically, a defect in barrier function and an impaired innate immune response to viral infection may provide the substrate upon which allergic sensitization takes place. Once sensitized, the repeated allergen exposure will lead to disease persistence. These mechanisms could also be used to explain airway wall remodelling and the susceptibility of the asthmatic lung to exacerbations provoked by respiratory viruses, air pollution episodes and exposure to biologically active allergens. Variable activation of this epithelial–mesenchymal trophic unit could also lead to the emergence of different asthma phenotypes and a more targeted approach to the treatment of these. It also raises the possibility of developing treatments that increase the lung's resistance to the inhaled environment rather than concentrating all efforts on trying to suppress inflammation once it has become established.
PMCID: PMC2805922  PMID: 20025610
allergen; asthma; inflammation; remodelling; T-cell; virus infection; BHR, bronchial hyper-responsiveness; CT, computed tomography; DC, dendritic cell; ADC, airway DC; EBUS, endobronchial ultrasound; EMTU, epithelial–mesenchymal trophic unit; ETS, environmental tobacco smoke; IFN, interferon; IL, interleukin; IoW, Isle of Wight; LT, leukotriene; mAb, monoclonal antibody; RV, rhinovirus; TGF-β, transforming growth factor-β; Th-2, T-helper-2; TJ, tight junction; TSLP, thymic stromal lymphopoietin
3.  Assessment of the potential impact of a reminder system on the reduction of diagnostic errors: a quasi-experimental study 
Computerized decision support systems (DSS) have mainly focused on improving clinicians' diagnostic accuracy in unusual and challenging cases. However, since diagnostic omission errors may predominantly result from incomplete workup in routine clinical practice, the provision of appropriate patient- and context-specific reminders may result in greater impact on patient safety. In this experimental study, a mix of easy and difficult simulated cases were used to assess the impact of a novel diagnostic reminder system (ISABEL) on the quality of clinical decisions made by various grades of clinicians during acute assessment.
Subjects of different grades (consultants, registrars, senior house officers and medical students), assessed a balanced set of 24 simulated cases on a trial website. Subjects recorded their clinical decisions for the cases (differential diagnosis, test-ordering and treatment), before and after system consultation. A panel of two pediatric consultants independently provided gold standard responses for each case, against which subjects' quality of decisions was measured. The primary outcome measure was change in the count of diagnostic errors of omission (DEO). A more sensitive assessment of the system's impact was achieved using specific quality scores; additional consultation time resulting from DSS use was also calculated.
76 subjects (18 consultants, 24 registrars, 19 senior house officers and 15 students) completed a total of 751 case episodes. The mean count of DEO fell from 5.5 to 5.0 across all subjects (repeated measures ANOVA, p < 0.001); no significant interaction was seen with subject grade. Mean diagnostic quality score increased after system consultation (0.044; 95% confidence interval 0.032, 0.054). ISABEL reminded subjects to consider at least one clinically important diagnosis in 1 in 8 case episodes, and prompted them to order an important test in 1 in 10 case episodes. Median extra time taken for DSS consultation was 1 min (IQR: 30 sec to 2 min).
The provision of patient- and context-specific reminders has the potential to reduce diagnostic omissions across all subject grades for a range of cases. This study suggests a promising role for the use of future reminder-based DSS in the reduction of diagnostic error.
PMCID: PMC1513379  PMID: 16646956

Results 1-3 (3)