Pharmacological management of acute severe behavioural disturbance: a survey of current protocols.

OBJECTIVES: The investigators reviewed protocols for the pharmacological management of acute severe behavioural disturbance (ASBD) used in Australasian psychiatric settings. Relevant literature was also examined, with a focus on Australian research. METHODS: All Fellows of the RANZCP were emailed on two occasions in 2014 requesting a copy of the guidelines for pharmacological management of the ASBD patient used in their workplace. A literature search was also undertaken. RESULTS: Thirty-six pharmacological management protocols for the ASBD patient were received. Twenty-six of these referred to patients aged 18-65 years and were selected for analysis. A number of recent publications provided new evidence in relation to the safe and effective management of patients with ASBD. CONCLUSIONS: ASBD is a heterogeneous, transnosological set of presentations requiring careful assessment and rational clinical decision making. Treatment protocols arising from an evolving evidence base provide safe and effective pathways for the majority of patients. However, sound clinical knowledge and a careful assessment of each presentation is required to enable the clinician to tailor treatment individually.

Quis custodiet ipsos custodes? An audit of records of involuntary detention.

OBJECTIVES: To determine the appropriateness and utility of the certificates issued under the New South Wales Mental Health Act (MHA) and compliance with the requirements of the MHA. The analysis also compares MHA documentation by different groups of health professionals and police. METHODS: The MHA certificates associated with 100 consecutive involuntary Emergency Department presentations were audited. RESULTS: Considerable variability exists between professional groups in the level of detail, appropriateness, clinical utility and compliance of MHA certificates. Over 10% of Schedule 1s failed to meet the requirements of the MHA, potentially invalidating the involuntary detention of these patients. Information provided by police was typically superior in informing initial risk assessment and emergency management. CONCLUSIONS: A number of patients are presently being detained under incomplete MHA certificates. Educational initiatives that aim to improve awareness of the MHA's requirements, and the potential uses of the information contained in MHA certificates, could encourage professionals to complete these certificates in a more appropriate and clinically useful manner.

Analysis, interpretation, and extrapolation of dermal permeation data using diffusion-based mathematical models.

New dermal penetration data have been measured in both "infinite" and finite dose experiments on a range of compounds of varying lipophilicities. The data are analyzed, using parameter fitting, to determine the values of parameters governing the overall skin absorption processes. Two one-dimensional diffusion models are used. The first is novel, and well suited to the modeling of dermal uptake in occupational exposure scenarios. The second is an implementation of a model taken from the literature. The models are compared in a variety of exposure scenarios, and exhibit good mutual agreement. Both successfully reproduce expected features of the absorption process. Penetration parameters are determined by analyzing both infinite and finite dose data. Prediction of dermal absorption with finite dose scenarios is carried out and compared with experimental data obtained under these conditions. Parameters determined may also have an important role in improving the reliability of predictive QSARs used to estimate the extent of penetration of untested molecules.

Release characteristics of anionic drug compounds from liquid crystalline gels III. Chemical and iontophoretic enhancement of delivery across non-rate-limiting membranes.

This paper investigates the release and transport of a range of anionic drugs from liquid crystalline gels using chemical and physical enhancement techniques. Previous papers [Fitzpatrick, D., Corish, J., 2005. Release characteristics of anionic drug compounds from liquid crystalline gels. I. Passive release across non-rate limiting membranes. Int. J. Pharm. 301, 226-236; Fitzpatrick, D., Corish, J., 2006. Release characteristics of anionic drug compounds from liquid crystalline gels. II. The effects of ion pairing and buffering on the passive delivery of anionic drugs across non rate-limiting membranes. Int. J. Pharm.] have reported on the passive release profiles and those resulting from the incorporation of a chemical enhancer in the vehicle. This paper investigates the behaviour of the system under iontophoretic conditions and also under those of combined physical and chemical enhancement. The data presented here are directly comparable to previous work by Nolan et al. [; Nolan, L.M.A., Corish, J., Corrigan, O.I., Fitzpatrick, D., 2006. Combined effects of iontophoretic and chemical enhancement on drug delivery. II. Transport across human and hairless murine skin. Int. J. Pharm., submitted for publication] which investigated the behaviour of cationic compounds under analogous conditions. The iontophoretic release of diclofenac in the presence of model enhancers is thoroughly investigated. It is also shown that a range of anionic drug molecules undergo an electrochemical change during the course of the experiments which leads to their poor detection. This may be a factor in the under reporting of iontophoretic delivery of anionic drugs in the literature. However, it has been shown that the transport of the drugs is greatly enhanced by the application of an iontophoretic current. Results of combined enhancement studies provide a positive basis on which to proceed with in vitro studies of the system across human skin.

Utilisation and clinical efficacy of echocardiography in a regional hospital.

OBJECTIVE: To determine utilisation and clinical efficacy of echocardiography in a regional setting. DESIGN: Consecutive patients referred for echocardiography studied prospectively using a pro-forma to be completed before and after echocardiography. SETTING: Regional hospital in New South Wales. PARTICIPANTS: A total of 103 consecutive patients. MAIN OUTCOME MEASURES: Utilisation and clinical efficacy of echocardiography. RESULTS: No significant abnormalities were detected in 41.7% of patients, but unexpected abnormalities were found in 31.1%. For 60% of pretest diagnoses there was a clinically important change in diagnostic certainty following the test and changes to treatment occurred in 30.1% of patients. A total of 19 patients with neurological events underwent echocardiography but none had cardiac thrombus demonstrated although thrombus was demonstrated in additional seven. CONCLUSIONS: Echocardiography appears to be used appropriately in our regional setting, resulting in major changes to diagnostic certainty and leading to alterations to treatments in almost one-third of patients. Education in relation to the use of echocardiography in patients with neurological events is warranted.

Release characteristics of anionic drug compounds from liquid crystalline gels. Part II. The effects of ion pairing and buffering on the passive delivery of anionic drugs across non-rate-limiting membranes.

This is the second in a series of papers that report on the release and transport of a range of anionic drugs (diclofenac, salicylic acid) from liquid crystalline gels and ultimately on their use in transdermal delivery. The previous paper [Fitzpatrick, D., Corish, J., 2005. Release characteristics of anionic drug compounds from liquid crystalline gels for transdermal delivery. Part I. Passive release across non-rate limiting membranes. Int. J. Pharm. 301, 226-236] investigated passive release profiles across a non-rate-limiting membrane: here we report on the search for a suitable model enhancer (benzyl dimethyldodecyl ammonium bromide) for the transdermal delivery of anionic compounds. The results presented reveal a significant role for ion pairing and for buffering, analogous to those found in the investigations of cationic species (salbutamol) by Nolan, L.M.A., Corish, J., Corrigan, O.I., Fitzpatrick, D., 2003. Iontophoretic and chemical enhancement of drug delivery. Part I. Across artificial membranes. Int. J. Pharm. 12, 41-55. The method of vehicle preparation is also investigated. It is shown that ion pairing of the drug with the enhancer decreases the amount of drug available for transport from the liquid crystalline gels into aqueous receptor media. This decrease is directly related to the ratio of the concentration of drug to that of the enhancer. Buffering the vehicle inhibits the ion-pair formation to some extent. Vehicle preparation was also found to influence the degree of ion-pair association. The inclusion of a similarly charged enhancer (oleic acid) to the drug was found not to impede the diffusion of the drug from the gels.

Release characteristics of anionic drug compounds from liquid crystalline gels I: Passive release across non-rate-limiting membranes.

Liquid crystalline gels (LCG) offer the formulator dynamic and flexible vehicles, into which actives, enhancers and other adjuvants with a wide range of physicochemical properties can be incorporated. This is achievable because of the biphasic oil/water composition of the gel. In this paper, the suitability of an isotropic liquid crystalline gel is investigated for a range of anionic drug molecules, with particular emphasis on sodium diclofenac. Parameters, which have been investigated, include the mode of vehicle preparation, the effect of the concentration of the drug and how buffering the gel and/or the receptor medium affect the release profiles. Such profiles have been measured for the sodium salts of benzoate, salicylate and indomethacin. The passive release from the standard system was found to adhere to matrix-controlled diffusion. An increase in concentration leads to a non-linear increase in the cumulative release of sodium diclofenac from the gels. In direct contrast to the result reported for cationic salbutamol base, optimum release from the gel was achieved when neither the receptor medium nor the aqueous phase of the gel was buffered. The percentages released of the sodium salts of benzoate, salicylate and indomethacin, after 24 h, were determined to be 25, 26 and 19%, respectively, and these are significantly greater than the release of sodium diclofenac. This suggests that diclofenac undergoes ion-pairing or complexation within the gel, which inhibits its diffusion from the vehicle. Future papers will report on the incorporation of enhancers and the effects of iontophoresis on the release profiles of drugs from these gels, and ultimately on the transdermal transport of drugs from these vehicles across human and porcine skin.