Toward better outcomes with tacrolimus therapy: Population pharmacokinetics and individualized dosage prediction in adult liver transplantation

Patient outcomes in transplantation would improve if dosing of immunosuppressive agents was individualized. The aim of this study is to develop a population pharmacokinetic model of tacrolimus in adult liver transplant recipients and test this model in individualizing therapy. Population analysis was performed on data from 68 patients. Estimates were sought for apparent clearance (CL/F) and apparent volume of distribution (V/F) using the nonlinear mixed effects model program (NONMEM). Factors screened for influence on these parameters were weight, age, sex, transplant type, biliary reconstructive procedure, postoperative day, days of therapy, liver function test results, creatinine clearance, hematocrit, corticosteroid dose, and interacting drugs. The predictive performance of the developed model was evaluated through Bayesian forecasting in an independent cohort of 36 patients. No linear correlation existed between tacrolimus dosage and trough concentration (r(2) = 0.005). Mean individual Bayesian estimates for CL/F and V/F were 26.5 8.2 (SD) L/hr and 399 +/- 185 L, respectively. CL/F was greater in patients with normal liver function. V/F increased with patient weight. CL/F decreased with increasing hematocrit. Based on the derived model, a 70-kg patient with an aspartate aminotransferase (AST) level less than 70 U/L would require a tacrolimus dose of 4.7 mg twice daily to achieve a steady-state trough concentration of 10 ng/mL. A 50-kg patient with an AST level greater than 70 U/L would require a dose of 2.6 mg. Marked interindividual variability (43% to 93%) and residual random error (3.3 ng/mL) were observed. Predictions made using the final model were reasonably nonbiased (0.56 ng/mL), but imprecise (4.8 ng/mL). Pharmacokinetic information obtained will assist in tacrolimus dosing; however, further investigation into reasons for the pharmacokinetic variability of tacrolimus is required.

Literacy skills of adults with intellectual disability in community-based day programs

A brief narrative description of the journal article, document, or resource. There is limited information available related to the literacy skills of adults with intellectual disabilities. In this project, information was collected about the contexts, current practices, and clients' abilities in literacy in two community-based disability service programs. Individual assessments were undertaken to collect details of the current literacy levels of adults with intellectual disabilities in day program settings. These assessments focused on receptive language, reading at the letter, word and sentence level, writing vocabulary and connected text, and literacy preferences. Audits were also conducted related to the provision of opportunities for clients accessing these services to engage with literacy including environmental print. Structured day program activities were observed to gather information about current literacy teaching and learning. Implications of the research findings and suggestions for provision of literacy education in these settings are discusse

Paediatric telecardiology services in Queensland: a review of three years' experience

Videoconferencing at 384 kbit/s for the transmission of echocardiograms has proved useful for the assessment of children with suspected cardiac disease, in regional areas of Queensland. A retrospective review of patient and management outcomes was conducted on cardiac teleconsultations performed at two regional hospitals during the period November 2000 to February 2004, inclusive. There were 106 echo studies. A subset of 72 cardiac teleconsultations performed between May 2001 and February 2004 was reviewed in detail. The median age of patients at the time of consultation was 3 months (range 1 day-17 years). Sixteen per cent of teleconsultations were classified as urgent and were conducted on the same day as referral. Following the videoconference, 90% of patients could be managed locally and reviewed by the paediatrician or visiting paediatric cardiologist during an outreach clinic. Six children (8%) had significant cardiac lesions that were initially managed locally, with subsequent elective transfer at the appropriate time for treatment. Only one child (1%) required urgent transfer to the tertiary centre for specialist care and surgery. Telecardiology was effective in accurately identifying congenital heart disease. Paediatric telecardiology is an evolving modality of assessment and communication, and is likely to result in continued improvements in patient care, patient outcomes and parental satisfaction, in provincial centres removed from the tertiary cardiac centre.

Complexity, conflict and uncertainty: Issues in collaboration between child protection and mental health services

This paper provides an analysis of data from a state-wide survey of statutory child protection workers, adult mental health workers, and child mental health workers. Respondents provided details of their experience of collaboration on cases where a parent had mental health problems and there were serious child protection concerns. The survey was conducted as part of a large mixed-method research project on developing best practice at the intersection of child protection and mental health services. Descriptions of 300 cases were provided by 122 respondents. Analyses revealed that a great deal of collaboration occur-red across a wide range of government and community-based agencies; that collaborative processes were often positive and rewarding for workers; and that collaboration was most difficult when the nature of the parental mental illness or the need for child protection intervention was contested. The difficulties experienced included communication, role clarity, competing primary focus, contested parental mental health needs, contested child protection needs, and resources. (C) 2004 Elsevier Ltd. All rights reserved.

Adult mental health needs and expenditure in Australia

Background Relatively little international work has examined whether mental health resource allocation matches need. This study aimed to determine whether adult mental health resources in Australia are being distributed equitably. Method Individual measures of need were extrapolated to Australian Areas, and Area-based proxies of need were considered. Particular attention was paid to the prevalence of mental health problems, since this is arguably the most objective measure of need. The extent to which these measures predicted public sector, private sector and total adult mental health expenditure at an Area level was examined. Results In the public sector, 41.6% of expenditure variation was explained by the prevalence of affective disorders, personality disorders, cognitive impairment and psychosis, as well as the Area's level of economic resources and State/Territory effects. In the private sector, 72.4% of expenditure variation was explained by service use and State/Territory effects (with an alternative model incorporating service use and State/Territory supply of private psychiatrists explaining 69.4% of expenditure variation). A relatively high proportion (58.7%) of total expenditure variation could be explained by service utilisation and State/Territory effects. Conclusions For services to be delivered equitably, the majority of variation in expenditure would have to be accounted for by appropriate measures of need. The best model for public sector expenditure included an appropriate measure of need but had relatively poor explanatory power. The models for private sector and total expenditure had greater explanatory power, but relied on less appropriate measures of need. It is concluded that mental health services in Australia are not yet being delivered equitably.

Why is Coccidoxenoides perminutus, a mealybug parasitoid, ineffective as a biocontrol agent - Inaccurate measures of parasitism or low adult survival?

Coccidoxenoides perminutus achieves only low levels of parasitism of its host Planococcus citri in southeast Queensland citrus. Two possible causes were investigated. Adult survival under natural conditions was assessed to determine whether providing adult food sources could enhance survival. Behavioural changes of hosts, induced by C perminutus parasitism, was also investigated to establish if parasitised P. citri move from their feeding site to seek protected shelters some distance away and are thus not accounted for in field assessments of parasitism rates. Unparasitised mealybugs placed in the field for two periods were retrieved before the effects of parasitism were manifested and parasitism rates were still low (0.3% at 5 days and 1.2% at 10 days). Levels of locomotion of P. citri exposed to C perminutus were compared with those of unexposed ones. Parasitised mealybugs, regardless of instar, undergo behavioural changes. In comparison to unparasitised controls, the mealybugs become highly active 7-14 days after exposure to wasps. All parasitised mealybugs undergo physical changes, their body becomes cylindrical, their legs go so rigid that the mealybugs become immobile, and this signifies the typical mummy appearance. All mealybugs that became mummies eventually fell from the host lemon fruit because of impaired locomotion and were caught on sticky traps that had been placed beneath the lemons. Consequently, their final site of mummification was not established. C perminutus adults provided with nectar or honey survived longer (about 5 days) in the field than those without food (about a day). Nectar from two plant species, Alpinia zerumbet and Datura candida, proved to be good sources of food for the adult wasps, and were comparable in quality to honey. The low level of parasitism achieved by C perminutus in southeast Queensland citrus thus appears to be a consequence of the short adult life and the negative effects of a harsh environment. Provision of a suitable food source (e.g., nectar) may well enhance levels of parasitism in the field. (c) 2005 Elsevier Inc. All rights reserved.

The psychoeducation needs of parents who have an adult son or daughter with a mental illness

Since deinstitutionalisation, parents of adults with mental disorders are increasingly utilised as a resource for their relatives’ care. This study used a general phenomenological perspective to capture people’s experiences. Semi-structured in-depth interviews were conducted with eight parents who were members of the Schizophrenia Fellowship of Southern Queensland to explore their perceptions of their psychoeducation needs. The themes that emerged included the usefulness of past experiences with psychoeducation, educational needs, barriers to accessing information and support, and other unmet carer needs, including the need for managing stress and emotional needs, recognition and inclusion of family members in decision-making, and negotiating the best care for their family member within the health care system. This study adds to an increasing body of knowledge that advocates for the greater inclusion and involvement of families in the care and treatment of their relatives. Further research into the needs of families, in particular barriers and supports in accessing information and services, is recommended.

Relationships of tacrolimus pharmacokinetic measures and adverse outcomes in stable adult liver transplant recipients

Alternative measures to trough concentrations [non-trough concentrations and limited area under the concentration-time curve (AUC)] have been shown to better predict tacrolimus AUC. The aim of this study was to determine if these are also better predictors of adverse outcomes in long term liver transplant recipients. The associations between tacrolimus trough concentrations (C-0), non-trough concentrations (C-1, C-2, C-4, C-6/8), and AUC(0-12) and the occurrence of hypertension, hyperkalaemia, hyperglycaemia and nephrotoxicity were assessed in 34 clinically stable liver transplant patients. The most common adverse outcome was hypertension, prevalence of 36%. Hyperkalaemia and hyperglycaemia had a prevalence of 21% and 13%, respectively. A sequential population pharmacokinetic/pharmacodynamic approach was implemented. No significant association between predicted C-0, C-1, C-2, C-4, C-6/8 or AUC(0-12) and adverse effects could be found. Tacrolimus concentrations and AUC measures were in the same range in patients with and without adverse effects. Measures reported to provide benefit, preventing graft rejection and minimizing acute adverse effects in the early post-transplant period, were not able to predict adverse effects in stable adult liver recipients whose trough concentrations were maintained in the notional target range.

Routine measurement of outcomes in Australia's public sector mental health services

OBJECTIVE: This paper describes the Australian experience to date with a national 'roll out' of routine outcome measurement in public sector mental health services. METHODS: Consultations were held with 123 stakeholders representing a range of roles. RESULTS: Australia has made an impressive start to nationally implementing routine outcome measurement in mental health services, although it still has a long way to go. All States/Territories have established data collection systems, although some are more streamlined than others. Significant numbers of clinicians and managers have been trained in the use of routine outcome measures, and thought is now being given to ongoing training strategies. Outcome measurement is now occurring 'on the ground'; all States/Territories will be reporting data for 2003-04, and a number have been doing so for several years. Having said this, there is considerable variability regarding data coverage, completeness and compliance. Some States/Territories have gone to considerable lengths to 'embed' outcome measurement in day-to-day practice. To date, reporting of outcome data has largely been limited to reports profiling individual consumers and/or aggregate reports that focus on compliance and data quality issues, although a few States/Territories have begun to turn their attention to producing aggregate reports of consumers by clinician, team or service. CONCLUSION: Routine outcome measurement is possible if it is supported by a co-ordinated, strategic approach and strong leadership, and there is commitment from clinicians and managers. The Australian experience can provide lessons for other countries.

The effect of music on preoperative anxiety in day surgery

Aim. This paper reports a study to test the hypothesis that day surgery patients who listen to music during their preoperative wait will have statistically significantly lower levels of anxiety than patients who receive routine care. Background. Although previous day surgery research suggests that music effectively reduces preoperative anxiety, methodological issues limit the generalizability of results. Methods. In early 2004, a randomized controlled trial design was conducted to assess anxiety before and after listening to patient preferred music. Participants were allocated to an intervention (n = 60), placebo (n = 60) or control group (n = 60). Pre- and post-test measures of anxiety were carried out using the State-Trait Anxiety Inventory. Results. Music statistically significantly reduced the state anxiety level of the music (intervention) group. No relationships were found between socio-demographic or clinical variables such as gender or type of surgery. Conclusion. The findings support the use of music as an independent nursing intervention for preoperative anxiety in patients having day surgery.

The effect of admission physiological variables on 30 day outcome after stroke

Introduction. Potentially modifiable physiological variables may influence stroke prognosis but their independence from modifiable factors remains unclear. Methods. Admission physiological measures (blood pressure, heart rate, temperature and blood glucose) and other unmodifiable factors were recorded from patients presenting within 48 hours of stroke. These variables were compared with the outcomes of death and death or dependency at 30 days in multivariate statistical models. Results. In the 186 patients included in the study, age, atrial fibrillation and the National Institutes of Health Stroke Score were identified as unmodifiable factors independently associated with death and death or dependency. After adjusting for these factors, none of the physiological variables were independently associated with death, while only diastolic blood pressure (DBP) >= 90 mmHg was associated with death or dependency at 30 days (p = 0.02). Conclusions. Except for elevated DBP, we found no independent associations between admission physiology and outcome at 30 days in an unselected stroke cohort. Future studies should look for associations in subgroups, or by analysing serial changes in physiology during the early post-stroke period.

Interagency collaboration between child protection and mental health services: Practices, attitudes and barriers

Objective: The aim of this paper is to examine some of the factors that facilitate and hinder interagency collaboration between child protection services and mental health services in cases where there is a parent with a mental illness and there are protection concerns for the child(ren). The paper reports on agency practices, worker attitudes and experiences, and barriers to effective collaboration. Method: A self-administered, cross-sectional survey was developed and distributed via direct mail or via line supervisors to workers in statutory child protection services, adult mental health services, child and youth mental health services, and Suspected Child Abuse and Neglect (SCAN) Teams. There were 232 completed questionnaires returned, with an overall response rate of 21%. Thirty-eight percent of respondents were statutory child protection workers. 39% were adult mental health workers, 16% were child and youth mental health workers, and 4% were SCAN Team medical officers (with 3% missing data). Results: Analysis revealed that workers were engaging in a moderate amount of interagency contact, but that they were unhappy with the support provided by their agency. Principle components analysis and multivariate analysis of variance (MANOVA) on items assessing attitudes toward other workers identified four factors, which differed in rates of endorsement: inadequate training, positive regard for child protection workers, positive regard for mental health workers, and mutual mistrust (from highest to lowest level of endorsement). The same procedure identified the relative endorsement of five factors extracted from items about potential barriers: inadequate resources, confidentiality, gaps in interagency processes, unrealistic expectations, and professional knowledge domains and boundaries. Conclusions: Mental health and child protection professionals believe that collaborative practice is necessary; however, their efforts are hindered by a lack of supportive structures and practices at the organizational level. (c) 2005 Published by Elsevier Ltd.

Inhibitors of cyclo-oxygenase-2 and secretory phospholipase A2 preserve bone architecture following ovariectomy in adult rats

Epidemiological evidence and in vitro data suggest that COX-2 is a key regulator of accelerated remodeling. Accelerated states of osteoblast and osteoclast activity are regulated by prostaglandins in vitro, but experimental evidence for specific roles of cyclooxygenase-2 (COX-2) and secretory phospholipase A(2) (sPLA(2)) in activated states of remodeling in vivo is lacking. The aim of this study was to determine the effect of specific inhibitors of sPLA(2)-IIa and COX-2 on bone remodeling activated by estrogen deficiency in adult female rats. One hundred and twenty-four adult female Wistar rats were ovariectomized (OVX) or sham-operated. Rats commenced treatment 14 days after surgery with either vehicle, a COX-2 inhibitor (DFU at 0.02 mg/kg/day and 2.0 mg/kg/day) or a sPLA(2)-group-IIa inhibitor (KH064 at 0.4 mg/kg/day and 4.0 mg/kg/day). Treatment continued daily until rats were sacrificed at 70 days or 98 days post-OVX. The right tibiae were harvested, fixed and embedded in methylmethacrylate for structural histomorphometric bone analysis at the proximal tibial metaphysis. The specific COX-2 or sPLA(2) inhibitors prevented ovariectomy-induced (OVX-induced) decreases in trabecular connectivity (P < 0.05); suppressed the acceleration of bone resorption; and maintained bone turnover at SHAM levels following OVX in the rat. The sPLA2 inhibitor significantly suppressed increases in osteoclast surface induced by OVX (P < 0.05), while the effect of COX-2 inhibition was less marked. These findings demonstrate that inhibitors of COX-2 and sPLA(2)-IIa can effectively suppress OVX-induced bone loss in the adult rat by conserving trabecular bone mass and architecture through reduced bone remodeling and decreased resorptive activity. Moreover, we report an important role of sPLA(2)-IIa in osteoclastogenesis that may be independent of the COX-2 metabolic pathway in the OVX rat in vivo. (c) 2006 Elsevier Inc. All rights reserved.

Genetic analyses of DSM-IV nicotine withdrawal in adult twins

Background. We examined whether there are genetic influences on nicotine withdrawal. and whether there are genetic factors specific to nicotine withdrawal, after controlling for factors responsible for risk of progression beyond experimentation with cigarettes and for quantity smoked (average number of cigarettes per day at peak lifetime use). Method. Epidemiologic and genetic analyses were conducted using telephone diagnostic interview data from Young adult Australian twins reporting any cigarette use (3026 women. 2553 men: mean age 30 years). Results. Genetic analysis of the eight symptoms of DSM-IV nicotine withdrawal suggests heritability is intermediate for most symptoms (26-43%). and Similar in men and women. The exceptions were depressed mood upon withdrawal. which had stronger additive genetic influences in men (53%) compared to worrien (29%). and decreased heart rate. which had low heritability (9%). Although prevalence rates were substantlally lower for DSM-IV nicotine withdrawal syndrome (15-9%), which requires impairment. than for the DSM-IV nicotine dependence withdrawal criterion (43.6%), heritability was similar for both measures: as high as 47%. Genetic modeling of smoking more than 1 or 2 cigarettes lifetime ('progression'). qualtity smoked and nicotine withdrawal found significant genetic overlap across all three components of nicotine use/dependence (genetic correlations = 0.53-0.76). Controlling for factors associated with risk of cigarette smoking beyond experimentation and quantity smoked, evidence for genetic influences specific to nicotine withdrawal (up to 23% of total variance) remained. Conclusions. Our results suggest that at least some individuals become 'hooked' or progress in the smoking habit, in part, because of it vulnerability to nicotine withdrawal.