Highlights • The application of low intensity TES in humans appears to be safe. • The profile of AEs in terms of frequency, magnitude and type is comparable in different populations. • Structured ...checklists and interviews as recommended procedures are provided in this paper.
EAACI Molecular Allergology User's Guide Matricardi, P. M.; Kleine-Tebbe, J.; Hoffmann, H. J. ...
Pediatric allergy and immunology,
20/May , Letnik:
27, Številka:
S23
Journal Article
Recenzirano
Odprti dostop
The availability of allergen molecules (‘components’) from several protein families has advanced our understanding of immunoglobulin E (IgE)‐mediated responses and enabled ‘component‐resolved ...diagnosis’ (CRD). The European Academy of Allergy and Clinical Immunology (EAACI) Molecular Allergology User's Guide (MAUG) provides comprehensive information on important allergens and describes the diagnostic options using CRD. Part A of the EAACI MAUG introduces allergen molecules, families, composition of extracts, databases, and diagnostic IgE, skin, and basophil tests. Singleplex and multiplex IgE assays with components improve both sensitivity for low‐abundance allergens and analytical specificity; IgE to individual allergens can yield information on clinical risks and distinguish cross‐reactivity from true primary sensitization. Part B discusses the clinical and molecular aspects of IgE‐mediated allergies to foods (including nuts, seeds, legumes, fruits, vegetables, cereal grains, milk, egg, meat, fish, and shellfish), inhalants (pollen, mold spores, mites, and animal dander), and Hymenoptera venom. Diagnostic algorithms and short case histories provide useful information for the clinical workup of allergic individuals targeted for CRD. Part C covers protein families containing ubiquitous, highly cross‐reactive panallergens from plant (lipid transfer proteins, polcalcins, PR‐10, profilins) and animal sources (lipocalins, parvalbumins, serum albumins, tropomyosins) and explains their diagnostic and clinical utility. Part D lists 100 important allergen molecules. In conclusion, IgE‐mediated reactions and allergic diseases, including allergic rhinoconjunctivitis, asthma, food reactions, and insect sting reactions, are discussed from a novel molecular perspective. The EAACI MAUG documents the rapid progression of molecular allergology from basic research to its integration into clinical practice, a quantum leap in the management of allergic patients.
The National Cancer Institute—Molecular Analysis for Therapy Choice (NCI-MATCH) is a national precision medicine study incorporating centralized genomic testing to direct refractory cancer patients ...to molecularly targeted treatment subprotocols. This treatment subprotocol was designed to screen for potential signals of efficacy of ado-trastuzumab emtansine (T-DM1) in HER2-amplified histologies other than breast and gastroesophageal tumors.
Eligible patients had HER2 amplification at a copy number (CN) >7 based on targeted next-generation sequencing (NGS) with a custom Oncomine AmpliSeq™ (ThermoFisher Scientific) panel. Patients with prior trastuzumab, pertuzumab or T-DM1 treatment were excluded. Patients received T-DM1 at 3.6 mg/kg i.v. every 3 weeks until toxicity or disease progression. Tumor assessments occurred every three cycles. The primary end point was centrally assessed objective response rate (ORR). Exploratory end points included correlating response with HER2 CN by NGS. The impact of co-occurring genomic alterations and PTEN loss by immunohistochemistry were also assessed.
Thirty-eight patients were enrolled and 36 included in efficacy analysis. Median prior therapies in the metastatic setting was 3 (range 0–9; unknown in one patient). Median HER2 CN was 17 (range 7–139). Partial responses were observed in two (5.6%) patients: one mucoepidermoid carcinoma of parotid gland and one parotid gland squamous cell cancer. Seventeen patients (47%) had stable disease including 8/10 (80%) with ovarian and uterine carcinomas, with median duration of 4.6 months. The 6-month progression-free survival rate was 23.6% 90% confidence interval 14.2% to 39.2%. Common toxicities included fatigue, anemia, fever and thrombocytopenia with no new safety signals. There was a trend for tumor shrinkage with higher levels of gene CN as determined by the NGS assay.
T-DM1 was well tolerated. While this subprotocol did not meet the primary end point for ORR in this heavily pre-treated diverse patient population, clinical activity was seen in salivary gland tumors warranting further study in this tumor type in dedicated trials.
This systematic review and meta-analysis summarizes the clinical effects of increasing perioperative blood flow using fluids with or without inotropes/vasoactive drugs to explicit defined goals in ...adults. We included randomized controlled trials of adult patients (aged 16 years or older) undergoing surgery. We included 31 studies of 5292 participants. There was no difference in mortality at the longest follow-up: 282/2615 (10.8%) died in the control group and 238/2677 (8.9%) in the treatment group, RR of 0.89 (95% CI: 0.76-1.05; P=0.18). However, the results were sensitive to analytical methods and withdrawal of studies with methodological limitations. The intervention reduced the rate of three morbidities (renal failure, respiratory failure, and wound infections) but not the rates of arrhythmia, myocardial infarction, congestive cardiac failure, venous thrombosis, and other types of infections. The number of patients with complications was also reduced by the intervention. Hospital length of stay was reduced in the treatment group by 1.16 days. There was no difference in critical care length of stay. The primary analysis of this review showed no difference between groups but this result was sensitive to the method of analysis, withdrawal of studies with methodological limitations, and was dominated by a single large study. Patients receiving this intervention stayed in hospital 1 day less with fewer complications. It is unlikely that the intervention causes harm. The balance of current evidence does not support widespread implementation of this approach to reduce mortality but does suggest that complications and duration of hospital stay are reduced.
The NCI-MATCH was designed to characterize the efficacy of targeted therapies in histology-agnostic driver mutation-positive malignancies. Sub-protocols F and G were developed to evaluate the role of ...crizotinib in rare tumors that harbored either ALK or ROS1 rearrangements. Patients with malignancies that progressed following at least one prior systemic therapy were accrued to the NCI-MATCH for molecular profiling, and those with actionable ALK or ROS1 rearrangements were offered participation in sub-protocols F or G, respectively. There were five patients who enrolled on Arm F (ALK) and four patients on Arm G (ROS1). Few grade 3 or 4 toxicities were noted, including liver test abnormalities, and acute kidney injury. For sub-protocol F (ALK), the response rate was 50% (90% CI 9.8-90.2%) with one complete response among the 4 eligible patients. The median PFS was 3.8 months, and median OS was 4.3 months. For sub-protocol G (ROS1) the response rate was 25% (90% CI 1.3-75.1%). The median PFS was 4.3 months, and median OS 6.2 months. Data from 3 commercial vendors showed that the prevalence of ALK and ROS1 rearrangements in histologies other than non-small cell lung cancer and lymphoma was rare (0.1% and 0.4% respectively). We observed responses to crizotinib which met the primary endpoint for ALK fusions, albeit in a small number of patients. Despite the limited accrual, some of the patients with these oncogenic fusions can respond to crizotinib which may have a therapeutic role in this setting.
Abstract Objectives To describe the reliability and validity of the Postoperative Morbidity Survey (POMS). To describe the level and pattern of short-term postoperative morbidity after major elective ...surgery using the POMS. Study Design and Setting This was a prospective cohort study of 439 adults undergoing major elective surgery in a UK teaching hospital. The POMS, an 18-item survey that address nine domains of postoperative morbidity, was recorded on postoperative days 3, 5, 8, and 15. Results Inter-rater reliability was perfect for 11/18 items (Kappa = 1.0), with Kappa = 0.94 for 6/18 items. A priori hypotheses that the POMS would discriminate between patients with known measures of morbidity risk, and predict length of stay were generally supported through observation of data trends, and there was statistically significant evidence of construct validity for all but the wound and neurological domains. POMS-defined morbidity was present in 325 of 433 patients (75.1%) remaining in hospital on postoperative day 3 after surgery, 231 of 407 patients (56.8%) on day 5, 138 of 299 patients (46.2%) on day 8, and 70 of 111 patients (63.1%) on day 15. Gastrointestinal (47.4%), infectious (46.5%), pain-related (40.3%), pulmonary (39.4%), and renal problems (33.3%) were the most common forms of morbidity. Conclusion The POMS is a reliable and valid survey of short-term postoperative morbidity in major elective surgery. Many patients remain in hospital without any morbidity as recorded by the POMS.
Aims/hypothesis
Maternal type 2 diabetes during pregnancy and gestational diabetes are associated with childhood adiposity; however, associations of lower maternal glucose levels during pregnancy ...with childhood adiposity, independent of maternal BMI, remain less clear. The objective was to examine associations of maternal glucose levels during pregnancy with childhood adiposity in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) cohort.
Methods
The HAPO Study was an observational epidemiological international multi-ethnic investigation that established strong associations of glucose levels during pregnancy with multiple adverse perinatal outcomes. The HAPO Follow-up Study (HAPO FUS) included 4832 children from ten HAPO centres whose mothers had a 75 g OGTT at ~28 weeks gestation 10–14 years earlier, with glucose values blinded to participants and clinical caregivers. The primary outcome was child adiposity, including: (1) being overweight/obese according to sex- and age-specific cut-offs based on the International Obesity Task Force (IOTF) criteria; (2) IOTF-defined obesity only; and (3) measurements >85th percentile for sum of skinfolds, waist circumference and per cent body fat. Primary predictors were maternal OGTT and HbA
1c
values during pregnancy.
Results
Fully adjusted models that included maternal BMI at pregnancy OGTT indicated positive associations between maternal glucose predictors and child adiposity outcomes. For one SD difference in pregnancy glucose and HbA
1c
measures, ORs for each child adiposity outcome were in the range of 1.05–1.16 for maternal fasting glucose, 1.11–1.19 for 1 h glucose, 1.09–1.21 for 2 h glucose and 1.12–1.21 for HbA
1c
. Associations were significant, except for associations of maternal fasting glucose with offspring being overweight/obese or having waist circumference >85th percentile. Linearity was confirmed in all adjusted models. Exploratory sex-specific analyses indicated generally consistent associations for boys and girls.
Conclusions/interpretation
Exposure to higher levels of glucose in utero is independently associated with childhood adiposity, including being overweight/obese, obesity, skinfold thickness, per cent body fat and waist circumference. Glucose levels less than those diagnostic of diabetes are associated with greater childhood adiposity; this may have implications for long-term metabolic health.
In this overview (introductory article to a special issue including 14 papers), we consider all main types of natural and artificial inland freshwater habitas (fwh). For each type, we identify the ...main biodiversity patterns and ecological features, human impacts on the system and environmental issues, and discuss ways to use this information to improve stewardship. Examples of selected key biodiversity/ecological features (habitat type): narrow endemics, sensitive (groundwater and GDEs); crenobionts, LIHRes (springs); unidirectional flow, nutrient spiraling (streams); naturally turbid, floodplains, large-bodied species (large rivers); depth-variation in benthic communities (lakes); endemism and diversity (ancient lakes); threatened, sensitive species (oxbow lakes, SWE); diverse, reduced littoral (reservoirs); cold-adapted species (Boreal and Arctic fwh); endemism, depauperate (Antarctic fwh); flood pulse, intermittent wetlands, biggest river basins (tropical fwh); variable hydrologic regime—periods of drying, flash floods (arid-climate fwh). Selected impacts: eutrophication and other pollution, hydrologic modifications, overexploitation, habitat destruction, invasive species, salinization. Climate change is a threat multiplier, and it is important to quantify resistance, resilience, and recovery to assess the strategic role of the different types of freshwater ecosystems and their value for biodiversity conservation. Effective conservation solutions are dependent on an understanding of connectivity between different freshwater ecosystems (including related terrestrial, coastal and marine systems).
Climate warming in the 20th Century has had profound effects on the limnology of High Arctic lakes, including substantial increases in autochthonous primary productivity (APP). Here, we report ...organic carbon and Hg core profiles from two lakes which support the hypothesis that 20th Century increases in sedimentary Hg at these latitudes were largely driven by APP increases, via Hg scavenging by algae and/or suspended detrital algal matter. Hydrocarbons quantitatively released by thermal cracking of algal-derived organic matter (“S2” carbon) were used to reconstruct past APP. Variation of S2 flux accounted for 87−91% of the variance in total Hg flux in the study lakes since 1854. Mercury and S2 carbon were also associated during the pre-Industrial Period, co-varying by as much as 30% during past warm/cool periods. As a test of the hypothesis, predicted values for 20th Century Hg were derived from pre-1900 Hg−S2 relationships. Measured 20th Century Hg was on average only 6−11% higher than that predicted in one lake, and 33% higher in the other. S2-normalization of Hg in the latter lake suggested that 78% of the average increase in 20th Century Hg could be explained by scavenging. These findings suggest that the atmospheric contribution of long-range anthropogenic Hg to High Arctic lakes may have been overestimated by several-fold because of this climate-driven process, and was responsible for no more than 22% of the 20th Century Hg increase in the study lakes.
Summary
Background
Psoriasis is a common long‐term, immune‐mediated skin condition associated with behavioural factors (e.g. smoking, excess alcohol, obesity), which increase the risk of psoriasis ...onset, flares and comorbidities. Motivational interviewing (MI) is an evidence‐based approach to health‐related behaviour change that has been used successfully for patients with long‐term conditions. This study assessed change in clinicians’ MI skills and psoriasis knowledge following Psoriasis and Wellbeing (Pso Well®) training.
Objectives
To investigate whether the Pso Well training intervention improves clinicians’ MI skills and knowledge about psoriasis‐related comorbidities and risk factors; and to explore the acceptability and feasibility of the Pso Well training content, delivery and evaluation.
Methods
Clinicians attended the 1‐day training programme focused on MI skills development in the context of psoriasis. MI skills were assessed pre‐ and post‐training using the Behaviour Change Counselling Index. Knowledge about psoriasis‐related comorbidity and risk factors was assessed with a novel 22‐point measure developed for the study. Interviews with clinicians were analysed qualitatively to identify perceptions about the feasibility and acceptability of the training.
Results
Sixty‐one clinicians completed the training (35 dermatology nurses, 23 dermatologists and three primary‐care clinicians). Clinicians’ MI skills (P < 0·001) and knowledge (P < 0·001) increased significantly post‐training. Clinicians found the training valuable and relevant to psoriasis management.
Conclusions
Attendance at the Pso Well training resulted in improvements in clinicians’ knowledge and skills to manage psoriasis holistically. Clinicians deemed the training itself and the assessment procedures used both feasible and acceptable. Future research should investigate how this training may influence patient outcomes.
What's already known about this topic?
Holistic care of people with psoriasis requires knowledge about and management of comorbidities and associated risk factors.
Motivational interviewing can support people with long‐term conditions to make necessary changes to health‐related behaviours.
What does this study add?
The first evaluation of motivational interviewing skills training for clinicians managing patients with psoriasis.
Psoriasis‐tailored motivational interviewing training assists clinicians to manage psoriasis holistically and support behaviour change.
What are the clinical implications of this work?
The Pso Well® training is acceptable to clinicians and feasible to run within U.K. healthcare settings.
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