Access to Oncology Medicines in Canada: Consensus Forum for Recommendations for Improvement.

Patient access to new oncology drugs in Canada is only possible after navigating multiple sequential systemic checkpoints for national regulatory approval, health technology assessment (HTA) and collective government price negotiation. These steps delay access and prevent health care providers from being able to prescribe optimal therapy. Eighteen Canadian oncology clinicians from the medicine, nursing and pharmacy professions met to develop consensus recommendations for defining reasonable government performance standards around process and timeliness to improve Canadian cancer patients' access to best care. A modified Delphi methodology was used to identify consensus on 30 questions involving five themes: accountability, disparities, endpoints, timeliness, and cost-effectiveness. It was agreed that greater transparency is required across regulatory and HTA processes. Health professionals in oncology are frustrated for their patients because they are unable to deliver the modern guideline-supported therapies they want to provide due to delays in approval or funding. Canadian health care providers request improvements in timely access to life-saving therapeutics in line with other comparator countries. Clinicians expect urgent improvements in Canadian health systems to give our patients their best chance of survival.

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.

Efficacy, Safety, and Practicality of Tacrolimus Monitoring after Bone Marrow Transplant: Assessment of a Change in Practice.

BACKGROUND: Currently, there is no standardized approach to the frequency of monitoring tacrolimus levels in patients who have undergone hematopoietic stem cell transplant (HSCT). Previously, the practice at the study hospital was to monitor tacrolimus levels daily throughout a patient's admission. A recent institutional study suggested that measurement of tacrolimus level is more frequent than needed to achieve consistent time in the therapeutic range (TTR), particularly after the first 7 days. As a result, tacrolimus monitoring was changed to daily measurement for the initial week of therapy, followed by measurements on Monday, Wednesday, and Friday in subsequent weeks. OBJECTIVE: To confirm the safety and efficacy of the recent practice change. METHODS: This retrospective chart review of HSCT patients admitted to The Ottawa Hospital involved 68 patients in the pre-practice change group and 43 patients in the post-practice change group. Data on tacrolimus measurement were collected for up to 21 days after initiation of this medication. The proportion of TTR was compared between the 2 groups. Differences in the incidence and severity of renal dysfunction and the incidence of acute graft versus host disease (GVHD) were determined and described. RESULTS: In the pre-practice change cohort, the median proportion of TTR for tacrolimus was 40.5% for days 1-7, 65.1% for days 8-14, and 78.9% for days 15-21, similar to the values for the post-practice change group (46.6% [p = 0.09], 62.9% [p = 0.93], and 70.0% [p = 0.22], respectively, for the same periods). The incidence of acute GVHD within 100 days after HSCT was 24% and 33% for the pre- and post-practice change cohorts, respectively. The incidence and severity of renal dysfunction were similar between the 2 groups. CONCLUSION: The proportion of TTR for tacrolimus was not significantly affected by the recent practice change. Similarly, the incidence and severity of renal dysfunction and the incidence of acute GVHD did not appear to differ between the pre- and post-practice change groups.

CONTEXTE: Il n'existe actuellement aucune approche standardisée portant sur la fréquence des contrôles des valeurs du tacrolimus pour les patients ayant subi une greffe de cellules souches hématopoïétiques (GCSH). Dans le passé, la pratique à l'hôpital où s'est déroulée l'étude consistait à les contrôler quotidiennement durant tout le séjour du patient. Une récente étude institutionnelle a laissé entendre que cette mesure était plus fréquente que nécessaire pour obtenir une marge thérapeutique régulière (TTR), particulièrement après les sept premiers jours. Par conséquent, une modification du contrôle des valeurs du tacrolimus préconise désormais des mesures quotidiennes pendant la première semaine de la thérapie, suivies de mesures le lundi, le mercredi et le vendredi au cours des semaines suivantes. OBJECTIF: Confirmer la sécurité et l'efficacité du récent changement apporté à la pratique. MÉTHODE: Cet examen rétrospectif des dossiers des patients GCSH admis à l'Hôpital d'Ottawa concernait 68 patients du groupe « avant le changement de pratique ¼ et 43 du groupe « après le changement de pratique ¼. Les données relatives aux mesures des valeurs du tacrolimus ont été recueillies pendant les 21 premiers jours après le début de l'administration de ce médicament. La comparaison entre les deux groupes portait sur la proportion de TTR. Les différences d'incidence et de gravité du dysfonctionnement rénal et l'apparition de réaction aiguë du greffon contre l'hôte (GVHD) ont été définies et décrites. RÉSULTATS: Dans la cohorte « avant le changement de pratique ¼, la proportion moyenne de TTR du tacrolimus était de 40,5 % du 1er au 7e jour; de 65,1 % du 8e au 14e jour et de 78,9 % du 15e au 21e jour. Ces valeurs sont similaires à celles du groupe « après le changement de pratique ¼ (respectivement 46,6 % [p = 0,09], 62,9 % [p = 0,93] et 70,0 % [p = 0,22] pendant les mêmes périodes). L'incidence de réaction aiguë du greffon contre l'hôte dans les 100 jours après la GCSH se montait respectivement à 24 % et à 33 % dans les cohortes « avant et après le changement de pratique ¼. L'incidence et la gravité du dysfonctionnement rénal étaient similaires dans les deux groupes. CONCLUSION: La proportion de TTR relative au tacrolimus n'a pas été modifiée de manière significative par le changement récent de pratique. De même, l'incidence et la gravité du dysfonctionnement rénal et l'incidence de réaction aiguë du greffon contre l'hôte ne semblaient pas différer entre les groupes avant et après le changement de pratique.

Impact of a Layered Learning Practice Model on Delivery of Clinical Pharmacy Key Performance Indicators under a Tertiary Care Centre Oncology Service.

BACKGROUND: The layered learning practice model (LLPM), within which a pharmacist supervises both a pharmacy resident and a student, mitigates the growing demand for clinical rotations that has accompanied national expansion of Doctor of Pharmacy programs. A Canadian collaborative of hospital pharmacists established consensus on 8 clinical pharmacy key performance indicators (cpKPIs), activities associated with improved patient outcomes. Increased implementation of the LLPM alongside cpKPI measurement offers opportunities to compare the LLPM with standard practice in terms of pharmaceutical care delivery. OBJECTIVE: To quantify clinical productivity, as measured by proportions of eligible patients receiving cpKPIs and absolute numbers of completed cpKPIs, across scenarios involving pharmacists working with and without pharmacy learners. METHODS: In this retrospective observational study, pharmacy students, pharmacy residents, and pharmacists recorded completion of 7 cpKPIs for oncology inpatients over a total of 6 months in 2017 and 2018. Clinical productivity was described across the following 3 scenarios: presence of one or more pharmacists with one resident and one or more students (P-R-S); presence of one or more pharmacists with one or more students (P-S); and presence of one or more pharmacists only (P; standard practice). RESULTS: During the study, there were 685 recorded admissions to the inpatient oncology service. Generally, the proportions of patients who received cpKPIs were similar for scenarios with and without pharmacy learners present. Standardized to 20 pharmacist workdays, the total number of cpKPIs 1, 2, 3, 5, 6, and 7 (255 with P-R-S scenario, 281 with P-S scenario, and 258 with P scenario) and the total number of drug therapy problems resolved (i.e., cpKPI 3; 153 with P-R-S scenario, 180 with P-S scenario, and 149 with P scenario) were similar across the scenarios. Scenario P had fewer admitted patients per pharmacist workday (3.2) than scenarios P-S and P-R-S (3.4 and 3.7, respectively), which may have contributed to a trend toward greater proportions of patients receiving cpKPIs under scenario P. CONCLUSIONS: Compared with standard practice, integration of pharmacy learners within an oncology unit did not appear to impair clinical productivity, as demonstrated by the comparable proportions of patients receiving cpKPIs and the total number of completed cpKPIs.

CONTEXTE: Le modèle de pratique avec apprentissage à plusieurs niveaux (traduction libre de : Layered Learning Practice Model, [LLPM]), où un pharmacien supervise un résident et un étudiant en pharmacie, permet de réduire la demande croissante de stages cliniques qui a suivi le développement national des programmes de doctorat en pharmacie. Un regroupement canadien composé de pharmaciens d'hôpitaux a établi un consensus sur huit indicateurs clés de rendement relatifs à la pharmacie clinique (ICRpc), activités associées à l'amélioration des résultats thérapeutiques. L'accélération de la mise en oeuvre du LLPM, parallèlement à l'évaluation des ICRpc, offre des occasions de comparer le LLPM aux pratiques courantes en ce qui a trait à la prestation de soins pharmaceutiques. OBJECTIF: Quantifier la productivité clinique, en fonction des proportions de patients admissibles, profitant des ICRpc et des nombres absolus d'ICRpc évalués, dans des scénarios où les pharmaciens travaillent ou non avec des étudiants ou des résidents. MÉTHODES: Dans la présente étude d'observation rétrospective, des étudiants et des résidents en pharmacie ainsi que des pharmaciens ont enregistré l'évaluation complète de sept ICRpc pour des patients hospitalisés en oncologie sur une durée totale de six mois en 2017 et 2018. La productivité clinique a été décrite à l'intérieur des trois scénarios suivants : participation d'au moins un pharmacien accompagné d'au moins un résident et un étudiant (P-R-É); participation d'au moins un pharmacien accompagné d'au moins un étudiant (P-É); et participation d'au moins un pharmacien, sans étudiant ou résident (P : pratique courante). RÉSULTATS: Au cours de l'étude, on a enregistré 685 admissions au service d'hospitalisation en oncologie. Généralement, les proportions de patients profitant des ICRpc étaient semblables dans les trois scénarios. Basé sur une unité de mesure de 20 jours de travail de pharmacien, le nombre total d'ICRpc 1, 2, 3, 5, 6 et 7 (255 pour le scénario P-R-É, 281 pour le scénario P-É et 258 pour le scénario P) et le nombre total de problèmes pharmacothérapeutiques réglés (c'est-à-dire ICRpc 3; 153 pour le scénario P-R-É, 180 pour le scénario P-É et 149 pour le scénario P) étaient semblables dans les différents scénarios. Le scénario P présentait moins de patients admis par jours de travail de pharmacien (3,2) que les scénarios P-É et P-R-É (respectivement 3,4 et 3,7), ce qui peut avoir contribué à créer une tendance montrant une plus grande proportion de patients profitant des ICRpc dans le scénario P. CONCLUSIONS: Comparée à la pratique courante, l'intégration d'étudiants ou de résidents en pharmacie dans un service d'oncologie ne semblait pas réduire la productivité clinique, comme l'illustrent les proportions comparables de patients profitant d'ICRpc et le nombre total d'ICRpc évalués.

Characterization of Serious Adverse Drug Reactions in Hospital to Determine Potential Implications of Mandatory Reporting.

BACKGROUND: The Protecting Canadians from Unsafe Drugs Act will eventually require institutions to report all serious adverse drug reactions (ADRs), although the proposed regulations do not yet define what will need to be reported and by whom. Knowledge about the occurrence of serious ADRs in the hospital setting is needed to optimize the effectiveness of reporting and to determine the potential implications of mandatory reporting. OBJECTIVES: To quantify and characterize suspected serious ADRs in patients admitted to a general medicine service, to assess the likelihood of causality, and to determine inter-rater agreement for identification of ADRs and assessment of their likelihood. METHODS: This prospective observational study involved 60 consecutive patients admitted to a general medicine service at a tertiary care teaching centre starting on March 28, 2016. The primary outcome was the number of serious ADRs, defined by Health Canada as ADRs that result in hospital admission, congenital malformation, persistent or significant disability or incapacity, or death; that are life-threatening; or that require significant intervention to prevent one of these outcomes. Medical records were reviewed independently by pairs of pharmacists for serious ADRs, and the likelihood of causality was assessed using the World Health Organization-Uppsala Monitoring Centre system. Inter-rater agreement was calculated using the kappa score, and disagreements were resolved by discussion and consensus. RESULTS: Twenty-three serious ADRs occurred in the sample of 60 patients. The proportion of patients experiencing a serious ADR that contributed to the original hospital admission was 19/60 (32%, 95% confidence interval [CI] 20%-43%), and 4 patients (7%, 95% CI 0%-13%) experienced a serious ADR during their hospital stay. Inter-rater agreement for occurrence of serious ADRs was moderate (kappa 0.58, 95% CI 0.35-0.76). CONCLUSION: Reportable serious ADRs were common among patients admitted to a general medicine service. Canadian hospitals would face difficulties reporting all serious ADRs because of the frequency of their occurrence and the subjectivity of their identification.

CONTEXTE: La Loi visant à protéger les Canadiens contre les drogues dangereuses obligera éventuellement les établissements à déclarer tout cas de réactions indésirables graves aux médicaments (RIM), quoique les règlements proposés n'indiquent pas encore ce qui devra être déclaré et par qui. Des données sur la survenue de RIM graves en milieu hospitalier sont nécessaires pour optimiser l'efficacité de la déclaration et pour déterminer les implications potentielles d'une déclaration obligatoire. OBJECTIFS: Quantifier les RIM graves soupçonnées chez les patients admis à un service de médecine générale et en offrir un portrait, évaluer la probabilité d'une relation de causalité et déterminer l'accord interévaluateurs pour le repérage des RIM et l'évaluation de leur probabilité. MÉTHODES: La présente étude observationnelle prospective comptait 60 patients admis consécutivement à partir du 28 mars 2016 à un service de médecine générale d'un centre hospitalier universitaire de soins tertiaires. Le principal paramètre d'évaluation était le nombre de RIM graves, définies par Santé Canada comme des RIM qui mènent à une hospitalisation, à une malformation congénitale, à une invalidité ou à une incapacité persistante ou importante; qui mettent la vie en danger ou entraînent la mort; ou qui nécessitent une intervention significative pour prévenir l'un de ces résultats. Les dossiers médicaux ont été examinés indépendamment par des paires de pharmaciens à la recherche de RIM graves et la probabilité d'une causalité a été évaluée à l'aide du système du Centre de pharmacovigilance d'Uppsala de l'Organisation mondiale de la Santé. L'accord interévaluateurs a été mesuré à l'aide du coefficient kappa et les désaccords ont été résolus par la discussion et l'atteinte d'un consensus. RÉSULTATS: Vingt-trois RIM graves sont survenues dans l'échantillon composé de 60 patients. La proportion de patients ayant subi une RIM grave qui a contribué à l'hospitalisation initiale était 19/60 (32 %, intervalle de confiance [IC] de 95 % de 20 %­43 %); de plus, 4 patients (7 %, IC de 95 % de 0 %­13 %) avaient subi une RIM grave au cours de leur séjour à l'hôpital. L'accord interévaluateurs sur la survenue de RIM graves était modéré (kappa = 0,58, IC de 95 % de 0,35­0,76). CONCLUSION: Les RIM graves à déclaration obligatoire étaient courantes chez les patients admis à un service de médecine générale. Les hôpitaux canadiens auraient de la difficulté à déclarer tous les cas de RIM graves à cause de leur fréquence et de la subjectivité de leur repérage.

Pharmacy Student Facilitation of Reporting of Adverse Drug Reactions in a Hospital.

BACKGROUND: Health Canada relies on health professionals to voluntarily report adverse reactions to the Canada Vigilance Program. Current rates of reporting adverse drug reactions (ADRs) are inadequate to detect important safety issues. OBJECTIVE: To assess the impact of pharmacy student facilitation of ADR reporting by pharmacists at a tertiary care teaching hospital in Canada. METHODS: The intervention of interest, implemented at one campus of the hospital, was facilitation of ADR reporting by pharmacy students. The students received training on how to submit ADR reports and presented information sessions on the topic to hospital pharmacists; the pharmacists were then encouraged to report ADRs to a designated student for formal reporting. Frequency of reporting by pharmacists at the intervention campus was compared with reporting at a control campus of the same hospital. Data were collected prospectively over a 6-month pilot period, starting in April 2015. RESULTS: During the pilot period, 27 ADR reports were submitted at the intervention campus, and 3 reports at the control campus. All student participants strongly agreed that they would recommend that responsibility for submitting ADR reports to the Canada Vigilance Program remain with pharmacy students during future rotations. CONCLUSIONS: Availability of a pharmacy student to facilitate reporting of ADRs may increase the frequency of ADR reporting and could alleviate pharmacist workload; this activity is also a potentially valuable learning experience for students.

CONTEXTE: Santé Canada compte sur les professionnels de la santé pour signaler sur une base volontaire les réactions indésirables au programme Canada Vigilance. Les taux actuels de déclaration des réactions indésirables aux médicaments (RIM) ne permettent pas de repérer les problèmes de sécurité importants. OBJECTIF: Évaluer l'effet d'une intervention permettant aux étudiants en pharmacie de faciliter la déclaration des RIM par les pharmaciens dans un hôpital universitaire de soins tertiaires au Canada. MÉTHODES: L'intervention en question, mise en place dans l'un des établissements de l'hôpital, se résumait à permettre aux étudiants en pharmacie de faciliter la déclaration de RIM. Les étudiants étaient formés pour soumettre des déclarations de RIM et ont présenté des séances d'information sur le sujet aux pharmaciens d'hôpitaux; ces derniers étaient ensuite encouragés à signaler les RIM à un étudiant désigné qui procédait alors à une déclaration formelle. La fréquence de déclaration par les pharmaciens à l'établissement où l'intervention était mise en place a été comparée à celle d'un établissement témoin du même hôpital. Les données ont été recueillies de façon prospective sur une période de six mois pour l'étude pilote qui a commencé en avril 2015. RÉSULTATS: Pendant l'étude pilote, on a procédé à 27 déclarations de RIM à l'établissement où a eu place l'intervention alors que, dans l'établissement témoin, on en a signalé que trois. L'ensemble des étudiants ayant participé étaient tout à fait d'accord pour que la responsabilité de produire des déclarations de RIM au programme Canada Vigilance demeure une tâche pour les étudiants en pharmacie au cours de stages futurs. CONCLUSIONS: La mise à contribution d'un étudiant en pharmacie pourrait accroître la fréquence de déclaration des RIM et pourrait réduire la charge de travail du pharmacien. De plus, cette tâche peut représenter une expérience d'apprentissage précieuse pour les étudiants.

Outcomes Associated with Reducing the Urine Alkalinization Threshold in Patients Receiving High-Dose Methotrexate.

STUDY OBJECTIVES: Urine alkalinization increases methotrexate (MTX) solubility and reduces the risk of nephrotoxicity. The objectives of this study were to determine whether a reduction in the urine pH threshold from 8 to 7 in patients receiving high-dose methotrexate (HDMTX) results in a shorter length of hospital stay, delayed MTX clearance, or higher rates of nephrotoxicity; and to determine whether specific factors were associated with prolonged MTX clearance. DESIGN: Retrospective cohort study. SETTING: Hematology service of a large university-affiliated teaching hospital in Ottawa, Canada. PATIENTS: Sixty-five adults with 150 HDMTX exposures who had elective admissions for HDMTX between September 1, 2014, and December 18, 2015, were included. Thirty-four patients (with 79 HDMTX exposures) had their urine alkalinized to a pH of 8 or higher, and 31 patients (with 71 HDMTX exposures) had their urine alkalinized to a pH of 7 or higher, after an institutional change in the urine pH threshold from 8 to 7 was implemented on May 1, 2015. MEASUREMENTS AND MAIN RESULTS: Data related to patient demographics, urine alkalinization, MTX serum concentration monitoring, hospital length of stay, and renal function were collected retrospectively from patients' electronic health records. Lowering the urine pH threshold from 8 to 7 did not significantly affect hospital length of stay (absolute difference 3.5 hrs, 95% confidence interval -4.0 to 10.9) or clearance of MTX (elimination rate constant 0.058 in the pH of 7 or higher group vs 0.064 in the pH of 8 or higher group, p=0.233). Nephrotoxicity rates were similar between groups (15.5% in the pH of 7 or higher group vs 10.1% in the pH of 8 or higher group, p=0.34). Higher MTX dose and interacting medications (e.g., proton pump inhibitors and sulfonamide antibiotics) were significantly associated with delayed MTX elimination. CONCLUSION: No significant differences in HDMTX-associated hospital length of stay, MTX clearance, or rates of nephrotoxicity were noted between patients in the urine pH of 7 or higher and 8 or higher groups. Interacting medications and higher MTX dose were associated with delayed MTX elimination, suggesting that a closer review of interacting medications before HDMTX administration may be warranted.

Canadian Cardiovascular Society Guidelines for Evaluation and Management of Cardiovascular Complications of Cancer Therapy.

Modern treatment strategies have led to improvements in cancer survival, however, these gains might be offset by the potential negative effect of cancer therapy on cardiovascular health. Cardiotoxicity is now recognized as a leading cause of long-term morbidity and mortality among cancer survivors. This guideline, authored by a pan-Canadian expert group of health care providers and commissioned by the Canadian Cardiovascular Society, is intended to guide the care of cancer patients with established cardiovascular disease or those at risk of experiencing toxicities related to cancer treatment. It includes recommendations and important management considerations with a focus on 4 main areas: identification of the high-risk population for cardiotoxicity, detection and prevention of cardiotoxicity, treatment of cardiotoxicity, and a multidisciplinary approach to cardio-oncology. All recommendations align with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Key recommendations for which the panel provides a strong level of evidence include: (1) that routine evaluation of traditional cardiovascular risk factors and optimal treatment of preexisting cardiovascular disease be performed in all patients before, during, and after receiving cancer therapy; (2) that initiation, maintenance, and/or augmentation of antihypertensive therapy be instituted per the Canadian Hypertension Educational Program guidelines for patients with preexisting hypertension or for those who experience hypertension related to cancer therapy; and (3) that investigation and management follow current Canadian Cardiovascular Society heart failure guidelines for cancer patients who develop clinical heart failure or an asymptomatic decline in left ventricular ejection fraction during or after cancer treatment. This guideline provides guidance to clinicians on contemporary best practices for the cardiovascular care of cancer patients.

Intrathecal Analgesia for Chronic Refractory Pain: Current and Future Prospects.

The intrathecal drug-delivery system (IDDS) is one mode of infusing analgesic medications directly into the cerebrospinal fluid in close proximity to their site of action. This modality has been employed in patients with refractory pain either due to malignant or non-malignant causes for over 30 years. Unfortunately, and despite the number of years it has been in use, there is still a scarcity of rigorous evidence to guide its integration into clinical practice. Current best evidence is inconclusive as to the comparative effectiveness and harms of the IDDS relative to routine medical care of patients. There are far more systematic reviews than high-quality primary comparative studies of the IDDS vs. conventional pain treatment. Existing clinical practice recommendations are best viewed as expert opinion with competing interests. This article will review the existing literature for indications, contraindications, consensus statements, different technologies, and complications of the IDDS. Although approved analgesics for IDDS delivery are limited to morphine and ziconotide, many other analgesics, alone or in combination, are routinely used in this setting. This review will also focus on the pharmacology, clinical efficacy, and safety of intrathecal medications extensively used in clinical practice; including agents approved, unapproved, and under development.

Clinical Experience of Patients Referred to a Multidisciplinary Cardiac Oncology Clinic: An Observational Study.

Cardiotoxicity is the second leading cause of long-term morbidity and mortality among cancer survivors. The purpose of this retrospective observational study is to report on the clinical and cardiac outcomes in patients with early stage and advanced cancer who were referred to our multidisciplinary cardiac oncology clinic (COC). A total of 428 patients were referred to the COC between October 2008 and January 2013. The median age of patients at time of cancer diagnosis was 60. Almost half of patients who received cancer therapy received first-line chemotherapy alone (169, 41.7%), of which 84 (49.7%) were exposed to anthracyclines. The most common reasons for referral to the cardiac oncology clinic were decreased LVEF (34.6%), prechemotherapy assessment (11.9%), and arrhythmia (8.4%). A total of 175 (40.9%) patients referred to the COC were treated with cardiac medications. The majority (331, 77.3%) of patients were alive as of January 2013, and 93 (21.7%) patients were deceased. Through regular review of cardiac oncology clinic referral patterns, management plans, and patient outcomes, we aim to continuously improve delivery of cardiac care to our patient population and optimize cardiac health.

Copper-mediated nuclease activity of jadomycin B.

The natural product jadomycin B, isolated from Streptomyces venezeulae ISP5230, has been found to cleave DNA in the presence of Cu(II) ions without the requirement for an external reducing agent. The efficiency of DNA cleavage was probed using supercoiled plasmid DNA in buffered solution as a model environment. EC50 and t(½) values for cleavage were 1.7 µM and 0.75 h, respectively, and varied ± 5% with the particular batch of plasmid and jadomycin employed. While UV-vis spectroscopy indicates that the cleavage event does not involve direct binding of jadomycin B to DNA, a stoichiometric Cu(II) preference for optimum cleavage suggests a weak binding interaction between jadomycin B and Cu(II) in the presence of DNA. The Cu(II)-mediated cleavage is greatly enhanced by UV light, which implicates the jadomycin B radical cation and Cu(I) as potential intermediates in DNA cleavage. Evidence in favor of this hypothesis was derived from a mechanistic assay which showed reduced cleavage as a function of added catalase and EDTA, scavengers of H2O2 and Cu(II), respectively. Thus, jadomycin B may serve as a source of electrons for Cu(II) reduction, producing Cu(I) which reacts with H2O2 to form hydroxyl radicals that cause DNA strand scission. In addition, scavengers of hydroxyl radicals and superoxide also display inhibitory effects, underscoring the ability of jadomycin B to produce a powerful arsenal of deleterious oxygen species when copper is present.

Diverse DNA-cleaving capacities of the jadomycins through precursor-directed biosynthesis.

Gel mobility assays were used to establish that some members of the jadomycin family of natural products act as DNA cleaving agents. Moreover, it was found that subtle structural changes generated through the use of precursor-directed biosynthesis lead to marked effects on the DNA-damaging properties of these glycosylated polyketide-derived natural products.

Antimicrobial activities of jadomycin B and structurally related analogues.

Natural products are leads for new antibiotics as a result of their structural complexity and diversity. We have isolated a series of structurally related polyketide-derived natural products from Streptomyces venezuelae ISP5230. The most active of these jadomycin analogues showed good activity against a variety of staphylococci, including methicillin-resistant Staphylococcus aureus.