Pharmacokinetics and pharmacodynamics of direct oral anticoagulants.

INTRODUCTION: Direct oral anticoagulants (DOACs) have overtaken vitamin K antagonists to become the most widely used method of anticoagulation for most indications. Their stable and predictable pharmacokinetics combined with relatively simple dosing, and the absence of routine monitoring has made them an attractive proposition for healthcare providers. Despite the benefits of DOACs as a class, important differences exist between individual DOAC drugs in respect of their pharmacokinetic and pharmacodynamic profiles with implications for dosing and reversal in cases of major bleeding. AREAS COVERED: This review summarizes the state of knowledge relating to the pharmacokinetics of dabigatran (factor IIa/thrombin inhibitor) and apixaban, edoxaban and rivaroxaban (factor Xa) inhibitors. We focus on pharmacokinetic differences between the drugs which may have clinically significant implications. EXPERT OPINION: Patient-centered care necessitates a careful consideration of the pharmacokinetic and pharmacodynamic differences between DOACs, and how these relate to individual patient circumstances. Prescribers should be aware of the potential for pharmacokinetic drug interactions with DOACs which may influence prescribing decisions in patients with multiple comorbidities. In order to give an appropriate dose of DOAC drugs, accurate estimation of renal function using the Cockcroft-Gault formula using actual body weight is necessary. An increasing body of evidence supports the use of DOACs in patients who are obese, and this is becoming more routine in clinical practice.

Stop and Go: Barriers and Facilitators to Care Home Research.

Barriers to care home research have always existed, but have been thrown into sharp relief by the COVID-19 pandemic. Existing infrastructure failed to deliver the research, or outcomes, which care home residents deserved and we need to look, again, at how these barriers can be taken down. Barriers can be categorised as procedural (encountered before research starts), system (encountered during research) or resident-specific. To tackle these, research regulatory bodies need to adopt a standardised approach to how care home research is developed and designed, reviewed and regulated, and how such approaches can enable recruitment of as wide a range of residents and their representatives as possible, including those without the mental capacity to consent for research. Establishment of local, inter-disciplinary collaborations between universities, general practices, health and social care providers and care homes is another priority. This should be based on pre-existing models such as the 'Living lab' model developed in The Netherlands and now being implemented in the UK and Austria. These changes are critical to develop a sustainable research model. If well designed this will deliver better outcomes for residents and align with the individual and organisational priorities of those who care for them.

Risk factors for post sternotomy wound complications across the patient journey: A systematised review of the literature.

BACKGROUND: Around 36,000 cardiac operations are undertaken in the United Kingdom annually, with most procedures undertaken via median sternotomy. Wound complications occur in up to 8% of operations, with an associated mortality rate of around 47% in late or undetected cases. OBJECTIVE: To undertake a systematised literature review to identify pre-operative, peri-operative and post-operative risk factors associated with sternal wound complications. METHODS: Healthcare databases were searched for articles written in the English language and published between 2013 and 2021. Inclusion criteria were quantitative studies involving patients undergoing median sternotomy for cardiac surgery; sternal complications and risk factors. RESULTS: 1360 papers were identified, with 25 included in this review. Patient-related factors included: high BMI; diabetes; comorbidities; gender; age; presenting for surgery in a critical state; predictive risk scores; vascular disease; severe anaemia; medication such as steroids or α-blockers; and previous sternotomy. Peri-operative risk increased with specific types and combinations of surgical procedures. Sternal reopening was also associated with increased risk of sternal wound infection. Post-operative risk factors included a complicated recovery; the need for blood transfusions; respiratory complications; renal failure; non-diabetic hyperglycaemia; sternal asymmetry and sepsis. CONCLUSION: Pre, peri and post-operative risk factors increase the risk of sternal wound complications in cardiac surgery. Generic risk assessment tools are primarily designed to provide mortality risk scores, with their ability to predict risk of wound infection questionable. Tools that incorporate factors throughout the operative journey are required to identify patients at risk of surgical wound infection.

The roles of alpha- and beta-adrenoceptor stimulation in myocardial ischaemia.

beta-Adrenoceptor (AR) ligands have been the mainstay of cardiovascular therapy for decades, with beta-AR antagonist being used for hypertension, angina and myocardial infarction and adrenaline in use for cardiopulmonary resuscitation for nearly 100 years. Ischaemia of the heart through coronary artery occlusion causes cell injury and death through necrosis and apoptosis. Reperfusion of the ischaemic myocardium results in cardiac dysfunction and infarction. Stimulation of alpha- and beta-ARs in the ischaemic heart have variable and inconsistent effects depending on when the agonist is applied. This review describes the different effects of stimulation of the three established beta-AR subtypes (beta(1)-, beta(2)- and beta(3)-ARs) either before ischaemia (preconditioning) or during ischaemia and reperfusion of the heart (postconditioning). Brief periods of ischaemia preceding a major ischaemic episode can have a protective effect against post-ischaemia-reperfusion damage, known as ischaemic preconditioning. This review considers the role of endogenous catecholamines released during preconditioning and the nature of the adrenoceptor subtypes that mediate these effects. The clinical significance of this to the use of beta-AR antagonists is considered. The transduction pathways and effects on apoptosis of the cardioprotective and deleterious effects of AR activation are considered. This commentary reviews the literature and attempts to bring together a unified synopsis of the effects of adrenoceptor stimulation in myocardial ischaemia and the potential clinical relevance.

Contagious equine metritis in Australia.

Contagious equine metritis (CEM) was first diagnosed in Australia in August 1977 and it has since been found on 6 farms in 3 states, having been isolated from about 24 mares and 2 stallions. Details are given of the epidemiology and control procedures used to combat CEM on one farm. Difficulty was experience in successfully treating one infected stallion; this was thought to be associated with inadequate cleaning and treating of the diverticulum of the urethral fossa. Introduction of the disease has had far-reaching consequences and may well result in the adoption of routine bacteriological tests on stallions and mares of unknown or dubious breeding history and other measures to minimize the possibility of spread between farms.