Purpose
To determine whether early goal-directed therapy (EGDT) reduces mortality compared with other resuscitation strategies for patients presenting to the emergency department (ED) with septic ...shock.
Methods
Using a search strategy of PubMed, EmBase and CENTRAL, we selected all relevant randomised clinical trials published from January 2000 to January 2015. We translated non-English papers and contacted authors as necessary. Our primary analysis generated a pooled odds ratio (OR) from a fixed-effect model. Sensitivity analyses explored the effect of including non-ED studies, adjusting for study quality, and conducting a random-effects model. Secondary outcomes included organ support and hospital and ICU length of stay.
Results
From 2395 initially eligible abstracts, five randomised clinical trials (
n
= 4735 patients) met all criteria and generally scored high for quality except for lack of blinding. There was no effect on the primary mortality outcome (EGDT: 23.2 % 495/2134 versus control: 22.4 % 582/2601; pooled OR 1.01 95 % CI 0.88–1.16,
P
= 0.9, with heterogeneity
I
2
= 57 %;
P
= 0.055). The pooled estimate of 90-day mortality from the three recent multicentre studies (
n
= 4063) also showed no difference pooled OR 0.99 (95 % CI 0.86–1.15),
P
= 0.93 with no heterogeneity (
I
2
= 0.0 %;
P
= 0.97). EGDT increased vasopressor use (OR 1.25 95 % CI 1.10–1.41;
P
< 0.001) and ICU admission OR 2.19 (95 % CI 1.82–2.65);
P
< 0.001. Including six non-ED randomised trials increased heterogeneity (
I
2
= 71 %;
P
< 0.001) but did not change overall results pooled OR 0.94 (95 % CI 0.82 to 1.07);
P
= 0.33.
Conclusion
EGDT is not superior to usual care for ED patients with septic shock but is associated with increased utilisation of ICU resources.
Summary Background Unexplained differences between classes of antihypertensive drugs in their effectiveness in preventing stroke might be due to class effects on intraindividual variability in blood ...pressure. We did a systematic review to assess any such effects in randomised controlled trials. Methods Baseline and follow-up data for mean (SD) of systolic blood pressure (SBP) were extracted from trial reports. Effect of treatment on interindividual variance (SD2 ) in blood pressure (a surrogate for within-individual variability), expressed as the ratio of the variances (VR), was related to effects on clinical outcomes. Pooled estimates were derived by use of random-effects meta-analysis. Findings Mean (SD) SBP at follow-up was reported in 389 (28%) of 1372 eligible trials. There was substantial heterogeneity between trials in VR (p<1×10−40 ), 68% of which was attributable to allocated drug class. Compared with other drugs, interindividual variation in SBP was reduced by calcium-channel blockers (VR 0·81, 95% CI 0·76–0·86, p<0·0001) and non-loop diuretic drugs (0·87, 0·79–0·96, p=0·007), and increased by angiotensin-converting enzyme (ACE) inhibitors (1·08, 1·02–1·15, p=0·008), angiotensin-receptor blockers (1·16, 1·07–1·25, p=0·0002), and β blockers (1·17, 1·07–1·28, p=0·0007). Compared with placebo only, interindividual variation in SBP was reduced the most by calcium-channel blockers (0·76, 0·67–0·85, p<0·0001). Effects were consistent in parallel group and crossover design trials, and in analyses of dose-response. Across all trials, effects of treatment on VR of SBP ( r2 =0·372, p=0·0006) and on mean SBP ( r2 =0·328, p=0·0015) accounted for effects on stroke risk (eg, odds ratio 0·79, 0·71–0·87, p<0·0001, for VR≤0·80), and both remained significant in a combined model. Interpretation Drug-class effects on interindividual variation in blood pressure can account for differences in effects of antihypertensive drugs on risk of stroke independently of effects on mean SBP. Funding None.
Climate change is driving an expansion of marine oxygen-deficient zones, which may alter the global cycles of carbon, sulfur, nitrogen, and trace metals. Currently, however, we lack a full ...mechanistic understanding of how oxygen deficiency affects organic carbon cycling and burial. Here, we show that cryptic microbial sulfate reduction occurs in sinking particles from the eastern tropical North Pacific oxygen-deficient zone and that some microbially produced sulfide reacts rapidly to form organic sulfur that is resistant to acid hydrolysis. Particle-hosted sulfurization could enhance carbon preservation in sediments underlying oxygen-deficient water columns and serve as a stabilizing feedback between expanding anoxic zones and atmospheric carbon dioxide. A similar mechanism may help explain more-extreme instances of organic carbon preservation associated with marine anoxia in Earth history.
Microplastics are increasingly being recognised as a potential threat to New Zealand's coastal waters, however there is limited data on abundance of microplastics in marine organisms for New Zealand. ...Microplastic ingestion by the iconic green-lipped mussel Perna canaliculus was assessed. Microplastics were found in Perna canaliculus from 6 out of 9 locations sampled at abundances ranging from 0 to 1.5 particles per mussel and tissue microplastic concentrations ranged from 0 to 0.48 particles g tissue -1 (wet wt). The microplastics ranged in size from 50 to 700 μm with a median diameter of 100 μm. Polyethylene was the most frequently detected polymer with fragments the most common morphotype. These results indicate that microplastics are widespread in New Zealand's coastal waters and further assessment of microplastic contamination of New Zealand coastal environments and biota is warranted.
•Microplastic ingestion by the iconic green-lipped mussel Perna canaliculus from around New Zealand was assessed.•Microplastics were found in Perna canaliculus at abundances ranging from 0 to 1.5 particles per mussel.•Polyethylene was the most frequently detected polymer with fragments the most common morphotype.
Intensity-modulated radiation therapy (IMRT) can sculpt the high-dose volume around the site of disease with hitherto unachievable precision. Conformal avoidance of normal tissues goes hand in hand ...with this. Inhomogeneous dose painting is possible. The technique has become a clinical reality and is likely to be the dominant approach this decade for improving the clinical practice of photon therapy. This Series will explore all aspects of the "IMRT chain". Only 15 years ago just a handful of physicists were working on this subject. IMRT has developed so rapidly that its recent past is also its ancient history. This article will review the history of IMRT with just a glance at precursors. The physical basis of IMRT is then described including an attempt to introduce the concepts of convex and concave dose distributions, ill-conditioning, inverse-problem degeneracy, cost functions and complex solutions all with a minimum of technical jargon or mathematics. The many techniques for inverse planning are described and the review concludes with a look forward to the future of image-guided IMRT (IG-IMRT).
Whether hydrocortisone reduces mortality among patients with septic shock is unclear. Patients with septic shock undergoing mechanical ventilation were assigned to receive an infusion of ...hydrocortisone or placebo. Hydrocortisone did not result in lower 90-day mortality.
Plant plasma-membrane (PM) proteins are involved in several vital processes, such as detection of pathogens, solute transport, and cellular signaling. For these proteins to function effectively there ...needs to be structure within the PM allowing, for example, proteins in the same signaling cascade to be spatially organized. Here we demonstrate that several proteins with divergent functions are located in clusters of differing size in the membrane using subdiffraction-limited Airyscan confocal microscopy. Single particle tracking reveals that these proteins move at different rates within the membrane. Actin and microtubule cytoskeletons appear to significantly regulate the mobility of one of these proteins (the pathogen receptor FLS2) and we further demonstrate that the cell wall is critical for the regulation of cluster size by quantifying single particle dynamics of proteins with key roles in morphogenesis (PIN3) and pathogen perception (FLS2). We propose a model in which the cell wall and cytoskeleton are pivotal for regulation of protein cluster size and dynamics, thereby contributing to the formation and functionality of membrane nanodomains.
Deep brain stimulation (DBS) is increasingly applied for the treatment of brain disorders, but its mechanism of action remains unknown. Here we evaluate the effect of basal ganglia DBS on cortical ...function using invasive cortical recordings in Parkinson's disease (PD) patients undergoing DBS implantation surgery. In the primary motor cortex of PD patients, neuronal population spiking is excessively synchronized to the phase of network oscillations. This manifests in brain surface recordings as exaggerated coupling between the phase of the beta rhythm and the amplitude of broadband activity. We show that acute therapeutic DBS reversibly reduces phase-amplitude interactions over a similar time course as that of the reduction in parkinsonian motor signs. We propose that DBS of the basal ganglia improves cortical function by alleviating excessive beta phase locking of motor cortex neurons.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SBMB, UILJ, UKNU, UL, UM, UPUK
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