A critical examination of human data for the biological activity of quercetin and its phase-2 conjugates.

This critical review examines evidence for beneficial effects of quercetin phase-2 conjugates from clinical intervention studies, volunteer feeding trials, and in vitro work. Plasma concentrations of quercetin-3-O-glucuronide (Q3G) and 3'-methylquercetin-3-O-glucuronide (3'MQ3G) after supplementation may produce beneficial effects in macrophages and endothelial cells, respectively, especially if endogenous deglucuronidation occurs, and lower blood uric acid concentration via quercetin-3'-O-sulfate (Q3'S). Unsupplemented diets produce much lower concentrations (<50 nmol/l) rarely investigated in vitro. At 10 nmol/l, Q3'S and Q3G stimulate or suppress, respectively, angiogenesis in endothelial cells. Statistically significant effects have been reported at 100 nmol/l in breast cancer cells (Q3G), primary neuron cultures (Q3G), lymphocytes (Q3G and3'MQ3G) and HUVECs (QG/QS mixture), but it is unclear whether these translate to a health benefit in vivo. More sensitive and more precise methods to measure clinically significant endpoints are required before a conclusion can be drawn regarding effects at normal dietary concentrations. Future requirements include better understanding of inter-individual and temporal variation in plasma quercetin phase-2 conjugates, their mechanisms of action including deglucuronidation and desulfation both in vitro and in vivo, tissue accumulation and washout, as well as potential for synergy or antagonism with other quercetin metabolites and metabolites of other dietary phytochemicals.

Excretion by subjects on a low (poly)phenol diet of phenolic gut microbiota catabolites sequestered in tissues or associated with catecholamines and surplus amino acids.

Phenolic catabolites excreted by fasting subjects with a functioning colon and ileostomists on a low (poly)phenol diet have been investigated. Urine was collected over a 12 h fasting period after adherence to a low (poly)phenol diet for 36 h. UHPLC-HR-MS quantified 77 phenolics. Some were present in the urine of both groups in similar trace amounts and others were excreted in higher amounts by participants with a colon indicating the involvement of the microbiota. Most were present in sub- or low-µmol amounts, but hippuric acid dominated accounting on average for 60% of the total for both volunteer categories indicating significant production from sources other than non-nutrient dietary (poly)phenols. The potential origins of the phenolics associated with the low (poly)phenol diet, include endogenous catecholamines, surplus tyrosine and phenylalanine, and washout of catabolites derived from pre-study intakes of non-nutrient dietary (poly)phenols.

Metabolism of phenolics in coffee and plant-based foods by canonical pathways: an assessment of the role of fatty acid ß-oxidation to generate biologically-active and -inactive intermediates.

ω-Phenyl-alkenoic acids are abundant in coffee, fruits, and vegetables. Along with ω-phenyl-alkanoic acids, they are produced from numerous dietary (poly)phenols and aromatic amino acids in vivo. This review addresses how phenyl-ring substitution and flux modulates their gut microbiota and endogenous ß-oxidation. 3',5'-Dihydroxy-derivatives (from alkyl-resorcinols, flavanols, proanthocyanidins), and 4'-hydroxy-phenolic acids (from tyrosine, p-coumaric acid, naringenin) are ß-oxidation substrates yielding benzoic acids. In contrast, 3',4',5'-tri-substituted-derivatives, 3',4'-dihydroxy-derivatives and 3'-methoxy-4'-hydroxy-derivatives (from coffee, tea, cereals, many fruits and vegetables) are poor ß-oxidation substrates with metabolism diverted via gut microbiota dehydroxylation, phenylvalerolactone formation and phase-2 conjugation, possibly a strategy to conserve limited pools of coenzyme A. 4'-Methoxy-derivatives (citrus fruits) or 3',4'-dimethoxy-derivatives (coffee) are susceptible to hepatic "reverse" hydrogenation suggesting incompatibility with enoyl-CoA-hydratase. Gut microbiota-produced 3'-hydroxy-4'-methoxy-derivatives (citrus fruits) and 3'-hydroxy-derivatives (numerous (poly)phenols) are excreted as the phenyl-hydracrylic acid ß-oxidation intermediate suggesting incompatibility with hydroxy-acyl-CoA dehydrogenase, albeit with considerable inter-individual variation. Further investigation is required to explain inter-individual variation, factors determining the amino acid to which C6-C3 and C6-C1 metabolites are conjugated, the precise role(s) of l-carnitine, whether glycine might be limiting, and whether phenolic acid-modulation of ß-oxidation explains how phenolic acids affect key metabolic conditions, such as fatty liver, carbohydrate metabolism and insulin resistance.

Dexmedetomidine infusion overdose during anesthesia: A case report.

A 12-kg infant was given intravenous dexmedetomidine 0.2 µg kg-1  min-1 as an adjunct for general anesthesia. The 60-fold increase in dexmedetomidine infusion rate caused a biphasic response with initial hypertension followed by bradycardia and hypotension requiring inotropic support. No postoperative or long-term sequelae were noted. Dexmedetomidine infusion is usually delivered as µg kg-1  h-1 .

Bioavailability and metabolism of chlorogenic acids (acyl-quinic acids) in humans.

Acyl-quinic acids (chlorogenic acids) are produced by many plants, including fruits, vegetables, and herbal remedies, with coffee and maté particularly rich dietary sources. Epidemiological and intervention studies suggest that they can reduce the risk of developing type 2 diabetes and cardiovascular disease. This review addresses their metabolic handling after oral consumption to provide a mechanistic basis to explain their possible effects on health. Intact acyl-quinic acids are absorbed only to a small extent in the small intestine, but the cinnamic acids are efficiently absorbed after hydrolysis by either digestive or microbial enzymes in the colon. Metabolism results in phenolic conjugates in the blood and urine, but varying dependent on the acyl-quinic acid, and subject to significant interperson variability. The balance between hydrogenation and complete ß-oxidation of the cinnamic acids, both by liver and gut microbiota, determines the profile of metabolites. Pharmacokinetic data suggest that some metabolites are bound to human serum albumin and/or sequestered in tissues, and some exhibit biological activity in vitro, consistent with proposed protective action in vivo. Significant gaps in the literature include lack of plasma and urinary data for free-living individuals, and pharmacokinetic data for groups who consume coffee or maté at regular short intervals. Data are required for cis isomers. There is a critical need for precise urinary biomarkers of consumption of acyl-quinic acids, accounting for variability in individual metabolism and in beverage composition, thus facilitating better translation of urinary metabolite measurements into accurate coffee consumption data to improve the outcomes of future epidemiological and intervention studies.

Phenyl-γ-valerolactones and phenylvaleric acids, the main colonic metabolites of flavan-3-ols: synthesis, analysis, bioavailability, and bioactivity.

Covering: 1958 to June 2018 Phenyl-γ-valerolactones (PVLs) and their related phenylvaleric acids (PVAs) are the main metabolites of flavan-3-ols, the major class of flavonoids in the human diet. Despite their presumed importance, these gut microbiota-derived compounds have, to date, in terms of biological activity, been considered subordinate to their parent dietary compounds, the flavan-3-ol monomers and proanthocyanidins. In this review, the role and prospects of PVLs and PVAs as key metabolites in the understanding of the health features of flavan-3-ols have been critically assessed. Among the topics covered, are proposals for a standardised nomenclature for PVLs and PVAs. The formation, bioavailability and pharmacokinetics of PVLs and PVAs from different types of flavan-3-ols are discussed, taking into account in vitro and animal studies, as well as inter-individual differences and the existence of putative flavan-3-ol metabotypes. Synthetic strategies used for the preparation of PVLs are considered and the methodologies for their identification and quantification assessed. Metabolomic approaches unravelling the role of PVLs and PVAs as biomarkers of intake are also described. Finally, the biological activity of these microbial catabolites in different experimental models is summarised. Knowledge gaps and future research are considered in this key area of dietary (poly)phenol research.

Postprandial glycaemic and lipaemic responses to chronic coffee consumption may be modulated by CYP1A2 polymorphisms.

There is much epidemiological evidence suggesting a reduced risk of development of type 2 diabetes (T2D) in habitual coffee drinkers, however to date there have been few longer-term interventions, directly examining the effects of coffee intake on glucose and lipid metabolism. Previous studies may be confounded by inter-individual variation in caffeine metabolism. Specifically, the rs762551 SNP in the CYP1A2 gene has been demonstrated to influence caffeine metabolism, with carriers of the C allele considered to be of a 'slow' metaboliser phenotype. This study investigated the effects of regular coffee intake on markers of glucose and lipid metabolism in coffee-naïve individuals, with novel analysis by rs762551 genotype. Participants were randomised to either a coffee group (n 19) who consumed four cups/d instant coffee for 12 weeks or a control group (n 8) who remained coffee/caffeine free. Venous blood samples were taken pre- and post-intervention. Primary analysis revealed no significant differences between groups. Analysis of the coffee group by genotype revealed several differences. Before coffee intake, the AC genotype ('slow' caffeine metabolisers, n 9) displayed higher baseline glucose and NEFA than the AA genotype ('fast' caffeine metabolisers, n 10, P<0·05). Post-intervention, reduced postprandial glycaemia and reduced NEFA suppression were observed in the AC genotype, with the opposite result observed in the AA genotype (P<0·05). These observed differences between genotypes warrant further investigation and indicate there may be no one-size-fits-all recommendation with regard to coffee drinking and T2D risk.

Chlorogenic acids and the acyl-quinic acids: discovery, biosynthesis, bioavailability and bioactivity.

Covering: 2000 up to late 2017This review is focussed upon the acyl-quinic acids, the most studied group within the ca. 400 chlorogenic acids so far reported. The acyl-quinic acids, the first of which was characterised in 1846, are a diverse group of plant-derived compounds produced principally through esterification of an hydroxycinnamic acid and 1l-(-)-quinic acid. Topics addressed in this review include the confusing nomenclature, quantification and characterisation by NMR and MS, biosynthesis and role in planta, and the occurrence of acyl-quinic acids in coffee, their transformation during roasting and delivery to the beverage. Coffee is the major human dietary source world-wide of acyl-quinic acids and consideration is given to their absorption and metabolism in the upper gastrointestinal tract, and the colon where the microbiota play a key role in the formation of catabolites. Evidence on the potential of the in vivo metabolites and catabolites of acyl-quinic acids to promote the consumer's health is evaluated.

Implementation of NAP4 emergency airway management recommendations in a quaternary-level pediatric hospital.

Emergency airway management, particularly outside of the operating room, is associated with a high incidence of life-threatening adverse events. Based on the recommendations of the 4th National Audit Project, we aimed to develop hospital-wide systems changes to improve the safety of emergency airway management. We describe a framework for governance in the form of a hospital airway special interest group. We describe the development and implementation of the following systems changes: 1. A local intubation algorithm modified from the Difficult Airway Society's plan A-B-C-D approach, including clear pathways for airway escalation, and emphasizing the concepts of resuscitation prior to intubation, planning for failure, and avoidance of fixation error. 2. Simplified and standardized airway equipment located in identical airway carts in all critical care areas. 3. A preintubation checklist and equipment template to standardize preparation for airway management. 4. Availability of continuous waveform endtidal capnography in all critical care areas for confirmation of correct endotracheal tube placement. 5. Multidisciplinary team training to address the technical and nontechnical aspects of nonoperating room intubation. In addition, we describe methodology for ongoing monitoring of performance through a quality assurance framework. In conclusion, changes in the process of emergency airway management at a hospital level are feasible through collaboration. Their impact on patient-based outcomes requires further study.

Clonidine as a First-Line Sedative Agent After Neonatal Cardiac Surgery: Retrospective Cohort Study.

OBJECTIVES: To determine the cardiovascular tolerance of clonidine used as a first-line sedative after cardiac surgery in small infants. DESIGN: Retrospective chart review. SETTING: A tertiary and quaternary referral cardiac PICU. PATIENTS: All infants younger than 2 months who received a clonidine infusion for sedation after cardiac surgery from October 2011 to July 2013. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Heart rate, blood pressure, central venous and left atrial pressure, vasoactive inotropic score, volume of fluid bolus, and lactate and central mixed venous saturation were assessed. Preinfusion values were compared with postinfusion values. Of 224 potentially eligible patients, only 23 infants met inclusion criteria, as most patients only received high doses of morphine and some received midazolam instead of clonidine. Clonidine administration was started at a median of 12 hours after surgery (Q1-Q3, 5-23), and infusion rate was 0.5-2 µg/kg/hr for a median duration of 30 hours (Q1-Q3, 12-54). Heart rate decreased (maximal mean decrease: 12% [149 beats/min (SD, 17) to 131 beats/min (SD, 17)]; p < 0.0001). Apart from a transient and limited drop in diastolic blood pressure of 13% (maximal mean decrease: from 42.8 mm Hg [SD, 5.9] to 37.1 mm Hg [SD, 4.0]; p = 0.018), all other cardiovascular variables were stable or improved. A contemporaneous cohort of patients who received midazolam, did so sooner after surgery, stayed longer in the PICU and showed less favorable hemodynamics. CONCLUSIONS: IV clonidine as sedative added to morphine in selected patients seems hemodynamically safe. The observed decrease in heart rate and diastolic blood pressure seems of minimal clinical importance as all other hemodynamic variables remained stable or improved. The safety of clonidine given early after cardiac surgery as alternative to midazolam merits further study.

A Comparative Analysis of Preemptive Versus Targeted Sedation on Cardiovascular Stability After High-Risk Cardiac Surgery in Infants.

OBJECTIVE: To compare the effect of two sedation practices on cardiovascular stability during the early postoperative period in young infants following cardiac surgery: the routine early use of midazolam infusion (preemptive sedation) and the discretionary use of sedatives tailored to the patient's clinical condition (targeted sedation). DESIGN: Retrospective cohort study with matched controls. SETTING: A 15-bedded pediatric cardiac ICU. PATIENTS: Sedation strategies were compared by matching patients before and after the introduction of a targeted sedation guideline, replacing the existing practice of preemptive sedation. Inclusion criteria were age less than 6 months and cardiopulmonary bypass time greater than 150 minutes. Matching criteria were surgical procedure, age, and duration of cardiopulmonary bypass and cross-clamp. The main outcome was cardiovascular instability, defined by the presence of one of the following criteria in the first 12 hours after PICU admission: 1) simultaneous administration of greater than or equal to two inotropic or vasopressor drugs; 2) administration of greater than 60 mL/kg fluid boluses. Secondary outcomes were: 1) markers of cardiac output adequacy (heart rate, blood pressure, vasoactive inotropic score, urine output, volume of fluid boluses, central venous oxygen saturation, lactate); 2) occurrence of adverse events (cardiac arrest, extracorporeal membrane oxygenation, death); 3) sedatives administered and depth of sedation. INTERVENTIONS: Introduction of a guideline of targeted sedation. MEASUREMENTS AND MAIN RESULTS: Thirty-three patients with preemptive sedation were matched to 33 patients with targeted sedation. Targeted sedation resulted in less frequent oversedation, without compromising cardiovascular stability, as indicated by similar occurrence of cardiovascular instability (68.8% with preemptive sedation vs 62.5% with targeted sedation; p = 0.53) and adverse events, and similar markers of cardiac output adequacy. Although all preemptively sedated patients received an infusion of midazolam in the first 12 hours after surgery, only 19.4% of patients in the targeted sedation group received a sedative infusion (p < 0.001). CONCLUSIONS: Our data suggest that after high-risk cardiac surgery in young infants, routine sedation with midazolam may not prevent low cardiac output syndrome. When accompanied by a careful assessment of level of sedation, routine sedation of infants after high-risk cardiac surgery can be avoided without compromising hemodynamic stability or patient safety. The potential benefit of this approach is reduced exposure to sedative.

Woodland recovery following drought-induced tree mortality across an environmental stress gradient.

Recent droughts and increasing temperatures have resulted in extensive tree mortality across the globe. Understanding the environmental controls on tree regeneration following these drought events will allow for better predictions of how these ecosystems may shift under a warmer, drier climate. Within the widely distributed piñon-juniper woodlands of the southwestern USA, a multiyear drought in 2002-2004 resulted in extensive adult piñon mortality and shifted adult woodland composition to a juniper-dominated, more savannah-type ecosystem. Here, we used pre- (1998-2001) and 10-year post- (2014) drought stand structure data of individually mapped trees at 42 sites to assess the effects of this drought on tree regeneration across a gradient of environmental stress. We found declines in piñon juvenile densities since the multiyear drought due to limited new recruitment and high (>50%) juvenile mortality. This is in contrast to juniper juvenile densities, which increased over this time period. Across the landscape, piñon recruitment was positively associated with live adult piñon densities and soil available water capacity, likely due to their respective effects on seed and water availability. Juvenile piñon survival was strongly facilitated by certain types of nurse trees and shrubs. These nurse plants also moderated the effects of environmental stress on piñon survival: Survival of interspace piñon juveniles was positively associated with soil available water capacity, whereas survival of nursed piñon juveniles was negatively associated with perennial grass cover. Thus, nurse plants had a greater facilitative effect on survival at sites with higher soil available water capacity and perennial grass cover. Notably, mean annual climatic water deficit and elevation were not associated with piñon recruitment or survival across the landscape. Our findings reveal a clear shift in successional trajectories toward a more juniper-dominated woodland and highlight the importance of incorporating biotic interactions and soil properties into species distribution modeling approaches.

A single serving of caffeinated coffee impairs postprandial glucose metabolism in overweight men.

UNLABELLED: Previous studies regarding the acute effects of coffee on glycaemic control have used a single large dose of coffee, typically containing the caffeine equivalent of 2-4 servings of coffee. This study investigates whether the acute effects of coffee are dose-dependent, starting with a single serving. A total of ten healthy overweight males participated in a two-part randomised double-blind cross-over study. In the first part, they ingested 2, 4 or 8 g instant decaffeinated coffee (DC) dissolved in 400 ml water with caffeine added in proportion to the DC (total 100, 200 or 400 mg caffeine) or control (400 ml water) all with 50 g glucose. In the second part, they ingested the same amounts of DC (2, 4, 8 g) or control, but with a standard 100 mg caffeine added to each. Capillary blood samples were taken every 15 min for 2 h after each drink and glucose and insulin levels were measured. Repeated measures ANOVA on glucose results found an effect when caffeine was varied in line with DC (P=0·008). Post hoc analysis revealed that both 2 and 4 g DC with varied caffeine content increased the glycaemic response v. CONTROL: There was no effect of escalating doses of DC when caffeine remained constant at 100 mg. These results demonstrate that one standard serving of coffee (2 g) is sufficient to affect glucose metabolism. Furthermore, the amount of caffeine found in one serving (100 mg) is sufficient to mask any potential beneficial effects of increasing other components. No dose-dependent effect was found.

The effect of visitation restrictions on ED error.

EDs restricted visitors during the COVID-19 pandemic on the assumption that the risks of disease spread outweighed the psychological benefits of liberal visitation. But data suggest that beyond providing emotional support, family and caregivers can clarify history, improve patient monitoring, and advocate for patients-actions that can improve quality of care. Our objective was to assess whether removing visitors from the bedside contributed to errors in emergency care. We reviewed a database of medical errors covering visits from 11/15/17 to 7/30/22 at an urban, tertiary-care, academic ED for five types of error amenable to visitor intervention: inadequate history gathering, inadequate monitoring, falls, giving a medication to which a patient is allergic, and inappropriate medication dosing. These records were reviewed by two investigators to determine the likelihood visitor presence could have prevented the error. For those errors judged susceptible to visitor intercession, the number in each category was compared for the period before and after strict restrictions took effect. Our review found 27/781 (3.5%) errors in the pre-pandemic period and 27/568 (4.8%) errors in the pandemic period fell into one of these five categories (p = 0.29). Visitors prevented harm from reaching the patient in three of 27 pre-pandemic errors (11.1%), compared to 0 out of 27 peri-pandemic errors (p = 0.23). On review by two attendings, 17/24 (70.8%) errors that reached the patient in the pre-pandemic period were judged amenable to visitor intervention, compared to 25/27 (92.6%) in the pandemic period (p = 0.09). There were no statistically significant differences in the categories of error between the two groups; monitoring errors came the closest: 1/17 (5.9%) pre-COVID errors amenable to visitor intervention in these categories were monitoring related, whereas 7/25 (28.0%) post-COVID errors were (p = 0.16). While this study did not demonstrate a statistically significant difference in error between lenient and restrictive visitation eras, we did find multiple cases in the pre-COVID era in which family presence prevented error, and qualitative review of post-COVID errors suggested many could have been prevented by family presence. Larger trials are needed to determine how frequent and consequential such errors are and how to balance the public health imperative of curbing disease spread with the harm caused by restricting visitation.

A Systematic Review and Comprehensive Evaluation of Human Intervention Studies to Unravel the Bioavailability of Hydroxycinnamic Acids.

Significance: Hydroxycinnamic acids (HCAs) are the main phenolic acids in the western diet. Harmonizing the available information on the absorption, distribution, metabolism, and excretion (ADME) of HCAs is fundamental to unraveling the compounds responsible for their health effects. This work systematically assessed pharmacokinetics, including urinary recovery, and bioavailability of HCAs and their metabolites, based on literature reports. Recent Advances: Forty-seven intervention studies with coffee, berries, herbs, cereals, tomato, orange, grape products, and pure compounds, as well as other sources yielding HCA metabolites, were included. Up to 105 HCA metabolites were collected, mainly acyl-quinic and C6-C3 cinnamic acids. C6-C3 cinnamic acids, such as caffeic and ferulic acid, reached the highest blood concentrations (maximum plasma concentration [Cmax] = 423 nM), with time to reach Cmax (Tmax) values ranging from 2.7 to 4.2 h. These compounds were excreted in urine in higher amounts than their phenylpropanoic acid derivatives (4% and 1% of intake, respectively), but both in a lower percentage than hydroxybenzene catabolites (11%). Data accounted for 16 and 18 main urinary and blood HCA metabolites, which were moderately bioavailable in humans (collectively 25%). Critical Issues: A relevant variability emerged. It was not possible to unequivocally assess the bioavailability of HCAs from each ingested source, and data from some plant based-foods were absent or inconsistent. Future Directions: A comprehensive study investigating the ADME of HCAs derived from their most important dietary sources is urgently required. Eight key metabolites were identified and reached interesting plasma Cmax concentrations and urinary recoveries, opening up new perspectives to evaluate their bioactivity at physiological concentrations. Antioxid. Redox Signal. 40, 510-541.

Exploring and disentangling the production of potentially bioactive phenolic catabolites from dietary (poly)phenols, phenylalanine, tyrosine and catecholamines.

Following ingestion of fruits, vegetables and derived products, (poly)phenols that are not absorbed in the upper gastrointestinal tract pass to the colon, where they undergo microbiota-mediated ring fission resulting in the production of a diversity of low molecular weight phenolic catabolites, which appear in the circulatory system and are excreted in urine along with their phase II metabolites. There is increasing interest in these catabolites because of their potential bioactivity and their use as biomarkers of (poly)phenol intake. Investigating the fate of dietary (poly)phenolics in the colon has become confounded as a result of the recent realisation that many of the phenolics appearing in biofluids can also be derived from the aromatic amino acids, l-phenylalanine and l-tyrosine, and to a lesser extent catecholamines, in reactions that can be catalysed by both colonic microbiota and endogenous mammalian enzymes. The available evidence, albeit currently rather limited, indicates that substantial amounts of phenolic catabolites originate from phenylalanine and tyrosine, while somewhat smaller quantities are produced from dietary (poly)phenols. This review outlines information on this topic and assesses procedures that can be used to help distinguish between phenolics originating from dietary (poly)phenols, the two aromatic amino acids and catecholamines.

Precipitation thresholds and drought-induced tree die-off: insights from patterns of Pinus edulis mortality along an environmental stress gradient.

Recent regional tree die-off events appear to have been triggered by a combination of drought and heat - referred to as 'global-change-type drought'. To complement experiments focused on resolving mechanisms of drought-induced tree mortality, an evaluation of how patterns of tree die-off relate to highly spatially variable precipitation is needed. Here, we explore precipitation relationships with a die-off event of pinyon pine (Pinus edulis Engelm.) in southwestern North America during the 2002-2003 global-change-type drought. Pinyon die-off and its relationship with precipitation was quantified spatially along a precipitation gradient in north-central New Mexico with standard field plot measurements of die-off combined with canopy cover derived from normalized burn ratio (NBR) from Landsat imagery. Pinyon die-off patterns revealed threshold responses to precipitation (cumulative 2002-2003) and vapor pressure deficit (VPD), with little to no mortality (< 10%) above 600 mm and below warm season VPD of c. 1.7 kPa. [Correction added after online publication 17 June 2013; in the preceding sentence, the word 'below' has been inserted.] Our results refine how precipitation patterns within a region influence pinyon die-off, revealing a precipitation and VPD threshold for tree mortality and its uncertainty band where other factors probably come into play - a response type that influences stand demography and landscape heterogeneity and is of general interest, yet has not been documented.

How does the introduction of a pain and sedation management guideline in the paediatric intensive care impact on clinical practice? A comparison of audits pre and post guideline introduction.

UNLABELLED: Despite the use of guidelines to inform practice for pain and sedation management there are few evaluations of the effect of their introduction on clinical practice. Previous evaluations of the protocols and guidelines used to manage pain and sedation in the paediatric intensive care unit (PICU) report increases in pain and sedation medication administration post guideline introduction. In most reported cases the guideline was accompanied by a treatment algorithm. To our knowledge there is no published data on the effect of introducing a guideline without a treatment algorithm on pain and analgesia administration. PURPOSE: To evaluate the impact the introduction of a pain and sedation guideline will have on clinical practice. METHODS: A 19 bed PICU was audited for one month prior to the introduction of a guideline and one month post. FINDINGS: The proportion of patients receiving oral Clonidine increased (p=0.001) and the administration of Ketamine, particularly via bolus (p=0.003), reduced after the introduction of the guideline. The use of a validated pain tool to assess pain increased by 25% and communication of management plans increased by 25%. The documentation of the use of boluses increased by 36%. CONCLUSION: The introduction of a clinical practice guideline for pain and sedation management in PICU contributes to changes in medication administration, use of validated pain assessments, improved documentation of boluses and communication of management plans.

Intervening with practitioners to improve the quality of prevention: one-year findings from a randomized trial of assets-getting to outcomes.

There continues to be a gap in prevention outcomes achieved in research trials versus those achieved in "real-world" practice. This article reports interim findings from a randomized controlled trial evaluating Assets-Getting To Outcomes (AGTO), a two-year intervention designed to build prevention practitioners' capacity to implement positive youth development-oriented practices in 12 community coalitions in Maine. A survey of coalition members was used to assess change on individual practitioners' prevention capacity between baseline and one year later. Structured interviews with 32 program directors (16 in the intervention group and 16 in the control group) were used to assess changes in programs' prevention practices during the same time period. Change in prevention capacity over time did not differ significantly between the intervention and control groups. However, in secondary analyses of only those assigned to the AGTO intervention, users showed greater improvement in their self-efficacy to conduct Assets-based programming and increases in the frequency with which they engaged in AGTO behaviors, whereas among non-users, self-efficacy to conduct Assets-based programming declined. Interview ratings showed improvement in several key areas of performance among intervention programs. Improvement was associated with the number of technical assistance hours received. These results suggest that, after one year, AGTO is beginning to improve the capacity of community practitioners who make use of it.