The clinicopathological features of thrombosis with thrombocytopenia syndrome following ChAdOx1-S (AZD1222) vaccination and case outcomes in Australia: a population-based study.

Background: Thrombosis with thrombocytopenia syndrome (TTS) associated with viral vector COVID-19 vaccines, including ChAdOx1-S (AstraZeneca AZD1222) vaccine, can result in significant morbidity and mortality. We report the clinicopathological features of TTS following ChAdOx1-S vaccination and summarise the case outcomes in Australia. Methods: In this cohort study, patients diagnosed with TTS in Australia between 23 March and 31 December 2021 were identified according to predefined criteria. Cases were included if they met the Therapeutic Goods Administration (TGA) probable and confirmed case definitions and were reclassified using Centres for Disease Control and Prevention (CDC) definition for analysis. Data were collected on patient baseline characteristics, clinicopathological features, risk factors, treatment and outcomes. Findings: A total of 170 TTS cases were identified, with most occurring after the first dose (87%) of ChAdOx1-S. The median time to symptom onset after vaccination and symptom onset to admission was 11 and 2 days respectively. The median age of cases was 66 years (interquartile range 55-74). All except two patients received therapeutic anticoagulation and 66% received intravenous immunoglobulin. Overall, 85.3% of cases were discharged home after a median hospitalisation of 6 days, 9.4% required ongoing rehabilitation and 5.3% died. Eight deaths were related to TTS, with another dying from an unrelated condition while receiving treatment for TTS. Deaths occurred more commonly in those classified as Tier 1 according to the CDC definition and were associated with more severe thrombocytopenia and disease-related haemorrhage. Interpretation: TTS, while rare, can be severe and have catastrophic outcomes in some individuals. In Australia, the mortality rate was low compared to that reported in other high-income countries. Almost all received therapeutic anticoagulation with no bleeding complications and were successfully discharged. This emphasises the importance of community education and an established pathway for early recognition, diagnosis and treatment of TTS. Funding: Australian Commonwealth Department of Health and Aged Care. H.A Tran, N. Wood, J. Buttery, N.W. Crawford, S.D. Chunilal, V.M. Chen are supported by Medical Research Future Funds (MRFF) grant ID 2015305.

Real-world screening for diabetes in early pregnancy: Improved screening uptake using universal glycated haemoglobin.

AIMS: To improve perinatal outcomes, screening for hyperglycaemia using 75 g oral glucose tolerance test (OGTT) is recommended for all pregnant women at 24-28 weeks gestation (routine), and earlier if high-risk. Screening coverage for remote and Aboriginal Australian women is less than ideal. This study examined OGTT completion (early and routine) by women from rural and remote Western Australia compared with early glycated haemoglobin (HbA1c). METHODS: In 2015-2018, 27 primary health care sites recruited 600 (233 Aboriginal) women aged ≥16-years, without pre-existing diabetes, who delivered >30-weeks gestation. All women presenting <20-weeks gestation (541) were offered an early study HbA1c. Early OGTTs were requested at the discretion of the local clinician, with routine OGTT offered at 24-28 weeks. RESULTS: HbA1c uptake was high (85.7% Aboriginal, 86.4% non-Aboriginal); OGTT completion in Aboriginal women was low (early OGTT: 38.6% v 69.6% non-Aboriginal, P < 0.001; routine OGTT: 44.5% v 84.7% non-Aboriginal, P < 0.001). Aboriginal women with both early tests had HbA1c completed 3-weeks prior to OGTT (9.6 ± 3.5 v 12.5 ± 3.5 weeks gestation, P < 0.001). CONCLUSIONS: Universal early pregnancy HbA1c appears feasible as an early screening test for women at risk of hyperglycaemia in pregnancy and would expedite and increase screening in Aboriginal women compared to an early OGTT.

Prediabetes and pregnancy: Early pregnancy HbA1c identifies Australian Aboriginal women with high-risk of gestational diabetes mellitus and adverse perinatal outcomes.

AIMS: To assess whether early pregnancy HbA1c can predict gestational diabetes mellitus (GDM) and adverse birth outcomes in Australian women. METHODS: Prospective study of 466 women without diabetes, aged ≥16-years at first antenatal presentation. Recruitment was from 27 primary healthcare sites in rural and remote Australia from 9-January 2015 to 31-May 2018. HbA1c was measured with first antenatal investigations (<20-weeks gestation). Primary outcome measure was predictive value of HbA1c for GDM, by routine 75 g oral glucose tolerance test (OGTT; ≥24-weeks gestation), and for large-for-gestational-age (LGA) newborn. RESULTS: Of 396 (129 Aboriginal) women with routine OGTT, 28.8% had GDM (24.0% Aboriginal). HbA1c ≥5.6% (≥38 mmol/mol) was highly predictive (71.4%, 95% CI; 47.8-88.7%) for GDM in Aboriginal women, and in the total cohort increased risk for LGA newborn (RR 2.04, 95% CI; 1.03-4.01, P = 0.040). There were clear differences between Aboriginal and non-Aboriginal women: 16.3% v 5.2% (P < 0.001) had elevated HbA1c whereas 12.4% v 29.6% (P < 0.001) developed hyperglycemia during pregnancy. CONCLUSIONS: Early pregnancy HbA1c ≥5.6% (≥38 mmol/mol) identifies Aboriginal women with apparent prediabetes and elevated risk of having an LGA newborn. Universal HbA1c at first antenatal presentation could facilitate earlier management of hyperglycemia and improved perinatal outcome in this high-risk population.

Neurosyphilis: Still prevalent and overlooked in an at risk population.

BACKGROUND: Neurosyphilis (NS) presents with a variety of clinical syndromes that can be attributed to other aetiologies due to difficulties in its diagnosis. We reviewed all cases of NS from the "Top End" of the Australian Northern Territory over a ten-year period to assess incidence, clinical and laboratory manifestations. METHODS: Patient data (2007-2016) were extracted from hospital records, centralised laboratory data and Northern Territory Centre for Disease Control records. Clinical records of patients with clinically suspected NS were reviewed. A diagnosis of NS was made based on the 2014 US CDC criteria. Results were also recategorized based on the 2018 US CDC criteria. RESULTS: The population of the "Top End" is 185,570, of whom 26.2% are Indigenous. A positive TPPA was recorded in 3126 individuals. A total of 75 (2.4%) of TPPA positive patients had a lumbar puncture (LP), of whom 25 (35%) were diagnosed with NS (9 definite, 16 probable). Dementia was the most common manifestation (58.3%), followed by epilepsy (16.7%), psychosis (12.5%), tabes dorsalis (12.5%) and meningovascular syphilis (8.3%). 63% of probable NS cases were not treated appropriately due to a negative CSF VDRL. Despite increased specificity of the 2018 US CDC criteria, 70% of patient in the probable NS group were not treated appropriately. The overall annual incidence [95%CI] of NS was 2.47[1.28-4.31] per 100 000py in the Indigenous population and 0.95[0.50-1.62] in the non-Indigenous population (rate ratio = 2.60 [1.19-5.70];p = 0.017). CONCLUSION: Neurosyphilis is frequently reported in the NT, particularly in Indigenous populations. Disturbingly, 60% of probable neurosyphilis patients based on the 2014 criteria, and 70% based on the 2018 criteria with were not treated appropriately. It is critical that clinicians should be aware of the diagnosis of NS and treat patients appropriately.

Understanding lived experiences of Aboriginal people with type 2 diabetes living in remote Kimberley communities: diabetes, it don't come and go, it stays!

This study aimed to explore the lived experiences of Kimberley Aboriginal people with type 2 diabetes managed by remote Aboriginal Community Controlled Health Services using phenomenological analysis. Semi-structured interviews formulated by Aboriginal Health Workers, researchers and other clinicians were used to obtain qualitative data from 13 adult Aboriginal patients with type 2 diabetes managed in two remote communities in the Kimberley. Together with expert opinion from local Aboriginal Health Workers and clinicians, the information was used to develop strategies to improve diabetes management. Of 915 regular adult patients in the two communities, 27% had type 2 diabetes; 83% with glycated haemoglobin A >10%. Key qualitative themes included: the need for culturally relevant education and pictorial resources; importance of continuous therapeutic relationships with healthcare staff; lifestyle management advice that takes into account local and cultural factors; and the involvement of Aboriginal community members and families in support roles. Recommendations to improve diabetes management in the remote communities have been made collaboratively with community input. This study provides a framework for culturally relevant recommendations to assist patients with diabetes, for collaborative research, and for communication among patients, Aboriginal Health Workers, community members, researchers and other clinicians. Interventions based on recommendations from this study will be the focus of further collaborative research.

Complex diabetes screening guidelines for high-risk adolescent Aboriginal Australians: a barrier to implementation in primary health care.

The aim of this study is to ascertain whether a simplified screening algorithm incorporating glycated haemoglobin (HbA1c) tests increases type 2 diabetes (T2D) screening in 10- to 14-year-old Aboriginal Australians presenting to primary healthcare (PHC) services. The study involved a 6-month pilot of a locally developed evidence-based screening algorithm in a remote Western Australian Kimberley town. A retrospective audit of electronic health records for the pilot period (27 June-26 December 2016) and a 6-month period before the screening algorithm was introduced (1 October 2015-31 March 2016) was conducted. Interviews were held with 30 PHC staff at participating PHC services, an Aboriginal Community Controlled Health Service (ACCHS) and a hospital-based general practice service. During the pilot, significantly more patients received an initial T2D screening test at the ACCHS (28/130 (22%) v. 50/139 (36%), P = 0.011), but there was no change at the hospital (0.02% v. 0.02%, P = 0.615). Staff feedback suggested measures to improve screening; these include simple guidelines, targeted screening, patient and staff education, point-of-care HbA1c tests and a whole-of-clinic approach to implementation. Implementing a screening algorithm for young-onset diabetes in Aboriginal Australians is challenging, but practical measures can be taken to improve screening.

Characteristics and Impact of Disseminated Gonococcal Infection in the "Top End" of Australia.

The "Top End" of Australia is presently experiencing a gonorrhea epidemic. Gonococcal infection is usually limited to mucosal tissues but can lead to disseminated gonococcal infection (DGI), joint destruction, and severe sepsis. This study aimed to explore the epidemiology, presentation, management, and health-care impact of DGI in the Top End of the Northern Territory. Health records of patients diagnosed with proven, probable, or possible DGI between January 2010 and September 2018 were analyzed retrospectively. One hundred six cases of DGI were identified. Ninety-four patients (88.7%) were Indigenous Australian. The incidence of proven and probable DGI in the Indigenous population was 27.1 per 100,000 person-years, compared with 7.1 in the Top End population overall. Of 7,540 laboratory-proven gonococcal notifications, 1.3% (n = 97) were complicated by DGI. The highest incidence was in the 15-19-year age-group. Thirteen cases (12.3%) occurred in patients younger than 15 years. High rates of comorbid alcohol misuse, diabetes, systemic lupus erythematosus, rheumatic fever, and complement deficiency were observed. The "classic triad" of tenosynovitis, dermatitis, and polyarthralgia was rare. Ninety-four patients (88.7%) presented with purulent arthritis. Disseminated gonococcal infection was estimated to cause at least 10.0% of nonpenetrating septic arthritis in the Top End and 1,234 days of hospitalization during the study period. DGI is an important cause of morbidity in the Top End, particularly in the young, remote Indigenous Australian population. Clinical presentation varies from classical teaching. Urgent action in the health and community sector is required, particularly for at-risk populations, to prevent further debilitating and costly complications of gonococcal infection.

Hyperglycaemic presentations in type 2 diabetes

BACKGROUND: Hyperosmolar hyperglycaemic state (HHS) is a syndrome that occurs in patients with type 2 diabetes mellitus (T2DM) and is comparable to diabetic ketoacidosis (DKA) seen in patients with type 1 diabetes. For a general practitioner working in a rural emergency department, recognition of HHS in a patient presenting with the triad of severe dehydration, hyperglycaemia and hyperosmolality is important to guide management and plan for disposition. OBJECTIVES: This article reviews the hyperglycaemic states that can occur in patients with T2DM. The reasons for the biochemical derangements in both HHS and DKA are outlined, with a focus on the recognition and management of HHS. DISCUSSION: Knowledge of the pathophysiology that influences HHS helps understand of its clinical presentation and treatment. HHS has a high mortality rate (5­20%), and having access to clinical guidelines from a referring hospital is useful to guide early management strategies.

Diabetes screening in pregnancy failing women in rural Western Australia: An audit of oral glucose tolerance test completion rates.

OBJECTIVE: To quantify screening rate for gestational diabetes mellitus and completion of oral glucose tolerance test in rural and remote Western Australia. DESIGN AND PARTICIPANTS: Retrospective audit of 551 antenatal records from women of 16 years and older without pre-existing diabetes and with singleton pregnancies delivered in 2013. MAIN OUTCOME MEASURES: Number of women recorded screened for gestational diabetes mellitus in second or third trimester using oral glucose tolerance test or other tests; gestational diabetes mellitus rate. RESULTS: Only 278 (50.5%) women were screened with oral glucose tolerance test; 113 (20.5%) had no record of any screening related to gestational diabetes mellitus. In a nested mixed-effects logistic regression model, women with a previous gestational diabetes mellitus diagnosis, two or more risk factors (excluding ethnicity) or high-risk gestational diabetes mellitus ethnicity other than Australian Aboriginal were more likely to be screened, while Australian Aboriginal women were less likely to be screened with oral glucose tolerance test. Clinicians reported patient and clinician factors and logistical difficulties as reasons for the oral glucose tolerance test not being completed at their site. Of those screened with oral glucose tolerance test, a high rate of gestational diabetes mellitus was diagnosed (14.7% versus Western Australia state-wide average of 7.4%). CONCLUSION: Adherence to oral glucose tolerance test screening in rural Western Australia is inadequate for effective screening for gestational diabetes mellitus. Screening was not acceptable or available for a significant proportion of women at risk. Efforts to improve oral glucose tolerance test adherence and exploration of alternative gestational diabetes mellitus screening strategies are required.

Using glycated haemoglobin testing to simplify diabetes screening in remote Aboriginal Australian health care settings.

OBJECTIVES: To determine whether a combination of point-of-care (POC) and laboratory glycated haemoglobin A (HbA1c) testing (HbA1c algorithm) is more effective in testing for diabetes in everyday practice in remote Australian Aboriginal primary health care, by providing a more rapid definitive result and diagnosing more cases than the standard glucose algorithm. DESIGN: Cross-sectional study that independently classified participants using both diagnostic algorithms and compared their outcomes. PARTICIPANTS: Two hundred and fifty-five Aboriginal Australians aged 15 years or more without confirmed diabetes and due for diabetes testing at participating clinics. SETTING: Six primary health care sites in the Kimberley region of Western Australia from 1 September 2011 to 30 November 2013. MAIN OUTCOME MEASURES: Number of participants with a definitive test result, a completed algorithm and a diagnosis of diabetes; time taken to deliver a test result. RESULTS: Participants were significantly more likely to have a definitive result within 7 days (249 v 199 of 255 participants; P < 0.001), be followed up if an initial laboratory measurement was abnormal (92 v 74 of 167 participants; P = 0.005), and be diagnosed with diabetes (15 v 4 of 255 participants; P = 0.003) using the HbA1c than with the glucose algorithm. Eight participants subsequently diagnosed with diabetes (four using the HbA1c test, four with additional oral glucose tolerance tests that would not normally have been requested) were incorrectly classified as normal by the glucose algorithm. No participants with normal HbA1c measurements were subsequently diagnosed with diabetes. CONCLUSIONS: Use of POC HbA1c testing and collection of venous blood on the same day for a confirmatory laboratory HbA1c testing if the POC HbA1c value is abnormal may simplify diabetes testing in remote areas, provide more timely diagnoses, and increase case detection.

Cross-sectional comparison of point-of-care with laboratory HbA1c in detecting diabetes in real-world remote Aboriginal settings.

OBJECTIVES: To determine if point-of-care (POC) glycated haemoglobin (HbA1c) is sufficiently accurate in real-world remote settings to predict or exclude the diagnosis of diabetes based on laboratory HbA1c measurements. DESIGN: Cross-sectional study comparing POC capillary HbA1c results with corresponding venous HbA1c levels measured in a reference laboratory. PARTICIPANTS: Aboriginal patients ≥15 years old who were due for diabetes screening at the participating clinics were invited to participate. Two hundred and fifty-five Aboriginal participants were enrolled and 241 were included in the analysis. SETTING: 6 primary healthcare sites in the remote Kimberley region of Western Australia from September 2011 to November 2013. MAIN OUTCOME MEASURES: Concordance and mean differences between POC capillary blood HbA1c measurement and laboratory measurement of venous blood HbA1c level; POC capillary blood HbA1c equivalence value for screening for diabetes or a high risk of developing diabetes; sensitivity, specificity and positive-predictive value for diagnosing and screening for diabetes; barriers to conducting POC testing. RESULTS: Concordance between POC and laboratory results was good (ρ=0.88, p<0.001). The mean difference was -0.15% (95% limits of agreement, -0.67% to 0.36%). POC HbA1c measurements ≥6.5%, 48 mmol/mol had a specificity of 98.2% and sensitivity of 73.7% for laboratory measurements ≥6.5%. The POC equivalence value for screening for diabetes or a high risk of developing diabetes was ≥5.7%, 39 mmol/mol (sensitivity, 91%; specificity, 76.7% for laboratory measurements ≥6.0%, 42 mmol/mol). Staff trained by other clinic staff 'on the job' performed as well as people with formal accredited training. Staff reported difficulty in maintaining formal accreditation. CONCLUSIONS: POC HbA1c testing is sufficiently accurate to be a useful component in screening for, and diagnosing, diabetes in remote communities. Limited local training is adequate to produce results comparable to laboratory results and accreditation processes need to reflect this.