The effects of pH and ionic strength on topical delivery of a negatively charged porphyrin (TPPS(4))

Meso-tetra-[4-sulfonatophenyl]-porphyrin (TPPS(4)) is a charged porphyrin derivate used in photodynamic therapy (PDT) by parenteral administration. This study means to investigate potential enhancement for its topical delivery by determining the TPPS(4) dependence on the environmental characteristics and applying iontophoresis. In order to accomplish this task, cathodal and anodal iontophoresis as well as passive delivery of the drug were studied in vitro and in vivo in function of its concentration, pH and ionic strength. A reduction in drug concentration as well as the NaCl elimination from donor formulation at pH 2.0 increased TPPS(4) passive permeation through the skin in vitro. Iontophoresis improved TPPS(4) delivery across the skin when applied in solutions containing NaCl at pH 2.0, regardless electrode polarity. However, at pH 7.4, the amount of TPPS(4) permeated by iontophoresis was not different from that one permeated after passive experiments from a solution containing NaCl. Despite the fact that iontophoresis did not improve TPPS(4) transdermal delivery at this specific condition, in vivo experiments showed that 10 min of iontophoresis quickly and homogeneously delivered TPPS(4) to deeper skin layers when compared to passive administration, which is an important condition for topical treatment of skin tumors with PDT. (C) 2008 Wiley-Liss, Inc. and the American Pharmacists Association.

Expo 1988 Information Service Centre, Brisbane

View to service centre during Expo 1988.

Family orientated delivery of routine nursing care in hospital

Hospital nursing may be better deployed to acute clinical patient care. The recruitment of family assistance will facilitate this process in patients in hospital awaiting placement and without acute care issues.

A Step-by-Step Approach to Transit Oriented Development Project Delivery

A major challenge in successfully implementing transit-oriented development (TOD) is having a robust process that ensures effective appraisal, initiation and delivery of multi-stakeholder TOD projects. A step-by step project development process can assist in the methodic design, evaluation, and initiation of TOD projects. Successful TOD requires attention to transit, mixed-use development and public space. Brisbane, Australia provides a case-study where recent planning policies and infrastructure documents have laid a foundation for TOD, but where barriers lie in precinct level planning and project implementation. In this context and perhaps in others, the research effort needs to shift toward identification of appropriate project processes and strategies. This paper presents the outcomes of research conducted to date. Drawing on the mainstream approach to project development and financial evaluation for property projects, key steps for potential use in successful delivery of TOD projects have been identified, including: establish the framework; location selection; precinct context review; preliminary precinct design; the initial financial viability study; the decision stage; establishment of project structure; land acquisition; development application; and project delivery. The appropriateness of this mainstream development and appraisal process will be tested through stakeholder research, and the proposed process will then be refined for adoption in TOD projects. It is suggested that the criteria for successful TOD should be broadened beyond financial concerns in order to deliver public sector support for project initiation.

Using household survey data to inform policy decisions regarding the delivery of evidence-based parenting interventions.

Background: This study used household survey data on the prevalence of child, parent and family variables to establish potential targets for a population-level intervention to strengthen parenting skills in the community. The goals of the intervention include decreasing child conduct problems, increasing parental self-efficacy, use of positive parenting strategies, decreasing coercive parenting and increasing help-seeking, social support and participation in positive parenting programmes. Methods: A total of 4010 parents with a child under the age of 12 years completed a statewide telephone survey on parenting. Results: One in three parents reported that their child had a behavioural or emotional problem in the previous 6 months. Furthermore, 9% of children aged 2–12 years meet criteria for oppositional defiant disorder. Parents who reported their child's behaviour to be difficult were more likely to perceive parenting as a negative experience (i.e. demanding, stressful and depressing). Parents with greatest difficulties were mothers without partners and who had low levels of confidence in their parenting roles. About 20% of parents reported being stressed and 5% reported being depressed in the 2 weeks prior to the survey. Parents with personal adjustment problems had lower levels of parenting confidence and their child was more difficult to manage. Only one in four parents had participated in a parent education programme. Conclusions: Implications for the setting of population-level goals and targets for strengthening parenting skills are discussed.

Delivery of multiple CD8 cytotoxic T cell epitopes by DNA vaccination

Development of CD8 alpha beta CTL epitope-based vaccines requires an effective strategy capable of co-delivering large numbers of CTL epitopes, Here we describe a DNA plasmid encoding a polyepitope or polytope protein, which contained multiple contiguous minimal murine CTL epitopes, Mice vaccinated with this plasmid made MHC-restricted CTL responses to each of the epitopes, and protective CTL were demonstrated in recombinant vaccinia virus, influenza virus, and tumor challenge models, CTL responses generated by polytope DNA plasmid vaccination lasted for 1 yr, could be enhanced by co-delivering a gene for granulocyte-macrophage CSF, and appeared to be induced in the absence of CD4 T cell-mediated help, The ability to deliver large numbers of CTL epitopes using relatively small polytope constructs and DNA vaccination technology should find application in the design of human epitope-based CTL vaccines, in particular in vaccines against EBV, HIV, and certain cancers.

Continuity of care and readmission in two service systems: a comparative Victorian and Groningen case-register study

Objective: We compared service consumption, continuity of care and risk of readmission in a record linkage follow-up study of cohorts of patients with schizophrenia and related disorders in Victoria (Australia) and in Groningen (The Netherlands). These areas are interesting to compare because mental health care is in a different stage of deiustitutionalization. More beds are available in Groningen and more community resources are available in Victoria. Method: The cohorts were followed for 4 years, since discharge from inpatient services using record linkage data available in the psychiatric case-registers in both areas. Survival analysis was used to study continuity of care and risk of readmission. Results: Available indicators showed a higher level of continuity of care in Victoria. While the relative risk of readmission was the same in both areas and not affected by aftercare contact after discharge, the number of days spent in hospital was much higher in the Groningen register area. Conclusion: These findings provide further support for earlier reports that the risk of readmission is predominantly affected by attributes of mental illness. However, the duration of admissions, is strongly affected by service system variables, including the provision of continuity of care.

HIV infection among women admitted to the gynaecology service of a district hospital in South Africa

Our objective was to determine the prevalence of HIV infection and disease-specific HIV prevalence among women admitted to the gynaecology service of a district hospital in South Africa over a 3-month period in 1997. This was done with the goal of developing HIV education and counselling services in this setting. HIV status was determined among 196 (96%) of 205 consecutive admissions; 82 (42%) tested HIV positive. The HIV-infected women were younger than the HIV uninfected women (mean age 27 vs 33 years, P=0.001). The disease-specific HIV prevalence was greater than or equal to 40% among women who had had abortions, pelvic inflammatory disease, or ectopic pregnancy. The length of hospital stay (mean 5.4 days) and mortality (1%) were similar in the 2 groups. Inpatient gynaecology services may be act important setting in Africa, within which to provide HIV education, counselling and care.

Providing evidence-based answers to clinical questions - A pilot information service for general practitioners

Objective: To pilot a clinical information service for general practitioners. Methods: A representative sample of 31 GPs was invited to submit clinical questions to a local academic department of general practice. Their views on the service and the usefulness of the information were obtained by telephone interview. Results: Over one month, nine GPs (29% of the sample, 45% of those stating an interest), submitted 20 enquiries comprising 45 discrete clinical questions. The median time to search for evidence, appraise it and write answers to each enquiry was 2.5 hours (range, 1.0-7.4 hours). The median interval between receipt of questions and dispatch of answers was 3 clays (range, 1-12 days). Conclusions: The GPs found the answers useful in clinical decision making; in four out of 20 cases patient management was altered.

Preliminary experiences with a single-patient trials service in general practice

Objective: To pilot a single-patient trials (SPTs) service in general practice, designed to improve decision-making about long-term medications for chronic conditions. Design: 12-week within-patient, randomised, double-blind, placebo-controlled, crossover comparison of ibuprofen with paracetamol for osteoarthritis, involving three pairs of two-week treatment periods for each participating patient. Setting and patients: Patients attending an academic general practice with a clinical diagnosis of osteoarthritis, with pain of at least a month's duration severe enough to warrant consideration of long-term non-steroidal anti-inflammatory drug (NSAID) use. Main outcome measures: Pain and stiffness; measures of overall arthritis compared with previous fortnight; preference for NSAID at the end of each two-week treatment period; use of escape analgesia; side effects; and management changes as a result of the SPTs. Results: Eight of 14 patients completed SPTs. One was a clear responder to NSAIDs, five were non-responders, and two were indefinite. Of the five who were using NSAIDs before the SPT, two continued and three ceased using them. Clinically useful information assisted decision-making for all eight participants. Medication management changed for six. Conclusions: Single-patient trials can be successfully implemented in general practice and might be a valuable method for GPs to identify patients who respond to medication for chronic stable conditions such as osteoarthritis, in which individual response to medication is variable.

Papillomavirus virus-like particles for the delivery of multiple cytotoxic T cell epitopes

Chimeric papillomavirus (PV) virus-like particles (VLPs) based on the bovine papillomavirus type 1 (BPV-1) L1 protein were constructed by replacing the 23-carboxyl-terminal amino acids of the BPV1 major protein L1 with an artificial polytope minigene, containing known CTL epitopes of human PV16 E7 protein, HIV IIIB gp120 P18, Nef, and reverse transcriptase (RT) proteins, and an HPV16 E7 linear B epitope. The CTL epitopes were restricted by three different MHC class 1 alleles (H-2(b), H-2(d), HLA-A*0201). The chimeric L1 protein assembled into VLPs when expressed in SF-9 cells by recombinant baculovirus. After immunization of mice with polytope VLPs in the absence of adjuvant, serum antibodies were detected which reacted with both polytope VLPs and wild-type BPV1L1 VLPs, in addition to the HPV16E7 linear B cell epitope. CTL precursors specific for the HPV16 E7, HIV P18, and RT CTL epitopes were also detected in the spleen of immunized mice. Polytope VLPs can thus deliver multiple B and T epitopes as immunogens to the MHC class I and class II pathways, extending the utility of VLPs as self-adjuvanting immunogen delivery systems. (C) 2000 Academic Press.

Suicidal ideation and suicide attempts as predictors of mental health service use

Objective: To examine the extent to which suicidal ideation and suicide attempts are predictive of service use. Design and setting: The National Survey of Mental Health and Wellbeing considered service utilisation in relation to self-reported mental health problems. Service utilisation was inquired of in relation to hospital-based care (including both specialist mental health and general care settings), as well as consultations with a range of health professionals (both specialist and non-specialist mental health professionals, including psychiatrists, psychologists and general practitioners) on an outpatient basis. Participants: Secondary analysis of self-report data from 10 641 randomly selected Australian adults who participated in the National Survey of Mental Health and Wellbeing in 1997. The key predictor variables were reported suicidal ideation and suicide attempts over the past 12 months. Main outcome measures: Use of services for mental health problems (past 12 months). Results: When considered in isolation, individuals reporting suicidal ideation were more likely to make use of at least one type of service for mental health problems than non-suicidal individuals (OR, 17.3; 95% Cl, 13.2-22.6), and individuals reporting suicide attempts were even more likely to do so (OR, 32.3; 95% CI, 9.0-115.4). In the case of suicidal ideation, this effect remained significant after controlling for a range of potential confounders. For suicide attempts, the effect of mental health service use was no longer significant after other variables were taken into account. Conclusions: Suicidal individuals are likely to make use of services, and a high proportion of suicides may be preventable through appropriate healthcare system responses.