Barriers to the introduction of novel advanced targeted treatments for Australian dermatology patients: Are skin diseases symptomatic of a systemic healthcare problem?

The aim of this article is to provide education to clinicians about certain barriers restricting the use of advanced targeted treatments in Australian health care. For illustrative purposes, the article focuses on dermatological conditions, but the content is relevant to all specialties that treat inflammatory and chronic diseases. Barriers to care discussed result in a lower than necessary standard of care for patients in Australia despite important advancements in medicine.

The Colorectal cancer RISk Prediction (CRISP) trial: a randomised controlled trial of a decision support tool for risk-stratified colorectal cancer screening.

BACKGROUND: A risk-stratified approach to colorectal cancer (CRC) screening could result in a more acceptable balance of benefits and harms, and be more cost-effective. AIM: To determine the effect of a consultation in general practice using a computerised risk assessment and decision support tool (Colorectal cancer RISk Prediction, CRISP) on risk-appropriate CRC screening. DESIGN AND SETTING: Randomised controlled trial in 10 general practices in Melbourne, Australia, from May 2017 to May 2018. METHOD: Participants were recruited from a consecutive sample of patients aged 50-74 years attending their GP. Intervention consultations included CRC risk assessment using the CRISP tool and discussion of CRC screening recommendations. Control group consultations focused on lifestyle CRC risk factors. The primary outcome was risk-appropriate CRC screening at 12 months. RESULTS: A total of 734 participants (65.1% of eligible patients) were randomised (369 intervention, 365 control); the primary outcome was determined for 722 (362 intervention, 360 control). There was a 6.5% absolute increase (95% confidence interval [CI] = -0.28 to 13.2) in risk-appropriate screening in the intervention compared with the control group (71.5% versus 65.0%; odds ratio [OR] 1.36, 95% CI = 0.99 to 1.86, P = 0.057). In those due CRC screening during follow-up, there was a 20.3% (95% CI = 10.3 to 30.4) increase (intervention 59.8% versus control 38.9%; OR 2.31, 95% CI = 1.51 to 3.53, P<0.001) principally by increasing faecal occult blood testing in those at average risk. CONCLUSION: A risk assessment and decision support tool increases risk-appropriate CRC screening in those due screening. The CRISP intervention could commence in people in their fifth decade to ensure people start CRC screening at the optimal age with the most cost-effective test.

Cost-Effectiveness of Single Versus Multifraction SABR for Pulmonary Oligometastases: The SAFRON II Trial.

PURPOSE: The use of stereotactic ablative body radiation therapy (SABR) in advanced cancer care is increasing, yet the cost-effectiveness of single-fraction (SF) versus multifraction (MF) SABR in pulmonary oligometastases is unknown. METHODS: A prespecified cost-effectiveness analysis was conducted of the Trans Tasman Radiation Oncology Group 13.01 - SAFRON II - randomized trial comparing SF with MF SABR in 87 patients with 133 pulmonary oligometastases. A partitioned survival model assessed costs and quality-adjusted life-years (QALY) over the within-trial period (4 years) and longer-term (10 years). Costs reflected a societal perspective, expressed in Australian dollars (A$) using 2020 prices and were estimated using patient level data on health care utilization for radiation therapy (including patient time), post-radiation systemic therapy and treatment of adverse effects. Quality of life was assessed using the EuroQoL EQ-5D-5L. The incremental cost-effectiveness ratio (ICER) was expressed as the cost per QALY gained for SF versus MF SABR, with uncertainty assessed using deterministic and probabilistic sensitivity analyses. RESULTS: SF cost less than MF for initial therapy (difference of A$1194/patient). Mean time to initiation of systemic drug therapy did not differ between arms (P = .94). Numerical differences in survival favoring SF resulted in greater overall health care use for the within-trial period. The within-trial ICER was A$15,821/QALY and A$23,265/QALY over the longer term. Results were most sensitive to the cost of postprogression therapies and utility values. The sensitivity analysis indicated that SF SABR has a 97% probability of being cost-effective at a willingness-to-pay of A$50,000/QALY. CONCLUSIONS: SF has lower initial costs and is highly likely to be cost-effective. Time to initiation of systemic therapy associated with disease progression is highly patient relevant and is a major driver of cost-effectiveness. Comparisons for SF SABR with nonradiation therapy approaches to the treatment of pulmonary oligometastases warrant further investigation.

Examining health-related quality of life in pediatric cancer patients with febrile neutropenia: Factors predicting poor recovery in children and their parents.

BACKGROUND: The impact febrile neutropenia (FN) has on the health-related quality of life (HRQoL) of children with cancer and their families is poorly understood. We sought to characterize the course of child and parent HRQoL during and following FN episodes. METHOD: Data on HRQoL were collected in the multisite Australian Predicting Infectious ComplicatioNs in Children with Cancer (PICNICC) study. Participants were enrolled between November 2016 to January 2018. The Child Health Utility (CHU9D) was used to assess HRQoL in children (N = 167 FN events) and the Assessment of Quality of Life (AQoL-8D) was used to assess HRQoL parents (N = 218 FN events) at three time points: 0-3 days, 7-days and 30-days following the onset of FN. Group-based trajectory modeling (GBTM) was used to characterize the course of HRQoL. FINDINGS: For children, three distinct groups were identified: persistently low HRQoL over the 30-day course of follow-up (chronic: N = 78/167; 47%), increasing HRQoL after the onset of FN to 30 days follow-up (recovering: N = 36/167; 22%), and persistently high HRQoL at all three timepoints (resilient: N = 53/167; 32%). Applying these definitions, parents were classified into two distinct groups: chronic (N = 107/218, 49%) and resilient (N = 111/218, 51%). The child being male, having solid cancer, the presence of financial stress, and relationship difficulties between the parent and child were significant predictors of chronic group membership for both parents and children. Children classified as high-risk FN were significantly more likely to belong to the recovery group. Being female, having blood cancers and the absence of financial or relationship difficulties were predictive of both parents and children being in the resilient group. INTERPRETATION: Approximately half the children and parents had chronically low HRQoL scores, which did not improve following resolution of the FN episode. The child's sex, cancer type, and presence of financial and relationship stress were predictive of chronic group membership for both parents and children. These families may benefit from increased financial and psychosocial support during anti-cancer treatment. FUNDING: National Health and Medical Research Council Grant (APP1104527).

A cost-effectiveness analysis of front-line treatment strategies in early-stage follicular lymphoma.

Recent data suggest the use of radiotherapy alone (RT) in Early-Stage Follicular Lymphoma is declining. Cost-effectiveness analysis of treatments has not been performed. We constructed a partitioning model (15-year horizon) to compare RT, combined-modality therapy (CMT) and immunochemotherapy with rituximab maintenance (ICT + RM) from a PET-staged cohort from the Australian Lymphoma Alliance. Lifetime direct health care costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) were calculated. AUD $75,000 was defined as the willingness-to-pay threshold (WTP). The direct healthcare costs were: RT $12,791, CMT $29,391 and ICT + RM $42,644. Compared with RT, CMT demonstrated minimal improvement in QALYs (+0.01) and an ICER well above the WTP threshold ($1,535,488). Compared with RT, ICT + RM demonstrated an improvement in QALYs (+0.41) with an ICER of $73,319. Modeling a 25% cost reduction with a rituximab biosimilar led to further ICER reductions with ICT + RM ($52,476). ICT + RM is cost-effective in early-stage FL from the Australian taxpayer perspective.

Economic evaluation of alternative testing regimes and settings to detect undiagnosed HIV in Australia.

BACKGROUND: The study aimed to estimate the comparative costs per positive diagnosis of previously undetected HIV in three testing regimes: conventional; parallel and point of care (POC) testing. The regimes are analysed in six testing settings in Australia where infection is concentrated but with low prevalence. METHODS: A cost model was developed to highlight the trade-offs between test and economic efficiency from a provider perspective. First, an estimate of the number of tests needed to find a true (previously undiagnosed) positive diagnosis was made. Second, estimates of the average cost per positive diagnosis in whole of population (WoP) and men who have sex with men (MSM) was made, then third, aggregated to the total cost for diagnosis of all undetected infections. RESULTS: Parallel testing is as effective as conventional testing, but more economically efficient. POC testing provide two significant advantages over conventional testing: they screen out negatives effectively at comparatively lower cost and, with confirmatory testing of reactive results, there is no loss in efficiency. The average and total costs per detection in WoP are prohibitive, except for Home Self Testing. The diagnosis in MSM is cost effective in all settings, but especially using Home Self Testing when the individual assumes the cost of testing. CONCLUSIONS: This study illustrates the trade-offs between economic and test efficiency and their interactions with population(s) prevalence. The efficient testing regimes and settings are presently under or not funded in Australia. Home Self Testing has the potential to dramatically increase testing rates at very little cost.

The Course of Posttraumatic Stress in Children: Examination of Symptom Trajectories and Predictive Factors Following Admission to Pediatric Intensive Care.

OBJECTIVES: This study investigated trauma symptom trajectories of children 2-16 years old following admission to pediatric intensive care and identified factors that predicted a child's trauma symptom trajectory. DESIGN: Prospective longitudinal design. SETTING: Two tertiary care PICUs in Brisbane, Qld, Australia. PATIENTS: Children 2-16 years old admitted to PICU for longer than 8 hours. MEASUREMENTS MAIN RESULTS: Maternal reported child posttraumatic stress symptoms (n = 272) on the Trauma Symptom Checklist for Young Children were used to assess posttraumatic stress symptoms up to 12 months post admission. Semiparametric group-based trajectory analyses were completed to identify patterns over time. Age, gender, length of stay, premorbid functioning, maternal perceived threat to life, and maternal acute distress were assessed as potential risk factors. Three likely trajectory groups were identified. The majority of children were resilient (83.8%); however, a significant minority experienced chronic symptoms (12.9%) or elevated stress symptoms which resolved quickly (3.3%). After controlling for other variables, maternal report of premorbid internalizing behavior significantly predicted both chronic (odds ratio, 6.3) and recovery (odds ratio, 38.0) trajectories. Maternal acute distress significantly predicted child chronic symptom trajectories (odds ratio, 5.2). CONCLUSIONS: Children with elevated trauma symptoms postintensive care need timely and effective intervention. The majority of children with high levels of acute symptoms will continue to have chronic, ongoing posttraumatic stress symptoms. In addition, acute maternal distress and preexisting internalizing child behavior predict ongoing psychologic distress after discharge from the PICU. Screening in the acute period post-PICU admission may identify children likely to experience ongoing chronic posttraumatic distress symptoms and enable targeted treatment of children at risk. This is the first study to examine symptom trajectories in children following pediatric intensive care admission and includes a sample of very young children.

Potential Country-level Health and Cost Impacts of Legalizing Domestic Sale of Vaporized Nicotine Products.

BACKGROUND: The net impact on population health and health system costs of vaporized nicotine products is uncertain. We modeled, with uncertainty, the health and cost impacts of liberalizing the vaporized nicotine market for a high-income country, New Zealand (NZ). METHODS: We used a multistate life-table model of 16 tobacco-related diseases to simulate lifetime quality-adjusted life-years (QALYs) and health system costs at a 0% discount rate. We incorporated transitions from never, former, and current smoker states to, and from, regularly using vaporized nicotine and literature estimates for relative risk of disease incidence for vaping compared with smoking. RESULTS: Compared with continuation of baseline trends in smoking uptake and cessation rates and negligible vaporized nicotine use, we projected liberalizing the market for these products to gain 236,000 QALYs (95% uncertainty interval [UI] = 27,000 to 457,000) and save NZ$3.4 billion (2011 NZ$) (95% UI = NZ$370 million to NZ$7.1 billion) or US$2.5 billion (2017 NZ$). However, estimates of net health gains for 0- to 14-year olds and 65+ year olds had 95% UIs including the null. Uncertainty around QALYs gained was mainly driven by uncertainty around the impact of vaporized nicotine products on population-wide cessation rates and the relative health risk of vaping compared with smoking. CONCLUSIONS: This modeling suggested that a fairly permissive regulatory environment around vaporized nicotine products achieves net health gain and cost savings, albeit with wide uncertainty. Our results suggest that optimal strategies will also be influenced by targeted smoking cessation advice, regulations around chemical constituents of these products, and marketing and age limits to prevent youth uptake of vaping.

Knowledge and awareness of HIV self-testing among Australian gay and bisexual men: a comparison of never, sub-optimal and optimal testers willingness to use.

This paper explores the willingness to use and pay for HIV Self-testing (HIVST) among Australian gay and bisexual men (GBM). Bivariate and univariate multinominal logistic regression of data from an online survey was performed. Thirty-one (13%) had never HIV tested and 41.9% (88) were testing sub-optimally by Australian guidelines. Half (58.4%, 136) had never heard of HIVST, however, 56.2% (131) reported willingness to use HIVST, with sub-optimal (OR=2.13; p < 0.01) and never-testers (OR=2.01; p < 0.10) significantly more likely to do so than optimal-testers. Most were confident (51.7%, 119) or somewhat confident (29.1%, 67) accessing support following a reactive result, however, never-testers were significantly less confident compared to previous testers (OR=3.47; p< 0.05). Less than a quarter (23.6%, 57) were willing to pay for a kit with AUD$15 (R2 = 0.9882) the estimated preferred price. This research confirms that HIVST is an important and accepted adjunct to established HIV testing modalities, particularly among sub-optimal and never-testers and that online (61.6%, 143) or clinic-based (61.6%, 143) dissemination are preferred. Research examining how best to disseminate HIVST in a range of safe and effective models needs to continue to ensure HIVST is part of a comprehensive strategy that facilitates usage and linkages to care.

Changing patterns in the prevalence of posttraumatic stress disorder, major depressive episode and generalized anxiety disorder over 24 months following a road traffic crash: Results from the UQ SuPPORT study.

OBJECTIVE: To examine the prevalence and changing patterns of PTSD, major depressive episode (MDE), and generalized anxiety disorder (GAD) in adult claimants who sustained a non-catastrophic injury in a road traffic crash (RTC) in Queensland, Australia. METHOD: Participants (N = 284) were assessed at approximately 6, 12, and 24 months post-RTC using the composite international diagnostic interview (CIDI) modules for PTSD, and CIDI-short form for MDE, and GAD. RESULTS: The prevalence of at least one of these disorders was 48.2%, 52.5%, and 49.3%, at 6, 12, and 24 months, respectively. Comorbidity was common (20.8% at 6 months, 27.1% at 12 months, and 21.1% at 24 months) and only 33.1% of participants never met PTSD, GAD, or MDE criteria. A substantial proportion of participants (42.3%) had an unstable diagnostic pattern over time. Participants with multiple diagnoses at 6 months were more likely to continue to meet diagnostic criteria for any disorder at 12 and 24 months than participants with a single diagnosis. Participants with PTSD (with or without MDE/GAD) were more likely to meet criteria for any disorder at 24 months than participants with another diagnosis. Preinjury psychiatric history increased the likelihood of any disorder at 24 months post-injury, but did not significantly increase the likelihood of PTSD. CONCLUSIONS: People injured in a RTC are at risk of having complex psychological presentations over time. Interventions to prevent mental disorders, especially PTSD, in the early post-injury period are needed to prevent chronic psychological injury, including consideration of comorbidity and dynamic course.