An education on pharmacologically active complementary and alternative medicine and its effects on cancer treatment: literature review.

PURPOSE: This literature review examines the provision of an education on pharmacologically active complementary and alternative medicines (CAMs), to people with cancer, their carers and oncology health professionals. METHODS: A search of the published literature between 2000 and 2020, in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, was conducted. The search retrieved 1121 studies, 1080 were excluded based on their title or abstract and 26 articles were excluded based on their text. One article was retrieved from the reference lists of the included articles and in total fifteen studies met the inclusion criteria. This review utilised Medical Education Research Quality Instrument (MERSQI) to evaluate the quality of the included studies. Four key outcomes were utilised for analysis and recommendations for future education and/or research were generated. The recommendations were graded according to the Strength of Recommendation Taxonomy (SORT). RESULTS: This review consistently found that people with cancer, their carers and oncology health professionals derived benefit from a pharmacologically active CAM education and recommends that this population receives one. Conversely, the review found many education formats utilised and no consensus on the most successful methods. CONCLUSION: Future research should examine who a CAM education should be delivered to, what type of delivery platform is most accessible and useful, and the features of the education that most increase CAM knowledge. The popularity of CAMs amongst people with cancer and the potential dangers associated with their use necessitates further research into how best to communicate CAMs to this population.

Comparison of potential pharmacokinetic drug interactions in patients with atrial fibrillation and changing from warfarin to non-vitamin K oral anticoagulant therapy.

There are now anticoagulant choices with proposed advantages of non-vitamin K oral anticoagulants (NOACs) over warfarin being less routine monitoring and less drug interactions. Interacting medication can impact the efficacy and safety of anticoagulant therapy with management remaining clinically challenging. There have been limited studies comparing the potential for pharmacokinetic (PK) drug interactions between different anticoagulants. Therefore, the aim of this study was to compare potential PK interactions in patients with atrial fibrillation (AF) changing from warfarin to NOAC therapy. A retrospective analysis was conducted of patients with AF enrolled in a dedicated warfarin program but exiting this program to commence a NOAC. Patient data was collected, and concurrent medications were utilised to identify potential PK drug interactions with both warfarin and the chosen NOAC therapy. Patients were grouped according to the number of medications with potential PK interactions and comparisons made between groups. Of the 712 eligible patients who ceased warfarin to commence a NOAC, most commenced either apixaban (45.9%) or rivaroxaban (41.9%). When comparing warfarin to NOACs, there were significant differences in the proportion of patients taking no medication with potential PK drug interactions (46.9% vs 62.8%, p < 0.0001), and taking one (35.2% vs 28.5%, p = 0.0067) and two (14.5% vs 7.3%, p < 0.0001) potentially PK interacting medications. This study found when patients with AF were switched from warfarin to a NOAC, the potential for PK drug interactions significantly reduced but remained around 40%. Identifying and managing potential PK drug interactions with NOACs remains a priority to optimise clinical benefit of these anticoagulants.

Time to Stable Therapeutic Range on Initiation of Warfarin as an Indicator of Control.

OBJECTIVES: Warfarin remains widely used with a time in therapeutic range (TiTR) above 65% recommended for best outcomes. Patients not achieving or maintaining this warfarin control may be better suited to alternate anticoagulants. Despite this, there is limited data defining a suitable trial time in patients initiating warfarin therapy, therefore the aim of this study was to determine the mean time to stable therapeutic range (TtSTR). MATERIALS AND METHODS: Retrospective data was collected for patients with atrial fibrillation enrolled in a dedicated warfarin program at a private pathology practice within 7 days of warfarin initiation. TiTR at specified timepoints was calculated and median TtSTR determined as defined by TiTR ≥ 65% over three months. Comparisons were made of populations with TtSTR above or below the median. RESULTS: The 566 patients included in the study had a mean TiTR of 64.9±16.5% at month three and median TtSTR of six months. Patients with TtSTR≤6 months achieved a mean TiTR of 68.9±12.8% at month two and maintained a TiTR over 75% from month 3 to 24. Patients with a TtSTR>6 months obtained a TiTR of 66.4±10.6% at month nine and continued to achieve lower TiTR throughout the 24 months study period. CONCLUSIONS: A majority of patients can achieve a stable TiTR above 65% within six months so review at six to nine months is likely to be a good indicator of warfarin control and to determine if patients should continue warfarin or switch to alternate anticoagulant therapy.

The SAMe-TT2R2 score as an indicator of warfarin control for patients with deep vein thrombosis in Queensland, Australia.

Oral anticoagulation options for patients with venous thromboembolism (VTE) include vitamin K antagonists like warfarin. Good warfarin control is linked to outcomes of therapy, and the SAMe-TT2R2 model has been reported to predict control in atrial fibrillation patients with scores ≥ 2 linked to poor control. There has been limited and conflicting data in VTE populations, therefore this study aimed at determining the predictive ability of this model in Australian patients with deep vein thrombosis. Retrospective data of patients receiving warfarin care at a private pathology clinic in Queensland was collected. The time in therapeutic range (TTR) and SAMe-TT2R2 score was calculated for individual patients. Mean TTR and patients with TTR ≥ 65% were used for analysis and comparison across patients categorised as a score of 0-1 and ≥ 2. Of the 533 patients, the majority had a SAMe-TT2R2 score of 0-1. No significant difference was found in mean TTR between patients with a score of 0-1 and ≥ 2 but there was a significantly higher percentage of patients with a TTR ≥ 65% between groups (93.8% vs. 69.2%, p < 0.0001, respectively). The SAMe-TT2R2 score may assist in identifying patients with VTE likely to achieve good control (TTR ≥ 65%), but further investigation is required to determine the most suitable model for predicting warfarin control in this population.

Non-prescription medicines may contribute to non-adherence to prescription medicines in people living with chronic health conditions.

BACKGROUND: Non-adherence to prescribed medicines is linked to adverse health outcomes in people living with chronic health conditions (CHCs). Multiple factors are known to contribute to non-adherence to medicines including polypharmacy, demographic features and disease and health systems. Both non-prescription and prescription medicines contribute to polypharmacy; however, there is limited data on the influence of non-prescription medicines to non-adherence. AIM: Therefore, the aim of the study was to investigate the influence of non-prescription medicines to non-adherence in an Australian population. METHODS: Data from the 2016 National Survey of a random sample of Australian adult residents were utilised in this study to investigate factors associated with non-adherence. Descriptive statistics, χ2 , regression and generalised linear models were used to assess the relationships between variables of interest. Narrative response and comments were used to provide further insight. RESULTS: This study recruited 1217 participants to explore factors associated with non-adherence to medicines. Weak but statistically significant correlations were identified showing the number of CHCs, patient's age, number of prescription medicines, number of non-prescription medicines and total number of medicines associated with non-adherence. DISCUSSION: The findings suggest that people living with CHCs and taking multiple medicines, including non-prescription medicines, are likely to be non-adherent to prescription medicines. This study shows the possible involvement of non-prescription medicines in contributing to non-adherence in an Australian population and suggests that future studies with a broader demographic are warranted.

Anticoagulant Initiation During Hospital Admissions for Atrial Fibrillation in South-East Queensland, Australia.

BACKGROUND: Anticoagulation reduces stroke risk in patients with atrial fibrillation (AF) but under-prescribing in eligible patients has been commonly reported. Introduction of the direct acting oral anticoagulants (DOACs) was considered to potentially improve prescribing due to increased anticoagulant options. At the time of release to the Australian market, there were limited studies investigating anticoagulant usage during hospitalisations for AF. Therefore, the aim of this study was to investigate prescribing of oral anticoagulants during hospitalisation admissions for AF during the time of DOAC introduction to the Australian market. METHOD: A retrospective study was conducted of admissions to a tertiary Queensland hospital during 1 July 2012 to 10 June 2015. Patients were categorised according to oral anticoagulant therapy on both hospital admission and discharge. Changes to therapy and patient factors associated with prescribing were analysed. RESULTS: A total of 1,911 patients were included with 3,396 admissions during the study period. There was a significant increase in the number of patients initiated on anticoagulant therapy during their first admission with higher rates of initiation of DOACs compared to warfarin. Ischaemic heart disease and high bleed risk were significantly associated with reduced prescribing of anticoagulant therapy on first and second admission respectively, while patients with a history of stroke or transient ischaemic attack were significantly more likely to receive therapy. CONCLUSION: The introduction of the DOACs to the Australian market increased initiation of anticoagulants to hospitalised patients with AF across all stroke risk categories. The availability of greater anticoagulant options has increased initiation of therapy but there remains potential to further optimise anticoagulant prescribing by targeting therapy according to guidelines and patient factors.

Proton pump inhibitors co-prescribed with warfarin reduce warfarin control as measured by time in therapeutic range.

INTRODUCTION: Warfarin is an oral anticoagulant that requires ongoing monitoring with time in therapeutic range (TTR), a common measure of the quality of warfarin control and likelihood of adverse events including bleeds. Numerous factors can influence these warfarin outcomes including drug interactions. Proton pump inhibitors (PPIs) have been reported to interact with warfarin but there remain conflicting reports with regard to the impact on bleeds and limited data on TTR. Therefore, the aim of this study was to determine the effect of PPIs on warfarin control using TTR and bleeds as endpoints. METHODS: Retrospective data were collected for patients managed by a warfarin management clinic in Queensland. Data collected included current medications, reported bleeds and INR results to calculate TTR. Patients were grouped as taking PPIs or not taking PPIs. Analysis of TTR and bleeds occurred for these groups both before and after exclusions of other medication reported to interact with warfarin. RESULTS: Of the 4494 included patients, almost half (44.5%) were taking PPIs with esomeprazole most commonly (34.8%) prescribed. Patients taking PPIs had significantly reduced TTR compared with patients not taking PPIs both before (78.5 ± 9.7% vs 81.7 ± 10.2%, P < 0.0001) and after (84.4 ± 5.1% vs 89.4 ± 8.0%, P < 0.0001) excluding all other interacting medications with warfarin. Patients taking PPIs also had significantly higher incidence of minor bleeds compared with patients not taking PPIs (32.4% vs 26.1%, P = 0.0487). DISCUSSION: Patients taking PPIs with warfarin had significantly lower TTRs and higher incidence of minor bleeds. This combination warrants additional caution and monitoring with warfarin control as measured by TTR potentially affected.

Warfarin control in patients transitioning to warfarin after non-vitamin K oral anticoagulant (NOAC) therapy.

Warfarin has long been the most widely prescribed oral anticoagulant. Introduction of non-vitamin K oral anticoagulants (NOACs) has provided anticoagulant options but also presented the potential challenge of transitioning between agents. Changes from NOACs to warfarin are particularly problematic with delays to therapeutic effect and limited real-world data regarding the impact on warfarin control. The aim of this study was to investigate the frequency of switching anticoagulants and the effect on warfarin control. Retrospective data was collected for patients at a warfarin program in Queensland Australia who had exited the program for NOACs plus those who had reverted to warfarin. Data included documented reasons for change and International Normalised Ratio (INR) results with time in therapeutic range (TTR) calculated as a measure of warfarin control. Over 5 years, a total of 3036 patients ceased warfarin to commence a NOAC but 142 (4.7%) reverted to warfarin. Majority of patients (60.6%) reverted to warfarin within 6 months of trialling NOACs with a median of 6 days to therapeutic INR. There was no significant difference in warfarin control before changing to NOACs and after reverting to warfarin (mean TTR 75%) but significantly more frequent testing and lower doses were required to achieve this control. Transitions from warfarin to NOACs results in almost a week to therapeutic effect and warfarin therapy may be further complicated by a need for increased frequency of testing. Further studies are required to refine transition strategies particularly from warfarin to NOAC and minimise potential risks to patients.

Dedicated warfarin care programme results in superior warfarin control in Queensland, Australia.

BACKGROUND: Warfarin is used to prevent stroke in patients with atrial fibrillation (AF). Ongoing monitoring of International normalised ratio (INR) and time in therapeutic range (TTR) commonly used to assess the quality of warfarin management are required. Anticoagulant clinics have demonstrated improved TTRs, particularly in countries with poorer control in primary care settings. Reported TTR in Australia has been relatively high; so, it is unknown if benefit would be seen from dedicated warfarin clinics in Australia. The aim of this study was to compare the level of warfarin control in patients managed by their general practitioner (GP) and a warfarin care programme (WCP) by Sullivan Nicolaides Pathology. METHOD: Retrospective data were collected for AF patients enrolled in the warfarin care programme at WCP, and included patients with INR tests available while managed by their GP. INR tests were used to calculate TTR and frequency of testing for the time managed by GP and WCP, with mean data used for analysis and comparison. RESULTS: The eligible 200 warfarin patients had a TTR of 69% with GP management and 82% with WCP management (<.0001). Significant differences were also found between GP and WCP management in the percentage of tests in range, total number of tests and frequency of testing. WCP had a reduced time to repeat test at extremes of INR results. CONCLUSION: Australian warfarin control was good when managed by either GP or WCP, but WCP management increased TTR by 13%. Dedicated warfarin programmes can improve warfarin control and optimise therapy for patients.

Identifying Warfarin Control With Stroke and Bleed Risk Scores.

Warfarin decreases stroke risk in atrial fibrillation patients, with efficacy and safety impacted by the quality of warfarin control, as measured by time in therapeutic range (TTR). Stroke and bleed risk scores are calculated prior to commencing warfarin, so it would be beneficial if these scores also identified likely warfarin control. Some studies have investigated CHADS2, CHA2DS2VASc, and HASBLED individually for this purpose, but application of all scores to diverse ethnic populations and at sites with differing overall control has not been investigated. The aim of this study was to determine if these commonly used risk scores could identify poor warfarin control. Retrospective data was collected for non-valvular AF patients receiving warfarin between January and June 2014 in Australia and Singapore. Patient data was used to calculate TTR and risk scores. Mean TTR was used for analysis and comparison to categorised scores. There were 3199 patients in Australia and 1171 in Singapore. At both sites, mean TTR decreased according to HASBLED category, and there was a statistically higher percentage of patients achieving a TTR>65% in the low HASBLED category. The association between HASBLED scores and TTR was independent of lower dosing in higher risk patients, particularly in Australia. No significant differences were found in mean TTR according to CHADS2 at either site. Time in therapeutic range significantly decreased according to high CHA2DS2VASc category in Singapore, but no differences were found in Australia. Of the bleed and stroke risk models, HASBLED is most suitable to identify a patient's potential TTR and ability to achieve TTR>65%. A high HASBLED score may assist prescribers in determining potential suitability to warfarin, and assist prescribers in deciding on the most suitable anticoagulant for patients.

The Sex, Age, Medical History, Treatment, Tobacco Use, Race Risk (SAMe TT2R2) Score Predicts Warfarin Control in a Singaporean Population.

BACKGROUND: Warfarin reduces stroke risk in atrial fibrillation (AF) patients but requires ongoing monitoring. Time in therapeutic range (TTR) is used as a measure of warfarin control, with a TTR less than 60% associated with adverse patient outcomes. The Sex, Age, Medical history, Treatment, Tobacco use, Race (SAMe-TT2R2) score has been identified as a model able to predict warfarin control, but this has been tested in mainly Caucasian populations. Therefore, the aim of this study was to determine the ability of the SAMe-TT2R2 score to predict warfarin control in a Singaporean population consisting of Chinese, Malay, and Indian race. METHODS: Retrospective data were collected from the National Heart Centre Singapore for AF patients receiving warfarin between January and June 2014. The TTR and the SAMe-TT2R2 score were calculated for each patient. RESULTS: The 1137 non-valvular AF patients had a mean TTR of 58.0 ± 34.3% and a median SAMe-TT2R2 score of 3. The categorized SAMe-TT2R2 scores (2 versus >2) showed a significant reduction in mean TTR for the entire population (63.2% versus 55.8%, P = .0004) and also when categorized according to race for Chinese (62.7% versus 56.9%, P = .0075) and Malay (68.4% versus 50.6%, P = .0131) populations. CONCLUSION: The SAMe-TT2R2 tool is effective in predicting warfarin control in a Singaporean population as patients with a score greater than 2 had poor control. The minimum score for non-Caucasian patients is 2; thus, in these patients, the presence of any additional risk factors identified in the SAMe-TT2R2 tool categorizes them as unlikely to achieve adequate warfarin control and possible candidates for alternative anticoagulants.

Interstate dispensing: a case for uniform, intuitive legislation.

Australian health practitioner registration is national, whereas legislation regarding the handling of medicines is governed by individual States and Territories. To align with the July 2010 national registration scheme some legislative modifications were made concerning scheduled drugs and poisons, but many differences between jurisdictions remain. In Queensland, the Health (Drugs and Poisons) Regulation 1996 (Qld) allows for dispensing of controlled drugs written by interstate prescribers but not lower scheduled specified restricted and regulated restricted drugs. The aim of this study was to assess awareness of seemingly counterintuitive legislation by pharmacists practising in South-East Queensland. Of 125 Gold Coast pharmacies contacted, 54 (43.2%) agreed to participate. The majority of pharmacists (88.9%) had good knowledge regarding controlled drugs. In contrast, they demonstrated confusion regarding specified restricted and regulated restricted drugs (51.9% correct awareness). Uniform legislation between jurisdictions or more intuitive legislation would ease practitioner confusion.

Provision of externally accredited immunisation certification within an Australian Professional Pharmacy University programme: a survey of graduates on benefits and outcomes.

OBJECTIVES: In Australia, pharmacists may become authorised immunisers by obtaining additional credentialling from certified providers. Some Australian Universities are providing externally accredited immunisation training to final year pharmacy students. Student satisfaction has been demonstrated, but graduate views on benefits and outcomes are yet to be determined. The aim of this study was to evaluate graduates' perceptions of providing an accredited immunisation certification during their University pharmacy programme. METHODS: A survey was sent to Griffith University pharmacy graduates of 2016-2020 inclusive. Respondents who completed the accredited immunisation training at University were asked to rank their agreement with five statements on a five-point Likert scale (1 = Strongly Disagree, 5 = Strongly Agree). Further information, including free-text responses, was collected on current area of practice and involvement in vaccinations. KEY FINDINGS: Of the 46 graduates who completed the survey, 42 (91.3%) completed the accredited immunisation training at University. Statements that the accredited immunisation training was considered a valuable additional offering to the pharmacy programme and the time commitment was worthwhile resulted in a mean agreement of 4.74 ± 0.73 and 4.64 ± 0.76, respectively. The majority of respondents (n = 27, 58.7%) were providing immunisations on a daily, weekly or monthly basis with over half reporting becoming more actively involved in immunisation due to COVID-19. CONCLUSIONS: Pharmacy graduates valued completing an externally accredited immunisation training within their University programme and reported benefits to their employability and current roles. Incorporating externally accredited training into the curriculum can ensure graduates are prepared and skilled in continually expanding roles for pharmacists.

Drivers of Radioresistance in Prostate Cancer.

Prostate cancer (PCa) is the second most commonly diagnosed cancer worldwide. Radiotherapy remains one of the first-line treatments in localised disease and may be used as monotherapy or in combination with other treatments such as androgen deprivation therapy or radical prostatectomy. Despite advancements in delivery methods and techniques, radiotherapy has been unable to totally overcome radioresistance resulting in treatment failure or recurrence of previously treated PCa. Various factors have been linked to the development of tumour radioresistance including abnormal tumour vasculature, oxygen depletion, glucose and energy deprivation, changes in gene expression and proteome alterations. Understanding the biological mechanisms behind radioresistance is essential in the development of therapies that are able to produce both initial and sustained response to radiotherapy. This review will investigate the different biological mechanisms utilised by PCa tumours to drive radioresistance.

Quinazoline alpha-adrenoreceptor blockers as an adjunct cancer treatment: From bench to bedside.

Drug repurposing has been increasingly used by both researchers and clinicians to identify new cancer treatments. The alpha-1 adrenoreceptor blockers are a class of drugs that have been used for many years in the treatment of hypertension and benign prostatic hyperplasia. Some of the drugs in this class, notably the quinazoline derivatives, have been found to display cytotoxic properties, identifying them as potential options in the treatment of cancer. This review will examine the currently available evidence that investigates the cytotoxic and anti-cancer properties of these agents, the mechanisms behind these properties and how the alpha-1 blockers fit within current cancer therapies. It aims to answer the question of whether these agents can go from the laboratory bench top into cancer clinics.

A clinical audit of oral anticoagulant therapy in aged care residents with atrial fibrillation.

Background Atrial fibrillation (AF) is a risk factor for stroke in older people. Oral anticoagulants can reduce stroke risk but they are commonly under prescribed in the elderly, often due to concerns regarding the risk of bleeding. Prescribing in aged care residents may also be further complicated by associated geriatric conditions such as dementia and risk of falls. Systematic assessment of stroke and bleed risk can help identify people with AF expected to benefit from anticoagulant therapy and optimise prescribing. Objective The aim of this study was to assess the prescribing of anticoagulants in elderly aged care residents in accordance with Australian guideline recommendations. Setting Nineteen aged care facilities across southeast Queensland. Method A clinical audit of anticoagulant therapy in aged care residents was conducted. Main outcome measure Information was collected from the records of residents with non-valvular AF to assess the risk of stroke and bleeding and compare this prescribing to current evidence-based guidelines for anticoagulation in AF. Results A total of 1754 residents were screened with 359 (20.4%) identified to have a diagnosis of non-valvular AF. There were 356 (99.2%) residents with non-valvular AF and a sufficiently high risk of stroke to warrant the use of an anticoagulant. Of these, 172 (48.3%) were prescribed an oral anticoagulant and 40 (11.2%) residents had a documented decision not to prescribe oral anticoagulants in their records. The majority of residents prescribed anticoagulation were receiving non-vitamin K antagonists (76.8%). The prescribed dose was consistent with recommendations for 44.8% of residents prescribed oral anticoagulant therapy. Conclusion Many residents with non-valvular AF and significant risk of stroke were not receiving oral anticoagulation despite a lack of documented reason for non-prescribing. Non-vitamin K antagonists were widely prescribed but dosing of these agents could still be improved. There remains a need to improve anticoagulant prescribing for aged care residents and optimise stroke prevention in this population.

Treatment Expectations, Convenience, and Satisfaction with Anticoagulant Treatment: Perceptions of Patients in South-East Queensland, Australia.

BACKGROUND: Warfarin has long been the only oral anticoagulant (OAC) available, but options now include non-vitamin K antagonists. Prescribing an OAC may be influenced by patient factors and preferences influenced by dosing, monitoring, and adverse effects, which may ultimately impact patient satisfaction and convenience. The aim of this study was to explore the perception of OAC treatment by Australian patients in terms of treatment expectations, convenience, and satisfaction. METHODS: The Perception of Anticoagulant Treatment Questionnaire was distributed to patients dispensed OAC medication from three pharmacies in South-East Queensland. Responses to questions using a five-point Likert scale were collated and mean results utilised to assess expectations, convenience, and satisfaction, including an analysis across demographic groups. RESULTS: A total of 56 (26.8%) surveys were returned, with the majority of respondent's male (58.2%). Highest mean scores for treatment expectation were for an OAC that was easy to take (4.85 ± 0.79) and that could be taken care of by the respondents themselves (4.11 ± 1.14). The mean overall score for convenience was 68.90 ± 11.44% and for satisfaction 69.43 ± 16.58%. Significantly higher mean convenience scores were found in females and patients with atrial fibrillation. CONCLUSIONS: Patients' highest expectations were for an OAC that would be easy to take, and overall satisfaction and convenience was around 69%. Factors including demographics can influence perceptions of therapy, and addressing individual preferences for OAC therapy may increase ratings of satisfaction and convenience.

Evaluation of adult stroke presentations at an Emergency Department in Queensland Australia.

BACKGROUND: Stroke is a leading cause of mortality and morbidity which places high demands on emergency departments (EDs). Currently there is limited data on stroke presentations to Australian EDs and the time performance management of these presentations. Therefore, the aim of this study was to evaluate stroke presentations at an ED in Queensland, Australia in terms of demographics and time performance measures over a five year period. METHODS: Retrospective analysis of ED presentations by patients ≥18 years with a final diagnosis of stroke between 1 July 2010 and 30 June 2015. RESULTS: Over the five years there was a 51.4% increase in presentations diagnosed with stroke. The majority of these patients arrived by ambulance (71.0%) and were admitted (94.9%) with death in ED for 1.4% of presentations. From 2010 to 2015 for both haemorrhagic and ischaemic stroke there was a significant decrease in median LOS in ED (435 to 215 min, p < 0.05 and 451 to 238 min, p < 0.001 respectively) and in the proportion of patients in ED greater than four hours (82.4% to 44%, p < 0.05 and 92.4% to 45.8%,p < 0.0001 respectively). CONCLUSION: Despite increased presentations of stroke, the ED improved in multiple time performance measures. Improving time-based targets in ED is particularly important for stroke presentations given the time critical nature of stroke management.

Comparison of oral vs. combined topical/intravenous/oral tranexamic acid in the prevention of blood loss in total knee arthroplasty: A randomised clinical trial.

BACKGROUND: Tranexamic acid (TXA) has long been used to reduce blood loss associated with total knee arthroplasty (TKA). Debate remains over the best administration route with limited data comparing regimes including, to date, no studies investigating the equivalence of oral TXA and a combined topical/intravenous (IV) regime. Therefore, the aim of this study was to compare the efficacy and safety of oral TXA to combined topical/IV/oral TXA. WORKING HYPOTHESIS: We postulated that oral TXA would offer the same efficacy and safety as combined topical/IV/oral regime. We asked: (1) Would blood loss and haemoglobin change be affected? (2) Would complication rates increase? PATIENTS AND METHODS: Patients were randomised into either the study group (oral TXA regimen) or the control group (combined topical/IV/oral TXA). Both groups were administered three doses of TXA and received the same post-operative venous thromboembolism prophylaxis. Efficacy outcomes including blood loss and haemoglobin (Hb) change were investigated, together with safety outcomes of incidence of deep vein thrombosis and adverse events. RESULTS: The study (n=25) and control (n=28) group were comparable at baseline (eg pre-op haemoglobin). No significant difference was found between the study and control group in terms of Hb change (32.9±8.9 vs. 31.8±10.4, p=0.687) or blood loss (measured 640.0±291.1 vs. 538.3±270.2, p=0.173 and total 1211.5±336.0 vs. 1092.9±341.4, p=0.214). No cases of DVT were reported for either group and no statistical differences were found in the incidence of adverse events (nausea, hypotension, constipation) between groups. DISCUSSION: This study has shown for the first time that an oral TXA regimen is non-inferior to a topical/IV/oral regimen in TKA in efficacy and safety. Utilising oral TXA in place of a combined topical/IV/oral regime can significantly reduce costs without compromising patient outcomes. LEVEL OF EVIDENCE: II, Randomised controlled trial.

The SAMe-TT2R2 Score Predicts Warfarin Control in an Australian Population with Atrial Fibrillation.

BACKGROUND: Warfarin requires regular monitoring with the time in therapeutic range (TTR), a common indicator of control and TTR > 70% is indicative of efficient anticoagulation. The SAMe-TT2R2 (sex, age, medical history, treatment, tobacco use, race) model has been utilised as a predictor of warfarin control, with a score ≥ 2 indicative of poor control. However, it has been suggested that race may be over-represented in this model. To date, no Australian studies have applied this model, possibly because race is not routinely recorded. Therefore, the aim of this study was to apply the SAMe-TT2R2 model in an Australian population on warfarin managed by both a warfarin care program (WCP) and general practitioner (GP). METHODS: Retrospective data was collected for patients receiving warfarin via a WCP in Queensland and whilst being managed by a GP. Patient data was used to calculate the SAMe-TT2R2 score and the TTR for each patient. Mean TTR was used for analysis and comparison with the categorised SAMe-TT2R2 score. RESULTS: Of the 3911 patients managed by a WCP, there was a significantly lower mean TTR for patients with a SAMe-TT2R2 score ≥ 2 compared to 0-1 (78.6 ± 10.7% vs. 80.9 ± 9.5%, p < 0.0001). Of these patients, 200 were analysed whilst managed by a GP and the categorised SAMe-TT2R2 score did not result in a statistically different mean TTR (69.3 ± 16.3% with 0-1 vs. 63.6 ± 15.0% with ≥2, p = 0.089), but a score ≥2 differentiated patients with a TTR less than 65%. CONCLUSIONS: The SAMe-TT2R2 model differentiated Australian patients with reduced warfarin control, despite the exclusion of race. In Australia, the SAMe-TT2R2 score could assist clinicians in identifying Australian patients who may obtain reduced warfarin control and benefit from additional interventions such as a dedicated WCP.