Study protocol of the PROUD48 study comparing the effects of pemafibrate and omega-3 fatty acid ethyl esters on ApoB-48 in statin-treated patients with dyslipidaemia: a prospective, multicentre, open-label, randomised, parallel group trial in Japan.

INTRODUCTION: This study will compare the lowering effects of pemafibrate and omega-3 fatty acid ethyl esters on fasting apolipoprotein B-48 (apoB-48), a surrogate marker reflecting postprandial hypertriglyceridaemia, which is a residual risk for atherosclerotic cardiovascular disease with statin treatment. METHODS AND ANALYSIS: This is a prospective, multicentre, open-label, randomised, parallel group, comparative trial. Adult Japanese patients with dyslipidaemia receiving statin treatment for more than 4 weeks with a fasting triglyceride level ≥177 mg/dL will be randomly assigned in a 1:1 ratio to receive pemafibrate (0.4 mg orally per day) or omega-3 fatty acid ethyl esters (4 g orally per day) for 16 weeks. The primary endpoint is the percentage change in fasting apoB-48 from baseline to 16 weeks. The key secondary endpoints include the change in fasting apoB-48 from baseline to 16 weeks, the percentage changes in clinical variables from baseline to 16 weeks and the incidence of adverse events. A total sample size of 128 was set by considering the increased drop-out rate due to the COVID-19 pandemic, in addition to estimation based on a two-sided alpha of 0.05 and a power of 0.8 for apoB-48. ETHICS AND DISSEMINATION: The study protocol has been approved by the Certified Review Board of the University of the Ryukyus for Clinical Research Ethics (No. CRB7200001) and will be performed in accordance with the Declaration of Helsinki. Written informed consent will be obtained from all participants. The results of the study will be disseminated through publications and conference presentations to participants, healthcare professionals and the public. TRIAL REGISTRATION NUMBER: jRCTs071200011.

COVID-19 pandemic unmasking cardiovascular risk factors and non-communicable diseases among migrant workers: a cross-sectional study in Singapore.

OBJECTIVES: This study aims to report the prevalence of cardiovascular risk factors (CVRFs) and other non-communicable diseases among migrant workers in Singapore admitted for COVID-19 infection, to highlight disease burden and the need for changes in health screening and healthcare delivery in this unique population. SETTING: The study was conducted in the largest tertiary hospital in Singapore. DESIGN: Retrospective cross-sectional study. PARTICIPANTS: 883 migrant workers who had mild or asymptomatic COVID-19 infection admitted to three isolation wards between 6 April 2020 and 31 May 2020 were included in this study. OUTCOME MEASURES: The outcome measures were the prevalence of pre-existing and newly diagnosed comorbid conditions and the prevalence of CVRFs-diabetes mellitus, hypertension and hyperlipidaemia-and non-communicable diseases at the time of discharge. The OR of having specific CVRFs depending on country of origin was generated via multivariate logistic regression analysis. RESULTS: The median age of our study population was 45 years. 17.0% had pre-existing conditions and 25.9% received new diagnoses. Of the new diagnoses, 15.7% were acute medical conditions and 84.3% chronic medical conditions. The prevalence of CVRFs was higher in Southeast Asian and South Asian migrant workers compared with Chinese. The prevalence of non-communicable diseases on discharge was highest among Southeast Asians (49.4%). CONCLUSIONS: The COVID-19 outbreak in a large number of migrant workers in Singapore unmasked a significant disease burden among them, increasing stakeholders' interests in their welfare. Moving forward, system-level changes are necessary to deliver healthcare sustainably and effect improvements in migrant workers' health.

Cardiovascular pathology and COVID-19 in residents of Yakutsk

A study was conducted on 161 citizens of Yakutsk who had a new coronavirus infection in the period from March to December 2020. A high incidence of arterial hypertension, obesity, and lipid-metabolic disorders was revealed. The relationship of lipids, glucose and uric acid in blood serum, arterial hypertension, waist circumference with the severity of the new coronavirus infection was shown. The high prevalence of cardiovascular pathology and its risk factors among study participants requires long-term follow-up of patients with post-COVID syndrome, which prevents premature death from diseases of the circulatory system.

Extensive papulonodular xanthoma: a diagnostic clue to homozygous familial hyperlipidaemia.

A man in his early 30s, presented with multiple soft tissue swellings over the buttocks, around the knees, ankles and dorsum of both the hands since childhood. His father and paternal uncle had similar lesions, and his father had coronary artery disease. One of his sisters had a history of sudden death due to an unknown cause at 14 years. The patient and his parents had very high serum levels of total cholesterol and low-density lipoprotein. Based on the above findings, a clinical diagnosis of familial hyperlipidaemia type II was made. Larger lesions were excised in stages, and histopathological evaluation revealed the lesions to be eruptive xanthoma. A cardiac assessment revealed no significant abnormality. Lipid-lowering agents and low-dose aspirin were started, and the patient was advised for regular cardiology and endocrine evaluation. This case emphasises its rare presentation and the importance of early diagnosis and management to prevent any untoward future incidence.

Severe acquired hypertriglyceridemia following COVID-19.

Severe hypertriglyceridemia is a major risk factor for acute pancreatitis. In exceptional cases, it is caused by plasma components inhibiting lipoprotein lipase activity. This phenomenon is predominantly associated with autoimmune diseases. Here, we report a case of severe hypertriglyceridemia due to a transient reduction in lipoprotein lipase activity following an episode of COVID-19 in an otherwise healthy 45-year-old woman. The lipoprotein lipase activity of the patient was markedly reduced compared with a healthy control and did recover to 20% of the healthy control's lipoprotein lipase activity 5 months after the COVID-19 episode. Mixing tests substantiated reduced lipolytic capacity in the presence of the patient's plasma at presentation compared with a homozygous lipoprotein lipase-deficient control, which was no longer present at follow-up. Western blotting confirmed that the quantity of lipoprotein lipase was not aberrant. Fibrate treatment and a strict hypolipidemic diet improved the patient's symptoms and triglyceride levels.

Study protocol: long-term effect of the New Nordic Renal Diet on phosphorus and lipid homeostasis in patients with chronic kidney disease, stages 3 and 4: a randomised controlled trial.

INTRODUCTION: Chronic kidney disease (CKD) causes severe disturbances in phosphate metabolism. New Nordic Renal Diet (NNRD) is a new dietary concept designed by the present research group that aims to offer patients with moderate CKD a whole food approach with a markedly reduction in dietary phosphorus intake, corresponding to 850 mg/day. The present protocol describes a randomised controlled trial aiming to test the long-term effects of dietary intervention with NNRD versus a non-restricted habitual diet on important parameters of phosphorus and lipid homeostasis. METHODS AND ANALYSIS: This trial will be executed at the Department of Nephrology, Rigshospitalet, University of Copenhagen, Denmark. Sixty patients aged >18 years with CKD stages 3 and 4 (estimated glomerular filtration rate between 15 and 45 mL/min) will be recruited and randomly assigned to the intervention or control group. The other inclusion criterion includes a medically stable condition for at least 2 months prior to the start of the study. Exclusion criteria are treatment with phosphate binders, metabolic disorders that require specific dietary regulation, pregnancy and breast feeding, any types of food allergies or those who are vegans. The observation period is 26 weeks including seven study visits at the outpatient clinic combined with a weekly telephone consultation in both groups. A follow-up visit 3 months after study completion finalises the intervention. The primary outcome is the difference in the change in 24-hour urine phosphorus excretion from baseline to week 26 between the two study groups. Secondary outcomes include changes in phosphate-related and lipid metabolism-related blood and urine biochemistry, blood pressure and body composition. Moreover, we wish to explore adherence to the diet as well as quality of life. ETHICS AND DISSEMINATION: The study has been approved by the Scientific Ethical Committee of the Capital Region of Denmark and the Danish Data Protection Agency. The results of the studies will be presented at national and international scientific meetings, and publications will be submitted to peer-reviewed journals. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (wwwclinicaltrialsgov) Registry (NCT04579315). PROTOCOL VERSION: The protocol, version 2, has been approved by the Ethical Committee Denmark on 18 September 2020. The protocol has also been approved by Data Protection Regulation and Data Protection Law on 15 September 2020. This study protocol is in accordance with the Standard Protocol Items: Recommendations for International Trials.

Atypical cutaneous and musculoskeletal manifestation of SARS-CoV-2: 'COVID-19 toes' and spasticity in a 48-year-old woman.

Establishing accurate symptomatology associated with novel diseases such as COVID-19 is a crucial component of early identification and screening. This case report identifies an adult patient with a history of clotting dysfunction presenting with rare cutaneous manifestations of COVID-19, known as 'COVID-19 toes'', previously described predominantly in children. Additionally, this patient presented with possible COVID-associated muscle spasticity of the lower limbs, as well as a prolonged and atypical timeline of COVID-19 infection. The rare occurrence of 'COVID-19 toes'' in this adult patient suggests that her medical history could have predisposed her to this symptom. This supports the coagulopathic hypothesis of this manifestation of COVID-19 and provides possible screening questions for patients with a similar history who might be exposed to the virus. Additionally, nervous system complaints associated with this disease are rare and understudied, so this novel symptom may also provide insight into this aspect of SARS-CoV-2.

Statin use and clinical outcomes in patients with COVID-19: An updated systematic review and meta-analysis.

PURPOSE: Observations studies have shown that prior use of statins is associated with a reduced risk of adverse clinical outcomes in patients with COVID-19. However, the available data are limited, inconsistent and conflicting. Besides, no randomised controlled trial exists in this regard. Hence, the present meta-analysis was conducted to provide an updated summary and collate the effect of statin use on clinical outcomes in COVID-19 using unadjusted and adjusted risk estimates. METHODS: PubMed, Scopus and Web of Science databases were systematically searched using appropriate keywords till December 18 2020, to identify observational studies reporting clinical outcomes in COVID-19 patients using statins versus those not using statins. Prior and in-hospital use of statins were considered. Study quality was assessed using the Newcastle-Ottawa Scale. Unadjusted and adjusted pooled odds ratio (OR) with 95% CIs were calculated. RESULTS: We included 14 observational studies pooling data retrieved from 19 988 patients with COVID-19. All the studies were of high/moderate quality. Pooled analysis of unadjusted data showed that statin use was not associated with improved clinical outcomes (OR 1.02; 95% CI 0.69 to 1.50, p=0.94, I2=94%, random-effects model). However, on pooling adjusted risk estimates, the use of statin was found to significantly reduce the risk of adverse outcomes (OR 0.51; 95% CI 0.41 to 0.63, p<0.0005, I2=0%, fixed-effects model). CONCLUSIONS: Statin use is associated with improved clinical outcomes in patients with COVID-19. Individuals with multiple comorbidities on statin therapy should be encouraged to continue the drug amid the ongoing pandemic.