Summary
These guidelines for the management of congenital ichthyoses have been developed by a multidisciplinary group of European experts following a systematic review of the current literature, an ...expert conference held in Toulouse in 2016, and a consensus on the discussions. These guidelines summarize evidence and expert‐based recommendations and intend to help clinicians with the management of these rare and often complex diseases. These guidelines comprise two sections. This is part two, covering the management of complications and the particularities of some forms of congenital ichthyosis.
What's already known about this topic?
Various symptomatic treatment options exist for congenital ichthyoses, but there are no European guidelines.
What does this study add?
These European guidelines for the management of congenital ichthyosis may help to improve outcomes and quality of life for patients.
Linked Comment: Akiyama. Br J Dermatol 2019; 180:449–450.
Plain language summary available online
Summary
These guidelines for the management of congenital ichthyoses have been developed by a multidisciplinary group of European experts following a systematic review of the current literature, an ...expert conference held in Toulouse in 2016 and a consensus on the discussions. They summarize evidence and expert‐based recommendations and are intended to help clinicians with the management of these rare and often complex diseases. These guidelines comprise two sections. This is part one, covering topical therapies, systemic therapies, psychosocial management, communicating the diagnosis and genetic counselling.
Linked Comment: Levy. Br J Dermatol 2019; 180:253.
We present comprehensive electron spin resonance (ESR) studies of in-plane oriented single crystals of α−RuCl3, a quasi-two-dimensional material with honeycomb structure, focusing on its high-field ...spin dynamics. The measurements were performed in magnetic fields up to 16 T, applied along the 110 and 100 directions. Several ESR modes were detected. Combining our findings with recent inelastic neutron- and Raman-scattering data, we identified most of the observed excitations. Most importantly, we show that the low-temperature ESR response beyond the boundary of the magnetically ordered region is dominated by single- and two-particle processes with magnons as elementary excitations. The peculiarities of the excitation spectrum in the vicinity of the critical field are discussed.
In α−RuCl3, an external magnetic field applied within the honeycomb plane can induce a transition from a magnetically ordered state to a disordered state that is potentially related to the Kitaev ...quantum spin liquid. In zero field, single crystals with minimal stacking faults display a low-temperature state with in-plane zigzag antiferromagnetic order and a three-layer periodicity in the direction perpendicular to the honeycomb planes. Here, we present angle-dependent magnetization, ac susceptibility, and thermal transport data that demonstrate the presence of an additional intermediate-field ordered state at fields below the transition to the disordered phase. Neutron-diffraction results show that the magnetic structure in this phase is characterized by a six-layer periodicity in the direction perpendicular to the honeycomb planes. Theoretically, the intermediate ordered phase can be accounted for by including spin-anisotropic couplings between the layers in a three-dimensional spin model. Together, this demonstrates the importance of interlayer exchange interactions in α−RuCl3.
Low-risk limits recommended for alcohol consumption vary substantially across different national guidelines. To define thresholds associated with lowest risk for all-cause mortality and ...cardiovascular disease, we studied individual-participant data from 599 912 current drinkers without previous cardiovascular disease.
We did a combined analysis of individual-participant data from three large-scale data sources in 19 high-income countries (the Emerging Risk Factors Collaboration, EPIC-CVD, and the UK Biobank). We characterised dose–response associations and calculated hazard ratios (HRs) per 100 g per week of alcohol (12·5 units per week) across 83 prospective studies, adjusting at least for study or centre, age, sex, smoking, and diabetes. To be eligible for the analysis, participants had to have information recorded about their alcohol consumption amount and status (ie, non-drinker vs current drinker), plus age, sex, history of diabetes and smoking status, at least 1 year of follow-up after baseline, and no baseline history of cardiovascular disease. The main analyses focused on current drinkers, whose baseline alcohol consumption was categorised into eight predefined groups according to the amount in grams consumed per week. We assessed alcohol consumption in relation to all-cause mortality, total cardiovascular disease, and several cardiovascular disease subtypes. We corrected HRs for estimated long-term variability in alcohol consumption using 152 640 serial alcohol assessments obtained some years apart (median interval 5·6 years 5th–95th percentile 1·04–13·5) from 71 011 participants from 37 studies.
In the 599 912 current drinkers included in the analysis, we recorded 40 310 deaths and 39 018 incident cardiovascular disease events during 5·4 million person-years of follow-up. For all-cause mortality, we recorded a positive and curvilinear association with the level of alcohol consumption, with the minimum mortality risk around or below 100 g per week. Alcohol consumption was roughly linearly associated with a higher risk of stroke (HR per 100 g per week higher consumption 1·14, 95% CI, 1·10–1·17), coronary disease excluding myocardial infarction (1·06, 1·00–1·11), heart failure (1·09, 1·03–1·15), fatal hypertensive disease (1·24, 1·15–1·33); and fatal aortic aneurysm (1·15, 1·03–1·28). By contrast, increased alcohol consumption was log-linearly associated with a lower risk of myocardial infarction (HR 0·94, 0·91–0·97). In comparison to those who reported drinking >0–≤100 g per week, those who reported drinking >100–≤200 g per week, >200–≤350 g per week, or >350 g per week had lower life expectancy at age 40 years of approximately 6 months, 1–2 years, or 4–5 years, respectively.
In current drinkers of alcohol in high-income countries, the threshold for lowest risk of all-cause mortality was about 100 g/week. For cardiovascular disease subtypes other than myocardial infarction, there were no clear risk thresholds below which lower alcohol consumption stopped being associated with lower disease risk. These data support limits for alcohol consumption that are lower than those recommended in most current guidelines.
UK Medical Research Council, British Heart Foundation, National Institute for Health Research, European Union Framework 7, and European Research Council.
Auditory and visual target locations are encoded differently in the brain, but must be co-calibrated to maintain cross-sensory concordance. Mechanisms that adjust spatial calibration across ...modalities have been described (for example, prism adaptation in owls), though rudimentarily in humans. We quantified the adaptation of human sound localization in response to spatially compressed vision (0.5x lenses for 2-3 days). This induced a corresponding compression of auditory localization that was most pronounced for azimuth (minimal for elevation) and was restricted to the visual field of the lenses. Sound localization was also affected outside the field of visual-auditory interaction (shifted centrally, not compressed). These results suggest that spatially modified vision induces adaptive changes in adult human sound localization, including novel mechanisms that account for spatial compression. Findings are consistent with a model in which the central processing of sound location is encoded by recruitment rather than by a place code.
Learning-induced synaptic plasticity commonly involves the interaction between cAMP and p42/44MAPK. To investigate the role of Rap1 as a potential signaling molecule coupling cAMP and p42/44MAPK, we ...expressed an interfering Rap1 mutant (iRap1) in the mouse forebrain. This expression selectively decreased basal phosphorylation of a membrane-associated pool of p42/44MAPK, impaired cAMP-dependent LTP in the hippocampal Schaffer collateral pathway induced by either forskolin or theta frequency stimulation, decreased complex spike firing, and reduced the p42/44MAPK-mediated phosphorylation of the A-type potassium channel Kv4.2. These changes correlated with impaired spatial memory and context discrimination. These results indicate that Rap1 couples cAMP signaling to a selective membrane-associated pool of p42/44MAPK to control excitability of pyramidal cells, the early and late phases of LTP, and the storage of spatial memory.
Addressing inaccurate penicillin allergies is encouraged as part of antibiotic stewardship in the inpatient setting. However, implementing interventions targeted at the 10% to 15% of inpatients ...reporting a previous penicillin allergy can pose substantial logistic challenges. We implemented a computerized guideline for patients with reported beta-lactam allergy at 5 hospitals within a single health care system in the Boston area. In this article, we describe our implementation roadmap, including both successes achieved and challenges faced. We explain key implementation steps, including assembling a team, stakeholder engagement, developing or selecting an approach, spreading the change, establishing measures, and measuring impact. The objective was to detail the lessons learned while empowering others to be part of this important, multidisciplinary work to improve the care of patients with reported beta-lactam allergies.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most frequently used medications in the United States. NSAID use can be limited by adverse drug reactions (ADRs), including ...hypersensitivity reactions (HSRs).
We aimed to use electronic health record data to determine the incidence and predictors of HSRs to prescription NSAIDs.
We performed a retrospective cohort study of all adult outpatients in a large health care system prescribed diclofenac, indomethacin, nabumetone, or piroxicam between January 1, 2004, and September 30, 2012. The primary outcome was an ADR or HSR attributed to the prescribed NSAID within 1 year of prescription, determined from a longitudinal allergy database. We used natural language processing to classify known ADRs as either HSRs or side effects. Multivariable logistic regression models were used to identify independent risk factors for NSAID HSRs.
Of 62,719 patients prescribed NSAIDs, 1,035 (1.7%) had an ADR, of which 189 (18.3%) were HSRs. Multivariable regression analysis identified that patients with prior drug HSR history (odds ratio OR 1.8 95% CI 1.3, 2.5), female sex (OR 1.8 95% CI 1.3, 2.4), autoimmune disease (OR 1.7 95% CI 1.1, 2.7), and those prescribed the maximum standing NSAID dose (OR 1.5 95% CI 1.1, 2.0) had increased odds of NSAID HSR.
NSAID therapeutic use can be limited by ADRs; about 1 in 5 NSAID ADRs is an HSR. Both patient and drug factors contribute to HSR risk and are important to guide patient counseling.
The translational linear vestibuloocular reflex compensates most accurately for high frequencies of head translation, with response magnitude decreasing with declining stimulus frequency. However, ...studies of the perception of translation typically report robust responses even at low frequencies or during prolonged motion. This inconsistency may reflect the incorporation of nondirectional sensory information associated with the vibration and noise that typically accompany translation, into motion perception. We investigated the perception of passive translation in humans while dissociating nondirectional cues from actual head motion. In a cue-dissociation experiment, interaural (IA) motion was generated using either a linear sled, the mechanics of which generated noise and vibration cues that were correlated with the motion profile, or a multiaxis technique that dissociated these cues from actual motion. In a trajectory-shift experiment, IA motion was interrupted by a sudden change in direction (+/-30 degrees diagonal) that produced a change in linear acceleration while maintaining sled speed and therefore mechanical (nondirectional) cues. During multi-axis cue-dissociation trials, subjects reported erroneous translation perceptions that strongly reflected the pattern of nondirectional cues, as opposed to nearly veridical percepts when motion and nondirectional cues coincided. During trajectory-shift trials, subjects' percepts were initially accurate, but erroneous following the direction change. Results suggest that nondirectional cues strongly influence the perception of linear motion, while the utility of cues directly related to translational acceleration is limited. One key implication is that "path integration" likely involves complex mechanisms that depend on nondirectional and contextual self-motion cues in support of limited and transient otolith-dependent acceleration input.
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