Therapy In Australia Research Articles

Survey of clinician opinions on the role of proton beam therapy in Australia and New Zealand.

We surveyed the Australian and New Zealand (ANZ) radiation oncology community to assess their perceptions, understanding and experience of the current role of proton beam therapy (PBT) and the existing referral process to access PBT overseas, ahead of the development of the first PBT centre in Australia. The survey was conducted between September and October 2019 using a 17-question instrument, which was distributed by email to all 632 radiation oncology fellows and trainees listed in the Royal Australian and New Zealand College of Radiologists database. One hundred and one respondents completed the survey, with an overall response rate of 16%. Most respondents were based in Australia (93%), with the majority working in public centres only (59%); 51% were >10years post fellowship and 17% were trainees. Most respondents (76%) reported moderate or high levels of confidence in the role of PBT. Only 28% had previously referred a patient for PBT overseas, with the most common referral indication being chordoma. Of those who had not previously referred a patient, 48% were not convinced about the rationale of PBT over current therapies available locally, 33% were not aware of the referral process, and 24% had concerns about the timeliness of a decision for government-funded PBT abroad. This survey has demonstrated that, although there is reasonable confidence in the role of PBT among ANZ radiation oncologists, there are a number of important aspects of PBT awareness, education and access that need to be developed prior to commencement of PBT in Australia.

Neonatal Occupational Therapy in Australia: A Survey and Recommendations for Developing Guidelines for Clinical Practice

Aim and Background: Occupational Therapists form an essential part of the development and care of infants and families in Neonatal Units (NNU) across the world, however, little is documented about their practice in Australia. This article aims to develop a greater understanding of the role of Occupational Therapy in NNU in Australia, compared with international practice guidelines, and recommends the adoption of UK guidelines until Australia specific guidelines emerge. Method: An online questionnaire was developed from a systematic scoping review and piloted by an expert panel. Invitations were sent to thirty Occupational Therapists working in NNUs around Australia. Data analysis included using descriptive statistics and qualitative themes. Results: Twenty two (73%) of NNU Occupational Therapists responded to the survey, representing all levels of NNU. Results describe the current Occupational Therapy role in Australia as encompassing assessment, intervention, teamwork and a variety of ‘other’ activities, all of which required advanced knowledge, skills and paediatric experience, and involved ongoing high-level professional development. Occupational Therapy has a unique role to play in neonatal units. Future development of the role is reliant upon good advocacy and promotion, specialised training opportunities, prospects for networking, support and mentorship for the many Therapists working part-time, and ongoing research. The Australian Occupational Therapy NNU role compares similarly with those cited internationally (UK & US). The development of guidelines for evidence based clinical practice of neonatal Occupational Therapy in Australia was highly sought by clinicians. The adoption of the ‘Occupational Therapy in neonatal services and early intervention: practice guideline’ (RCOT 2017) is proposed until the emergence of specific Australian guidelines.

Low hepatitis C virus reinfection rate despite ongoing risk following universal access to direct-acting antiviral therapy among people living with HIV.

To evaluate changes in injecting and sexual risk behaviours, and hepatitis C virus (HCV) reinfection incidence among people with HIV/HCV coinfection following unrestricted access to direct-acting antiviral therapy in Australia. Prospective observational cohort study (2014-2018). Among people enrolled in the Control and Elimination of HCV from HIV-infected individuals within Australia study, changes in injecting and sexual behaviour were evaluated, including injecting drug use (IDU) in the last 6 months and last month, frequency of IDU and equipment sharing, condom-less anal intercourse with casual male partner(s), and group sex. HCV reinfection incidence was evaluated with follow-up through May 2018. Overall, 272 HIV/HCV antibody-positive participants [median age; 50 years, 96% male, 83% identified as gay and bisexual men (GBM)] had behavioural data at enrolment and follow-up (median 2.91 years) available for analysis. The proportion reporting IDU in the last 6 months remained stable from enrolment (35%) to follow-up (39%). Among GBM, the proportion reporting condom-less anal intercourse with casual partner(s) at enrolment (48%) and follow-up (46%) was also similar. Reinfection was detected in five individuals (all GBM) during total follow-up of 474 person-years for an overall incidence of 1.05 per 100 person-years (95% confidence interval, 0.44-2.53). No change was observed in levels of injecting or sexual risk behaviour for HCV infection following unrestricted access to direct-acting antiviral therapy in an Australian HIV/HCV cohort. Incidence of HCV reinfection was low potentially reflecting high levels of treatment coverage within this population. Continued screening and rapid retreatment of reinfection will be required to maintain progress towards elimination.

Ocular Tissue for Research in Australia: Strategies for Potential Research Utility of Surplus and Transplant-Ineligible Deceased Donations.

A 2016 Price Waterhouse Cooper Report, commissioned by the Australian Commonwealth Government's Organ and Tissue Authority, indicated that Australia had been meeting its human ocular tissue for transplant needs. It further suggested that Australia should consider exportation as a management strategy for excess tissue. Although we do not seek to discuss how the Price Waterhouse Cooper Report determined that need was being met, nor the potential value of exportation in this article, we propose that Ocular Tissue for Research (OTR), and particularly identification of donors for research, and timely access to fresh domestic tissue, be considered as an alternate or simultaneous surplus management strategy. A robust OTR system could provide long-term domestic support and investment into research and development of therapies in Australia. Such a system would also provide a meaningful donation option for those otherwise unable to donate for transplant. This article attempts to document, for the first time to our knowledge, the current recovery and distribution processes of deceased OTR in Australia. It maps the process steps, identifies the stakeholders and needs, discusses the limitations and barriers, and proposes key policy and practice reform strategies that may assist in improving access to OTR.Translational RelevanceTo improve and increase access to human ocular tissue for research, and in turn, advance vision science and clinical application.

SUN-188 PATIENT MORTALITY RISK FOR PERITONEAL DIALYSIS (PD) VERSUS FACILITY HEMODIALYSIS (HD) BY DIABETES MELLITUS STATUS OVER 1997-2017 IN THE AUSTRALIAN AND NEW ZEALAND DIALYSIS POPULATION

Older literature suggests that mortality risk in patients with diabetes mellitus is higher on PD compared to HD. However, more recent literature from numerous health jurisdictions suggest that the overall mortality risk on PD is improving compared to that on HD (e.g. Sci Rep. 2019 Apr 11;9(1):5905). This may invalidate the findings in these older studies showing higher mortality with PD in diabetic patients. Here, we directly compare survival on PD versus facility HD by diabetes mellitus status (Type 1 or 2 vs. none) across different eras of the recent past. We studied all adult patients commencing renal replacement therapy in Australia and New Zealand in the 20 years prior 31-December-2017 using the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA). We looked for the effect of PD versus facility HD on mortality risk by diabetic status across different eras of dialysis inception. We used Cox proportional hazards regression, adjusting for time-varying co-morbidity, demographics, late referral, primary renal disease, eGFR at dialysis inception, and initial treating center as a shared frailty. For the main analysis, we used an as-treated framework with time-varying modality and a 90-day lag for the attribution of death to modality. We performed a sensitivity analysis using an intention-to-treat framework with modality assigned at 90 days post-dialysis inception and no lag for the attribution of death. Given the non-proportional hazards for mortality between PD and HD, we repeated the analyses using eras of different lengths (4 x 5-year intervals, 3 x 7-year ones, 2 x 10-year ones). We censored patients at the end of each era to ensure the same maximum duration of follow-up within each era. The study cohort contained a maximum of 52,103 subjects with 19,667 deaths over 140,183 patient-years. 61% were males, median (IQR) age was 62 (22), 46.6% had diabetes mellitus. In those with diabetes mellitus, survival on PD was associated with worse survival compared to facility HD in the cohorts before 2013, but is associated with similar survival in cohorts initiating dialysis thereafter (e.g. hazard ratio for PD versus HD in those with diabetes mellitus starting 2013-2017 is 1.01, 95% confidence intervals 0.91 to 1.13). Increasing the length of the era and therefore duration of follow-up in each era did not abrogate improvement in mortality risk on PD relative to HD over time. The sensitivity analysis with the intention to treat framework did not meaningfully change estimates. Our study indicates that, despite increased comorbidity, survival outcomes on PD relative to facility HD are improving with time. This is the case also for patients with diabetes mellitus. Compared to previously, the survival of such patients is not meaningfully different on PD versus facility HD at the current time. Our analyses have potential for residual confounding from the limited collection of co-morbidity, and lack of socioeconomic, medication and biochemical data in analyses. The results of our study may be due to improved pre-dialysis care, patient selection (eg dialysis modality selection and dialysis versus conservative care in the elderly), improvements in general care of patient co-morbidities and advances in dialysis technology and practice.

SUN-187 MORTALITY RISK BY DIALYSIS MODALITY OVER 1997 TO 2017 IN THE AUSTRALIAN AND NEW ZEALAND DIALYSIS POPULATION

The relationship between mortality risk and modality can vary by era. We recently showed that improvements in mortality risk on home hemodialysis (HD) and peritoneal dialysis (PD) are outpacing those on facility HD in Australia and New Zealand (Am J Kidney Dis. 2015 Sep;66(3):489-98). Here, we extend those analyses by directly comparing mortality risk on home HD and PD relative to facility HD across different eras of the recent past. We studied all adult patients commencing renal replacement therapy in Australia and New Zealand in the 20 years prior 31-December-2017 using the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA). We compared mortality risk by modality across different eras of dialysis inception using Cox proportional hazards regression, adjusting for time-varying co-morbidity, demographics, presence and type of diabetes mellitus, late referral, primary renal disease, eGFR at dialysis inception, and initial treating center as a shared frailty. For the main analysis, we used an as-treated framework with time-varying modality and a 90-day lag for the attribution of death to modality. We performed a sensitivity analysis using an intention-to-treat framework with modality assigned at 90 days post-dialysis inception and no lag for the attribution of death. Given the non-proportional hazards for mortality between PD and HD, we repeated the analyses using eras of different lengths (4 x 5-year intervals, 3 x 7-year ones, 2 x 10-year ones). We censored patients at the end of each era to ensure the same maximum duration of follow-up within each era. The study cohort contained a maximum of 52,103 subjects with 19,667 deaths over 140,183 patient-years. 61% were males, median (IQR) age was 62 (22), 46.6% had diabetes mellitus. Compared to facility HD, home HD was associated with better survival by 30-50% across all eras. Compared to facility HD, all forms of PD were associated with poorer survival in earlier eras, but with similar or better survival in cohorts initiating dialysis more recently (e.g. for 2013-2017: continuous ambulatory PD hazard ratio 0.87, 95% confidence intervals 0.78-0.99; automated PD HR 0.90, 95% confidence intervals 0.82-1.00). The sensitivity analysis using the intention-to-treat framework did not meaningfully change estimates. Our study indicates that, despite increased comorbidity, survival outcomes on dialysis are improving with time. Most recently, home HD is associated with better survival relative to facility HD, and PD with similar or better survival. Our analyses have potential for residual confounding from the limited collection of co-morbidity, and lack of socioeconomic, medication and biochemical data in analyses. The results of our study may be due to improved pre-dialysis care, patient selection (eg dialysis modality selection and dialysis versus conservative care in the elderly), improvements in general care of patient co-morbidities and advances in dialysis technology and practice.

Development, Implementation, and Evaluation of Treatment Guidelines for Herpes Simplex Keratitis in Sydney, Australia.

To develop and measure the uptake of a local guideline for herpes simplex keratitis (HSK) and to standardize initial antiviral therapy in Australia. The Registered Nurses' Association of Ontario Toolkit: "Implementation of Best Practice Guidelines" was used to develop, implement, and evaluate the guideline at Sydney Eye Hospital. An implementation team was established to reach consensus on antiviral therapy guidelines through review of available evidence, identifying stakeholders, facilitators and barriers, creating strategies for implementation, and developing a sustainability plan. An audit of all adult HSK cases during a 6-month postguideline implementation period was conducted, and the results were compared with a preimplementation audit. A web-based survey was created to assess clinician awareness, usage, and level of knowledge of the guideline. Clinicians, pharmacists, and administrative staff were identified as stakeholders. Changing clinician's behavior was the major barrier to implementation. Implementation strategies included printed and online materials and lectures to clinicians. A postimplementation audit included 85 patients, and 95 clinicians received a web-based survey. The dose of the prescribed antiviral medication was in alignment with the local guideline in 80% (51/64) of the patients compared with 73% (163/223) before implementation (P = 0.331). Stromal HSK with ulceration and keratouveitis were excluded because there were no recommendations before implementation. Over 70% of clinicians (30/41) were aware of the guideline and accessed them through educational resources. Guidelines for the management of HSK may improve standardization of initial antiviral therapy in HSK. In practice, most clinicians were aware of and adhered to the local guideline.

The Emergence and Development of Cognitive Behaviour Therapy in Australia: Observations from an Early Player

The Emergence and Development of Cognitive Behaviour Therapy in Australia: Observations from an Early Player

Long-term outcomes of patients with end-stage kidney disease due to membranoproliferative glomerulonephritis: an ANZDATA registry study

BackgroundMembranoproliferative glomerulonephritis (MPGN) is an uncommon cause of end stage kidney disease (ESKD) and the clinical outcomes of patients with MPGN who commence kidney replacement therapy have not been comprehensively studied.MethodsAll adult patients with ESKD due to glomerulonephritis commencing kidney replacement therapy in Australia and New Zealand from January 1, 1996 to December 31, 2016 were reviewed. Patients with ESKD due to MPGN were compared to patients with other forms of glomerulonephritis. Patient survival on dialysis and following kidney transplantation, kidney recovery on dialysis, time to transplantation, allograft survival, death-censored allograft survival and disease recurrence post-transplant were compared between the two groups using Kaplan Meier survival curves and Cox proportional hazards regression.ResultsOf 56,481 patients included, 456 (0.8%) had MPGN and 12,660 (22.4%) had another form of glomerulonephritis. Five-year patient survival on dialysis and following kidney transplantation were similar between patients with ESKD from MPGN and other forms of glomerulonephritis (Dialysis: 59% vs. 62% p = 0.61; Transplant: 93% vs. 93%, p = 0.49). Compared to patients with other forms of glomerulonephritis, patients with MPGN had significantly poorer 5-year allograft survival (70% vs. 81% respectively, p = 0.02) and death censored allograft survival (74% vs. 87%, respectively; p < 0.01). The risk of disease recurrence was significantly higher in patients with MPGN compared to patients with other glomerulonephritidites (18% vs. 5%; p < 0.01). In patients with MPGN who had allograft loss, patients with MPGN recurrence had a significantly shorter time to allograft loss compared to patients with MPGN who had allograft loss due to any other cause (median time to allograft loss 3.2 years vs. 4.4 years, p < 0.01).ConclusionsCompared with other forms of glomerulonephritis, patients with MPGN experienced comparable rates of survival on dialysis and following kidney transplantation, but significantly higher rates of allograft loss due to disease recurrence.

Moving Towards Hepatitis C Microelimination Among People Living With Human Immunodeficiency Virus in Australia: The CEASE Study.

Microelimination of hepatitis C virus (HCV) among people living with human immunodeficiency virus (HIV) may be feasible in Australia, given unrestricted access to direct-acting antiviral (DAA) therapy from 2016. Our aim was to evaluate progress towards elimination goals within HIV/HCV-coinfected adults in Australia following universal DAA access. The CEASE prospective cohort study enrolled adults with HIV/HCV, irrespective of viremic status, from 14 primary and tertiary clinics in Australia. Annual and cumulative HCV treatment uptake, outcome, and HCV RNA prevalence were evaluated, with follow-up through May 2018 (median follow-up, 2.63 years). Factors associated with DAA uptake were analyzed. Between July 2014 and March 2017, 402 participants who were HIV/HCV antibody positive were enrolled (95% male [80% gay and bisexual men,], 13% cirrhosis, 80% history of injecting drug use [39% currently injecting]). Following universal DAA access, annual HCV treatment uptake in those eligible increased from 7% and 11% per year in 2014 and 2015, respectively, to 80% in 2016. By 2018, cumulative HCV treatment uptake in those ever eligible for treatment was 91% (336/371). HCV viremic prevalence declined from 82% (95% CI, 78-86%) in 2014 to 8% (95% CI, 6-12%) in 2018. Reinfection was reported in only 5 participants for a reinfection incidence of 0.81 per 100 person-years (95% CI, 0.34-1.94). High uptake and effectiveness of unrestricted DAA therapy in Australia have permitted rapid treatment scale-up, with a dramatic reduction in HCV infection burden and low reinfection rate among people living with HIV, suggesting that microelimination is feasible. NCT02102451.

Treat and Extend Treatment Interval Patterns with Anti-VEGF Therapy in nAMD Patients.

Treat and extend (T&E) is a standard treatment regimen for treating neovascular age-related macular degeneration (nAMD) with anti-vascular endothelial growth factors (anti-VEGFs), but the treatment intervals attained are not well documented. This retrospective, non-comparative, non-randomised study of eyes with nAMD classified treatment interval sequences in a T&E cohort in Australia using Electronic Medical Records (EMR) data. We analysed data from 632 treatment-naïve eyes from 555 patients injected with ranibizumab, aflibercept or unlicensed bevacizumab between January 2012 and June 2016 (mean baseline age 78.0). Eyes were categorised into non-overlapping clusters of interval sequences based on the first 12 months of follow-up. We identified 523 different treatment interval sequences. The largest cluster of 197 (31.5%) eyes attained an 8-week treatment interval before dropping to a shorter frequency, followed by 168 (26.8%) eyes that did not reach or attained a single 8-week interval at the end of the study period. A total of 65 (10.4%) and 83 (13.3%) eyes reached and sustained (≥2 consecutive injection intervals of the same length) an 8 and 12 weekly interval, respectively. This study demonstrates highly individualised treatment patterns in the first year of anti-VEGF therapy in Australia using T&E regimens, with the majority of patients requiring more frequent injections than once every 8 weeks.

Long-term outcomes of patients with end-stage kidney disease due to membranous nephropathy: A cohort study using the Australia and New Zealand Dialysis and Transplant Registry.

BackgroundClinical outcomes of patients with end-stage kidney disease (ESKD) secondary to membranous nephropathy (MN) have not been well described. This study aimed to evaluate patient and/or allograft outcomes of dialysis or kidney transplantation in patients with ESKD secondary to MN.Material and methodsAll adult patients with ESKD commencing renal replacement therapy in Australia and New Zealand from January 1998 to December 2010 were extracted retrospectively from ANZDATA registry on 31st December 2013. Outcomes of MN were compared to other causes of ESKD. In a secondary analysis, outcomes of MN were compared to all patients with ESKD due to other forms of glomerulonephritis.ResultsOf 32,788 included patients, 417 (1.3%) had MN. Compared to other causes of ESKD, MN experienced lower mortality on dialysis (adjusted hazard ratio [aHR] 0.79, 95% CI 0.68–0.92, p = 0.002) and following kidney transplantation (aHR 0.57, 95% CI 0.33–0.97, p = 0.04), had a higher risk of death-censored kidney allograft failure (aHR 1.55, 95% CI: 1.00–2.41, p = 0.05) but comparable risk of overall kidney allograft failure (aHR 1.35, 95% CI 0.91–2.01, p = 0.13). Similar results were obtained using competing-risk regression analyses. MN patients were significantly more likely to receive a kidney transplant (aHR 1.38, 95% CI 1.16–1.63, p<0.001) and to experience primary kidney disease recurrence in the allograft (aHR 4.92, 95% CI 3.02–8.01, p<0.001). Compared to other forms of glomerulonephritis, MN experienced comparable dialysis and transplant patient survival, but higher rates of kidney transplantation, primary renal disease recurrence and death-censored allograft failure.ConclusionMN was associated with superior survival on dialysis and following kidney transplantation compared to patients with other causes of ESKD, and comparable patient survival compared to patients with other forms of glomerulonephritis. However, patients with MN exhibited a higher rate of death-censored allograft loss as a result of primary kidney disease recurrence.

Primary immunodeficiency disease: a cost-utility analysis comparing intravenous vs subcutaneous immunoglobulin replacement therapy in Australia.

Hospital-based intravenous immunoglobulin (IVIg) treatment has been the standard treatment mode for patients with primary immunodeficiency disease (PID). With the newer home-based subcutaneous immunoglobulin (SCIg) becoming approved for use in most countries, the question arises as to whether SCIg is a cost-effective treatment mode compared to IVIg in Australia. We developed a Markov cohort simulation model with six health states: PID without infection, PID with infection treated at home or hospital, bronchiectasis without infection, bronchiectasis with infection treated at home or hospital, bronchiectasis with chronic Pseudomonas aeruginosa infection, and death, from an Australian healthcare system perspective. A 10-year time horizon with weekly cycles was chosen, and the expected costs and quality-adjusted life-years (QALYs) of the two treatment options estimated. The cumulative 10-year cost per patient was 297,547 Australian dollars (A$) with IVIg and A$ 251,713 for SCIg. IVIg resulted in 5.55 QALYs and SCIg 5.57 QALYs. Thus, SCIg appears to be a cost-saving option and possibly improves QALY from the Australian healthcare system perspective (i.e., the dominant treatment option). A probabilistic sensitivity analysis showed that the SCIg option is preferred in 93.2% of simulations given willingness to pay of A$ 50,000 per QALY gained. The results suggest that home-based SCIg is a cost-effective treatment option for patients with PID in Queensland, Australia.

PB2349 EXTRACORPOREAL PHOTOPHERESIS FOR PEDIATRIC PATIENTS WITH GRAFT‐VS‐HOST DISEASE AFTER HAEMATOPOIETIC STEM CELL TRANSPLANTATION: AN AUSTRALIAN EXPERIENCE

Background:Graft‐versus‐host disease (GVHD) remains a major cause of morbidity and mortality following pediatric allogeneic hematopoietic stem cell transplant (HSCT). Extracorporeal photopheresis (ECP) is a cellular immuno‐modulatory therapy licensed for the treatment of steroid‐dependent or refractory GVHD. ECP has been shown to be effective in the treatment of GVHD in the adult population, however there is little data in the pediatric setting. Here we present our Australian experience in paediatric patients with GVHD.Aims:To assess the outcome and feasibility of ECP as a treatment modality for GVHD in the pediatric allograft patients in Australia.Methods:A retrospective case note analysis of all patients receiving ECP for the treatment of GVHD between August 2010 and December 2018 at the Royal Children's Hospital and Peter MacCallum Cancer Centre, Victoria.Results:14 patients were identified, with a median age of 4.4 years (range 0.5‐14.8). Demographic and transplant characteristics are summarised in Table 1. ECP was used to treat both acute (aGVHD, n = 7) and chronic (cGVHD, n = 8) GVHD. One patient required two treatment episodes for acute and subsequently chronic GVHD. All patients were refractory to prior immunosuppressive therapy, with a median of 3 agents used (range 2‐5). Median steroid dose was 0.8 mg/kg/day methylprednisolone equivalent (range 0‐2). An overall response was obtained in 6 of 7 (86%) acute and 6 of 8 (75%) chronic GVHD patients. Overall survival was 79% (11 of 14 patients).Of those treated for aGVHD varying from grade II – IV, 86% (n = 6) showed a partial response or better, with 43% (n = 3) achieving a complete response. Median steroid dose was reduced by 94% from 1.8 mg/kg/day methylprednisolone equivalent to 0.1 mg/kg/day from beginning to end of ECP. ECP duration was a median of 1.9 months (range 1.4‐5.7), with a median of 16 treatments (range 12‐25).The majority of cGVHD patients had extensive disease (n = 7, 88%), with 75% (n = 6) achieving at least a partial response, with a complete response in 37.5% (n = 3). Median steroid dose was reduced by 88% from 0.18 mg/kg/day methylprednisolone equivalent to 0.02 mg/kg/day from beginning to end of ECP. ECP was used for a median period of 7.1 months (range 1.9‐39.1) with a median of 25 treatments (range 7‐61).Catheter‐related sepsis was the most common reason for premature discontinuation of ECP in our cohort, occurring in 6 patients (43%). Other noted complications included haemodynamic instability requiring admission, occurring in 3 patients (21%). This caused discontinuation of ECP in one patient weighing 7.5 kg. Of the 3 patients who died, two had grade IV aGVHD with progressive disease post‐ECP, and one with refractory extensive cGVHD. The causes of death were sepsis (n = 2) and relapsed primary malignancy (n = 1).Summary/Conclusion:This is the first report of ECP therapy in Australia for pediatric patients with GVHD. Our results demonstrate that ECP is an effective and feasible treatment modality for both acute and chronic GVHD post‐HSCT. In our cohort, ECP allowed for tapering of corticosteroids, which has been shown to be associated with improved survival. Although ECP was well tolerated overall, specific consideration should be given when used in the pediatric population, especially with regard to the risk of haemodynamic instability, the use of blood prime of the circuit and catheter‐related sepsis.image

Knowing thyself: an audit of cell therapy manufacturing in Australia and New Zealand

Background & Aim We conducted a survey to assess cell therapy manufacturing capacity in Australia and New Zealand. We examined the number and types of cell therapy manufacturing facilities; the number of projects, parallel processes and clinical trials; the types of products; and manufacturing and quality staffing levels. We identified participant cell therapy manufacturing facilities by contacting individuals working in the field of cell therapy in Australia and New Zealand and inviting submissions on a one per cell manufacturing facility basis. Methods, Results & Conclusion The overall response rate was 59% (23 of 38 eligible facilities). Of the 23 responding facilities, 21 are in Australia and 2 are in New Zealand. Eighteen are run by public organisations and five by private organisations and a diverse range of accreditations were represented. There were 43 GMP laboratories across 14 of 22 facilities that reported on this parameter and approximately 4.6 manufacturing staff and 1.7 quality staff per facility. Products included hematopoietic progenitor cells, mononuclear cells, T-cells, peripheral blood mononuclear cells, CD34+ cells, mesenchymal stem cells and chimeric antigen receptor T-cells, therapeutic T-cell subsets, cell banks, autologous serum eye drops, keratinocytes, human amnion epithelial cells, pancreatic islets, dendritic cells and chondrocytes. Research interests were processing and storage optimization; the effect of methodologies on engraftment; gene and cell therapy; the biology of manufactured cell types; cell tracking and imaging; cell culture platforms; bioscaffolds; 3-D bioprinting; transplantation and the diseases treated. Reported collaborations included within Australia and with groups in Basel, Busan, Boston, Cambridge MA, Hong Kong, Los Angeles, Montreal, Nagoya, New York, Philadelphia, Stockholm and Toronto. Other national manufacturing-relevant assets are the Centre of Research Excellence in MedTech in New Zealand, the Cooperative Research Centre for Cell Therapy Manufacturing in Australia, the Australian National Health and Medical Research Council Clinical Trials Centre and Advanced Health Research and Translation Centres and Therapeutic Innovation Australia. Australian and New Zealand provide a platform for cell therapy manufacturing, infrastructure and capacity building. These form the foundation to enable both countries to meet the growing need for cell and gene therapy and regenerative medicine in our region.

Comparison of cause of death between Australian and New Zealand Dialysis and Transplant Registry and the Australian National Death Index

The aim of the present study was to understand the differences in how cause of death for patients receiving renal replacement therapy in Australia is recorded in The Australian and New Zealand Dialysis and Transplant Registry (ANZDATA) compared to the National Death Index (NDI). Data linkage was performed between ANZDATA and NDI for all deaths in the period 1980-2013. Cause of death was classified according to ICD-10 chapter. Overall and chapter specific agreement were assessed using the Kappa statistic. Descriptive analysis was used to explore differences where there was disagreement on primary cause of death. The analysis cohort included 28 675 patients. Ninety five percent of ANZDATA reported deaths fell within +/- 3 days of the date recorded by NDI. Circulatory death was the most common cause of death in both databases (ANZDATA 48%, NDI 32%). Overall agreement at ICD chapter level of primary cause was poor (36%, kappa 0.22). Agreement was best for malignancy (kappa 0.71). When there was disagreement on primary cause of death these were most commonly coded as genitourinary (35%) and endocrine (25.0%) in NDI, and circulatory (39%) and withdrawal (24%) in ANZDATA. Sixty-nine percent of patients had a renal related cause documented as either primary or a contributing cause of death in the NDI. There is poor agreement in primary cause of death between ANZDATA and NDI which is in part explained by the absence of diabetes and renal failure as causes of death in ANZDATA and the absence of 'withdrawal' in NDI. These differences should be appreciated when interpreting epidemiological data on cause of death in the Australian end stage kidney disease population.

Cross‐sex hormone therapy in Australia: the prescription patterns of clinicians experienced in adult transgender healthcare

Despite increasing demand for transgender healthcare, guidelines for cross-sex hormone therapy are based on low-level evidence only. As most data are based on international expert opinions, interpretations and practices vary significantly. To aid the development of Australian clinical guidelines, we aimed to identify cross-sex hormone therapy prescribing patterns among medical practitioners experienced in adult transgender healthcare. We conducted an anonymous online survey of experienced hormone prescribers who were members of the Australian and New Zealand Professional Association for Transgender Health (ANZPATH). We received 35 responses from 43 individuals listed with ANZPATH. Mental health assessments prior to commencement of hormonal therapy were recommended by 80% of prescribers. The preferred first-line masculinising hormone therapy was intramuscular testosterone undecanoate (46% of respondents). The most commonly prescribed feminising agents were oral estradiol valerate (first line in 71.4%), with either spironolactone or cyproterone acetate. Most respondents (>90%) targeted sex steroid reference ranges of the affirmed gender, and 71.4% reviewed individuals every 2-3 months in the first year. Better training for doctors was seen as the most pressing priority for government funding, and 79.3% supported the development of local Australian-based guidelines. Experienced hormone prescribers in Australia largely use medication regimens and monitor sex steroid levels and potential adverse effects of sex hormone therapy in accordance with broad, subjective recommendations listed in international guidelines. Additional practitioner training is necessary, and local Australian-based guidelines would offer specific, relevant guidance to clinicians in the initiation and monitoring of cross-sex hormone therapy for adult transgender individuals.

Anticoagulation therapy in Australia

Anticoagulant therapy is prescribed for many clinical indications, including treatment and prevention of venous thromboembolism (VTE), such as deep vein thrombosis (DVT) and pulmonary embolism (PE), as well as stroke prophylaxis in atrial fibrillation (AF) and to reduce the risk of prosthetic heart valve thrombosis and thromboembolism. In this narrative review, we briefly outline the anticoagulants available in Australia, their relative strengths and weaknesses, and the ever-changing local landscape with regards to anticoagulation therapy.

Association between rapid utilisation of direct hepatitis C antivirals and decline in the prevalence of viremia among people who inject drugs in Australia

The World Health Organization (WHO) established targets to eliminate hepatitis C virus (HCV) infection as a public health threat by 2030. Evidence that HCV treatment can lower viraemic prevalence among people who inject drugs (PWID) is limited. Broad accessibility of direct-acting antiviral (DAA) therapy in Australia, since March 2016, provides an opportunity to assess the efficacy of these treatments at a population level in a real-world setting. Data from Australia's annual bio-behavioural surveillance examined treatment uptake and estimated viraemic prevalence among PWID attending needle syringe programs nationally between 2015 and 2017. Multivariate logistic regression identified variables independently associated with HCV treatment among those considered eligible (anti-HCV positive excluding HCV RNA negative with no self-reported history of HCV treatment) in 2017. Annual samples ranged from 1,995-2,380 PWID. Anti-HCV prevalence declined from 57% (2015) to 49% (2017, χ2p trend <0.001), with 40-56% of anti-HCV positive respondents providing sufficient sample for HCV RNA testing. Between 2015 and 2017, treatment uptake among those eligible increased from 10% to 41% (χ2p trend <0.001) and viraemic prevalence among the overall sample declined from 43% to 25% (χ2p trend <0.001). In multivariable analysis, older age (≥50 years adjusted odds ratio [aOR] 1.82; 95% CI 1.09-3.06;p = 0.023 and 44-49 years aOR 1.75; 95% CI 1.03-3.00;p = 0.038 vs. ≤37 years) and history of opioid substitution therapy (aOR 2.06; 95% CI 1.30-3.26; p = 0.002) were independently associated with treatment. This study confirms PWID are willing to initiate treatment when HCV DAA therapy is available and provides population-level evidence of a decline in viraemic prevalence among people most at risk of ongoing HCV transmission. Scaled up surveillance and monitoring are required to evaluate progress toward WHO HCV elimination goals. The World Health Organization's goal to reduce hepatitis C virus incidence by 80% will be difficult to achieve without widespread scale up and a corresponding reduction in viraemic prevalence among those most at risk of onward transmission. Our results indicate that a population-level reduction in viraemic prevalence is achievable through high levels of treatment and cure among people who inject drugs.

Fifty years of RhD immunoglobulin (anti-D) therapy in Australia: celebrating a public health success story.

Fifty years of RhD immunoglobulin (anti-D) therapy in Australia: celebrating a public health success story.