Promoting End-of-Life Care and Healthcare Worker Well-Being: Implementing the 3 Wishes Project in an Oncology Intensive Care Unit.

This scholarly project implemented the 3 Wishes Project (3WP), which aims to fulfill the final wishes of dying critically ill patients, in a 16-bed tertiary intensive care unit (ICU). The project assessed outcomes through sur.

Exploring nurses' emotional reactions to and reporting of patient-on-nurse workplace violence: A mixed-methods study.

BACKGROUND: Workplace violence, including violent, intimidating, and disruptive acts, commonly occurs in healthcare settings. Type 2 workplace violence in nursing refers to patient/visitor behaviors directed toward clinicians, contributing to physical and psychological harm. Nurse victims often do not report these events to employers or law enforcement, making it challenging to address workplace violence. OBJECTIVES: Our research examined nurse reactions to Type 2 workplace violence by identifying what behaviors they perceived as aggressive and reportable. Specific aims included: 1) developing and testing video vignettes to portray realistic patient aggression scenarios; 2) identifying nurse understandings of aggressive events that prompt affective reactions, and; 3) examining clinical characteristics related to the nurse victim's likelihood to report. DESIGN: Through a sequential mixed-methods design, we qualitatively developed novel video vignettes portraying Type 2 workplace violence to experimentally examine how nurses interpreted them within a quantitative repeated measures survey. METHODS: Two expert nurse research panels (n = 10) created five vignettes, from which nurses (n = 282) completed a survey with 1382 unique responses. Analyses included descriptive statistics and repeated measures ANOVA/regression models. RESULTS: Video vignettes realistically portrayed workplace violence events, eliciting negative emotional responses among nurses that increased in magnitude with statistical significance as the level of displayed aggression escalated. Statistically significant factors influencing nurse reporting of workplace violence included; 1) the level of aggression displayed by the patient; 2) the level of harm received by the nurse; 3) whether the nurse felt the patient's actions were intentional, and; 4) the nurse's perceived frequency of exposure to workplace violence. CONCLUSIONS: Results suggested that nurse victims of Type 2 workplace violence experience depression, anger, fear, and anxiety, which may contribute to long-term mental health consequences. Findings also identified factors related to nurse reporting behaviors, which may help mitigate workplace violence in healthcare settings by informing research and promoting workplace practices that encourage reporting and safety. REGISTRATION: Not registered. TWEETABLE ABSTRACT: Nurse reactions to workplace violence: Video vignettes reveal escalating aggression's impact on reporting. #EndNurseAbuse #WorkplaceViolence.

Understanding Nursing Workplace Violence Trends for Safer Clinical Oncology Settings.

BACKGROUND: Workplace violence (WPV) against nursing professionals by patients and visitors occurs frequently, and rates of WPV increased during the COVID-19 pandemic. All nursing teams, including oncology nursing professionals, are at risk for WPV and need current WPV-related information applicable to their clinical experiences. OBJECTIVES: This overview aims to increase awareness of trends and personal safety issues related to clinical oncology nursing practice and provide strategies and resources to enhance personal safety in nursing practice. METHODS: This overview used literature reviews, publicly reported sources, other scholarly resources, and real-world examples to identify and synthesize WPV trends related to clinical nursing. FINDINGS: This overview's findings suggest that the COVID-19 pandemic contributed to the increased rate of WPV and subsequent harm to nursing staff victims. Oncology nursing professionals can implement best practices to reduce their risk of being harmed, and healthcare institutions can operationalize best practices by having systems and resources in place that prevent and mitigate WPV.

Why nurses do not report patient aggression: A review and appraisal of the literature.

AIM: To establish the current state of the science about why nurses do or do not report being the victim of patient aggression, a form of type II workplace violence. This aim includes identifying and analysing current gaps in the literature. BACKGROUND: It is increasingly more common for patients to instigate aggressive acts towards nurses, leading to significant consequences. Nursing victims often do not report acts of patient aggression to others, making it difficult for health care leaders and researchers to address this challenge. EVALUATION: The review process involved searching five databases, using the PRISMA framework to reduce 355 records to 65 sources for review and synthesis. KEY ISSUES: The findings of this review highlight key takeaways about why nursing victims do not report episodes of patient aggression, which include their fears, attitudes and abilities related to reporting; and their perspective of the patient aggression event. Workplace environments are central to most of these factors, emphasizing the importance of nursing and other health care leaders to put systems in place that promote nurse reporting behaviours. CONCLUSIONS: Patient aggression is a widespread problem with severe consequences. Review findings can inform future research while having practical relevance for health care leaders. IMPLICATIONS FOR NURSING MANAGEMENT: Health care leaders need to consider how workplace structures, practices, and cultures can encourage or stifle nurse reporting behaviours. By understanding nurse reporting behaviours, processes can be developed to promote nursing victim reporting and deter patient aggression.

Reducing Patient Aggression Through a Nonviolent Patient De-escalation Program: A Descriptive Quality Improvement Process.

BACKGROUND: Patients commonly display aggressive and violent behaviors toward nursing staff, contributing to severe consequences. Healthcare institutions must develop and implement systems addressing this global safety problem. AIM: To improve clinical practice safety for inpatient acute care settings by providing healthcare teams throughout a large academic medical center with a Behavioral Emergency Response Team (BERT) program, that is, a system for reporting and de-escalating aggressive patient encounters. METHODS: This descriptive quality improvement process took place within two inpatient acute care departments using simulation-based training, patient safety rounds, and a BERT activation system. Participant groups included nursing personnel who completed a baseline survey (n = 302), telecommunication dispatchers (n = 20), BERT responders (n = 78), and bedside nursing staff (n = 43) recipients of BERT program resources. Methods included a baseline questionnaire, pre- and post-intervention surveys, formal reports of aggressive patient encounters, documentation from patient safety rounds, and records of activated BERT responses. Data analysis included descriptive statistics, boxplots, and the Wilcoxon signed-rank test. RESULTS: This project mitigated patient aggression episodes by successfully designing and implementing an evidence-based BERT program. Findings suggested bedside nursing program participants felt more confident and capable of managing aggressive patient behaviors. A strong partnership between security officers and nursing staff limited the risk of harm to clinical staff by identifying and intervening with 41 potentially aggressive patients. Finally, formal reports of patient aggression episodes did not increase during this project, which may have indicated early prevention and detection of aggression while reflecting the broader problem of aggression under-reporting in nursing. LINKING EVIDENCE TO ACTION: Healthcare organizations need to have robust systems to manage aggressive patient encounters. Comprehensive strategies for managing patient aggression include simulation-based training, the use of BERT responders, and a strong partnership between nursing and security officer teams.

COVID-19 pandemic impact on experiences and perceptions of nurse graduates.

BACKGROUND: Transitioning from education to practice is stressful for new nurses and those entering new roles and can lead to workforce attrition and burnout. This dynamic is likely complicated when graduates are transitioning to practice during a pandemic. PURPOSE: The purpose of this study was to describe recent nurse graduates' perceptions of the impact of the COVID-19 pandemic on their transition from education to practice. METHODS: We conducted an online survey of BSN, RN-BSN, and DNP students who graduated between December 2019 and April 2020 (n = 82), including demographics, employment information, and free-response questions about the impact of the pandemic on their transition experiences, post-graduation plans, and perceptions of nursing. We used a qualitative descriptive approach to content analysis to synthesize and summarize the data. RESULTS: Participants expressed three overarching concerns: 1) altered plans such as difficulty finding employment; 2) logistical, system-related stressors including licensing delays and chaotic onboarding; and 3) feeling pride in profession despite perceiving ambivalence in public discourse. CONCLUSION: COVID-19 exacerbated challenges often experienced by new graduates. Common stressors, intensified during the pandemic, could exert long-term effects on the workforce. Educators and healthcare organizations must work to ensure nursing graduates receive the necessary support for a successful transition.

Phase 1 study of alisertib (MLN8237) and weekly irinotecan in adults with advanced solid tumors.

PURPOSE: Aurora kinases are overexpressed or amplified in numerous malignancies. This study was designed to determine the safety and tolerability of the Aurora A kinase inhibitor alisertib (MLN8237) when combined with weekly irinotecan. METHODS: In this single-center phase 1 study, adult patients with refractory advanced solid tumors received 100 mg/m2 irinotecan intravenously on day 1 and 8 of a 21-day cycle. Alisertib at planned escalating dose levels of 20-60 mg was administered orally twice per day on days 1-3 and 8-10. Patients homozygous for UGT1A1*28 were excluded. The primary objective was the safety of alisertib when combined with irinotecan to determine the maximum tolerated dose (MTD). Secondary objectives included overall response rate by RECIST and pharmacokinetics in a planned expansion cohort of patients with colorectal cancer treated at the MTD. RESULTS: A total of 17 patients enrolled at three dose levels. Dose-limiting toxicities included diarrhea, dehydration, and neutropenia. The MTD of alisertib combined with weekly irinotecan was 20 mg twice per day on days 1-3 and 8-10. One fatal cardiac arrest at the highest dose level tested was deemed possibly related to drug treatment. One partial response in 11 efficacy evaluable patients (9%) occurred in a patient with small cell lung cancer. The study was terminated prior to the planned expansion in patients with colorectal cancer. CONCLUSION: In contrast to prior results in a pediatric population, adult patients did not tolerate alisertib combined with irinotecan at clinically meaningful doses due to hematologic and gastrointestinal toxicities. The study was registered with ClinicalTrials.gov under study number NCT01923337 on Aug 15, 2013.

Combined Immune Checkpoint Blockade and Stereotactic Ablative Radiotherapy Can Stimulate Response to Immunotherapy in Metastatic Melanoma: A Case Report.

Skin cancer is the most commonly diagnosed malignancy in the United States, and invasive cutaneous melanoma is responsible for the vast majority of skin cancer-related deaths. Treatment options for patients with regional nodal disease, in-transit metastases, or locally advanced or distant metastatic disease are challenging. Historically survival rates in this patient population are dismal. Improved systemic control is possible using targeted agents and checkpoint inhibitors have redefined treatment outcomes. Furthermore, multi-modal therapy incorporating radiation may improve survival outcomes by priming the immune system for antigen release and help in reversing T-cell exhaustion. Herein, we describe a patient with widespread metastatic melanoma with progressive systemic disease while receiving checkpoint inhibition therapy that was reversed after combined immunoradiotherapy. The patient is now more than 41 months from diagnosis with durable, stable systemic disease.

Escape from the diffusion of responsibility: A review and guide for nurses.

AIMS: This review aims to help nurse leaders and professionals to understand, recognize, and mitigate the phenomenon known as the diffusion of responsibility, while also bridging a gap in nursing literature by highlighting Milgram's and Zimbardo's research. BACKGROUND: Nurses are uninformed of how responsibility is diffused when obeying authority figures, fulfilling roles, and conforming in groups. It is important to recognize and address this potential for unethical practices, given the high risk for these behaviours to occur in health care settings. EVALUATION: Sources discussing the diffusion of responsibility were identified through databases using terms such as: "Diffusion of Responsibility," "Nursing," "Ethics," "Obedience," "Groupthink," "Bully," "Milgram," and "Zimbardo." KEY ISSUES: Social psychology examples of diffused responsibility from Milgram, Zimbardo, and Janis are explored, applied to the field of nursing, and leadership implications are discussed. CONCLUSION: Nurses can unintentionally ascribe accountability for personal action to others. It is therefore essential for nurses to escape the cycle of diffused responsibility. IMPLICATIONS FOR NURSING MANAGEMENT: Examples in this review provide important clues for addressing the negative effects of diffused responsibility. The onus is on nurses to personally enhance the ethics of their practice by surveying, pondering, and applying these concepts.

Can I relate? A review and guide for nurse managers in leading generations.

AIMS: The purpose of this review is to help the nurse leader develop an understanding of the five generations currently in the health care workforce by providing defining characteristics, general behaviours, and strategies for the nurse manager to employ for each generational cohort. BACKGROUND: Generations are groups of people born during the same 15-20 year time period who share similar experiences before adulthood, which shape long-term behaviours. Key descriptors and characteristics are provided. EVALUATION: The current generational cohorts in the health care workforce are Traditionalists (born between 1922 and 1945), baby boomers (born between 1946 and 1964), Generation X (born between 1965 and 1979), millennials (born between 1980 and 1995), and Generation Z (born after 1995). KEY ISSUES: Health care teams often comprise members of three or more generations. Intergenerational differences in team members can result in challenges; however, different perspectives provided by multiple generations can be used advantageously to strengthen the team's efficiency and outcomes. CONCLUSIONS: There are strengths in each generation. Key differences can be harnessed to build stronger teams through comprehensive communication strategies, customized reward systems, and workplace flexibility. Examples are provided for each area. IMPLICATIONS: Managers can use intergenerational differences to create a rich environment that bridges generational differences and fosters workforce cohesion.

Acute Coronary Syndrome: Current Treatment.

Acute coronary syndrome continues to be a significant cause of morbidity and mortality in the United States. Family physicians need to identify and mitigate risk factors early, as well as recognize and respond to acute coronary syndrome events quickly in any clinical setting. Diagnosis can be made based on patient history, symptoms, electrocardiography findings, and cardiac biomarkers, which delineate between ST elevation myocardial infarction and non-ST elevation acute coronary syndrome. Rapid reperfusion with primary percutaneous coronary intervention is the goal with either clinical presentation. Coupled with appropriate medical management, percutaneous coronary intervention can improve short- and long-term outcomes following myocardial infarction. If percutaneous coronary intervention cannot be performed rapidly, patients with ST elevation myocardial infarction can be treated with fibrinolytic therapy. Fibrinolysis is not recommended in patients with non-ST elevation acute coronary syndrome; therefore, these patients should be treated with medical management if they are at low risk of coronary events or if percutaneous coronary intervention cannot be performed. Post-myocardial infarction care should be closely coordinated with the patient's cardiologist and based on a comprehensive secondary prevention strategy to prevent recurrence, morbidity, and mortality.

A High-Resolution National-Scale Hydrologic Forecast System from a Global Ensemble Land Surface Model.

Warning systems with the ability to predict floods several days in advance have the potential to benefit tens of millions of people. Accordingly, large-scale streamflow prediction systems such as the Advanced Hydrologic Prediction Service or the Global Flood Awareness System are limited to coarse resolutions. This article presents a method for routing global runoff ensemble forecasts and global historical runoff generated by the European Centre for Medium-Range Weather Forecasts model using the Routing Application for Parallel computatIon of Discharge to produce high spatial resolution 15-day stream forecasts, approximate recurrence intervals, and warning points at locations where streamflow is predicted to exceed the recurrence interval thresholds. The processing method involves distributing the computations using computer clusters to facilitate processing of large watersheds with high-density stream networks. In addition, the Streamflow Prediction Tool web application was developed for visualizing analyzed results at both the regional level and at the reach level of high-density stream networks. The application formed part of the base hydrologic forecasting service available to the National Flood Interoperability Experiment and can potentially transform the nation's forecast ability by incorporating ensemble predictions at the nearly 2.7 million reaches of the National Hydrography Plus Version 2 Dataset into the national forecasting system.

Diagnosis and Management of Foodborne Illness.

The Centers for Disease Control and Prevention estimates that each year, one in six Americans will experience a foodborne illness. The most common causes in the United States are viruses, such as norovirus; bacteria, such as Salmonella, Escherichia coli, Campylobacter, and Listeria; and parasites, such as Toxoplasma gondii and Giardia. Resources are available to educate consumers on food recalls and proper handling, storage, and cooking of foods. Diagnosis and management of a foodborne illness are based on the history and physical examination. Common symptoms of foodborne illnesses include vomiting, diarrhea (with or without blood), fever, abdominal cramping, headache, dehydration, myalgia, and arthralgias. Definitive diagnosis can be made only through stool culture or more advanced laboratory testing. However, these results should not delay empiric treatment if a foodborne illness is suspected. Empiric treatment should focus on symptom management, rehydration if the patient is clinically dehydrated, and antibiotic therapy. Foodborne illnesses should be reported to local and state health agencies; reporting requirements vary among states.

100% Complete response rate in patients with cutaneous metastatic melanoma treated with intralesional interleukin (IL)-2, imiquimod, and topical retinoid combination therapy: results of a case series.

BACKGROUND: Patients with cutaneous melanoma metastases have experienced excellent responses to intralesional interleukin (IL)-2. This has led to its recent inclusion into the US National Comprehensive Cancer Network guidelines for management of cutaneous melanoma metastases. Despite this, intralesional IL-2 has not been highlighted in the US literature nor have US physicians adopted it. OBJECTIVE: We sought to evaluate the effectiveness of intralesional IL-2 combined with topical imiquimod and retinoid for treatment of cutaneous metastatic melanoma. METHODS: A retrospective case series of 11 patients with cutaneous metastatic melanoma were treated with intralesional IL-2 combined with topical imiquimod and retinoid. RESULTS: A 100% complete local response rate with long-term follow-up (average of 24 months) was seen in all 11 patients treated with this proposed regimen. Biopsy specimens of treated sites confirmed absence of malignant cells. The most common treatment-related adverse event was rigors. LIMITATIONS: Small number of patients, retrospective review of charts, and lack of a comparison group were limitations. CONCLUSION: Intralesional IL-2 administered concomitantly with topical imiquimod and a retinoid cream is a promising therapeutic option for managing cutaneous melanoma metastases. The regimen was well tolerated and should be considered as a reasonable alternative to surgical excision.

Critical analysis of the efficacy of meditation therapies for acute and subacute phase treatment of depressive disorders: a systematic review.

BACKGROUND: Recently, the application of meditative practices to the treatment of depressive disorders has met with increasing clinical and scientific interest, owing to a lower side-effect burden, potential reduction of polypharmacy, and theoretical considerations that such interventions may target some of the cognitive roots of depression. OBJECTIVE: We aimed to determine the state of the evidence supporting this application. METHODS: Randomized controlled trials of techniques meeting the Agency for Healthcare Research and Quality definition of meditation, for participants having clinically diagnosed depressive disorders, not currently in remission, were selected. Meditation therapies were separated into praxis (i.e., how they were applied) components, and trial outcomes were reviewed. RESULTS: 18 studies meeting the inclusion criteria were identified, encompassing 7 distinct techniques and 1173 patients. Mindfulness-Based Cognitive Therapy comprised the largest proportion of studies. Studies including patients having acute major depressive episodes (n = 10 studies), and those with residual subacute clinical symptoms despite initial treatment (n = 8), demonstrated moderate to large reductions in depression symptoms within the group, and relative to control groups. There was significant heterogeneity of techniques and trial designs. CONCLUSIONS: A substantial body of evidence indicates that meditation therapies may have salutary effects on patients having clinical depressive disorders during the acute and subacute phases of treatment. Owing to methodologic deficiencies and trial heterogeneity, large-scale, randomized controlled trials with well-described comparator interventions and measures of expectation are needed to clarify the role of meditation in the depression treatment armamentarium.

Phase I trial of neoadjuvant conformal radiotherapy plus sorafenib for patients with locally advanced soft tissue sarcoma of the extremity.

BACKGROUND: Despite effective local therapy with surgery and radiotherapy (RT), ~50 % of patients with high-grade soft tissue sarcoma (STS) will relapse and die of disease. Since experimental data suggest a significant synergistic effect when antiangiogenic targeted therapies such as sorafenib are combined with RT, we chose to evaluate preoperative combined modality sorafenib and conformal RT in a phase I/II trial among patients with extremity STS amenable to treatment with curative intent. METHODS: For the phase I trial, eight patients with intermediate- or high-grade STS >5 cm in maximal dimension or low-grade STS >8 cm in maximal dimension received concomitant sorafenib (dose escalation cohort 1:200 twice daily, cohort 2:200/400 daily) and preoperative RT (50 Gy in 25 fractions). Sorafenib was continued during the entire period of RT as tolerated. Surgical resection was completed 4-6 weeks following completion of neoadjuvant sorafenib/RT. Three sorafenib dose levels were planned. Primary endpoints of the phase I trial were maximal tolerated dose and dose-limiting toxicity (DLT). RESULTS: Eight patients were enrolled in the phase I (five females, median age 44 years, two high-grade pleomorphic, two myxoid/round cell liposarcoma, four other). Median tumor size was 16 cm (range 8-29), and all tumors were located in the lower extremity. Two of five patients treated at dose level 2 developed DLT consisting of grade 3 rash not tolerating drug reintroduction. Other grade 3 side effects included anemia, perirectal abscess, and supraventricular tachycardia. Radiation toxicity (grade 1 or 2 dermatitis; N = 8) and post-surgical complications (three grade 3 wound complications) were comparable to historical controls and other series of preoperative RT monotherapy. Complete pathologic reponse (≥95 % tumor necrosis) was observed in three patients (38 %). CONCLUSION: Neoadjuvant sorafenib in combination with RT is tolerable and appears to demonstrate activity in locally advanced extremity STS. Further study to determine efficacy at dose level 1 is warranted. (ClinicalTrials.gov identifier NCT00805727).

Patient-reported outcomes of quality of life, functioning, and depressive symptom severity in major depressive disorder comorbid with panic disorder before and after SSRI treatment in the star*d trial.

BACKGROUND: Panic disorder (PD) is highly comorbid with major depressive disorder (MDD) with potential impact on patient-reported outcomes of quality of life (QOL), functioning, and depressive symptom severity. METHODS: Using data from the sequenced treatment alternatives to relieve depression (STAR*D) trial, we compared entry and post-SSRI-treatment QOL, functioning, and depressive symptom severity scores in MDD patients with comorbid PD (MDD+PD) to MDD patients without PD (MDDnoPD). We also compared pre- and posttreatment proportions of patients with severe impairments in quality of life and functioning. RESULTS: MDD+PD patients experienced significantly lower QOL and functioning and more severe depressive symptoms than MDDnoPD patients at entry. Following treatment with citalopram, both groups showed significant improvements, however, nearly 30-60% of patients still suffered from severe quality of life and functioning impairments. MDD+PD patients exited with lower QOL and functioning than MDDnoPD patients, a difference that became statistically insignificant after adjusting for baseline measures of depressive symptom severity, functioning, and QOL, comorbid anxiety disorders (PTSD, GAD, social, and specific phobias), age, and college education. CONCLUSIONS: Functional outcomes using QOL and functioning measures should be utilized in treating and researching MDD so that shortfalls in traditional treatment can be identified and additional interventions can be designed to address severe baseline QOL and functioning deficits in MDD comorbid with PD.

Phase I study evaluating the combination of lapatinib (a Her2/Neu and EGFR inhibitor) and everolimus (an mTOR inhibitor) in patients with advanced cancers: South West Oncology Group (SWOG) Study S0528.

PURPOSE: Everolimus, an oral inhibitor of mammalian target of rapamycin, can augment the efficacy of HER inhibitors in preclinical studies. This study was conducted to determine the safety and pharmacokinetics (PK) of the combination of lapatinib, a Her1 and 2 inhibitor, and everolimus and to describe its anti-tumor activity in the Phase I setting. METHODS: In Part I, dose escalation to define the maximum tolerated dose (MTD) was performed. In Part II, PK of both drugs were analyzed to assess drug-drug interaction. RESULTS: Twenty-three evaluable patients with advanced cancers were treated on six different dose levels in Part I of the study. The dose-limiting toxicities were diarrhea, rash, mucositis, and fatigue. The MTD of the combination was 1,250 mg of lapatinib and 5 mg of everolimus once daily. In Part II of the study, 54 patients were treated with the combination at the MTD. The mean everolimus time to maximum concentration was increased by 44 %, and mean clearance was decreased by 25 % when co-administered with lapatinib, though these differences were not statistically significant. There was no significant influence on the PK of lapatinib by everolimus. Two patients achieved a partial response [thymic cancer (45+ months) and breast cancer (unconfirmed PR; 7 months)]; 11 patients attained stable disease of at least 4 months. CONCLUSIONS: Lapatinib and everolimus are well tolerated at doses of 1,250 and 5 mg po daily, respectively. Stable disease ≥4 months/PR was achieved in 13 of 78 patients (17 %).

Phase I study of the combination of temsirolimus and pazopanib in advanced solid tumors.

Inhibition of either vascular endothelial growth factor receptor or mammalian target of rapamycin (mTOR) signaling improves outcomes in patients with several advanced solid tumors. We conducted a phase I trial of temsirolimus with pazopanib to investigate the feasibility of simultaneous 'vertical inhibition' of vascular endothelial growth factor receptor and mTOR pathways. Patients with advanced solid tumors, no previous pazopanib or mTOR inhibitor, good performance status, and acceptable end-organ function were eligible. In a typical 3+3 escalation design starting at temsirolimus 15 mg by an intravenous infusion weekly and pazopanib 400 mg orally daily, we defined dose-limiting toxicity (DLT) as attributable grade 3 or higher nonhematologic adverse events in the first 28-day cycle and the maximum tolerable dose as the maximum dose level at which less than two patients experienced DLT. At the initial dose level, two patients had four DLTs (anorexia, fatigue, hyponatremia, and hypophosphatemia). After reduction to temsirolimus 10 mg intravenous infusion weekly and pazopanib 200 mg orally daily, one of three patients had DLT (fatigue) and the first patient in the subsequent expansion had dose-limiting hypophosphatemia. Attributable grade 3 or higher adverse events in more than one patient included leukopenia, neutropenia, fatigue, and hypophosphatemia. Tumor reduction not fulfilling the RECIST criteria for partial response was the best response in four of seven evaluable patients. The combination of temsirolimus and pazopanib was not feasible at clinically meaningful doses in this population because of constitutional and electrolyte disturbances.