Implementing changes to a residency program curriculum before competency-based medical education: a survey of Canadian medical oncology program directors.

Background: Postgraduate medical education is undergoing a paradigm shift in many universities worldwide, transitioning from a time-based model to competency-based medical education (cbme). Residency programs might have to alter clinical rotations, educational curricula, assessment methods, and faculty involvement in preparation for cbme, a process not yet characterized in the literature. Methods: We surveyed Canadian medical oncology program directors on planned or newly implemented residency program changes in preparation for cbme. Results: Prior to implementing cbme, all program directors changed at least 1 clinical rotation, most commonly making hematology/oncology (74%) entirely outpatient and eliminating radiation oncology (64%). Introductory rotations were altered to focus on common tumour sites, and later rotations were changed to increase learner autonomy. Most program directors planned to enhance resident learning with electronic teaching modules (79%), new training experiences (71%), and academic half-day changes (50%). Most program directors (64%) planned to change assessment methods to be entirely based on entrustable professional activities. All programs had developed a competence committee to review learner progress, and most (86%) had integrated academic coaches. Conclusions: Transitioning to cbme led to major structural and curricular changes within medical oncology training programs. Identifying these commonly implemented changes could help other programs transition to cbme.

Correction to: Quality Improvement and Personalization for Statins: the QUIPS Quality Improvement Randomized Trial of Veterans' Primary Care Statin Use.

Dr. Sussman's name displayed incorrectly in the html of this paper.

Surgical attitudes toward preoperative breast magnetic resonance imaging in women with early-stage breast cancer.

Background: Preoperative breast magnetic resonance imaging (mri) is commonly requested by surgeons in the initial workup of women with breast cancer; however, its use is controversial. We performed a survey of breast cancer surgeons across Canada to investigate current knowledge about, attitudes to, and self-reported use of preoperative breast mri in a publicly funded health care system in light of the limited evidence to support it. Methods: All identified general surgeons in Canada were mailed a survey instrument designed to probe current practice and knowledge of published trials. Results: Of 403 responding surgeons, 233 (58%) indicated that they performed breast cancer surgery. Of those 233, 218 (94%) had access to breast mri and completed the entire survey. Overall, 54.6% of responding surgeons felt that breast mri was useful in surgical planning, and more than half (58.3%) indicated that their frequency of use was likely to increase over the next 5 years. Surgeons found preoperative mri most useful in detecting mammographically occult disease (71.5% of respondents) and in planning for breast-conserving surgery (57.3%). The main limitations reported were timely access to mri (51%) and false positives (36.7%). Responses suggest a knowledge gap in awareness of published trials in breast mri. Conclusions: Our study found that, in early-stage breast cancer, self-reported use of mri by breast cancer surgeons in Canada varied widely. Reported indications did not align with published data, and significant gaps in self-reported knowledge of the data were evident. Our results would support the development and dissemination of guidelines to optimize use of mri.

MEDiastinal Irradiation and CArdio-Toxic Effects (MEDICATE): Exploring the Relationship between Cardiac Irradiation and High Sensitivity Troponins.

AIMS: Radiation-induced heart disease is a late effect of cardiac irradiation and has been shown in patients with lymphoma and thoracic cancers. There is no established measurement tool to detect acute cardiac damage. However, high sensitivity troponin I and T (HsTnI and HsTnT) and echocardiograms have shown promise in some studies. A pilot trial was conducted to characterise whether these instruments may detect subclinical radiotherapy-induced cardiac damage. MATERIALS AND METHODS: Eligible patients received high cardiac doses defined by either at least 30 Gy to 5% of cardiac volume or a mean dose of 4 Gy. HsTnI and HsTnT were measured before radiotherapy and after 2 and 4 weeks of radiotherapy; three-dimensional echocardiograms were completed before and 1 year after radiotherapy. RESULTS: Of 19 patients, the median 'mean left ventricular dose' was 3.1 Gy and the 'mean cardiac dose' was 8.6 Gy. Significant positive associations between HsTnI and HsTnT were observed at all time points, but there was no significant association with cardiac dose. The mean left ventricular dose and the maximum left ventricular dose were, however, associated with a decrease in ejection fraction (P = 0.054, 0.043) as well as an increase in left ventricular strain (P = 0.058). CONCLUSION: This study suggests that HsTnI and HsTnT are intimately related, but detection of acute cardiac damage was not shown, potentially due to limitations of these markers or low radiotherapy doses using conformal techniques. Our results also suggest subacute damage at 1 year may depend on the dose to the left ventricle. Further studies are needed, as identification of early damage could facilitate the ability to closely monitor and intervene in patients at risk for radiation-induced heart disease.

Integrating primary care providers through the seasons of survivorship.

Traditionally, the role of primary care providers (pcps) across the cancer care trajectory has focused on prevention and early detection. In combination with screening initiatives, new and evolving treatment approaches have contributed to significant improvements in survival in a number of cancer types. For Canadian cancer survivors, the 5-year survival rate is now better than it was a decade ago, and the survivor population is expected to reach 2 million by 2031. Notwithstanding those improvements, many cancer survivors experience late and long-term effects, and comorbid conditions have been noted to be increasing in prevalence for this vulnerable population. In view of those observations, and considering the anticipated shortage of oncology providers, increasing reliance is being placed on the primary care workforce for the provision of survivorship care. Despite the willingness of pcps to engage in that role, further substantial efforts to elucidate the landscape of high-quality, sustainable, and comprehensive survivorship care delivery within primary care are required. The present article offers an overview of the integration of pcps into survivorship care provision. More specifically, it outlines known barriers and potential solutions in five categories: ■ Survivorship care coordination■ Knowledge of survivorship■ pcp-led clinical environments■ Models of survivorship care■ Health policy and organizational advocacy.

Tube Feed Necrosis after Major Gastrointestinal Oncologic Surgery: Institutional Lessons and a Review of the Literature.

BACKGROUND: Small bowel necrosis after enteral feeding through a jejunostomy tube (tube feed necrosis, TFN) is a rare, serious complication of major abdominal surgery. However, strategies to reduce the incidence and morbidity of TFN are not well established. Here, in the largest series of TFN presented to date, we report our institutional experience and a comprehensive review of the literature. METHODS: Eight patients who experienced TFN from 2000 to 2014 after major abdominal surgery for oncologic indications at the University of Cincinnati were reviewed. Characteristics of post-operative courses and outcomes were reviewed prior to and after a change in tube-feeding protocol. The existing literature addressing TFN over the last three decades was also reviewed. RESULTS: Patients with TFN ranged from 50 to 74 years old and presented with upper gastrointestinal tract malignancies amenable to surgical resection. Six and two cases of TFN occurred following pancreatectomy and esophagectomy, respectively. Prior to TF protocol changes, which included initiation at a low rate, titrating up more slowly and starting at one-half strength TF, three of six cases of TFN (50%) resulted in mortality. With the new TF protocol, there were no deaths, goal TF rate was achieved 3 days later, symptoms of TFN were recognized 3 days earlier, and re-operation was conducted 1 day earlier. CONCLUSION: This case series describes a change in clinical practice that is associated with decreased morbidity and mortality of TFN. Wider implementation and further refinement of this tube-feeding protocol may reduce TFN incidence at other institutions and in patients with other conditions requiring enteral nutrition.

Multigene expression profile testing in breast cancer: is there a role for family physicians?

BACKGROUND: Family physicians (fps) play a role in aspects of personalized medicine in cancer, including assessment of increased risk because of family history. Little is known about the potential role of fps in supporting cancer patients who undergo tumour gene expression profile (gep) testing. METHODS: We conducted a mixed-methods study with qualitative and quantitative components. Qualitative data from focus groups and interviews with fps and cancer specialists about the role of fps in breast cancer gep testing were obtained during studies conducted within the pan-Canadian canimpact research program. We determined the number of visits by breast cancer patients to a fp between the first medical oncology visit and the start of chemotherapy, a period when patients might be considering results of gep testing. RESULTS: The fps and cancer specialists felt that ordering gep tests and explaining the results was the role of the oncologist. A new fp role was identified relating to the fp-patient relationship: supporting patients in making adjuvant therapy decisions informed by gep tests by considering the patient's comorbid conditions, social situation, and preferences. Lack of fp knowledge and resources, and challenges in fp-oncologist communication were seen as significant barriers to that role. Between 28% and 38% of patients visited a fp between the first oncology visit and the start of chemotherapy. CONCLUSIONS: Our findings suggest an emerging role for fps in supporting patients who are making adjuvant treatment decisions after receiving the results of gep testing. For success in this new role, education and point-of-care tools, together with more effective communication strategies between fps and oncologists, are needed.

Management of Early-stage Hodgkin Lymphoma: A Practice Guideline.

In the past, treatment for patients with early-stage Hodgkin lymphoma consisted mainly of radiotherapy. Now, chemotherapy alone and chemoradiotherapy are treatment options. These guidelines aim to provide recommendations on the optimal management of early-stage Hodgkin lymphoma. We conducted a systematic review searching MEDLINE, EMBASE, the Cochrane Library and other literature sources from 2003 to 2015, and applied the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Two authors independently reviewed and selected studies, and appraised the evidence quality. The document underwent internal and external review by content, methodology experts, a patient representative and clinicians in Ontario. We have issued recommendations for patients with classical Hodgkin lymphoma and with nodular lymphocyte predominant Hodgkin lymphoma; with favourable and unfavourable prognosis; and for the use of positron emission tomography to direct treatment. We have provided our interpretation of the evidence and considerations for implementation. Examples of recommendations are: 'Patients with early-stage classical Hodgkin lymphoma should not be treated with radiotherapy alone'; 'chemotherapy plus radiotherapy or chemotherapy alone are recommended treatment options for patients with early-stage non-bulky Hodgkin lymphoma'; 'The Working Group does not recommend the use of a negative interim positron emission tomography scan alone to identify patients with early-stage Hodgkin lymphoma for whom radiotherapy can be omitted without a reduction in progression-free survival'. Through the use of GRADE, recommendations were geared towards patient important outcomes and their strength reflected the available evidence and its interpretation from the patients' point of view.

Follow-up care for survivors of lymphoma who have received curative-intent treatment.

OBJECTIVE: This evidence summary set out to assess the available evidence about the follow-up of asymptomatic survivors of lymphoma who have received curative-intent treatment. METHODS: The medline and embase databases and the Cochrane Database of Systematic Reviews were searched for evidence published between 2000 and August 2015 relating to lymphoma survivorship follow-up. The evidence summary was developed by a Working Group at the request of the Cancer Care Ontario Survivorship and Cancer Imaging programs because of the absence of evidence-based practice documents in Ontario for the follow-up and surveillance of asymptomatic patients with lymphoma in complete remission. RESULTS: Eleven retrospective studies met the inclusion criteria. The proportion of relapses initially detected by clinical manifestations ranged from 13% to 78%; for relapses initially detected by imaging, the proportion ranged from 8% to 46%. Median time for relapse detection ranged from 8.6 to 19 months for patients initially suspected because of imaging and from 8.6 to 33 months for those initially suspected because of clinical manifestations. Only one study reported significantly earlier relapse detection for patients initially suspected because of clinical manifestations (mean: 4.5 months vs. 6.0 months, p = 0.042). No benefit in terms of overall survival was observed for patients depending on whether their relapse was initially detected because of clinical manifestations or surveillance imaging. SUMMARY: Findings in the present study support the importance of improving awareness on the part of survivors and clinicians about the symptoms that might be associated with recurrence. The evidence does not support routine imaging for improving outcomes in this patient population.

Cost trajectories for cancer patients.

BACKGROUND: Health care spending is known to be highly skewed, with a small subset of the population consuming a disproportionate amount of health care resources. Patients with cancer are high-cost users because of high incremental health care costs for treatment and the growing prevalence of cancer. The objectives of the present study included characterizing cancer-patient trajectories by cost, and identifying the patient and health system characteristics associated with high health system costs after cancer treatment. METHODS: This retrospective cohort study identified Ontario adults newly diagnosed with cancer between 1 April 2009 and 30 September 2010. Costs of health care use before, during, and after cancer episodes were used to develop trajectories of care. Descriptive analyses examined differences between the trajectories in terms of clinical and health system characteristics, and a logistic regression approach identified predictors of being a high-cost user after a cancer episode. RESULTS: Ten trajectories were developed based on whether patients were high- or low-cost users before and after their cancer episode. The most common trajectory represented patients who were low-cost in the year before cancer, survived treatment, and continued to be low-cost in the year after cancer (31.4%); stage ii cancer of the male genital system was the most common diagnosis within that trajectory. Regression analyses identified increases in age and in multimorbidity and low continuity of care as the strongest predictors of high-cost status after cancer. CONCLUSIONS: Findings highlight an opportunity to proactively identify patients who might transition to high-cost status after cancer treatment and to remediate that transition.

Views of family physicians about survivorship care plans to provide breast cancer follow-up care: exploration of results from a randomized controlled trial.

BACKGROUND: The U.S. Institute of Medicine recommends that cancer patients receive survivorship care plans, but evaluations to date have found little evidence of the effectiveness of such plans. We conducted a qualitative follow-on study to a randomized controlled trial (rct) to understand the experiences of family physicians using survivorship care plans to support the follow-up of breast cancer patients. METHODS: A subset of family physicians whose patients were enrolled in the parent rct in Ontario and Nova Scotia were eligible for this study. In interviews, the physicians discussed survivorship care plans (intervention) or usual discharge letters (control), and their confidence in providing follow-up cancer care. RESULTS: Of 123 eligible family physicians, 18 (10 intervention, 8 control) were interviewed. In general, physicians receiving a survivorship care plan found only the 1-page care record to be useful. Physicians who received only a discharge letter had variable views about the letter's usefulness; several indicated that it lacked information about potential cancer- or treatment-related problems. Most physicians were comfortable providing care 3-5 years after diagnosis, but desired timely and informative communication with oncologists. CONCLUSIONS: Although family physicians did not find extensive survivorship care plans useful, discharge letters might not be sufficiently comprehensive for follow-up breast cancer care. Effective strategies for two-way communication between family physicians and oncologists are still lacking.

Does routine symptom screening with ESAS decrease ED visits in breast cancer patients undergoing adjuvant chemotherapy?

BACKGROUND: In 2007, the provincial cancer agency in Ontario, Canada initiated a wide-scale program to screen for symptoms in the cancer population using the Edmonton Symptom Assessment Scale (ESAS). The purpose of this study is to evaluate the impact of screening with ESAS on emergency department (ED) visit rates in women with breast cancer receiving adjuvant chemotherapy. PATIENTS AND METHODS: This retrospective cohort study used linked administrative health care data from across the province of Ontario, Canada. The cohort included all women aged ≥18 who were diagnosed with stage I-III breast cancer between January 2007 and December 2009 and received adjuvant chemotherapy within 6 months of diagnosis. Using an adjusted recurrent event model, we examined the association of screening with ESAS at a clinic visit on the ED visit rate. RESULTS: The relative rate of ED visits was 0.57 when prior ESAS screening occurred compared to when it did not. The relative rate of ED visits was 0.83 when the prior number of ESAS screens was modeled as a continuous variable. Alternatively stated, the rate of ED visits was 43 % lower among patients previously screened with ESAS compared to those not previously screened. For each additional prior ESAS assessment, there was a 17 % decreased rate of ED visits. CONCLUSIONS: Our results demonstrate that screening with ESAS is associated with decreased ED visits. To our knowledge, this is the first report on the effectiveness of routinely documenting a patient reported outcome on ED visits, in a real-world setting.

Sleep disturbance in adults with cancer: a systematic review of evidence for best practices in assessment and management for clinical practice.

Sleep disturbance is prevalent in cancer with detrimental effects on health outcomes. Sleep problems are seldom identified or addressed in cancer practice. The purpose of this review was to identify the evidence base for the assessment and management of cancer-related sleep disturbance (insomnia and insomnia syndrome) for oncology practice. The search of the health literature included grey literature data sources and empirical databases from June 2004 to June 2012. The evidence was reviewed by a Canadian Sleep Expert Panel, comprised of nurses, psychologists, primary care physicians, oncologists, physicians specialized in sleep disturbances, researchers and guideline methodologists to develop clinical practice recommendations for pan-Canadian use reported in a separate paper. Three clinical practice guidelines and 12 randomized, controlled trials were identified as the main source of evidence. Additional guidelines and systematic reviews were also reviewed for evidence-based recommendations on the assessment and management of insomnia not necessarily in cancer. A need to routinely screen for sleep disturbances was identified and the randomized, controlled trial (RCT) evidence suggests benefits for cognitive behavioural therapy for improving sleep quality in cancer. Sleep disturbance is a prevalent problem in cancer that needs greater recognition in clinical practice and in future research.

Stereo-specific synthesis of analogs of nerve agents and their utilization for selection and characterization of paraoxonase (PON1) catalytic scavengers.

Fluorogenic organophosphate inhibitors of acetylcholinesterase (AChE) homologous in structure to nerve agents provide useful probes for high throughput screening of mammalian paraoxonase (PON1) libraries generated by directed evolution of an engineered PON1 variant with wild-type like specificity (rePON1). Wt PON1 and rePON1 hydrolyze preferentially the less-toxic R(P) enantiomers of nerve agents and of their fluorogenic surrogates containing the fluorescent leaving group, 3-cyano-7-hydroxy-4-methylcoumarin (CHMC). To increase the sensitivity and reliability of the screening protocol so as to directly select rePON1 clones displaying stereo-preference towards the toxic S(P) enantiomer, and to determine accurately K(m) and k(cat) values for the individual isomers, two approaches were used to obtain the corresponding S(P) and R(P) isomers: (a) stereo-specific synthesis of the O-ethyl, O-n-propyl, and O-i-propyl analogs and (b) enzymic resolution of a racemic mixture of O-cyclohexyl methylphosphonylated CHMC. The configurational assignments of the S(P) and R(P) isomers, as well as their optical purity, were established by X-ray diffraction, reaction with sodium fluoride, hydrolysis by selected rePON1 variants, and inhibition of AChE. The S(P) configuration of the tested surrogates was established for the enantiomer with the more potent anti-AChE activity, with S(P)/R(P) inhibition ratios of 10-100, whereas the R(P) isomers of the O-ethyl and O-n-propyl were hydrolyzed by wt rePON1 about 600- and 70-fold faster, respectively, than the S(P) counterpart. Wt rePON1-induced R(P)/S(P) hydrolysis ratios for the O-cyclohexyl and O-i-propyl analogs are estimated to be >>1000. The various S(P) enantiomers of O-alkyl-methylphosphonyl esters of CHMC provide suitable ligands for screening rePON1 libraries, and can expedite identification of variants with enhanced catalytic proficiency towards the toxic nerve agents.

Clinician-patient communication: evidence-based recommendations to guide practice in cancer.

GOALS OF WORK: To develop recommendations for effective communication between cancer health care providers and patients based on a systematic review of methods of clinician-patient communication that may affect patient outcomes associated with distress at critical points in the course of cancer care. MATERIALS AND METHODS: A systematic review of the literature was conducted, and evidence-based recommendations were formulated to guide clinician-patient communication in cancer care. A formal external review was conducted to validate the relevance of these recommendations. MAIN RESULTS: Recommendations for communication in cancer care are presented, based on guidelines from the Australian National Breast Cancer Centre and the Australian National Cancer Control Initiative,an updated systematic review of the research evidence, and a consensus by the Clinician-Patient Communications Working Panel of the Program in Evidence-Based Care of Cancer Care Ontario. The recommendations were sent to 110 Ontario practitioners for external review: 33 responded (30% response rate). Most of these respondents (87%) agreed with the draft recommendations and approved of their use as a practice guideline (90%). A condensed version of the recommendations, including 10 key points, was also created. CONCLUSIONS: There is evidence to support general clinician-patient communication approaches, although the preferences of cancer patients regarding such communication exhibit individual and cultural variability. Recommendations are provided, based on evidence, the consensus of an expert panel, and feedback from a survey of external practitioners. Evidence evaluating the role of decision aids and strategies to facilitate better communication is inconsistent, although such tools may be of value for some patients.

A mixed-method evaluation of nurse-led community-based supportive cancer care.

GOALS OF WORK: The study purpose was to evaluate a nurse-led supportive care clinical case management program in the community using multi-methods to delineate care processes prior to outcome evaluation. MATERIALS AND METHODS: Multiple data sources including program service records, chart reviews and interviews with nurses and key interdisciplinary informants were used to identify population served (coverage and reach), processes of care (implementation), and providers' perceptions of the effectiveness of the nurse-led program (reaction). MAIN RESULTS: The program provided care to over 700 cancer patients in a 1-year period. Nurse-led support interventions were focused on direct care inclusive of teaching/coaching for symptom management, counseling and support, and mobilization of services through system navigation based on an initial comprehensive assessment of supportive care needs. CONCLUSIONS: Nurse-led models of supportive care have the potential to reduce unmet supportive care needs, improve continuity of care, and overall health-related quality of life that should be tested in future trials.

Structural disorder serves as a weak signal for intracellular protein degradation.

Targeted turnover of proteins is a key element in the regulation of practically all basic cellular processes. The underlying physicochemical and/or sequential signals, however, are not fully understood. This issue is particularly pertinent in light of the recent recognition that intrinsically unstructured/disordered proteins, common in eukaryotic cells, are extremely susceptible to proteolytic degradation in vitro. The in vivo half-lives of proteins were determined recently in a high-throughput study encompassing the entire yeast proteome; here we examine whether these half-lives correlate with the presence of classical degradation motifs (PEST region, destruction-box, KEN-box, or the N-terminal residue) or with various physicochemical characteristics, such as the size of the protein, the degree of structural disorder, or the presence of low-complexity regions. Our principal finding is that, in general, the half-life of a protein does not depend on the presence of degradation signals within its sequence, even of ubiquitination sites, but correlates mainly with the length of its polypeptide chain and with various measures of structural disorder. Two distinct modes of involvement of disorder in degradation are proposed. Susceptibility to degradation of longer proteins, containing larger numbers of residues in conformational disorder, suggests an extensive function, whereby the effect of disorder can be ascribed to its mere physical presence. However, after normalization for protein length, the only signal that correlates with half-life is disorder, which indicates that it also acts in an intensive manner, that is, as a specific signal, perhaps in conjunction with the recognition of classical degradation motifs. The significance of correlation is rather low; thus protein degradation is not determined by a single characteristic, but is a multi-factorial process that shows large protein-to-protein variations. Protein disorder, nevertheless, plays a key signalling role in many cases.

Bivalent ligands derived from Huperzine A as acetylcholinesterase inhibitors.

The naturally occurring alkaloid Huperzine A (HupA) is an acetylcholinesterase (AChE) inhibitor that has been used for centuries as a Chinese folk medicine in the context of its source plant Huperzia Serrata. The potency and relative safety of HupA rendered it a promising drug for the ameliorative treatment of Alzheimer's disease (AD) vis-à-vis the "cholinergic hypothesis" that attributes the cognitive decrements associated with AD to acetylcholine deficiency in the brain. However, recent evidence supports a neuroprotective role for HupA, suggesting that it could act as more than a mere palliative. Biochemical and crystallographic studies of AChE revealed two potential binding sites in the active-site gorge of AChE, one of which, the "peripheral anionic site" at the mouth of the gorge, was implicated in promoting aggregation of the beta amyloid (Abeta) peptide responsible for the neurodegenerative process in AD. This feature of AChE facilitated the development of dual-site binding HupA-based bivalent ligands, in hopes of concomitantly increasing AChE inhibition potency by utilizing the "chelate effect", and protecting neurons from Abeta toxicity. Crystal structures of AChE allowed detailed modeling and docking studies that were instrumental in enhancing the understanding of underlying principles of bivalent inhibitor-enzyme dynamics. This monograph reviews two categories of HupA-based bivalent ligands, in which HupA and HupA fragments serve as building blocks, with a focus on the recently solved crystallographic structures of Torpedo californica AChE in complex with such bifunctional agents. The advantages and drawbacks of such structured-based drug design, as well as species differences, are highlighted and discussed.

Honing the in silico toolkit for detecting protein disorder.

Not all proteins form well defined three-dimensional structures in their native states. Some amino-acid sequences appear to strongly favour the disordered state, whereas some can apparently transition between disordered and ordered states under the influence of changes in the biological environment, thereby playing an important role in processes such as signalling. Although important biologically, for the structural biologist disordered regions of proteins can be disastrous even preventing successful structure determination. The accurate prediction of disorder is therefore important, not least for directing the design of expression constructs so as to maximize the chances of successful structure determination. Such design criteria have become integral to the construct-design strategies of laboratories within the Structural Proteomics In Europe (SPINE) consortium. This paper assesses the current state of the art in disorder prediction in terms of prediction reliability and considers how best to use these methods to guide construct design. Finally, it presents a brief discussion as to how methods of prediction might be improved in the future.