Delivery of systemic anti-cancer therapy during the COVID-19 pandemic.

BACKGROUND: The first confirmed case of COVID-19 in Ireland was on February 29th 2020. From March until late April, the number of cases increased exponentially. The delivery of anti-cancer therapy during the COVID-19 pandemic was extremely challenging. In order to balance the benefits of continuing anti-cancer therapy with the associated increased hospital visits, combined with the risk of COVID-19 infection, we undertook a series of system changes in the delivery of cancer care. METHODS: Patients who attended our dayward over a 4-month period were included. Data were obtained from patient and chemotherapy prescribing records. Patients were screened for symptoms of COVID-19 at two separate timepoints: prior to their visit via telephone, and using a symptom questionnaire on arrival at the hospital. If patients displayed COVID-19 symptoms, they were isolated and a viral swab arranged. RESULTS: A total of 456 patients attended from January 1st to April 30th. The numbers of visits from January to April were 601, 586, 575, and 607, respectively. During this period, there were 2369 patient visits to the dayward and 1953 (82%) intravenous regimens administered. Of the 416 visits that did not lead to treatment, 114 (27%) were scheduled non-treatment review visits, 194 (47%) treatments were held due to disease-related illness, and 108 (26%) treatments were held due to treatment-related complications. Screening measurements were implemented on March 18th due to rising COVID-19 prevalence in the general population. Overall, 53 treatments were held due to the screening process: 19 patients (36%) elicited COVID-19 symptoms via telephone screening; 34 patients (64%) were symptomatic in our pre-assessment area and referred for swabs, of which 4 were positive. Those with a negative swab were rescheduled for chemotherapy the following week. CONCLUSIONS: With careful systematic changes, safe and continued delivery of systemic anti-cancer therapy during the COVID-19 pandemic is possible.

Chemotherapy in the Covid-19 era: the patient's perception.

BACKGROUND: The Covid-19 pandemic poses significant challenges for the management of patients with cancer. In our institution, we adapted our delivery of outpatient systemic anti-cancer therapy (SACT) by introducing a number of 'risk-reducing' measures including pre-assessment screening. AIMS: We sought to evaluate the experience and perceptions of patients with cancer undergoing SACT during the Covid-19 pandemic. METHODS: Patients on SACT during the Covid-19 pandemic were eligible for participation. Data were collected by anonymous survey over a 1 week period during the most intensive phase of government restrictions. Patients were asked questions under three headings: perceived risk of infection exposure, changes to treatment plan and psychological impact of Covid-19. RESULTS: One hundred patients were assessed, 60% were male, 41% were > 65 years of age and 67% had advanced cancer. Eleven percent of patients were living alone. Fifty-seven percent reported feeling at increased risk in general of contracting Covid-19. Sixty-eight percent of patients did not feel worried about contracting Covid-19 in the hospital. Ninety-two percent of patients reported wanting to continue on SACT as originally planned. Fifty-eighty percent felt isolated and 40% reported increased anxiety. CONCLUSION: Though patients on active treatment for cancer during the Covid-19 pandemic reported increased anxiety and feelings of isolation due to Covid-19, the majority of patients wanted to continue SACT as originally planned. Patients would benefit from enhanced psycho-oncological supports in the event of a prolonged Covid-19 pandemic.

Patient safety content and delivery in pre-registration nursing curricula: A national cross-sectional survey study.

BACKGROUND: Patient safety is a core principle of health professional practice and as such requires significant attention within undergraduate curricula. However, patient safety practice is complex requiring a broad range of skills and behaviours including the application of sound clinical knowledge within a range of health care contexts and cultures. There is very little research that explores how this is taught within Australian nursing curricula. OBJECTIVES: To examine how Australian nursing curricula address patient safety; identify where and how patient safety learning occurs; and describe who is responsible for facilitating this learning. DESIGN: A cross-sectional study. SETTING: Eighteen universities across seven Australian States and Territories. PARTICIPANTS: The sample consisted of 18 nursing course coordinators or those responsible for the inclusion of patient safety content within a Bachelor of Nursing course at Australian universities. METHODS: An online survey was conducted to evaluate the patient safety content included and teaching methods used in Australian pre-registration nursing curricula. RESULTS: Approaches to teaching patient safety vary considerably between universities where patient safety tended to be integrated within undergraduate nursing course subjects rather than explicitly taught in separate, stand-alone subjects. Three-quarters of the surveyed staff believed patient safety was currently being adequately covered in their undergraduate nursing curricula. CONCLUSION: Although there is consensus in relation to the importance of patient safety across universities, and similarity in views about what knowledge, skills and attitudes should be taught, there were differences in: the amount of time allocated, who was responsible for the teaching and learning, and in which setting the learning occurred and was assessed. There was little indication of the existence of a systematic approach to learning patient safety, with most participants reporting emphasis on learning applied to infection control and medication safety.

Sun protective behaviors at an outdoor entertainment event in Australia.

An observational study was conducted to examine the use of sun protective hats, clothing, and sunglasses of people attending an outdoor entertainment event in an area of high-to-extreme ultraviolet radiation in New South Wales, Australia. Armidale is unique, as it is a highly-elevated area, almost 1000 m above sea level, and temperatures are often mild with very high-to-extreme levels of ultraviolet radiation. Four trained data collectors observed attendees as they entered the event, and recorded their use of sun protective hats, clothing, and sunglasses. While more than half of the attendees wore sun protective hats, only 14% wore sun protective clothing. Broad-brimmed hats were considered sun protective, while sun protective clothing was defined by shirts with at least three-quarter-length sleeves. Females were more likely to wear both a sun protective hat and clothing than males, and children were less protected than adults. Legislative changes are required to ensure that organizers of outdoor events have a legal responsibility to provide a safe environment for attendees, including strategies to help reduce ultraviolet radiation exposure.

Therapeutic potential of N-acetylcysteine as an antiplatelet agent in patients with type-2 diabetes.

BACKGROUND: Platelet hyperaggregability is a pro-thrombotic feature of type-2 diabetes, associated with low levels of the antioxidant glutathione (GSH). Clinical delivery of N-acetylcysteine (NAC), a biosynthetic precursor of GSH, may help redress a GSH shortfall in platelets, thereby reducing thrombotic risk in type-2 diabetes patients. We investigated the effect of NAC in vitro, at concentrations attainable with tolerable oral dosing, on platelet GSH concentrations and aggregation propensity in blood from patients with type-2 diabetes. METHODS: Blood samples (n = 13) were incubated (2 h, 37°C) with NAC (10-100 micromolar) in vitro. Platelet aggregation in response to thrombin and ADP (whole blood aggregometry) was assessed, together with platelet GSH concentration (reduced and oxidized), antioxidant status, reactive oxygen species (ROS) generation, and plasma NOx (a surrogate measure of platelet-derived nitric oxide; NO). RESULTS: At therapeutically relevant concentrations (10-100 micromolar), NAC increased intraplatelet GSH levels, enhanced the antioxidant effects of platelets, and reduced ROS generation in blood from type-2 diabetes patients. Critically, NAC inhibited thrombin- and ADP-induced platelet aggregation in vitro. Plasma NOx was enhanced by 30 micromolar NAC. CONCLUSIONS: Our results suggest that NAC reduces thrombotic propensity in type-2 diabetes patients by increasing platelet antioxidant status as a result of elevated GSH synthesis, thereby lowering platelet-derived ROS. This may increase bioavailability of protective NO in a narrow therapeutic range. Therefore, NAC might represent an alternative or additional therapy to aspirin that could reduce thrombotic risk in type-2 diabetes.

2-arachidonyl glycerol activates platelets via conversion to arachidonic acid and not by direct activation of cannabinoid receptors.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: There are conflicting views in the literature as to whether cannabinoids have an impact on platelet activity and to what extent cannabinoid receptors are involved. This is an important issue to resolve because platelet effects of putative therapeutic cannabinoid inhibitors and stimulators will have an impact on their potential benefits and safety. WHAT THIS PAPER ADDS: The data presented in this manuscript clearly show that the endocannabinoid 2-arrachidonyl glycerol can activate platelet activity, but that the effects are mediated through an aspirin-sensitive pathway that is not affected by cannabinoid receptor antagonists or FAAH inhibition, but is abolished by MAGL inhibition. The findings question the role of cannabinoid receptors in platelet function and suggest that platelet function is unlikely to be directly affected by cannabinoid receptor antagonists, at least in the acute phase. AIMS: Cannabinoid receptor-1 (CB(1)) antagonists suppress appetite and induce weight loss. Direct antagonism of CB(1) receptors on platelets might be an additional benefit for CB(1) antagonists, but the role of CB(1) receptors in platelets is controversial. We tested the hypothesis that the endocannabinoid, 2-arachidonyl glycerol (2-AG), induces platelet aggregation by a COX-mediated mechanism rather than through CB(1) receptor activation, in blood obtained from healthy volunteers and patients with coronary artery disease receiving low dose aspirin. METHODS: Aggregatory responses to the cannabinoids 2-AG and Delta(9)-THC were examined in blood sampled from healthy volunteers (n= 8) and patients (n= 12) with coronary artery disease receiving aspirin using whole blood aggregometry. The effects of CB(1) (AM251) and CB(2) (AM630) antagonists, as well as fatty acid amide hydrolase (FAAH) and monoacyl glycerol lipase (MAGL) inhibitors and aspirin on 2-AG-induced aggregation were also assessed. RESULTS: AM251 (100 nm-30 microm) had no effect on platelet aggregation induced by either ADP (P= 0.90) or thrombin (P= 0.86). 2-AG, but not Delta(9)-THC, induced aggregation. 2-AG-induced aggregation was unaffected by AM251 and AM630 but was abolished by aspirin (P < 0.001) and by the MAGL inhibitor, URB602 (P < 0.001). Moreover, the aggregatory response to 2-AG was depressed (by >75%, P < 0.001) in blood from patients with coronary artery disease receiving aspirin compared with that from healthy volunteers. CONCLUSIONS: 2-AG-mediated activation of platelets is via metabolism to arachidonic acid by MAGL, and not through direct action on CB(1) or CB(2) receptors, at least in the acute phase.

Evaluation of the antioxidant properties of N-acetylcysteine in human platelets: prerequisite for bioconversion to glutathione for antioxidant and antiplatelet activity.

N-Acetylcysteine (NAC) is a frequently used "antioxidant" in vitro, but the concentrations applied rarely correlate with those encountered with oral dosing in vivo. Here, we investigated the in vitro antioxidant and antiplatelet properties of NAC at concentrations (10-100 microM) that are achievable in plasma with tolerable oral dosing. The impact of NAC pretreatment (2 hours) on aggregation of platelets from healthy volunteers in response to thrombin and adenosine diphosphate and on platelet-derived nitric oxide (NO) was examined. NAC was found to be a weak reducing agent and a poor antioxidant compared with glutathione (reduced form) (GSH). However, platelets treated with NAC showed enhanced antioxidant activity and depression of reactive oxygen species generation associated with increases in intraplatelet GSH levels. An approximately 2-fold increase in NO synthase-derived nitrite was observed with 10 microM NAC treatment, but the effect was not concentration dependent. Finally, NAC significantly reduced both thrombin-induced and adenosine diphosphate-induced platelet aggregation. NAC should be considered a weak antioxidant that requires prior conversion to GSH to convey antioxidant and antithrombotic benefit at therapeutically relevant concentrations. Our results suggest that NAC might be an effective antiplatelet agent in conditions where increased oxidative stress contributes to heightened risk of thrombosis but only if the intraplatelet machinery to convert it to GSH is functional.