Activity and outcomes of autologous stem cell transplantation in the private sector in Australia.

BACKGROUND: Few Australasian autologous stem cell transplantation (ASCT) programmes perform ASCT in the private sector. Relatively little is known about ASCT outcomes in the private sector, which varies in care delivery models to the public system. AIMS: To investigate transplantation activity and survival outcomes at Icon Cancer Centre's Brisbane-based private clinical and laboratory ASCT programme over a 23-year period. METHODS: Retrospective, observational study of all adults who underwent ASCT at Icon between 1996 and 2018. Main outcome measures were transplant activity, overall survival (OS) and 100-day and 1-year transplant-related mortality (TRM). Outcomes were benchmarked against the Australasian Bone Marrow Transplant Recipient Registry (ABMTRR). RESULTS: Between 1996 and 2018, 1676 ASCT were performed in 1454 patients. From 2010 to 2018, ASCT performed at Icon contributed 40% of all South East Queensland ASCT. In the past 5 years, 21% of Icon's patients were aged ≥70 years, compared with 5% across Australasia. For the entire cohort, 100-day and 1-year TRM was 1.1% and 1.7%, respectively, while for those aged ≥70 years, it was 2.0% and 3.1%. For ASCT performed between 2014 and 2018, 100-day and 1-year TRM was 0.8% and 1.4%, which was half the TRM rates reported by the ABMTRR. The 10-year post-transplant OS at Icon was higher than the ABMTRR data, across all disease subtypes. CONCLUSION: We report excellent OS and low TRM, demonstrating the critical role of the private sector in the administration of this highly complex therapy. The Icon ASCT programme is the largest ASCT contributor in Queensland. It is inclusive of patients aged ≥70 years, demonstrating low and acceptable TRM.

Pulmonary Disease Is Associated With Human T-Cell Leukemia Virus Type 1c Infection: A Cross-sectional Survey in Remote Aboriginal Communities.

BACKGROUND: The human T-cell leukemia virus type 1 (HTLV-1) subtype c is endemic to central Australia. We report the first large-scale, community-based, health survey of HTLV-1 and its disease associations in this setting. METHODS: Aboriginal community residents aged >2 years in 7 remote communities were invited to do a health survey that included a questionnaire, spirometry, and clinical examination by a physician blinded to HTLV-1 status, clinical records, and spirometry results. Blood was drawn for HTLV-1 serology and proviral load (PVL). Pulmonary disease was assessed clinically and spirometrically and, where records were available, radiologically after the clinical assessment. Associations between specific diseases and HTLV-1 status were determined using logistic regression, adjusting for available confounders. RESULTS: Overall, 579 residents (164 children aged 3-17 years; 415 adults) were examined (37.7% of the estimated resident population). HTLV-1 prevalences for children and adults were 6.1% and 39.3%, respectively. No associations were found between HTLV-1 and any assessed clinical condition among children. Chronic pulmonary disease and gait abnormalities were more common among adults with HTLV-1 infection. Adjusted odds ratios among participants with PVL ≥1000 per 105 peripheral blood leukocytes were 7.08 (95% confidence interval [CI], 2.67-18.74; P < .001), 9.81 (95% CI, 3.52-27.35; P < .001), and 14.4 (95% CI, 4.99-41.69; P < .001) for clinically defined chronic pulmonary disease, moderate-severe expiratory airflow limitation, and radiologically determined bronchiectasis/bronchiolitis, respectively, and 5.21 (95% CI, 1.50-18.07; P = .009) for gait abnormalities. CONCLUSIONS: In the first study of HTLV-1 disease associations based on community recruitment and blinded assessment, HTLV-1 infection was strongly associated with pulmonary disease and gait abnormalities.

Atrial Fibrillation in Indigenous Australians: A Multisite Screening Study Using a Single-Lead ECG Device in Aboriginal Primary Health Settings.

BACKGROUND: Circulatory diseases continue to be the greatest cause of mortality for Australian Aboriginal and Torres Strait Islander people, and a major cause of persistently lower life expectancy compared with non-Aboriginal Australians. The limited information that exists on atrial fibrillation (AF) prevalence in Aboriginal and Torres Strait Islander communities is mostly based on hospital admission data. This shows AF as principal or additional admission diagnosis was 1.4 times higher compared to non-Aboriginal Australians, a higher incidence of AF across the adult life span after age 20 years and a significantly higher prevalence among younger patients. Our study estimates the first national community prevalence and age distribution of AF (including paroxysmal) in Australian Aboriginal people. A handheld single-lead electrocardiograph (ECG) device (iECG), known to be acceptable in this population, was used to record participant ECGs. METHODS: This co-designed, descriptive cross-sectional study was conducted in partnership with 16 Aboriginal Community Controlled Health organisations at their facilities and/or with their services delivered elsewhere. The study was also conducted at one state community event. Three (3) Australian jurisdictions were involved: New South Wales, Western Australia and the Northern Territory. Study sites were located in remote, regional and urban areas. Opportunistic recruitment occurred between June 2016 and December 2017. People <45 years of age were excluded. RESULTS: Thirty (30) of 619 Aboriginal people received a 'Possible AF' and 81 an 'Unclassified' result from a hand-held smartphone ECG device. A final diagnosis of AF was made in 29 participants (4.7%; 95%CI 3.0-6.4%), 25 with known AF (five paroxysmal), and four with previously unknown AF. Three (3) of the four with unknown AF were aged between 55-64 years, consistent with a younger age of AF onset in Aboriginal people. Estimated AF prevalence increased with age and was higher in those aged >55 years than the general population (7.2% compared with 5.4%). Slightly more men than women were diagnosed with AF. CONCLUSIONS: This study is a significant contribution to the evidence which supports screening for AF in Aboriginal and Torres Strait Islander people commencing at a younger age than as recommended in the Australian guidelines (>65 years). We recommend the age of 55 years. Consideration should be given to the inclusion of AF screening in the Australian Government Department of Health annual 'Aboriginal and Torres Strait Islander Health Assessment'. CLINICAL TRIAL REGISTRATION: ACTRN12616000459426.

The impact of workplace culture on the accountability of mental health nurses to involve consumers in care planning: A focused ethnography.

Recovery-oriented mental health practice guidelines recommend regular consumer involvement in care plans, yet in many acute settings, these are not routinely created thereby compromising accountability. This study explored the impact of workplace culture on the capacity of mental health nurses to involve consumers in care planning and consequently to work accountably. A focused ethnography was undertaken in one Australian inpatient unit involving mental health nurses and other health professionals. Data were derived from in-depth semistructured interviews with 12 nurses and 6 months of nonparticipant observation of multidisciplinary meetings and clinical handovers. Workplace culture had an impact on mental health nurses' accountability practices. A culture that prioritized reduction in length of stay resulted in less recovery-oriented care. Health professionals who paid more attention to crisis and risk management resulted in fewer opportunities for consumer-involved care planning.

Azacitidine with or without lenalidomide in higher risk myelodysplastic syndrome & low blast acute myeloid leukemia.

Standard treatment for higher risk myelodysplastic syndromes, chronic myelomonocytic leukemia and low blast acute myeloid leukemia is azacitidine. In single arm studies, adding lenalidomide had been suggested to improve outcomes. The ALLG MDS4 phase II trial randomized such patients to standard azacitidine or combination azacitidine (75mg/m2/d days 1 to 5) with lenalidomide (10mg days 1-21 of 28-day cycle from cycle 3) to assess clinical benefit (alive without progressive disease) at 12 months. A total of 160 patients were enrolled; median age 70.7 years (range 42.5-87.2), 31.3% female with 14% chronic myelomonocytic leukemia, 12% acute myeloid leukemia and 74% myelodysplastic syndromes. Adverse events were similar in both arms. There was excellent delivery of protocol therapy (median azacitidine cycles 11 both arms) with few dose reductions, delays or early cessations. At median follow up 33.1 months (range 0.7-59.5), the rate of clinical benefit at 12 months was 65% azacitidine arm and 54% lenalidomide+azacitidine arm (P=0.2). There was no difference in clinical benefit between each arm according to WHO diagnostic subgroup or IPSS-R. Overall response rate was 57% in azacitidine arm and 69% in lenalidomide+azacitidine (P=0.14). There was no difference in progression- free or overall survival between the arms (each P>0.12). Although the combination of lenalidomide and azacitidine was tolerable, there was no improvement in clinical benefit, response rates or overall survival in higher risk myelodysplastic syndrome, chronic myelomonocytic leukemia or low blast acute myeloid leukemia patients compared to treatment with azacitidine alone. This trial was registered at www.anzc-tr.org.au as ACTRN12610000271000.

Brentuximab vedotin or physician's choice in CD30-positive cutaneous T-cell lymphoma (ALCANZA): an international, open-label, randomised, phase 3, multicentre trial.

BACKGROUND: Cutaneous T-cell lymphomas are rare, generally incurable, and associated with reduced quality of life. Present systemic therapies rarely provide reliable and durable responses. We aimed to assess efficacy and safety of brentuximab vedotin versus conventional therapy for previously treated patients with CD30-positive cutaneous T-cell lymphomas. METHODS: In this international, open-label, randomised, phase 3, multicentre trial, we enrolled adult patients with CD30-positive mycosis fungoides or primary cutaneous anaplastic large-cell lymphoma who had been previously treated. Patients were enrolled across 52 centres in 13 countries. Patients were randomly assigned (1:1) centrally by an interactive voice and web response system to receive intravenous brentuximab vedotin 1·8 mg/kg once every 3 weeks, for up to 16 3-week cycles, or physician's choice (oral methotrexate 5-50 mg once per week or oral bexarotene 300 mg/m2 once per day) for up to 48 weeks. The primary endpoint was the proportion of patients in the intention-to-treat population achieving an objective global response lasting at least 4 months per independent review facility. Safety analyses were done in all patients who received at least one dose of study drug. This trial was registered with ClinicalTrials.gov, number NCT01578499. FINDINGS: Between Aug 13, 2012, and July 31, 2015, 131 patients were enrolled and randomly assigned to a group (66 to brentuximab vedotin and 65 to physician's choice), with 128 analysed in the intention-to-treat population (64 in each group). At a median follow-up of 22·9 months (95% CI 18·4-26·1), the proportion of patients achieving an objective global response lasting at least 4 months was 56·3% (36 of 64 patients) with brentuximab vedotin versus 12·5% (eight of 64) with physician's choice, resulting in a between-group difference of 43·8% (95% CI 29·1-58·4; p<0·0001). Grade 3-4 adverse events were reported in 27 (41%) of 66 patients in the brentuximab vedotin group and 29 (47%) of 62 patients in the physician's choice group. Peripheral neuropathy was seen in 44 (67%) of 66 patients in the brentuximab vedotin group (n=21 grade 2, n=6 grade 3) and four (6%) of 62 patients in the physician's choice group. One of the four on-treatment deaths was deemed by the investigator to be treatment-related in the brentuximab vedotin group; no on-treatment deaths were reported in the physician's choice group. INTERPRETATION: Significant improvement in objective response lasting at least 4 months was seen with brentuximab vedotin versus physician's choice of methotrexate or bexarotene. FUNDING: Millennium Pharmaceuticals Inc (a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd), Seattle Genetics Inc.

Pathological assessment of gastrointestinal biopsies from patients with idelalisib-associated diarrhea and colitis.

AIM: Idelalisib (IDELA) treatment is associated with diarrhea/colitis (incidence of ∼15% grade ≥3). We performed a retrospective analysis of gastrointestinal biopsies from 29 patients treated with IDELA across nine clinical trials. METHODS: A central core laboratory performed histopathologic review, immunohistochemistry, and droplet digital PCR viral studies. These results were correlated with tissue immune profiling data and morphologic features per modified Geboes score. RESULTS: Out of 29 eligible patients with abdominal pain or diarrhea, 24 (82.8%) had reported adverse event terms of diarrhea and/or colitis. Infectious pathogens were detected in 9/29 samples. Most biopsies presented with mixed/inflammatory infiltrates and contained increased numbers of FOXP3+ cells versus normal controls. CONCLUSION: This study revealed evidence of T-cell dysregulation and a substantial infectious component in association with IDELA-related diarrhea/colitis.

Specific pathogen free macaque colonies: a review of principles and recent advances for viral testing and colony management.

Specific pathogen free (SPF) macaques provide valuable animal models for biomedical research. In 1989, the National Center for Research Resources [now Office of Research Infrastructure Programs (ORIP)] of the National Institutes of Health initiated experimental research contracts to establish and maintain SPF colonies. The derivation and maintenance of SPF macaque colonies is a complex undertaking requiring knowledge of the biology of the agents for exclusion and normal physiology and behavior of macaques, application of the latest diagnostic technology, facilitiy management, and animal husbandry. This review provides information on the biology of the four viral agents targeted for exclusion in ORIP SPF macaque colonies, describes current state-of-the-art viral diagnostic algorithms, presents data from proficiency testing of diagnostic assays between laboratories at institutions participating in the ORIP SPF program, and outlines management strategies for maintaining the integrity of SPF colonies using results of diagnostic testing as a guide to decision making.

The prevalence and clinical associations of HTLV-1 infection in a remote Indigenous community.

OBJECTIVE: Hospital and laboratory data indicate that human T-lymphotropic virus type 1 (HTLV-1) is endemic to central Australia, but no community-based studies of its prevalence or disease burden have been reported. We determined the prevalence rates of HTLV-1 infection and of HTLV-1-associated diseases in a remote Indigenous community. SETTING: A remote Northern Territory community. DESIGN: All residents were asked to complete a health survey and offered a limited clinical examination, together with serological tests for HTLV-1 and Strongyloides, and HTLV-1 proviral load (PVL) assessment. MAIN OUTCOME MEASURES: HTLV-1 seropositivity rates; HTLV-1 PVL (copies/105 peripheral blood leucocytes [PBL]); presentation with HTLV-1-related clinical disease. RESULTS: HTLV-1 serostatus was determined for 97 of 138 residents (70%). The prevalence of HTLV-1 infection was significantly higher among adults (30 of 74 people tested) than children (1 of 23; P = 0.001). Nine of 30 HTLV-1-positive adults had a clinical syndrome that was potentially attributable to HTLV-1 infection (chronic lung disease, seven; symptomatic strongyloidiasis, two). The median HTLV-1 PVL was significantly higher for adults with chronic lung disease than for those who were asymptomatic (chronic lung disease, 649 copies/105 PBL [IQR, 162-2220]; asymptomatic adults, 40 copies/105 PBL [IQR, 0.9-229]; P = 0.017). Ten of 72 adults tested were seropositive for Strongyloides (six of 28 HTLV-1-positive participants and four of 44 HTLV-1-negative participants; P = 0.17), as were three of 15 children tested; the three children were HTLV-1-negative. CONCLUSION: The prevalence of HTLV-1 infection and the rate of disease potentially attributable to HTLV-1 were high among adults in this remote community.

8. Resilience and self-preservation; taking care of one another.

Preceptorship is the 15th series of 'Midwifery basics' targeted at practising midwives. The aim of these articles is to provide information to raise awareness of the impact of the work of midwives on women's experience, and encourage midwives to seek further information through a series of activities relating to the topic. In this final article in the preceptorship basics series, Kerry Taylor and Megan Blease look at the importance of resilience, self-preservation and taking care of one another. Embarking on a career in midwifery can be a stressful, isolating and challenging time. This article considers the stresses of providing modern maternity care, taking into consideration personal values, qualities and coping strategies. They address the challenges of workplace culture, the importance of building each other up and of caring for ourselves in order to effectively care for others.

4. Managing workload and prioritising care: top tips.

Preceptorship is the 15th series of 'Midwifery basics' targeted at practising midwives. The aim of these articles is to provide information to raise awareness of the impact of the work of midwives on women's experience, and encourage midwives to seek further information through a series of activities relating to the topic. In this fourth article of the series, Neesha Ridley and Kerry Taylor look into the barriers and challenges that present to all midwives, particularly in the prioritisation of care and management of workload. They provide top tips in order to help support newly qualified midwives manage their work well, thus providing safe, effective care to all women and newborns at all times.

7. Perineal suturing.

Preceptorship is the 15th series of 'Midwifery basics' targeted at practising midwives. The aim of these articles is to provide information to raise awareness of the impact of the work of midwives on women's experience, and encourage midwives to seek further information through a series of activities relating to the topic. During the transition from student midwife, the newly qualified practitioner (NQM) is required to obtain experience of perineal suturing. With exposure varying from student to student and inconsistency in teaching methods between hospital trusts, the NQM can be left feeling apprehensive and unsupported to learn this skill. Suturing is a major and sometimes traumatic event for childbearing women, whose experience can vary greatly, depending upon many factors, including environment, skill of those suturing, effective analgesia and waiting times. In this penultimate article of the series, Megan Blease and Kerry Taylor address the current issues and provide learning hints and tips for NQMs learning and practising the skill.

5. Revalidation and preceptorship--safe practice for everyone, always.

Preceptorship is the 15th series of 'Midwifery basics' targeted at practising midwives. The aim of these articles is to provide information to raise awareness of the impact of the work of midwives on women's experience, and encourage midwives to seek further information through a series of activities relating to the topic. In this fifth article of the series, Kerry Taylor, Anna Byrom and Colette Gregory look at how preceptorship can help you prepare for and contribute to the process of revalidation. Whether you are a newly qualified midwife on a preceptorship programme or a preceptor, being involved in preceptorship is not only a beneficial way to promote and maintain safe practice, but it is the ideal opportunity to gather your evidence for revalidation and demonstrate that you are working within the Nursing and Midwifery Council (NMC) Code (2015a).

Using shared governance to empower nurses.

Service improvement is a key theme of nurse education and nurses are encouraged to continually improve care outcomes. However, in practice, nurses often lack time and support for continuous improvement. Amid a national shortage of nurses and midwives, as well as high turnovers of staff, shared governance offers a structure in which quality improvement is the main aim and career development is a benefit. This article explains the concept and outlines the benefits and barriers of such a structure.

Being a preceptor - rewarding yet challenging.

Preceptorship is the 15th series of 'Midwifery basics' targeted at practising midwives.The aim of these articles is to provide information to raise awareness of the impact of the work of midwives on women's experience, and encourage midwives to seek further information through a series of activities relating to the topic. In this third article of the series, Kerry Taylor and Megan Blease look into the role of the preceptor and the value it offers newly qualified midwives, with key recommendations to help trusts support preceptors in this acquired role.

2. Newly qualified midwives.

Preceptorship is the 15th series of 'Midwifery basics' targeted at practising midwives. The aim of these articles is to provide information to raise awareness of the impact of the work of midwives on women's experience, and encourage midwives to seek further information through a series of activities relating to the topic. In this second article of the series, Kerry Taylor, Stephanie Heys and Jessemy Evans look first hand at the positive and negative aspects of a preceptorship programme from the view of newly qualified midwives, and offer top tips. to help other newly qualified midwives embarking on their exciting new careers.

All-trans-retinoic acid, idarubicin, and IV arsenic trioxide as initial therapy in acute promyelocytic leukemia (APML4).

The treatment of acute promyelocytic leukemia has improved considerably after recognition of the effectiveness of all-trans-retinoic acid (ATRA), anthracycline-based chemotherapy, and arsenic trioxide (ATO). Here we report the use of all 3 agents in combination in an APML4 phase 2 protocol. For induction, ATO was superimposed on an ATRA and idarubicin backbone, with scheduling designed to exploit antileukemic synergy while minimizing cardiotoxicity and the severity of differentiation syndrome. Consolidation comprised 2 cycles of ATRA and ATO without chemotherapy, followed by 2 years of maintenance with ATRA, oral methotrexate, and 6-mercaptopurine. Of 124 evaluable patients, there were 4 (3.2%) early deaths, 118 (95%) hematologic complete remissions, and all 112 patients who commenced consolidation attained molecular complete remission. The 2-year rate for freedom from relapse is 97.5%, failure-free survival 88.1%, and overall survival 93.2%. These outcomes were not influenced by FLT3 mutation status, whereas failure-free survival was correlated with Sanz risk stratification (P[trend] = .03). Compared with our previously reported ATRA/idarubicin-based protocol (APML3), APML4 patients had statistically significantly improved freedom from relapse (P = .006) and failure-free survival (P = .01). In conclusion, the use of ATO in both induction and consolidation achieved excellent outcomes despite a substantial reduction in anthracycline exposure. This trial was registered at the Australian New Zealand Clinical Trials Registry (www.anzctr.org.au) as ACTRN12605000070639.

Reducing the risk of harm from intravenous potassium: a multi-factorial approach in the haematology setting.

AIMS: To describe the implementation of safety systems for the use of intravenous potassium chloride in haematology patients. METHODS: We assessed the use of intravenous potassium in a haematology ward at a tertiary hospital. Initially, we prospectively analysed the prescribing and administration of intravenous potassium to all patients over a two-week period. To complement this data, we retrospectively analysed all clinical incidents involving intravenous potassium and the dispensing patterns of potassium ampoules for the past 12 months. Drawing on evidence and recommendations from international safety literature, gaps in the safe use of potassium were identified, and a multi-factorial approach to system change was implemented. RESULTS: A total of 18 patients were analysed with 90 intravenous bags of potassium prepared on the ward using 624 ampoules. We identified multiple opportunities for error and a lack of standardisation of therapy. The following safety systems were introduced: (i) a new prescribing and monitoring form that included dose calculation, prescriber support and pre-printed orders; (ii) removal of potassium ampoules and introduction of premixed bags; (iii) independent double checking by nursing staff at point of administration; (iv) dedicated labelling of intravenous lines; (v) extensive clinician training supported by guidelines; and (vi) introduction of 'smart pump' infusion software. The number of incidents significantly reduced from 23 to 9 (p < 0.001), and the number of ampoules dispensed reduced from 10,100 to 0. CONCLUSIONS: A multi-factorial approach to the safe prescribing, dispensing and administration of intravenous potassium has reduced the potential for patient harm in the haematology setting.