Effectiveness of commercial inhibitors against subtype F HIV-1 protease

Subtype F wild type HIV protease has been kinetically characterized using six commercial inhibitors (amprenavir, indinavir, lopinavir, nelfinavir, ritonavir and saquinavir) commonly used for HIV/AIDS treatment, as well as inhibitor TL-3 and acetylpepstatin. We also obtained kinetic parameters for two multi-resistant proteases (one of subtype B and one of subtype F) harboring primary and secondary mutations selected by intensive treatment with ritonavir/nelfinavir. This newly obtained biochemical data shows that all six studied commercially available protease inhibitors are significantly less effective against subtype F HIV proteases than against HIV proteases of subtype B, as judged by increased K(i) and biochemical fitness (vitality) values. Comparison with previously reported kinetic values for subtype A and C HIV proteases show that subtype F wild type proteases are significantly less susceptible to inhibition. These results demonstrate that the accumulation of natural polymorphisms in subtype F proteases yields catalytically more active enzymes with a large degree of cross-resistance, which thus results in strong virus viability.

Effectiveness of artemether-lumefantrine provided by community health workers in under-five children with uncomplicated malaria in rural Tanzania : an open label prospective study

Background: Home-management of malaria (HMM) strategy improves early access of anti-malarial medicines to high-risk groups in remote areas of sub-Saharan Africa. However, limited data are available on the effectiveness of using artemisinin-based combination therapy (ACT) within the HMM strategy. The aim of this study was to assess the effectiveness of artemether-lumefantrine (AL), presently the most favoured ACT in Africa, in under-five children with uncomplicated Plasmodium falciparum malaria in Tanzania, when provided by community health workers (CHWs) and administered unsupervised by parents or guardians at home. Methods: An open label, single arm prospective study was conducted in two rural villages with high malaria transmission in Kibaha District, Tanzania. Children presenting to CHWs with uncomplicated fever and a positive rapid malaria diagnostic test (RDT) were provisionally enrolled and provided AL for unsupervised treatment at home. Patients with microscopy confirmed P. falciparum parasitaemia were definitely enrolled and reviewed weekly by the CHWs during 42 days. Primary outcome measure was PCR corrected parasitological cure rate by day 42, as estimated by Kaplan-Meier survival analysis. This trial is registered with ClinicalTrials.gov, number NCT00454961. Results: A total of 244 febrile children were enrolled between March-August 2007. Two patients were lost to follow up on day 14, and one patient withdrew consent on day 21. Some 141/241 (58.5%) patients had recurrent infection during follow-up, of whom 14 had recrudescence. The PCR corrected cure rate by day 42 was 93.0% (95% CI 88.3%-95.9%). The median lumefantrine concentration was statistically significantly lower in patients with recrudescence (97 ng/mL [IQR 0-234]; n = 10) compared with reinfections (205 ng/mL [114-390]; n = 92), or no parasite reappearance (217 [121-374] ng/mL; n = 70; p <= 0.046). Conclusions: Provision of AL by CHWs for unsupervised malaria treatment at home was highly effective, which provides evidence base for scaling-up implementation of HMM with AL in Tanzania.

Comparison of treatment of incomplete abortion with misoprostol by physicians and midwives at district level in Uganda : a randomised controlled equivalence trial

BACKGROUND: Misoprostol is established for the treatment of incomplete abortion but has not been systematically assessed when provided by midwives at district level in a low-resource setting. We investigated the effectiveness and safety of midwives diagnosing and treating incomplete abortion with misoprostol, compared with physicians. METHODS: We did a multicentre randomised controlled equivalence trial at district level at six facilities in Uganda. Eligibility criteria were women with signs of incomplete abortion. We randomly allocated women with first-trimester incomplete abortion to clinical assessment and treatment with misoprostol either by a physician or a midwife. The randomisation (1:1) was done in blocks of 12 and was stratified for study site. Primary outcome was complete abortion not needing surgical intervention within 14-28 days after initial treatment. The study was not masked. Analysis of the primary outcome was done on the per-protocol population with a generalised linear-mixed effects model. The predefined equivalence range was -4% to 4%. The trial was registered at ClinicalTrials.gov, number NCT01844024. FINDINGS: From April 30, 2013, to July 21, 2014, 1108 women were assessed for eligibility. 1010 women were randomly assigned to each group (506 to midwife group and 504 to physician group). 955 women (472 in the midwife group and 483 in the physician group) were included in the per-protocol analysis. 452 (95·8%) of women in the midwife group had complete abortion and 467 (96·7%) in the physician group. The model-based risk difference for midwife versus physician group was -0·8% (95% CI -2·9 to 1·4), falling within the predefined equivalence range (-4% to 4%). The overall proportion of women with incomplete abortion was 3·8% (36/955), similarly distributed between the two groups (4·2% [20/472] in the midwife group, 3·3% [16/483] in the physician group). No serious adverse events were recorded. INTERPRETATION: Diagnosis and treatment of incomplete abortion with misoprostol by midwives is equally safe and effective as when provided by physicians, in a low-resource setting. Scaling up midwives' involvement in treatment of incomplete abortion with misoprostol at district level would increase access to safe post-abortion care. FUNDING: The Swedish Research Council, Karolinska Institutet, and Dalarna University.

Cost-effectiveness of cognitive-behavioural therapy and drug interventions for major depression

Objective: Antidepressant drugs and cognitive–behavioural therapy (CBT) are effective treatment options for depression and are recommended by clinical practice guidelines. As part of the Assessing Cost-effectiveness – Mental Health project we evaluate the available evidence on costs and benefits of CBT and drugs in the episodic and maintenance treatment of major depression.

Method: The cost-effectiveness is modelled from a health-care perspective as the cost per disability-adjusted life year. Interventions are targeted at people with major depression who currently seek care but receive non-evidence based treatment. Uncertainty in model inputs is tested using Monte Carlo simulation methods.

Results: All interventions for major depression examined have a favourable incremental cost-effectiveness ratio under Australian health service conditions. Bibliotherapy, group CBT, individual CBT by a psychologist on a public salary and tricyclic antidepressants (TCAs) are very cost-effective treatment options falling below $A10 000 per disability-adjusted life year (DALY) even when taking the upper limit of the uncertainty interval into account. Maintenance treatment with selective serotonin re-uptake inhibitors (SSRIs) is the most expensive option (ranging from $A17 000 to $A20 000 per DALY) but still well below $A50 000, which is considered the affordable threshold.

Conclusions: A range of cost-effective interventions for episodes of major depression exists and is currently underutilized. Maintenance treatment strategies are required to significantly reduce the burden of depression, but the cost of long-term drug treatment for the large number of depressed people is high if SSRIs are the drug of choice. Key policy issues with regard to expanded provision of CBT concern the availability of suitably trained providers and the funding mechanisms for therapy in primary care.

Cost-effectiveness of psychological and pharmacological interventions for generalized anxiety disorder and panic disorder

Objective: To assess from a health sector perspective the incremental cost-effectiveness of interventions for generalized anxiety disorder (cognitive behavioural therapy [CBT] and serotonin and noradrenaline reuptake inhibitors [SNRIs]) and panic disorder (CBT, selective serotonin reuptake inhibitors [SSRIs] and tricyclic antidepressants [TCAs]).

Method: The health benefit is measured as a reduction in disability-adjusted life years (DALYs), based on effect size calculations from meta-analyses of randomised controlled trials. An assessment on second stage filters ('equity', 'strength of evidence', 'feasibility' and 'acceptability to stakeholders') is also undertaken to incorporate additional factors that impact on resource allocation decisions. Costs and benefits are calculated for a period of one year for the eligible population (prevalent cases of generalized anxiety disorder/panic disorder identified in the National Survey of Mental Health and Wellbeing, extrapolated to the Australian population in the year 2000 for those aged 18 years and older). Simulation modelling techniques are used to present 95% uncertainty intervals (UI) around the incremental cost-effectiveness ratios (ICERs).

Results: Compared to current practice, CBT by a psychologist on a public salary is the most cost-effective intervention for both generalized anxiety disorder (A$6900/DALY saved; 95% UI A$4000 to A$12 000) and panic disorder (A$6800/DALY saved; 95% UI A$2900 to A$15 000). Cognitive behavioural therapy results in a greater total health benefit than the drug interventions for both anxiety disorders, although equity and feasibility concerns for CBT interventions are also greater.

Conclusions: Cognitive behavioural therapy is the most effective and cost-effective intervention for generalized anxiety disorder and panic disorder. However, its implementation would require policy change to enable more widespread access to a sufficient number of trained therapists for the treatment of anxiety disorders.

The effectiveness of the levonorgestrel-releasing intrauterine system in menorrhagia: a systematic review

Objective: To determine whether the levonorgestrel-releasing intrauterine device (LNG-IUS), licensed at present for contraceptive use, may reduce menstrual blood loss with few side effects. If effective, surgery could be avoided with consequent resource savings. Methods: A systematic review addressing the effectiveness and cost effectiveness of the LNG-IUS for menorrhagia was undertaken. Results: Five controlled trials and five case series were found which measured menstrual blood loss. Nine studies recorded statistically significant average menstrual blood loss reductions with LNG-IUS (range 74%–97%). Another showed reduction in menstrual disturbance score. The LNG-IUS was more effective than tranexamic acid, but slightly less effective than endometrial resection at reducing menstrual blood loss. In one study, 64% of women cancelled surgery at six months, compared with 14% of control group women. In another, 82% were taken off surgical waiting lists at one year. No cost effectiveness studies were found. Discussion: Small studies of moderate quality indicate the LNG-IUS is an effective treatment for menorrhagia. Costs may be less than for tranexamic acid in primary and secondary care. Although its use may reduce surgical waiting lists, cost effectiveness assessment requires longer follow up. Conclusion: Effectiveness and cost effectiveness relative to other treatments and the effect on surgical waiting lists can only be established in larger trials measuring patient-centred outcomes in women with menorrhagia.

Assessing cost-effectiveness of drug interventions for schizophrenia

Objective: To assess from a health sector perspective the incremental cost-effectiveness of eight drug treatment scenarios for established schizophrenia.

Method: Using a standardized methodology, costs and outcomes are modelled over the lifetime of prevalent cases of schizophrenia in Australia in 2000. A two-stage approach to assessment of health benefit is used. The first stage involves a quantitative analysis based on disability-adjusted life years (DALYs) averted, using best available evidence. The robustness of results is tested using probabilistic uncertainty analysis. The second stage involves application of 'second filter' criteria (equity, strength of evidence, feasibility and acceptability) to allow broader concepts of benefit to be considered.

Results: Replacing oral typicals with risperidone or olanzapine has an incremental costeffectiveness ratio (ICER) of A$48 000 and A$92 000/DALY respectively. Switching from low-dose typicals to risperidone has an ICER of A$80 000. Giving risperidone to people experiencing side-effects on typicals is more cost-effective at A$20 000. Giving clozapine to people taking typicals, with the worst course of the disorder and either little or clear deterioration, is cost-effective at A$42 000 or A$23 000/DALY respectively. The least costeffective intervention is to replace risperidone with olanzapine at A$160 000/DALY.

Conclusions: Based on an A$50 000/DALY threshold, low-dose typical neuroleptics are indicated as the treatment of choice for established schizophrenia, with risperidone being reserved for those experiencing moderate to severe side-effects on typicals. The more expensive olanzapine should only be prescribed when risperidone is not clinically indicated. The high cost of risperidone and olanzapine relative to modest health gains underlie this conclusion. Earlier introduction of clozapine however, would be cost-effective. This work is limited by weaknesses in trials (lack of long-term efficacy data, quality of life and consumer satisfaction evidence) and the translation of effect size into a DALY change. Some stakeholders, including SANE Australia, argue the modest health gains reported in the literature do not adequately reflect perceptions by patients, clinicians and carers, of improved quality of life with these atypicals.

Cost-effectiveness of cognitive behavioural therapy and selective serotonin reuptake inhibitors for major depression in children and adolescents

Objective:
To assess from a health sector perspective the incremental cost-effectiveness of cognitive behavioural therapy (CBT) and selective serotonin reuptake inhibitors (SSRIs) for the treatment of major depressive disorder (MDD) in children and adolescents, compared to ‘current practice’.
Method:
The health benefit is measured as a reduction in disability-adjusted life years (DALYs), based on effect size calculations from meta-analysis of randomised controlled trials. An assessment on second stage filter criteria (‘equity’; ‘strength of evidence’, ‘feasibility’ and ‘acceptability to stakeholders’) is also undertaken to incorporate additional factors that impact on resource allocation decisions. Costs and benefits are tracked for the duration of a new episode of MDD arising in eligible children (age 6–17 years) in the Australian population in the year 2000. Simulation-modelling techniques are used to present a 95% uncertainty interval (UI) around the cost-effectiveness ratios.
Results:
Compared to current practice, CBT by public psychologists is the most costeffective intervention for MDD in children and adolescents at A$9000 per DALY saved (95% UI A$3900 to A$24 000). SSRIs and CBT by other providers are less cost-effective but likely to be less than A$50 000 per DALY saved (> 80% chance). CBT is more effective than SSRIs in children and adolescents, resulting in a greater total health benefit (DALYs saved) than could be achieved with SSRIs. Issues that require attention for the CBT intervention include equity concerns, ensuring an adequate workforce, funding arrangements and acceptability to various stakeholders.
Conclusions:
Cognitive behavioural therapy provided by a public psychologist is the most
effective and cost-effective option for the first-line treatment of MDD in children and adolescents. However, this option is not currently accessible by all patients and will require change in policy to allow more widespread uptake. It will also require ‘start-up’ costs and attention to ensuring an adequate workforce.

Effectiveness of pain management in hospital in the home programs

Alternative health care delivery models such as HITH facilitate the care of patients requiring acute treatments in their own homes. There are over 570 Diagnostic Related Groups managed in HITH programs and many of these are known to have associated physical pain. The impact of the home environment on patients’ experience of pain or how pain is managed is poorly understood. The purpose of this presentation is to
present the background and preliminary findings of a study that aims to increase our understanding of the issues related to providing optimal pain management for acute care patients who are transferred to Hospital in the Home. This knowledge will enable the development of effective practice guidelines to improve patient outcomes. More specifically, the aims are:
• To identify whether patients are transferred to HITH in pain or develop
   significant pain while in the program
• To identify the frequency and intensity of pain experienced by patients in 3      HITH programs.
• To describe patients’ experience of pain in the home environment.
• To investigate whether patients receive adequate pain relief once                      transferred to HITH.
• To explore the strategies patients use to manage pain at home.

The study will be carried out over 12 months in three HITH units in Victoria: Box Hill Hospital, Alfred Hospital and Epworth Hospital. The design is a descriptive survey of patients’ experience of pain and pain management using a modified version of The American Pain Society’s Patient Outcome Questionnaire. 360 consecutive surgical patients transferred to HITH care in the three participating programs will be interviewed by telephone between 48 and 72 hours of admission to the program.

The findings of this study will identify issues in providing optimum pain management for patients receiving acute care in non-traditional treatment environments.

Personality change and personality disorder : some initial thoughts on the application of McAdams' triarchic model to the treatment of personality disorder

It is increasingly accepted that psychological therapies have an important role to play in the management and treatment of those who are considered to have disorders of personality, particularly those with forensic histories. Whilst there appears to be an emerging evidence base supporting the effectiveness of treatment for this group, there have been relatively few attempts to link treatment approaches to current models of normal personality. In this paper we use McAdams' (1994) triarchic model of personality as a basis for understanding the effective treatment of personality disorders. We conclude that the model may be useful in assisting clinicians to engage patients in treatment, identify innovative methods of intervention, and conceptualise therapeutic progress.

Effectiveness of psychological interventions for depressed elderly people in hostels

Thesis: Depression among older adults is a significant health concern. Research involved development and implementation of psychological intervention among older adults living in residential care. Poor participation was encountered amongst residential care facilities and older adults. The research identified barriers impeding provision of care for older adults with mental health concerns. The portfolio presents case studies demonstrating the flow-on effects of negative childhood experiences into adult relationships. The analyses illustrate how difficulties in childhood are associated with the development of depression and anxiety in later life.

Effectiveness of asthma education camps as a learning environment for children

This study's main purpose was to determine if the children attending one of the Asthma Foundation of Victoria's camps learnt about asthma management and developed skills and behavior that are positive for self management to occur. Final conclusions showed that the program has a positive effect on the management of a child's asthma.

Case study demonstration of the family context of anxiety disorders across the lifespan and the effectiveness of cognitive-behavioural interventions

This portfolio aims to explore some of the issues related to the treatment of anxiety disorders in clinical practice by reviewing the literature on anxiety disorders across the lifespan and presenting four clinical case studies of individuals with different anxiety disorders.

Violent offender rehabilitation and the therapeutic community model of treatment : towards integrated service provision?

Rehabilitation programs for violent offenders are at an early stage in their development, and there is currently only a very limited empirical base from which to draw any conclusions about treatment effectiveness (Jolliffe and Farrington, 2007). Therapeutic communities for offender populations have a much longer history, although the effects of applying this model of treatment to violent offenders have not been systematically investigated. This paper reviews the content and evidence supporting both violent offender treatment programs and therapeutic community models, concluding that approaches to treatment which combine features of both may prove to be most successful, and warrant further development and evaluation.

A preliminary analysis of the cost-effectiveness of the National Bowel Cancer Screening Program – demonstrating the potential value of comprehensive real world data

Background The complexity and cost of treating cancer patients is escalating rapidly and increasingly difficult decisions are being made regarding which interventions provide value for money. BioGrid Australia supports collection and analysis of comprehensive treatment and outcome data across multiple sites. Here we use preliminary data regarding the National Bowel Cancer Screening Program (NBCSP) and stage-specific treatment costs for colorectal cancer (CRC) to demonstrate the potential value of real world data for cost-effectiveness analyses (CEA).

Methods Data regarding the impact of NBCSP on stage at diagnosis was combined with stage-specific CRC treatment costs and existing literature. An incremental CEA was undertaken from a government healthcare perspective, comparing NBCSP to no-screening. The 2008 invited population (n=681,915) was modelled in both scenarios. Effectiveness was expressed as CRC-related life years saved (LYS). Costs and benefits were discounted at 3% per annum.

Results Over the lifetime and relative to no-screening, NBCSP was predicted to save 1,265 life-years, prevent 225 CRC cases and cost an additional $48.3 million, equivalent to a cost-effectiveness ratio of $38,217 per LYS. A scenario analysis assuming full participation improved this to $23,395.

Conclusions This preliminary CEA based largely on contemporary real world data suggests population-based FOBT screening for CRC is attractive. Planned ongoing data collection will enable repeated analyses over time, using the same methodology in the same patient populations, permitting an accurate analysis of the impact of new therapies and changing practice. Similar CEA using real world data related to other disease types and interventions appears desirable.