Dexmedetomidine use in the ED for control of methamphetamine-induced agitation.

BACKGROUND: Chemical restraint is often required to control agitation induced by methamphetamine. Dexmedetomidine is an α-2 adrenergic receptor agonist with sedative, analgesic, and sympatholytic properties. Its use in the emergency department (ED) to control methamphetamine-induced agitation has not been reported. OBJECTIVE: To report two cases of methamphetamine-induced agitation successfully sedated with dexmedetomidine in the ED. CASE REPORT: The first case was a 42-year-old man with unstable emotion and violent behaviours after smoking methamphetamine. His agitation did not respond to a large cumulative dose of benzodiazepines (10mg of diazepam and 332mg of midazolam) administered over 48h and sedation was achieved with dexmedetomidine. The second case was a 38-year-old methamphetamine user with unstable emotion and recurrent episodes of agitation despite repeated doses of benzodiazepines, whose agitation was controlled with dexmedetomidine infusion. DISCUSSION: In both cases, dexmedetomidine apparently reduced the dose of benzodiazepines needed to achieve adequate sedation. Transient falls in blood pressure and slowing of the heart rate were noted, which resolved either spontaneously or after reducing the infusion rate without requiring drug treatment. CONCLUSION: Dexmedetomidine can be considered as an adjunct for chemical restraint when standard treatment fails to control the agitation induced by methamphetamine, but patient's hemodynamic state should be monitored closely during administration. Its efficacy and safety in the ED warrant further evaluation with prospective controlled trials.

Can prehospital Modified Early Warning Score identify non-trauma patients requiring life-saving intervention in the emergency department?

OBJECTIVE: We aim to investigate whether prehospital Modified Early Warning Score (MEWS) can identify non-trauma patients requiring life-saving intervention (LSI) within 4 h of presentation to the ED. METHODS: It was a prospective study of non-trauma ED patients by ambulance who were 16 years or older from 1 to 27 November 2013. Prehospital MEWS was calculated according to vital signs measured by the ambulance crew. Data on patients' demographics, triage category, LSI within 4 h of ED presentation and 24 h mortality were retrieved. LSI was defined as emergency interventions to airway, breathing and circulation, emergency procedures and medications administered. The performance of prehospital MEWS was analysed with sensitivity, specificity, predictive values (PV), likelihood ratios (LR) and the receiver operating characteristic curve. RESULTS: Recruited during the study period were 1493 patients. The median age was 78 years. Of the patients, 49.9% belonged to critical, emergent or urgent triage categories. LSI was required in 321 patients (21.5%). Thirteen died within 24 h of ED presentation. The area under the receiver operating characteristic curve of prehospital MEWS relating to LSI was 0.72 (95% confidence interval 0.69 to 0.75). The sensitivity, specificity, positive PV, negative PV, positive LR and negative LR were 0.57, 0.76, 0.40, 0.87, 2.43 and 0.56, respectively, when prehospital MEWS ≥3 was chosen as the cut-off value. CONCLUSIONS: Prehospital MEWS is useful in identifying non-trauma patients requiring LSI within 4 h of ED presentation. This may in turn enhance the triage accuracy in the ED in addition to clinical assessment.

Utilization of the Accident & Emergency Departments by Chinese elderly in Hong Kong.

BACKGROUND: The epidemiological data on elderly patients attending Accident and Emergency Departments (AEDs) in Hong Kong is lacking. The study aimed to examine the epidemiology of geriatric patient visits to AEDs in Hong Kong, including demographic data and predictors of life-saving interventions (LSI) and admission. METHODS: A retrospective cross-sectional study of geriatric patients older than 64 years old attending three AEDs during the year 2012, with a sample of 1 200 patient visits recruited. The data were retrieved from the medical records of the respective hospitals. Descriptive characteristics of the visits were provided. Multivariate logistic regression was performed to evaluate the predictors of LSI and hospital admission. RESULTS: The mean age of the patients was 79.1 years. Totally 49.7% of the patients were male. "Diseases of the respiratory system" was the commonest diagnosis in AEDs as well as that required admission. The admission rate was 56.8%. Logistic regression demonstrated that dependent activity of daily living (ADL), arrival by ambulance, and the higher number of co-morbidities were predictors of LSI, while advanced age, dependent ADL, institutionalized patients, arrival by ambulance, and higher number of co-morbidities were predictors of hospital admission. CONCLUSIONS: Ageing population is creating an imminent burden on the emergency service in Hong Kong. Previously unavailable epidemiological information about geriatric attendance to AEDs was described. This forms the basis for development of future studies concerning the medical services on this specific group of patients.

Evaluation of the clinimetrics of transcutaneous oxygen measurement and its application in wound care.

Transcutaneous oxygen (TcPO2) measurement is a non-invasive diagnostic tool increasingly being used in clinical practice. Existing evidence suggests that reduction of TcPO2 is correlated with an increase in skin ischaemia, and its measurement has been shown to have predictive value for wound healing in diabetic patients, success rate of hyperbaric oxygen therapy, amputation rate in patients suffering from peripheral vascular disease or with ischaemic ulcers. This article evaluates the clinimetrics of TcPO2 measurement in adults with discussion of its potential application in clinical practice.

The influence of polysorbate 80 on the radiochemical synthesis of a PET tracer in the FASTlab.

PURPOSE: The aim of current study was to investigate the influence of a common non-ionic surfactant, polysorbate 80 (PS80), on radioactive labelling process of a novel PET tracer, [(18)F]Flutemetamol. METHODS: Ferrous oxidation-xylenol orange (FOX) assay, in addition to UV/VIS and (1)H NMR spectroscopies were applied to characterise the composition of the PS80 solution after storage. Multivariate Curve Resolution (MCR) and PLS analysis was used to establish correlation between quality of the PS80 solution and the RCP obtained after labelling. RESULTS: The levels of unsaturated fatty acid moieties of PS80 were negatively correlated to RCP of [(18)F]Flutemetamol after synthesis. This explains the slight increase in RCP when stored PS80 solutions were applied in the synthesis. The mechanism behind this observation is suggested to be related to radiation induced radical formation in the unsaturated fatty acids, which subsequently causes instability of the PET tracer. UV/VIS spectroscopy was demonstrated to have the ability as a possible control tool for quality assurance of the studied radioactive labelling process. CONCLUSIONS: The presence of unsaturated fatty acid moieties in PS80 was found to be one of the most important factors responsible for the reduction in RCP of [(18)F]Flutemetamol after synthesis.

Influence of oxygen on wound healing.

Oxygen has an important role in normal wound healing. This article reviews the evidence concerning the role of oxygen in wound healing and its influence on the different stages of wound healing. The evidence reviewed has demonstrated that improving oxygenation may be helpful in limiting wound infection, although there is a lack of good quality studies on the role of oxygen in the proliferative phase and in reepithelialisation. Overall, the relationship between oxygen and wound healing is complex. Knowledge of this aspect is important as many treatment modalities for refractory wounds are based on these principles.

Classification of structurally related commercial contrast media by near infrared spectroscopy.

Near infrared spectroscopy (NIRS) is a non-destructive measurement technique with broad application in pharmaceutical industry. Correct identification of pharmaceutical ingredients is an important task for quality control. Failure in this step can result in several adverse consequences, varied from economic loss to negative impact on patient safety. We have compared different methods in classification of a set of commercially available structurally related contrast media, Iodixanol (Visipaque(®)), Iohexol (Omnipaque(®)), Caldiamide Sodium and Gadodiamide (Omniscan(®)), by using NIR spectroscopy. The performance of classification models developed by soft independent modelling of class analogy (SIMCA), partial least squares discriminant analysis (PLS-DA) and Main and Interactions of Individual Principal Components Regression (MIPCR) were compared. Different variable selection methods were applied to optimize the classification models. Models developed by backward variable elimination partial least squares regression (BVE-PLS) and MIPCR were found to be most effective for classification of the set of contrast media. Below 1.5% of samples from the independent test set were not recognized by the BVE-PLS and MIPCR models, compared to up to 15% when models developed by other techniques were applied.

Strategies for multivariate modeling of moisture content in freeze-dried mannitol-containing products by near-infrared spectroscopy.

Accurate determination of residual moisture content of a freeze-dried (FD) pharmaceutical product is critical for prediction of its quality. Near-infrared (NIR) spectroscopy is a fast and non-invasive method routinely used for quantification of moisture. However, several physicochemical properties of the FD product may interfere with absorption bands related to the water content. A commonly used stabilizer and bulking agent in FD known for variation in physicochemical properties, is mannitol. To minimize this physicochemical interference, different approaches for multivariate correlation between NIR spectra of a FD product containing mannitol and the corresponding moisture content measured by Karl Fischer (KF) titration have been investigated. A novel method, MIPCR (Main and Interactions of Individual Principal Components Regression), was found to have significantly increased predictive ability of moisture content compared to a traditional PLS approach. The philosophy behind the MIPCR is that the interference from a variety of particle and morphology attributes has interactive effects on the water related absorption bands. The transformation of original wavelength variables to orthogonal scores gives a new set of variables (scores) without covariance structure, and the possibility of inclusion of interaction terms in the further modeling. The residual moisture content of the FD product investigated is in the range from 0.7% to 2.6%. The mean errors of cross validated prediction of models developed in the investigated NIR regions were reduced from a range of 24.1-27.6% for traditional PLS method to 15.7-20.5% for the MIPCR method. Improved model quality by application of MIPCR, without the need for inclusion of a large number of calibration samples, might increase the use of NIR in early phase product development, where availability of calibration samples is often limited.

Characterization of polysorbate 80 with liquid chromatography mass spectrometry and nuclear magnetic resonance spectroscopy: specific determination of oxidation products of thermally oxidized polysorbate 80.

The polysorbate species in polysorbate 80 (PS 80) have been characterized with (1)H NMR, LC-UV/MS and MS/MS. The MS was operated with both negative and positive electrospray ionization (ESI). PS 80 was found to contain mono- and di-fatty acid esters of polyoxyethylene (POE) sorbitan, POE isosorbide and of POE. In addition, the same species were also present without fatty acid esters. The polysorbate species were esterified with C12:0, C14:0, C16:1, C16:0, C18:2, C18:1 and C18:0 fatty acids. The main species were polysorbate esters of C18:1. The C18:2 polysorbate species were shown, by (1)H NMR, to have a large component of fatty acids with a conjugated double bond of ZE and/or EZ configuration. The positive ESI mass spectra of the polysorbate species displayed a specific in-source fatty acid fragment for each fatty acid ester. The mass chromatograms of the in-source fatty acid fragments were used to determine the degradation of specific polysorbate species in PS 80. The C18:2 polysorbate species were completely degraded after 8 weeks at 40°C under an atmosphere of air, while the main C18:1 polysorbate species were reduced to ca. 80-86% accompanied by an increase of short-chain POE C18:1 species. Polysorbate species esterified with C18:1-OH, C18:1 keto and C18:0 epoxy acids were found as degradation products of PS 80 stored at 40°C for 8 weeks under air. C18:1-OH, C18:1 keto and C18:0 epoxy acids were believed to be oxidation products of C18:1. With the present conditions, the positive ESI mass spectra of C18:1-OH and C18:0 epoxy polysorbate species displayed identical ions to the C18:2 polysorbate species due to a facile in-source loss of H(2)O from the protonated molecules. The presence of polysorbate esters of C18:1-OH and C18:0 epoxy acids were established using negative ESI MS. The presence of oxidized fatty acids in degraded PS 80 was also confirmed by saponification and extraction followed by negative ESI LC-MS analysis of the free fatty acids.

Targeted delivery and enhanced cytotoxicity of cetuximab-saporin by photochemical internalization in EGFR-positive cancer cells.

Photochemical internalization (PCI) is a novel technology of macromolecular delivery. By PCI, endocytosed membrane-impermeable therapeutic drugs are photochemically released from entrapment in endo-lysosomal compartments to the cytosol of target cells. In the present report, we describe the in vitro proof-of-concept for PCI of cetuximab-saporin, an immunotoxin targeting EGFR-expressing cells. This immunotoxin consists of the chimeric murine-human IgG1 monoclonal antibody cetuximab (C225 or Erbitux) bound to the type I ribosome-inactivating protein toxin saporin by a biotin-streptavidin linkage. The photochemical treatment enhanced the cytotoxicity of the immunotoxin in a synergistic manner in three different EGFR-expressing carcinoma cell lines derived from different tumor tissues (colorectal, HCT-116; prostate, DU-145; and epidermis, A-431). Both cytotoxicity of cetuximab-saporin and epifluorescence of Alexa488-cetuximab were evaluated by competition with cetuximab demonstrating specific binding and uptake of cetuximab-saporin in EGFR positive cells. In the EGFR-negative uterine sarcoma cell line MES-SA, neither binding nor preferential accumulation of Alexa488-cetuximab was detected. In addition, PCI enhanced the cytotoxicity of cetuximab-saporin to the same extent as streptavidin-saporin in the MES-SA cells. In conclusion, PCI enhances selectivity of the cytotoxicity of the immunotoxin cetuximab-saporin in EGFR-expressing cells.