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•VITT is a complication ChAdOx1 nCoV19 vaccination (AZD1222) vaccination.•Clinicopathological features suggest a less severe phenotype when compared to confirmed cases of VITT post 1st dose AZD1222.•Fatalities were seen in cases of VITT post dose 2 in the context of concomitant factors.•Antibody-mediated platelet activation remains the hallmark of the disease.•Low levels of anti-PF4 raises the possibility of alternative pathways for platelet activation. Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare but established complication of 1st dose ChAdOx1 nCoV19 vaccination (AZD1222), however this complication after dose 2 remains controversial. To describe the clinicopathological features of confirmed cases of VITT post dose 2 AZD1222 vaccination in Australia, and to compare this cohort to confirmed cases of VITT post 1st dose. Sequential cases of clinically suspected VITT (thrombocytopenia, D-Dimer > 5x upper limit normal and thrombosis) within 4–42 days of dose 2 AZD1222 referred to Australia’s centralised testing centre underwent platelet activation confirmatory testing in keeping with the national diagnostic algorithm. Final classification was assigned after adjudication by an expert advisory committee. Descriptive statistics were performed on this cohort and comparative analyses carried out on confirmed cases of VITT after 1st and 2nd dose AZD1222. Of 62 patients referred, 15 demonstrated presence of antibody mediated platelet activation consistent with VITT after dose 2 AZD1222. Four were immunoassay positive. Median time to presentation was 13 days (range 1–53) platelet count 116x10^9/L (range 63–139) and D-dimer elevation 14.5xULN (IQR 11, 26). Two fatalities occurred. In each, the dosing interval was less than 30 days. In comparison to 1st dose, dose 2 cases were more likely to be male (OR 4.6, 95% CI 1.3–15.8, p = 0.03), present with higher platelet counts (p = 0.05), lower D-Dimer (p = 01) and less likely to have unusual site thromboses (OR 0.14, 95% CI 0.04–0.28, p = 0.02). VITT is a complication of dose 2 AZD1222 vaccination. Whilst clinicopathological features are less severe, fatalities occurred in patients with concomitant factors.

Unlabelled Box Idiopathic immune thrombocytopenia (ITP) is an autoimmune disorder characterized by relapsing/ remitting thrombocytopenia. Bleeding complications are infrequent with platelet counts above 30×109/L, and this level is commonly used as a threshold for treatment. The question of another/ co‐existent diagnosis or an alternate mechanism of platelet destruction arises when bleeding is experienced with platelet counts above this threshold. We report a case of anti‐GPVI mediated ITP that was diagnosed following investigations performed to address this key clinical question. A patient with ITP experienced exaggerated bruising symptoms despite a platelet count of 91×109/L. Platelet functional testing showed an isolated platelet defect of collagen‐induced aggregation. Next generation sequencing excluded a pathogenic variant of GP6, and anti‐GPVI antibodies that curtailed GPVI function were confirmed by extended platelet phenotyping. We propose that anti‐GPVI mediated ITP may be under‐recognized, and that inclusion of GPVI in antibody detection assays may improve their diagnostic utility and in turn, facilitate a better understanding of ITP pathophysiology and aid individualized treatment approaches.

Mental health disorders are on the rise globally, with policies promoting programmes that aim to enhance mental wellbeing across various population domains. This scoping review aims to examine the literature to identify and map the mental health programmes in Singapore, while identifying critical knowledge gaps and scope for future systematic reviews. A systematic search was conducted across multiple databases including Medline, PsycINFO, CINAHL, OpenGrey and ProQuest, complemented by hand and bibliography searches. Articles published from 2000 onwards in English language were included. Independent parallel reviews were conducted by multiple reviewer pairs. Data was extracted into standardised, pre-piloted templates that incorporated the Template for Intervention Description and Replication (TIDieR) checklist. One hundred and six studies were included in the review, demonstrating diverse programmes targeting different age groups, with particular focus on older adults in hospital and community settings. The programmes addressed mental health outcomes in individuals with mental disorders, physical conditions, neurodevelopmental and learning disabilities, and among healthy individuals. Implemented by trained care teams or multidisciplinary professionals, these programmes generally showed positive outcomes. However, significant gaps were identified in the literature regarding user experiences, with minimal focus on implementation barriers and enablers. Notably, there was limited evidence of successful community-level implementation beyond the experimental phase, raising questions about programme sustainability and real-world effectiveness. Critical gaps were also identified in youth-specific suicide prevention programmes, despite suicide being a leading cause of death among youths, and programmes targeting the impact of built environment on mental health outcomes and workplace wellbeing. These areas represent important opportunities for future research and intervention development in Singapore's mental health landscape. Singapore has developed an active research network over the past decade to design and implement programmes aimed at improving mental health across different populations and settings. However, stronger collaborative approaches between academics and policymakers are needed to better utilise research findings and understand which programmes add value to the public health domain. Future research should focus on implementation science, long-term sustainability, and cost-effectiveness of these programmes in real-world settings.

Uveal melanoma (UM) is the most common primary intraocular malignancy, despite comprising <5% of all melanomas. To date, relatively few case series of UM have been published. Moreover, the factors influencing survival remain largely unknown. This study sought to analyze the impact of demographics, histology, clinical presentation, and treatments on the clinical outcomes of UM in a large modern nationwide patient cohort. Demographics and clinical data were abstracted on 277,120 histologically confirmed melanoma patients from the Surveillance, Epidemiology, and End Results database between 1973 and 2012. A total of 7,516 cases of UM represented 3.2% of all recorded cases of melanoma. The mean age-adjusted incidence was 5.1 per million (95% CI 4.2-6.1) and was higher in males (5.9, CI =4.4-7.6) compared to females (4.5, CI =3.3-5.8), <0.001. UM occurred most commonly in the sixth decade of life (61.4±15) and among Caucasians (94.7%). A total of 52.3% of cases were reported in the Western US (35.7% in California). The initial diagnoses in 65.2% of cases were by histopathology, followed by clinical diagnosis (18.8%) and radiographic imaging (16.0%). The percentage of UM cases managed by surgery alone decreased by 69.4% between the 1973-1977 and 2006-2012 time periods, concomitant with a 62% increase in primary radiotherapy, <0.001. The UM mean overall and cancer-specific 5-year relative survival rates were 79.8%±5.8% and 76%±5.3%, respectively. The mean 5-year cancer-specific survival rate (76%) remained stable during the study period between 1973 and 2012. The mean survival for patients treated with primary radiotherapy was significantly improved compared to those treated with surgery alone (15.4±0.4 vs 13.6±0.3, <0.001). Multivariate analysis identified male sex (odds ratio [OR] 1.1, CI =1.0-1.3), age >50 years (OR 4.0, CI =3.4-4.6), distant metastases (OR 8.6, CI =4.7-15), and primary surgical treatment (OR 2.6, CI =2.0-3.3) as independently associated with increased mortality, <0.005. Conversely, patients identified as Hispanic (OR 0.6, CI =0.5-0.8) and patients receiving radiation treatment (OR 0.5, CI =0.4-0.7) were independently associated with reduced mortality, <0.005. UM remains a rare form of melanoma that occurs primarily in Caucasian patients older than 50 years. More than two-thirds of UM patients are curatively treated with primary radiotherapy as opposed to surgery, which has resulted in a significant improvement in both overall survival and cancer-specific survival. Despite this shift in management strategy, the mean 5-year cancer-specific survival rate remained relatively unchanged during the study period. Male sex, older age, distant disease, and primary surgical therapy rather than radiotherapy are associated with an increased risk of mortality.

Botryococcus braunii is a colonial microalga that appears early in the fossil record and is a sensitive proxy of environmental and hydroclimatic conditions. Palaeozoic Botryococcus fossils which contribute up to 90% of oil shales and approximately 1% of crude oil, co-localise with diagnostic geolipids from the degradation of source-signature hydrocarbons. However more recent Holocene sediments demonstrate no such association. Consequently, Botryococcus are identified in younger sediments by morphology alone, where potential misclassifications could lead to inaccurate paleoenvironmental reconstructions. Here we show that a combination of flow cytometry and ancient DNA (aDNA) sequencing can unambiguously identify Botryococcus microfossils in Holocene sediments with hitherto unparalleled accuracy and rapidity. The application of aDNA sequencing to microfossils offers a far-reaching opportunity for understanding environmental change in the recent geological record. When allied with other high-resolution palaeoenvironmental information such as aDNA sequencing of humans and megafauna, aDNA from microfossils may allow a deeper and more precise understanding of past environments, ecologies and migrations.