Objective -To present a series of evidence-based, consensus guidelines for veterinary CPR in dogs and cats. Design -Standardized, systematic evaluation of the literature, categorization of relevant articles according to level of evidence and quality, and development of consensus on conclusions for application of the concepts to clinical practice. Questions in five domains were examined: Preparedness and Prevention, Basic Life Support, Advanced Life Support, Monitoring, and Post-Cardiac Arrest Care. Standardized worksheet templates were used for each question, and the results reviewed by the domain members, by the RECOVER committee, and opened for comments by veterinary professionals for 4 weeks. Clinical guidelines were devised from these findings and again reviewed and commented on by the different entities within RECOVER as well as by veterinary professionals. Setting -Academia, referral practice and general practice. Results -A total of 74 worksheets were prepared to evaluate questions across the five domains. A series of 101 individual clinical guidelines were generated. In addition, a CPR algorithm, resuscitation drug-dosing scheme, and postcardiac arrest care algorithm were developed. Conclusions -Although many knowledge gaps were identified, specific clinical guidelines for small animal veterinary CPR were generated from this evidence-based process. Future work is needed to objectively evaluate the effects of these new clinical guidelines on CPR outcome, and to address the knowledge gaps identified through this process. (J Vet Emerg Crit Care 2012; 22(S1): 102-131)
Drug misuse in prisons contributes to increased disruption and violence and negatively impacts prisoner safety, rehabilitation, and recovery. Synthetic cannabinoid receptor agonists (SCRAs), colloquially known as “spice”, are infused into papers and are of particular concern in a prison setting where they are commonly vaped. Methods for the qualitative and quantitative analysis of SCRA infused papers, including impurity profiling, were developed using gas chromatography–mass spectrometry (GC–MS) with qualitative confirmation by ultra high pressure liquid chromatography with photodiode array and quadrupole time of flight mass spectrometry detection (UPLC‐PDA‐QToF‐MS) and applied to 354 individual seized paper samples originating from 168 seizures from three Scottish prisons. Of these samples, 41% (146 samples from 101 seizures) contained at least one SCRA and multiple SCRAs were detected on 23% of these papers. Concentrations ranged from < 0.05–1.17 mg/cm2 paper, representing the first reported quantitative data for SCRA infused papers. An evolution in the SCRAs detected was demonstrated; 5F‐MDMB‐PINACA (5F‐ADB) predominated until late 2018, after which time 5F‐MDMB‐PICA and 4F‐MDMB‐BINACA became increasingly more prevalent, followed by the arrival of MDMB‐4en‐PINACA in June 2019. Concentration mapping data from two seized paper samples demonstrated that SCRA concentrations across larger papers were highly variable (0.47–2.38 mg/cm2 paper) making consistent dosing by users, and representative sampling by laboratory analysts, difficult. Near real‐time qualitative and quantitative information on SCRAs circulating in prisons acts as an early warning system for SCRAs emerging on the wider illicit market, inform the methods used to detect them and limit supply, and provide information to support harm reduction measures.
Background: The influence of sleep on the equine electroencephalogram (EEG) has not been well documented. Hypothesis: The objectives were to develop a noninvasive method of electrode placement for recording the EEG in horses and to establish normal EEG parameters for the various states of vigilance. Findings are compared with previously published reports on equine sleep based on electrocorticography (ECoG).Animals: Five neurologically normal horses. Methods: Overnight EEGs were recorded digitally in association with simultaneous videotaping of the horses' behavior. Data were analyzed by visual inspection, states of vigilance were identified, and representative segments were quantitatively processed. Transient EEG events were examined.Results: Slow wave sleep (SWS) was significantly different (P o .05) in frequency and power from drowsiness and rapid eye movement (REM) sleep. Second-degree heart block was associated with SWS as were transient events commonly recognized in EEGs of humans. Drowsiness and REM sleep were similar. In both, background activity was low-amplitude b activity admixed with prominent activity of approximately 4 Hz. Standing REM sleep was associated with numerous partial collapses in 1 horse.Conclusions and Clinical Importance: Normative data for several states were described and probable benign variants identified. This information will serve as control data for sedative and anesthetic studies in this species. The sleep patterns observed during this study are those of horses removed from their usual surroundings, and thus may represent those encountered in a clinical environment.
Hydroxylation and fluorination of proline alters the pyrrolidine ring pucker and the trans:cis amide bond ratio in a stereochemistry-dependent fashion, affecting molecular recognition of proline-containing molecules by biological systems. While hydroxyprolines and fluoroprolines are common motifs in medicinal and biological chemistry, the synthesis and molecular properties of prolines containing both modifications, i.e., fluoro-hydroxyprolines, have not been described. Here we present a practical and facile synthesis of all four diastereoisomers of 3-fluoro-4-hydroxyprolines (F-Hyps), starting from readily available 4-oxo-l-proline derivatives. Small-molecule X-ray crystallography, NMR spectroscopy, and quantum mechanical calculations are consistent with fluorination at C having negligible effects on the hydrogen bond donor capacity of the C hydroxyl, but inverting the natural preference of Hyp from C-exo to C-endo pucker. In spite of this, F-Hyps still bind to the von Hippel-Lindau (VHL) E3 ligase, which naturally recognizes C-exo Hyp in a stereoselective fashion. Co-crystal structures and electrostatic potential calculations support and rationalize the observed preferential recognition for (3 R,4 S)-F-Hyp over the corresponding (3 S,4 S) epimer by VHL. We show that (3 R,4 S)-F-Hyp provides bioisosteric Hyp substitution in both hypoxia-inducible factor 1 alpha (HIF-1α) substrate peptides and peptidomimetic ligands that form part of PROTAC (proteolysis targeting chimera) conjugates for targeted protein degradation. Despite a weakened affinity, Hyp substitution with (3 S,4 S)-F-Hyp within the PROTAC MZ1 led to Brd4-selective cellular degradation at concentrations >100-fold lower than the binary K for VHL. We anticipate that the disclosed chemistry of 3-fluoro-4-hydroxyprolines and their application as VHL ligands for targeted protein degradation will be of wide interest to medicinal organic chemists, chemical biologists, and drug discoverers alike.
Dogs with SHP have evidence of hypocoagulability, protein C deficiency, and hyperfibrinolysis. Parameters of hyperfibrinolysis were related to plasma lactate concentrations and volume of plasma transfused during hospitalization. These derangements resemble those found in people with acute coagulopathy of trauma and shock, and activation of protein C may be a common feature to both syndromes.
Objective -To systematically examine the evidence on basic life support (BLS) in veterinary CPR and to determine knowledge gaps. Design -Standardized, systematic evaluation of the literature, categorization of relevant articles according to level of evidence and quality, and development of consensus on conclusions for application of the concepts to clinical practice. Relevant questions were answered on a worksheet template and reviewed by the Reassessment Campaign on Veterinary Resuscitation (RECOVER) BLS domain members, by the RECOVER committee and opened for comments by veterinary professionals for 30 days. Setting -Academia, referral practice, and general practice. Results -Sixteen worksheets were prepared to evaluate techniques for chest compression and ventilation strategies as well as identification of cardiopulmonary arrest (CPA). Major recommendations arising from this evidence review include performing chest compressions at a rate of at least 100/min at a compression depth of one-third to half the width of the chest with minimal pauses, and early instigation of ventilation at a rate of 8-10 breaths/min in intubated patients, or using a 30:2 compression/ventilation ratio in nonintubated patients. Conclusions -Although veterinary clinical trials are lacking, much of the experimental literature on BLS utilized canine models. The major conclusions from this analysis of the literature are the importance of early identification of CPA, and immediate initiation of BLS in these patients. Many knowledge gaps exist, most importantly in our understanding of the optimal hand placement and technique for chest compressions, warranting coordinated future studies targeted at questions of relevance to differences between veterinary species and humans. (J Vet Emerg Crit Care 2012; 22(S1): 26-43)
There is strong evidence supporting the use of standard-dose (0.01 mg/kg) epinephrine in CPR, as well as early electrical defibrillation for animals experiencing CPA due to ventricular fibrillation or pulseless ventricular tachycardia, preferentially using a biphasic defibrillator. For CPA due to certain causes and with the availability of advanced postcardiac arrest support, open chest CPR is preferred. Many knowledge gaps regarding other pharmacologic and advanced therapies were identified, and further studies are recommended to better systematically address these questions.
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