High-Risk Merkel Cell Carcinoma of the Skin Treated With Synchronous Carboplatin/Etoposide and Radiation: A Trans-Tasman Radiation Oncology Group Study-TROG 96:07

Purpose: The effectiveness of synchronous carboplatin, etoposide, and radiation therapy was prospectively assessed in a group of patients with high-risk Merkel cell carcinoma (MCC) of the skin. Patients and Methods: Patients were eligible if they had disease localized to the primary site and nodes, and were required to have at least one of the following high risk features: recurrence after initial therapy, involved nodes, primary tumor size greater than 1 cm, gross residual disease after surgery, or occult primary with nodes. Radiation was delivered to the primary site and nodes to a dose of 50 Gy in 25 fractions over 5 weeks and synchronous carboplatin (area under the curve, 4.5) and intravenous etoposide 80 mg/m(2) days 1 to 3 was given in weeks 1, 4, 7, and 10. The median age of the group was 67 (range, 43-86) years, and there were 39 males and 14 females. Involved nodes (stage II) were present in 33 cases (62%). The sites involved were head and neck (22 patients), occult primary (13 patients), upper limb (eight patients), lower limb (eight patients), and trunk (two patients). Results: Fifty-three patients were entered between 1996 and 2001. The median potential follow-up was 48 months. There were no treatment related deaths. The 3-year overall survival, locoregional control, and distant control were 76%, 75%, and 76%, respectively. Tumor site and the presence of nodes were factors that were predictive for local control and survival. Multivariate analysis indicated that the major factor influencing survival was the presence of nodes; however, this was not a significant factor in locoregional control. Conclusion: High levels of locoregional control and survival have been achieved with the addition of chemotherapy to radiation treatment for high-risk MCC of the skin. The role of chemoradiotherapy for high-risk MCC warrants further investigation. (C) 2003 by American Society of Clinical Oncology.

What the family brings: Gathering evidence for strengths-based work

Families attending child and adolescent mental health (CAMH) services are often assumed to have problems in key areas such as communication, belonging/acceptance and problem-solving. Family therapy is often directed towards addressing these difficulties. With increasing emphasis in family therapy and human services fields over the last decade on identifying and building from strengths, a different starting point has been advocated. This paper describes a large survey of the self-reported pre-therapy functioning of children and families using a public CAMH service (n = 416). Before commencing family therapy parents identified family strengths across a range of key areas, despite the burden of caring for children with moderate to severe mental health problems. This evidence supports theoretical and clinical work that advocates a strengths perspective, and highlights how resilience framed in family (and social) rather than individual terms enables a greater appreciation of how strengths may be harnessed in therapeutic work.

Electronic patient records: Achieving best practice in information transfer between hospital and community providers - an integration success story

Effective healthcare integration is underpinned by clinical information transfer that is timely, legible and relevant. The aim of this study was to describe and evaluate a method for best practice information exchange. This was achieved based on the generic Mater integration methodology. Using this model the Mater Health Services have increased effective community fax discharge from 34% in 1999 to 86% in 2002. These results were predicated on applied information technology excellence involving the development of the Mater Electronic Health Referral Summary and effective change management methodology, which included addressing issues around patient consent, engaging clinicians, provision of timely and appropriate education and training, executive leadership and commitment and adequate resourcing. The challenge in achieving best practice information transfer is not solely in the technology but also in implementing the change process and engaging clinicians. General practitioners valued the intervention highly. Hospital and community providers now have an inexpensive, effective product for critical information exchange in a timely and relevant manner, enhancing the quality and safety of patient care.

The influence of financial participation and participation in decision-making on employee job attitudes

This study investigates the direct and indirect effects of financial participation (FP) and participation in decision-making (PDM) on employee job attitudes. The central premise is that both financial participation and participation in decision-making have effects on job attitudes, such as integration, involvement and commitment, perceived pay equity, performance-reward contingencies, satisfaction and motivation. After reviewing the theoretical and empirical literature and testing two theoretical frameworks, developed by Long (1978a) and Florkowski ( 1989), a new model was constructed to consider a combined effects of both FP and PDM, herein referred to as employee participation (EP). The underpinning of the model is based on the assumption that both ( a) the combination of financial participation and participation in decision-making ('employee participation'), and (b) participation in decision-making produce favourable effects on employee job attitudes. The test of the new model showed that employee participation does not produce more favourable effects on employee job attitudes, than does participation in decision-making on its own. The data were gathered from a questionnaire study administered in a large British retail organization that operates two types of ownership schemes - profit-sharing and SAYE schemes.

Trinity, love, and pastorial mirroring

This paper focuses on the positive mirroring (admiration, acceptance, and approval) that Heinz Kohut posits as the primary healing agency in work with clients with narcissistic personality disorder. Donald Capps has demonstrated the pastoral significance of Kohut's theory. Capps' work is extended through an analysis of the role love plays in mirroring. It is suggested that mirror love has agapic, erotic, and philial elements. The loving action of the counselor is viewed as an image of the love of the triune God.

Continuous infusion of ticarcillin-clavulanate for home treatment of serious infections: clinical efficacy, safety, pharmacokinetics and pharmacodynamics

Continuous infusion (CI) ticarcillin-clavulanate is a potential therapeutic improvement over conventional intermittent dosing because the major pharmacodynamic (PD) predictor of efficacy of beta-lactams is the time that free drug levels exceed the MIC. This study incorporated a 6-year retrospective arm evaluating efficacy and safety of CI ticarcillin-clavulanate in the home treatment of serious infections and a prospective arm additionally evaluating pharmacokinetics (PK) and PD. In the prospective arm, steady-state serum ticarcillin and clavulanate levels and MIC testing of significant pathogens were performed. One hundred and twelve patients (median age, 56 years) were treated with a CI dose of 9.3-12.4 g/day and mean CI duration of 18.0 days. Infections treated included osteomyelitis (50 patients), septic arthritis (6), cellulitis (17), pulmonary infections (12), febrile neutropenia (7), vascular infections (7), intra-abdominal infections (2), and Gram-negative endocarditis (2); 91/112 (81%) of patients were cured, 14 (13%) had partial response and 7 (6%) failed therapy. Nine patients had PICC line complications and five patients had drug adverse events. Eighteen patients had prospective PK/PD assessment although only four patients had sufficient data for a full PK/PD evaluation (both serum steady-state drug levels and ticarcillin and clavulanate MICs from a bacteriological isolate), as this was difficult to obtain in home-based patients, particularly as serum clavulanate levels were found to deteriorate rapidly on storage. Three of four patients with matched PK/PD assessment had free drug levels exceeding the MIC of the pathogen. Home Cl of ticarcillin-clavulanate is a safe, effective, convenient and practical therapy and is a therapeutic advance over traditional intermittent dosing when used in the home setting. (c) 2005 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Caregiver burden, time spent caring and health status in the first 12 months following stroke

Objective: To quantify time caring, burden and health status in carers of stroke patients after discharge from rehabilitation; to identify the potentially modifiable sociodemographic and clinical characteristics associated with these outcomes. Methods: Patients and carers prospectively interviewed 6 (n = 71) and 12 (n = 57) months after discharge. Relationships of carer and patient variables with burden, health status and time analysed by Gaussian and Poisson regression. Results: Carers showed considerable burden at 6 and 12 months. Carers spent 4.6 and 3.6 hours per day assisting patients with daily activities at 6 and 12 months, respectively. Improved patient motor and cognitive function were associated with reductions of up to 20 minutes per day in time spent in daily activities. Better patient mental health and cognitive function were associated with better carer mental health. Conclusions: Potentially modifiable factors such as these may be able to be targeted by caregiver training, support and education programmes and outpatient therapy for patients.

Crisis management and risk communication: Why the food industry must get it right

There is public unease about food-related issues including food additives, food poisoning bacteria and GM ingredients. The public wants evidence of no risks, but all regulators can ever offer is no evidence of risk or evidence of a very small risk. The situation is complex because experts and non-experts can perceive the same risk in vastly different ways. The way in which the food industry manages crises and communicates risks will determine the public acceptance and success of new technologies such as GM foods and nanomaterials. There is a need for the food industry (including regulators and scientific experts) to sharpen up their risk communication skills to ensure that technical innovations are accepted by consumers, and crises such as food recalls do not undermine the public's confidence in the food industry. The AIFST has a key role to play in driving the risk communication process and allaying public unease about food-related issues.

Does chemotherapy improve survival in high-risk Stage I and II Merkel cell carcinoma of the skin?

Purpose: The effectiveness of synchronous carboplatin, etoposide, and radiation therapy in improving survival was evaluated by comparison of a matched set of historic control subjects with patients treated in a prospective Phase II study that used synchronous chemotherapy and radiation and adjuvant chemotherapy. Patients and Methods: Patients were included in the analysis if they had disease localized to the primary site and nodes, and they were required to have at least one of the following high-risk features: recurrence after initial therapy, involved nodes, primary size greater than 1 cm, or gross residual disease after surgery. All patients who received chemotherapy were treated in a standardized fashion as part of a Phase II study (Trans-Tasman Radiation Oncology Group TROG 96:07) from 1997 to 2001. Radiation was delivered to the primary site and nodes to a dose of 50 Gy in 25 fractions over 5 weeks, and synchronous carboplatin (AUC 4.5) and etoposide, 80 mg/m(2) i.v. on Days 1 to 3, were given in Weeks 1, 4, 7, and 10. The historic group represents a single institution's experience from 1988 to 1996 and was treated with surgery and radiation alone, and patients were included if they fulfilled the eligibility criteria of TROG 96:07. Patients with occult cutaneous disease were not included for the purpose of this analysis. Because of imbalances in the prognostic variables between the two treatment groups, comparisons were made by application of Cox's proportional hazard modeling. Overall survival, disease-specific survival, locoregional control, and distant control were used as endpoints for the study. Results: Of the 102 patients who had high-risk Stage I and II disease, 40 were treated with chemotherapy (TROG 96:07) and 62 were treated without chemotherapy (historic control subjects). When Cox's proportional hazards modeling was applied, the only significant factors for overall survival were recurrent disease, age, and the presence of residual disease. For disease-specific survival, recurrent disease was the only significant factor. Primary site on the lower limb had an adverse effect on locoregional control. For distant control, the only significant factor was residual disease. Conclusions: The multivariate analysis suggests chemotherapy has no effect on survival, but because of the wide confidence limits, a chemotherapy effect cannot be excluded. A study of this size is inadequately powered to detect small improvements in survival, and a larger randomized study remains the only way to truly confirm whether chemotherapy improves the results in high-risk MCC. (c) 2006 Elsevier Inc.

Engineered T cell receptors and their potential in molecular medicine

T cell receptors are among the most specific biological structures found in nature and are therefore excellent candidates for the molecular targeting of antigen. It is becoming increasingly apparent that common sets of T cell receptors are frequently used in humans to combat pathogen and cancer derived threats. Given that many of these conserved T cell receptors have high affinity for their target ligands, there is potential to amass virtual banks of “off-the-shelf” receptors for use in a wide range of immunotherapeutic strategies. Additionally, such T cell receptors could become basic blueprints for artificial enhancement through mutagenesis, thereby creating an even better 3-dimensional fit for their cognate targets. Indeed, preliminary approaches using both “natural” and “supernatural” T cell receptors have shown promise in treating autoimmunity and malignancy. This review will discuss these studies and other approaches through which T cell receptors can be exploited in immunodiagnostics, pathogen control and gene therapy.

Relations between social support, appraisal and coping and both positive and negative outcomes for children of a parent with multiple sclerosis and comparisons with children of healthy parents

Objective: To examine adjustment in children of a parent with multiple sclerosis within a stress and coping framework and compare them with those who have 'healthy' parents. Subjects: A total of 193 participants between 10 and 25 years completed questionnaires; 48 youngsters who had a parent with multiple sclerosis and 145 youngsters who reported that they did not have a parent with an illness or disability. Method: A questionnaire survey methodology was used. Variable sets included caregiving context (e.g. additional parental illness, family responsibilities, parental functional impairment, choice in helping), social support (network size, satisfaction), stress appraisal, coping (problem solving, seeking support, acceptance, wishful thinking, denial), and positive (life satisfaction, positive affect, benefits) and negative (distress, health) adjustment outcomes. Results: Caregiving context variables significantly correlated with poorer adjustment in children of a parent with multiple sclerosis included additional parental illness, higher family responsibilities, parental functional impairment and unpredictability of the parent's multiple sclerosis, and less choice in helping. As predicted, better adjustment in children of a parent with multiple sclerosis was related to higher levels of social support, lower stress appraisals, greater reliance on approach coping strategies (problem solving, seeking support and acceptance) and less reliance on avoidant coping (wishful thinking and denial). Compared with children of 'healthy' parents, children of a parent with multiple sclerosis reported greater family responsibilities, less reliance on problem solving and seeking social support coping, higher somatization and lower life satisfaction and positive affect. Conclusions: Findings delineate the key impacts of young caregiving and support a stress and coping model of adjustment in children of a parent with multiple sclerosis.

Zinc and vitamin A supplementation in Indigenous Australian children hospitalised with lower respiratory tract infection: a randomised controlled trial

Objective: To evaluate the efficacy of supplementation with zinc and vitamin A in Indigenous children hospitalised with acute lower respiratory infection (ALRI). Design: Randomised controlled, 2-by-2 factorial trial of supplementation with zinc and vitamin A. Setting and participants: 187 Indigenous children aged < 11 years hospitalised with 215 ALRI episodes at Alice Springs Hospital (April 2001 to July 2002). Interventions: Vitamin A was administered on Days 1 and 5 of admission at a dose of 50 000 IU (infants under 12 months), or 100 000 IU; and zinc sulfate was administered daily for 5 days at a daily dose of 20 mg (infants under 12 months) or 40 mg. Main outcome measure: Time to clinical recovery from fever and tachypnoea, duration of hospitalisation, and readmission for ALRI within 120 days. Results: There was no clinical benefit of supplementation with vitamin A, zinc or the two combined, with no significant difference between zinc and no-zinc, vitamin A and no-vitamin A or zinc + vitamin A and placebo groups in time to resolution of fever or tachypnoea, or duration of hospitalisation. Instead, we found increased morbidity; children given zinc had increased risk of readmission for ALRI within 120 days (relative risk, 2.4; 95% CI, 1.003–6.1). Conclusion: This study does not support the use of vitamin A or zinc supplementation in the management of ALRI requiring hospitalisation in Indigenous children living in remote areas. Even in populations with high rates of ALRI and poor living conditions, vitamin A and zinc therapy may not be useful. The effect of supplementation may depend on the prevalence of deficiency of these micronutrients in the population.

Increased health care utilization and increased antiretroviral use in HIV-infected individuals with mental health disorders

Objectives The aims of the study were to describe the prevalence and associations of mental health disorder (MHD) among a cohort of HIV-infected patients attending the Victorian HIV/AIDS Service between 1984 and 2000, and to examine whether antiretroviral therapy use or mortality was influenced by MHD (defined as a record of service provision by psychiatric services on the Victorian Psychiatric Case Register). It was hypothesized that HIV-positive individuals with MHD would have poorer treatment outcomes, reduced responses to highly active antiretroviral therapy (HAART) and increased mortality compared with those without MHD. Methods This is a retrospective cohort of 2981 individuals (73% of the Victorian population diagnosed with HIV infection) captured on an HIV database which was electronically matched with the public Victorian Psychiatric Case Register (VPCR) (accounting for 95% of public system psychiatry service provision). The prevalence, dates and recorded specifics of mental health disorders at the time of the electronic match on 1 June 2000 are described. The association with recorded MHD, gender, age, AIDS illness, HIV exposure category, duration and type of antiviral therapy, treatment era (prior to 1986, post-1987 and pre-HAART, and post-HAART) on hospitalization and mortality at 1 September 2001 was assessed. Results Five hundred and twenty-five individuals (17.6% of the Victorian HIV-positive population) were recorded with MHD, most frequently coded as attributable to substance dependence/abuse or affective disorder. MHD was diagnosed prior to HIV in 33% and, of those diagnosed after HIV, 93.8% were recorded more than 1 year after the HIV diagnosis. Schizophrenia was recorded in 6% of the population with MHD. Hospitalizations for both psychiatric and nonpsychiatric illness were more frequent in those with MHD (relative risk 5.4; 95% confidence interval 3.7, 8.2). The total number of antiretrovirals used (median 6.4 agents vs 5.5 agents) was greater in those with MHD. When adjusted for antiretroviral treatment era, HIV exposure category, CD4 cell count and antiretroviral therapy, survival was not affected by MHD. Conclusions MHD is frequent in this population with HIV infection and is associated with increased healthcare utilization but not with reduced survival.