Prevention of Atopic Dermatitis

Despite advances in atopic dermatitis (AD) treatments, research into AD prevention has been slow. Systematic reviews of prevention strategies promoting exclusive and prolonged breastfeeding, or interventions that reduce ingested or airborne allergens during pregnancy and after birth have generally not shown convincing benefit. Maternal/infant supplements such as Vitamin D have also not shown any benefit with the possible exception of omega-3 fatty acids. Systematic reviews suggest that probiotics could reduce AD incidence by around 20%, although the studies are quite variable and might benefit from individual patient data meta-analysis. Skin barrier enhancement from birth to prevent AD and food allergy has received recent interest, and results from national trials are awaited. It is possible that trying to influence major immunological changes that characterise AD at birth through infant-directed interventions may be too late, and more attention might be directed at fetal programming in utero

Cardiovascular disease and air pollution in Scotland: no association or insufficient data and study design?

<p><b>Background:</b> Coronary heart disease and stroke are leading causes of mortality and ill health in Scotland, and clear associations have been found in previous studies between air pollution and cardiovascular disease. This study aimed to use routinely available data to examine whether there is any evidence of an association between short-term exposure to particulate matter (measured as PM10, particles less than 10 micrograms per cubic metre) and hospital admissions due to cardiovascular disease, in the two largest cities in Scotland during the years 2000 to 2006.</p> <p><b>Methods:</b> The study utilised an ecological time series design, and the analysis was based on overdispersed Poisson log-linear models.</p> <p><b>Results:</b> No consistent associations were found between PM10 concentrations and cardiovascular hospital admissions in either of the cities studied, as all of the estimated relative risks were close to one, and all but one of the associated 95% confidence intervals contained the null risk of one.</p> <p><b>Conclusions:</b> This study suggests that in small cities, where air quality is relatively good, then either PM10 concentrations have no effect on cardiovascular ill health, or that the routinely available data and the corresponding study design are not sufficient to detect an association.</p&gt

Is the Scottish population living dangerously? Prevalence of multiple risk factors: the Scottish Health Survey 2003

<b>Background:</b> Risk factors are often considered individually, we aimed to investigate the prevalence of combinations of multiple behavioural risk factors and their association with socioeconomic determinants.<p></p> <b>Methods:</b> Multinomial logistic regression was used to model the associations between socioeconomic factors and multiple risk factors from data in the Scottish Health Survey 2003. Prevalence of five main behavioural risk factors - smoking alcohol, diet, overweight/obesity, and physical inactivity, and the odds in relation to demographic, individual and area socioeconomic factors.<p></p> <b>Results:</b> Full data were available on 6,574 subjects (80.7% of the survey sample). Nearly the whole adult population (97.5%) reported to have at least one behavioural risk factor; while 55% have three or more risk factors; and nearly 20% have four or all five risk factors. The most important determinants for having four or five multiple risk factors were low educational attainment which conferred around a 3-fold increased odds compared to high education; and residence in the most deprived communities (relative to least deprived) which had greater than 3-fold increased odds.<p></p> <b>Conclusions:</b> The prevalence of multiple behavioural risk factors was high and the prevalence of absence of all risk factors very low. These behavioural patterns were socioeconomically determined. Policy to address factors needs to be joined up and better consider underlying socioeconomic circumstances.<p></p&gt

Prior events predict cerebrovascular and coronary outcomes in the PROGRESS trial

<p><b>Background and Purpose:</b> The relationship between baseline and recurrent vascular events may be important in the targeting of secondary prevention strategies. We examined the relationship between initial event and various types of further vascular outcomes and associated effects of blood pressure (BP)–lowering.</p> <p><b>Methods:</b> Subsidiary analyses of the Perindopril Protection Against Recurrent Stroke Study (PROGRESS) trial, a randomized, placebo-controlled trial that established the benefits of BP–lowering in 6105 patients (mean age 64 years, 30% female) with cerebrovascular disease, randomly assigned to either active treatment (perindopril for all, plus indapamide in those with neither an indication for, nor a contraindication to, a diuretic) or placebo(s).</p> <p><b>Results:</b> Stroke subtypes and coronary events were associated with 1.5- to 6.6-fold greater risk of recurrence of the same event (hazard ratios, 1.51 to 6.64; P=0.1 for large artery infarction, P<0.0001 for other events). However, 46% to 92% of further vascular outcomes were not of the same type. Active treatment produced comparable reductions in the risk of vascular outcomes among patients with a broad range of vascular events at entry (relative risk reduction, 25%; P<0.0001 for ischemic stroke; 42%, P=0.0006 for hemorrhagic stroke; 17%, P=0.3 for coronary events; P homogeneity=0.4).</p> <p><b>Conclusions:</b> Patients with previous vascular events are at high risk of recurrences of the same event. However, because they are also at risk of other vascular outcomes, a broad range of secondary prevention strategies is necessary for their treatment. BP–lowering is likely to be one of the most effective and generalizable strategies across a variety of major vascular events including stroke and myocardial infarction.</p&gt

Modelling the evaporation of nanoparticle suspensions from heterogeneous surfaces

We present a Monte Carlo (MC) grid-based model for the drying of drops of a nanoparticle suspension upon a heterogeneous surface. The model consists of a generalised lattice-gas in which the interaction parameters in the Hamiltonian can be varied to model different properties of the materials involved. We show how to choose correctly the interactions, to minimise the effects of the underlying grid so that hemispherical droplets form. We also include the effects of surface roughness to examine the effects of contact-line pinning on the dynamics. When there is a `lid' above the system, which prevents evaporation, equilibrium drops form on the surface, which we use to determine the contact angle and how it varies as the parameters of the model are changed. This enables us to relate the interaction parameters to the materials used in applications. The model has also been applied to drying on heterogeneous surfaces, in particular to the case where the suspension is deposited on a surface consisting of a pair of hydrophilic conducting metal surfaces that are either side of a band of hydrophobic insulating polymer. This situation occurs when using inkjet printing to manufacture electrical connections between the metallic parts of the surface. The process is not always without problems, since the liquid can dewet from the hydrophobic part of the surface, breaking the bridge before the drying process is complete. The MC model reproduces the observed dewetting, allowing the parameters to be varied so that the conditions for the best connection can be established. We show that if the hydrophobic portion of the surface is located at a step below the height of the neighbouring metal, the chance of dewetting of the liquid during the drying process is significantly reduced.Comment: 14 pages, 14 figure

Bronchiectasis insanity:Doing the same thing over and over again and expecting different results?

Bronchiectasis is an increasingly common disease with a significant impact on quality of life and morbidity of affected patients. It is also a very heterogeneous disease with numerous different underlying etiologies and presentations. Most treatments for bronchiectasis are based on low-quality evidence; consequently, no treatments have been approved by the US Food and Drug Administration or the European Medicines Agency for the treatment of bronchiectasis. The last several years have seen numerous clinical trials in which the investigational agent, thought to hold great promise, did not demonstrate a clinically or statistically significant benefit. This commentary will review the likely reasons for these disappointing results and a potential approach that may have a greater likelihood of defining evidence-based treatment for bronchiectasis

Periodontal effects of the reversible dipeptidyl peptidase 1 inhibitor brensocatib in bronchiectasis

Aims: Brensocatib is a reversible inhibitor of dipeptidyl peptidase 1 (cathepsin C), in development to treat chronic non-cystic fibrosis bronchiectasis. The phase 2, randomized, placebo-controlled WILLOW trial (NCT03218917) was conducted to examine whether brensocatib reduced the incidence of pulmonary exacerbations. Brensocatib prolonged the time to the first exacerbation and led to fewer exacerbations than placebo. Because brensocatib potentially affects oral tissues due to its action on neutrophil-mediated inflammation, we analyzed periodontal outcomes in the trial participants.Materials and Methods: Patients with bronchiectasis were randomized 1:1:1 to receive once-daily oral brensocatib 10 or 25 mg or placebo. Periodontal status was monitored throughout the 24-week trial in a prespecified safety analysis. Periodontal pocket depth (PPD) at screening, week 8, and week 24 was evaluated. Gingival inflammation was evaluated by a combination of assessing bleeding upon probing and monitoring the Löe-Silness Gingival Index on 3 facial surfaces and the mid-lingual surface.Results: At week 24, mean ± SE PPD reductions were similar across treatment groups: -0.07 ± 0.007, -0.06 ± 0.007, and -0.15 ± 0.007 mm with brensocatib 10 mg, brensocatib 25 mg, and placebo, respectively. The distribution of changes in PPD and the number of patients with multiple increased PPD sites were similar across treatment groups at weeks 8 and 24. The frequencies of gingival index values were generally similar across treatment groups at each assessment. An increase in index values 0-1 and a decrease in index values 2-3 over time and at the end of the study were observed in all groups, indicating improved oral health.Conclusions: In patients with non-cystic fibrosis bronchiectasis, brensocatib 10 or 25 mg had an acceptable safety profile after 6 months' treatment, with no changes in periodontal status noted. Improvement in oral health at end of the study may be due to regular dental care during the trial and independent of brensocatib treatment.Knowledge Transfer Statement: The results of this study suggest that 24 weeks of treatment with brensocatib does not affect periodontal disease progression. This information can be used by clinicians when considering treatment approaches for bronchiectasis and suggests that the use of brensocatib will not be limited by periodontal disease risks. Nevertheless, routine dental/periodontal care should be provided to patients irrespective of brensocatib treatment.</p

Dynamical density functional theory for the evaporation of droplets of nanoparticle suspension

We develop a lattice gas model for the drying of droplets of a nanoparticle suspension on a planar surface, using dynamical density functional theory (DDFT) to describe the time evolution of the solvent and nanoparticle density profiles. The DDFT assumes a diffusive dynamics but does not include the advective hydrodynamics of the solvent, so the model is relevant to highly viscous or near to equilibrium systems. Nonetheless, we see an equivalent of the coffee-ring stain effect, but in the present model it occurs for thermodynamic rather the fluid-mechanical reasons. The model incorporates the effect of phase separation and vertical density variations within the droplet and the consequence of these on the nanoparticle deposition pattern on the surface. We show how to include the effect of slip or no-slip at the surface and how this is related to the receding contact angle. We also determine how the equilibrium contact angle depends on the microscopic interaction parameters.Comment: 35 pages, 10 figure