Lipid, sugar and liposaccharide based delivery systems 2

The vast majority of biologically active compounds will never be considered as potential drugs due to inherently poor bioavailability. This review discusses the progress in the development of chemical systems to improve the metabolic stability, absorption and physicochemical properties of potential drugs. Delivery systems that involve the conjugation of lipid and/or sugar moieties are highlighted, as well as novel methods of conjugation of these groups to drugs. The use of sugar molecules to target drugs to particular organs or cells is also discussed, as is the use of lipids in the growing area of gene delivery. This is an update of a previous review [1].

Estimating cause-specfic mortality from community- and facility-based data sources in the United Republic of Tanzania: options and implications for mortality burden estimates

Objective To compare mortality burden estimates based on direct measurement of levels and causes in communities with indirect estimates based on combining health facility cause-specific mortality structures with community measurement of mortality levels. Methods. Data from sentinel vital registration (SVR) with verbal autopsy (VA) were used to determine the cause-specific mortality burden at the community level in two areas of the United Republic of Tanzania. Proportional cause-specific mortality structures from health facilities were applied to counts of deaths obtained by SVR to produce modelled estimates. The burden was expressed in years of life lost. Findings. A total of 2884 deaths were recorded from health facilities and 2167 recorded from SVR/VAs. In the perinatal and neonatal age group cause-specific mortality rates were dominated by perinatal conditions and stillbirths in both the community and the facility data. The modelled estimates for chronic causes were very similar to those from SVR/VA. Acute febrile illnesses were coded more specifically in the facility data than in the VA. Injuries were more prevalent in the SVR/VA data than in that from the facilities. Conclusion. In this setting, improved International classification of diseases and health related problems, tenth revision (ICD-10) coding practices and applying facility-based cause structures to counts of deaths from communities, derived from SVR, appears to produce reasonable estimates of the cause-specific mortality burden in those aged 5 years and older determined directly from VA. For the perinatal and neonatal age group, VA appears to be required. Use of this approach in a nationally representative sample of facilities may produce reliable national estimates of the cause-specific mortality burden for leading causes of death in adults.

Mediated approaches for influencing physical activity: Update of the evidence on mass media, print, telephone and website delivery of interventions

The aim of this paper is to review evidence published since 1997 on the effectiveness of mass media, print, telephone and website-delivered physical activity (PA) interventions. For mass media, there is consistent evidence for impacts on recall of campaign tag lines and message content and modest evidence of short-term impacts on behaviour in some population subgroups. Print-based delivery of programs can have a modest impact on behaviour; research is needed on supplementary strategies to support print programs. Although there is a strong case for the potential of telephone and Internet delivered interventions, there is as yet little evidence that they can be effective. All of these 'mediated' approaches to PA program delivery are likely to be important elements of future public health interventions. The body of evidence for their effectiveness in changing behaviour is currently modest, however, and it is clear that these approaches have not yet been fully developed and evaluated. Combinations of different media and mutually supportive, integrated strategies are likely to be more effective and need to be developed and evaluated systematically, building on the current research evidence base.

Classifying client goals in community-based ABI rehabilitation: a taxonomy for profiling service delivery and conceptualizing outcomes

Purpose: To develop, confirm and trial a framework for analysing the content of goals set within community-based rehabilitation. This framework (taxonomy) is proposed as a tool to assist in service evaluation and outcome exploration. Method: Qualitative thematic analysis and categorization of 1765 rehabilitation goal statements in a four phase process of synthesis, refinement, verification and application. Results: A taxonomy of goal content was developed comprising 21 categories within five domains, utilizing 125 descriptors. The taxonomy demonstrated good inter-rater consistency and was able to discriminate between similar but related data sets comprising goal statements. Conclusion: Structured analysis of the content of goal setting (particularly in community rehabilitation) utilizing a framework such as the proposed taxonomy has considerable potential as a 'window' into service delivery to broaden the parameters of existing service evaluation and to more clearly link outcome exploration to intervention.

Group A streptococcal vaccine delivery by immunization with a self-adjuvanting M protein-based lipid core peptide construct

Background & objectives: To develop a broad strain coverage GAS vaccine, several strategies have been investigated which included multi-epitope approaches as well as targeting the M protein conserved C-region. These approaches, however, have relied on the use of adjuvants that are toxic for human application. The development of safe and effective adjuvants for human use is a key issue in the development of effective vaccines. In this study, we investigated the lipid polylysine core peptide (LCP) system as a self-adjuvanting GAS vaccine delivery approach. Methods: An LCP-GAS construct was synthesised incorporating multiple copies of a protective peptide epitope (J8) from the conserved carboxy terminal C-repeat region of the M protein. B10.BR mice were immunized parenterally with the LCP-J8 construct, with or without conventional adjuvant, prior to the assessment of immunogenicity and the induction of serum opsonic antibodies. Results: Our data demonstrated immunogenicity of LCP-J8 when coadministered in complete Freund's adjuvant (CFA), or administered in the absence of conventional adjuvant. In both cases, immunization led to the induction of high-titre J8 peptide-specific serum IgG antibody responses, and the induction of heterologous opsonic antibodies that did not cross-react with human heart tissue proteins. Interpretation & conclusion: These data indicated the potential of a novel self-adjuvanting LCP vaccine delivery system incorporating a synthetic GAS M protein C-region peptide immunogen in the induction of broadly protective immune responses, and pointed to the potential application of this system in human vaccine development against infectious diseases.

Lipid based particulate formulations for the delivery of antigen

Particulate adjuvant systems are largely classified according to their functional characteristics, such as the nature of the typical immune response they induce, or their perceived mode of action. From a formulation science perspective, it is practical to classify antigen delivery systems according to the physical nature of the formulations. This article discusses lipid based particulate systems, grouped according to the nature of their predominant lipid constituent.

Lipid and carbohydrate based adjuvant/carriers in immunology

This review discusses various issues regarding vaccines:what are they and how they work, safety aspects, the role of adjuvants and carriers in vaccination, synthetic peptides as immunogens, and new technologies for vaccine development and delivery including the identification of novel adjuvants for mucosal vaccine delivery. There has been a recent increase of interest, in the use of lipids and carbohydrates as adjuvants, and so a particular emphasis is placed on adjuvants derived from lipids or carbohydrates, or from both. Copyright (C) 2003 European Peptide Society and John Wiley Sons, Ltd.

The cost of allied health assessments delivered by videoconference to a residential facility for elderly people

We calculated the cost of providing allied health assessments to high-dependency residents of a rural facility for elderly people. The costs of conducting assessments via videoconferencing were compared with the costs of conducting assessments face to face. The observed costs in a three-month pilot trial were used to estimate the annual costs. Given an annual workload of 1000 occasions of service, each videoconference assessment would cost $84.93, compared with $90.25 for face-to-face assessments. Allied health assessments delivered by videoconferencing became cheaper at workloads of approximately 850 occasions of service annually. Additional increases in the workload further improved the financial viability of this approach to service delivery.

Physical enhancement of transdermal drug application: is delivery technology keeping up with pharmaceutical development?

Advances in molecular biology have given us a wide range of protein and peptide-based drugs that are unsuitable for oral delivery because of their high degree of first-pass metabolism. Though parenteral delivery is the obvious answer, for the successful development of commercial chronic and self-administration usage formulations it is not the ideal choice. Transdermal delivery is emerging as the biggest application target for these agents, however, the skin is extremely efficient at keeping out such large molecular weight compounds and therapeutic levels are never going to be realistically achieved by passive absorption. Physical enhancement mechanisms including: iontophoresis, electroporation, ultrasound, photomechanical waves, microneedles and jet-propelled particles are emerging as solutions to this topical delivery dilemma. Adding proteins and peptides to the list of other large molecular weight drugs with insufficient passive transdermal fluxes to be therapeutically useful, we have a collection of pharmacological agents waiting for efficient delivery methods to be introduced. This article reviews the current state of physical transdermal delivery technology, assesses the pros and cons of each technique and summarises the evidence-base of their drug delivery capabilities.

Evidence-based practice and rehabilitation: occupational therapy in Australia and New Zealand experiences

Evidence-based practice has become the dominant paradigm in the delivery of rehabilitation programme. However, occupational therapists in Australia and New Zealand have been slow in making the transition to become evidence-based practitioners. Collaboration between the university/ tertiary institute and clinical setting is one way that clinicians can be assisted with incorporating research into their practice. Two case examples are presented outlining how collaborative practice can result in improved out.. comes for all concerned.

Acceptability and feasibility of a community-based screening programme for melanoma in Australia

The evaluation of a community-based screening programme for melanoma (SkinWatch) in 18 regional communities (total adult population >30 years 63 035) in Queensland, Australia is described. The aim of the SkinWatch programme was to promote whole-body skin screening for melanoma by primary care physicians. The programme included community education, education and support for local medical practitioners and open-access skin screening clinics. Programme delivery was achieved through assistance of local volunteers. All programme activities and resources were recorded for process evaluation. A baseline telephone survey (n = 3110) and a telephone survey four months after programme launch (n = 680) assessed community awareness of the SkinWatch programme and, 37 face-to-face interviews with community members, doctors and community leaders were conducted to assess satisfaction with the programme. A sample of 1043 of 16 383 residents who attended the skin screening clinics provided as part of the programme were interviewed to assess reasons for attending, and positive and negative aspects of SkinWatch programme. Community awareness of the SkinWatch programme increased by over 30% (p < 0.001) within four months of the start of the programme. Interview participants described the SkinWatch programme as a useful service for the communities and 90% stated they would revisit the clinics. A total of 43% of all attendees were over 50 years old, and nearly 50% were men. These findings demonstrate the acceptability and feasibility of a community-based screening programme for melanoma in rural areas. Volunteers were instrumental in increasing community ownership of and involvement in the SkinWatch programme.