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1.
Article in English | WHO IRIS | ID: who-329533

ABSTRACT

Drawing on published work from the Asia Pacific Observatory on Health Systems and Policies, this paper presents a framework for undertaking comparative studies on the health systems of countries. Organized under seven types of research approaches, such as national case-studies using a common format, this framework is illustrated using studies of low- and middle-income countries published by the Asia Pacific Observatory. Such studies are important contributions, since much of the health systems research literature comes from high-income countries. No one research approach, however, can adequately analyse a health system, let alone produce a nuanced comparison of different countries. Multiple comparative studies offer a better understanding, as a health system is a complex entity to describe and analyse. Appreciation of context and culture is crucial: what works in one country may not do so in another. Further, a single research method, such as performance indicators, or a study of a particular health system function or component, produces only a partial picture. Applying a comparative framework of several study approaches helps to inform and explain progress against health system targets, to identify differences among countries, and to assess policies and programmes. Multi-method comparative research produces policy-relevant learning that can assist countries to achieve Sustainable Development Goal 3: ensure healthy lives and promoting well-being for all at all ages by 2030


Subject(s)
Health Systems
2.
Article in English | MEDLINE | ID: mdl-29582843

ABSTRACT

Drawing on published work from the Asia Pacific Observatory on Health Systems and Policies, this paper presents a framework for undertaking comparative studies on the health systems of countries. Organized under seven types of research approaches, such as national case-studies using a common format, this framework is illustrated using studies of low- and middle-income countries published by the Asia Pacific Observatory. Such studies are important contributions, since much of the health systems research literature comes from high-income countries. No one research approach, however, can adequately analyse a health system, let alone produce a nuanced comparison of different countries. Multiple comparative studies offer a better understanding, as a health system is a complex entity to describe and analyse. Appreciation of context and culture is crucial: what works in one country may not do so in another. Further, a single research method, such as performance indicators, or a study of a particular health system function or component, produces only a partial picture. Applying a comparative framework of several study approaches helps to inform and explain progress against health system targets, to identify differences among countries, and to assess policies and programmes. Multi-method comparative research produces policy-relevant learning that can assist countries to achieve Sustainable Development Goal 3: ensure healthy lives and promoting well-being for all at all ages by 2030.


Subject(s)
Delivery of Health Care/organization & administration , Health Policy , Health Services Research/methods , Asia , Humans , Pacific Islands
3.
Glob Health Action ; 10(1): 1271594, 2017.
Article in English | MEDLINE | ID: mdl-28452652

ABSTRACT

BACKGROUND: Migrant health is receiving increasing international attention, reflecting recognition of the health inequities experienced among many migrant populations and the need for health systems to adapt to diverse migrant populations. In the Greater Mekong Subregion (GMS) there is increasing migration associated with uneven economic integration and growth, socio-economic vulnerabilities, and disparities between countries. There has been limited progress, however, in improving migrant access to health services in the Subregion. This paper examines the health needs, access barriers, and policy responses to cross-border migrants in five GMS countries. METHODS: A review of published literature and research was conducted on migrant health and health service access in Cambodia, Lao People's Democratic Republic, Myanmar, Thailand, and Viet Nam, as well as analysis of current migration trends and universal health coverage (UHC) indicators in the Subregion. The review included different migrant types: i.e. migrant workers, irregular migrants, victims of trafficking, refugees and asylum seekers, and casual cross-border migrants. RESULTS: There is substantial diversity in the capacity of GMS health systems to address migrant populations. Thailand has sought to enhance migrant health coverage, including development of migrant health policies/programs, bilateral migrant worker agreements, and migrant health insurance schemes; Viet Nam provides health protection for emigrant workers. Overall, however, access to good quality health care remains weak for many citizens in GMS countries let alone migrants. Migrant workers - and irregular migrants in particular - face elevated health risks yet are not adequately covered and incur high out-of-pocket (OOP) payments for health services. CONCLUSIONS: UHC implies equity: UHC is only achieved when everyone has the opportunity to access and use good-quality health care. Efforts to achieve UHC in the GMS require deliberate policy decisions to include migrants. The emergence of the UHC agenda, and the focus on migrant health among policy makers and partners, present an opportunity to tackle barriers to health service access, extend coverage, and strengthen partnerships in order to improve migrant health. This is an opportune time for GMS countries to develop migrant-inclusive health systems.


Subject(s)
Health Equity/statistics & numerical data , Health Services Accessibility/statistics & numerical data , Transients and Migrants/statistics & numerical data , Asia, Southeastern , Health Expenditures , Health Services/statistics & numerical data , Humans , Needs Assessment , Policy , Quality of Health Care , Universal Health Insurance/statistics & numerical data
4.
Health Syst Reform ; 3(3): 171-181, 2017 Jul 03.
Article in English | MEDLINE | ID: mdl-31157585

ABSTRACT

This paper explores whether middle-income Asian countries are reorienting their health services in response to non-communicable diseases (NCDs). Malaysia, Sri Lanka, and Thailand were selected as case studies of Asian societies experiencing rapid increases both in NCDs and an aging population. While NCD programs, especially those related to diabetes and stroke, are well-established in Thailand, health services struggle to respond to increasing numbers of people with chronic health problems. Health services at all levels must plan ahead for more patients with chronic and often multiple conditions who require better integrated health care.

5.
Aust Health Rev ; 41(5): 527-532, 2017 Oct.
Article in English | MEDLINE | ID: mdl-27764646

ABSTRACT

Objective This paper explores how hospital complaints managers react to recommendations for systemic quality reforms by health complaints commissions in response to complaints by patients in Queensland and New South Wales. Methods Semi-structured qualitative interviews were conducted with complaints managers in 17 hospitals. Interview transcripts were then thematically analysed and data on responses to health complaint commissions was organised in relation to Valerie Braithwaite's typology of motivational postures. Results Respondents supported involvement by an independent authority where patients had serious complaints about the services they received in hospital, but wanted more negotiation with commissions on service improvement recommendations. Conclusions Hospital complaints managers mostly responded as virtuous or rational actors to the symbolic power of complaints commissions. This may be context dependent because Australian health commissions operate within a pro-reform context as a result of recent publicity around health system failures. What is known about the topic? Little is known about regulatory relationships between complaints commissions and hospitals. There has been no Australian research considering how complaints managers respond to commission recommendations for quality improvements and reforms to hospital services. What does the paper add? The paper uses a novel theoretical framework based on regulatory theory to understand and describe the reactions of complaints managers to commission recommendations. What are the implications for practitioners? Commissions should seek commentary from complaints managers through open dialogue before making final recommendations. This will ease the progress of reforms and make recommendations more acceptable and 'genuine' in the specific context of the hospital.


Subject(s)
Hospital Administrators , Patient Advocacy , Patient Satisfaction , Quality Improvement , Interviews as Topic , New South Wales , Qualitative Research , Queensland
6.
Int J Qual Health Care ; 28(2): 240-5, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26826722

ABSTRACT

OBJECTIVE: To explore the applicability of a patient complaint taxonomy to data on serious complaint cases. DESIGN: Qualitative descriptive study. SETTING: Complaints made to the New South Wales (NSW) Health Care Complaints Commission, Australia between 2005 and 2010. PARTICIPANTS: All 138 cases of serious complaints by patients about public hospitals and other health facilities investigated in the 5-year period. MAIN OUTCOME MEASURE: A thematic analysis of the complaints was conducted to identify particular complaint issues and the Reader et al. (Patient complaints in healthcare systems: a systematic review and coding taxonomy. BMJ Qual Saf 2014;23:678-89.) patient complaint taxonomy was then used to classify these issues into categories and sub-categories. RESULTS: The 138 investigated cases revealed 223 complaint issues. Complaint issues were distributed into the three domains of the patient complaint taxonomy: clinical, management and relationships. Complaint issue most commonly related to delayed diagnosis, misdiagnosis, medication errors, inadequate examinations, inadequate/nil treatment and quality of care including nursing care. CONCLUSIONS: The types of complaints from patients about their healthcare investigated by the NSW Commission were similar to those received by other patient complaint entities in Australia and worldwide. The application of a standard taxonomy to large numbers of complaints cases from different sources would enable the creation of aggregated data. Such data would have better statistical capacity to identify common safety and quality healthcare problems and so point to important areas for improvement. Some conceptual challenges in devising and using a taxonomy must be addressed, such as inherent problems in ensuring coding consistency, and giving greater weight to patient concerns about their treatment.


Subject(s)
Hospitals/standards , Patient Satisfaction , Classification , Hospitals, Public/standards , Humans , Medical Errors/classification , Medication Errors/classification , New South Wales , Patient Satisfaction/statistics & numerical data
7.
Rand Health Q ; 4(1): 1, 2014.
Article in English | MEDLINE | ID: mdl-28083315

ABSTRACT

This study is concerned with "standards of quality and safety" within health and social care systems. Care standards are intended to support efforts in maintaining and improving the quality of care; they have been developed across countries, although the ways in which they are implemented and applied differs between nations. Taking a range of six countries, we review the regulatory mechanisms that have been implemented to ensure that essential standards of care are applied and are being adhered to, and consider the range of policy instruments used to encourage and ensure continuous quality improvement. We report on Australia, England, Finland, Germany, the Netherlands and the USA. The study is intended to inform policy thinking for the Department of Health and others in developing the regulation of safety and quality of health and social care in England. It was prepared as part of the project "An 'On-call' Facility for International Healthcare Comparisons" funded by the Department of Health in England through its Policy Research Programme.

8.
Health Policy ; 106(1): 37-49, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22265340

ABSTRACT

This paper explores leadership and governance arrangements in seven developed health systems: Australia, England, Germany, the Netherlands, Norway, Sweden and Switzerland. It presents a cybernetic model of leadership and governance comprising three fundamental functions: priority setting, performance monitoring and accountability arrangements. The paper uses a structured survey to examine critically current arrangements in the seven countries. Approaches to leadership and governance vary substantially, and have to date been developed piecemeal and somewhat arbitrarily. Although there seems to be reasonable consensus on broad goals of the health system there is variation in approaches to setting priorities. Cost-effectiveness analysis is in widespread use as a basis for operational priority setting, but rarely plays a central role. Performance monitoring may be the domain where there is most convergence of thinking, although countries are at different stages of development. The third domain of accountability is where the greatest variation occurs, and where there is greatest uncertainty about the optimal approach. We conclude that a judicious mix of accountability mechanisms is likely to be appropriate in most settings, including market mechanisms, electoral processes, direct financial incentives, and professional oversight and control. The mechanisms should be aligned with the priority setting and monitoring processes.


Subject(s)
Delivery of Health Care/organization & administration , Developed Countries , Leadership , Australia , Europe , Humans
9.
Int J Qual Health Care ; 24(1): 88-94, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22140202

ABSTRACT

OBJECTIVE: To analyse the strategies used by hospital leaders to improve compliance with the 'ensuring correct patient, correct site and correct procedure protocol'. While following such a protocol saves lives according to an international study of the World Health Organization safe surgery checklist, promoting compliance in hospitals has proved to be a regulatory challenge. SETTING AND PARTICIPANTS: Using a qualitative research design and 'responsive regulation' theory, this study explored implementation strategies used by hospital leaders in 20 Australian public hospitals. Semi-structured interviews were conducted with 72 informants to analyse how front-line leaders improved compliance with the safe surgery protocol in their hospitals. INTERVENTIONS: Implementation analysis of the safe surgery protocol. MAIN OUTCOME MEASURES: The use of implementation strategies located on a 'responsive regulation' pyramid. RESULTS: Informants identified many strategies used to improve protocol compliance typically beginning with persuasion. Supportive strategies were located on a regulatory pyramid beginning with softer interventions: persuade, enlist leaders, train, remind, relax protocol requirements, redesign hospital systems and reward compliance. In response to low and slow compliance, many hospital leaders switched to a pyramid of escalating sanctions: direct, delegate, monitor, publicly report, reprimand and penalize. CONCLUSIONS: A multiplex problem requires graduated and multiplex regulation. Hospital leaders proved to be responsive regulators in applying both multiple supports and sanctions that improved compliance over 3 years. These experiences with protocol implementation illustrate the multifaceted challenge of health sector regulation and offer lessons for embedding future patient safety solutions.


Subject(s)
Clinical Protocols , Hospital Administration , Leadership , Safety Management/organization & administration , Surgical Procedures, Operative/standards , Attitude of Health Personnel , Australia , Guideline Adherence , Humans , Inservice Training , Motivation , Organizational Culture , Patient Safety , Policy , Practice Guidelines as Topic
11.
Med J Aust ; 188(4): 247-9, 2008 Feb 18.
Article in English | MEDLINE | ID: mdl-18279136

ABSTRACT

The first aim of a medical registration scheme should be to protect patients. Medical registration boards currently offer variable information to the public on doctors' registration status. Current reform proposals for a national registration scheme should include free public access to professional profiles of registered medical practitioners. Practitioner profiles should include: practitioner's full name and practice address; type of qualifications; year first registered, and duration and type of registration; any conditions on registration and practice; any disciplinary action taken; and participation in continuing professional education.


Subject(s)
Access to Information , Credentialing , Internet , Physicians/standards , Registries/statistics & numerical data , Australia , Education, Medical, Continuing , Humans , Physicians/statistics & numerical data , Registries/standards
12.
Acc Chem Res ; 41(1): 130-8, 2008 Jan.
Article in English | MEDLINE | ID: mdl-18193823

ABSTRACT

Aptamers are non-naturally occurring structured oligonucleotides that may bind to small molecules, peptides, and proteins. Typically, aptamers are generated by an in vitro selection process referred to as SELEX (systematic evolution of ligands by exponential enrichment). Aptamers that bind with high affinity and specificity to proteins that reside on the cell surface have potential utility as therapeutic antagonists, agonists, and diagnostic agents. When the target protein requires the presence of the cell membrane (e.g., G-protein-coupled receptors, ion channels) or a co-receptor to fold properly, it is difficult or impossible to program the SELEX experiment with purified, soluble protein target. Recent advances in which the useful range of SELEX has been extended from comparatively simple purified forms of soluble proteins to complex mixtures of proteins in membrane preparations or in situ on the surfaces of living cells offer the potential to discover aptamers against previously intractable targets. Additionally, in cases in which a cell-type specific diagnostic is sought, the most desirable target on the cell surface may not be known. Successful application of aptamer selection techniques to complex protein mixtures can be performed even in the absence of detailed target knowledge and characterization. This Account presents a review of recent work in which membrane preparations or whole cells have been utilized to generate aptamers to cell surface targets. SELEX experiments utilizing a range of target "scaffolds" are described, including cell fragments, parasites and bacteria, viruses, and a variety of human cell types including adult mesenchymal stem cells and tumor lines. Complex target SELEX can enable isolation of potent and selective aptamers directed against a variety of cell-surface proteins, including receptors and markers of cellular differentiation, as well as determinants of disease in pathogenic organisms, and as such should have wide therapeutic and diagnostic utility.


Subject(s)
Aptamers, Nucleotide/therapeutic use , Drug Design , Membrane Proteins/antagonists & inhibitors , SELEX Aptamer Technique/methods , Animals , Aptamers, Nucleotide/chemistry , Humans , Membrane Proteins/chemistry
13.
Circulation ; 116(23): 2678-86, 2007 Dec 04.
Article in English | MEDLINE | ID: mdl-18025536

ABSTRACT

BACKGROUND: ARC1779 is a therapeutic aptamer antagonist of the A1 domain of von Willebrand Factor (vWF), the ligand for receptor glycoprotein 1b on platelets. ARC1779 is being developed as a novel antithrombotic agent for use in patients with acute coronary syndromes. METHODS AND RESULTS: This was a randomized, double-blind, placebo-controlled study in 47 healthy volunteers of doses of ARC1779 from 0.05 to 1.0 mg/kg. Pharmacodynamic effects were measured by an ELISA for free vWF A1 binding sites and by a platelet function analyzer. In terms of pharmacokinetics, the concentration-time profile of ARC1779 appeared monophasic. The observed concentration and area under the curve were dose proportional. The mean apparent elimination half-life was approximately 2 hours, and mean residence time was approximately 3 hours. The mean apparent volumes of distribution (at steady state and during terminal phase) were approximately one half the blood volume, suggesting that ARC1779 distribution is in the central compartment. The mean clearance ranged from approximately 10% to approximately 21% of the glomerular filtration rate, suggesting that renal filtration may not be a major mechanism of clearance of ARC1779. Inhibition of vWF A1 binding activity was achieved with an EC(90) value of 2.0 mug/mL (151 nmol/L) and of platelet function with an EC(90) value of 2.6 mug/mL (196 nmol/L). ARC1779 was generally well tolerated, and no bleeding was observed. Adverse events tended to be minor and not dose related. CONCLUSIONS: This is the first-in-human evaluation of a novel aptamer antagonist of vWF. ARC1779 produced dose- and concentration-dependent inhibition of vWF activity and platelet function with duration of effect suitable for the intended clinical use in acute coronary syndromes.


Subject(s)
Acute Coronary Syndrome/drug therapy , Aptamers, Nucleotide/pharmacokinetics , Fibrinolytic Agents/pharmacokinetics , von Willebrand Factor/antagonists & inhibitors , Adolescent , Adult , Aged , Aptamers, Nucleotide/adverse effects , Dose-Response Relationship, Drug , Double-Blind Method , Female , Fibrinolytic Agents/adverse effects , Humans , Male , Middle Aged , Platelet Function Tests , Platelet Glycoprotein GPIb-IX Complex/agonists , Protein Structure, Tertiary , Time Factors
14.
Aust Health Rev ; 31(3): 385-92, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17669061

ABSTRACT

We administered an electronic survey in October-November 2006 to gauge stakeholder perspectives on Australia's recently adopted health workforce policies. Nearly all of the 41 survey respondents (65% response rate) ranked workforce as very important to overall health policy. Respondents identified decreasing health disparities and rates of disease and mortality as top goals, and identified improved quality and safety and more professionals in rural areas as priority measures for success. Lack of coordination between the governments and insufficient long-range planning were seen as threats to the success of the new workforce initiatives. The survey results suggest the need for clear goals and measurable outcomes. Although they represented different organisations and perspectives, the health workforce policy opinion leaders that participated in this survey reflected remarkable commonality in goals, measures, alternatives, and potential threats.


Subject(s)
Health Care Reform , Health Workforce , Policy Making , Attitude to Health , Australia , Health Care Surveys , Humans , Leadership , National Health Programs , Rural Health Services , Socioeconomic Factors
15.
Med J Aust ; 184(S10): S56-9, 2006 05 15.
Article in English | MEDLINE | ID: mdl-16719738

ABSTRACT

Self-regulation by the health professions, while improving, is no longer enough; external drivers for safer health care include governments, funders and consumers. Enforced self-regulation is often more promising than a "command and control" strategy. Research evidence on the responsive regulatory pyramid and its options offers lessons for health care policy makers and managers. Start at the base of the regulatory pyramid - try persuasion first; move up the pyramid to secure compliance, and then be willing to move back down. Use existing capacities and structures, and if possible avoid new bureaucracies of control.


Subject(s)
Hospitals/standards , Medical Errors/prevention & control , Quality Assurance, Health Care/standards , Safety Management/standards , Australia , Government Regulation , Guideline Adherence , Humans , Models, Organizational , Organizational Culture , Persuasive Communication , Quality Assurance, Health Care/legislation & jurisprudence , Quality Assurance, Health Care/organization & administration , Safety Management/legislation & jurisprudence , Safety Management/organization & administration
16.
Health Systems in Transition, vol. 8 (5)
Article in English | WHO IRIS | ID: who-107803

ABSTRACT

The Health Systems in Transition (HiT) profiles are country-based reports that provide a detailed description of a health system and of policy initiatives in progress or under development. HiTs examine different approaches to the organization, financing and delivery of health services and the role of the main actors in health systems; describe the institutional framework, process, content and implementation of health and health care policies; and highlight challenges and areas that require more in-depth analysis. Australia is a prosperous country with GDP per capita near the OECD average and with a culturally diverse population of 20 million. The population generally enjoys good health and increasing life expectancy. Most Australians have access to comprehensive health care of a high standard, financed mainly through general taxation. Fiscal and functional responsibilities for health care are divided between the Australian Government and six States and two Territories, and between public and private providers, so that the ability of any one actor to plan or regulate is limited. Equity is maintained in that health care is funded primarily by progressive taxation, but several disparities have arisen, including increased out-of-pocket payments, differential access to dental care, and concerns that increased private health insurance will encourage a two-tier health system. Efficiency can be improved given duplicated governance and despite gains in microeconomic reforms. Quality is receiving more attention, despite limited monitoring of clinical outcomes. Some endemic problems have eluded solutions: whether rising health expenditure is sustainable, tensions between levels of government, long waiting lists for elective surgery, disparities in urban and rural service access, and the continuing poor health status of Indigenous Australians.


Subject(s)
Delivery of Health Care , Evaluation Study , Healthcare Financing , Health Care Reform , Health Systems Plans , Australia
17.
Oligonucleotides ; 15(3): 183-95, 2005.
Article in English | MEDLINE | ID: mdl-16201906

ABSTRACT

Here, we examine biodistribution of radiolabeled aptamers and assess the relative ability of different stabilized aptamer compositions (mixed 2'-F/2'-O-Me; fully 2'-O-Me modified) to access inflamed tissues in a murine inflammation model. Biodistribution of 3H-labeled aptamers, including pegylated and unpegylated compositions, was assessed 3 hours postadministration using quantitative whole body autoradiography (QWBA). Aptamer penetration of cells in kidney and liver was also examined at a qualitative level by microautoradiography. To evaluate aptamer distribution to diseased tissues, inflammation was induced locally in animal hind limbs by treatment with carrageenan just prior to aptamer dosing. Aptamer compositions examined exhibited significant variation in distribution levels among organs and tissues. Highest concentrations of radioactivity in whole body tissues for all animals were observed in the kidney and urinary bladder contents. Relatively little radioactivity was associated with brain, spinal cord, and adipose tissue. Overall, the total level of radioactivity in whole body tissues was significantly higher for a 20-kDa PEG conjugate than for other aptamers. Comparatively high levels of the 20-kDa conjugate were seen in well-perfused organs and tissues, including liver, lungs, spleen, bone marrow, and myocardium. A fully 2'-O-Me composition aptamer had the lowest level of radioactivity in whole body tissues but distributed to higher concentrations in the gastrointestinal tract contents relative to other aptamers. Interestingly, the 20-kDa PEG-conjugated aptamer showed significantly higher levels of distribution to inflamed paw tissues than did either unconjugated or fully 2'-O-Me-modified aptamers.


Subject(s)
Polyethylene Glycols/pharmacokinetics , Animals , Autoradiography , Base Sequence , Biological Availability , Carrageenan , Disease Models, Animal , Dose-Response Relationship, Drug , Extremities , Gastrointestinal Tract/metabolism , Inflammation/chemically induced , Lower Extremity , Male , Mice , Mice, Inbred Strains , Molecular Sequence Data , Molecular Weight , Polyethylene Glycols/chemistry , Polyethylene Glycols/metabolism , Polymers/chemistry , Tissue Distribution/drug effects , Tissue Distribution/physiology , Tritium/metabolism
18.
J Biomol Tech ; 16(3): 224-34, 2005 Sep.
Article in English | MEDLINE | ID: mdl-16461946

ABSTRACT

In the simplest view, aptamers can be thought of as nucleic acid analogs to antibodies. They are able to bind specifically to proteins, and, in many cases, that binding leads to a modulation of protein activity. New aptamers are rapidly generated through the SELEX (Systematic Evolution of Ligands by Exponential enrichment) process and have a very high target affinity and specificity (picomoles to nanomoles). Furthermore, aptamers composed of modified nucleotides have a long in vivo half-life (hours to days), are nontoxic and nonimmunogenic, and are easily produced using standard nucleic acid synthesis methods. These properties make aptamers ideal for target validation and as a new class of therapeutics. As a target validation tool, aptamers provide important information that complements that provided by other methods. For example, siRNA is widely used to demonstrate that protein knock-out in a cellular assay can lead to a biological effect. Aptamers extend that information by showing that the dose-dependent modulation of protein activity can be used to derive a therapeutic benefit. That is, aptamers can be used to demonstrate that the protein is a good target for drug development. As a new class of therapeutics, aptamers bridge the gap between small molecules and biologics. Like biologics, biologically active aptamers are rapidly discovered, have no class-specific toxicity, and are adept at disrupting protein-protein interaction. Like small molecules, aptamers can be rationally engineered and optimized, are nonimmunogenic, and are produced by scalable chemical procedures at moderate cost. As such, aptamers are emerging as an important source of new therapeutic molecules.


Subject(s)
Nucleic Acids/chemistry , Nucleic Acids/therapeutic use , Animals , Antithrombins/chemistry , Antithrombins/pharmacokinetics , Antithrombins/therapeutic use , Drug Costs , Nucleic Acids/administration & dosage , Nucleic Acids/pharmacokinetics , Platelet-Derived Growth Factor/antagonists & inhibitors , Vascular Endothelial Growth Factor A/antagonists & inhibitors
19.
Pharm Res ; 21(12): 2234-46, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15648255

ABSTRACT

PURPOSE: Aptamers are highly selective nucleic acid-based drugs that are currently being developed for numerous therapeutic indications. Here, we determine plasma pharmacokinetics and tissue distribution in rat of several novel aptamer compositions, including fully 2'-O-methylated oligonucleotides and conjugates bearing high-molecular weight polyethylene glycol (PEG) polymers, cell-permeating peptides, and cholesterol. METHODS: Levels of aptamer conjugates in biological samples were quantified radiometrically and by a hybridization-based dual probe capture assay with enzyme-linked fluorescent readout. Intact aptamer in urine was detected by capillary gel electrophoresis and matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF). RESULTS: Aptamer compositions examined exhibited a wide range of mean residence times in circulation (0.6-16 h) and significant variation in distribution levels among organs and tissues. Among the conjugates tested, in vivo properties of aptamers were altered most profoundly by conjugation with PEG groups. Complexation with a 20 kDa PEG polymer proved nearly as effective as a 40 kDa PEG polymer in preventing renal clearance of aptamers. Conjugation with 20 kDa PEG prolonged aptamer circulatory half-life, while reducing both the extent of aptamer distribution to the kidneys and the rate of urinary elimination. In contrast, the fully 2'-O-Me aptamer composition showed rapid clearance from circulation, and elimination with intact aptamer detectable in urine at 48 h post-administration. CONCLUSIONS: We find that conjugation and chemical composition can alter fundamental aspects of aptamer residence in circulation and distribution to tissues. Though the primary effect of PEGylation was on aptamer clearance, the prolonged systemic exposure afforded by presence of the 20 kDa moiety appeared to facilitate distribution of aptamer to tissues, particularly those of highly perfused organs.


Subject(s)
Oligonucleotides/chemistry , Oligonucleotides/pharmacokinetics , Animals , Biological Availability , Chemistry, Pharmaceutical , Dose-Response Relationship, Drug , Male , Oligonucleotides/metabolism , Rats , Rats, Sprague-Dawley , Tissue Distribution/drug effects , Tissue Distribution/physiology
20.
Aust N Z J Public Health ; 27(6): 642-4, 2003 Dec.
Article in English | MEDLINE | ID: mdl-14723414

ABSTRACT

This commentary paper argues that the Asia-Pacific region would benefit from a home-grown version of the European Observatory on Health Care Systems to inform health sector policy: an Asia-Pacific Observatory. The countries in this diverse region, ranging from highly developed to very poor countries, are undergoing dramatic and diverse health sector changes, often on the basis of little evidence and with little information on successes and failures in neighbouring countries. The international community also is interested in knowing more about the many distinctive models of Asia-Pacific health care. While statistical comparisons are important, health policymakers and researchers need to understand the story behind the statistics in order to interpret the numbers and to formulate policies and strategies. Health system profiles therefore are useful instruments that describe how a complex health sector works, offer a comparative framework for cross-national comparisons, identify trends in health system design, and with standardised measures and regular updates measure progress against benchmarks. These reports and expanded analyses have influenced both national and Europe-wide debates on health policy. In the Asia-Pacific region, health systems research has built up a critical mass of studies and people with strong links across countries. The next ambitious steps are to identify sponsors able to support an enterprise that transcends national boundaries and to begin a project of comparative studies of national health systems.


Subject(s)
Delivery of Health Care/organization & administration , Health Policy , Health Services Research , Asia, Southeastern , Data Interpretation, Statistical , Delivery of Health Care/statistics & numerical data , Health Care Sector/organization & administration , Health Care Sector/statistics & numerical data , Health Transition , Humans , Pacific Islands , Policy Making , Quality Assurance, Health Care
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