Pharmaceutical benefits in Australia and Sweden: welfare policy and the cost of prescription drugs

Pharmaceutical benefits provide a stable framework within which consumers, prescribers, suppliers, pharmacists and other actors undertake transactions. The state in effect delivers a good that enhances individual autonomy. A major reason for the legitimacy enjoyed by pharmaceutical benefits in both Australia and Sweden is that these programs have strong attributes of universalism (rather than targeting). Sweden's predominantly public health system allows greater scope for pharmaceutical policy innovation. Australia's Pharmaceutical Benefits Scheme (PBS), while historically resilient and effective, is now wedged precariously between traditional considerations of equity and public health on the one hand, and constant pressure for increased marketisation on the other.

The initiation and administration of drugs for advanced life support by critical care nurses in the absence of a medical practitioner

Current legislation does not permit the administration of first line resuscitation medications by suitably qualified Division 1 registered nurses (RNs) in the absence of a medical officer. This omission by the Drugs,  Poisons and Controlled Substances Act 1981 (Vic) and the Drugs, Poisons and The Controlled Substances Regulations 1995 (Vic) leaves many critical care nurses in a vulnerable legal position.

The primary aim of this study was to gauge the view of critical care nurses with respect to lobbying for change to the current legislation. In addition, the study aimed to explore and describe the educational preparation, practice perceptions and experiences of RNs working in critical care regarding cardiopulmonary resuscitation and the administration of first line advanced life support (ALS) medications in the absence of a medical officer. It was anticipated that data collected would demonstrate some of the dilemmas associated with the initiation and administration of ALS medications for practising critical care nurses and could be used to inform controlling bodies in order for them to gain an appreciation of the issues facing critical care nurses during resuscitation.

A mailout survey was sent to all members of the Victorian Branch of the Australian College of Critical Care Nurses (ACCCN). The results showed that the majority of nurses underwent an annual ALS assessment and had current ALS accreditation. Nurses indicated that they felt educationally prepared and were confident to manage cardiopulmonary resuscitation without a medical officer; indeed, the majority had done so. The differences in practice issues for metropolitan, regional and rural nurses were highlighted. There is therefore clear evidence to suggest that legislative amendments are appropriate and necessary, given the time critical nature of cardiopulmonary arrest. There was overwhelming support for ACCCN Vic. Ltd to lobby the Victorian government for changes to the law.

Generic drugs: international trends and policy developments in Australia

Public and private third-party payers in many countries encourage or mandate the use of generic drugs. This article examines the development of generics policy in Australia, against the background of a description of international trends in this area, and related experiences of reference pricing programs. The Australian generics market remains underdeveloped due to a historical legacy of small Pharmaceutical Benefits Scheme price differentials between originator brands and generics. It is argued that policy measures open to the Australian government can be conceived as clustering around two different approaches: incremental changes within the existing regulatory framework, or a shift towards a high volume/low price role of generics which would speed up the delivery of substantial cost savings, and could provide enhanced scope for the financing of new, patented drugs.

Emerging trends in the use of drugs to manage the challenging behaviour of people with intellectual disability

Background Concerns about the pharmacological management of the behaviour of individuals with intellectual disability have resulted in the development of legislative and procedural controls.
Method This Australian study provided a comparison of 873 reported cases where drugs were administered to manage behaviour in March 2000, with 762 cases reported in March 1993. Drug use in individuals who remained medicated across time (n = 316: recurrent sample) was also compared with those who were reported only in 1993 (n = 329: limited sample).
Results A small decrease in the proportion of individuals who were reported to have received medication was evident over time (from 5% to 4.5% of total population). However, this was accompanied by an increase in drug diversity and interclass polypharmacy. An increase in antidepressant use was evident (from 7.4% to 13.8% of reported drugs), and there was a trend towards greater reporting of medication for acute behavioural problems and medication use with children. Greater use of antipsychotic drugs was evident in individuals who remained medicated across time compared with those who did not.
Conclusions The findings suggest the need for continuous research into practice. The fact that many individuals receive medication over long periods makes it incumbent on service providers to engage in regular, comprehensive and individualized review and evaluation of medication regimes.

Freedom and slavery: constructions of ideologies in illicit drugs treatment

Freedom, autonomy, enslavement and coercion have a multitude of meanings which are determined by the writer’s discipline background and intent, even more so in the area of illicit drugs’ policy and treatment. This paper proposes to begin to untangle the multiplicity of meanings which are attached to two contrasting forms of illicit drugs treatment, harm minimisation and abstinence-based treatments. Both treatment regimes lay claim to the high moral ground in this regard - freedom and autonomy are explicit terms used in the rhetoric of both. How this can best be understood and what sociologists can contribute to the debates about illicit drug treatments is the terrain this paper traverses. It does this by laying out the different meanings of the terms in social theory and then by trying to understand the ‘truth’ claims of treatment proponents and using a Foucauldian perspective to critique these claims.

Systematic review and meta-analysis of evidence for increasing numbers of drugs in antiretroviral combination therapy

Objective: To assess the evidence for the effectiveness of increasing numbers of drugs in antiretroviral combination therapy.

Design: Systematic review, meta-analysis, and meta-regression of fully reported randomised controlled trials. All studies included compared quadruple versus triple therapy, triple versus double therapy, double versus monotherapy, or monotherapy versus placebo or no treatment.

Participants: Patients with any stage of HIV infection who had not received antiretroviral therapy.

Main outcome measures: Changes in disease progression or death (clinical outcomes); CD4 count and plasma viral load (surrogate markers).
Search strategy: Six electronic databases, including Medline, Embase, and the Cochrane Library, searched up to February 2001.

Results: 54 randomised controlled trials, most of good quality, with 66 comparison groups were included in the analysis. For both the clinical outcomes and surrogate markers, combinations with up to and including three (triple therapy) were progressively and significantly more effective. The odds ratio for disease progression or death for triple therapy compared with double therapy was 0.6 (95% confidence interval 0.5 to 0.8). Heterogeneity in effect sizes was present in many outcomes but was largely related to the drugs used and trial quality.

Conclusions: Evidence from randomised controlled trials supports the use of triple therapy. Research is needed on the effectiveness of quadruple therapies and the relative effectiveness of specific combinations of drugs.

Disentangling the stigma of HIV/AIDS from the stigmas of drugs use, commercial sex and commercial blood donation - a factorial survey of medical students in China

Background
HIV/AIDS related stigma interferes with the provision of appropriate care and support for people living with HIV/AIDS. Currently, programs to address the stigma approach it as if it occurs in isolation, separate from the co-stigmas related to the various modes of disease transmission including injection drug use (IDU) and commercial sex (CS). In order to develop better programs to address HIV/AIDS related stigma, the inter-relationship (or 'layering') between HIV/AIDS stigma and the co-stigmas needs to be better understood. This paper describes an experimental study for disentangling the layering of HIV/AIDS related stigmas.

Methods
The study used a factorial survey design. 352 medical students from Guangzhou were presented with four random vignettes each describing a hypothetical male. The vignettes were identical except for the presence of a disease diagnosis (AIDS, leukaemia, or no disease) and a co-characteristic (IDU, CS, commercial blood donation (CBD), blood transfusion or no co-characteristic). After reading each vignette, participants completed a measure of social distance that assessed the level of stigmatising attitudes.

Results
Bivariate and multivariable analyses revealed statistically significant levels of stigma associated with AIDS, IDU, CS and CBD. The layering of stigma was explored using a recently developed technique. Strong interactions between the stigmas of AIDS and the co-characteristics were also found. AIDS was significantly less stigmatising than IDU or CS. Critically, the stigma of AIDS in combination with either the stigmas of IDU or CS was significantly less than the stigma of IDU alone or CS alone.

Conclusion
The findings pose several surprising challenges to conventional beliefs about HIV/AIDS related stigma and stigma interventions that have focused exclusively on the disease stigma. Contrary to the belief that having a co-stigma would add to the intensity of stigma attached to people with HIV/AIDS, the findings indicate the presence of an illness might have a moderating effect on the stigma of certain co-characteristics like IDU. The strong interdependence between the stigmas of HIV/AIDS and the co-stigmas of IDU and CS suggest that reducing the co-stigmas should be an integral part of HIV/AIDS stigma intervention within this context.

Design of new oxazaphosphorine anticancer drugs

The oxazaphosphorines including cyclophosphamide (CPA, Cytoxan, or Neosar), ifosfamide (IFO, Ifex) and trofosfamide (Ixoten) represent an important group of therapeutic agents due to their substantial antitumor and immunomodulating activity. However, several intrinsic limitations have been uncounted during the clinical use of these oxazaphosphorines, including substantial pharmacokinetic variability, resistance and severe host toxicity. To circumvent these problems, new oxazaphosphorines derivatives have been designed and evaluated with an attempt to improve the selectivity and response with reduced host toxicity. These include mafosfamide (NSC 345842), glufosfamide (D19575, β-Dglucosylisophosphoramide mustard), S-(-)-bromofosfamide (CBM-11), NSC 612567 (aldophosphamide perhydrothiazine) and NSC 613060 (aldophosphamide thiazolidine). Mafosfamide is an oxazaphosphorine analog that is a chemically stable 4-thioethane sulfonic acid salt of 4-hydroxy-CPA. Glufosfamide is IFO derivative in which the isophosphoramide mustard, the alkylating metabolite of IFO, is glycosidically linked to a β-D-glucose molecule. Phase II studies of glufosfamide in the treatment of pancreatic cancer, non-small cell lung cancer (NCSLC), and recurrent glioblastoma multiform (GBM) have recently completed and Phase III trials are ongoing, while Phase I studies of intrathecal mafosfamide have recently completed for the treatment of meningeal malignancy secondary to leukemia, lymphoma, or solid tumors. S-(-)- bromofosfamide is a bromine-substituted IFO analog being evaluated in a few Phase I clinical trials. The synthesis and development of novel oxazaphosphorine analogs with favourable pharmacokinetic and pharmacodynamic properties still constitutes a great challenge for medicinal chemists and cancer pharmacologists.

Mechanism-based inhibition of cytochrome P450 3A4 by therapeutic drugs

Consistent with its highest abundance in humans, cytochrome P450 (CYP) 3A is responsible for the metabolism of about 60% of currently known drugs. However, this unusual low substrate specificity also makes CYP3A4 susceptible to reversible or irreversible inhibition by a variety of drugs. Mechanism-based inhibition of CYP3A4 is characterised by nicotinamide adenine dinucleotide phosphate hydrogen (NADPH)-, time- and concentration-dependent enzyme inactivation, occurring when some drugs are converted by CYP isoenzymes to reactive metabolites capable of irreversibly binding covalently to CYP3A4. Approaches using in vitro, in silico and in vivo models can be used to study CYP3A4 inactivation by drugs. Human liver microsomes are always used to estimate inactivation kinetic parameters including the concentration required for half-maximal inactivation (K(I)) and the maximal rate of inactivation at saturation (k(inact)).Clinically important mechanism-based CYP3A4 inhibitors include antibacterials (e.g. clarithromycin, erythromycin and isoniazid), anticancer agents (e.g. tamoxifen and irinotecan), anti-HIV agents (e.g. ritonavir and delavirdine), antihypertensives (e.g. dihydralazine, verapamil and diltiazem), sex steroids and their receptor modulators (e.g. gestodene and raloxifene), and several herbal constituents (e.g. bergamottin and glabridin). Drugs inactivating CYP3A4 often possess several common moieties such as a tertiary amine function, furan ring, and acetylene function. It appears that the chemical properties of a drug critical to CYP3A4 inactivation include formation of reactive metabolites by CYP isoenzymes, preponderance of CYP inducers and P-glycoprotein (P-gp) substrate, and occurrence of clinically significant pharmacokinetic interactions with coadministered drugs.Compared with reversible inhibition of CYP3A4, mechanism-based inhibition of CYP3A4 more frequently cause pharmacokinetic-pharmacodynamic drug-drug interactions, as the inactivated CYP3A4 has to be replaced by newly synthesised CYP3A4 protein. The resultant drug interactions may lead to adverse drug effects, including some fatal events. For example, when aforementioned CYP3A4 inhibitors are coadministered with terfenadine, cisapride or astemizole (all CYP3A4 substrates), torsades de pointes (a life-threatening ventricular arrhythmia associated with QT prolongation) may occur.However, predicting drug-drug interactions involving CYP3A4 inactivation is difficult, since the clinical outcomes depend on a number of factors that are associated with drugs and patients. The apparent pharmacokinetic effect of a mechanism-based inhibitor of CYP3A4 would be a function of its K(I), k(inact) and partition ratio and the zero-order synthesis rate of new or replacement enzyme. The inactivators for CYP3A4 can be inducers and P-gp substrates/inhibitors, confounding in vitro-in vivo extrapolation. The clinical significance of CYP3A inhibition for drug safety and efficacy warrants closer understanding of the mechanisms for each inhibitor. Furthermore, such inactivation may be exploited for therapeutic gain in certain circumstances.

Sibling peer support group for young people with a sibling using drugs: a pilot study

Siblings of young people abusing drugs are at particular risk for drug abuse and other health compromising behaviors. A Sibling Peer Support Group was developed by the Centre for Adolescent Health (Melbourne, Australia) for young people aged 13 to 18 years with a problematic drug user in their family. Groups aimed to provide support and information, promote harm minimization, and reduce the sense of isolation. The project emanated from the recognized need for specific support for adolescent siblings of problematic drug users. Evaluation of two pilot groups indicated positive benefits for group members, who reported feeling better informed, more supported, and having a reduced sense of isolation. Parents reported that their adolescent attending the group demonstrated improved communication with, and greater understanding and tolerance of, the family member using drugs. Promising indicators at a community level were manifested in enthusiastic collaboration among schools, police and local service agencies, and the organization of a local drug forum. There appeared to be little evidence that the groups inadvertently encouraged drug use. Recruitment of young people into groups was the major challenge for the project, but among drug and alcohol and family organizations there was support for the concept of a Sibling Peer Support Group. A new model to overcome the challenge of recruitment is proposed.

Drugs and police

Discusses the corruption-cloud hanging over the Victoria police drug squad. What does it mean for criminal investigations and trials? And, speaking more generally, what is it about the drugs-trade and the way the law deals with it - that can lead law enforcers down the wrong path?