Exploring a case for education about sexual and gender minorities in postgraduate emergency medicine training: forming recommendations for change.

Social medicine and health advocacy curricula are known to be uncommon in postgraduate medical education. As justice movements work to unveil the systemic barriers experienced by sexual and gender minority (SGM) populations, it is imperative that the emergency medicine (EM) community progress in its efforts to provide equitable, accessible, and competent care for these vulnerable groups. Given the paucity of literature on this subject in the context of EM in Canada, this commentary borrows evidence from other specialties across North America. Trainees across specialties and of all stages are caring for an increasing number of SGM patients. Lack of education at all levels of training is identified as a significant barrier to adequately caring for these populations, thereby precipitating significant health disparities. Cultural competency is often mistakenly attributed to a willingness to treat rather than the provision of quality care. However, positive attitudes do not necessarily correlate with trainee knowledge. Barriers to creating and implementing culturally competent curricula are plentiful, yet facilitating policies and resources are rare. While international bodies continuously publish position statements and calls to action, concrete change is seldom made. The scarcity of SGM curricula can be attributed to the universal absence of formal acknowledgment of SGM health as a required competency by accreditation boards and professional membership associations. This commentary synthesizes hand-picked literature in an attempt to inform healthcare professionals on their journey toward developing culturally competent postgraduate medical education. By thematically organizing evidence into a stepwise approach, the goal of this article is to borrow ideas across medical and surgical specialties to inform the creation of recommendations and make a case for an SGM curriculum for EM programs in Canada.

Education about sexual and gender minorities within Canadian emergency medicine residency programs.

OBJECTIVES: The CAEP 2021 2SLGBTQIA +i panel sought whether a gap exists within Canadian emergency medicine training pertaining to sexual and gender minority communities. This panel aimed to generate practical recommendations on improving emergency medicine education about sexual and gender minorities, thereby improving access to equitable healthcare. METHODS: From August 2020 to June 2021, a panel of emergency medicine practitioners, residents, students, and community representatives met monthly via videoconference. A literature review was undertaken, and three mixed methods surveys were distributed to the CAEP member list, CAEP Resident Section, College of Family Physicians of Canada (CFPC)iii Emergency Medicine Members Interest Group, and to emergency medicine residency program directors and their residents. Informed by the review and surveys, recommendations were drafted and refined by panel members before presentation at the 2021 CAEP Academic Symposium. A plenary was presented to symposium attendees composed of national emergency medicine community members, which reported the survey results and literature review. All attendees were divided into small groups to develop an action plan for each recommendation. CONCLUSIONS: The panel outlines eight recommendations for closing the curricular gap. It identifies three perceived or real barriers to the inclusion of sexual and gender minority content in emergency medicine residency curricula. It acknowledges three enabling recommendations that are beyond the scope of individual emergency medicine programs or emergency departments (EDs), that if enacted would enable the implementation of the recommendations. Each recommendation is accompanied by two action items as a guide to implementation. Each of the three barriers is accompanied by two action items that offer specific solutions to overcome these obstacles. Each enabling recommendation suggests an action that would shift emergency medicine towards sociocultural competence nationally. These recommendations set the primary steps towards closing the educational gap.

RéSUMé: OBJECTIFS: Le panel ACMU 2021 2SLGBTQIA+ i a cherché à savoir s'il existe une lacune dans la formation en médecine d'urgence au Canada en ce qui concerne les communautés de minorités sexuelles et de genre. Ce panel visait à générer des recommandations pratiques sur l'amélioration de l'éducation en médecine d'urgence sur les minorités sexuelles et de genre, améliorant ainsi l'accès à des soins de santé équitables. MéTHODES: D'août 2020 à juin 2021, un groupe de praticiens en médecine d'urgence, de résidents, d'étudiants et de représentants communautaires se sont réunis chaque mois par vidéoconférence. Une revue de la littérature a été entreprise et trois enquêtes à méthodes mixtes ont été distribuées à la liste des membres de l'ACMU, à la Section des résidents de l'ACMU, au Groupe d'intérêt des membres en médecine d'urgence du Collège des médecins de famille du Canada (CMFC) iii, ainsi qu'aux directeurs des programmes de résidence en médecine d'urgence et à leurs résidents. À la lumière de l'examen et des sondages, les recommandations ont été rédigées et peaufinées par les membres du comité avant d'être présentées au Symposium universitaire de l'ACMU de 2021. Une séance plénière a été présentée aux participants du symposium, composés de membres de la communauté nationale de la médecine d'urgence, qui ont fait état des résultats du sondage et de la revue de la littérature. Tous les participants ont été répartis en petits groupes afin d'élaborer un plan d'action pour chaque recommandation. CONCLUSIONS: Le groupe d'experts formule huit recommandations pour combler le fossé entre les programmes d'enseignement. Il identifie trois obstacles perçus ou réels à l'inclusion du contenu sur les minorités sexuelles et de genre dans les programmes de résidence en médecine d'urgence. Il reconnaît trois recommandations habilitantes qui dépassent la portée des programmes de médecine d'urgence individuels ou des services d'urgence (SU) et qui, si elles étaient adoptées, permettraient la mise en œuvre des recommandations. Chaque recommandation est accompagnée de deux mesures de suivi comme guide de mise en œuvre. Chacun des trois obstacles est accompagné de deux éléments d'action qui offrent des solutions spécifiques pour surmonter ces obstacles. Chaque recommandation habilitante suggère une action qui ferait évoluer la médecine d'urgence vers une compétence socioculturelle au niveau national. Ces recommandations établissent les principales étapes pour combler l'écart en matière d'éducation.

Attitudes, behaviour, and comfort of Canadian emergency medicine residents and physicians in caring for 2SLGBTQI+ patients.

OBJECTIVES: Physicians working in the emergency department (ED) will interact with two-spirited, lesbian, gay, bisexual, transgender, queer/questioning and intersex (2SLGBTQI+) persons as colleagues and patients. These patients have unique healthcare needs and encounter negative experiences when seeking medical care, leading to poorer health outcomes and inequities. This study aims to explore the attitudes, behaviour, and comfort of Canadian emergency medicine (EM) physicians in caring for 2SLGBTQI+ patients. METHODS: An anonymous survey was distributed to EM staff physicians and residents through the Canadian Association of Emergency Physicians (CAEP) network and social media channels. Demographic information was collected, and participants were asked about their comfort, current knowledge, and desire to gain new knowledge in caring for 2SLGBTQI+ patients. Personal perceptions and practice patterns in treating cisgender heterosexual (cis-het) and 2SLGBTQI+ patients were analysed using five-point Likert scales. Residents were asked additional questions regarding availability of learning experiences during training. RESULTS: 266 surveys were included in the final analysis consisting of 229 (86%) staff physicians and 37 (14%) residents. 97% (n = 258) of all respondents believed 2SLGBTQI+ patients deserve the same quality care from medical institutions as other patients. Further, 83% (n = 221) respondents agreed that they would like to increase their knowledge in taking care of 2SLGBTQI+ patients, while 34% (n = 91) agreed that performing physical examinations on transgender or intersex patients was more challenging than on cis-het patients. Among resident respondents, 46% indicated a lack of didactic teaching devoted to 2SLGBTQI+ care during residency (n = 17/37), while 38% encountered discrimination towards 2SLGBTQI+ patients, with most comments from senior faculty and nursing staff. CONCLUSIONS: This study suggests that Canadian EM physicians feel that 2SLGBTQI+ patients deserve equitable care when compared to cis-het patients. Future work should focus on educational needs and curricular enhancements in residency programs and continuing professional development for physicians to improve care for 2SLGBTQI+ patients in the ED.

RéSUMé: OBJECTIFS: Les médecins travaillant dans les services d'urgence interagiront avec des personnes bispirituelles, lesbiennes, gaies, bisexuelles, transgenres, queer/en questionnement et intersexes (2SLGBTQI+) en tant que collègues et patients. Ces patients ont des besoins uniques en matière de soins de santé et vivent des expériences négatives lorsqu'ils cherchent à obtenir des soins médicaux, ce qui entraîne des résultats moins bons en matière de santé et des inégalités. Cette étude vise à explorer les attitudes, les comportements et le confort des médecins d'urgence canadiens dans la prise en charge des patients 2SLGBTQI+. MéTHODES: Un sondage anonyme a été distribué aux médecins membres du personnel d'urgence et aux résidents par l'intermédiaire du réseau de l'Association canadienne des médecins d'urgence et des canaux de médias sociaux. Des informations démographiques ont été recueillies, et les participants ont été interrogés sur leur confort, leurs connaissances actuelles et leur désir d'acquérir de nouvelles connaissances sur la prise en charge des patients 2SLGBTQI+. Les perceptions personnelles et les modèles de pratique dans le traitement des patients cisgenre-hétérosexuels (cis-het) et 2SLGBTQI+ ont été analysés à l'aide d'échelles de Likert à cinq points. Des questions supplémentaires ont été posées aux résidents concernant la disponibilité des expériences d'apprentissage pendant la formation. RéSULTATS: 266 sondages ont été inclus dans l'analyse finale consistant en 229 (86 %) médecins du personnel et 37 (14 %) résidents. 97 % (n = 258) de tous les répondants pensent que les patients 2SLGBTQI+ méritent la même qualité de soins de la part des institutions médicales que les autres patients. En outre, 83 % (n = 221) des répondants ont convenu qu'ils aimeraient améliorer leurs connaissances dans la prise en charge des patients 2SLGBTQI+, tandis que 34 % (n = 91) ont convenu que la réalisation d'examens physiques sur des patients transgenres ou intersexes était plus difficile que sur des patients cis-het. Parmi les répondants résidents, 46 % ont indiqué un manque d'enseignement didactique consacré aux soins 2SLGBTQI+ pendant la résidence (n = 17/37), tandis que 38 % ont été victimes de discrimination à l'égard des patients 2SLGBTQI+, la plupart des commentaires provenant du corps professoral supérieur et du personnel infirmier. CONCLUSIONS: Cette étude suggère que les médecins d'urgence canadiens estiment que les patients 2SLGBTQI+ méritent des soins équitables par rapport aux patients cis-het. Les travaux futurs devraient se concentrer sur les besoins éducatifs et l'amélioration des programmes d'études dans les programmes de résidence et le développement professionnel continu des médecins afin d'améliorer les soins aux patients 2SLGBTQI+ dans les urgences.

Factors Associated with Family Physician Follow-up 30 Days Post-discharge from a Local Canadian Community Emergency Department.

Introduction Close outpatient follow-up with a specialist or family physician post-discharge from the emergency department (ED) has been shown to increase adherence to antihypertensive medications, decrease mortality in heart failure, and reduce the odds of myocardial infarction or death after ED presentation for chest pain. A Canadian study demonstrated that 21% of patients who left the ED with a new diagnosis of atrial fibrillation, heart failure, or hypertension were not seen by a physician within 30 days. There is a paucity of research investigating why this follow-up does not occur. This study aimed to elucidate factors that are associated with outpatient follow-up by a family physician clinic following discharge from a local Canadian community emergency department. Methods A retrospective chart review of patients rostered to a family physician who presented to the community ED in the past two years was conducted. The primary outcome examined was a documented follow-up visit with any physician at the clinic within 30 days of the index ED visit. Patients aged 18 or older at the time of the initial ED visit were eligible for inclusion in the study. Exclusion criteria were the following: patients aged 17 or younger at the time of the initial ED visit, those who were not fully assessed at ED visit (i.e., left against medical advice), those whose charts corresponding to the ED visit were unable to be found, patients who were admitted to any facility within 30 days of ED visit, and patients who died within 30 days of the ED visit. Variables of interest extracted from the ED chart and clinic electronic medical record were the following: Canadian Triage and Acuity Scale (CTAS) score, documented discharge instructions, age, sex, primary residence distance from the clinic, last documented clinic visit before ED visit, and the date of and presenting complaint of the next clinic visit after the ED visit. Data were collected as continuous and categorical variables. Descriptive statistics were used to show the number and percentages of patients who followed up in clinic. Binomial regression analysis was used to determine if a specific variable was associated with patient follow-up. Inter-rater reliability between data abstractors was calculated using Fleiss Κ. An alpha-value of 0.05 was chosen, and SPSS version 25.0 (IBM Corp., Armonk, NY) was used for all statistical analyses. Results A total of 234 patients out of 1292 patients met inclusion criteria. 53% of patients were female, and the mean age was 50. Seventy-two (31%) received discharge instructions from the ED physician to follow up with their family doctor. In total, 93 of the 234 patients proceeded to have a documented clinic visit within 30 days (40%). 52% (n = 48) of these were women. Receiving specific discharge instructions increased the adjusted odds of follow-up (OR 3.07, 95% CI: 1.64-5.76; P < 0.05). Patients who followed up also tended to have been seen in clinic in the last three months, but this was not statistically significant. Conclusion Receiving specific discharge instructions to follow-up increased the odds that patients followed up with their family physician after discharge from the ED. ED physicians may consider giving explicit instructions to patients to improve monitoring of ongoing clinical issues. More research needs to be conducted on how to improve transitions of care. Countries with different healthcare models may have other barriers to appropriate follow-up.

A Randomized Comparative Trial of the Knowledge Retention and Usage Conditions in Undergraduate Medical Students Using Podcasts and Blog Posts.

Introduction Podcasts and blog posts have gained popularity in Free Open Access Medical education (FOAM). Previous work suggests that podcasts may be useful for knowledge acquisition in undergraduate medical education. However, there remains a paucity of research comparing the two mediums. This study aims to investigate if there are differences in knowledge acquisition and usage conditions by medical students using podcasts and blog posts. Methods Medical students were randomized to either the podcast or blog post group. They completed an initial online assessment of their baseline knowledge on the subject matter. Participants then received access to learning materials and were given four weeks to complete the follow-up assessment on their own time. Independent t-test, paired samples t-test, and a mixed ANOVA (analysis of variance) were conducted to assess knowledge acquisition. An intention-to-teach analysis was used to impute missing data from students lost to follow-up. Simple descriptive statistical data was used to describe media usage conditions. Results Completion of at least one follow-up assessment was comparable (68% podcasts (n = 21/31), 73% blog posts (n = 22/30)). Both groups showed significant improvements in their test scores, with an average 22% improvement for the podcast group and 29% for the blog post group. There was no significant statistical difference in knowledge acquisition between educational modalities overall. Students in the blog post group that completed both post-intervention quizzes showed a larger improvement than the podcast group in the toxicology topic, with similar improvements in the asthma topic. The podcast group tended to engage in multiple activities while using the learning materials (e.g. at least two to three of the following: driving, eating, chores, taking notes, exercising/walking), while the blog readers tended to do fewer activities (e.g. only one of the following: note taking, eating). Conclusion This study suggests that podcasts and blog posts are useful for extracurricular knowledge acquisition by undergraduate medical students with no significant difference between the two modalities. The usage conditions for each type of media differ.

Neoadjuvant treatments for locally advanced, resectable esophageal cancer: A network meta-analysis.

The relative survival benefits and postoperative mortality among the different types of neoadjuvant treatments (such as chemotherapy only, radiotherapy only or chemoradiotherapy) for esophageal cancer patients are not well established. To evaluate the relative efficacy and safety of neoadjuvant therapies in resectable esophageal cancer, a Bayesian network meta-analysis was performed. MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched for publications up to May 2016. ASCO and ASTRO annual meeting abstracts were also searched up to the 2015 conferences. Randomized controlled trials that compared at least two of the following treatments for resectable esophageal cancer were included: surgery alone, surgery preceded by neoadjuvant chemotherapy, neoadjuvant radiotherapy or neoadjuvant chemoradiotherapy. The primary outcome assessed from the trials was overall survival. Thirty-one randomized controlled trials involving 5496 patients were included in the quantitative analysis. The network meta-analysis showed that neoadjuvant chemoradiotherapy improved overall survival when compared to all other treatments including surgery alone (HR 0.75, 95% CR 0.67-0.85), neoadjuvant chemotherapy (HR 0.83. 95% CR 0.70-0.96) and neoadjuvant radiotherapy (HR 0.82, 95% CR 0.67-0.99). However, the risk of postoperative mortality increased when comparing neoadjuvant chemoradiotherapy to either surgery alone (RR 1.46, 95% CR 1.00-2.14) or to neoadjuvant chemotherapy (RR 1.58, 95% CR 1.00-2.49). In conclusion, neoadjuvant chemoradiotherapy improves overall survival but may also increase the risk of postoperative mortality in patients locally advanced resectable esophageal carcinoma.

A network meta-analysis of the sequencing and types of systemic therapies with definitive radiotherapy in locally advanced squamous cell carcinoma of the head and neck (LASCCHN)☆.

OBJECTIVES: The current standard therapy for locally advanced squamous cell carcinoma of the head and neck (LASCCHN) is platinum-based chemotherapy plus concurrent radiotherapy (CRT), but several systemic therapies have been evaluated. We performed a Bayesian network meta-analysis (NMA) with random effects to enable direct and indirect comparisons of all existing treatment modalities for LASCCHN simultaneously. MATERIAL AND METHODS: A systematic review was conducted using MEDLINE, EMBASE, ASCO abstracts, ASTRO abstracts and the Cochrane Central of Registered Trials using Cochrane methodology to identify randomized controlled trials (RCTs) up to June 2016. Only abstracts that involved the same definitive radiotherapy in the arms for the RCT were included. RESULTS: Sixty-five RCTs involving 13,574 patients and 16 different treatment strategies were identified. Chemotherapy plus concurrent radiation (CRT) was superior to RT with a HR of 0.74 (95%CR 0.69-0.79) for OS in the NMA. Only 3 trials compared RT alone to concurrent therapy with an EGFR antibody (ERT), demonstrating a superior OS (HR 0.75, 95% CR 0.60-0.94), but this difference was not statistically significant when interpreted in a NMA (HR 0.84, 95%CR 0.65-1.08). ERT was not superior to CRT (HR 1.19, 95%CR 0.93-1.54), and the addition of neo-adjuvant taxane-based chemotherapy to CRT was not beneficial (HR 0.86, 95% CR 0.70-1.07). CONCLUSION: The addition of either adjuvant or neoadjuvant chemotherapy to the CRT backbone does not confer an OS benefit in the treatment of LASCCHN. Similarly, ERT does not confer an OS benefit for patients who are eligible for CRT.

Cost-Effectiveness Analysis of Systemic Therapies in Advanced Pancreatic Cancer in the Canadian Health Care System.

OBJECTIVES: To assess the cost-effectiveness of gemcitabine (G), G + 5-fluorouracil, G + capecitabine, G + cisplatin, G + oxaliplatin, G + erlotinib, G + nab-paclitaxel (GnP), and FOLFIRINOX in the treatment of advanced pancreatic cancer from a Canadian public health payer's perspective, using data from a recently published Bayesian network meta-analysis. METHODS: Analysis was conducted through a three-state Markov model and used data on the progression of disease with treatment from the gemcitabine arms of randomized controlled trials combined with estimates from the network meta-analysis for the newer regimens. Estimates of health care costs were obtained from local providers, and utilities were derived from the literature. The model estimates the effect of treatment regimens on costs and quality-adjusted life-years (QALYs) discounted at 5% per annum. RESULTS: At a willingness-to-pay (WTP) threshold of greater than $30,666 per QALY, FOLFIRINOX would be the most optimal regimen. For a WTP threshold of $50,000 per QALY, the probability that FOLFIRINOX would be optimal was 57.8%. There was no price reduction for nab-paclitaxel when GnP was optimal. CONCLUSIONS: From a Canadian public health payer's perspective at the present time and drug prices, FOLFIRINOX is the optimal regimen on the basis of the cost-effectiveness criterion. GnP is not cost-effective regardless of the WTP threshold.

Association of hospital and physician case volumes with cardiac monitoring and cardiotoxicity during adjuvant trastuzumab treatment for breast cancer: a retrospective cohort study.

BACKGROUND: Adjuvant trastuzumab is the standard of care for patients with HER2 overexpressing breast cancer, but use of trastuzumab may lead to cardiotoxicity. Our goal was to evaluate the relationship between hospital and physician case volume and cardiac outcomes in this population. METHODS: In this retrospective cohort study, we identified all female patients in Ontario with a breast cancer diagnosis in 2003-2009 who underwent treatment with trastuzumab through a provincial drug-funding program and linked these patients to administrative databases to ascertain patient demographics, treating hospital and physician characteristics, admissions to hospital, cardiac risk factors, cardiac imaging and comorbidities. Insufficient cardiac monitoring was defined as per the Canadian Trastuzumab Working Group guideline. Cardiotoxicity was defined as receiving fewer than 16 of 18 doses of trastuzumab because of heart failure admission, heart failure diagnosis or discontinuation of the drug after cardiac imaging. We constructed hierarchical multivariable logistic regression models to evaluate the effect of annual hospital volume, cumulative physician volume and treatment period on cardiac monitoring and cardiotoxicity. RESULTS: Of 3777 women treated by 214 oncologists at 68 hospitals, 918 (24.3%) had insufficient cardiac monitoring and cardiotoxicity developed in 640 (16.9%). Cardiotoxicity occurred in 389 (42.4%) and 251 (8.8%) patients in the insufficient- and sufficient-monitoring groups, respectively. Higher annual hospital and cumulative physician volumes, and more recent calendar period, were all independent predictors for decreased cardiotoxicity. Adjustment for rates of cardiac monitoring annulled the relationships between case volume and cardiotoxicity. INTERPRETATION: Greater hospital and physician case volumes are associated with reduced rates of trastuzumab-related cardiotoxicity, most likely because of better cardiac monitoring at higher volume centres.

Cost-Effectiveness Analysis of Different Sequences of the Use of Epidermal Growth Factor Receptor Inhibitors for Wild-Type KRAS Unresectable Metastatic Colorectal Cancer.

PURPOSE: Patients with unresectable wild-type KRAS metastatic colorectal cancer benefit from fluoropyrimidines (FP), oxaliplatin (O), irinotecan (I), bevacizumab (Bev), and epithelial growth factor receptor inhibitors (EGFRI). The most cost-effective regimen remains unclear. METHODS: A Markov model was constructed to examine the costs and outcomes of three treatment strategies: strategy A (reference strategy): EGFRI monotherapy in third line ([3L]; ie, first-line [1L]: Bev + FOLFIRI [FP + I] or FOLFOX [FP + O]; second line [2L]: FOLFIRI/FOLFOX; 3L: EGFRI); strategy B: EGFRI and I in 3L (ie, 1L: Bev + FOLFIRI/FOLFOX; 2L: FOLFIRI/FOLFOX; 3L: EGFRI + I); and strategy C: EGFRI in 1L (ie, 1L: EGFRI + FOLFIRI/FOLFOX; 2L: Bev + FOLFIRI/FOLFOX; 3L: best supportive care). Efficacy data of the treatments were obtained from the literature. Health system resource use information was derived from chart review and the literature. Using Euro-QOL 5 Dimensions, utilities were obtained by surveying medical oncologists and costs from the Ontario Ministry of Health and the literature. The perspective of the Canadian public health care system was used over a 5-year time horizon with a 5% discount in 2012 Canadian dollars. RESULTS: All three strategies had similar efficacy, but strategy C was most expensive. The incremental cost-effectiveness ratios (ICERs) for strategies B and C compared with A were 119,623 and 3,176,591, respectively. The model was primarily driven by the acquisition cost of the drugs. Strategy B was most cost effective when the willingness-to-pay threshold was > $130,000 per quality-adjusted life-year. Sensitivity analysis showed that strategy C would be cost-effective only when the progression-free survival of EGFRI is better than Bev in 1L with hazard ratio < 0.23 at willingness-to-pay of $150,000 per quality-adjusted life-year. CONCLUSION: First-line use of EGFRI in metastatic colorectal cancer is not cost effective at its current pricing relative to Bev.

The Temporal Risk of Heart Failure Associated With Adjuvant Trastuzumab in Breast Cancer Patients: A Population Study.

BACKGROUND: The late cardiac effect of adjuvant trastuzumab and its potential interaction with anthracycline have not been well-studied on a population level. METHODS: In this retrospective population-based cohort study, female breast cancer patients in Ontario, diagnosed between 2003 and 2009, were identified by the Ontario Cancer Registry and linked to administrative databases to ascertain demographics, cardiac risk factors, comorbidities, and use of adjuvant trastuzumab and other chemotherapy. Patients with pre-existing heart failure (HF) were excluded. The main endpoint was new diagnosis of HF. Analyses included Kaplan-Meier (KM) survival analysis, multivariable piecewise Cox regression, and competing risk and propensity score analyses. All statistical tests were two-sided. RESULTS: Nineteen thousand seventy-four women with breast cancer treated with adjuvant chemotherapy were identified, of whom 3371 (17.7%) also received adjuvant trastuzumab. Anthracycline use was 84.9% overall. After a median follow-up of 5.9 years, patients treated with trastuzumab and chemotherapy were more likely to develop HF than patients on chemotherapy alone (5-year cumulative incidences of 5.2% vs 2.5%; log-rank P < .001). After adjusting for confounders, adjuvant trastuzumab remained independently associated with incident HF in the first 1.5 years (HR = 5.77, 95% CI = 4.38 to 7.62, P < .001), but not thereafter (HR = 0.87, 95% CI = 0.57 to 1.33, P = .53). Anthracycline use did not increase the risk of HF with trastuzumab synergistically, neither within (P interaction = .92) nor beyond 1.5 years (P interaction = .23). CONCLUSION: Adjuvant trastuzumab was associated with increased risk of new incidence of HF in breast cancer survivors during the period of adjuvant treatment but not thereafter. Routine intensive monitoring may not be necessary after completing adjuvant therapy.

The use of EGFR inhibitors in colorectal cancer: is it clinically efficacious and cost-effective?

Cetuximab (Erbitux) and panitumumab (Vectibix) are monoclonal antibodies to the EGFR. They are used as monotherapy or in combination with cytotoxic chemotherapy and increase both progression-free survival and overall survival in patients with wild-type RAS metastatic colorectal cancer. The most common side effects of therapy are dermatological, including skin (acneiform) rash, pruritus and hair changes. Despite their clinical activity, cost-effectiveness of the two drugs should be addressed in a discussion of their usage in everyday care. This study provides an up-to-date review of the clinical efficacy and cost-effectiveness of anti-EGFR inhibitors.

A Bayesian meta-analysis of multiple treatment comparisons of systemic regimens for advanced pancreatic cancer.

BACKGROUND: For advanced pancreatic cancer, many regimens have been compared with gemcitabine (G) as the standard arm in randomized controlled trials. Few regimens have been directly compared with each other in randomized controlled trials and the relative efficacy and safety among them remains unclear. METHODS: A systematic review was performed through MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and ASCO meeting abstracts up to May 2013 to identify randomized controlled trials that included advanced pancreatic cancer comparing the following regimens: G, G+5-fluorouracil, G+ capecitabine, G+S1, G+ cisplatin, G+ oxaliplatin, G+ erlotinib, G+ nab-paclitaxel, and FOLFIRINOX. Overall survival and progression-free survival with 95% credible regions were extracted using the Parmar method. A Bayesian multiple treatment comparisons was performed to compare all regimens simultaneously. RESULTS: Twenty-two studies were identified and 16 were included in the meta-analysis. Median overall survival, progression free survival, and response rates for G arms from all trials were similar, suggesting no significant clinical heterogeneity. For overall survival, the mixed treatment comparisons found that the probability that FOLFIRINOX was the best regimen was 83%, while it was 11% for G+ nab-paclitaxel and 3% for G+ S1 and G+ erlotinib, respectively. The overall survival hazard ratio for FOLFIRINOX versus G+ nab-paclitaxel was 0.79 [0.50-1.24], with no obvious difference in toxicities. The hazard ratios from direct pairwise comparisons were consistent with the mixed treatment comparisons results. CONCLUSIONS: FOLFIRINOX appeared to be the best regimen for advanced pancreatic cancer probabilistically, with a trend towards improvement in survival when compared with other regimens by indirect comparisons.

A systematic literature analysis of correlative studies in low-dose metronomic chemotherapy trials.

Low-dose metronomic (LDM) chemotherapy is a beneficial and very well-tolerated form of chemotherapy utilization characterized by the frequent and uninterrupted administration of low doses of conventional chemotherapeutic agents over prolonged periods of time. While patients resistant to standard maximum tolerated dose (MTD) chemotherapy may still benefit from LDM chemotherapy, there is a lack of predictive markers of response to LDM chemotherapy. We searched the MEDLINE, EMBASE, CENTRAL and PubMed databases for correlative studies conducted as part of LDM chemotherapy trials in order to identify the most promising biomarker candidates. Given the antiangiogenic properties of LDM chemotherapy, angiogenesis-related biomarkers were most commonly studied. However, significant correlations between angiogenesis-related biomarkers and study end points were rare and variable, even so far as biomarkers correlating positively with an end point in some studies and negatively with the same end point in other studies. Pursuing biomarkers outside the angiogenesis field may be more promising.