A guideline that both evaluates current practice and provides recommendations to address sedation, pain, and delirium management with regard for neuromuscular blockade and withdrawal is not currently ...available.
To develop comprehensive clinical practice guidelines for critically ill infants and children, with specific attention to seven domains of care including pain, sedation/agitation, iatrogenic withdrawal, neuromuscular blockade, delirium, PICU environment, and early mobility.
The Society of Critical Care Medicine Pediatric Pain, Agitation, Neuromuscular Blockade, and Delirium in critically ill pediatric patients with consideration of the PICU Environment and Early Mobility Guideline Taskforce was comprised of 29 national experts who collaborated from 2009 to 2021 via teleconference and/or e-mail at least monthly for planning, literature review, and guideline development, revision, and approval. The full taskforce gathered annually in-person during the Society of Critical Care Medicine Congress for progress reports and further strategizing with the final face-to-face meeting occurring in February 2020. Throughout this process, the Society of Critical Care Medicine standard operating procedures Manual for Guidelines development was adhered to.
Taskforce content experts separated into subgroups addressing pain/analgesia, sedation, tolerance/iatrogenic withdrawal, neuromuscular blockade, delirium, PICU environment (family presence and sleep hygiene), and early mobility. Subgroups created descriptive and actionable Population, Intervention, Comparison, and Outcome questions. An experienced medical information specialist developed search strategies to identify relevant literature between January 1990 and January 2020. Subgroups reviewed literature, determined quality of evidence, and formulated recommendations classified as "strong" with "we recommend" or "conditional" with "we suggest." Good practice statements were used when indirect evidence supported benefit with no or minimal risk. Evidence gaps were noted. Initial recommendations were reviewed by each subgroup and revised as deemed necessary prior to being disseminated for voting by the full taskforce. Individuals who had an overt or potential conflict of interest abstained from relevant votes. Expert opinion alone was not used in substitution for a lack of evidence.
The Pediatric Pain, Agitation, Neuromuscular Blockade, and Delirium in critically ill pediatric patients with consideration of the PICU Environment and Early Mobility taskforce issued 44 recommendations (14 strong and 30 conditional) and five good practice statements.
The current guidelines represent a comprehensive list of practical clinical recommendations for the assessment, prevention, and management of key aspects for the comprehensive critical care of infants and children. Main areas of focus included 1) need for the routine monitoring of pain, agitation, withdrawal, and delirium using validated tools, 2) enhanced use of protocolized sedation and analgesia, and 3) recognition of the importance of nonpharmacologic interventions for enhancing patient comfort and comprehensive care provision.
Summary
Background
Many reflux patients remain symptomatic on a standard dose of proton pump inhibitor (PPI). Alginates decrease the number of reflux events by forming a raft on top of the stomach ...content and thus offer a supplemental mechanism of action to acid suppression.
Aim
To assess the efficacy of an alginate (Gaviscon Advance, Reckitt Benckiser, Slough, UK) on reflux symptoms in patients with persistent symptoms despite once daily PPI.
Methods
This was a multicentre, randomised, placebo‐controlled, 7‐day double‐blind trial preceded by a 7‐day run‐in period. Reflux symptoms were assessed using the Heartburn Reflux Dyspepsia Questionnaire (HRDQ). Based on symptom score during run‐in, eligible patients were randomised to Gaviscon Advance 10 mL four times a day or placebo in addition to a once daily PPI. The primary endpoint was change in HRDQ score post‐treatment compared to baseline.
Results
One hundred and thirty‐six patients were randomised. Change in HRDQ reflux score was significantly greater for Gaviscon Advance (mean: −5.0, s.d.: 4.7) than for placebo (mean: −3.5, s.d.: 5.5) with an LS mean difference of 1.6 95% CI −3.1 to −0.1, P = 0.03. A decrease in the mean (s.d.) number of nights with symptoms was observed from 3.6 (2.8) to 3.0 (3.0) in the placebo group and from 3.9 (2.8) to 2.2 (2.7) for the Gaviscon Advance group. This reduction was significantly greater in the Gaviscon Advance group than in the placebo group LS mean difference = −0.9, 95% CI (−1.6 to −0.2), P < 0.01.
Conclusion
In patients with residual reflux symptoms despite PPI treatment, adding an alginate offers additional decrease in the burden of reflux symptoms (EudraCT/IND Number: 2011‐005486‐21).
We report on simultaneous radio and X-ray observations of the repeating fast radio burst source FRB 180916.J0158+65 using the Canadian Hydrogen Intensity Mapping Experiment (CHIME), Effelsberg, and ...Deep Space Network (DSS-14 and DSS-63) radio telescopes and the Chandra X-ray Observatory. During 33 ks of Chandra observations, we detect no radio bursts in overlapping Effelsberg or Deep Space Network observations and a single burst during CHIME/FRB source transits. We detect no X-ray events in excess of the background during the Chandra observations. These non-detections imply a 5 limit of <5 × 10−10 erg cm−2 for the 0.5-10 keV fluence of prompt emission at the time of the radio burst and 1.3 × 10−9 erg cm−2 at any time during the Chandra observations. Given the host-galaxy redshift of FRB 180916.J0158+65 (z ∼ 0.034), these correspond to energy limits of <1.6 × 1045 erg and <4 × 1045 erg, respectively. We also place a 5 limit of <8 × 10−15 erg s−1 cm−2 on the 0.5-10 keV absorbed flux of a persistent source at the location of FRB 180916.J0158+65. This corresponds to a luminosity limit of <2 × 1040 erg s−1. Using an archival set of radio bursts from FRB 180916.J0158+65, we search for prompt gamma-ray emission in Fermi/GBM data but find no significant gamma-ray bursts, thereby placing a limit of 9 × 10−9 erg cm−2 on the 10-100 keV fluence. We also search Fermi/LAT data for periodic modulation of the gamma-ray brightness at the 16.35 days period of radio burst activity and detect no significant modulation. We compare these deep limits to the predictions of various fast radio burst models, but conclude that similar X-ray constraints on a closer fast radio burst source would be needed to strongly constrain theory.
Abstract Background Pheochromocytoma is associated with catecholamine-induced cardiac toxicity, but the extent and nature of cardiac involvement in clinical cohorts is not well-characterized. ...Objectives This study characterized the cardiac phenotype in patients with pheochromocytoma using cardiac magnetic resonance (CMR). Methods A total of 125 subjects were studied, including patients with newly diagnosed pheochromocytoma (n = 29), patients with previously surgically cured pheochromocytoma (n = 31), healthy control subjects (n = 51), and hypertensive control subjects (HTN) (n = 14), using CMR (1.5-T) cine, strain imaging by myocardial tagging, late gadolinium enhancement, and native T1 mapping (Shortened Modified Look-Locker Inversion recovery ShMOLLI). Results Patients who were newly diagnosed with pheochromocytoma, compared with healthy and HTN control subjects, had impaired left ventricular (LV) ejection fraction (<56% in 38% of patients), peak systolic circumferential strain (p < 0.05), and diastolic strain rate (p < 0.05). They had higher myocardial T1 (974 ± 25 ms, as compared with 954 ± 16 ms in healthy and 958 ± 23 ms in HTN subjects; p < 0.05), areas of myocarditis (median 22% LV with T1 >990 ms, as compared with 1% in healthy and 2% in HTN subjects; p < 0.05), and focal fibrosis (59% had nonischemic late gadolinium enhancement, as compared with 14% in HTN subjects). Post-operatively, impaired LV ejection fraction typically normalized, but systolic and diastolic strain impairment persisted. Focal fibrosis (median 5% LV) and T1 abnormalities (median 12% LV) remained, the latter of which may suggest some diffuse fibrosis. Previously cured patients demonstrated abnormal diastolic strain rate (p < 0.001), myocardial T1 (median 12% LV), and small areas of focal fibrosis (median 1% LV). LV mass index was increased in HTN compared with healthy control subjects (p < 0.05), but not in the 2 pheochromocytoma groups. Conclusions This first systematic CMR study characterizing the cardiac phenotype in pheochromocytoma showed that cardiac involvement was frequent and, for some variables, persisted after curative surgery. These effects surpass those of hypertensive heart disease alone, supporting a direct role of catecholamine toxicity that may produce subtle but long-lasting myocardial alterations.
Feeding arms carrying coelomic extensions of the theca are thought to be unique to crinoids among stemmed echinoderms. However, a new two-armed echinoderm from the earliest Middle Cambrian of Spain ...displays a highly unexpected morphology. X-ray microtomographic analysis of its arms shows they are polyplated in their proximal part with a dorsal series of uniserial elements enclosing a large coelomic lumen. Distally, the arm transforms into the more standard biserial structure of a blastozoan brachiole. Phylogenetic analysis demonstrates that this taxon lies basal to rhombiferans as sister-group to pleurocystitid and glyptocystitid blastozoans, drawing those clades deep into the Cambrian. We demonstrate that Cambrian echinoderms show surprising variability in the way their appendages are constructed, and that the appendages of at least some blastozoans arose as direct outgrowths of the body in much the same way as the arms of crinoids.
Stem-cell-based therapies provide a biological basis for the regeneration of mineralised tissues. Stem cells isolated from adipose tissue (ADSCs), bone marrow (BMSCs) and dental pulp (DPSCs) have the ...capacity to form mineralised tissue. However, studies comparing the capacity of ADSCs with BMSCs and DPSCs for mineralised tissue engineering are lacking, and their ability to regenerate dental tissues has not been fully explored. Characterisation of the cells using fluorescence-activated cell sorting and semi-quantitative reverse transcription PCR for MSC markers indicated that they were immunophenotypically similar. Alizarin red (AR) staining and micro-computed tomography (µCT) analyses demonstrated that the osteogenic potential of DPSCs was significantly greater than that of BMSCs and ADSCs. Scanning electron microscopy and AR staining showed that the pattern of mineralisation in DPSC cultures differed from ADSCs and BMSCs, with DPSC cultures lacking defined mineralised nodules and instead forming a diffuse layer of low-density mineral. Dentine matrix components (DMCs) were used to promote dentinogenic differentiation. Their addition to cultures resulted in increased amounts of mineral deposited in all three cultures and significantly increased the density of mineral deposited in BMSC cultures, as determined by µCT analysis. Addition of DMCs also increased the relative gene expression levels of the dentinogenic markers dentine sialophosphoprotein and dentine matrix protein 1 in ADSC and BMSC cultures. In conclusion, DPSCs show the greatest potential to produce a comparatively high volume of mineralised matrix; however, both dentinogenesis and mineral volume was enhanced in ADSC and BMSC cultures by DMCs, suggesting that these cells show promise for regenerative dental therapies.
We have previously reported successful induction of renal allograft tolerance via a mixed chimerism approach in nonhuman primates. In those studies, we found that costimulatory blockade with ...anti‐CD154 mAb was an effective adjunctive therapy for induction of renal allograft tolerance. However, since anti‐CD154 mAb is not clinically available, we have evaluated CTLA4Ig as an alternative agent for effecting costimulation blockade in this treatment protocol. Two CTLA4Igs, abatacept and belatacept, were substituted for anti‐CD154 mAb in the conditioning regimen (low dose total body irradiation, thymic irradiation, anti‐thymocyte globulin and a 1‐month posttransplant course of cyclosporine CyA). Three recipients treated with the abatacept regimen failed to develop comparable lymphoid chimerism to that achieved with anti‐CD154 mAb treatment and these recipients rejected their kidney allografts early. With the belatacept regimen, four of five recipients developed chimerism and three of these achieved long‐term renal allograft survival (>861, >796 and >378 days) without maintenance immunosuppression. Neither chimerism nor long‐term allograft survival were achieved in two recipients treated with the belatacept regimen but with a lower, subtherapeutic dose of CyA. This study indicates that CD28/B7 blockade with belatacept can provide a clinically applicable alternative to anti‐CD154 mAb for promoting chimerism and renal allograft tolerance.
This study shows that belatacept promotes induction of mixed chimerism and renal allograft tolerance in nonhuman primates.
Waterborne releases to the Techa River from the Mayak plutonium facility in Russia during 1949-1956 resulted in significant doses to persons living downstream. The dosimetry system Techa River ...Dosimetry System-2016D has been developed, which provides individual doses of external and internal exposure for the members of the Techa River cohort and other persons who were exposed to releases of radioactive material to the Southern Urals. The results of computation of individual doses absorbed in red bone marrow and extraskeletal tissues for the Techa River cohort members (29,647 persons) are presented, which are based on residence histories on the contaminated Techa River and the East Urals Radioactive Trace, which was formed in 1957 as a result of the Kyshtym Accident. Available Sr body-burden measurements and available information on individual household locations have been used for refinement of individual dose estimates. Techa River Dosimetry System-2016D-based dose estimates will be used for verification of risk of low-dose-rate effects of ionizing radiation in the Techa River cohort.
Superheavy elements are formed in fusion reactions which are hindered by fast nonequilibrium processes. To quantify these, mass-angle distributions and cross sections have been measured, at beam ...energies from below-barrier to 25% above, for the reactions of ^{48}Ca, ^{50}Ti, and ^{54}Cr with ^{208}Pb. Moving from ^{48}Ca to ^{54}Cr leads to a drastic fall in the symmetric fission yield, which is reflected in the measured mass-angle distribution by the presence of competing fast nonequilibrium deep inelastic and quasifission processes. These are responsible for reduction of the compound nucleus formation probablity P_{CN} (as measured by the symmetric-peaked fission cross section), by a factor of 2.5 for ^{50}Ti and 15 for ^{54}Cr in comparison to ^{48}Ca. The energy dependence of P_{CN} indicates that cold fusion reactions (involving ^{208}Pb) are not driven by a diffusion process.
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