Adding Hyponatremia to the "Rule-of-6" Prediction Tool Improves Performance in Identifying Hospitalised Patients with COVID-19 at Risk of Adverse Clinical Outcomes.

The 'rule-of-6' prediction tool was shown to be able to identify COVID-19 patients at risk of adverse outcomes. During the pandemic, we frequently observed hyponatremia at presentation. We sought to evaluate if adding hyponatremia at presentation could improve the 'rule-of-6' prediction tool. We retrospectively analysed 1781 consecutive patients admitted to a single tertiary academic institution in Singapore with COVID-19 infection from February 2020 to October 2021. A total of 161 (9.0%) patients had hyponatremia. These patients were significantly older, with more co-morbidities and more likely to be admitted during the Delta wave (2021). They were more likely to have radiographic evidence of pneumonia (46.0% versus 13.0%, p < 0.001) and more adverse outcomes (25.5% vs. 4.1%, p < 0.001). Hyponatremia remained independently associated with adverse outcomes after adjusting for age, lack of medical co-morbidities, vaccination status, year of admission, CRP, LDH, and ferritin. The optimised cut-off for serum sodium in predicting adverse outcomes was approximately <135 mmol/L as determined by the Youden index. Although derived in early 2020, the 'rule-of-6' prediction tool continued to perform well in our later cohort (AUC: 0.72, 95%CI: 0.66-0.78). Adding hyponatremia to the 'rule-of-6' improved its performance (AUC: 0.76, 95%CI: 0.71-0.82). Patients with hyponatremia at presentation for COVID-19 had poorer outcomes even as new variants emerged.

Trends in electrocardiographic and cardiovascular manifestations of patients hospitalised with COVID-19.

INTRODUCTION: Early in the coronavirus disease 2019 (COVID-19) pandemic, a low incidence of cardiovascular complications was reported in Singapore. Little was known about the trend of cardiovascular complications as the pandemic progressed. In this study, we examined the evolving trends in electrocardiographic and cardiovascular manifestations in patients hospitalised with COVID-19. METHODS: We examined the first 1781 consecutive hospitalised patients with polymerase chain reaction-confirmed COVID-19. We divided the population based on whether they had abnormal heart rate (HR) or electrocardiography (ECG) or normal HR and ECG, comparing the baseline characteristics and outcomes. Cardiovascular complications were defined as acute myocardial infarction, stroke, pulmonary embolism, myocarditis and mortality. RESULTS: The 253 (14.2%) patients who had abnormal HR/ECG at presentation were more likely to be symptomatic. Sinus tachycardia was commonly observed. Troponin I levels (97.0 ± 482.9 vs. 19.7 ± 68.4 ng/L, P = 0.047) and C-reactive protein levels (20.1 ± 50.7 vs. 13.9 ± 24.1 µmol/L, P = 0.003) were significantly higher among those with abnormal HR/ECGs, with a higher prevalence of myocarditis (2.0% vs. 0.5%, P = 0.019), pulmonary embolism (2.0% vs. 0.3%, P = 0.008) and acute myocardial infarction (1.2% vs. 0.1%, P = 0.023). After adjusting for age and comorbidities, abnormal HR/ECG (adjusted odds ratio 4.41, 95% confidence interval 2.21-8.77; P < 0.001) remained independently associated with adverse cardiovascular complications. Over time, there was a trend towards a higher proportion of hospitalised patients with cardiovascular complications. CONCLUSION: Cardiovascular complications appear to be increasing in proportion over time among hospitalised patients with COVID-19. A baseline ECG and HR measurement may be helpful for predicting these complications.

Inflammatory phenotypes may be more important than age and comorbidities in predicting clinical outcomes in hospitalised patients with COVID-19.

Objectives: In critically ill patients with COVID-19, distinct hyperinflammatory and hypoinflammatory phenotypes have been described, with different outcomes and responses to therapy. We investigated if similar phenotypes exist in non-severe illness. Methods: Consecutive patients with polymerase chain reaction (PCR) confirmed SARS-CoV-2 were examined. Baseline demographics and laboratory investigations were tabulated, including serum C-reactive protein. Patients were divided into those who were hyperinflammatory (defined as C-reactive protein >17 mg/l) or hypoinflammatory. Adverse outcomes, defined as requiring oxygenation, intensive care, or death, were recorded during the hospital stay. Clinical characteristics and outcomes were compared. Results: Of the 1781 patients examined, 276 (15.5%) had a hyperinflammatory phenotype. They were older (51.8 ± 17.2 vs 40.3 ± 13.8 years, P <0.001), had a lower PCR cycle threshold (PCR cycle threshold value 19.3 ± 6.3 vs 22.7 ± 15.4, P = 0.025) at presentation, and more medical comorbidities. The hyperinflammatory phenotype was independently associated with adverse clinical outcomes, even after adjusting for age, medical history and viral load on multivariable analyses (adjusted odds ratio 5.78, 95% confidence interval 2.86-11.63). Conclusion: Even in non-severe COVID-19, there are distinct hyper- and hypoinflammatory phenotypes, with the hyperinflammatory phenotype strongly associated with adverse clinical outcomes, that could be distinguished with a simple biomarker.

Continued demographic shifts in hospitalised patients with COVID-19 from migrant workers to a vulnerable and more elderly local population at risk of severe disease.

OBJECTIVES: In the early months of the COVID-19 pandemic in Singapore, the vast majority of infected persons were migrant workers living in dormitories who had few medical comorbidities. In 2021, with the Delta and Omicron waves, this shifted to the more vulnerable, elderly population within the local community. We examined evolving trends among the hospitalised cases of COVID-19. METHODS: All patients with polymerase chain reaction-positive SARS-CoV-2 admitted from February 2020 to October 2021 were included and subsequently stratified by their year of admission (2020 or 2021). We compared the baseline clinical characteristics, clinical course, and outcomes. RESULTS: A majority of cases were seen in 2020 (n = 1359), compared with 2021 (n = 422), due to the large outbreaks in migrant worker dormitories. Nevertheless, the greater proportion of locally transmitted cases outside of dormitories in 2021 (78.7% vs 12.3%) meant a significantly older population with more medical comorbidities had COVID-19. This led to an observably higher proportion of patients with severe disease presenting with raised inflammatory markers, need for therapeutics, supplemental oxygenation, and higher mortality. CONCLUSION: Changing demographics and the characteristics of the exposed populations are associated with distinct differences in clinical presentation and outcomes. Older age remained consistently associated with adverse outcomes.

Malignancy and all-cause mortality; incidence in adolescents and young adults living with perinatally acquired HIV.

BACKGROUND: Adults living with HIV have an increased risk of malignancy yet there is a paucity of data for adolescents and young adults (AYA) with perinatally acquired HIV (PaHIV). METHODS: Retrospective cohort analysis of all-cause mortality and malignancies in AYA with PaHIV aged 10-24 years attending a tertiary unit from 01 January 2004 to 31 December 2017, assessing cancer presentation, immunology and comparing mortality and malignancy incidence to age-matched UK general population rates. RESULTS: A total of 290 AYA with PaHIV contributed 2644 person-years of follow up. Six (2.0%) died within the study period at a median age of 17 years (interquartile range [IQR]15-19), 3 of malignancy, 2 with end-stage HIV and 1 with cryptococcal meningitis. Overall mortality rate was 2.3/1000 person-years, with an age-matched general population rate of 0.2/1000 person-years. Eight (2.8%) were diagnosed with a malignancy; 6 with lymphoma (n=3 Hodgkin's, n=1 Burkitt's, n=2 B-cell) and one each with hepatocellular carcinoma and gastrointestinal adenocarcinoma. At cancer diagnosis the median age was 19 years (IQR 14-23), median CD4 T cell count was 453 cells/mm3 (IQR 231-645) and median length of HIV viremia was 15 years (IQR 12-17). The incidence rate of a malignancy was 3.0/1000 person-years in AYA with PaHIV, whilst that in the age-matched general population is 0.2/1000 person-years. CONCLUSION: AYA living with PaHIV had an increased risk of all-cause mortality and of malignancy compared to their uninfected peers, with the excess in malignancy driven by lymphomas. It is hoped that earlier access to antiretroviral therapy will mitigate some of the AIDS-defining and non-AIDS defining risks for future generations.

The management and referral of iliofemoral deep venous thrombosis in North West London.

BACKGROUND: Post-thrombotic syndrome is a common complication of iliofemoral deep venous thrombosis (IFDVT). Existing evidence and National Institute for Health and Care Excellence guidelines suggest that this can be reduced by prompt thrombolytic therapy or thrombectomy. We aimed to evaluate the characteristics of IFDVT patients and to identify whether patients are being offered the recommended treatment pathway. METHODS: A multicenter cross-sectional study was conducted across eight hospital sites in the North West London region, of which two were hub hospitals in their local vascular service networks. Patients with proximal DVT were identified using International Classification of Diseases, Tenth Revision coding during a 1-year period. Data on demographics, diagnostic methods used, interventions, and referrals were extracted from electronic and paper medical records. RESULTS: During the study period, 132 patients with IFDVT were identified (mean age, 59.4 years; 55% female); 75% of these patients had an IFDVT. In this cohort, the biggest predisposing factors were previous DVT (n = 35), malignant disease (n = 35), and immobility (n = 20). In total, 104 patients were administered anticoagulation, and 88 of these patients received anticoagulation within 24 hours. The cases of 45 patients were either discussed with or promptly referred to a vascular service, after which 20 patients were treated solely with anticoagulation, whereas 20 patients received thrombolysis of varying methods. CONCLUSIONS: A significant proportion (56%) of symptomatic IFDVT patients are not being appropriately referred to or discussed with vascular services. Of these, 43% would have been eligible for consideration of early thrombus removal. Adherence to the National Institute for Health and Care Excellence guidelines could be improved by increasing awareness among emergency department colleagues.

Clinical outcomes post transition to adult services in young adults with perinatally acquired HIV infection: mortality, retention in care and viral suppression.

OBJECTIVE: Adolescence is the only age group globally where HIV-associated mortality is rising, with poorer outcomes at all stages of the care cascade compared with adults. We examined post transition outcomes for young adults living with perinatal HIV. DESIGN: Retrospective cohort analysis. SETTING: A tertiary Youth Friendly Service London, UK. PARTICIPANTS: A total of 180 young adults living with perinatal HIV registered between 1 January 2006 and 31 December 2017 contributed 921 person-years of follow-up post transition to adult services. INTERVENTION: Youth Friendly Service with multidisciplinary care and walk-in access. MAIN OUTCOME MEASURES: Mortality, morbidity, retention in care, antiretroviral therapy (ART) uptake and HIV-viral load suppression. Crude incidence rates are reported per 1000 person-years. RESULTS: Of 180 youth registered, four (2.2%) died, 14 (7.8%) transferred care and four (2.2%) were lost to follow-up. For the 158 retained in care, the median age was 22.9 years [interquartile ranges (IQR) 20.3-25.4], 56% were female, 85% Black African, with a median length of follow-up in adult care of 5.5 years (IQR 2.9-7.3). 157 (99.4%) ever received an ART prescription, 127/157 (81%) with a latest HIV-viral load less than 200 copies RNA/ml, median CD4 cell count of 626 cells/µl (IQR 441-820). The all-cause mortality was 4.3/1000 person-years [95% confidence interval (CI) 1.2-11.1], 10 fold the aged-matched UK HIV-negative population [0.43/1000 person-years (95% CI 0.41-0.44)]. Post transition, 17/180 (9.4%) developed a new AIDS diagnosis; crude incidence rates 18.5/1000 person-years (95% CI 10.8-29.6). CONCLUSION: While this youth-friendly multidisciplinary service achieved high engagement and coverage of suppressive ART, mortality remains markedly increased compared with the general UK population.

Clinical research cerebral MRI findings in HIV-positive subjects and appropriate controls.

: Abnormalities in cerebral MRI are frequently reported in persons living with HIV (PLWH). We compared clinical cerebral MRI reports in 59 PLWH and 29 lifestyle matched controls. Although clinical abnormalities were highly prevalent (47.7%), and included white-matter lesions (46.6%), microvascular disease (22.7%) and cerebral volume loss (11.4%), no differences were apparent between PLWH and controls, with abnormalities being associated with age and hypertension rather than HIV serostatus.