Summary
Patients with atopic dermatitis (AD) have an increased risk of bacterial skin infections, which cause significant morbidity and, if untreated, may become systemic. Staphylococcus aureus ...colonizes the skin of most patients with AD and is the most common organism to cause infections. Overt bacterial infection is easily recognized by the appearance of weeping lesions, honey‐coloured crusts and pustules. However, the wide variability in clinical presentation of bacterial infection in AD and the inherent features of AD – cutaneous erythema and warmth, oozing associated with oedema, and regional lymphadenopathy – overlap with those of infection, making clinical diagnosis challenging. Furthermore, some features may be masked because of anatomical site‐ and skin‐type‐specific features, and the high frequency of S. aureus colonization in AD makes positive skin swab culture of suspected infection unreliable as a diagnostic tool. The host mechanisms and microbial virulence factors that underlie S. aureus colonization and infection in AD are incompletely understood. The aim of this article is to present the latest evidence from animal and human studies, including recent microbiome research, to define the clinical features of bacterial infections in AD, and to summarize our current understanding of the host and bacterial factors that influence microbial colonization and virulence.
The relationship between evidence-based medicine (EBM) and shared decision making (SDM) is discussed. The areas in which a disconnect tends to be seen between EBM and SDM are highlighted.
Background
Survivors of critical illness often experience a multitude of problems that begin in the intensive care unit (ICU) or present and continue after discharge. These can include muscle ...weakness, cognitive impairments, psychological difficulties, reduced physical function such as in activities of daily living (ADLs), and decreased quality of life. Early interventions such as mobilizations or active exercise, or both, may diminish the impact of the sequelae of critical illness.
Objectives
To assess the effects of early intervention (mobilization or active exercise), commenced in the ICU, provided to critically ill adults either during or after the mechanical ventilation period, compared with delayed exercise or usual care, on improving physical function or performance, muscle strength and health‐related quality of life.
Search methods
We searched CENTRAL, MEDLINE, Embase and CINAHL. We searched conference proceedings, reference lists of retrieved articles, databases of trial registries and contacted experts in the field on 31 August 2017. We did not impose restrictions on language or location of publications.
Selection criteria
We included all randomized controlled trials (RCTs) or quasi‐RCTs that compared early intervention (mobilization or active exercise, or both), delivered in the ICU, with delayed exercise or usual care delivered to critically ill adults either during or after the mechanical ventilation period in the ICU.
Data collection and analysis
Two researchers independently screened titles and s and assessed full‐text articles against the inclusion criteria of this review. We resolved any disagreement through discussion with a third review author as required. We presented data descriptively using mean differences or medians, risk ratios and 95% confidence intervals. A meta‐analysis was not possible due to the heterogeneity of the included studies. We assessed the quality of evidence with GRADE.
Main results
We included four RCTs (a total of 690 participants), in this review. Participants were adults who were mechanically ventilated in a general, medical or surgical ICU, with mean or median age in the studies ranging from 56 to 62 years. Admitting diagnoses in three of the four studies were indicative of critical illness, while participants in the fourth study had undergone cardiac surgery. Three studies included range‐of‐motion exercises, bed mobility activities, transfers and ambulation. The fourth study involved only upper limb exercises. Included studies were at high risk of performance bias, as they were not blinded to participants and personnel, and two of four did not blind outcome assessors. Three of four studies reported only on those participants who completed the study, with high rates of dropout. The description of intervention type, dose, intensity and frequency in the standard care control group was poor in two of four studies.
Three studies (a total of 454 participants) reported at least one measure of physical function. One study (104 participants) reported low‐quality evidence of beneficial effects in the intervention group on return to independent functional status at hospital discharge (59% versus 35%, risk ratio (RR) 1.71, 95% confidence interval (CI) 1.11 to 2.64); the absolute effect is that 246 more people (95% CI 38 to 567) per 1000 would attain independent functional status when provided with early mobilization. The effects on physical functioning are uncertain for a range measures: Barthel Index scores (early mobilization: median 75 control: versus 55, low quality evidence), number of ADLs achieved at ICU (median of 3 versus 0, low quality evidence) or at hospital discharge (median of 6 versus 4, low quality evidence). The effects of early mobilization on physical function measured at ICU discharge are uncertain, as measured by the Acute Care Index of Function (ACIF) (early mobilization mean: 61.1 versus control: 55, mean difference (MD) 6.10, 95% CI ‐11.85 to 24.05, low quality evidence) and the Physical Function ICU Test (PFIT) score (5.6 versus 5.4, MD 0.20, 95% CI ‐0.98 to 1.38, low quality evidence). There is low quality evidence that early mobilization may have little or no effect on physical function measured by the Short Physical Performance Battery score at ICU discharge from one study of 184 participants (mean 1.6 in the intervention group versus 1.9 in usual care, MD ‐0.30, 95% CI ‐1.10 to 0.50), or at hospital discharge (MD 0, 95% CI ‐1.00 to 0.90). The fourth study, which examined postoperative cardiac surgery patients did not measure physical function as an outcome.
Adverse effects were reported across the four studies but we could not combine the data. Our certainty in the risk of adverse events with either mobilization strategy is low due to the low rate of events. One study reported that in the intervention group one out of 49 participants (2%) experienced oxygen desaturation less than 80% and one of 49 (2%) had accidental dislodgement of the radial catheter. This study also found cessation of therapy due to participant instability occurred in 19 of 498 (4%) of the intervention sessions. In another study five of 101 (5%) participants in the intervention group and five of 109 (4.6%) participants in the control group had postoperative pulmonary complications deemed to be unrelated to intervention. A third study found one of 150 participants in the intervention group had an episode of asymptomatic bradycardia, but completed the exercise session. The fourth study reported no adverse events.
Authors' conclusions
There is insufficient evidence on the effect of early mobilization of critically ill people in the ICU on physical function or performance, adverse events, muscle strength and health‐related quality of life at this time. The four studies awaiting classification, and the three ongoing studies may alter the conclusions of the review once these results are available. We assessed that there is currently low‐quality evidence for the effect of early mobilization of critically ill adults in the ICU due to small sample sizes, lack of blinding of participants and personnel, variation in the interventions and outcomes used to measure their effect and inadequate descriptions of the interventions delivered as usual care in the studies included in this Cochrane Review.
Ultrashort terahertz pulses derived from femtosecond table-top sources have become a valuable tool for time-resolved spectroscopy during the last two decades. Until recently, the pulse energies and ...field strengths of these pulses have been generally too low to allow for the use as pump pulses or the study of nonlinear effects in the terahertz range. In this review article we will describe methods of generation of intense single cycle terahertz pulses with emphasis on optical rectification using the tilted-pulse-front pumping technique. We will also discuss some applications of these intense pulses in the emerging field of nonlinear terahertz spectroscopy.
The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, published in 2009, was designed to help systematic reviewers transparently report why the review was done, ...what the authors did, and what they found. Over the past decade, advances in systematic review methodology and terminology have necessitated an update to the guideline. The PRISMA 2020 statement replaces the 2009 statement and includes new reporting guidance that reflects advances in methods to identify, select, appraise, and synthesise studies. The structure and presentation of the items have been modified to facilitate implementation. In this article, we present the PRISMA 2020 27-item checklist, an expanded checklist that details reporting recommendations for each item, the PRISMA 2020 abstract checklist, and the revised flow diagrams for original and updated reviews.
The methods and results of systematic reviews should be reported in sufficient detail to allow users to assess the trustworthiness and applicability of the review findings. The Preferred Reporting ...Items for Systematic reviews and Meta-Analyses (PRISMA) statement was developed to facilitate transparent and complete reporting of systematic reviews and has been updated (to PRISMA 2020) to reflect recent advances in systematic review methodology and terminology. Here, we present the explanation and elaboration paper for PRISMA 2020, where we explain why reporting of each item is recommended, present bullet points that detail the reporting recommendations, and present examples from published reviews. We hope that changes to the content and structure of PRISMA 2020 will facilitate uptake of the guideline and lead to more transparent, complete, and accurate reporting of systematic reviews.
The hypothalamic neuropeptide oxytocin (OT), which controls childbirth and lactation, receives increasing attention for its effects on social behaviors, but how it reaches central brain regions is ...still unclear. Here we gained by recombinant viruses selective genetic access to hypothalamic OT neurons to study their connectivity and control their activity by optogenetic means. We found axons of hypothalamic OT neurons in the majority of forebrain regions, including the central amygdala (CeA), a structure critically involved in OT-mediated fear suppression. In vitro, exposure to blue light of channelrhodopsin-2-expressing OT axons activated a local GABAergic circuit that inhibited neurons in the output region of the CeA. Remarkably, in vivo, local blue-light-induced endogenous OT release robustly decreased freezing responses in fear-conditioned rats. Our results thus show widespread central projections of hypothalamic OT neurons and demonstrate that OT release from local axonal endings can specifically control region-associated behaviors.
► We constructed a virus to express any protein, e.g., ChR2, only in oxytocin neurons ► Fluorescent oxytocin neurons project simultaneously to the forebrain and pituitary ► Blue-light exposure of oxytocin axons in vitro affects amygdala neuronal activity ► Blue-light amygdala exposure in vivo evokes oxytocin-mediated decreases in fear
To address the role of the hypothalamic oxytocin (OT)-expressing neurons, Knobloch et al. expressed channelrhodopsin-2 in these neurons. OT neurons project to the central amygdala, as well as other forebrain regions, and activation of these neurons induced oxytocin release and freezing responses in fear-conditioned rats.
To ensure a systematic review is valuable to users, authors should prepare a transparent, complete, and accurate account of why the review was done, what they did (such as how studies were identified ...and selected) and what they found (such as characteristics of contributing studies and results of meta-analyses). ...technological advances have enabled the use of natural language processing and machine learning to identify relevant evidence 22,23,24, methods have been proposed to synthesise and present findings when meta-analysis is not possible or appropriate 25,26,27, and new methods have been developed to assess the risk of bias in results of included studies 28, 29. ...the publishing landscape has transformed, with multiple avenues now available for registering and disseminating systematic review protocols 33, 34, disseminating reports of systematic reviews, and sharing data and materials, such as preprint servers and publicly accessible repositories. ...extensions to the PRISMA 2009 statement have been developed to guide reporting of network meta-analyses 49, meta-analyses of individual participant data 50, systematic reviews of harms 51, systematic reviews of diagnostic test accuracy studies 52, and scoping reviews 53; for these types of reviews we recommend authors report their review in accordance with the recommendations in PRISMA 2020 along with the guidance specific to the extension.
We present the first demonstration of THz driven bunch compression and timing stabilization of a relativistic electron beam. Quasi-single-cycle strong field THz radiation is used in a shorted ...parallel-plate structure to compress a few-fC beam with 2.5 MeV kinetic energy by a factor of 2.7, producing a 39 fs rms bunch length and a reduction in timing jitter by more than a factor of 2 to 31 fs rms. This THz driven technique offers a significant improvement to beam performance for applications like ultrafast electron diffraction, providing a critical step towards unprecedented timing resolution in ultrafast sciences, and other accelerator applications using femtosecond-scale electron beams.
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