Liver transplantation for HCV-associated liver cirrhosis: Predictors of outcomes in a population with significant genotype 3 and 4 distribution

End-stage liver disease associated with hepatitis C virus (HCV) infection is now the leading indication for liver transplantation in adults. However, reinfection of the graft is universal. We aimed to determine predictors of outcome of HCV-Iiver transplant recipients in the Australian and New Zealand communities. The following variables were analysed: demographic factors, coexistent pathology at the time of transplantation, HCV genotype, and donor age. Outcomes measures were: 1. mortality; 2. development of HCV-related complications, which were stage 3 or 4 fibrosis, or mortality from HCV-related graft failure, or both. Between January 1989 and December 30, 1999, 182 patients were transplanted for HCV-associated cirrhosis. The median follow-up period was 4 years (range, 0 to 13 years). Genotype data were available on 157 patients. The distribution of genotypes among the 157 patients was as follows: 36 (23%) genotype la, 30 (19%) genotype 1b, 4 (9%) genotype 1, 17 (11%) genotype 2, 41 (26%) genotype 3a, and 16 (10%) genotype 4. Eight (5%) patients were HCV-polymerase chain reaction (PCR)-negative (but HCV-antibody positive). Donor age and genotype 4 were associated with an increased risk of retransplantation or death (P < .001 and.05, respectively). Meanwhile, donor age, genotype 4, and pretransplant excess alcohol were risk factors for the development of HCV-related complications (P = .004, .008, and .02, respectively). In contrast, patients with genotype 3a were less likely to develop HCV-related complications (P = .05). In a population of HCV liver transplant recipients with a heterogeneous genotype distribution, donor age, and genotype 4, were predictors of a worse outcome, whereas genotype 3 was associated with a more favorable outcome.

Evaluation of clinically relevant changes in patient reported outcomes in knee and hip osteoarthritis: the minimal clinically important improvement

Background: In clinical trials, at the group level, results are usually reported as mean and standard deviation of the change in score, which is not meaningful for most readers. Objective: To determine the minimal clinically important improvement (MCII) of pain, patient's global assessment of disease activity, and functional impairment in patients with knee and hip osteoarthritis (OA). Methods: A prospective multicentre 4 week cohort study involving 1362 outpatients with knee or hip OA was carried out. Data on assessment of pain and patient's global assessment, measured on visual analogue scales, and functional impairment, measured on the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) function subscale, were collected at baseline and final visits. Patients assessed their response to treatment on a five point Likert scale at the final visit. An anchoring method based on the patient's opinion was used. The MCII was estimated in a subgroup of 814 patients ( 603 with knee OA, 211 with hip OA). Results: For knee and hip OA, MCII for absolute ( and relative) changes were, respectively, ( a) -19.9 mm (-40.8%) and -15.3 mm (-32.0%) for pain; ( b) -18.3 mm ( - 39.0%) and -15.2 mm ( -32.6%) for patient's global assessment; ( c) -9.1 ( -26.0%) and -7.9 ( -21.1%) for WOMAC function subscale score. The MCII is affected by the initial degree of severity of the symptoms but not by age, disease duration, or sex. Conclusion: Using criteria such as MCII in clinical trials would provide meaningful information which would help in interpreting the results by expressing them as a proportion of improved patients.

Evaluation of clinically relevant states in patient reported outcomes in knee and hip osteoarthritis: the patient acceptable symptom state

Background: The patient acceptable symptom state ( PASS) is the value beyond which patients can consider themselves well. This concept can help in interpreting results of clinical trials. Objective: To determine the PASS estimate for patients with knee and hip osteoarthritis (OA) by assessing pain, patient's global assessment of disease activity, and functional impairment. Methods: A 4 week prospective multicentre cohort study of 1362 outpatients with knee or hip OA was carried out. Data on assessment of pain and patient's global assessment of disease, measured on visual analogue scales, and functional impairment, measured on the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) function subscale, were collected at baseline and final visits. The patients assessed their satisfaction with their current state at the final visit. An anchoring method based on the patient's opinion was used. Results: For patients with knee and hip OA, the estimates of PASS were, respectively, 32.3 and 35.0 mm for pain, 32.0 and 34.6 mm for patient global assessment of disease activity, and 31.0 and 34.4 points for WOMAC function score. The PASS varied moderately across the tertiles of baseline scores but not across age, disease duration, or sex. Conclusion: The use of PASS in clinical trials would provide more meaningful results expressed as a proportion of patients in an acceptable symptom state.

Relationships between sirolimus dosing, concentration and outcomes in renal transplant recipients

Aim To explore relationships between sirolimus dosing, concentration and clinical outcomes. Methods Data were collected from 25 kidney transplant recipients (14 M/11 F), median 278 days after transplantation. Outcomes of interest were white blood cell (WBC) count, platelet (PLT) count, and haematocrit (HCT). A naive pooled data analysis was performed with outcomes dichotomized (Mann-Whitney U-tests). Results Several patients experienced at least one episode when WBC (n = 9), PLT (n = 12), or HCT (n = 21) fell below the lower limits of the normal range. WBC and HCT were significantly lower (P < 0.05) when sirolimus dose was greater than 10 mg day(-1), and sirolimus concentration greater than 12 mu g l(-1). No relationship was shown for PLT and dichotomized sirolimus dose or concentration. Conclusions Given this relationship between sirolimus concentration and effect, linked population pharmacokinetic-pharmacodynamic modelling using data from more renal transplant recipients should now be used to quantify the time course of these relationships to optimize dosing and minimize risk of these adverse outcomes.

Does health assessment improve health outcomes in Indigenous people? An RCT with 13 years of follow-up

Objective: To examine the impact of a multi-component health assessment on mortality and morbidity in Kimberley Aboriginal residents during a 13-year follow-up. Method. A population-based randomised controlled trial using linked hospital, cancer and death records to evaluate outcomes in 620 intervention and 6,736 control subjects. Results: The intervention group had a higher rate of first-time hospitalisation for any reason (IRR = 1.37; 95 % Cl 1.25-1.50), a higher rate of injury-related hospital episodes (IRR = 1.31; 95 % Cl 1.15-1.48) and a higher notification rate of alcohol-related cancers. There was a smaller difference in the rates of multiple hospitalisations (IRR = 1.14; 95 % Cl 0.751.74) and no improvement in overall mortality compared with controls (IRR = 1.08; 95 % Cl 0.91-1.29). Conclusions: There was no overall mortality benefit despite increased health service contact associated with the intervention. Implications: Although not influencing mortality rates, multi-component health assessment may result in a period of increased health service use in Aboriginal and Torres Strait Islander populations, thus constituting an 'intervention'. However, this should not be confused with systematic and sustained interventions and investment in community development to achieve better health outcomes.

Differential motor speech outcomes in children treated for mid-line cerebellar tumour

Primary objective: To investigate the nature of the motor speech impairments and dysarthria that can arise subsequent to treatment for childhood mid-line cerebellar tumours (CMCT). Research design: The motor speech ability of six cases of children with CMCT was analysed using perceptual and physiological measures and compared with that of a group of non-neurologically impaired children matched for age and sex. Main outcome and results: Three of the children with CMCT were perceived to exhibit dysarthric speech, while the remaining three were judged to have normal speech. The speech disorder in three of the children with CMCT was marked by deviances in prosody, articulation and phonation. The underlying pathophysiology was linked to cerebellar damage and expressed as difficulty in co-ordinating the motor speech musculature as required for speech production. These deficits were not identified in the three non-dysarthric children with CMCT. Conclusion: Differential motor speech outcomes occur for children treated for CMCT and these are discussed within the realm of possible mechanisms responsible for these differences. The need for further investigation of the risk factors for development of motor speech impairment in children treated for CMCT is also highlighted.

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.

Relations between coping and positive and negative outcomes in carers of persons with multiple sclerosis (MS)

This study examined relations between stress and coping predictors and negative and positive outcomes in MS caregiving. A total of 222 carers and their care-recipients completed questionnaires at Time 1 and three months later, Time 2 ( n = 155). Predictors included care-recipient characteristics ( age, time since diagnosis, course and life satisfaction), and Times 1 and 2 carer problems, stress appraisal and coping. Dependent variables were Time 2 negative ( anxiety, depression) and positive outcomes ( life satisfaction, positive affect, benefits). Regressions indicated that, overall, the hypothesised direct effects of stress appraisal and coping strategies on positive and negative outcomes were supported. The hypothesised stress-buffering effects of positive reframing coping were also supported. All but one of the coping strategies were related to both positive and negative outcomes; specifically, practical assistance coping emerged as a unique predictor of distress. Of the model predictors, care-recipient life satisfaction emerged as the strongest and most consistent predictor of both positive and negative outcomes except benefit finding. Findings support the role of care-recipient characteristics and the carer's appraisal and coping processes in shaping both positive and negative outcomes. The guiding framework and findings have the potential to inform interventions designed to promote well-being in carers.

Impact of Australia's Better Outcomes in Mental Health Care program on psychologists

The aim of this paper was to consider the impact on psychologists of one component of the Australian Government's Better Outcomes in Mental Health Care (BOiMHC) program, namely the Access to Allied Psychological Services (ATAPS) component. This supports psychologists and general practitioners (GPs) to work together to provide optimal mental health care, via 102 projects being conducted by Divisions of General Practice. The paper was informed by data from five sources: a project-based minimum dataset; local project evaluation reports; a forum; a survey of projects: and a survey of Australian Psychological Society (APS) members. Taken together, the data from these sources showed that a significant number of psychologists are providing services through the projects, and the majority are finding it a positive and professionally rewarding experience. There is considerable variability regarding models of retaining, locating and referring to psychologists, and there are pros and cons associated with each. The major problem identified by psychologists is the level of remuneration. BOiMHC is currently moving into a new phase of continuation and expansion, and consideration was given to whether the data point to any changes that could be made to the ATAPS projects during this period of transition. In the main, the data suggest that the status quo should be retained, but the issue of remuneration must be addressed.

No more free beer tomorrow? Economic policy and outcomes in Australia and New Zealand since 1984

There are no controlled experiments in macroeconomic policy, nor in systematic programs of microeconomic reform, but a comparison between New Zealand and Australia over the period since 1984 provides as close an approach to such an experiment as is ever likely to be possible. From quite similar starting points the two countries pursued liberal reform programs that differed sharply, mainly as a result of exogenous differences in constitutional structures and the personal styles of the central actors. Australia followed a more cautious, piecemeal, consensus-based approach, whereas New Zealand, in contrast, adopted a radical, rapid, 'purist' platform. The NZ reform package was generally seen by contemporary commentators as representing a 'textbook' model for best practice reform. However, Australia since 1984 has performed much better than New Zealand, whose per capita GDP growth indeed ranked at or near the bottom of the OECD. In this paper, we assess a variety of explanations for the divergences in policies and outcomes.

Models of psychological service provision under Australia's better outcomes in mental health care program

The Access to Allied Psychological Services component of Australia's Better Outcomes in Mental Health Care program enables eligible general practitioners to refer consumers to allied health professionals for affordable, evidence-based mental health care, via 108 projects conducted by Divisions of General Practice. The current study profiled the models of service delivery across these projects, and examined whether particular models were associated with differential levels of access to services. We found: 76% of projects were retaining their allied health professionals under contract, 28% via direct employment, and 7% some other way; Allied health professionals were providing services from GPs' rooms in 63% of projects, from their own rooms in 63%, from a third location in 42%; and The referral mechanism of choice was direct referral in 51% of projects, a voucher system in 27%, a brokerage system in 24%, and a register system in 25%. Many of these models were being used in combination. No model was predictive of differential levels of access, suggesting that the approach of adapting models to the local context is proving successful.