Therapeutic versus prophylactic anticoagulation for patients admitted to hospital with COVID-19 and elevated D-dimer concentration (ACTION): an open-label, multicentre, randomised, controlled trial.

BACKGROUND: COVID-19 is associated with a prothrombotic state leading to adverse clinical outcomes. Whether therapeutic anticoagulation improves outcomes in patients hospitalised with COVID-19 is unknown. We aimed to compare the efficacy and safety of therapeutic versus prophylactic anticoagulation in this population. METHODS: We did a pragmatic, open-label (with blinded adjudication), multicentre, randomised, controlled trial, at 31 sites in Brazil. Patients (aged ≥18 years) hospitalised with COVID-19 and elevated D-dimer concentration, and who had COVID-19 symptoms for up to 14 days before randomisation, were randomly assigned (1:1) to receive either therapeutic or prophylactic anticoagulation. Therapeutic anticoagulation was in-hospital oral rivaroxaban (20 mg or 15 mg daily) for stable patients, or initial subcutaneous enoxaparin (1 mg/kg twice per day) or intravenous unfractionated heparin (to achieve a 0·3-0·7 IU/mL anti-Xa concentration) for clinically unstable patients, followed by rivaroxaban to day 30. Prophylactic anticoagulation was standard in-hospital enoxaparin or unfractionated heparin. The primary efficacy outcome was a hierarchical analysis of time to death, duration of hospitalisation, or duration of supplemental oxygen to day 30, analysed with the win ratio method (a ratio >1 reflects a better outcome in the therapeutic anticoagulation group) in the intention-to-treat population. The primary safety outcome was major or clinically relevant non-major bleeding through 30 days. This study is registered with ClinicalTrials.gov (NCT04394377) and is completed. FINDINGS: From June 24, 2020, to Feb 26, 2021, 3331 patients were screened and 615 were randomly allocated (311 [50%] to the therapeutic anticoagulation group and 304 [50%] to the prophylactic anticoagulation group). 576 (94%) were clinically stable and 39 (6%) clinically unstable. One patient, in the therapeutic group, was lost to follow-up because of withdrawal of consent and was not included in the primary analysis. The primary efficacy outcome was not different between patients assigned therapeutic or prophylactic anticoagulation, with 28 899 (34·8%) wins in the therapeutic group and 34 288 (41·3%) in the prophylactic group (win ratio 0·86 [95% CI 0·59-1·22], p=0·40). Consistent results were seen in clinically stable and clinically unstable patients. The primary safety outcome of major or clinically relevant non-major bleeding occurred in 26 (8%) patients assigned therapeutic anticoagulation and seven (2%) assigned prophylactic anticoagulation (relative risk 3·64 [95% CI 1·61-8·27], p=0·0010). Allergic reaction to the study medication occurred in two (1%) patients in the therapeutic anticoagulation group and three (1%) in the prophylactic anticoagulation group. INTERPRETATION: In patients hospitalised with COVID-19 and elevated D-dimer concentration, in-hospital therapeutic anticoagulation with rivaroxaban or enoxaparin followed by rivaroxaban to day 30 did not improve clinical outcomes and increased bleeding compared with prophylactic anticoagulation. Therefore, use of therapeutic-dose rivaroxaban, and other direct oral anticoagulants, should be avoided in these patients in the absence of an evidence-based indication for oral anticoagulation. FUNDING: Coalition COVID-19 Brazil, Bayer SA.

Familial hyperaldosteronism type III a novel case and review of literature.

Less than 15% of hypertension cases in children are secondary to a primary hyperaldosteronism. This is idiopathic in 60% of the cases, secondary to a unilateral adenoma in 30% and 10% remaining by primary adrenal hyperplasia, familial hyperaldosteronism, ectopic aldosterone production or adrenocortical carcinoma.To date, four types of familial hyperaldosteronism (FH I to FH IV) have been reported. FH III is caused by germline mutations in KCNJ5, encoding the potassium channel Kir3.4. The mutations cause the channel to lose its selectivity for potassium, allowing large quantities of sodium to enter the cell. As a consequence, the membrane depolarizes, voltage-gated calcium channels open, calcium enters the cell, initiating the cascade that leads to aldosterone synthesis. Somatic mutations in KCNJ5 has also been described in aldosterone-producing adenomas. The most frequent presentation of FH III is with severe hyperaldosteronism symptoms and resistance to pharmacological therapy which leads to bilateral adrenalectomy. We will review current literature and describe a child with FH III due to a novel de novo deletion in KCNJ5 with wild phenotype as a sign of clinical variability of this disease.

Role of the Healico© Wound Care Smartphone Application in Preventing a Foot Amputation in a 65-Year-Old Patient with Diabetes.

BACKGROUND Healico© is an innovative smartphone application designed to assist healthcare professionals in managing wounds in their daily practice. The application records all clinical information of the wound, facilitating its monitoring, and may lead to the selection of the best treatment for the patient. In addition, the application allows secure data sharing among healthcare professionals. CASE REPORT We report the successful use of Healico© in aiding the avoidance of foot amputation in a 65-year-old patient with diabetes. The patient had a diabetic foot ulcer, the main cause of lower limb amputation in Spain. Amputations negatively impact the quality of life of patients and are an enormous economic burden. The treatment of diabetic foot ulcers requires a multidisciplinary approach with good coordination between healthcare professionals from different fields and between different levels of care (primary care centers, sociosanitary centers, and hospitals). Through the use of Healico©, the patient with severe clinical signs of infection was referred urgently from primary care to the referral hospital and was quickly treated with antibiotics and underwent surgery. As a result, the infection was successfully delimited and excision of the foot was prevented. CONCLUSIONS Healico© promoted rapid communication between the primary care center and hospital, enabling urgent referral of the patient to a specialist. This clinical case reports the value that a digital application can bring to the healthcare sector and, in particular, the value of Healico© implementation in the daily practice of healthcare professionals to optimize the management of wounds, such as diabetic foot ulcers.

Carotid artery stiffness as an early marker of vascular lesions in children and adolescents with cardiovascular risk factors.

INTRODUCTION AND OBJECTIVES: The availability of a noninvasive marker of vascular lesions that enables their detection in the preclinical phase would be of great benefit for cardiovascular disease prevention. The aim of this study was to investigate the usefulness of a range of indices of arterial wall stiffness in the common carotid artery, as derived using high-resolution Doppler ultrasonography, for identifying vascular damage in children with risk factors. METHODS: The study involved 99 children (age, 8-16 years) divided into two groups: 65 had cardiovascular risk factors (45 obesity, 20 dyslipidemia) and 34 were controls. Family histories of cardiovascular risk factors and anthropometric and biochemical measurements were recorded. Functional parameters of arterial stiffness (i.e., arterial compliance, elastic modulus, beta stiffness index, pulse wave velocity, and augmentation index) and the intima-media thickness were also measured. RESULTS: Some functional vascular parameters were higher in obese children than controls: there were significant differences in beta stiffness index (P< .02), elastic modulus (P< .001) and pulse wave velocity (P< .01). There was a significant difference in arterial compliance between dyslipidemics and controls (P< .05). No significant difference in intima-media thickness was found between the groups. In obese children, there were positive correlations between body mass index, systolic pressure and triglyceride levels and vascular parameters (i.e., elastic modulus and pulse wave velocity); in dyslipidemic children, triglyceride levels and the same parameters were correlated. CONCLUSIONS: Ultrasonographic measurement of arterial stiffness is a sensitive technique that can detect vascular damage in children with cardiovascular risk factors earlier than intima-media thickness measurement.