Human inflammatory and resolving lipid mediator responses to resistance exercise and ibuprofen treatment

Classical proinflammatory eicosanoids, and more recently discovered lipid mediators with anti-inflammatory and proresolving bioactivity, exert a complex role in the initiation, control, and resolution of inflammation. Using a targeted lipidomics approach, we investigated circulating lipid mediator responses to resistance exercise and treatment with the NSAID ibuprofen. Human subjects undertook a single bout of unaccustomed resistance exercise (80% of one repetition maximum) following oral ingestion of ibuprofen (400 mg) or placebo control. Venous blood was collected during early recovery (0–3 h and 24 h postexercise), and serum lipid mediator composition was analyzed by LC-MS-based targeted lipidomics. Postexercise recovery was characterized by elevated levels of cyclooxygenase (COX)-1 and 2-derived prostanoids (TXB2, PGE2, PGD2, PGF2α, and PGI2), lipooxygenase (5-LOX, 12-LOX, and 15-LOX)-derived hydroxyeicosatetraenoic acids (HETEs), and leukotrienes (e.g., LTB4), and epoxygenase (CYP)-derived epoxy/dihydroxy eicosatrienoic acids (EpETrEs/DiHETrEs). Additionally, we detected elevated levels of bioactive lipid mediators with anti-inflammatory and proresolving properties, including arachidonic acid-derived lipoxins (LXA4 and LXB4), and the EPA (E-series) and DHA (D-series)-derived resolvins (RvD1 and RvE1), and protectins (PD1 isomer 10S, 17S-diHDoHE). Ibuprofen treatment blocked exercise-induced increases in COX-1 and COX-2-derived prostanoids but also resulted in off-target reductions in leukotriene biosynthesis, and a diminished proresolving lipid mediator response. CYP pathway product metabolism was also altered by ibuprofen treatment, as indicated by elevated postexercise serum 5,6-DiHETrE and 8,9-DiHETrE only in those receiving ibuprofen. These findings characterize the blood inflammatory lipid mediator response to unaccustomed resistance exercise in humans and show that acute proinflammatory signals are mechanistically linked to the induction of a biological active inflammatory resolution program, regulated by proresolving lipid mediators during postexercise recovery.

Implementation of pressure ulcer prevention best practice recommendations in acute care: an observational study

Pressure ulcers are a common but preventable problem in hospitals. Implementation of best practice guideline recommendations can prevent ulcers from occurring. This 9-year cohort study reports prevalence data from point prevalence surveys during the observation period, and three practice metrics to assess implementation of best practice guideline recommendations: (i) nurse compliance with use of a validated pressure ulcer risk assessment and intervention checklist; (ii) accuracy of risk assessment scoring in usual-care nurses and experienced injury prevention nurses; and (iii) use of pressure ulcer prevention strategies. The prevalence of hospital-acquired pressure ulcers decreased following implementation of an evidence-based prevention programme from 12·6% (2 years preprogramme implementation) to 2·6% (6 years postprogramme implementation) (P < 0·001). Audits between 2003 and 2011 of 4368 patient medical records identified compliance with pressure ulcer prevention documentation according to best practice guidelines was high (>84%). A sample of 270 patients formed the sample for the study of risk assessment scoring accuracy and use of prevention strategies. It was found usual-care nurses under-estimated patients' risk of pressure ulcer development and under-utilised prevention strategies compared with experienced injury prevention nurses. Despite a significant reduction in prevalence of hospital-acquired pressure ulcers and high documentation compliance, use of prevention strategies could further be improved to achieve better patient outcomes. Barriers to the use of prevention strategies by nurses in the acute hospital setting require further examination. This study provides important insights into the knowledge translation of pressure ulcer prevention best practice guideline recommendations at The Northern Hospital.

Effects of acute alkalosis and acidosis on performance

Ingestion of agents that modify blood buffering action may affect high-intensity performance. Here we present a meta-analysis of the effects of acute ingestion of three such agents - sodium bicarbonate, sodium citrate and ammonium chloride - on performance and related physiological variables (blood bicarbonate, pH and lactate). A literature search yielded 59 useable studies with 188 observations of performance effects. To perform the mixed- model meta-analysis, all performance effects were converted into a percentage change in mean power and were weighted using standard errors derived from exact p-values, confidence limits (CLs) or estimated errors of measurement. The fixed effects in the meta-analytic model included the number of performance-test bouts (linear), test duration (log linear), blinding (yes/no), competitive status (athiete/nonathlete) and sex (male/female). Dose expressed as buffering mmoL/kg/body mass (BM) was included as a strictly proportional linear effect interacted with all effects except blinding. Probabilistic inferences were derived with reference to thresholds for small and moderate effects on performance of 0.5% and 1.5%, respectively. Publication bias was reduced by excluding study estimates with a standard error >2.7%. The remaining 38 studies and 137 estimates for sodium bicarbonate produced a possibly mod- erate performance enhancement of 1.7% (90% CL ± 2.0%) with a typical dose of 3.5mmoL/kg/BM (-0.3g/kgIBM) in a single 1-minute sprint, following blinded consumption by male athletes. In the 16 studies and 45 estimates for sodium citrate, a typical dose of l.SmmoL/kgIBM (-0.5gIkgJBM) had an unclear effect on performance of 0.0% (±1.3%), while the five studies and six estimates for ammonium chloride produced a possibly moderate impairment of 1.6% (±1.9%) with a typical dose of 5.5mmoL/kgIBM (-0.3glkg/BM). Study and subject characteristics had the following modifying small effects on the enhancement of performance with sodium bicarbonate: an increase of 0.5% (±0.6%) with a 1 mmoL/kg/BM increase in dose; an increase of 0.6% (±0.4%) with five extra sprint bouts; a reduction of 0.6% (±0.9%) for each 10-fold increase in test duration (e.g. 1-10 minutes); reductions of 1.1% (± 1 .1%) with nonathletes and 0.7% (±1.4%) with females. Unexplained variation in effects between research settings was typically ± 1.2%. The only noteworthy effects involving physiological variables were a small correlation between performance and pre-exercise increase in blood bicarbonate with sodium bi- carbonate ingestion, and a very large correlation between the increase in blood bicarbonate and time between sodium citrate ingestion and exercise. The approximate equal and opposite effects of sodium bicarbonate and am- monium chloride are consistent with direct performance effects of pH, but sodium citrate appears to have some additional metabolic inhibitory effect. Important future research includes studies of sodium citrate ingestion several hours before exercise and quantification of gastrointestinal symptoms with sodium bicarbonate and citrate. Although individual responses may vary, we recommend ingestion of 0.3-0.5 glkg/BM sodium bicarbonate to improve mean power by 1.7% (±2.0%) in high-intensity races of short duration. ABSTRACT FROM AUTHOR

Two-year results of a randomized placebo-controlled trial of vertebroplasty for acute osteoporotic vertebral fractures

We previously reported the results of a randomized controlled trial that found no benefit of vertebroplasty over a sham procedure for acute osteoporotic vertebral fractures up to 6 months. We report here the 12-month and 24-month clinical outcomes of this trial. Eligible participants (n = 78) were randomly assigned to receive either vertebroplasty (n = 38) or a sham procedure (n = 40). Randomization was stratified by treatment center, sex, and symptom duration (<6 weeks or ≥6 weeks). Participants, investigators (except the treating radiologists), and outcome assessors were blinded to group assignments. Enrolment occurred between April 2004 and October 2008 with follow-up completed October 2010. The primary outcome was overall pain measured on a scale of 0 (no pain) to 10 (maximal imaginable pain). Secondary outcomes included pain at rest and at night, disability, quality of life, perceived recovery, and adverse events, including incident clinically apparent vertebral fractures. At 12 and 24 months, complete data were available for 67 (86%) and 57 (73%) participants, respectively. At 12 months participants in the active group improved by 2.4 ± 2.7 (mean ± SD) units in overall pain compared with 1.9 ± 2.8 units in the sham group, adjusted between-group mean difference (MD) 0.3 (95% confidence interval [CI], –0.9 to 1.5), whereas at 24 months participants in the active group had improved by 3.0 ± 3.1 units compared with 1.9 ± 3.0 units in the sham group, MD 1.1 (95% CI, –0.3 to 2.4). No significant between-group differences were observed for any of the secondary efficacy outcomes at 12 or 24 months. There were no between-group differences in incident clinical vertebral fractures up to 24 months (active: n = 14, sham: n = 13), although the study had inadequate power for this outcome. These results provide further evidence that the use of this treatment in routine care is unsupported.

A longitudinal cohort study evaluating the impact of a geriatrician-led residential care out-reach service on acute health care utilisation

Background: Over the last decade, high demand for acute health care services by long-term residents of residential care facilities (RCF) has stimulated interest in exploring alternative models of care. The Residential Care Intervention Program in the Elderly (RECIPE) service provides expert outreach services to RCFs residents, interventions include: comprehensive care planning, management of intercurrent illness and rapid access to acute care substitution services.Objective: To evaluate whether the RECIPE service decreased acute health care utilisation.Design: A retrospective cohort study using interrupted time series analysis to analyse change in acute healthcare utilisation before and after enrolment.Setting: A 300 bed metropolitan teaching hospital in Australia and 73 RCF within its catchment.Subjects: There were 1327 patients enrolled in the service with a median age 84 years, 61% were female. Methods: Data was collected prospectively on all enrolled patients from 2004 to 2011 and linked to the acute health service administrative dataset. Primary outcomes change in admission rates, length of stay and beddays per quarter.Results: In the two years prior to enrolment the mean number of acute care admissions per patient per year was 3.03 (SD 2.9) versus post 2.4 (SD 3.3), the service reducing admissions by 0.13 admissions per patient per quarter (p=0.046). Prior to enrolment the mean length of stay was 8.6 (SD 11.0) versus post 3.5 (SD 5.0), a reduction of 1.5 days per patient per quarter (p=0.003). Conclusions:This study suggests that an outreach service comprising a geriatrician-led multidisciplinary team can reduce acute hospital utilisation rates.

Validity of the Hospital Anxiety and Depression Scale and Patient Health Questionnaire-9 to screen for depression in patients with coronary artery disease.

Depression is common but frequently undetected in patients with coronary artery disease (CAD). Self-report screening instruments for assessing depression such as the Hospital Anxiety and Depression Scale (HADS) and the Patient Health Questionnaire-9 (PHQ-9) are available but their validity is typically determined in depressed patients without comorbid somatic illness. We investigated the validity of these instruments relative to a referent diagnostic standard in recently hospitalized patients with CAD.

Acute human lethal toxicity of agricultural pesticides: a prospective cohort study

BACKGROUND: agricultural pesticide poisoning is a major public health problem in the developing world, killing at least 250,000-370,000 people each year. Targeted pesticide restrictions in Sri Lanka over the last 20 years have reduced pesticide deaths by 50% without decreasing agricultural output. However, regulatory decisions have thus far not been based on the human toxicity of formulated agricultural pesticides but on the surrogate of rat toxicity using pure unformulated pesticides. We aimed to determine the relative human toxicity of formulated agricultural pesticides to improve the effectiveness of regulatory policy. METHODS AND FINDINGS: we examined the case fatality of different agricultural pesticides in a prospective cohort of patients presenting with pesticide self-poisoning to two clinical trial centers from April 2002 to November 2008. Identification of the pesticide ingested was based on history or positive identification of the container. A single pesticide was ingested by 9,302 patients. A specific pesticide was identified in 7,461 patients; 1,841 ingested an unknown pesticide. In a subset of 808 patients, the history of ingestion was confirmed by laboratory analysis in 95% of patients. There was a large variation in case fatality between pesticides-from 0% to 42%. This marked variation in lethality was observed for compounds within the same chemical and/or WHO toxicity classification of pesticides and for those used for similar agricultural indications. CONCLUSION: the human data provided toxicity rankings for some pesticides that contrasted strongly with the WHO toxicity classification based on rat toxicity. Basing regulation on human toxicity will make pesticide poisoning less hazardous, preventing hundreds of thousands of deaths globally without compromising agricultural needs. Ongoing monitoring of patterns of use and clinical toxicity for new pesticides is needed to identify highly toxic pesticides in a timely manner.

Evaluation of the Test-mate ChE (cholinesterase) field kit in acute organophosphorus poisoning

STUDY OBJECTIVE: Measurement of acetylcholinesterase (AChE) is recommended in the management of organophosphorus poisoning, which results in 200,000 deaths worldwide annually. The Test-mate ChE 400 is a portable field kit designed for detecting occupational organophosphorus exposure that measures RBC AChE and plasma cholinesterase (PChE) within 4 minutes. We evaluate Test-mate against a reference laboratory test in patients with acute organophosphorus self-poisoning. METHODS: This was a cross-sectional comparison study of 14 patients with acute organophosphorus poisoning between May 2007 and June 2008. RBC AChE and PChE were measured in 96 and 91 samples, respectively, with the Test-mate ChE field kit and compared with a reference laboratory, using the limits of agreement method (Bland and Altman), κ statistics, and Spearman's correlation coefficients. RESULTS: There was good agreement between the Test-mate ChE and the reference laboratory for RBC AChE. The mean difference (Test-mate-reference) was -0.62 U/g hemoglobin, 95% limits of agreement -10.84 to 9.59 U/g hemoglobin. Good agreement was also observed between the categories of mild, moderate, and severe RBC AChE inhibition (weighted κ 0.85; 95% confidence interval [CI] 0.83 to 0.87). Measurement of PChE also showed good agreement, with a mean difference (Test-mate-reference) of +0.06 U/mL blood, 95% limits of agreement -0.41 to 0.53 U/mL blood. Spearman's correlation coefficients were 0.87 (95% CI 0.81 to 0.91) for RBC AChE and 0.76 (95% CI 0.66 to 0.84) for PChE. Analysis for within-subject correlation of subjects did not change the limits of agreement. CONCLUSION: The Test-mate ChE field kit reliably provides rapid measurement of RBC AChE in acute organophosphorus poisoning.

Adding a new anticoagulant or antiplatelet agent for patient receiving aspirin after an acute coronary syndrome? - Results from a pairwise and network meta-analysis of randomized-controlled trials

 Objectives: To synthesize the efficacy and safety outcomes from randomized-controlled trials (RCTs) regarding new oral anticoagulant, protease-activated receptor-1 (PAR-1) antagonist, and warfarin adjunctive to aspirin for patients after acute coronary syndrome (ACS) via pair-wise and network meta-analyses.
Methods: A comprehensive literature search was performed in Embase, Medline, Cochrane Library Web of Knowledge, and Scopus. The pair-wise meta-analysis was undertaken respectively to each agent/treatment category via Revmen 5.1. In order to estimate the relative efficacy of each agent/treatment category whilst preserving the randomized comparisons within each trial, a Bayesian network meta-analysis was conducted in WinBUGS using both fixed- and random-effects model. Covariate analysis was performed to explore the effects of length of follow-up and age of subject on the final results.
Results: In total, 23 RCTs were included in the meta-analysis. As shown by the results (OR,95%CI) for the pair-wise meta-analysis, new oral anticoagulants (0.85, [0.78, 0.93] and 3.04, [2.21, 4.19]), PAR-1 antagonists (0.80, [0.52, 1.22] and 1.55, [1.25, 1.93]) and warfarin (0.87, [0.74, 1.02] and 1.77, [1.46, 2.14]) might be able to provide better outcome in the incidences of major adverse events (MAE) but with higher bleeding risk comparing to aspirin treatment alone. Based on the model fit assessment, the random-effects model was adopted. The network meta-analysis (treatment effect comparing to aspirin lone) identified ximelagatran (-0.3044, [-0.8601, 0.2502]), dabigatran (-0.2144, [-0.8666, 0.4525]), rivoroxaban (-0.2179, [-0.5986, 0.1628]) and vorapaxar (-0.2272, [-0.81, 0.1664]) produced better improvements in MAE incidences whereas vorapaxar (0.3764, [-0.4444, 1.124]), warfarin (0.663, [0.3375, 1.037]), ximelagatran (0.7509, [-0.4164, 2.002]) and apixaban (0.8594, [-0.0049, 1.7]) produced less major bleeding events. The indirect comparisons among drug category (difference in incidence comparing to aspirin lone) showed new oral anticoagulants (-0.1974, [-0.284, -0.111]) and PAR-1 antagonists (-0.1239, [-0.215, -0.033]) to besuperior to warfarin (-0.1004, [-0.166, -0.035]) in the occurrences of MAE whereas PAR-1 antagonists (0.4292, [0.2123, 0.6476]) afforded better outcomes in major bleeding events against warfarin (0.5742, [0.3889, 0.7619]) and new oral anticoagulants (1.169, [0.8667, 1.485]).
Conclusion: Based on the study results, we cannot recommend the routine administration of new oral anticoagulant as add-on treatment for patients after ACS. However, for ACS patients comorbid with atrial fibrillation, new oral anticoagulant might be superior to warfarin in both efficacy and safety outcomes.

The acute physiological stress response to an emergency alarm and mobilization during the day and at night

The purpose of this study was to investigate the acute physiological stress response to an emergency alarm and mobilization during the day and at night. Sixteen healthy males aged 25 ± 4 years (mean ± SD) spent four consecutive days and nights in a sleep laboratory. This research used a within-participants design with repeated measures for time, alarm condition (alarm or control), and trial (day or night). When an alarm sounded, participants were required to mobilize immediately. Saliva samples for cortisol analysis were collected 0 min, 15 min, 30 min, 45 min, 60 min, 90 min, and 120 min after mobilization, and at corresponding times in control conditions. Heart rate was measured continuously throughout the study. Heart rate was higher in the day (F20,442 = 9.140, P < 0.001) and night (F23,459 = 8.356, P < 0.001) alarm conditions compared to the respective control conditions. There was no difference in saliva cortisol between day alarm and day control conditions. Cortisol was higher (F6,183 = 2.450, P < 0.001) following the night alarm and mobilization compared to the night control condition. The magnitude of difference in cortisol between night control and night alarm conditions was greater (F6,174 = 4.071, P < 0.001) than the magnitude of difference between the day control and day alarm conditions. The augmented heart rate response to the day and night alarms supports previous observations in field settings. Variations in the cortisol responses between conditions across the day and night may relate to differences in participants' ability to interpret the alarm when sleeping versus when awake.