We know this: How to apply what you already know to treat alcohol and other drug problems

Background Implementing effective AOD supports and treatments into our daily practice can occur via a range of strategies. While specialist treatments exclusively targeting pathways toward substance reduction are an option, it is often not within the scope of many psychologists working in generalist or tertiary mental health settings. Regardless of the perceived barriers for integrating AOD practice into our work, there are key principles and approaches that can be adopted to improve the outcomes for many clients. Aim Irrespective of the client’s perceived need to address AOD issues, significant substance use will impact on the development, prognosis and treatment of most mental health conditions. Embedding AOD practice across our clinical work requires an openness to consider evidence-based approaches for all levels of substance use. Method This presentation will outline a series of approaches that all practitioners can adopt, based on the principles of harm reduction and empowerment of client’s choice. An emphasis will be made toward outlining approaches that are consistent with best practice, easily accessible and do not require extensive resources to embed. Conclusion Applying effective AOD treatments as a standard treatment component is achievable for all practitioners and is essential for achieving better outcomes for a high proportion of the community accessing treatment from psychologists.

Targeting glucocorticoid receptors that promote resilience in the treatment of addiction

There is strong evidence to suggest that the combination of alcohol and chronic repetitive stress leads to long-lasting effects on brain function, specifically areas associated with stress, motivation and decision-making such as the amygdala, nucleus accumbens and prefrontal cortex. Alcohol and stress together facilitate the imprinting of long-lasting memories. The molecular mechanisms and circuits involved are being studied but are not fully understood. Current evidence suggests that corticosterone (animals) or cortisol (humans), in addition to direct transcriptional effects on the genome, can directly regulate pre- and postsynaptic synaptic transmission through membrane bound glucocorticoid receptors (GR). Indeed, corticosterone-sensitive synaptic receptors may be critical sites for stress regulation of synaptic responses. Direct modulation of synaptic transmission by corticosterone may contribute to the regulation of synaptic plasticity and memory during stress (Johnson et al., 2005; Prager et al., 2010). Specifically, previous data has shown that long term alcohol (1) increases the expression of NR2Bcontaining NMDA receptors at glutamate synapses, (2) changes receptor density, and (3) changes morphology of dendritic spines (Prendergast and Mulholland; 2012). During alcohol withdrawal these changes are associated with increased glucocorticoid signalling and increased neuronal excitability. It has therefore been proposed that these synapse changes lead to the anxiety and alcohol craving associated with withdrawal (Prendergast and Mulholland; 2012). My lab is targeting this receptor system and the amygdala in order to understand the effect of combining alcohol and stress on these pathways. Lastly, we are testing GR specific compounds as potential new medications to promote the development of resilience to developing addiction.

Dichotomy of food and inhalant allergen sensitization in eosinophilic esophagitis

Background: Eosinophilic esophagitis (EE) is an emerging condition where patients commonly present with symptoms of gastroesophageal reflux disease and fail to respond adequately to anti-reflux therapy. Food allergy is currently recognized as the main immunological cause of EE; recent evidence suggests an etiological role for inhalant allergens. The presence of EE appears to be associated with other atopic illnesses. Objectives: To report the sensitization profile of both food and inhalant allergens in our EE patient cohort in relation to age, and to profile the prevalence of other allergic conditions in patients with EE. Method: The study prospectively analyzed allergen sensitization profiles using skin prick tests to common food allergens and inhalant allergens in 45 children with EE. Patch testing to common food allergens was performed on 33 patients in the same cohort. Comorbidity of atopic eczema, asthma, allergic rhinitis and anaphylaxis were obtained from patient history. Results: Younger patients with EE showed more IgE and patch sensitization to foods while older patients showed greater IgE sensitization to inhalant allergens. The prevalence of atopic eczema, allergic rhinitis and asthma was significantly increased in our EE cohort compared with the general Australian population. A total of 24% of our cohort of patients with EE had a history of anaphylaxis. Conclusion: In children with EE, the sensitization to inhalant allergens increases with age, particularly after 4 years. Also, specific enquiry about severe food reactions in patients presenting with EE is strongly recommended as it appears this patient group has a high incidence of anaphylaxis. © 2007 The Authors.

Effects of PTPN22 C1858T polymorphism on susceptibility and clinical characteristics of British Caucasian rheumatoid arthritis patients

Objectives. To confirm the association of a functional single-nucleotide polymorphism (SNP), C1858T (rs2476601), in the PTPN22 gene of British Caucasian rheumatoid arthritis (RA) patients and to evaluate its influence on the RA phenotype. Methods. A total of 686 RA patients and 566 healthy volunteers, all of British Caucasian origin, were genotyped for C1858T polymorphism by PCR-restriction fragment length polymorphism assay. Data were analysed using SPSS software and the χ 2 test as applicable. Results. The PTPN22 1858T risk allele was more prevalent in the RA patients (13.9%) compared with the healthy controls (10.3%) (P = 0.008, odds ratio 1.4, 95% confidence interval 1.09-1.79). The association of the T allele was restricted to those with rheumatoid factor (RF)-positive disease (n = 524, 76.4%) (P = 0.004, odds ratio 1.5, 95% confidence interval 1.1-1.9). We found no association between PTPN22 and the presence of the HLA-DRB1 shared epitope or clinical characteristics. Conclusions. We confirmed the previously reported association of PTPN22 with RF-positive RA, which was independent from the HLA-DRB1 genotype.

Predictors of clinical improvement in children with recurrent abdominal pain

Forty-three children with recurrent abdominal pain who had received treatment from a paediatric gastroenterology clinic were reassessed 6 and 12 months after initial presentation. Measures of children's pain included a pain diary (PD) which measured pain intensity, a parent observation record (POR) which assessed pain behaviour and a structured interview to assess the degree to which pain interferes with the child's activities. Pretreatment measures of the child's history of pain, coping strategies in dealing with pain, and their mother's caregiving strategies were examined as predictors of two indices of clinical improvement: the extent of change in pain on the child's pain diary from pre-test to 6 months follow-up, and the degree of interference to the child's activities. All children had shown significant improvement in the level of pain at follow up, with 74.4% being pain free at 12 month follow-up on the PD and 83.7% being pain free on the POR. The amount of change they showed varied, with some showing residual impairment even though they were significantly improved. Regression analyses showed that children with greatest reductions on the child's pain diary at the 6 month follow-up were those with a stress-related mode of onset, whose mothers used more adaptive caregiving strategies, and who received cognitive behavioural family intervention. There was also a non significant trend for younger children to fare better. These data suggest the importance of early diagnosis and routinely assessing parental caregiving behaviour and beliefs about the origins of pain in planning treatment for children with RAP.

Pre-operative nutritional support in children with end-stage liver disease accepted for liver transplantation: An approach to management

Pre-operative nutritional support was studied in 28 children with end-stage liver disease awaiting orthotopic liver transplantation. Nasogastric supplemental administration of a standard semi-elemental enteral nutritional formula was compared with a similar formula enriched with branched chain amino acids, and with a group receiving oral nutrition only. The duration of treatment in all groups was similar (mean 90 days). Energy intakes in the supplemented groups were 120-150% of recommended daily intakes (RDI), whereas ad libitum intakes in the oral group ranged 58-100% RDI. A significant improvement in mean Z-score for body weight (denoting catch-up) was noted only in those children who received nasogastric supplements enriched with branched-chain amino acids. The standard enterally-fed group maintained their body weight and Z-scores did not change significantly. In contrast, body weight Z-scores in those fed orally declined significantly. Nutritional supportive therapy of malnourished children with end-stage liver disease can minimize or improve nutritional status in children awaiting liver transplantation. The use of nutritional formulae rich in branche-chain amino acids may have nutritional advantages in children with chronic liver disease which require further study and evaluation.

Use of electronic portal imaging devices for electron treatment verification

This study aims to help broaden the use of electronic portal imaging devices (EPIDs) for pre-treatment patient positioning verification, from photon-beam radiotherapy to photon- and electron-beam radiotherapy, by proposing and testing a method for acquiring clinicallyuseful EPID images of patient anatomy using electron beams, with a view to enabling and encouraging further research in this area. EPID images used in this study were acquired using all available beams from a linac configured to deliver electron beams with nominal energies of 6, 9, 12, 16 and 20 MeV, as well as photon beams with nominal energies of 6 and 10 MV. A widely-available heterogeneous, approximately-humanoid, thorax phantom was used, to provide an indication of the contrast and noise produced when imaging different types of tissue with comparatively realistic thicknesses. The acquired images were automatically calibrated, corrected for the effects of variations in the sensitivity of individual photodiodes, using a flood field image. For electron beam imaging, flood field EPID calibration images were acquired with and without the placement of blocks of water-equivalent plastic (with thicknesses approximately equal to the practical range of electrons in the plastic) placed upstream of the EPID, to filter out the primary electron beam, leaving only the bremsstrahlung photon signal. While the electron beam images acquired using a standard (unfiltered) flood field calibration were observed to be noisy and difficult to interpret, the electron beam images acquired using the filtered flood field calibration showed tissues and bony anatomy with levels of contrast and noise that were similar to the contrast and noise levels seen in the clinically acceptable photon beam EPID images. The best electron beam imaging results (highest contrast, signal-to-noise and contrast-to-noise ratios) were achieved when the images were acquired using the higher energy electron beams (16 and 20 MeV) when the EPID was calibrated using an intermediate (12 MeV) electron beam energy. These results demonstrate the feasibility of acquiring clinically-useful EPID images of patient anatomy using electron beams and suggest important avenues for future investigation, thus enabling and encouraging further research in this area. There is manifest potential for the EPID imaging method proposed in this work to lead to the clinical use of electron beam imaging for geometric verification of electron treatments in the future.

Preparation and in vitro release of drug-loaded microparticles for oral delivery using wholegrain sorghum kafirin protein

Kafirin microparticles have been proposed as an oral nutraceutical and drug delivery system. This study investigates microparticles formed with kafirin extracted from white and raw versus cooked red sorghum grains as an oral delivery system. Targeted delivery to the colon would be beneficial for medication such as prednisolone, which is used in the management of inflammatory bowel disease. Therefore, prednisolone was loaded into microparticles of kafirin from the different sources using phase separation. Differences were observed in the protein content, in vitro protein digestibility, and protein electrophoretic profile of the various sources of sorghum grains, kafirin extracts, and kafirin microparticles. For all of the formulations, the majority of the loaded prednisolone was not released in in vitro conditions simulating the upper gastrointestinal tract, indicating that most of the encapsulated drug could reach the target area of the lower gastrointestinal tract. This suggests that these kafirin microparticles may have potential as a colon-targeted nutraceutical and drug delivery system.

Formulation and characterization of drug-loaded microparticles using distillers dried grain kafirin

Kafirin, a protein extracted from sorghum grain, has been formulated into microparticles and proposed for use as a delivery system owing to the resistance of kafirin to upper gastrointestinal digestion. However, extracting kafirin from sorghum distillers dried grains with solubles (DDGS) may be more efficient, because the carbohydrate component has been removed by fermentation. This study investigated the properties and use of kafirin extracted from DDGS to formulate microparticles. Prednisolone, an anti-inflammatory drug that could benefit from a delayed and targeted delivery system to the colon, was loaded into DDGS kafirin microparticles by phase separation with sodium chloride. Scanning electron micrographs revealed that the empty and prednisolone-loaded microparticles were round in shape and varied in size. Surface binding studies indicated prednisolone was loaded within the microparticles rather than being solely bound on the surface. These findings demonstrate DDGS kafirin can be formulated into microparticles and loaded with medication. Future studies could investigate the potential applications of DDGS kafirin microparticles as an orally administered targeted drug-delivery system.

The missing link of crime analysis: A systematic approach to testing competing hypotheses

Crime analysts have traditionally received little guidance from academic researchers in key tasks in the analysis process, specifically the testing of multiple hypotheses and evaluating evidence in a scientific fashion. This article attempts to fill this gap by outlining a method (the Analysis of Competing Hypotheses) of systematically analysing multiple explanations for crime problems. The method is systematic, avoids many cognitive errors common in analysis, and is explicit. It is argued that the implementation of this approach makes analytic products audit-able, the reasoning underpinning them transparent, and provides intelligence managers a rational professional development tool for individual analysts.

Age-related changes in hepatic function: An update on implications for drug therapy

The accumulation of deficits with increasing age results in a decline in the functional capacity of multiple organs and systems. These changes can have a significant influence on the pharmacokinetics and pharmacodynamics of prescribed drugs. Although alterations in body composition and worsening renal clearance are important considerations, for most drugs the liver has the greatest effect on metabolism. Age-related change in hepatic function thereby causes much of the variability in older people’s responses to medication. In this review, we propose that a decline in the ability of the liver to inactivate toxins may contribute to a proinflammatory state in which frailty can develop. Since inflammation also downregulates drug metabolism, medication prescribed to frail older people in accordance with disease-specific guidelines may undergo reduced systemic clearance, leading to adverse drug reactions, further functional decline and increasing polypharmacy, exacerbating rather than ameliorating frailty status. We also describe how increasing chronological age and frailty status impact liver size, blood flow and protein binding and enzymes of drug metabolism. This is used to contextualise our discussion of appropriate prescribing practices. For example, while the general axiom of ‘start low, go slow’ should underpin the initiation of medication (titrating to a defined therapeutic goal), it is important to consider whether drug clearance is flow or capacity-limited. By summarising the effect of age-related changes in hepatic function on medications commonly used in older people, we aim to provide a guide that will have high clinical utility for practising geriatricians.

The development and preliminary testing of an instrument for assessing fatigue self-management outcomes in patients with advanced cancer

Background: Fatigue is one of the most distressing and commonly experienced symptoms in patients with advanced cancer. Although the self-management (SM) of cancer-related symptoms has received increasing attention, no research instrument assessing fatigue SM outcomes for patients with advanced cancer is available. Objectives: to describe the development and preliminary testing of an interviewer administered instrument for assessing the frequency, and perceived levels of effectiveness and self-efficacy associated with fatigue SM behaviors in patients with advanced cancer. Methods: The development and testing of the Self-efficacy in Managing Symptoms Scale- Fatigue Subscale for Patients with Advanced Cancer (SMSFS-A) involved a number of procedures: item-generation using a comprehensive literature review and semi-structured interviews, content validity evaluation using expert panel reviews, and face validity and test-retest reliability evaluation using pilot testing. Results: Initially, 23 items (22 specific behaviors with one global item) were generated from the literature review and semi-structured interviews. After two rounds of expert panel review, the final scale was reduced to 17 items (16 behaviors with one global item). Participants in the pilot test (n=10) confirmed that the questions in this scale were clear and easy to understand. Bland-Altman analysis showed agreement of results over a one-week interval. Conclusions: The SMSFS-A items were generated using multiple sources. This tool demonstrated preliminary validity and reliability. Implications for practice: The SMSFS-A has the potential to be used for clinical and research purposes. Nurses can use this instrument for collecting data to inform the initiation of appropriate fatigue SM support for this population.

The antihypertensive drug pindolol attenuates long-term but not short-term binge-like ethanol consumption in mice

Alcohol dependence is a debilitating disorder with current therapies displaying limited efficacy and/or compliance. Consequently, there is a critical need for improved pharmacotherapeutic strategies to manage alcohol use disorders (AUDs). Previous studies have shown that the development of alcohol dependence involves repeated cycles of binge-like ethanol intake and abstinence. Therefore, we used a model of binge-ethanol consumption (drinking-in-the-dark) in mice to test the effects of compounds known to modify the activity of neurotransmitters implicated in alcohol addiction. From this, we have identified the FDA-approved antihypertensive drug pindolol, as a potential candidate for the management of AUDs. We show that the efficacy of pindolol to reduce ethanol consumption is enhanced following long-term (12-weeks) binge-ethanol intake, compared to short-term (4-weeks) intake. Furthermore, pindolol had no effect on locomotor activity or consumption of the natural reward sucrose. Because pindolol acts as a dual beta-adrenergic antagonist and 5-HT1A/1B partial agonist, we examined its effect on spontaneous synaptic activity in the basolateral amygdala (BLA), a brain region densely innervated by serotonin- and norepinephrine-containing fibres. Pindolol increased spontaneous excitatory post-synaptic current frequency in BLA principal neurons from long-term ethanol consuming mice but not naïve mice. Additionally, this effect was blocked by the 5-HT1A/1B receptor antagonist methiothepin, suggesting that altered serotonergic activity in the BLA may contribute to the efficacy of pindolol to reduce ethanol intake following long-term exposure. Although further mechanistic investigations are required, this study demonstrates the potential of pindolol as a new treatment option for AUDs that can be fast-tracked into human clinical studies.

Oral medication delivery in impaired swallowing: Thickening liquid medications for safe swallowing alters dissolution characteristics

Acetaminophen (paracetamol) is available in a wide range of oral formulations designed to meet the needs of the population across the age-spectrum, but for people with impaired swallowing, i.e. dysphagia, both solid and liquid medications can be difficult to swallow without modification. The effect of a commercial polysaccharide thickener, designed to be added to fluids to promote safe swallowing by dysphagic patients, on rheology and acetaminophen dissolution was tested using crushed immediate-release tablets in water, effervescent tablets in water, elixir and suspension. The inclusion of the thickener, comprised of xanthan gum and maltodextrin, had a considerable impact on dissolution; acetaminophen release from modified medications reached 12-50% in 30 minutes, which did not reflect the pharmacopeia specification for immediate release preparations. Flow curves reflect the high zero-shear viscosity and the apparent yield stress of the thickened products. The weak gel nature, in combination with high G’ values compared to G” (viscoelasticity) and high apparent yield stress, impact drug release. The restriction on drug release from these formulations is not influenced by the theoretical state of the drug (dissolved or dispersed), and the approach typically used in clinical practice (mixing crushed tablets into pre-prepared thickened fluid) cannot be improved by altering the order of incorporation or mixing method.

Evaluation of a workplace alcohol and other drug policy

BACKGROUND The current impetus for developing alcohol and/or other drugs (AODs) workplace policies in Australia is to reduce workplace AOD impairment, improve safety, and prevent AOD-related injury in the workplace. For these policies to be effective, they need to be informed by scientific evidence. Evidence to inform the development and implementation of effective workplace AOD policies is currently lacking. There does not currently appear to be conclusive evidence for the effectiveness of workplace AOD policies in reducing impairment and preventing AOD-related injury. There is also no apparent evidence regarding which factors facilitate or impede the success of an AOD policy, or whether, for example, unsuccessful policy outcomes were due to poor policy or merely poor implementation of the policy. It was the aim of this research to undertake a process, impact, and outcome evaluation of a workplace AOD policy, and to contribute to the body of knowledge on the development and implementation of effective workplace AOD policies. METHODS The research setting was a state-based power-generating industry in Australia between May 2008 and May 2010. Participants for the process evaluation study were individuals who were integral to either the development or the implementation of the workplace AOD policy, or both of these processes (key informants), and comprised the majority of individuals who were involved in the process of developing and/or implementing the workplace AOD policy. The sample represented the two main groups of interest—management and union delegates/employee representatives—from all three of the participating organisations. For the impact and outcome evaluation studies, the population included all employees from the three participating organisations, and participants were all employees who consented to participate in the study and who completed both the pre-and post-policy implementation questionnaires. Qualitative methods in the form of interviews with key stakeholders were used to evaluate the process of developing and implementing the workplace AOD policy. In order to evaluate the impact of the policy with regard to the risk factors for workplace AOD impairment, and the outcome of the policy in terms of reducing workplace AOD impairment, quantitative methods in the form of a non-randomised single group pre- and post-test design were used. Changes from Time 1 (pre) to Time 2 (post) in the risk factors for workplace AOD impairment, and changes in the behaviour of interest—(self-reported) workplace AOD impairment—were measured. An integration of the findings from the process, impact, and outcome evaluation studies was undertaken using a combination of qualitative and quantitative methods. RESULTS For the process evaluation study Study respondents indicated that their policy was developed in the context of comparable industries across Australia developing workplace AOD policies, and that this was mainly out of concern for the deleterious health and safety impacts of workplace AOD impairment. Results from the process evaluation study also indicated that in developing and implementing the workplace AOD policy, there were mainly ‗winners', in terms of health and safety in the workplace. While there were some components of the development and implementation of the policy that were better done than others, and the process was expensive and took a long time, there were, overall, few unanticipated consequences to implementing the policy and it was reported to be thorough and of a high standard. Findings also indicated that overall the policy was developed and implemented according to best-practice in that: consultation during the policy development phase (with all the main stakeholders) was extensive; the policy was comprehensive; there was universal application of the policy to all employees; changes in the workplace (with regard to the policy) were gradual; and, the policy was publicised appropriately. Furthermore, study participants' responses indicated that the role of an independent external expert, who was trusted by all stakeholders, was integral to the success of the policy. For the impact and outcome evaluation studies Notwithstanding the limitations of pre- and post-test study designs with regard to attributing cause to the intervention, the findings from the impact evaluation study indicated that following policy implementation, statistically significant positive changes with regard to workplace AOD impairment were recorded for the following variables (risk factors for workplace AOD impairment): Knowledge; Attitudes; Perceived Behavioural Control; Perceptions of the Certainty of being punished for coming to work impaired by AODs; Perceptions of the Swiftness of punishment for coming to work impaired by AODs; and Direct and Indirect Experience with Punishment Avoidance for workplace AOD impairment. There were, however, no statistically significant positive changes following policy implementation for Behavioural Intentions, Subjective Norms, and Perceptions of the Severity of punishment for workplace AOD impairment. With regard to the outcome evaluation, there was a statistically significant reduction in self-reported workplace AOD impairment following the implementation of the policy. As with the impact evaluation, these findings need to be interpreted in light of the limitations of the study design in being able to attribute cause to the intervention alone. The findings from the outcome evaluation study also showed that while a positive change in self-reported workplace AOD impairment following implementation of the policy did not appear to be related to gender, age group, or employment type, it did appear to be related to levels of employee general alcohol use, cannabis use, site type, and employment role. Integration of the process, impact, and outcome evaluation studies There appeared to be qualitative support for the relationship between the process of developing and implementing the policy, and the impact of the policy in changing the risk factors for workplace AOD impairment. That is, overall the workplace AOD policy was developed and implemented well and, following its implementation, there were positive changes in the majority of measured risk factors for workplace AOD impairment. Quantitative findings lend further support for a relationship between the process and impact of the policy, in that there was a statistically significant association between employee perceived fidelity of the policy (related to the process of the policy) and positive changes in some risk factors for workplace AOD impairment (representing the impact of the policy). Findings also indicated support for the relationship between the impact of the policy in changing the risk factors for workplace AOD impairment and the outcome of the policy in reducing workplace AOD impairment: positive changes in the risk factors for workplace AOD impairment (impact) were related to positive changes in self reported workplace AOD impairment (representing the main goal and outcome of the policy). CONCLUSIONS The findings from the research indicate support for the conclusion that the policy was appropriately implemented and that it achieved its objectives and main goal. The Doctoral research findings also addressed a number of gaps in the literature on workplace AOD impairment, namely: the likely effectiveness of AOD policies for reducing AOD impairment in the workplace, which factors in the development and implementation of a workplace AOD policy are likely to facilitate or impede the effectiveness of the policy to reduce workplace AOD impairment, and which employee groups are less likely to respond well to policies of this type. The findings from this research not only represent an example of translational, applied research—through the evaluation of the study industry's policy—but also add to the body of knowledge on workplace AOD policies and provide policy-makers with evidence which may be useful in the development and implementation of effective workplace AOD policies. Importantly, the findings espouse the importance of scientific evidence in the development, implementation, and evaluation of workplace AOD policies.