Background Additional topical treatments for atopic dermatitis (AD) are needed that provide relief while minimizing risks. Objective We sought to assess the efficacy and safety of crisaborole ...ointment, a phosphodiesterase 4 inhibitor, in two phase III AD studies (AD-301: NCT02118766 ; AD-302: NCT02118792 ). Methods Two identically designed, vehicle-controlled, double-blind studies enrolled and randomly assigned (2:1, crisaborole:vehicle) patients aged 2 years or older with an Investigator's Static Global Assessment (ISGA) score of mild or moderate for twice-daily application for 28 days. The primary end point was ISGA score at day 29 of clear (0)/almost clear (1) with 2-grade or greater improvement from baseline. Additional analyses included time to success in ISGA score, percentage of patients achieving clear/almost clear, reduction in severity of AD signs, and time to improvement in pruritus. Results More crisaborole- than vehicle-treated patients achieved ISGA score success (clear/almost clear with ≥2-grade improvement; AD-301: 32.8% vs 25.4%, P = .038; AD-302: 31.4% vs 18.0%, P < .001), with a greater percentage with clear/almost clear (51.7% vs 40.6%, P = .005; 48.5% vs 29.7%, P < .001). Crisaborole-treated patients achieved success in ISGA score and improvement in pruritus earlier than those treated with vehicle (both P ≤ .001). Treatment-related adverse events were infrequent and mild to moderate in severity. Limitations Short study duration was a limitation. Conclusions Crisaborole demonstrated a favorable safety profile and improvement in all measures of efficacy, including overall disease severity, pruritus, and other signs of AD.
The subcutaneous implantable defibrillator (S-ICD) provides an alternative to the transvenous ICD for the prevention of sudden cardiac death, but has not been well studied in the most commonly ...treated transvenous ICD patient population, namely, primary prevention (PP) patients with left ventricular dysfunction.
The analyses in the present study were designed to compare clinical outcomes for PP patients with and without a reduced ejection fraction (EF) and secondary prevention (SP) patients implanted with the S-ICD.
All patients 18 years and older from the S-ICD IDE study and the EFFORTLESS Registry with available data as of November 18, 2013, were included (n = 856; mean follow-up duration 644 days). Outcomes were evaluated in 2 analyses: (1) comparing all PP patients (n = 603, 70.4%) with all SP patients (n = 253, 29.6%) and (2) comparing all PP patients with an EF ≤35% (n = 379) with those with an EF >35% (n = 149, 17.4%).
No differences were observed in mortality, complications, inappropriate therapy, or ability to convert ventricular tachyarrhythmias between SP and PP patients. However, SP patients had a higher incidence of appropriate therapy than did PP patients (11.9% vs 5.0%; P = .0004). In the PP subanalysis, the cohort with an EF ≤35% had significantly older patients with more comorbidities and higher mortality (3.0% annually vs 0.0%). Despite these differences, device-related complications, conversion efficacy, and incidence of inappropriate shock therapies were not significantly different between PP subgroups.
The S-ICD performs well in protecting patients with either PP or SP implant indications from sudden cardiac death. Within PP patients, device performance was independent of EF.
Multiple sclerosis is a heterogeneous disease with varying clinical picture. There have been substantial efforts to develop outcome measurements for therapeutic interventions but very few studies ...have addressed the value of bodily functions from the patient perspective. In a randomly selected cohort of early (<5 years, n = 84) and longer lasting disease courses (>15 years, n = 82) patients we asked for a weighting of 13 bodily functions and compared results with actual disability as measured by the United Kingdom Disability Scale. Lower limb function was given the highest priority in both patient groups followed by visual functioning and cognition especially in longer lasting MS. Actual disability did not correlate with the given priorities indicating that experienced deficits do not influence the subjective ratings of bodily functions. These results underline that ambulation-focused scales in MS represent a key dimension from the patient perspective. Visual functioning should be taken more into account.
Background:
Exercise may have beneficial effects on both well-being and walking ability in multiple sclerosis (MS). Exercise is shown to be neuroprotective in rodents and may also enhance cognitive ...function in humans. It may, therefore, be particularly useful for MS patients with pronounced neurodegeneration.
Objective:
To investigate the potential of standardized exercise as a therapeutic intervention for progressive MS, in a randomized-controlled pilot trial.
Methods:
Patients with progressive MS and moderate disability (Expanded Disability Status Scale (EDSS) of 4–6) were randomized to one of three exercise interventions (arm ergometry, rowing, bicycle ergometry) for 8–10 weeks or a waitlist control group. We analyzed the drop-out rate as a measure of feasibility. The primary endpoint of the study was aerobic fitness. Secondary endpoints were walking ability, cognitive function as measured by a neuropsychological test battery, depression and fatigue.
Results:
A total of 42 patients completed the trial (10.6% drop-out rate). Significant improvements were seen in aerobic fitness. In addition, exercise improved walking ability, depressive symptoms, fatigue and several domains of cognitive function.
Conclusion:
This study indicated that aerobic training is feasible and could be beneficial for patients with progressive MS. Larger exercise studies are needed to confirm the effect on cognition.
Trial Registration:
ISRCTN (trial number 76467492) http://isrctn.org
We present a time‐of‐flight mass spectrometer design for the measurement of ions in the ~30 keV to 10 MeV range for protons (up to ~40 MeV and ~150 MeV for He and heavy ions, respectively) and ~30 ...keV to 1 MeV range for electrons, covering half of the sky with 80 apertures. The instrument, known as the “Mushroom,” owing to its shape, solves the field of view problem for magnetospheric and heliospheric missions that employ three‐axis stabilized spacecraft, yet still require extended angular coverage; the Mushroom is also compatible with a spinning spacecraft. The most important new feature of the Mushroom is the method through which uncomplicated electrostatic optics and clean position sensing combine to permit many apertures to fit into a compact, low‐mass sensor head (or wedge), several of which (ideally eight) compose a full instrument. Most of the sensor head's volume is an empty, equipotential region, resulting in the modest 250 g mass of each 10‐aperture wedge. The Mushroom is capable of separating ion species across most of its energy range and angular field of view. For example, separation of the neighboring 3He and 4He isotopes is excellent; the full width at half maximum mass resolution has been measured to be 0.24 amu to 0.32 amu, respectively. Converting this to a Gaussian width σm in mass m, this represents a σm/m mass resolution better than 0.04. This separation is highly desirable for the flight program for which the first Mushroom was built, the Solar Probe Plus mission. More generally, we estimate the mass resolution to be σm/m ≈ 0.1, but this is energy, mass, and angularly dependent. We also discuss the solid‐state detector stack capability, which extends the energy range of protons and helium, with composition, to ~100 MeV.
Key Points
Anisotropy, pitch angle distributions, and large field of view are important for energetic ion and electron science
The “Mushroom” instrument has been developed by JHU/APL to provide needed large FOV and angular resolution
The first Mushroom, EPI‐Lo, part of the ISʘIS investigation on Solar Probe Plus, has achieved excellent composition and spatial separation
Background Although ambient air pollution has been linked to reduced lung function in healthy children, longitudinal analyses of pollution effects in asthmatic patients are lacking. Objective We ...sought to investigate pollution effects in a longitudinal asthma study and effect modification by controller medications. Methods We examined associations of lung function and methacholine responsiveness (PC20 ) with ozone, carbon monoxide (CO), nitrogen dioxide, and sulfur dioxide concentrations in 1003 asthmatic children participating in a 4-year clinical trial. We further investigated whether budesonide and nedocromil modified pollution effects. Daily pollutant concentrations were linked to ZIP/postal code of residence. Linear mixed models tested associations of within-subject pollutant concentrations with FEV1 and forced vital capacity (FVC) percent predicted, FEV1 /FVC ratio, and PC20 , adjusting for seasonality and confounders. Results Same-day and 1-week average CO concentrations were negatively associated with postbronchodilator percent predicted FEV1 (change per interquartile range, −0.33 95% CI, −0.49 to −0.16 and −0.41 95% CI, −0.62 to −0.21, respectively) and FVC (−0.19 95% CI, −0.25 to −0.07 and −0.25 95% CI, −0.43 to −0.07, respectively). Longer-term 4-month CO averages were negatively associated with prebronchodilator percent predicted FEV1 and FVC (−0.36 95% CI, −0.62 to −0.10 and −0.21 95% CI, −0.42 to −0.01, respectively). Four-month averaged CO and ozone concentrations were negatively associated with FEV1 /FVC ratio ( P < .05). Increased 4-month average nitrogen dioxide concentrations were associated with reduced postbronchodilator FEV1 and FVC percent predicted. Long-term exposures to sulfur dioxide were associated with reduced PC20 (percent change per interquartile range, −6% 95% CI, −11% to −1.5%). Treatment augmented the negative short-term CO effect on PC20. Conclusions Air pollution adversely influences lung function and PC20 in asthmatic children. Treatment with controller medications might not protect but rather worsens the effects of CO on PC20 . This clinical trial design evaluates modification of pollution effects by treatment without confounding by indication.
The purpose of this study was to evaluate risk factors for antepartum depressive symptoms that can be assessed in routine obstetric care. We evaluated articles in the English-language literature from ...1980 through 2008. Studies were selected if they evaluated the association between antepartum depressive symptoms and ≥1 risk factors. For each risk factor, 2 blinded, independent reviewers evaluated the overall trend of evidence. In total, 57 studies met eligibility criteria. Maternal anxiety, life stress, history of depression, lack of social support, unintended pregnancy, Medicaid insurance, domestic violence, lower income, lower education, smoking, single status, and poor relationship quality were associated with a greater likelihood of antepartum depressive symptoms in bivariate analyses. Life stress, lack of social support, and domestic violence continued to demonstrate a significant association in multivariate analyses. Our results demonstrate several correlates that are consistently related to an increased risk of depressive symptoms during pregnancy.
Highlights • Nerve ultrasound may be used in quantifying pathological cross sectional area changes. • The Bochum Ultrasound score allows a distinction of CIDP from AIDP. • Both the CIDP and AIDP show ...peripheral nerve and brachial plexus enlargements.
Storm events dominate riverine loads of dissolved organic carbon (DOC) and nitrate and are expected to increase in frequency and intensity in many regions due to climate change. We deployed three ...high‐frequency (15 min) in situ absorbance spectrophotometers to monitor DOC and nitrate concentration for 126 storms in three watersheds with agricultural, urban, and forested land use/land cover. We examined intrastorm hysteresis and the influences of seasonality, storm size, and dominant land use/land cover on storm DOC and nitrate loads. DOC hysteresis was generally anticlockwise at all sites, indicating distal and plentiful sources for all three streams despite varied DOC character and sources. Nitrate hysteresis was generally clockwise for urban and forested sites, but anticlockwise for the agricultural site, indicating an exhaustible, proximal source of nitrate in the urban and forested sites, and more distal and plentiful sources of nitrate in the agricultural site. The agricultural site had significantly higher storm nitrate yield per water yield and higher storm DOC yield per water yield than the urban or forested sites. Seasonal effects were important for storm nitrate yield in all three watersheds and farm management practices likely caused complex interactions with seasonality at the agricultural site. Hysteresis indices did not improve predictions of storm nitrate yields at any site. We discuss key lessons from using high‐frequency in situ optical sensors.
Key Points
An improved hysteresis index revealed remarkable variation in storm dynamics for 126 storms in watersheds with varied land use/land cover
Seasonality influenced storm nitrate loading; interactions between farm practices and seasonal dynamics were captured by sensors
Sites had generally anticlockwise storm hysteresis for DOC, though storm nitrate hysteresis direction varied by land use/land cover
Background The gut microbiome in infancy influences immune system maturation, and may have an important impact on allergic disease risk. Objective We sought to determine how prenatal and early life ...factors impact the gut microbiome in a relatively large, ethnically diverse study population of infants at age 3 to 6 months, who were enrolled in Vitamin D Antenatal Asthma Reduction Trial, a clinical trial of vitamin D supplementation in pregnancy to prevent asthma and allergies in offspring. Methods We performed 16S rRNA gene sequencing on 333 infants' stool samples. Microbial diversity was computed using the Shannon index. Factor analysis applied to the top 25 most abundant taxa revealed 4 underlying bacterial coabundance groups; the first dominated by Firmicutes ( Lachnospiraceae / Clostridiales ), the second by Proteobacteria ( Klebsiella / Enterobacter ), the third by Bacteriodetes , and the fourth by Veillonella . Scores for coabundance groups were used as outcomes in regression models, with prenatal/birth and demographic characteristics as independent predictors. Multivariate analysis, using all microbial community members, was also conducted. Results White race/ethnicity was associated with lower diversity but higher Bacteroidetes coabundance scores. C-section birth was associated with higher diversity, but decreased Bacteroidetes coabundance scores. Firmicutes scores were higher for infants born by C-section. Breast-fed infants had lower proportions of Clostridiales . Cord blood vitamin D was linked to increased Lachnobacterium , but decreased Lactococcus. Conclusions The findings presented here suggest that race, mode of delivery, breast-feeding, and cord blood vitamin D levels are associated with infant gut microbiome composition, with possible long-term implications for immune system modulation and asthma/allergic disease incidence.
PDF
