Optimal administration of bronchodilators with valved holding chambers in preschool children: a review of literature

Our aim was to synthesize the published literature on factors that potentially affect the delivery of bronchodilators using valved holding chambers (VHC) in preschool children. We also aimed to identify those attributes that are not yet incorporated or clearly stated in the guidelines and those topics that are still lacking sufficient data. There is strong evidence supporting several recommendations in current guidelines. Based on present knowledge, bronchodilators should be delivered by VHC administering each puff separately. Face mask should be omitted as soon as the child can hold the mouthpiece of the VHC tightly between the lips and teeth. Based on the review, we suggest adding a specific note to current guidelines about the effect of chamber volume and the impact of co-operation during drug administration. Calming the child and securing a tight face-to-mask seal is critical for successful drug delivery. There is not enough evidence to make specific recommendations on the most reliable VHC and face mask for children. There is an urgent need for studies that evaluate and compare the effectiveness of VHCs in various clinical settings in wide age-groups and respiratory patterns. In addition, there is insufficient data on ideal chamber volume, material, and effective antistatic treatment. What is Known: Valved holding chambers (VHC) should not be considered interchangeable when used with pressurized metered dose inhalers (pMDI). Drug delivery is influenced by VHC volume, aerodynamic and electrostatic properties; mask fit; respiratory pattern and co-operation during inhalation; and the number of puffs actuated. What is New: The impact of co-operation, VHC volume, and good mask-to-face fit during drug inhalation is not stressed enough in the guidelines. Studies are urgently needed to evaluate the effectiveness of different VHCs in various clinical settings focusing on VHC electrostatic properties, respiratory patters, face masks, and ideal pMDI+VHC combinations.Peer reviewe

Safety of the SQ tree sublingual immunotherapy tablet: Pooled safety analysis of clinical trials

Background The standardized quality (SQ) tree sublingual immunotherapy (SLIT)-tablet has recently been approved for treatment of tree pollen allergy. Healthcare workers should be provided with detailed safety data for clinical use. Objective To assess the tolerability and safety of the SQ tree SLIT-tablet (12 SQ-Bet) in adults and adolescents. Methods Safety data were pooled from three double-blinded, randomized, placebo-controlled trials (2 phase-II/1 phase-III) including adults and adolescents 12-65 years with allergic rhinitis and/or conjunctivitis treated before and during one pollen season once-daily with 12 SQ-Bet (n = 471) or placebo (n = 458): EudraCT no: 2012-000031-59; NCT02481856; EudraCT 2015-004821-15. Results The most frequently reported investigational medicinal product (IMP)-related AEs with 12 SQ-Bet were oral pruritis (39% of subjects) and throat irritation (29%). IMP-related AEs were mainly mild or moderate in severity, and the majority resolved without treatment and did not lead to treatment interruption/discontinuation. With 12 SQ-Bet, oral pruritus was more frequent among subjects with pollen food syndrome (PFS) (45%) than without PFS (29%). The 12 SQ-Bet did not seem to induce an increased risk of asthma: 7 events were reported in 7 subjects with 12 SQ-Bet and 11 in 10 subjects with placebo. No differences were seen in the risk of moderate-to-severe IMP-related AEs regardless of age, PFS status and asthma medical history. Conclusions The 12 SQ tree SLIT-tablet was well tolerated in tree pollen allergic subjects with no major safety concerns detected. This safety profile supports daily at-home sublingual administration once the first dose is tolerated when administered under medical supervision.Peer reviewe

Laparoscopic ventral rectopexy in male patients with external rectal prolapse is associated with a high reoperation rate

Background Laparoscopic ventral rectopexy has been used to treat male patients with external rectal prolapse, but evidence to support this approach is scarce. The aim of this study was to evaluate the results of this new abdominal rectopexy surgical technique in men. Methods This was a retrospective multicenter study. Adult male patients who were operated on for external rectal prolapse using ventral rectopexy in five tertiary hospitals in Finland between 2006 and 2014 were included in the study. Patient demographics, detailed operative, postoperative and short-term follow-up data were collected from patient registers in participating hospitals. A questionnaire and informed consent form was sent to all patients. The questionnaire included scores for anal incontinence, obstructed defecation syndrome, urinary symptoms and sexual dysfunction. The main outcome measure was the incidence of recurrent rectal prolapse. Surgical morbidity, the need for surgical repair due to recurrent symptoms and functional outcomes were secondary outcome measures. Results A total of 52 adult male patients with symptoms caused by external rectal prolapse underwent ventral rectopexy. The questionnaire response rate was 64.4 %. Baseline clinical characteristics and perioperative results were similar in the responder and non-responder groups. A total of 9 (17.3 %) patients faced complications. There were two (3.8 %) serious surgical complications during the 30-day period after surgery that necessitated reoperation. None of the complications were mesh related. Recurrence of the prolapse was noticed in nine patients (17 %), and postoperative mucosal anal prolapse symptoms persisted in 11 patients (21 %). As a result, the reoperation rate was high. Altogether, 17 patients (33 %) underwent reoperation during the follow-up period due to postoperative complications or recurrent rectal or mucosal prolapse. According to the postoperative questionnaire data, patients under 40 had good functional results in terms of anal continence, defecation, urinary functions and sexual activity. Conclusions Laparoscopic ventral rectopexy is a safe surgical procedure in male patients with external prolapse. However, a high overall reoperation rate was noticed due to recurrent rectal and residual mucosal prolapse. This suggests that the ventral rectopexy technique should be modified or combined with other abdominal or perineal methods when treating male rectal prolapse patients.Peer reviewe

The contributions of snow, fog, and dry deposition to the summer flux of anions and cations at Summit, Greenland

Experiments were performed during the period May–July of 1993 at Summit, Greenland. Aerosol mass size distributions as well as daily average concentrations of several anionic and cationic species were measured. Dry deposition velocities for SO42− were estimated using surrogate surfaces (symmetric airfoils) as well as impactor data. Real-time concentrations of particles greater than 0.5 μm and greater than 0.01 μm were measured. Snow and fog samples from nearly all of the events occurring during the field season were collected. Filter sampler results indicate that SO42− is the dominant aerosol anion species, with Na+, NH4+, and Ca2+being the dominant cations. Impactor results indicate that MSA and SO42− have similar mass size distributions. Furthermore, MSA and SO42− have mass in both the accumulation and coarse modes. A limited number of samples for NH4+ indicate that it exists in the accumulation mode. Na, K, Mg, and Ca exist primarily in the coarse mode. Dry deposition velocities estimated from impactor samples and a theory for dry deposition to snow range from 0.017 cm/s +/− 0.011 cm/s for NH4+ to 0.110 cm/s +/− 0.021 cm/s for Ca. SO42− dry deposition velocity estimates using airfoils are in the range 0.023 cm/s to 0.062 cm/s, as much as 60% greater than values calculated using the airborne size distribution data. The rough agreement between the airfoil and impactor-estimated dry deposition velocities suggests that the airfoils may be used to approximate the dry deposition to the snow surface. Laser particle counter (LPC) results show that particles \u3e 0.5 μm in diameter efficiently serve as nuclei to form fog droplets. Condensation nuclei (CN) measurements indicate that particles \u3c 0.5 μm are not as greatly affected by fog. Furthermore, impactor measurements suggest that from 50% to 80% of the aerosol SO42−serves as nuclei for fog droplets. Snow deposition is the dominant mechanism transporting chemicals to the ice sheet. For NO3−, a species that apparently exists primarily in the gas phase as HNO3(g), 93% of the seasonal inventory (mass of a deposited chemical species per unit area during the season) is due to snow deposition, which suggests efficient scavenging of HNO3(g) by snowflakes. The contribution of snow deposition to the seasonal inventories of aerosols ranges from 45% for MSA to 76% for NH4+. The contribution of fog to the seasonal inventories ranges from 13% for Na+ and Ca2+ to 26% and 32% for SO42− and MSA. The dry deposition contribution to the seasonal inventories of the aerosol species is as low as 5% for NH4+ and as high as 23% for MSA. The seasonal inventory estimations do not take into consideration the spatial variability caused by blowing and drifting snow. Overall, results indicate that snow deposition of chemical species is the dominant flux mechanism during the summer at Summit and that all three deposition processes should be considered when estimating atmospheric concentrations based on ice core chemical signals

Robust artificial neural networks and outlier detection. Technical report

Large outliers break down linear and nonlinear regression models. Robust regression methods allow one to filter out the outliers when building a model. By replacing the traditional least squares criterion with the least trimmed squares criterion, in which half of data is treated as potential outliers, one can fit accurate regression models to strongly contaminated data. High-breakdown methods have become very well established in linear regression, but have started being applied for non-linear regression only recently. In this work, we examine the problem of fitting artificial neural networks to contaminated data using least trimmed squares criterion. We introduce a penalized least trimmed squares criterion which prevents unnecessary removal of valid data. Training of ANNs leads to a challenging non-smooth global optimization problem. We compare the efficiency of several derivative-free optimization methods in solving it, and show that our approach identifies the outliers correctly when ANNs are used for nonlinear regression

Socioeconomic deprivation, urban-rural location and alcohol-related mortality in England and Wales

Background: Many causes of death are directly attributable to the toxic effects of alcohol and deaths from these causes are increasing in the United Kingdom. The aim of this study was to investigate variation in alcohol-related mortality in relation to socioeconomic deprivation, urban-rural location and age within a national context. Methods: An ecological study design was used with data from 8797 standard table wards in England and Wales. The methodology included using the Carstairs Index as a measure of socioeconomic deprivation at the small-area level and the national harmonised classification system for urban and rural areas in England and Wales. Alcohol-related mortality was defined using the National Statistics definition, devised for tracking national trends in alcohol-related deaths. Deaths from liver cirrhosis accounted for 85% of all deaths included in this definition. Deaths from 1999-2003 were examined and 2001 census ward population estimates were used as the denominators. Results: The analysis was based on 28,839 deaths. Alcohol-related mortality rates were higher in men and increased with increasing age, generally reaching peak levels in middle-aged adults. The 45-64 year age group contained a quarter of the total population but accounted for half of all alcohol-related deaths. There was a clear association between alcohol-related mortality and socioeconomic deprivation, with progressively higher rates in more deprived areas. The strength of the association varied with age. Greatest relative inequalities were seen amongst people aged 25-44 years, with relative risks of 4.73 (95% CI 4.00 to 5.59) and 4.24 (95% CI 3.50 to 5.13) for men and women respectively in the most relative to the least deprived quintiles. People living in urban areas experienced higher alcohol-related mortality relative to those living in rural areas, with differences remaining after adjustment for socioeconomic deprivation. Adjusted relative risks for urban relative to rural areas were 1.35 (95% CI 1.20 to 1.52) and 1.13 (95% CI 1.01 to 1.25) for men and women respectively. Conclusions: Large inequalities in alcohol-related mortality exist between sub-groups of the population in England and Wales. These should be considered when designing public health policies to reduce alcohol-related harm

A next-generation inverse-geometry spallation-driven ultracold neutron source

The physics model of a next-generation spallation-driven high-current ultracold neutron (UCN) source capable of delivering an extracted UCN rate of around an-order-of-magnitude higher than the strongest proposed sources, and around three-orders-of-magnitude higher than existing sources, is presented. This UCN-current-optimized source would dramatically improve cutting-edge UCN measurements that are currently statistically limited. A novel "Inverse Geometry" design is used with 40 L of superfluid $^4$He (He-II), which acts as a converter of cold neutrons (CNs) to UCNs, cooled with state-of-the-art sub-cooled cryogenic technology to $\sim$1.6 K. Our design is optimized for a 100 W maximum heat load constraint on the He-II and its vessel. In our geometry, the spallation target is wrapped symmetrically around the UCN converter to permit raster scanning the proton beam over a relatively large volume of tungsten spallation target to reduce the demand on the cooling requirements, which makes it reasonable to assume that water edge-cooling only is sufficient. Our design is refined in several steps to reach $P_{UCN}=2.1\times10^9\,/$s under our other restriction of 1 MW maximum available proton beam power. We then study effects of the He-II scattering kernel as well as reductions in $P_{UCN}$ due to pressurization to reach $P_{UCN}=1.8\times10^9\,/$s. Finally, we provide a design for the UCN extraction system that takes into account the required He-II heat transport properties and implementation of a He-II containment foil that allows UCN transmission. We estimate a total useful UCN current from our source of $R_{use}=5\times10^8\,/$s from a 18 cm diameter guide 5 m from the source. Under a conservative "no return" approximation, this rate can produce an extracted density of $>1\times10^4\,/$cm$^3$ in $<$1000~L external experimental volumes with a $^{58}$Ni (335 neV) cut-off potential.Comment: Submitted to Journal of Applied Physic

Empowering patient education on self-care activity among patients with colorectal cancer - a research protocol for a randomised trial

Background: Chemotherapy-induced side effects may have a negative effect on nutrition intake, thus increasing the risk of malnutrition and consequently, other serious complications for patients with cancer. The prevalence of malnutrition is common among patients with colorectal cancer. Nurse-led empowering education may have a positive effect on self-care activity in this patient group. Therefore, our purpose is to develop an empowering educational nursing intervention and test its effect on self-care activation and knowledge level among patients with colorectal cancer during chemotherapy. Secondary outcomes are quality of life and risk of malnutrition. Methods: An interdisciplinary expert group developed a face-to-face empowering educational intervention using teach-back method. A two-arm, single-centre, superiority trial with stratified randomisation (1:1) and pre-post measures will be used to assess the effect of the intervention compared to standard care. Patients (N = 40 + 40) will be recruited in one university hospital outpatient clinic in Finland. Eligibility criteria are adult patients diagnosed with colorectal cancer starting oral fluoropyrimidine or combination chemotherapy treatment. A registered nurse experienced in oncology will deliver the intervention 2 weeks after the first chemotherapy. Outcomes are measured before intervention (M0) and after a two-month follow-up period (M1). Discussion: This study will assess whether nurse-led empowering education using teach-back method is effective on self-care activity among patients with colorectal cancer. If the intervention has a positive effect, it may be implemented into patient education in a corresponding context.Peer reviewe