Clinical Pharmacy Services in Ambulatory Oncology: An Environmental Scan of the Canadian Practice Landscape.

Background: Canadian clinical pharmacy key performance indicators (cpKPIs) have been developed for inpatient hospital practice but are not established for ambulatory oncology. This study represents the first step in developing cpKPIs for ambulatory oncology. Objectives: To describe the current landscape of pharmacy services in ambulatory oncology in Canada and to identify perspectives related to the development and implementation of cpKPIs in this practice setting. Methods: In this national cross-sectional study, a web-based questionnaire was distributed to pharmacists working in ambulatory oncology settings. Potential participants who self-identified as pharmacists practising in an ambulatory oncology setting were eligible. Survey questions focused on participants' demographic characteristics, oncology pharmacy services provided, metrics captured, and pharmacists' perceptions of cpKPIs. All data were analyzed using descriptive statistics. Results: A total of 44 responses were received, with most respondents practising in community hospitals in British Columbia, Ontario, and Atlantic Canada. The services most commonly provided were chemotherapy order verification, laboratory monitoring, identification and resolution of drug therapy problems, and counselling on anticancer medications. Twenty-six of the 44 respondents (59%) indicated that performance metrics or patient outcomes were tracked at their respective institutions, with none being universally captured. Overall, 43 (98%) of the respondents favoured the development of cpKPIs for ambulatory oncology practice. Conclusions: Despite growing patient care needs in ambulatory oncology, there is significant heterogeneity in the scope of pharmacy services offered and the outcomes used to qualify their impact within this setting across Canada. This study demonstrates a clear need for national consensus cpKPIs to inform pharmacy resource utilization and patient-centred quality improvement initiatives.

Contexte: Des indicateurs clés de performance de la pharmacie clinique canadienne (cpKPI) ont été élaborés pour la pratique hospitalière en milieu hospitalier, mais n'ont pas été définis pour l'oncologie ambulatoire. Cette étude constitue la première étape de l'élaboration de cpKPI pour l'oncologie ambulatoire. Objectifs: Décrire le paysage actuel des services pharmaceutiques en oncologie ambulatoire au Canada et cerner les perspectives liées au développement et à la réalisation de cpKPI dans ce contexte de pratique. Méthodes: Dans cette étude transversale nationale, un questionnaire en ligne a été distribué aux pharmaciens qui travaillent en oncologie ambulatoire. Les participants potentiels qui se sont identifiés comme des pharmaciens exerçant dans ce contexte étaient autorisés à participer. Les questions de l'étude portaient sur les caractéristiques démographiques des participants, les services de pharmacie offerts en oncologie, les paramètres saisis et les perceptions des pharmaciens à l'égard des cpKPI. Toutes les données ont été analysées à l'aide de statistiques descriptives. Résultats: Au total, 44 réponses ont été reçues, la plupart des répondants exerçant dans des hôpitaux communautaires de la Colombie-Britannique, de l'Ontario et du Canada atlantique. Les services les plus couramment fournis étaient : la vérification des ordonnances de chimiothérapie, la surveillance en laboratoire, l'identification et la résolution des problèmes de pharmacothérapie et les conseils portant sur les médicaments anticancéreux. Vingt-six des 44 répondants (59 %) ont indiqué que les indicateurs de performance ou les résultats pour les patients faisaient l'objet d'un suivi dans leurs établissements respectifs, bien qu'aucun ne soit universellement saisi. Dans l'ensemble, 43 répondants (98 %) étaient favorables à l'élaboration de cpKPI pour la pratique de l'oncologie ambulatoire. Conclusions: Malgré les besoins croissants des patients en oncologie ambulatoire, la portée des services pharmaceutiques offerts et les résultats utilisés pour qualifier leur effet dans ce contexte au Canada sont fortement hétérogènes. Cette étude démontre un besoin évident de consensus portant sur les cpKPI à l'échelle nationale pour éclairer l'utilisation des ressources pharmaceutiques et les initiatives d'amélioration de la qualité centrées sur le patient.

Bone Microarchitecture in Transgender Adults: A Cross-Sectional Study.

Gender-affirming hormone therapy aligns physical characteristics with an individual's gender identity, but sex hormones regulate bone remodeling and influence bone morphology. We hypothesized that trans men receiving testosterone have compromised bone morphology because of suppression of ovarian estradiol production, whereas trans women receiving estradiol, with or without anti-androgen therapy, have preserved bone microarchitecture. We compared distal radial and tibial microarchitecture using high-resolution peripheral quantitative computed tomography images in a cross-sectional study of 41 trans men with 71 cis female controls, and 40 trans women with 51 cis male controls. Between-group differences were expressed as standardized deviations (SD) from the mean in age-matched cisgender controls with 98% confidence intervals adjusted for cross-sectional area (CSA) and multiple comparisons. Relative to cis women, trans men had 0.63 SD higher total volumetric bone mineral density (vBMD; both p = 0.01). Cortical vBMD and cortical porosity did not differ, but cortices were 1.11 SD thicker (p < 0.01). Trabeculae were 0.38 SD thicker (p = 0.05) but otherwise no different. Compared with cis men, trans women had 0.68 SD lower total vBMD (p = 0.01). Cortical vBMD was 0.70 SD lower (p < 0.01), cortical thickness was 0.51 SD lower (p = 0.04), and cortical porosity was 0.70 SD higher (p < 0.01). Trabecular bone volume (BV/TV) was 0.77 SD lower (p < 0.01), with 0.57 SD fewer (p < 0.01) and 0.30 SD thicker trabeculae (p = 0.02). There was 0.56 SD greater trabecular separation (p = 0.01). Findings at the distal radius were similar. Contrary to each hypothesis, bone microarchitecture was not compromised in trans men, perhaps because aromatization of administered testosterone prevented bone loss. Trans women had deteriorated bone microarchitecture either because of deficits in microstructure before treatment or because the estradiol dosage was insufficient to offset reduced aromatizable testosterone. Prospective studies are needed to confirm these findings. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Impact of coronavirus of 2019 on the delivery of pharmacy services to patients with cancer: An international survey of oncology pharmacy practitioners.

INTRODUCTION: The coronavirus of 2019 pandemic has necessitated vast and rapid changes in the way oncology pharmacy services are delivered around the world. METHODS/AIMS: An international survey of oncology pharmacists and technicians was conducted via the International Society of Oncology Pharmacy Practitioners and collaborating global pharmacy organisations to determine the impact that the coronavirus of 2019 has had on pharmacy service delivery, pharmacy practitioners and oncology practice. RESULTS: The survey received 862 responses from 40 different countries from September to October 2020. The majority of respondents were pharmacists (n = 841, 97.6%), with 24% involved in the direct care of patients with the coronavirus of 2019. Of the survey participants, 55% increased their time working remotely, with remote activities including dispensing, patient assessment/follow-up and attending multi-disciplinary rounds. Respondents reported a 72% increase in the use of technology to perform remote patient interaction activities and that participation in educational meetings and quality improvement projects was reduced by 68% and 44%, respectively. Workforce impacts included altered working hours (50%), cancelled leave (48%) and forced leave/furloughing (30%). During the pandemic, respondents reported reduced access to intensive care (19%) and anti-cancer (15%) medications. In addition, 39% of respondents reported reduced access to personal protective equipment, including N95 masks for chemotherapy compounding. Almost half of respondents (49%) reported that cancer treatments were delayed or intervals were altered for patients being treated with curative intent. A third of practitioners (30%) believed that patient outcomes would be adversely impacted by changes to pharmacy services. Sixty-five percent of respondents reported impacts on their mental health, with 12% utilising support services. CONCLUSION: The coronavirus of 2019 pandemic has altered the way oncology pharmacy services are delivered. These results demonstrate the adaptability of the oncology pharmacy profession and highlight the importance of formal evaluation of the varied practice models to determine the evidence-based practices that enhance pharmacy services and, thus, should be reinstated as soon as practical and reasonable.

A randomized controlled trial to assess the influence of a picture-based antiemetic medication calendar on medication-taking behavior in adults receiving chemotherapy.

OBJECTIVE: A prospective open-label randomized controlled trial to assess the role of a picture-based medication calendar on adherence to antiemetic regimens for adult patients receiving chemotherapy and assess the effect on other medication taking behaviors as well as patient satisfaction with the tool. METHODS: Participants were randomly assigned 1:1 to routine care with or without calendar. RESULTS: Adherence, stratified by education (university or postgraduate, p = 0.09; grade school, high school or college p = 0.32), was non-significantly different between study arms. At least 70% of intervention arm participants moderately or completely agreed that the calendar helped with medication taking behaviors. There was no statistical difference between study arms for perceived regimen complexity (p = 0.16). Medication Use and Self Efficacy score (adjusted for age) used to assess perceived self-efficacy with medication taking behaviors were not statistically significant between study arms (p = 0.09). CONCLUSION: The picture-based medication calendar did not statistically affect adherence to scheduled antiemetics among outpatients receiving chemotherapy for solid organ tumor origins. However, participants indicated that the calendar was effective for keeping track of medications, had an easy-to-understand layout, and provided help around when and how to take medications related to the oncology regimen.

Cost-Effectiveness Analysis of Afatinib, Erlotinib, and Gefitinib as First-Line Treatments for EGFR Mutation-Positive Non-Small-Cell Lung Cancer in Ontario, Canada.

OBJECTIVE: The objective of this study was to compare the cost effectiveness of first-line epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) for the treatment of non-small-cell lung cancer. METHODS: This study used Ontario Cancer Registry-linked administrative data to identify patients with a primary diagnosis of lung cancer who received EGFR-TKIs as first-line treatment between 1 January, 2014 and 31 August, 2019. A net benefit regression approach accounting for baseline covariates and propensity scores was used to estimate incremental net benefits and incremental cost-effectiveness ratios. Outcome measures were calculated over a 68-month period and were discounted with an annual rate of 1.5%. Sensitivity analyses were conducted to assess and characterize the uncertainties. RESULTS: A total of 547 patients were included in the study, of whom 20.1%, 23.6%, and 56.3% received afatinib, erlotinib, and gefitinib, respectively. Erlotinib was dominated by afatinib and gefitinib. Compared to gefitinib, afatinib was associated with higher effectiveness (adjusted incremental quality-adjusted life-year: 0.21), higher total costs (adjusted incremental costs: $9745), and an incremental cost-effectiveness ratio of $46,506 per quality-adjusted life-year gained. Results from the sensitivity analyses indicated the findings of the base-case analysis were robust. CONCLUSIONS: Contrary to previously published studies, our study established head-to-head comparisons of effectiveness and treatment-related costs of first-line EGFR-TKIs. Our findings suggest afatinib was the most cost-effective option among the three EGFR-TKIs.

Factors affecting treatment selection and overall survival for first-line EGFR-tyrosine kinase inhibitor therapy in non-small-cell lung cancer.

Aim: To investigate the factors associated with treatment selection and overall survival for first-line EGFR-tyrosine kinase inhibitors (EGFR-TKIs) therapy among patients with non-small-cell lung cancer. Materials & methods: We conducted a retrospective cohort study of linked administrative health databases in Ontario, Canada. Results: A total of 1011 patients received an EGFR-TKI as first-line therapy. Treatment selection and overall survival associated with these treatments were affected by age, sex, geographical residency, comorbidities and different sites of metastasis. Conclusion: Though recent approval of osimertinib offers a potential new standard of care in the first-line setting, earlier generation TKIs remain pillars in treatment of non-small-cell lung cancer therapeutic armamentarium. Our findings may contribute to optimizing treatment sequencing of EGFR-TKIs to maximize clinical benefits.

Controlled substances in hospices after patient death: a cross-sectional survey of Ontario hospices.

Background Practices related to the handling of controlled substances (CS) in Ontario hospices have not been previously published and therefore, are unknown. Objective The objective of this study was to determine current practices, and policies, standard operating procedures (SOPs) and guidelines related to handling and disposal of CS at hospices across Ontario. Setting This study was a cross-sectional survey of hospices in Ontario. Method A list of all hospices in Ontario, 39 in total, was obtained from Hospice and Palliative Care Ontario. The Director at each hospice was contacted to request contact information on the person most likely to be knowledgeable about handling procedures related to CS. All participants who provided consent were asked to complete a telephone survey composed of 32 questions: 20 multiple-choice and 12 open-ended. Of the 20 multiple-choice, eight requested demographics of the hospice, nine were related to disposal and documentation practices. Main outcome measure Demographic information, disposal practices and patterns of care were summarized and presented as frequencies or means. Responses to open-ended questions were analyzed qualitatively to identify themes related to the handling and disposal of controlled substances in hospices. Results Twelve hospices (12/39; 31%) participated in the survey, 25 did not, and two were ineligible. Two (2/12, 17%) hospices served both pediatric and adult patients while 10 (83%) served adults only; 100% indicated that 76-100% of their patients were on CS at time of death. Eight (67%) had a policy for controlled substances handling, two had policy and SOPs and two had no policies, guidelines or SOPs. Qualitative analysis indicated variability in procedures for obtaining CS (patient's own supply, other patient's supply, hospice associated pharmacy), storage and dispensation of CS (location, secure lock, dispensing by staff or family), documentation (dispensing records, double signature, tracking returns and disposal), and disposal of CS (return to pharmacy, disposal at hospice, return to families). Conclusion Although most of the hospices have a policy, guideline or SOP on the handling of CS, there is considerable variation in practice of dispensing CS to patients, documentation and disposal of CS, which may provide an avenue for inappropriate use, abuse or diversion of CS.

Real-world effectiveness of nivolumab in patients with non-small-cell lung cancer: a systematic review and meta-analysis.

Background: The effectiveness of immunotherapies for non-small-cell lung cancer under real-world clinical settings remains uncertain. Materials & methods: Systematic searches of PubMed, EMBASE and Web of Science were conducted. Random-effects models were used to estimate pooled median overall survival and progression-free survival estimates. Results: 36 studies of nivolumab were included for narrative synthesis and 11 of these studies were included for meta-analysis. Age, sex, histology and prior lines of treatment did not affect survival outcomes, while Eastern Cooperative Oncology Group Performance Status and brain metastasis were inversely associated with survival. In the meta-analysis, nivolumab was associated with 9.6 months (95% CI: 8.4-10.9) of overall survival and 2.6 months (95% CI: 1.6-3.6) of progression-free survival. Conclusion: Very-low-certainty evidence suggested the real-world effectiveness of nivolumab was consistent with those observed in the clinical trials.

The tetraspanin Tspan15 is an essential subunit of an ADAM10 scissor complex.

A disintegrin and metalloprotease 10 (ADAM10) is a transmembrane protein essential for embryonic development, and its dysregulation underlies disorders such as cancer, Alzheimer's disease, and inflammation. ADAM10 is a "molecular scissor" that proteolytically cleaves the extracellular region from >100 substrates, including Notch, amyloid precursor protein, cadherins, growth factors, and chemokines. ADAM10 has been recently proposed to function as six distinct scissors with different substrates, depending on its association with one of six regulatory tetraspanins, termed TspanC8s. However, it remains unclear to what degree ADAM10 function critically depends on a TspanC8 partner, and a lack of monoclonal antibodies specific for most TspanC8s has hindered investigation of this question. To address this knowledge gap, here we designed an immunogen to generate the first monoclonal antibodies targeting Tspan15, a model TspanC8. The immunogen was created in an ADAM10-knockout mouse cell line stably overexpressing human Tspan15, because we hypothesized that expression in this cell line would expose epitopes that are normally blocked by ADAM10. Following immunization of mice, this immunogen strategy generated four Tspan15 antibodies. Using these antibodies, we show that endogenous Tspan15 and ADAM10 co-localize on the cell surface, that ADAM10 is the principal Tspan15-interacting protein, that endogenous Tspan15 expression requires ADAM10 in cell lines and primary cells, and that a synthetic ADAM10/Tspan15 fusion protein is a functional scissor. Furthermore, two of the four antibodies impaired ADAM10/Tspan15 activity. These findings suggest that Tspan15 directly interacts with ADAM10 in a functional scissor complex.

Lenvatinib Versus Sorafenib as First-Line Treatment of Unresectable Hepatocellular Carcinoma: A Cost-Utility Analysis.

BACKGROUND: In a global, phase III, open-label, noninferiority trial (REFLECT), lenvatinib demonstrated noninferiority to sorafenib in overall survival and a statistically significant increase in progression-free survival in patients with unresectable hepatocellular carcinoma (HCC). Recently, lenvatinib became the first agent in more than 10 years to receive approval as first-line therapy for unresectable HCC, along with the previously approved sorafenib. The objective of this study was to determine the comparative cost-effectiveness of lenvatinib and sorafenib as a first-line therapy of unresectable HCC. MATERIALS AND METHODS: A state-transition model of unresectable HCC was developed in the form of a cost-utility analysis. The model time horizon was 5 years; the efficacy of the model was informed by the REFLECT trial, and costs and utilities were obtained from published literature. Probabilistic sensitivity analyses and subgroup analyses were performed to test the robustness of the model. RESULTS: Lenvatinib dominated sorafenib in the base case analysis. A probabilistic sensitivity analysis indicated that lenvatinib remains a cost-saving measure in 64.87% of the simulations. However, if the cost of sorafenib was reduced by 57%, lenvatinib would no longer be the dominant strategy. CONCLUSION: Lenvatinib offered a similar clinical effectiveness at a lower cost than sorafenib, suggesting that lenvatinib would be a cost-saving alternative in treating unresectable HCC. However, lenvatinib may fail to remain cost-saving if a significantly cheaper generic sorafenib becomes available. IMPLICATIONS FOR PRACTICE: This analysis suggests an actionable clinical policy that will achieve cost saving. This cost-utility analysis showed that lenvatinib had a similar clinical effectiveness at a lower cost than sorafenib, indicating that lenvatinib may be a cost-saving measure in patients with unresectable HCC, in which $23,719 could be saved per patient. The introduction of a new therapeutic option for the first time in 10 years in Canada provides an important opportunity for clinicians, researchers, and health care decision-makers to explore potential modifications in recommendations and practice guidelines.

Cutaneous toxicities of new targeted cancer therapies: must know for diagnosis, management, and patient-proxy empowerment.

The world of oncology treatment is rapidly changing, and with the investigation into and utilization of molecular signaling pathways for cancer treatment, many new targeted small-molecule oral agents have been introduced as therapies, with more new drugs appearing every year. These agents, while generally considered less toxic overall than traditional chemotherapy, are not without adverse effects. The authors undertook an extensive literature search to determine the incidence, severity, and management strategies for small-molecule oral targeted agents approved by the FDA between 2013 and 2018. Dermatologic adverse effects are among the most frequently seen with many of these targeted therapies, and may include rashes, palmar-plantar dysesthesia, alopecia, secondary skin malignancies, and hair and nail changes. Rarely, more severe cutaneous toxicities are seen, such as Stevens-Johnson Syndrome and toxic epidermal necrolysis. In many cases, there is no specific management strategy suggested in the literature for these toxicities, but frequent monitoring of the skin, prophylactic management of palmar-plantar dysesthesia, use of corticosteroids and/or antihistamines, and intervention with dose interruption are suggested depending on circumstance and severity. Patient education and timely intervention is warranted in order to ensure that patient treatment is optimized.

Impact and Attitudes about Peer Review of Teaching in a Canadian Pharmacy School.

Objective. To evaluate attitudes toward peer review of teaching and its impact on teaching practices and perceptions. Methods. The University of Waterloo School of Pharmacy implemented a peer-review process for its teaching program in 2015. Those reviewed were invited to complete an electronic survey that captured their attitudes toward teaching, attitudes toward peer review, and changes in teaching practices, and to participate in semi-structured follow-up interviews for more in-depth discussion of these issues. Results. Twenty-six (76%) instructors completed the survey. Instructors agreed that peer reviews of teaching are a development opportunity (96%), and 73% were comfortable with the idea of peer review. Over half (58%) indicated that the review made them feel more confident that their teaching strategies were effective, and the same percentage indicated that they planned to make changes to their teaching as a result of the feedback received from the peer review. Only a few instructors indicated that peer review changed their attitudes toward teaching (12%) or increased the value they placed on teaching (34%). Eight instructors (23.5%) participated in the semi-structured interviews. Themes that emerged included: attempts to make the reviewee comfortable during the peer review were successful; the feedback provided to instructors regarding their teaching was positive but not critical enough; there was lack of clarity as to the purpose of the feedback; and instructors planned to make only minor changes to their teaching as a result of the review. Conclusion. Peer review of teaching was well received and feedback was confirmatory in nature but had minimal impact on teaching practices as it was not deemed to be critical enough. Changes to the peer review program are needed to increase its impact on teaching practices.

Management of anticoagulation in patients with metastatic castration-resistant prostate cancer receiving abiraterone + prednisone.

PURPOSE: Abiraterone has been proven to be an effective agent used in the management of metastatic castration-resistant prostate cancer, significantly improving overall and progression-free survival. Due to the pharmacodynamic and pharmacokinetic properties of abiraterone, concurrent use with anticoagulation may pose a challenge for clinicians. Thrombosis within the cancer setting continues to increase patient mortality; therefore, appropriate anticoagulation through the use of a management algorithm can reduce adverse events and increase quality of life. METHODS: A review of the literature was preformed by a medical oncologist, haematologist and pharmacists to identify relevant randomized controlled trials, meta-analyses and retrospective studies. Major society guidelines were reviewed to further aid in developing the anticoagulation protocol for non-valvular atrial fibrillation and venous thromboembolism within this patient population. After reviewing the literature, a clinical framework was designed to aid clinicians in the management of those patients receiving abiraterone concurrently with an anticoagulant. RESULTS: In this review, we describe the potential interactions between abiraterone and various anticoagulants and provide management strategies based on the most recent literature for atrial fibrillation, venous thromboembolism and mechanical heart valves to avoid potential drug-drug interactions. CONCLUSION: Abiraterone therapy has become a mainstay of the management of advanced prostate cancer and is often used over prolonged years. In this review, we have summarized a framework of how to use abiraterone in men with prostate cancer on anticoagulants. Evidence available to date suggests that patients with an indication for anticoagulation such as atrial fibrillation, venous thromboembolism and mechanical heart valves can be treated safely with abiraterone in the appropriate setting, with appropriate monitoring.

Evolution of antiemetic studies for radiation-induced nausea and vomiting within an outpatient palliative radiotherapy clinic.

PURPOSE: Radiation-induced nausea and vomiting (RINV) is a common side effect of radiotherapy and can affect up to 50-80% of patients, potentially causing detrimental effects to physical health, clinical efficacy, and patient quality of life. Antiemetic drugs act on receptors involved in the emesis pathway to block the uptake of neurotransmitters and inhibit stimulation of vomiting centers in the brain to prevent and treat RINV. The most commonly prescribed antiemetics for RINV are 5-hydroxytryptamine receptor antagonists (5-HT3 RA). Guidelines describing the optimal management of RINV are produced by the Multinational Association for Supportive Care in Cancer, the European Society of Medical Oncology, the American Society of Clinical Oncology, and the National Comprehensive Cancer Network. This review will present findings from research on antiemetic management for RINV conducted at our center. METHODS: A selective review of research conducted in a palliative outpatient radiotherapy clinic relating to antiemetic management for RINV was performed. RESULTS: Several studies investigating the efficacy of different routes of administration, new antiemetic drug types, and novel combinations of antiemetics have been tested at our clinic to elucidate which approach provides the best response. These include studies on the use of ondansetron rapidly dissolving film, palonosetron, and the addition of a neurokinin-1 receptor antagonist to traditional 5-HT3 RA regimens. CONCLUSIONS: These studies provide a framework for future research and could potentially inform changes to future guidelines to include the use of these novel regimens and techniques.

Radiation-induced nausea and vomiting: a comparison between MASCC/ESMO, ASCO, and NCCN antiemetic guidelines.

PURPOSE: Radiation-induced nausea and vomiting (RINV) can affect 50-80% of patients undergoing radiotherapy and negatively impacts quality of life. This review aimed to compare the most recent RINV antiemetic guidelines produced by the Multinational Association for Supportive Care in Cancer (MASCC), the European Society of Clinical Oncology (ESMO), the American Society of Clinical Oncology (ASCO), and the National Comprehensive Cancer Network (NCCN). Future improvements to the guidelines and the need for further research in RINV were also discussed. METHODS: Antiemetic guidelines produced by MASCC/ESMO, ASCO, and NCCN were examined to identify similarities, differences, and inadequacies within the guidelines. RESULTS: Areas of dissension within the guidelines include the addition of dexamethasone to moderate-risk antiemetic regimens, the prophylactic treatment of RINV in the low-risk categories, and the appropriate treatment for breakthrough emesis. The guidelines are in accordance that high-risk radiotherapy regimens should be treated prophylactically with a serotonin receptor antagonist and for those undergoing concurrent chemotherapy and radiotherapy, antiemetic treatment should be prescribed according to the emetic risk associated with their respective chemotherapy regimen. Low- and minimal-risk recommendations are based on low-level evidence and informal consensus. CONCLUSION: RINV is a frequent and distressing side effect of radiotherapy and requires further research to establish effective antiemetic guidelines and ensure optimal treatment outcomes.

ASCO, NCCN, MASCC/ESMO: a comparison of antiemetic guidelines for the treatment of chemotherapy-induced nausea and vomiting in adult patients.

Chemotherapy-induced nausea and vomiting (CINV) is a common toxicity that may impair the quality of life of patients with a variety of early- and end-stage malignancies. In light of recent changes in the optimal management of CINV, we undertook this narrative review to compare the latest guidelines published by ASCO (2017), NCCN (2018), and MASCC/ESMO (2016). The processes undertaken by each organization to evaluate existing literature were also described. Although ASCO, NCCN, and MASCC/ESMO guidelines for the treatment and prevention of CINV share many fundamental similarities, literature surrounding low and minimal emetic risk regimens is lacking. Data regarding the use of complementary alternative medicine for CINV is particularly scarce and in need of further investigation.

Risk factors for candidaemia and their cumulative effect over time in a cohort of critically ill, non-neutropenic patients.

OBJECTIVES: There is an increasing incidence of invasive candidal infections in critically ill patients worldwide, which has prompted development of various risk prediction rules, both clinical and microbiological. To date, however, there is a lack of research into how cumulative risk factors over time affect transition to candidaemia. The aim of this study was to investigate the association of risk factor accumulation over time with candidaemia in a cohort of critically ill, non-neutropenic adult patients. DESIGN, SETTING AND PARTICIPANTS: A single centre, retrospective, matched case-control study in a tertiary referral intensive care unit (ICU). Data were retrieved and analysed from 108 patients (54 cases and 54 controls) admitted between 1 January 2008 and 1 August 2016. MAIN OUTCOME MEASURES: Primary outcome was the association between time-dependent risk factors and candidaemia. Secondary outcomes were ICU and inhospital mortality. RESULTS: Baseline demographic and clinical factors were similar across both groups. Time dependent univariate factors associated with candidaemia were days of mechanical ventilation, systemic antibiotic use, renal replacement therapy, central venous access, total parenteral nutrition (TPN), systemic inflammatory response syndrome, Candida site colonisation and number of surgeries. Factors persisting on multivariate analysis were days of TPN use (odds ratio [OR], 1.8; 95% CI, 1.02-3.22; P = 0.041) and total Candida site colonisation days (OR, 2.41; 95% CI, 1.30-4.46; P = 0.005). Mortality and length of stay (LOS) was greater in patients with candidaemia v control patients (ICU mortality, 15 [28%] v 10 [19%]; P = 0.254; hospital mortality, 26 [48%] v 16 [30%]; P = 0.048; ICU LOS median, 13 days [interquartile range (IQR), 5-29 days] v 2 days [IQR, 1-5 days]; P < 0.001; hospital LOS median, 36 days [IQR,19- 63 days] v 13 days [IQR, 6-28 days]; P < 0.001). CONCLUSION: This study demonstrates an association between TPN use, Candida colonisation and cumulative risk over time of developing candidaemia.

Gender-affirming hormone therapy and the risk of sex hormone-dependent tumours in transgender individuals-A systematic review.

BACKGROUND: Cancers are a leading cause of death worldwide, and transgender individuals are no exception. The effects of gender-affirming hormone therapy (GAHT) on sex hormone-dependent tumours are unclear. Therefore, this review seeks to determine whether tumour risk in transgender individuals differs from the general population, to guide clinical screening recommendations. METHODS: We performed a systematic review based on the PRISMA guidelines. MEDLINE, Embase and PsycINFO databases were searched for studies examining tumour incidence, prevalence or cancer-related mortality in transgender individuals. All English peer-reviewed publications were included if histological type and temporal relation to GAHT were reported. Case reports were included if there were ≥2 cases of the same histological type. RESULTS: The search strategy identified 307 studies. Excluding those that did not meet inclusion criteria, 43 studies (7 cohort studies, 2 cross-sectional studies and 34 case reports) were reviewed. Retrospective cohort studies suggest no increase in risk of tumour development in transgender individuals receiving GAHT compared to the general population. Notably, the mean ages of cohorts were young and were treated with GAHT for insufficient durations to assess tumour risk. Case reports raise potential associations between high-dose oestradiol and anti-androgen therapy with prolactinoma and meningioma, respectively. CONCLUSIONS: Further longitudinal studies are required to assess the risk of GAHT and hormone-dependent tumour development. Until further evidence is available, tumour screening should be based on guidelines for the general population and the presence of organs in transgender individuals rather than gender identity or hormonal therapy status.

Cost-Effectiveness of Nivolumab in Recurrent Metastatic Head and Neck Squamous Cell Carcinoma.

BACKGROUND: Treatment options for patients with platinum-refractory, recurrent, metastatic head and neck squamous cell carcinoma (r/m HNSCC) are limited and prognosis is poor. The recent CheckMate 141 clinical trial demonstrated that nivolumab, an anti-programmed cell death protein 1 monoclonal antibody, was efficacious in extending the median overall survival (OS) in this patient population compared with standard therapies. We conducted a cost-effectiveness analysis to determine whether nivolumab is a cost-effective treatment in this patient population and examined various subgroups to determine for which, if any, the treatment is more cost-effective. MATERIALS AND METHODS: We implemented a state transition model for HNSCC with a patient cohort who had tumor progression 6 months after the last dose of platinum-containing chemotherapy and compared the cost-effectiveness of nivolumab with docetaxel. Treatment effect estimates and adverse event rates were obtained from CheckMate 141. Costs, utilities, and other model inputs were gathered from published sources. We used a Canadian perspective, a 5-year time horizon, and a 1.5% discount rate for the analysis. RESULTS: Nivolumab extended mean OS by 4 months compared with docetaxel and resulted in fewer treatment-related adverse events, producing an incremental effectiveness of 0.13 quality-adjusted life years (QALY). The incremental cost of treatment with nivolumab was $18,823. At a willingness-to-pay threshold of $100,000/QALY, nivolumab was not a cost-effective treatment option for r/m HNSCC, with an incremental cost-effectiveness ratio of $144,744/QALY. Nivolumab would be cost-effective if its price was reduced by 20%. Our subgroup analysis seemed to indicate that nivolumab might be cost-effective for tumors with expression of programmed death-ligand 1 >5%. CONCLUSION: We conclude that although nivolumab offers clinical benefit for the treatment of r/m HNSCC over current regimens, it is not cost-effective based on its list price. We have also established a value-based price estimate for nivolumab to be cost-effective in this patient population. Further study is required to draw a definitive conclusion on biomarkers for cost-effectiveness. IMPLICATIONS FOR PRACTICE: In health care settings in which cost considerations are a constraint on choice of therapy, patient selection should be carefully considered to maintain efficiency in the system. Until a biomarker for response to therapy is identified for nivolumab, this medication is unlikely to be cost-effective for most patients with recurrent, metastatic head and neck squamous cell carcinoma.