Systematic review of drug–drug interactions between rifamycins and anticoagulant and antiplatelet agents and considerations for management

Rifamycins (rifampin, rifabutin, and rifapentine) play an essential role in the treatment of mycobacterial and some nonmycobacterial infections. They also induce the activity of various drug transporting and metabolizing enzymes, which can impact the concentrations and efficacy of substrates. Many anticoagulant and antiplatelet (AC/AP) agents are substrates of these enzymes and have narrow therapeutic indices, leading to risks of thrombosis or bleeding when coadministered with rifamycins. The objective of this systematic review was to evaluate the effects on AC/AP pharmacokinetics, laboratory markers, and clinical safety and efficacy of combined use with rifamycins. A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidance was performed. The PubMed, Embase, and Web of Science databases were queried for English-language reports on combination use of rifamycins and AC/AP agents from database inception through August 2021. The 29 studies identified examined warfarin (n = 17), direct oral anticoagulants (DOACs) (n = 8), and antiplatelet agents (n = 4) combined with rifampin (n = 28) or rifabutin (n = 1). Eleven studies were case reports or small case series; 14 reported on pharmacokinetic or laboratory markers in healthy volunteers. Rifampin-warfarin combinations led to reductions in warfarin area under the curve (AUC) of 15%–74%, with variability by warfarin isomer and study. Warfarin dose increases of up to 3–5 times prerifampin doses were required to maintain coagulation parameters in the therapeutic range. DOAC AUCs were decreased by 20%–67%, with variability by individual agent and with rifampin versus rifabutin. The active metabolite of clopidogrel increased substantially with rifampin coadministration, whereas prasugrel was largely unaffected and ticagrelor saw decreases. Our review suggests most combinations of AC/AP agents and rifampin are problematic. Further studies are required to determine whether rifabutin or rifapentine could be safe alternatives for coadministration with AC/AP drugs.     

A Type 1 diabetes technology pathway: consensus statement for the use of technology in Type 1 diabetes

In both adults and children with diabetes, technologies such as continuous subcutaneous insulin infusion using insulin pumps and continuous glucose monitoring can help improve diabetes control, reduce hypoglycaemia and improve quality of life. Access to these technologies in the UK is very variable. Some technologies are recommended by the National Institute for Health and Care Excellence, while others have not been appraised, and new technologies are emerging all the time. Additionally, different guidelines for adults and children further complicate access to diabetes technology in the transition from paediatric to adult care. Against this background, Diabetes UK and NHS England have brought together a multidisciplinary group of experts, including clinicians and people with diabetes, to develop this consensus guideline, combining the different technologies into a common pathway to aid clinical and policy decision‐making. We created a pathway that supports the incremental addition of technology as monotherapy and then dual therapy in the same way that we incrementally add in therapeutic agents to support people with Type 2 diabetes to achieve their personalized glycaemic targets. The pathway emphasizes the importance of structured education, specialist support and appropriate access to psychological therapies, as essential pillars for optimized use of diabetes‐related technology, and recommends the re‐evaluation of its use when the individual is unable either to use the technology appropriately or to achieve the intended outcomes. This pathway is endorsed by UK‐wide clinical and patient associations and we recommend that providers and commissioners use it to ensure the right individual with diabetes has access to the right technology in a timely way to help achieve better outcomes.     

Contribution to the rheological testing of pharmaceutical semisolids

Rheological behaviour of pharmaceutical semisolid preparations significantly affects manufacturing process, administration, stability, homogeneity of incorporated drug, accuracy of dosing, adhesion in the place of application, drug release, and resulting therapeutic effect of the product. We performed test of consistency by penetrometry, rotational, oscillation and creep tests, and squeeze and tack tests of model samples to introduce methods suitable for characterization and comparison of semisolids in practice. Penetrometry is a simple method allowing sorting the semisolids to low and high stress-resistant materials but deficient for rheological characterization of semisolids. Value of yield stress, generally considered to be appropriate feature of semisolids, is significantly influenced by the method of testing and the way of evaluation. The hysteresis loops of model semisolids revealed incomplete thixotropy, therefore, three-step thixotropy test was employed. Semisolids showed nonlinear response in the creep phase of tests and partial recovery of structure by storing energy in the recovery phase. Squeeze and tack tests seem to be convenient ways for comparison of semisolids. Our study can contribute to a better understanding of different flow behaviour of semisolids given by different physicochemical properties of excipients and can bring useful approaches to evaluation and comparison of semisolids in practice.     

Niven and Scott (2003): Sixteen years of hindsight

This paper revisits a 2003 publication in Nursing Philosophy: The need for accurate perception and informed judgement in determining the appropriate use of the nursing resource: hearing the patient's voice. The author suggests that the basic ideas and focus of this 16‐year‐old paper are still topical and relevant in considerations of nursing care. However, it is also suggested that greater attention to the importance of the nurse–patient relationship in considerations of resource allocation, and potential rationing of nursing care, would have strengthened the original paper.     

Motivation for participating in phase 1 vaccine trials: Comparison of an influenza and an Ebola randomized controlled trial

Introduction/Hypothesis

Recruitment of participants into phase 1 vaccine clinical trials can be challenging since these vaccines have not been used in humans and there is no perceived benefit to the participant. Occasionally, as was the case with a phase 1 clinical trial of an Ebola vaccine in Halifax, Canada, during the 2014–2016 West African Ebola virus outbreak, recruitment is less difficult. In this study, we explored the motivations of participants in two phase 1 vaccine trials that were concurrently enrolling at the same centre and compared the motivations of participants in a high-profile phase 1 Ebola vaccine trial to those in a less high-profile phase 1 adjuvanted seasonal influenza vaccine study.