Osteoporosis medication dispensing for older Australian women from 2002 to 2010: Influences of publications, guidelines, marketing activities and policy

Purpose Developments in anti-osteoporosis medications (AOMs) have led to changes in guidelines and policy, which, along with media and marketing strategies, have had an impact upon the prescribing of AOM. The aim was to examine patterns of AOM dispensing in older women (aged 76–81 years at baseline) from 2002 to 2010. Methods Administrative claims data were used to describe AOM dispensing in 4649 participants (born in 1921–1926 and still alive in 2011) in the Australian Longitudinal Study on Women's Health. The patterns were interpreted in the context of changes in guidelines, indications for subsidy, publications (scholarly and general media), and marketing activities. Results Total use of AOM increased from 134 DDD/1000/day in 2002 to 216 DDD/1000/day in 2007 but then decreased to 184 DDD/1000/day in 2010. Alendronate was the most commonly dispensed AOM but decreased from 2007, while use of risedronate (2002 onward), strontium ranelate (2007 onward) and zoledronic acid (2008 onward) increased. Etidronate and hormone replacement therapy (HRT) prescriptions gradually decreased over time. The decline in alendronate dispensing coincided with increases of other bisphosphonates and publicity about potential adverse effects of bisphosphonates, despite relaxing indications for bone density testing and subsidy for AOM. Conclusions Overall dispense of AOM from 2002 reached a peak in 2007 and thereafter declined despite increases in therapeutic options and improved subsidised access. The recent decline in overall AOM dispensing seems to be explained largely by negative publicity rather than specific changes in guidelines and policy.

Effect of an interactive therapeutic robotic animal on engagement, mood states, agitation and psychotropic drug use in people with dementia: A cluster-randomised controlled trial protocol

Introduction: Apathy, agitated behaviours, loneliness and depression are common consequences of dementia. This trial aims to evaluate the effect of a robotic animal on behavioural and psychological symptoms of dementia in people with dementia living in long-term aged care. Methods and analysis: A cluster-randomised controlled trial with three treatment groups: PARO (robotic animal), Plush-Toy (non-robotic PARO) or Usual Care (Control). The nursing home sites are Australian Government approved and accredited facilities of 60 or more beds. The sites are located in South-East Queensland, Australia. A sample of 380 adults with a diagnosis of dementia, aged 60 years or older living in one of the participating facilities will be recruited. The intervention consists of three individual 15 min non-facilitated sessions with PARO or Plush- Toy per week, for a period of 10 weeks. The primary outcomes of interest are improvement in agitation, mood states and engagement. Secondary outcomes include sleep duration, step count, change in psychotropic medication use, change in treatment costs, and staff and family perceptions of PARO or Plush-Toy. Video data will be analysed using Noldus XT Pocket Observer; descriptive statistics will be used for participants’ demographics and outcome measures; cluster and individual level analyses to test all hypotheses and Generalised Linear Models for cluster level and Generalised Estimation Equations and/or Multi-level Modeling for individual level data. Ethics and dissemination: The study participants or their proxy will provide written informed consent. The Griffith University Human Research Ethics Committee has approved the study (NRS/03/14/HREC). The results of the study will provide evidence of the efficacy of a robotic animal as a psychosocial treatment for the behavioural and psychological symptoms of dementia. Findings will be presented at local and international conference meetings and published in peer-reviewed journals.

Application of data mining techniques in the prediction of coronary artery disease : use of anaesthesia time-series and patient risk factor data

The high morbidity and mortality associated with atherosclerotic coronary vascular disease (CVD) and its complications are being lessened by the increased knowledge of risk factors, effective preventative measures and proven therapeutic interventions. However, significant CVD morbidity remains and sudden cardiac death continues to be a presenting feature for some subsequently diagnosed with CVD. Coronary vascular disease is also the leading cause of anaesthesia related complications. Stress electrocardiography/exercise testing is predictive of 10 year risk of CVD events and the cardiovascular variables used to score this test are monitored peri-operatively. Similar physiological time-series datasets are being subjected to data mining methods for the prediction of medical diagnoses and outcomes. This study aims to find predictors of CVD using anaesthesia time-series data and patient risk factor data. Several pre-processing and predictive data mining methods are applied to this data. Physiological time-series data related to anaesthetic procedures are subjected to pre-processing methods for removal of outliers, calculation of moving averages as well as data summarisation and data abstraction methods. Feature selection methods of both wrapper and filter types are applied to derived physiological time-series variable sets alone and to the same variables combined with risk factor variables. The ability of these methods to identify subsets of highly correlated but non-redundant variables is assessed. The major dataset is derived from the entire anaesthesia population and subsets of this population are considered to be at increased anaesthesia risk based on their need for more intensive monitoring (invasive haemodynamic monitoring and additional ECG leads). Because of the unbalanced class distribution in the data, majority class under-sampling and Kappa statistic together with misclassification rate and area under the ROC curve (AUC) are used for evaluation of models generated using different prediction algorithms. The performance based on models derived from feature reduced datasets reveal the filter method, Cfs subset evaluation, to be most consistently effective although Consistency derived subsets tended to slightly increased accuracy but markedly increased complexity. The use of misclassification rate (MR) for model performance evaluation is influenced by class distribution. This could be eliminated by consideration of the AUC or Kappa statistic as well by evaluation of subsets with under-sampled majority class. The noise and outlier removal pre-processing methods produced models with MR ranging from 10.69 to 12.62 with the lowest value being for data from which both outliers and noise were removed (MR 10.69). For the raw time-series dataset, MR is 12.34. Feature selection results in reduction in MR to 9.8 to 10.16 with time segmented summary data (dataset F) MR being 9.8 and raw time-series summary data (dataset A) being 9.92. However, for all time-series only based datasets, the complexity is high. For most pre-processing methods, Cfs could identify a subset of correlated and non-redundant variables from the time-series alone datasets but models derived from these subsets are of one leaf only. MR values are consistent with class distribution in the subset folds evaluated in the n-cross validation method. For models based on Cfs selected time-series derived and risk factor (RF) variables, the MR ranges from 8.83 to 10.36 with dataset RF_A (raw time-series data and RF) being 8.85 and dataset RF_F (time segmented time-series variables and RF) being 9.09. The models based on counts of outliers and counts of data points outside normal range (Dataset RF_E) and derived variables based on time series transformed using Symbolic Aggregate Approximation (SAX) with associated time-series pattern cluster membership (Dataset RF_ G) perform the least well with MR of 10.25 and 10.36 respectively. For coronary vascular disease prediction, nearest neighbour (NNge) and the support vector machine based method, SMO, have the highest MR of 10.1 and 10.28 while logistic regression (LR) and the decision tree (DT) method, J48, have MR of 8.85 and 9.0 respectively. DT rules are most comprehensible and clinically relevant. The predictive accuracy increase achieved by addition of risk factor variables to time-series variable based models is significant. The addition of time-series derived variables to models based on risk factor variables alone is associated with a trend to improved performance. Data mining of feature reduced, anaesthesia time-series variables together with risk factor variables can produce compact and moderately accurate models able to predict coronary vascular disease. Decision tree analysis of time-series data combined with risk factor variables yields rules which are more accurate than models based on time-series data alone. The limited additional value provided by electrocardiographic variables when compared to use of risk factors alone is similar to recent suggestions that exercise electrocardiography (exECG) under standardised conditions has limited additional diagnostic value over risk factor analysis and symptom pattern. The effect of the pre-processing used in this study had limited effect when time-series variables and risk factor variables are used as model input. In the absence of risk factor input, the use of time-series variables after outlier removal and time series variables based on physiological variable values’ being outside the accepted normal range is associated with some improvement in model performance.

Substance use disorders

Basic competencies in assessing and treating substance use disorders should be core to the training of any clinical psychologist, because of the high frequency of risky or problematic substance use in the community, and its high co-occurrence with other problems. Skills in establishing trust and a therapeutic alliance are particularly important in addiction, given the stigma and potential for legal sanctions that surround it. The knowledge and skills of all clinical practitioners should be sufficient to allow valid screening and diagnosis of substance use disorders, accurate estimation of consumption and a basic functional analysis. Practitioners should also be able to undertake brief interventions including motivational interviews, and appropriately apply generic interventions such as problem solving or goal setting to addiction. Furthermore, clinical psychologists should have an understanding of the nature, evidence base and indications for biochemical assays, pharmacotherapies and other medical treatments, and ways these can be integrated with psychological practice. Specialists in addiction should have more sophisticated competencies in each of these areas. They need to have a detailed understating of current addiction theories and basic and applied research, be able to undertake and report on a detailed psychological assessment, and display expert competence in addiction treatment. These skills should include an ability to assess and manage complex or co-occurring problems, to adapt interventions to the needs of different groups, and to assist people who have not responded to basic treatments. They should also be able to provide consultation to others, undertake evaluations of their practice, and monitor and evaluate emerging research data in the field.

Psychoanalytic perspectives on substance use and antisocial personality disorder

Psychoanalysis and related psychodynamic psychotherapies have historically had a limited engagement with substance use and antisocial personality disorders. This in part reflects an early preoccupation with ‘transference neuroses’ and in part reflects later de-emphasis of diagnosis and focus on therapeutic process. Nonetheless, psychoanalytic perspectives can usefully inform thinking about approaches to treatment of such disorders and there are psychoanalytic constructs that have specific relevance to their treatment. This paper reviews some prominent strands of psychoanalytic thinking as they pertain to the treatment of substance abuse and antisocial personality disorders. It is argued that, while Freudian formulations lead to a primarily pessimistic view of the prospect of treatment of such disorders, both the British object relations and the North American self psychology traditions suggest potentially productive approaches. Finally the limited empirical evidence from brief psychodynamically informed treatments of substance use disorders is reviewed. It is concluded that such treatments are not demonstrably effective but that, since no form of psychotherapy has established high efficacy with substance use disorders, brief psychdynamic therapies are not necessarily of lesser value than other treatments and may have specific value for particular individuals and in particular treatment contexts.

The role of insulin and IGF2 signalling on metabolic pathways in prostate cancer progression

Prostate cancer (CaP) is the most commonly diagnosed cancer in males in Australia, North America, and Europe. If found early and locally confined, CaP can be treated with radical prostatectomy or radiation therapy; however, 25-40% patients will relapse and go on to advanced disease. The most common therapy in these cases is androgen deprivation therapy (ADT), which suppresses androgen production from the testis. Lack of the testicular androgen supply causes cells of the prostate to undergo apoptosis. However, in some cases the regression initially seen with ADT eventually gives way to a growth of a population of cancerous cells that no longer require testicular androgens. This phenotype is essentially fatal and is termed castrate resistant prostate cancer (CRPC). In addition to eventual regression, there are many undesirable side effects which accompany ADT, including development of a metabolic syndrome, which is defined by the U.S. National Library of Medicine as “a combination of medical disorders that increase the risk of developing cardiovascular disease and diabetes.” This project will focus on the effect of ADT induced hyperinsulinemia, as mimicked by treating androgen receptor positive CaP cells with insulin in a serum (hormone) deprived environment. While this side effect is not widely explored, in this thesis it is demonstrated for the first time that insulin upregulates pathways important to CaP progression. Our group has previously shown that during CaP progression, the enzymes necessary for de novo steroidogenesis are upregulated in the LNCaP xenograft model, total steroid levels are increased in tumours compared to pre castrate levels, and de novo steroidogenesis from radio-labelled acetate has been demonstrated. Because of the CaP dependence on AR for survival, we and other groups believe that CaP cells carry out de novo steroidogenesis to survive in androgen deprived conditions. Because (a) men on ADT often develop metabolic syndrome, and (b) men with lifestyle-induced obesity and hyperinsulinemia have worse prognosis and faster disease progression, and because (c) insulin causes steroidogenesis in other cell lines, the hypothesis that insulin may contribute to CaP progression through upregulation of steroidogenesis was explored. Insulin upregulates steroidogenesis enzymes at the mRNA level in three AR positive cell lines, as well as upregulating these enzymes at the protein level in two cell lines. It has also been demonstrated that insulin increases mitochondrial (functional) levels of steroid acute regulatory protein (StAR). Furthermore, insulin causes increased levels of total steroids in and induction of de novo steroid synthesis by insulin has been demonstrated at levels induced sufficient to activate AR. The effect of insulin analogs on CaP steroidogenesis in LNCaP and VCaP cells has also been investigated because epidemiological studies suggest that some of the analogs developed may have more cancer stimulatory effects than normal insulin. In this project, despite the signalling differences between glargine, X10, and insulin, these analogs did not appear to induce steroidogenesis any more potently that normal insulin. The effect of insulin of MCF7breast cancer cells was also investigated with results suggesting that breast cancer cells may be capable of de novo steroidogenesis, and that increase in estradiol production may be exacerbated by insulin. Insulin has also been long known to stimulate lipogenesis in the liver and adipocytes, and has been demonstrated to increase lipogenesis in breast cancer cells; therefore, investigation of the effect of insulin on lipogenesis, which is a hallmark of aggressive cancers, was investigated. In CaP progression sterol regulatory element binding protein (SREBP) is dysregulated and upregulates fatty acid synthase (FASN), acetyl CoA-carboxylase, and other lipogenesis genes. SREBP is important for steroidogenesis and in this project has been shown to be upregulated by insulin in CaP cells. Fatty acid synthesis provides building blocks of membrane growth, provides substrates for acid oxidation, the main energy source for CaP cells, provides building blocks for anti-apoptotic and proinflammatory molecules, and provides molecules that stimulate steroidogenesis. In this project it has been shown that insulin upregulates FASN and ACC, which synthesize fatty acids, as well as upregulating hormone sensitive lipase (HSL), diazepam-binding inhibitor (DBI), and long-chain acyl-CoA synthetase 3 (ACSL3), which contribute to lipid activation of steroidogenesis. Insulin also upregulates total lipid levels and de novo lipogenesis, which can be suppressed by inhibition of the insulin receptor (INSR). The fatty acids synthesized after insulin treatment are those that have been associated with CaP; furthermore, microarray data suggests insulin may upregulate fatty acid biosynthesis, metabolism and arachidonic acid metabolism pathways, which have been implicated in CaP growth and survival. Pharmacological agents used to treat patients with hyperinsulinemia/ hyperlipidemia have gained much interest in regards to CaP risk and treatment; however, the scientific rationale behind these clinical applications has not been examined. This thesis explores whether the use of metformin or simvastatin would decrease either lipogenesis or steroidogenesis or both in CaP cells. Simvastatin is a 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) inhibitor, which blocks synthesis of cholesterol, the building block of steroids/ androgens. It has also been postulated to down regulate SREBP in other metabolic disorders. It has been shown in this thesis, in LNCaP cells, that simvastatin inhibited and decreased insulin induced steroidogenesis and lipogenesis, respectively, but increased these pathways in the absence of insulin. Conversely, metformin, which activates AMP-activated protein kinase (AMPK) to shut down lipogenesis, cholesterol synthesis, and protein synthesis, highly suppresses both steroidogenesis and lipogenesis in the presence and absence of insulin. Lastly, because it has been demonstrated to increase steroidogenesis in other cell lines, and because the elucidation of any factors affecting steroidogenesis is important to understanding CaP, the effect of IGF2 on steroidogenesis in CaP cells was investigated. In patient samples, as men progress to CRPC, IGF2 mRNA and the protein levels of the receptors it may signal through are upregulated. It has also been demonstrated that IGF2 upregulates steroidogenic enzymes at both the mRNA and protein levels in LNCaP cells, increases intracellular and secreted steroid/androgen levels in LNCaPs to levels sufficient to stimulate the AR, and upregulated de novo steroidogenesis in LNCaPs and VCaPs. As well, inhibition of INSR and insulin-like growth factor 1 receptor (IGF1R), which IGF2 signals through, suggests that induction of steroidogenesis may be occurring predominantly through IGF1R. In summary, this project has illuminated for the first time that insulin is likely to play a large role in cancer progression, through upregulation of the steroidogenesis and lipogenesis pathways at the mRNA and protein levels, and production levels, and demonstrates a novel role for IGF-II in CaP progression through stimulation of steroidogenesis. It has also been demonstrated that metformin and simvastatin drugs may be useful in suppressing the insulin induction of these pathways. This project affirms the pathways by which ADT- induced metabolic syndrome may exacerbate CaP progression and strongly suggests that the monitoring and modulation of the metabolic state of CaP patients could have a strong impact on their therapeutic outcomes.

Problem-solving courts, therapeutic jurisprudence and the constitution : if two is company, is three a crowd?

Court costs, resource-intensive trials, booming prison populations and the obduracy of recidivism rates all present as ugly excesses of the criminal law adversarial paradigm. To combat these excesses, problem-solving courts have evolved with an edict to address the underlying issues that have caused an individual to commit a crime. When a judge seeks to help a problem-solving court participant deal with issues like addiction, mental health or poverty, they are performing a very different role to that of a judicial officer in the traditional court hierarchy. They are no longer the removed, independent arbiter — a problem-solving court judge steps into the ‘arena’ with the participant and makes active use of their judicial authority to assist in rehabilitation and positive behavioural change. Problem-solving court judges employing the principles of therapeutic jurisprudence appreciate that their interaction with participants can have therapeutic and anti-therapeutic consequences. This article will consider how the deployment of therapeutic measures (albeit with good intention) can lead to the behavioural manifestation of partiality and bias on the part of problem-solving court judges. Chapter III of the Commonwealth Constitution will then be analysed to highlight why the operation and functioning of problem solving courts may be deemed unconstitutional. Part IV of this article will explain how a problem-solving court judge who is not acting impartially or independently will potentially contravene the requirements of the Constitution. It will finally be suggested that judges who possess a high level of emotional intelligence will be the most successful in administering an independent and impartial problem solving court.

The effect of oral metformin on insulin sensitivity in insulin-resistant ponies

Metformin may be an effective therapeutic option for insulin-resistant (I-R) horses/ponies because, in humans, it reportedly enhances insulin sensitivity (SI) of peripheral tissues without stimulating insulin secretion. To determine the effect of metformin on insulin and glucose dynamics in I-R ponies, six ponies were studied in a cross-over design by Minimal Model analysis of a frequently-sampled intravenous glucose tolerance test (FSIGT). Metformin was administered at 15. mg/kg bodyweight (BW), orally, twice-daily, for 21. days to the metformin-treated group. The control group received a placebo. A FSIGT was conducted before and after treatment. The Minimal Model of glucose and insulin dynamics rendered indices describing SI, glucose effectiveness (Sg), acute insulin response to glucose (AIRg) and the disposition index (DI). The body condition score (BCS), BW and cresty neck score (CNS) were also assessed. There was no significant change in SI, Sg, AIRg, DI, BW, BCS or CNS in response to metformin, or over time in the control group. There were no measurable benefits of metformin on SI, consistent with recent work showing that the bioavailability of metformin in horses is poor, and chronic dosing may not achieve therapeutic blood concentrations. Alternatively, metformin may only be effective in obese ponies losing weight or with hyperglycaemia.

Direct fabrication as a patient-targeted therapeutic in a clinical environment

A paradigm shift is taking place in orthopaedic and reconstructive surgery. This transition from using medical devices and tissue grafts towards the utilization of a tissue engineering approach combines biodegradable scaffolds with cells and/or biological molecules in order to repair and/or regenerate tissues. One of the potential benefits offered by solid freeform fabrication (SFF) technologies is the ability to create such biodegradable scaffolds with highly reproducible architecture and compositional variation across the entire scaffold due to their tightly controlled computer-driven fabrication. Many of these biologically activated materials can induce bone formation at ectopic and orthotopic sites, but they have not yet gained widespread use due to several continuing limitations, including poor mechanical properties, difficulties in intraoperative handling, lack of porosity suitable for cellular and vascular infiltration, and suboptimal degradation characteristics. In this chapter, we define scaffold properties and attempt to provide some broad criteria and constraints for scaffold design and fabrication in combination with growth factors for bone engineering applications. Lastly, we comment on the current and future developments in the field, such as the functionalization of novel composite scaffolds with combinations of growth factors designed to promote cell attachment, cell survival, vascular ingrowth, and osteoinduction.

The process and patterns of combining the use of traditional Chinese medicine and Western medicine in Taiwanese people with cancer

Objective: The nature of contemporary cancer therapy means that patients are faced with difficult treatment decisions about surgery, chemotherapy and radiotherapy. For some, this process may also involve consideration of therapies that sit outside the biomedical approach to cancer treatment, in our research, traditional Chinese medicine (TCM). Thus, it is important to explore how cancer patients in Taiwan incorporate TCM into their cancer treatment journey. This paper aims to explore of the patterns of combining the use of TCM and Western medicine into cancer treatment journey in Taiwanese people with cancer. Methods: The sampling was purposive and the data collected through in-depth interviews. Data collection occurred over an eleven month. The research was grounded in the premises of symbolic interactionism and adopted the methods of grounded theory. Twenty four participants who were patients receiving cancer treatment were recruited from two health care settings in Taiwan. Results: The study findings suggest that perceptions of health and illness are mediated through ongoing interactions with different forms of therapy. The participants in this study had a clear focus on “process and patterns of using TCM and Western medicine”. Further, ‘different importance in Western medicine and TCM’, ‘taken for granted to use TCM’, ‘each has specialized skills in Western medicine and TCM’ and ‘different symptoms use different approaches (Western medicine or TCM)’ may explicit how the participants in this study see CAM and Western medicine. Conclusions/Implications for practice: The descriptive frame of the study suggests that TCM and Western medicine occupy quite distinct domains in terms of decision making over their use. People used TCM based on interpretations of the present and against a background of an enduring cultural legacy grounded in Chinese philosophical beliefs about health and healthcare. The increasingly popular term of 'integrative medicine' obscures the complex contexts of the patterns of use of both therapeutic modalities. It is this latter point that is worthy of further exploration.

A Process and Outcome Evaluation of the Under the Limit (UTL) Therapeutic Drink Driving Program for Recidivist and High Range Offenders

Drink driving is a major public health issue and this report examines the experiences of convicted offenders who participated in an established drink driving rehabilitation program Under the Limit (UTL). Course completers were surveyed at least three months after they had finished the 11-week UTL course. The aim of this study was to examine whether the UTL program reduced the level of alcohol consumption either directly as a result of participation in the UTL drink driving program or through increased use of community alcohol program by participants. The research involved a self-report outcome evaluation to determine whether the self-reported levels of alcohol use after the course had changed from the initial alcohol use reported by offenders. The findings are based on the responses of 30 drink-driving offenders who had completed the UTL program (response rate: 20%). While a process evaluation was proposed in the initial application, the low response rate meant that this follow up research was not feasible. The response rate was low for two reasons, it was difficult to: recruit participants who consented to follow up, and subsequently locate and survey those who had consented to involvement.

Managing the therapeutic relationship in online cognitive behavioural therapy for depression: Therapists' treatment of clients' contributions

This article examines how therapists and clients manage the therapeutic relationship in online psychotherapy. Our study focuses on early sessions of therapy involving 22 therapist-client pairs participating in online Cognitive Behavioural Therapy (CBT) for depression. Using Conversation Analysis (CA), we examine how therapists can orient to clients’ contributions, while also retaining control of the therapeutic trajectory. We report two practices that therapists can use, at their discretion, following clients’ responses to requests for information. The first, thanking, accepts clients’ responses, orienting to the neutral affective valence of those responses. The second, commiseration, orients to the negative affective valence of clients’ responses. We argue that both practices are a means by which therapists can simultaneously manage developing rapport, while also retaining control of the therapeutic process.

Psychotropic medication use in adolescents with intellectual disability living in the community

Purpose Information on the use of psychotropic medications in adolescents with intellectual disability is scant. Such information can guide interventions to improve psychotropic medication use in this population. We investigated the prevalence of, and factors associated with, psychotropic medication use in adolescents with intellectual disability in Australia who live in the community. Methods Cross-sectional data were obtained from adolescents with intellectual disability living in the community in South East Queensland, Australia, between February 2007 and September 2010. Self-reported information on medication use was extracted from a health screening tool. Demographic and medical data were collected through parent/caregiver surveys. Medications were classified according to the Anatomical Therapeutic Chemical classification system. Psychopathology was assessed using the Developmental Behaviour Checklist Short Form. Logistic regression analysis was used to assess the association of demographic and medical characteristics with psychotropic medication use. Results There were 176 participants (median age = 16 years, range = 11–19 years; 55% male). Psychotropics were used by 20% of participants. Psychostimulants were the commonest psychotropic class, used by 9% of participants. Multipsychotropic prescribing was not common with only seven participants using more than one psychotropic agent. After adjusting for potentially confounding variables, use of psychotropic medications was significantly associated with male gender (adjusted odds ratio = 3.6; 95% confidence interval = 1.3–9.5) and having major behaviour problems (3.1; 1.1–8.9). Conclusions Adolescents with intellectual disability use a wide range of psychotropic medications. Being male and having major behaviour problems are associated with the use of psychotropic medications. Research examining the rationale for psychotropic prescribing in this population is needed. Copyright © 2013 John Wiley & Sons, Ltd.

Controlling whole blood activation and resultant clot properties by carboxyl and alkyl functional groups on material surfaces : a possible therapeutic approach for enhancing bone healing

Most research virtually ignores the important role of a blood clot in supporting bone healing. In this study, we investigated the effects of surface functional groups carboxyl and alkyl on whole blood coagulation, complement activation and blood clot formation. We synthesised and tested a series of materials with different ratios of carboxyl (–COOH) and alkyl (–CH3, –CH2CH3 and –(CH2)3CH3) groups. We found that surfaces with –COOH/–(CH2)3CH3 induced a faster coagulation activation than those with –COOH/– CH3 and –CH2CH3, regardless of the –COOH ratios. An increase in –COOH ratios on –COOH/–CH3 and –CH2CH3 surfaces decreased the rate of coagulation activation. The pattern of complement activation was entirely similar to that of surface-induced coagulation. All material coated surfaces resulted in clots with thicker fibrin in a denser network at the clot/material interface and a significantly slower initial fibrinolysis when compared to uncoated glass surfaces. The amounts of platelet-derived growth factor-AB (PDGF-AB) and transforming growth factor-b (TGF-b1) released from an intact clot were higher than a lysed clot. The release of PDGF-AB was found to be correlated with the fibrin density. This study demonstrated that surface chemistry can significantly influence the activation of blood coagulation and complement system, resultant clot structure, susceptibility to fibrinolysis as well as release of growth factors, which are important factors determining the bone healing process.

The role of the arachidonic acid pathway in NSCLC development and progression : novel approaches for therapeutic intervention

Arachidonic acid metabolism through cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P-450 epoxygenase (EPOX) pathways is responsible for the formation of biologically active eicosanoids, including prostanoids, leukotrienes, hydroxyeicosatetraenoic acid, epoxyeicosatrienoic acid and hydroperoxyeicosatetraenoic acids. Altered eicosanoid expression levels are commonly observed during tumour development and progression of a range of malignancies, including non-small cell lung cancer (NSCLC). Arachidonic acid-derived eicosanoids affect a range of biological phenomena to modulate tumour processes such as cell growth, survival, angiogenesis, cell adhesion, invasion and migration and metastatic potential. Numerous studies have demonstrated that eicosanoids modulate NSCLC development and progression, while targeting these pathways has generally been shown to inhibit tumour growth/progression. Modulation of these arachidonic acid-derived pathways for the prevention and/or treatment of NSCLC has been the subject of significant interest over the past number of years, with a number of clinical trials examining the potential of COX and LOX inhibitors in combination with traditional and novel molecular approaches. However, results from these trials have been largely disappointing. Furthermore, enthusiasm for the use of selective COX-2 inhibitors for cancer prevention/treatment waned, due to their association with adverse cardiovascular events in chemoprevention trials. While COX and LOX targeting may both retain promise for NSCLC prevention and/or treatment, there is an urgent need to understand the downstream signalling mechanisms through which these and other arachidonic acid-derived signalling pathways mediate their effects on tumourigenesis. This will allow for development of safer and potentially more effective strategies for NSCLC prevention and/or treatment. Chemoprevention studies with PGI2 analogues have demonstrated considerable promise, while binding to/signalling through PGE2 receptors have also been the subject of interest for NSCLC treatment. In this chapter, the role of the eicosanoid signalling pathways in non-small cell lung cancer will be discussed. In particular, the effect of the eicosanoids on tumour cell proliferation, their roles in induction of cell death, effects on angiogenesis, migration, invasion and their regulation of the immune response will be assessed, with signal transduction pathways involved in these processes also discussed. Finally, novel approaches targeting these arachidonic acid-derived eicosanoids (using pharmacological or natural agents) for chemoprevention and/or treatment of NSCLC will be outlined. Elucidating the molecular mechanisms underlying the effects of specific or general arachidonic acid pathway modulators may lead to the design of biologically and pharmacologically targeted therapeutic strategies for NSCLC prevention/treatment, which may be used alone or in combination with conventional therapies.