Skeletal muscle mitochondrial correlates of critical power and W' in healthy active individuals.

The asymptote (critical power; CP) and curvature constant (W') of the hyperbolic power-duration relationship can predict performance within the severe-intensity exercise domain. However, the extent to which these parameters relate to skeletal muscle mitochondrial content and respiratory function is not known. Fifteen males (peak O2 uptake, 52.2 ± 8.7 mL kg-1 min-1; peak work rate, 366 ± 40 W; and gas exchange threshold, 162 ± 41 W) performed three to five constant-load tests to task failure for the determination of CP (246 ± 44 W) and W' (18.6 ± 4.1 kJ). Skeletal muscle biopsies were obtained from the vastus lateralis to determine citrate synthase (CS) activity, as a marker of mitochondrial content, and the ADP-stimulated respiration (P) and maximal electron transfer (E) through mitochondrial complexes (C) I-IV. The CP was positively correlated with CS activity (absolute CP, r = 0.881, P < 0.001; relative CP, r = 0.751, P = 0.001). The W' was not correlated with CS activity (P > 0.05). Relative CP was positively correlated with mass-corrected CI + IIE (r = 0.659, P = 0.038), with absolute CP being inversely correlated with CS activity-corrected CIVE (r = -0.701, P = 0.024). Relative W' was positively correlated with CS activity-corrected CI + IIP (r = 0.713, P = 0.021) and the phosphorylation control ratio (r = 0.661, P = 0.038). There were no further correlations between CP or W' and mitochondrial respiratory variables. These findings support the assertion that skeletal muscle mitochondrial oxidative capacity is positively associated with CP and that this relationship is strongly determined by mitochondrial content.

Adapting to change: exploring perceptions and demands of the coronavirus (COVID-19) workforce changes - an Australian multi-institutional radiation oncology survey.

ObjectiveTo evaluate the perceptions of the coronavirus disease 2019 (COVID-19) initiated workplace strategies implemented in radiation oncology departments across Australia.MethodsA multidisciplinary team from Princess Alexandra Hospital developed a survey to address the impact of the pandemic strategies on areas such as patient care, staff education, well-being, flexible working arrangements, and research. The survey was conducted from November 2020 to April 2021.ResultsOut of 210 respondents from seven institutions, 45% reported burnout and 57% experienced work work-related stress. A significant majority of respondents were in favour of continued remote work (86%, 131/153). Radiation oncologists identified administrative or non-clinical work (92%, 34/37), telehealth clinics (32%, 12/37), or radiation therapy planning (22%, 8/37) as suitable for remote work. Additionally, 54% (21/39) of the radiation oncologists plan to use telehealth more frequently, with 67% (26/39) feeling more confident with the technology. The majority (81%, 171/210) of participants favoured continuation of hybrid in-person and virtual meetings. Virtual solutions were adopted for quality assurance activities (72%, 118/165) and 52% (60/116) indicated preference for ongoing utility of virtual platforms. However, 38% (79/210) of the respondents expressed concerns about the negative impact on junior staff training.ConclusionThese findings reveal a strong inclination towards technological advancements and remote work arrangements to enable flexible working conditions. Our study suggests the need for ongoing reforms, focusing on improving clinical service delivery efficiencies and enhancing job satisfaction among clinicians.

Preference Signaling for the Diagnostic Radiology Match: A Single Institution Experience.

The Association of American Medical Colleges announced the addition of preference signaling to the 2022-2023 residency match cycle for Diagnostic and Interventional Radiology. This new offering provided applicants the option to indicate their specific interest in up to 6 residency programs during initial application submission. Our institutional diagnostic radiology residency program received a total of 1294 applications. One hundred and eight applicants signaled the program. Interview invitations were sent to 104 applicants, 23 of which signaled the program. Out of the top 10 ranked applicants, 6 applicants signaled the program. Out of the 5 matched applicants, 80% used the program signal, and 100% did the geographic preference. Opting to signal programs during the initial application submission may be beneficial for both the applicants and the programs in finding the optimal match.

A systematic review of multimodal prehabilitation in breast cancer.

PURPOSE: Breast cancer is the most prevalent malignancy in women. Prehabilitation may offer improvements in physical and psychological wellbeing among participants prior to treatment. This systematic review aimed to determine the efficacy of prehabilitation in participants diagnosed with breast cancer. METHODS: A systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Guidelines. Studies exploring the impact of prehabilitation in participants with breast cancer were included. Studies were assessed independently according to pre-eligibility criteria, with data extraction and methodological quality assessed in parallel. RESULTS: 3184 records were identified according to our search criteria, and 14 articles were included. Articles comprised of quantitative randomised controlled trials (n = 7), quantitative non-randomised studies (n = 5), a qualitative study (n = 1), and a mixed-method study (n = 1). The majority of selected studies completed exercise programs (n = 4) or had exercise components (n = 2), with two focusing on upper-limb exercise. Five articles reported complementary and alternative therapies (n = 5). Two articles reported smoking cessation (n = 2), with a single study reporting multi-modal prehabilitation (n = 1). Mostly, prehabilitation improved outcomes including physical function, quality of life, and psychosocial variables (P < 0.05). The qualitative data identified preferences for multimodal prehabilitation, compared to unimodal with  an interest in receiving support for longer. CONCLUSIONS: Prehabilitation for patients with breast cancer is an emerging research area that appears to improve outcomes, however, ensuring that adequate intervention timeframes, follow-up, and population groups should be considered for future investigations. IMPLICATIONS FOR CANCER SURVIVORS: The implementation of prehabilitation interventions for individuals diagnosed with breast cancer should be utilised by multidisciplinary teams to provide holistic care to patients as it has the potential to improve outcomes across the cancer care trajectory.

Are Standardized Video Interviews Useful for Selecting Integrated Interventional Radiology Residents?

The objective of this project is to evaluate the usefulness of the asynchronous or standardized video interview (SVI) for selecting integrated interventional radiology residents. All selected interviewees were asked to provide a brief recorded video answering 2 standardized questions. The applicants were interviewed in the virtual real-time format by 8 interviewers and ranked by group consensus. The SVIs were independently reviewed by a separate group of 4 interviewers and ranked by group consensus. These consensus ranks were compared to each other to determine similarities and differences in rank order. The results show that the SVIs are not statistically reliable as compared to the real-time interviews. There was a trend for an agreement for the lowest tiers in ranking; however, this was not statistically significant. The asynchronous interview is not equivalent to the virtual real-time interview and would not represent an equivalent replacement. However, the SVI may be useful for screening applicants to interview.

Platelet storage pool disorder: multidisciplinary planning in pregnancy.

A 32-year old primigravida woman presented for antenatal care giving a history that her mother had platelet storage pool disorder (PSPD). The patient was subsequently diagnosed with PSPD during her pregnancy and had a caesarean delivery for breech presentation at 39 weeks. In this paper, we discuss the basic science, inheritance pattern, symptoms and management of this condition, alongside the antenatal and intrapartum and postnatal management specific to it, highlighting the need for a multidisciplinary approach to care. PSPD refers to a group of rare conditions involving defects in platelet granule storage or secretion, which leads to abnormal aggregation and activation of platelets. There are both genetic and acquired forms of the condition. It is a functional platelet disorder, meaning platelet counts will usually remain in the normal range. The diagnosis may be suspected due to characteristic signs and symptoms, but patients may also be asymptomatic. There have been only a few documented cases of pregnant women with PSPD; therefore, management is not clear. Vaginal delivery is not contraindicated, however, postpartum haemorrhage should be anticipated and planned for the use of deamino D-arginine vasopressin (DDAVP), tranexamic acid, prophylactic oxytocics and prompt access to blood products, including platelets, if required. This case highlights the need for effective multidisciplinary teamwork between obstetricians, anaesthetists and haematologists to ensure high-quality care and enable careful intrapartum management planning.

A first pass, using pre-history and contemporary history, at understanding why Australia and England have such different policies towards electronic nicotine delivery systems, 1970s-c. 2018.

AIMS: The United Kingdom and Australia have developed highly divergent policy responses to electronic nicotine delivery systems (ENDS). To understand the historical origins of these differences, we describe the history of tobacco control in each country and the key roles played in setting ENDS policy in its early stages by public health regulations and policy networks, anti-smoking organizations, 'vaper' activist networks and advocates of harm reduction policies towards injecting drug use. METHODS: We analysed key government reports, policy statements from public health bodies and non-government organizations (e.g. cancer councils and medical organizations) on ENDS; submissions to an Australian parliamentary inquiry; media coverage of policy debates in medical journals; and the history of tobacco control policy in Australia and England. Key discourses about ENDS were identified for each country. These were compared across countries during a multi-day face-to-face meeting, where consensus was reached on the key commonalities and divergences in historical approaches to nicotine policy. This paper focuses on England, as different policy responses were apparent in constituent countries of the United Kingdom, and Scotland in particular. RESULTS: Policymakers in Australia and England differ markedly in the priority that they have given to using ENDS to promote smoking cessation or restricting smokers' access to prevent uptake among young people. In understanding the origins of these divergent responses, we identified the following key differences between the two countries' approaches to nicotine regulation: an influential scientific network that favoured nicotine harm reduction in the United Kingdom and the absence of such a network in Australia; the success of different types of health activism both in England and in Europe in opposing more restrictive policies; and the greater influence on policy in England of the field of illicit drug harm reduction. CONCLUSIONS: An understanding of the different policy responses to electronic nicotine delivery systems (ENDS) in England and Australia requires an appreciation of how actors within the different policy structures, scientific networks and activist organizations in each country and region have interpreted the evidence and the priority that policymakers have given to the competing goals of preventing adolescent uptake and encouraging smokers to use ENDS to quit smoking.

The use of therapeutic untruths by learning disability nursing students.

BACKGROUND: The use of therapeutic untruths raises a number of ethical issues, which have begun to be explored to some extent, particularly in dementia care services, where their use has been found to be high. Little is known, however, about their use by health professionals working in learning disability services. RESEARCH QUESTION: The study aimed to explore the frequency of use of therapeutic untruths by student learning disability nurses, and by their colleagues; how effective the students perceived them to be as a means of responding to behaviours that challenge; and their level of comfort with using them. RESEARCH DESIGN: A correlational design was used to gather data from an online version of the Best Interest Scale, adapted for a learning disability context. Participants were 30 learning disability student nurses (female = 28, ages 18-48 years, M = 26.8, standard deviation = 7.3) studying at a university in the North-East of England. ETHICAL CONSIDERATIONS: The study was reviewed and received ethical approval from the first author's university ethics committee. FINDINGS: Overall, 96% of participants reported using therapeutic untruths. 'Omission' was the most frequently used type of therapeutic untruths, the most effective and the type that the students felt most comfortable using. Frequency of use of therapeutic untruths correlated significantly and positively with perceived effectiveness and the level of comfort that the students felt when using them, for all types of therapeutic untruths. CONCLUSION: The use of therapeutic untruths by the student nurses was consistent with that found in research in dementia care services in the United Kingdom and abroad. Further research to explore the generalisability of the results to the wider context of learning disability services is needed. The study highlights that there may be a need for more formal guidance and educational input to student nurses in the use of therapeutic untruths with people with a learning disability.

Cardiovascular and neuropsychiatric safety of smoking cessation pharmacotherapies in non-depressed adults: a retrospective cohort study.

BACKGROUND AND AIMS: Pharmacotherapies for smoking cessation are widely prescribed, despite substantial concerns being raised regarding the potential increased risk of cardiovascular (CV) and neuropsychiatric adverse events associated with these treatments. This study aimed to assess the relative CV and neuropsychiatric safety between varenicline and bupropion compared with nicotine replacement therapies (NRT) in adults without a recent history of depression. DESIGN: Retrospective new-user cohort study. SETTING: US administrative data from 2006 to 2016 covering more than 100 million individuals. PARTICIPANTS: Three study cohorts of new users, aged 18 years or older, limited to patients with no diagnosis or treatment for depression in the prior 12 months. MEASUREMENTS: Propensity score adjusted log-binomial regression models. The primary outcome was a composite of hospitalized CV events. Secondary outcomes included a composite of hospitalized neuropsychiatric events and individual components of the primary outcome. FINDINGS: A total of 618 497 participants were included in our study cohorts. Compared with NRT (n = 32 237), varenicline (n = 454 698) was associated with a 20% lower 1-year CV risk [adjusted relative risk (RR) = 0.80, 95% confidence interval (CI) = 0.75-0.85], and bupropion (n = 131 562) was associated with a 25% lower 1-year CV risk (RR = 0.75, 95% CI = 0.69-0.81). Varenicline was associated with a 35% lower 1-year risk of neuropsychiatric hospitalization versus NRT (RR = 0.65, 95% CI = 0.59-0.72), and bupropion was associated with a 21% increase in 1-year risk of neuropsychiatric hospitalization (RR = 1.21, 95% CI = 1.09-1.35). CONCLUSION: Varenicline compared with nicotine replacement therapy does not appear to be associated with an increased risk of cardiovascular or neuropsychiatric hospitalizations. Bupropion appears to be associated with a lower risk of cardiovascular hospitalization and a higher risk of neuropsychiatric hospitalization, compared with nicotine replacement therapy.

Identifying sequential episodes of pharmacotherapy as a method for assessing treatment failure in comparative effectiveness research.

PURPOSE: To describe and implement a novel method of measuring comparative effectiveness using sequential episodes of pharmacotherapy as a proxy for treatment failure. METHODS: Retrospective cohort study using linked deidentified data from the British Columbia Ministry of Health during a government-sponsored smoking cessation reimbursement program.Three study cohorts were created based on first use of varenicline, bupropion, or nicotine replacement therapy (NRT), for adults aged 18 or older, in the period September 30th, 2011 to March 31st, 2013. The study cohorts were analyzed for sequential episodes of pharmacotherapy, defined as re-initiating a smoking cessation pharmacotherapy after an initial episode of treatment and washout period. The statistical analysis used propensity score adjusted log-binomial regression models with one-year and two-year fixed follow-up after a 12-week washout period. A sensitivity analysis excluded the washout period. A secondary analysis investigated predictors of receiving a sequential episode of smoking cessation pharmacotherapy RESULTS: 116,442 participants of the B.C. Smoking Cessation Program were analyzed. Compared to NRT, varenicline users were 13% less likely, and bupropion users were 18% less likely, to re-start smoking cessation therapy within 1-year after an initial course of treatment. CONCLUSIONS: Sequential episodes of pharmacotherapy identified treatment failures to smoking cessation therapy. Based on sequential episodes of pharmacotherapy during a drug benefit policy of smoking cessation medications, varenicline and bupropion were more effective aids to smoking cessation than NRT. The method was also used to identify patient characteristics associated with treatment effectiveness.

Beta-sarcoglycan-deficient muscular dystrophy presenting as chronic bronchopneumonia in a young cat.

CASE SUMMARY: A 5-month-old cat was evaluated for a 3 week history of cough, nasal discharge, decreased appetite and weight loss. Musculoskeletal examination was normal and serum creatine kinase (CK) activity was within the reference interval. The cat was treated during the next 10 months for chronic, persistent pneumonia. Weakness then became apparent, the cat developed dysphagia and was euthanized. Post-mortem evaluation revealed chronic aspiration pneumonia and muscular dystrophy associated with beta (ß)-sarcoglycan deficiency. RELEVANCE AND NOVEL INFORMATION: This is the first report of a cat with muscular dystrophy presenting for chronic pneumonia without obvious megaesophagus, dysphagia or prominent neuromuscular signs until late in the course of the disease. The absence of gait abnormalities, marked muscle atrophy or hypertrophy and normal serum CK activity delayed the diagnosis in this cat with ß-sarcoglycan deficiency.

Community-Dwelling Older Adults' Adherence to Environmental Fall Prevention Recommendations.

This study examined the impact of personalized versus generalized education about environmental fall prevention recommendations on older adults' adherence with recommendations. Secondary aims focused on the impact of recent falls and perceived susceptibility of future falls on adherence with recommendations. Twenty-four community-dwelling older adults aged 65 to 89 years were randomized into two groups to receive either personalized or generalized education intervention on environmental fall prevention recommendations. A significant difference was found in the mean total percentage of adherence with recommendations of those receiving personalized education (69%) compared with those receiving generalized education (37%). No statistically significant relationship was found between sustaining recent falls, nor perceived susceptibility to future falls, and their extent of adherence with environmental fall prevention recommendations. Providing personalized education for environmental fall prevention recommendations may improve older adults' adherence with the recommendations given.

Measuring Success: Goals and Outcomes for Educational Programs.

Measuring outcomes for educational programs can be challenging for many nursing professional development (NPD) practitioners. Alignment of goals with outcomes provides the foundation for the educator to justify, evaluate, and improve programs with more efficiency. This article highlights lessons learned by NPD practitioners after successful justification for continued support of educational programs. J Contin Nurs Educ. 2017;48(12):537-538.

Evidence-based policy? The re-medicalization of cannabis and the role of expert committees in the UK, 1972-1982.

BACKGROUND: Cannabis was introduced to the UK as a medical product in the nineteenth century. However, with questions over its safety, efficacy, and possible harms its medical role diminished and by the 1950s it was viewed as a drug of misuse. Nonetheless, scientific and lay knowledge around cannabis expanded from the 1960s and cannabis re-appeared in different therapeutic forms. In re-medicalizing cannabis, science-policy transfer proved important and was enabled by the developing mechanism of expert committees, most notably the Advisory Council on the Misuse of Drugs (ACMD). METHODS: This article draws upon previously unknown archival material on the ACMD held at the National Archives and covers the period 1972-1982. It considers how expert groups were established, their membership, and the evolving discussion over therapeutic cannabis within the broader drug policy debate. RESULTS: Three distinct periods emerged: 1972-1976 with the creation of the Working Group on Cannabis; 1977-1979 when the Working Group focused on potential amendments to the Misuse of Drugs Act and recommended downgrading cannabis from Class B to Class C; 1980-1982 when the Expert Group on the Effects of Cannabis recommended downgrading cannabis and encouraged research into cannabis as a medicine. Sources reveal that driven by drug control imperatives the ACMD stimulated research on cannabis leading to increased research on medical applications. CONCLUSION: Expert advice was critical in the process of re-medicalization. Initially, discourse occurred in the closed expert committees of the ACMD. The drug problem had been framed under the criminal justice system but as the limitations of this were revealed, and there was continuing uncertainty over cannabis' impact, new approaches to cannabis were sought. It was this combination of more relaxed attitudes towards cannabis, research incentives, as well as a developing desire to draw medical needs away from discussion of drug control that was to allow re-medicalization to develop.

Training and Assessing Interprofessional Virtual Teams Using a Web-Based Case System.

PURPOSE: Today, clinical care is often provided by interprofessional virtual teams-groups of practitioners who work asynchronously and use technology to communicate. Members of such teams must be competent in interprofessional practice and the use of information technology, two targets for health professions education reform. The authors created a Web-based case system to teach and assess these competencies in health professions students. METHOD: They created a four-module, six-week geriatric learning experience using a Web-based case system. Health professions students were divided into interprofessional virtual teams. Team members received profession-specific information, entered a summary of this information into the case system's electronic health record, answered knowledge questions about the case individually, then collaborated asynchronously to answer the same questions as a team. Individual and team knowledge scores and case activity measures--number of logins, message board posts/replies, views of message board posts--were tracked. RESULTS: During academic year 2012-2013, 80 teams composed of 522 students from medicine, nursing, pharmacy, and social work participated. Knowledge scores varied by profession and within professions. Team scores were higher than individual scores (P < .001). Students and teams with higher knowledge scores had higher case activity measures. Team score was most highly correlated with number of message board posts/replies and was not correlated with number of views of message board posts. CONCLUSIONS: This Web-based case system provided a novel approach to teach and assess the competencies needed for virtual teams. This approach may be a valuable new tool for measuring competency in interprofessional practice.

A randomized trial assessing the impact of a personal printed feedback portrait on statin prescribing in primary care.

INTRODUCTION: Knowledge translation (KT) initiatives have the potential to improve prescribing quality and produce savings that exceed the cost of the KT program itself, including the cost of evaluation using pragmatic study methods. Our objective was to measure the impact and estimated savings resulting from the distribution of individualized physician portraits of statin prescribing along with therapeutic recommendations in British Columbia, Canada. METHODS: A paired community design was used to study 2 725 family physicians in British Columbia. Communities were paired according to number of physicians and geographic location, with one community of each pair randomly assigned to an early (n = 1 349) or delayed (n = 1 376) intervention group. The intervention was a personalized prescribing portrait on statins that included therapeutic recommendations. The primary outcome was the impact on new prescribing (defined as statin naive) for primary prevention (defined as no diagnosis of cardiovascular disease) as recorded in the administrative claims databases of the BC Ministry of Health. RESULTS: Compared to the delayed control group, the relative probability of a new statin prescription for primary prevention decreased by 6% in the 12 months after the Education for Quality Improvement in Patient Care (EQIP) portrait compared to the preceding 12 months (relative risk [RR] 0.94; 95% confidence interval [CI] 0.91-0.98). There was also a non-statistically significant decrease in new prescribing for secondary prevention in patients diagnosed with cardiovascular disease (RR 0.96; 95% CI 0.91-1.01). We estimated that 572 fewer patients started statins for primary prevention in the first year after the portrait was mailed compared to patients in the delayed practices. We estimated the statin cost for those patients as $465,000 in the first two years, while the KT program to provide statin portraits cost less than $100,000. DISCUSSION: The individualized prescribing portrait had a significant beneficial effect on new statin prescribing for primary prevention but not secondary prevention. Provincial drug plan costs appear to have been reduced to a level that exceeded the cost of the program.

Guidelines for health technologies: specific guidance for oncology products in Canada.

OBJECTIVE: Specific methodological challenges are often encountered during cancer-related economic evaluations. The objective of this study was to provide specific guidance to analysts on the methods for the conduct of high-quality economic evaluations in oncology by building on the Canadian Agency for Drugs and Technologies in Health Guidelines for the Economic Evaluation of Health Technologies (third edition). METHODS: Fifteen oncologists, health economists, health services researchers, and decision makers from across Canada identified sections in Canadian Agency for Drugs and Technologies in Health guidelines that would benefit from oncology-specific guidance. Fifteen sections of the guidelines were reviewed to determine whether 1) Canadian Agency for Drugs and Technologies in Health guidelines were sufficient for the conduct of oncology economic evaluations without further guidance specific for oncology products or 2) additional guidance was necessary. A scoping review was conducted by using a comprehensive and replicable search to identify relevant literature to inform recommendations. Recommendations were reviewed by representatives of academia, government, and the pharmaceutical industry in an iterative and formal review of the recommendations. RESULTS: Major adaptations for guidance related to time horizon, effectiveness, modeling, costs, and resources were required. Recommendations around the use of final outcomes over intermediate outcomes to calculate quality-adjusted life-years and life-years gained, the type of evidence, the source of evidence, and the use of time horizon and modeling were made. CONCLUSIONS: This article summarizes key recommendations for the conduct of economic evaluations in oncology and describes methods required to ensure that economic assessments in oncology are conducted in a standardized manner.

Influence of relative age on diagnosis and treatment of attention-deficit/hyperactivity disorder in children.

BACKGROUND: The annual cut-off date of birth for entry to school in British Columbia, Canada, is Dec. 31. Thus, children born in December are typically the youngest in their grade. We sought to determine the influence of relative age within a grade on the diagnosis and pharmacologic treatment of attention-deficit/hyperactivity disorder (ADHD) in children. METHODS: We conducted a cohort study involving 937 943 children in British Columbia who were 6-12 years of age at any time between Dec. 1, 1997, and Nov. 30, 2008. We calculated the absolute and relative risk of receiving a diagnosis of ADHD and of receiving a prescription for a medication used to treat ADHD (i.e., methylphenidate, dextroamphetamine, mixed amphetamine salts or atomoxetine) for children born in December compared with children born in January. RESULTS: Boys who were born in December were 30% more likely (relative risk [RR] 1.30, 95% confidence interval [CI] 1.23-1.37) to receive a diagnosis of ADHD than boys born in January. Girls born in December were 70% more likely (RR 1.70, 95% CI 1.53-1.88) to receive a diagnosis of ADHD than girls born in January. Similarly, boys were 41% more likely (RR 1.41, 95% CI 1.33-1.50) and girls 77% more likely (RR 1.77, 95% CI 1.57-2.00) to be given a prescription for a medication to treat ADHD if they were born in December than if they were born in January. INTERPRETATION: The results of our analyses show a relative-age effect in the diagnosis and treatment of ADHD in children aged 6-12 years in British Columbia. These findings raise concerns about the potential harms of overdiagnosis and overprescribing. These harms include adverse effects on sleep, appetite and growth, in addition to increased risk of cardiovascular events.

Assessing the real-world cost-effectiveness of adjuvant trastuzumab in HER-2/neu positive breast cancer.

BACKGROUND: Among women with surgically removed, high-risk HER-2/neu-positive breast cancer, trastuzumab has demonstrated significant improvements in disease-free and overall survival. The objective of this study is to evaluate the cost-effectiveness of the currently recommended 12-month adjuvant protocol of trastuzumab using a Markov modeling approach and real-world cost data. METHODS: A 10-health-state Markov model tracked patients' quarterly transitions between health states in the local and advanced states of breast cancer. Clinical data were obtained from the joint analysis of the National Surgical Adjuvant Breast and Bowel Project and North Central Cancer Treatment Group, as well as from the metastatic study conducted by Norum et al. Clinical outcomes were adjusted for quality of life using utility estimates published in a systematic review. Real cost data were obtained from the British Columbia Cancer Agency and were evaluated from a payer perspective. Costs and utilities were discounted at 5% per year, respectively, for a 28-year time horizon. RESULTS: In the base case analysis, treatment with a 12-month adjuvant trastuzumab regimen resulted in a gain of 1.38 quality-adjusted life years or 1.17 life years gained at a cost of $18,133 per patient. Thus, the cost per QALY gained for the base case is $13,095. Cost per LYG is $15,492. CONCLUSIONS: Over the long term, treatment of HER-2/neu mutation positive breast cancer with a 12-month protocol of trastuzumab in the adjuvant setting is predicted to be cost-effective in a Canadian context.