A Retrospective Cohort Study of Red Cell Alloimmunisation in Rural, Remote, and Aboriginal and Torres Strait Islander Peoples Admitted to Intensive Care in the Northern Territory, Australia

Red cell (RC) alloantibodies occur on exposure to non-self RC antigens in transfusion and pregnancy (typically IgG and clinically significant) or in association with non-RC immune environmental factors (typically IgM and not clinically significant). In Australia, the risk of RC alloimmunisation in First Nations peoples is unknown. We assessed the epidemiology, specificity, and antecedents of RC alloimmunisation via a data linkage retrospective cohort study of Northern Territory (NT) intensive care unit (ICU) patients (2015–2019). Of 4183 total patients, 50.9% were First Nations. In First Nations versus non-First Nations patients, the period prevalence of alloimmunisation was 10.9% versus 2.3%, with 390 versus 72 prevalent alloantibodies detected in 232 versus 48 alloimmunised patients, of which 135 (34.6%) versus 52 (72.2%) were clinically significant specificities. Baseline and follow-up alloantibody testing were available for 1367 patients, in whom new incident clinically significant alloantibodies developed in 4.5% First Nations versus 1.1% non-First Nations patients. On Cox proportional hazards modelling, adjusted hazard ratios (HR) showed First Nations status (HR 2.67 (95% CI 1.05–6.80), p = 0.04) and cumulative RC unit transfusion exposure (HR 1.03 (95% CI 1.01–1.05), p = 0.01) were independent predictors of clinically significant alloimmunisation. First Nations Australian patients are at increased risk of alloimmunisation due to RC transfusion, underscoring the importance of very judicious use of RC transfusions and shared decision-making with patients. Further studies are recommended to explore the role of other (non-RC) immune host factors, given the relative high prevalence of non-clinically significant IgM alloantibodies within alloimmunised First Nations patients

Snakebite associated thrombotic microangiopathy: a systematic review of clinical features, outcomes, and evidence for interventions including plasmapheresis.

Snakebite is a neglected tropical disease with significant morbidity and mortality. Thrombotic microangiopathy (TMA) is an important but poorly understood complication of snakebite associated with acute kidney injury (AKI). Numerous treatments have been attempted based on limited evidence. We conducted a systematic review of TMA following snakebite using a pre-determined case definition of blood film red cell schistocytes or histologically diagnosed TMA. The search strategy included major electronic databases and grey literature. We present a descriptive synthesis for the outcomes of AKI, dialysis free survival (DFS), other end-organ damage, overall survival, and interventions with antivenom and therapeutic plasmapheresis (TPE). This study was prospectively registered with PROSPERO (CRD42019121436). Seventy-two studies reporting 351 cases were included, predominantly small observational studies. Heterogeneity for study selection, design, reporting and outcomes were observed. The commonest envenoming species were hump-nosed vipers (Hypnale spp.), Russell's viper (Daboia russelii) and Australian brown snakes (Pseudechis spp.). The prevalence of TMA was at least 5.4% in proven and probable Hypnale bites, and 10-15% of Australian elapid envenomings, AKI occurred in 94% (293/312) of TMA cases, excluding case reports. The majority of cases with AKI required dialysis. Included prospective and retrospective cohort studies reporting interventions and renal outcomes showed no evidence for benefit from antivenom or TPE with respect to DFS in dialysis dependant AKI. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) assessment for quality of accumulated evidence for interventions was low. The major complication of TMA following snakebite is AKI. AKI improves in most cases. We found no evidence to support benefit from antivenom in snakebite associated TMA, but antivenom remains the standard of care for snake envenoming. There was no evidence for benefit of TPE in snakebite associated TMA, so TPE cannot be recommended. The quality of accumulated evidence was low, highlighting a need for high quality larger studies

Snakebite Associated Thrombotic Microangiopathy and Recommendations for Clinical Practice

Snakebite is a significant and under-resourced global public health issue. Snake venoms cause a variety of potentially fatal clinical toxin syndromes, including venom-induced consumption coagulopathy (VICC) which is associated with major haemorrhage. A subset of patients with VICC develop a thrombotic microangiopathy (TMA). This article reviews recent evidence regarding snakebite-associated TMA and its epidemiology, diagnosis, outcomes, and effectiveness of interventions including antivenom and therapeutic plasma-exchange. Snakebite-associated TMA presents with microangiopathic haemolytic anaemia (evidenced by schistocytes on the blood film), thrombocytopenia in almost all cases, and a spectrum of acute kidney injury (AKI). A proportion of patients require dialysis, most survive and achieve dialysis free survival. There is no evidence that antivenom prevents TMA specifically, but early antivenom remains the mainstay of treatment for snake envenoming. There is no evidence for therapeutic plasma-exchange being effective. We propose diagnostic criteria for snakebite-associated TMA as anaemia with >1.0% schistocytes on blood film examination, together with absolute thrombocytopenia (<150 × 109/L) or a relative decrease in platelet count of >25% from baseline. Patients are at risk of long-term chronic kidney disease and long term follow up is recommended

A Retrospective Cohort Study of Red Cell Alloimmunisation in Rural, Remote, and Aboriginal and Torres Strait Islander Peoples Admitted to Intensive Care in the Northern Territory, Australia

Red cell (RC) alloantibodies occur on exposure to non-self RC antigens in transfusion and pregnancy (typically IgG and clinically significant) or in association with non-RC immune environmental factors (typically IgM and not clinically significant). In Australia, the risk of RC alloimmunisation in First Nations peoples is unknown. We assessed the epidemiology, specificity, and antecedents of RC alloimmunisation via a data linkage retrospective cohort study of Northern Territory (NT) intensive care unit (ICU) patients (2015–2019). Of 4183 total patients, 50.9% were First Nations. In First Nations versus non-First Nations patients, the period prevalence of alloimmunisation was 10.9% versus 2.3%, with 390 versus 72 prevalent alloantibodies detected in 232 versus 48 alloimmunised patients, of which 135 (34.6%) versus 52 (72.2%) were clinically significant specificities. Baseline and follow-up alloantibody testing were available for 1367 patients, in whom new incident clinically significant alloantibodies developed in 4.5% First Nations versus 1.1% non-First Nations patients. On Cox proportional hazards modelling, adjusted hazard ratios (HR) showed First Nations status (HR 2.67 (95% CI 1.05–6.80), p = 0.04) and cumulative RC unit transfusion exposure (HR 1.03 (95% CI 1.01–1.05), p = 0.01) were independent predictors of clinically significant alloimmunisation. First Nations Australian patients are at increased risk of alloimmunisation due to RC transfusion, underscoring the importance of very judicious use of RC transfusions and shared decision-making with patients. Further studies are recommended to explore the role of other (non-RC) immune host factors, given the relative high prevalence of non-clinically significant IgM alloantibodies within alloimmunised First Nations patients

The Northern Territory Medical Program - growing our own in the NT

CONTEXT: The Northern Territory (NT) is characterised by major health inequalities. A high proportion of the population is Indigenous, with poor socioeconomic conditions and a high burden of disease. The small NT population - 1% of the total Australian population - is dispersed over one-sixth of Australia's land mass. Given this very low population density and the geographical isolation of many small communities, access to services is often difficult. Medical workforce recruitment and retention have been persistent problems. Prior to 2011, NT residents who aspired to study medicine had to leave the NT. This was the only Australian state or territory that did not have the capacity for students to complete an entire medical degree within the jurisdiction. This article describes the development, implementation and outcomes of the Northern Territory Medical Program (NTMP), which commenced in Darwin in 2011. This was a major development of the Flinders University distributed program, which aimed to develop the medical workforce for the challenging NT environment. ISSUES: Based on evidence regarding the importance of selection in achieving rural workforce outcomes, and a national priority to graduate more Indigenous Australian doctors, NT residents and Indigenous applicants to the NTMP were prioritised in the selection process. Aspiring doctors would not now have to move interstate to study. The curriculum of Flinders University, based in Adelaide, South Australia, would be contextualised to the NT. The NTMP was developed and implemented in collaboration with Charles Darwin University, the major university in the NT. LESSONS LEARNED: Some of the lessons learned may be useful to others contemplating the delivery of a distributed program that includes a full medical program in a remote area. These include: Leadership at the highest levels of the university is crucial. Expect faculty turnover and avoid single person vulnerabilities. Actively engage local clinicians. Ensure a strong focus on new or alternative selection processes that are able to predict progression. Provide preparatory skills and support for students, especially Indigenous students, with non-science backgrounds. Appreciate and accommodate the community and family pressures experienced by some Indigenous students. Anticipate that the first pioneering cohort of students will not be typical of future cohorts, and work with them to adapt the curriculum, teaching and selection methods. Whilst exemplary telecommunications are needed, some elements of the curriculum will be able to be delivered far better locally than at the larger campus. Do not underestimate the level of student and staff support required both locally and centrally. Develop a 'network' rather than a 'hub and spoke' model. The network may include multiple dispersed placement sites, requiring infrastructure, staffing and ongoing support. The 'new kid' will mean the 'older sibling' will change for the better and use the small size and agility to explore innovations. Focus on the goals. We wanted to contribute to improved economic, social and health outcomes for NT residents by developing an appropriately prepared medical workforce, thereby eliminating the need to recruit doctors from interstate and overseas, and by graduating more Indigenous doctors - potential medical leaders for Australia. Build your expectation for success based on past successes in innovation. Flinders University was able to build on its experience in developing the first 4-year medical program in Australia