A comparison of educational events for physicians and nurses in Australia sponsored by opioid manufacturers.

BACKGROUND: Educational activities for physicians sponsored by opioid manufacturers are implicated in the over- and mis-prescribing of opioids. However, the implications of promotion to nurses are poorly understood. Nurses play a key role in assessing pain, addressing the determinants of pain, and administering opioid medications. We sought to understand the nature and content of pain-related educational events sponsored by opioid manufacturers and to compare events targeting physicians and nurses. METHODS: We conducted a cross sectional, descriptive analysis of pharmaceutical company reports detailing 116,845 sponsored educational events attended by health professionals from 2011 to 2015 in Australia. We included events that were sponsored by manufacturers of prescription opioid analgesics and were pain related. We compared event characteristics across three attendee groups: (a) physicians only; (b) at least one nurse in attendance; and (c) nurses only. We coded the unstructured data using iteratively generated keywords for variables related to location, format, and content focus. RESULTS: We identified 3,411 pain-related events sponsored by 3 companies: bioCSL/CSL (n = 15), Janssen (n = 134); and Mundipharma (n = 3,262). Pain-related events were most often multidisciplinary, including at least one nurse (1,964/3,411; 58%); 38% (1,281/3,411) included physicians only, and 5% (166/3,411) nurses only. The majority of events were held in clinical settings (61%) and 43% took the form of a journal club. Chronic pain was the most common event topic (26%) followed by cancer pain and palliative care (18%), and then generic or unspecified references to pain (15%); nearly a third (32%) of event descriptions contained insufficient information to determine the content focus. Nurse-only events were less frequently held in clinical settings (32%; p < .001) and more frequently were product launches (17%; p < .001) and a significantly larger proportion focused on cancer or palliative care (33%; p < .001), generic pain topics (27%; p < .001), and geriatrics (25%; p < .001) than physician-only or multidisciplinary events. DISCUSSION: Opioid promotion via sponsored educational events extends beyond physicians to multidisciplinary teams and specifically, nurses. Despite lack of evidence that opioids improve outcomes for long-term chronic non-cancer pain, hundreds of sponsored educational events focused on chronic pain. Regulators should consider the validity of distinguishing between pharmaceutical companies' "promotional" and "non-promotional" activities.

Optimising weight-loss interventions in cancer patients-A systematic review and network meta-analysis.

BACKGROUND: Excess weight has been associated with increased morbidity and a worse prognosis in adult patients with early-stage cancer. The optimal lifestyle interventions to optimize anthropometric measures amongst cancer patients and survivors remain inconsistent. OBJECTIVE: To conduct a systematic review and network meta-analysis (NMA) of randomized controlled trials (RCTs) comparing the effects of exercise and dietary interventions alone or in combination on anthropometric measures of adult cancer patients and survivors. METHODS: A systematic search of Medline, Embase and the Cochrane Trials Registry was performed. Outcomes of interest included changes in weight, body mass index (BMI), and waist circumference. Screening and data collection were performed by two reviewers. Bayesian NMAs were performed. RESULTS: Overall, 98 RCTs were included; 75 were incorporated in NMAs (n = 12,199). Groups of intervention strategies included: 3 exercise interventions, 8 dietary interventions, 7 combination interventions of diet and exercise and standard care. Median intervention duration was 26 weeks. NMA suggested that diet alone (mean difference [MD] -2.25kg, 95% CrI -3.43 to -0.91kg) and combination strategies (MD -2.52kg, 95% CrI -3.54 to -1.62kg) were associated with more weight loss compared to standard care. All dietary interventions achieved a similar magnitude of weight loss (MD range from -2.03kg to -2.52kg). Both diet alone and combination strategies demonstrated greater BMI reductions versus standard care, and each of diet alone, exercise alone and combination strategies demonstrated greater reductions in waist circumference than standard care. CONCLUSION: Diet and exercise alone or in combination are effective lifestyle interventions to improve anthropometric measures in cancer patients and survivors. All reputable diets appear to be similarly effective to achieve weight loss.

A randomised trial of 4- versus 12-weekly administration of bone-targeted agents in patients with bone metastases from breast or castration-resistant prostate cancer.

BACKGROUND: Optimal dosing of bone-targeted agents (BTAs), in patients with bone metastases remains an important clinical question. This trial compared 4-weekly versus 12-weekly therapy. PATIENTS AND METHODS: Patients with bone metastases from breast or castration-resistant prostate cancer (CRPC), who were going to start or already on BTAs, were randomised 1:1 to 4-weekly or 12-weekly BTA treatment for one year. Primary end point was change in health-related quality of life (HRQoL)-physical function European Organisation for Research and Treatment of Cancer (EORTC)-QLQ-C30). Secondary end points included pain (EORTC-QLQ-BM22), global health status (EORTC-QLQ-C30), symptomatic skeletal events (SSEs) rates and time to SSEs. Primary analysis was per protocol and a non-inferiority margin of 5 points was used. RESULTS: Of 263 patients (160 breast cancer, 103 CRPC), 133 (50.6%) and 130 (49.4%) were randomised to the 4- and 12-weekly groups, respectively. BTAs included denosumab (56.3%), zoledronate (24.0%) and pamidronate (19.8%). Using repeated-measures analysis, across all time points, patients in the 4-weekly arm had a mean HRQL-physical subdomain score which was 1.2 (95% confidence interval: -1.6 to 4.0) higher than the 12-weekly arm. The study met the definition of non-inferiority for our primary outcome. Secondary outcomes showed no significant difference in scores for pain, global health status, SSE rates and SSE-free survival between arms. Subgroup analyses for cancer type, prior BTA use or BTA type showed no significant difference between arms. CONCLUSION: These results in addition to those previously reported for de-escalating zoledronate and systematic reviews in both breast and prostate cancers, would support that de-escalation of commonly used BTAs is a reasonable treatment option.

Comparing Interventions for Management of Hot Flashes in Patients With Breast and Prostate Cancer: A Systematic Review With Meta-Analyses.

PROBLEM IDENTIFICATION: Hot flashes are common and bothersome in patients with breast and prostate cancer and can adversely affect patients' quality of life. LITERATURE SEARCH: Databases were searched for randomized controlled trials (RCTs) evaluating the effects of one or more interventions for hot flashes in patients with a history of breast or prostate cancer. DATA EVALUATION: Outcomes of interest included changes in hot flash severity, hot flash frequency, quality of life, and harms. Pairwise meta-analyses and network meta-analyses were performed where feasible, with narrative synthesis used where required. SYNTHESIS: 40 RCTs were included. Findings from network meta-analysis for hot flash frequency suggested that several therapies may offer benefits compared to no treatment, but little data suggested differences between active therapies. Findings from network meta-analysis for hot flash score were similar. IMPLICATIONS FOR RESEARCH: Although many interventions may offer improvements for hot flashes versus no treatment, minimal data suggest important differences between therapies. SUPPLEMENTARY MATERIALS CAN BE FOUND BY VISITING&NBSP;HTTPS: //bit.ly/2WGzi30.

The Efficacy and Safety of Low Molecular Weight Heparin Administration to Improve Survival of Cancer Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Low molecular weight heparins (LMWH) are often used as a first-line therapy for the prevention of thrombosis in cancer patients. Preclinical evidence from animal models suggests that LMWH may have antimetastatic properties. Clinical evidence of this effect is inconclusive. The objective of this systematic review is to evaluate the effect of LMWH on overall survival in patients with solid tumor malignancies. METHODS: MEDLINE, Embase, and The Cochrane Central Register of Controlled trials were searched from inception to November 26, 2018. We included randomized controlled trials that compared LMWH to placebo, a no-treatment arm, or a short-term prophylactic course of LMWH in adult patients with solid tumors. The primary outcome was overall survival. Secondary outcomes included progression-free survival, the occurrence of venous thromboembolism, and major bleeding events. The risk of bias was assessed in duplicate using the Cochrane Risk-of-Bias tool. RESULTS: Forty-five articles were included in the review. Overall, no difference in overall survival was observed between groups (risk ratio: 1.00; 95% confidence interval: 0.98-1.02; I2 = 36.5%). In our a priori defined subgroup analyses, the effect was not shown to vary by the type of LMWH, duration of LMWH use, length of study follow-up, comparator used in the study, or the setting in which the LMWH was administered. The majority of studies had an unclear risk of bias for at least one methodological criterion. CONCLUSION: Although LMWH is thought to possess antimetastatic properties and thus have the potential to improve survival in cancer patients, existing data do not support this hypothesis.

Risk Factors for Failure to Rescue in Myocardial Infarction after Noncardiac Surgery: A Cohort Study.

BACKGROUND: Compared to other perioperative complications, failure to rescue (i.e., death after suffering a complication) is highest after perioperative myocardial infarction (a myocardial infarction that occurs intraoperatively or within 30 days after surgery). The purpose of this study was to identify patient and surgical risk factors for failure to rescue in patients who have had a perioperative myocardial infarction. METHODS: Individuals who experienced a perioperative myocardial infarction after noncardiac surgery between 2012 and 2016 were identified from the American College of Surgeons (Chicago, Illinois) National Surgical Quality Improvement Program database. Multivariable logistic regression was used to identify risk factors for failure to rescue. Subgroup and sensitivity analyses evaluated the robustness of primary findings. RESULTS: The authors identified 1,307,884 individuals who had intermediate to high-risk noncardiac surgery. A total of 8,923 (0.68%) individuals had a perioperative myocardial infarction, of which 1,726 (19.3%) experienced failure to rescue. Strongest associations (adjusted odds ratio greater than 1.5) were age 85 yr or older (2.52 [95% CI, 2.05 to 3.09] vs. age younger than 65 yr), underweight body mass index (1.53 [95% CI, 1.17 to 2.01] vs. normal body mass index), American Society of Anesthesiologists class IV (1.76 [95% CI, 1.33 to 2.31] vs. class I or II) and class V (3.48 [95% CI, 2.20 to 5.48] vs. class I or II), and presence of: ascites (1.81 [95% CI, 1.15 to 2.87]), disseminated cancer (1.54 [95% CI, 1.18 to 2.00]), systemic inflammatory response syndrome (1.55 [95% CI, 1.26 to 1.90]), sepsis (1.75 [95% CI, 1.39 to 2.20]), septic shock (1.79 [95% CI, 1.34 to 2.37]), and dyspnea at rest (1.94 [95% CI, 1.32 to 2.86]). Patients who had emergency surgery, high-risk procedures, and postoperative complications were at higher risk of failure to rescue. CONCLUSIONS: Routinely identified patient and surgical factors predict risk of failure to rescue after perioperative myocardial infarction.

A comparison of policy provisions for managing "financial" and "non-financial" interests across health-related research organizations: A qualitative content analysis.

It is largely taken-for-granted, and sometimes advocated that the same strategies to identify, assess, and manage financial conflicts of interest may also be applied to so-called non-financial conflicts of interest. We conducted a qualitative content analysis of 22 conflict of interest policies from prominent organizations engaged in health-related research to compare and critically analyze the range of policy approaches for managing financial and non-financial interests. We extracted and analyzed policy content using an instrument based on the normative framework for evaluating conflict of interest policy proposed by the Institute of Medicine. Policy authors implicitly applied the same principles and provisions to both financial and non-financial conflicts of interest or failed to specify how they might be treated separately. Provisions related to the identification of "perceived" conflicts of interest, consequences for non-disclosure, ineligibility for participation, and management strategies thus, tended to under-regulate financial and over-regulate non-financial conflicts of interest. Consequently, these approaches may particularly violate principles of proportionality and fairness and risk interference from industry, sometimes intentionally so. Policymakers should strengthen approaches to identification and prevention of financial conflicts of interest and explore alternative approaches to enhancing individuals' accountability for their positions and perspectives.

A randomized trial comparing vascular access strategies for patients receiving chemotherapy with trastuzumab for early-stage breast cancer.

PURPOSE: Trastuzumab-based chemotherapy is usually administered through either a peripherally inserted central catheter (PICC) or a totally implanted vascular access device (PORT). As the most effective type of access is unknown, a feasibility trial, prior to conducting a large pragmatic trial, was undertaken. METHODS: The trial methodology utilized the integrated consent model incorporating oral consent. Patients receiving trastuzumab-based neo/adjuvant chemotherapy for early-stage breast cancer were randomized to a PICC or PORT insertion. Feasibility was reflected through a combination of endpoints; however, the a priori definition of feasibility was > 25% of patients approached agreed to randomization and > 25% of physicians approached patients. Secondary outcomes included rates of line-associated complications such as thrombotic events requiring anticoagulation, line infections or phlebitis. RESULTS: During the study period, 4/15 (26.7%) medical oncologists approached patients about study participation. Of 59 patients approached, 56 (94.9%) agreed to randomization, 29 (51.8%) were randomized to PICC and 27 (48.2%) to PORT access. Overall, 17.2% (5/29) and 14.8% (4/27) of patients had at least one line-associated complication in the PICC and PORT arms respectively. The study was terminated early due to slow accrual. CONCLUSION: The study met its feasibility endpoints with respect to patient and physician engagement. However, the slow rate of accrual (56 patients in 2 years) means that conducting a large pragmatic trial would require additional strategies to make such a study possible. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02632435.

Conflict of interest as ethical shorthand: understanding the range and nature of "non-financial conflict of interest" in biomedicine.

OBJECTIVES: The aim of the study was to identify the range of issues labeled as "non-financial conflicts of interest" in biomedicine, articulate the associated concerns, and analyze the implications of defining these issues as conflicts of interest. STUDY DESIGN AND SETTING: This was a qualitative study, triangulating data from three purposively sampled sources: (1) literature, (2) policies, and (3) interviews. Participants were corresponding authors of sampled literature (December 2017 to January 2019). A critical, interpretive approach served as the analytic strategy. RESULTS: A total of 99 articles provided the sampling frame; we recruited 16 participants and sampled 20 policies. Participants labeled a wide range of personal attributes, social relationships, professional experiences, intellectual endeavors, and financial interests as "non-financial conflicts of interest." Despite a lack of consensus regarding the nature of the problem, many "non-financial" interests are currently subject to policy action. The term serves as ethical shorthand to describe the ways that (1) "strong beliefs," (2) "predetermined views," (3) experiences, and (4) relationships shape evidence-led processes. CONCLUSION: Expansion of the definition of conflict of interest to include non-financial interests may have unintended consequences, including exclusion of diverse perspectives. Problems labeled "non-financial conflicts of interest" should be defined in terms of what they are rather than what they are not (i.e., "non"-financial). We suggest instead, preventing financial conflicts of interest and ensuring inclusive and equitable representation within evidence-based processes.

A multicentre, randomized pilot trial comparing vascular access strategies for early stage breast cancer patients receiving non-trastuzumab containing chemotherapy.

PURPOSE: All vascular access strategies foradministering chemotherapy in early stage breast cancer (EBC) are associated with risks and benefits. As the most effective type of access is unknown a feasibility trial, prior to conducting a large pragmatic trial, was undertaken. METHODS: The trial methodology utilized broad eligibility criteria and the integrated consent model incorporating oral consent. EBC patients receiving non-trastuzumab-containing chemotherapy were randomized to peripheral access or central line insertion. The a priori definition of feasibility was: > 25% of patients approached agreed to randomisation and > 25% of physicians approached patients. Secondary outcomes included rates of line-associated complications. RESULTS: Of 159 patients approached, 150 (94.3%) agreed to randomisation, 77 (51.3%) were randomized to peripheral and 73 (48.7%) to central access. 6/26 (23.1%) of medical oncologists approached patients. Rates of complications per chemotherapy cycles in the peripheral vs central access groups with risk difference (RD) (95% CI) were: thrombotic events requiring anticoagulation [1 (0.3%) vs. 3 (1.0%), RD - 0.7(- 1.9,0.5)], line infections [0 (0%) vs. 1 (0.3%), RD - 0.3(- 0.9,0.3)], phlebitis [2 (0.6%) vs. 0 (0%), RD 0.3(- 0.3,0.8)], and tissue infiltrations [4 (1.1%) vs. 1 (0.3%), RD 0.8(- 0.4,2.1)]. Overall, 8.0% (6/75) and 7.7% (5/65) of patients had at least one of these complications in the peripheral and central access arms respectively [RD - 0.9(- 9.4,7.6)]. The study was terminated early due to slow accrual. CONCLUSION: While meeting its a priori feasibility criteria for patient engagement, the slow accrual means that conducting a large pragmatic trial would require overcoming the barriers to physician recruitment. TRIAL REGISTRATION: NCT02688998.

Postoperative shared-care for patients undergoing non-cardiac surgery: a systematic review and meta-analysis.

BACKGROUND: Collaborative ("shared-care") models of postoperative care improve outcomes in patients undergoing surgery for hip fracture. Despite being widely adopted, it is unclear if similar benefits of shared-care models exist for other at-risk surgical patient populations. Thus, we performed a systematic review to understand the impact of shared-care models. METHODS: EMBASE, MEDLINE, CINAHL, and Cochrane Central Register databases were searched for prospective studies examining an in-hospital shared-care approach to postoperative management of adult non-cardiac surgery patients. The primary outcome was a composite of in-hospital mortality and mortality of up to 30 days. Secondary outcomes were long-term mortality (> 90 days) and hospital length of stay. Tertiary outcomes included quality of life and health utility measures. Risk of bias was assessed using Cochrane Collaboration tools. RESULTS: Six thousand eight hundred and ninety-six citations were reviewed and four studies (n = 987 patients) met the inclusion criteria-two randomized-controlled trials (RCT, n = 729 patients) and two non-randomized-controlled trials (NRCT, n = 258 patients). All studies were conducted in the elective surgical setting. There was no association between shared-care and control groups for in-hospital mortality (Peto odds ratio, 1.76; 95% confidence interval [CI], 0.65 to 4.80), or hospital length of stay (mean difference, -1.41; 95% CI, -3.18 to 0.35). Reporting of other outcomes was limited. Both RCTs were judged to be at high risk of bias for blinding and both NRCTs were judged to be at moderate risk of bias for reported outcomes. CONCLUSION: Overall, there was limited high-quality evidence to evaluate the effect of postoperative shared-care. Well-designed interventional studies, perhaps targeting higher risk surgical populations, are needed. REGISTRATION: PROSPERO (CRD42018094943); registered 16 May, 2018.

De-escalation of bone-modifying agents in patients with bone metastases from breast cancer: a systematic review and meta-analysis.

PURPOSE: Bone-modifying agents (BMAs) such as bisphosphonates and denosumab are usually administered every 4 weeks (standard) in patients with bone metastases from breast cancer to prevent skeletal-related events (SREs). Recent randomized controlled trials suggest every 12-week (de-escalated) dosing interval may be non-inferior. The objective of this systematic review and meta-analysis was to compare the efficacy and harms of standard with de-escalated administration of BMA's in patients with bone metastases from breast cancer. METHODS: We searched Medline, PubMed, and the Cochrane Register of Controlled Trials from 1947 to March 14, 2018 and conference abstracts from (2014-March 14, 2018) for randomized clinical trials comparing every 4-week and every 12-week dosing interval of bone-modifying agents. Using PRISMA guidelines, meta-analyses were performed using random-effects models, with findings reported as risk ratios with 95% confidence intervals (CI). RESULTS: From a total of 1311 citations, we identified 8 full-text articles and 1 abstract comprising data from 5 completed randomized clinical trials (n = 1807). Zoledronate administration every 12 weeks compared to every 4 weeks produced a summary risk ratio of 1.05 (95% CI 0.88-1.25) for patients with ≥ 1 on-study SRE indicating similar efficacy. These results did not differ whether patients had received prior intravenous bisphosphonate. De-escalation was associated with a non-statistically significant lower risk of increased creatinine (summary risk ratio 0.41 [95% CI 0.15-1.16]). Currently, there are insufficient data for pamidronate and denosumab de-escalation. CONCLUSIONS: These data are supportive of de-escalation of zoledronate from onset for patients with bone metastases from breast cancer.

Does integration of Magee equations into routine clinical practice affect whether oncologists order the Oncotype DX test? A prospective randomized trial.

OBJECTIVE: The three Magee Equations provide an estimate of the Oncotype DX recurrence score using commonly available clinicopathologic information (tumour size, grade, oestrogen receptor, progesterone receptor, HER2, and Ki67). We assessed whether integration of Magee Equations into routine clinical practice affected the frequency of Oncotype DX requests. METHODS: Patients with newly diagnosed, node negative, hormone receptor positive, and HER2 negative invasive breast cancer were randomized to undergo a Magee calculation or not. At the first clinic assessment, the oncologist was provided with all routinely available clinicopathologic information (including Ki67) either with or without the results of Magee Equations. Primary outcome was frequency of Oncotype DX ordering. Secondary outcomes included frequency of chemotherapy use, time to commencement of radiotherapy, or systemic therapy. Physician comfort with systemic therapy choices and the use of Ki67 and Magee Equations was also assessed. RESULTS: Data from 175 randomized patients was available, 84 patients (48%) with and 91 (52%) without calculated Magee Equations. Oncotype DX was ordered in 10 (12.05%) and 13 (14.44%) (RR 0.83, 0.39-1.80; P = 0.64) in the Magee and no Magee groups, respectively. There were no statistically or clinically significant differences between the randomized groups for any of the secondary outcomes. Availability of both Ki67 and Magee Equations was associated with increased physician comfort around systemic treatment decisions. CONCLUSIONS: In a practice where Ki67 is routinely available, addition of Magee Equations into routine clinic practice was not associated with a reduction in Oncotype DX use. Availability of both Ki67 and Magee Equations did however increase physician comfort with systemic therapy decisions.

Feasibility of using a pragmatic trials model to compare two primary febrile neutropenia prophylaxis regimens (ciprofloxacin versus G-CSF) in patients receiving docetaxel-cyclophosphamide chemotherapy for breast cancer (REaCT-TC).

PURPOSE: Optimal primary febrile neutropenia (FN) prophylaxis (i.e. ciprofloxacin or granulocyte-colony stimulating factors [G-CSF]) for patients receiving docetaxel-cyclophosphamide (TC) chemotherapy is unknown. We assessed the feasibility of using a novel pragmatic comparative effectiveness trial to compare these standard-of-care options. METHODS: Early-stage breast cancer patients receiving TC chemotherapy were randomised to either ciprofloxacin or G-CSF. Trial methodology consists of broad eligibility criteria, simply-defined endpoints, integrated consent model incorporating oral consent, and web-based randomisation in the clinic. Primary feasibility endpoints included patient and physician engagement (if > 50% of patients approached agree to participate and if > 50% of physicians approached patients for the study). Secondary clinical endpoints included the following: first occurrence rates of FN, treatment-related hospitalisation, or chemotherapy dose reduction/delay/discontinuation, as well as patient satisfaction with the oral consent process. RESULTS: Of 204 patients approached, 91.2% (186/204) agreed to randomisation. Sixteen of twenty (80%) participating medical oncologists randomised patients. Median patient age was 57.7 (range 31.8-84.1). The 186 patients received 557 cycles of chemotherapy. Overall incidences of first events by patient (n = 186) were as follows: FN (18/186, 21.43%), treatment-related hospitalisation (11/186, 13.10%), chemotherapy reduction (19/186, 22.62%), chemotherapy discontinuation (16/186, 19.05%), and chemotherapy delays (5/186, 5.95%). A total of 37.77% (69/186) of patients and 12.39% (69/557) of chemotherapy cycles had at least one of these first events. Patients were highly satisfied with the oral consent process. CONCLUSION: This study met its feasibility endpoints. This model offers a means of comparing standard-of-care treatments in a practical and cost-efficient manner. TRIAL REGISTRATION: Trial registration: ClinicalTrials.gov : NCT02173262.

A prospective intervention to improve happiness and reduce burnout in oncologists.

BACKGROUND: There is a paucity of data about effective interventions to improve happiness and reduce burnout in oncologists. Benjamin Franklin developed a 13-week program of "necessary activities" or "virtues" (temperance, silence, order, resolution, frugality, industry, sincerity, justice, moderation, cleanliness, tranquility, chastity, and humility) to follow, in his attempt at self-improvement. In this pilot study, we explored whether using a modified version of this was associated with any discernable impact on physician happiness, burnout, or compliance with each of the virtues. METHODS: Self-reported happiness (Oxford happiness scores) and burnout (Abbreviated Maslach Burnout Inventory) were completed at baseline (pre-study), week 13, and 1 month after completion of the program. Each day during the 13-week program, oncologists were emailed a list of virtues to focus on and scored how they felt they were complying with them. The oncologist's spouses also assessed how they felt the oncologist was complying with the virtues. RESULTS: Thirteen physicians completed the baseline scores, 11 completed Maslach/Oxford scores at the end of the study, and 8 the 1-month post-study assessment. No significant improvements in happiness and burnout (emotional exhaustion, depersonalization, personal accomplishment) scores were observed. Statistically significant changes in self-rated virtue scores were observed for temperance (p = 0.046), order (p = 0.049), and resolution (p = 0.014). Additionally, although not reaching statistical significance, 11 of 13 virtues (excepting sincerity and chastity) assessed by spouses indicated a positive change over time. CONCLUSION: In this hypothesis generating study, daily reflection on personal virtues was not associated with any statistically significant change in happiness or burnout scores. Alternative strategies should be considered.

Physician Survey of Timing of Adjuvant Endocrine Therapy Relative to Radiotherapy in Early Stage Breast Cancer Patients.

BACKGROUND: Patients can start endocrine therapy before, concurrently with, or sequentially after radiotherapy. The optimal timing of starting adjuvant endocrine therapy is unknown. This survey was performed to evaluate physician recommendations. METHODS: Canadian oncologists were surveyed to evaluate institutional and personal practices regarding the prescription of adjuvant endocrine therapy and radiotherapy. Perspectives regarding the design of a clinical trial to compare concurrent versus sequential therapy, and the optimum end points for such a trial, were also sought. RESULTS: The overall response rate was 30% (65/220), with responses mainly from medical (35/65, 54%) and radiation (28/65, 43%) oncologists. Eighty-four percent of respondents reported an absence of institutional protocols. The majority of physicians (57%, 36/65) identified endocrine therapy provided after radiotherapy as the preferred sequence of treatments. Twenty-two percent (14/65) had no preference, while 21%, (14/65) started endocrine therapy either before or concurrent with radiotherapy. Practice patterns were largely based on the physician's own clinical experience. Thirty-two percent of physicians (21/65) had concerns regarding concurrent endocrine therapy and radiotherapy, including increased adverse effects with endocrine therapy (13/21, 62%), reduced efficacy of radiotherapy (4/21, 19%), reduced compliance with endocrine therapy (3/21, 14%), and increased radiation toxicity (1/21, 5%). Most thought a pragmatic clinical trial addressing this question would help standardize and improve patient care. CONCLUSION: Decisions around the timing of endocrine therapy and radiotherapy are largely being made on the basis of physicians' personal choices. In the absence of data to support these decisions, appropriately powered trials are needed.

Primary Febrile Neutropenia Prophylaxis for Patients Who Receive FEC-D Chemotherapy for Breast Cancer: A Systematic Review.

PURPOSE: Despite widespread use of fluorouracil, epirubicin, cyclophosphamide, docetaxel (FEC-D) chemotherapy in breast cancer, the optimal strategy for primary febrile neutropenia (FN) prophylaxis remains unknown. A systematic review was therefore performed. METHODS: Embase, Ovid MEDLINE, PubMed, Cochrane Database of Systematic Reviews, Cochrane Register of Controlled Trials, and conference proceedings were searched from 1946 to April 2016 for trials that reported the effectiveness of primary FN prophylaxis with FEC-D chemotherapy. Outcome measures were incidence of FN; treatment-related hospitalizations; chemotherapy dose delays, reductions, and discontinuations; and adverse events from prophylaxis. RESULTS: Of 2,205 identified citations, eight studies (n = 1,250) met our eligibility criteria. Three additional studies (n = 293) were identified from a prior systematic review. Three randomized controlled trials (n = 576), one phase IV single-arm trial (n = 69), one prospective observational study (n = 37), and six retrospective studies (n = 861) were identified. Agents investigated were pegfilgrastim (n = 108), filgrastim (n = 1,119), and ciprofloxacin (n = 89). The heterogeneity of studies meant that a narrative synthesis of results was performed. Median FN rates for patients who received FEC-D with and without primary prophylaxis were 10.1% (interquartile range [IQR], 3.9% to 22.6%) and 23.9% (IQR, 9.2% to 27.3%), respectively. In the absence of primary prophylaxis, FN was more common during docetaxel than during FEC. Data from six studies showed a median rate of dose reductions and delays of 6.1% (IQR, 3.1% to 14.3%) and 19.3% (IQR, 10.5% to 32.8%), respectively, that occurred as a consequence of FN. Toxicity from prophylaxis itself was rarely reported. CONCLUSION: Primary FN prophylaxis is effective in patients who receive FEC-D chemotherapy. The paucity of prospective data makes optimal recommendations about the choice and timing of prophylaxis challenging.

Safety and Efficacy of Adult Stem Cell Therapy for Acute Myocardial Infarction and Ischemic Heart Failure (SafeCell Heart): A Systematic Review and Meta-Analysis.

Preclinical and clinical evidence suggests that mesenchymal stem cells (MSCs) may be beneficial in treating both acute myocardial infarction (AMI) and ischemic heart failure (IHF). However, the safety profile and efficacy of MSC therapy is not well-known. We conducted a systematic review of clinical trials that evaluated the safety or efficacy of MSCs for AMI or IHF. Embase, PubMed/Medline, and Cochrane Central Register of Controlled Trials were searched from inception to September 27, 2017. Studies that examined the use of MSCs administered to adults with AMI or IHF were eligible. The Cochrane risk of bias tool was used to assess bias of included studies. The primary outcome was safety assessed by adverse events and the secondary outcome was efficacy which was assessed by mortality and left ventricular ejection fraction (LVEF). A total of 668 citations were reviewed and 23 studies met eligibility criteria. Of these, 11 studies evaluated AMI and 12 studies evaluated IHF. There was no association between MSCs and acute adverse events. There was a significant improvement in overall LVEF in patients who received MSCs (SMD 0.73, 95% CI 0.24-1.21). No significant difference in mortality was noted (Peto OR 0.68, 95% CI 0.38-1.22). Results from our systematic review suggest that MSC therapy for ischemic heart disease appears to be safe. There is a need for a well-designed adequately powered randomized control trial (with rigorous adverse event reporting and evaluations of cardiac function) to further establish a clear risk-benefit profile of MSCs. Stem Cells Translational Medicine 2018;7:857-866.

Randomised feasibility trial to compare three standard of care chemotherapy regimens for early stage triple-negative breast cancer (REaCT-TNBC trial).

INTRODUCTION: Despite the importance of chemotherapy in the treatment of early stage triple negative breast cancer (TNBC), no one optimal regimen has been identified. We conducted a pilot trial comparing outcomes for the three most commonly used chemotherapy regimens to assess the feasibility of conducting a larger definitive trial. METHODS: Using integrated consent, newly diagnosed TNBC patients were randomised to one of three standard regimens: dose-dense doxorubicin-cyclophosphamide then paclitaxel, doxorubicin-cyclophosphamide then weekly paclitaxel or 5-FU-epirubicin-cyclophosphamide then docetaxel. Feasibility endpoints included; physician engagement, accrual rates, physician compliance and patient satisfaction with the integrated consent model. Our anticipated pilot trial sample size was 35 randomised patients in one year. RESULTS: Between August 30th, 2016 and January 31st 2017, 2 patients met eligibility and were randomised. A survey of 10 participating oncologists was performed to identify potential strategies to enhance accrual. Most investigators (9/10) believed that the best regimen for TNBC was unknown, and 4/10 felt this was a pressing clinical question. Physicians' responses suggested that poor accrual was due to: a lack of interest in some study arms as oncologists already had a preferred regimen (4/10) and concerns about trial demands in busy clinics (3/10). The pilot feasibility endpoints were not met and the study was closed. CONCLUSIONS: Despite initial interest in the trial question and multiple investigators agreeing to approach patients, this trial failed to meet feasibility endpoints. The reasons for poor accrual were multiple and require further evaluation if this important patient-centred question is to be answered. TRIAL REGISTRATION: ClinicalTrials.gov NCT02688803.

Optimal vascular access strategies for patients receiving chemotherapy for early-stage breast cancer: a systematic review.

IMPORTANCE: Systemic chemotherapy can be administered either through a peripheral vein (IV), or centrally through peripherally inserted central catheter (PICC), totally implanted vascular access devices (PORTs) or tunnelled cuffed catheters. Despite the widespread use of systemic chemotherapy in patients with breast cancer, the optimal choice of vascular access is unknown. OBJECTIVE: This systematic review evaluated complication rates and patient satisfaction with different access strategies for administering neo/adjuvant chemotherapy for breast cancer. EVIDENCE REVIEWED: Ovid Medline, EMBASE and the Cochrane Central Register of Controlled Trials were searched from 1946 to September 2017. Two reviewers independently assessed each citation. The Newcastle-Ottawa scale was used to assess the quality of cohort and case-control studies. FINDINGS: Of 1584 citations identified, 15 unique studies met the pre-specified eligibility criteria. There were no randomised studies comparing types of vascular access. Reports included six single-institution retrospective cohort studies, one retrospective multi-institution cohort, one retrospective cohort database study, five prospective single-institution studies, one prospective multi-institution study and one nested case-control study. Median complication rates were infection: 6.0% PICC (2 studies) versus 2.1% PORT (8 studies); thrombosis: 8.9% PICC (2 studies) versus 2.6% PORT (9 studies); extravasation: 0 PICC (1 study) versus 0.4% PORT (4 studies) and mechanical issues: PICC 3.8% (1 study) versus 1.8% PORT (9 studies). Satisfaction/quality of life appeared high with each device. CONCLUSION: In the absence of high-quality data comparing vascular access strategies, randomised, adequately powered, prospective studies would be required to help inform clinical practice and reduce variation.