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ImportanceThe administration of a high fraction of oxygen following return of spontaneous circulation in out-of-hospital cardiac arrest may increase reperfusion brain injury.ObjectiveTo determine whether targeting a lower oxygen saturation in the early phase of postresuscitation care for out-of-hospital cardiac arrest improves survival at hospital discharge.Design, Setting, and ParticipantsThis multicenter, parallel-group, randomized clinical trial included unconscious adults with return of spontaneous circulation and a peripheral oxygen saturation (Spo2) of at least 95% while receiving 100% oxygen. The trial was conducted in 2 emergency medical services and 15 hospitals in Victoria and South Australia, Australia, between December 11, 2017, and August 11, 2020, with data collection from ambulance and hospital medical records (final follow-up date, August 25, 2021). The trial enrolled 428 of a planned 1416 patients.InterventionsPatients were randomized by paramedics to receive oxygen titration to achieve an oxygen saturation of either 90% to 94% (intervention; n = 216) or 98% to 100% (standard care; n = 212) until arrival in the intensive care unit.Main Outcomes and MeasuresThe primary outcome was survival to hospital discharge. There were 9 secondary outcomes collected, including hypoxic episodes (Spo2 ResultsThe trial was stopped early due to the COVID-19 pandemic. Of the 428 patients who were randomized, 425 were included in the primary analysis (median age, 65.5 years; 100 [23.5%] women) and all completed the trial. Overall, 82 of 214 patients (38.3%) in the intervention group survived to hospital discharge compared with 101 of 211 (47.9%) in the standard care group (difference, −9.6% [95% CI, −18.9% to −0.2%]; unadjusted odds ratio, 0.68 [95% CI, 0.46-1.00]; P = .05). Of the 9 prespecified secondary outcomes collected during hospital stay, 8 showed no significant difference. A hypoxic episode prior to intensive care was observed in 31.3% (n = 67) of participants in the intervention group and 16.1% (n = 34) in the standard care group (difference, 15.2% [95% CI, 7.2%-23.1%]; OR, 2.37 [95% CI, 1.49-3.79]; P Conclusions and RelevanceAmong patients achieving return of spontaneous circulation after out-of-hospital cardiac arrest, targeting an oxygen saturation of 90% to 94%, compared with 98% to 100%, until admission to the intensive care unit did not significantly improve survival to hospital discharge. Although the trial is limited by early termination due to the COVID-19 pandemic, the findings do not support use of an oxygen saturation target of 90% to 94% in the out-of-hospital setting after resuscitation from cardiac arrest.Trial RegistrationClinicalTrials.gov Identifier: NCT03138005

Objectives The current exploratory cross-sectional study was designed to examine and characterize survivorship issues among patients treated with radiation for head and neck cancer with regard to dental health, shoulder-neck dysfunction, and overall quality of life (QOL). Methods Patients (N = 58) being seen for follow-up at a radiation oncology clinic at least 1 year beyond the end of treatment completed three survey questionnaires regarding general QOL as well as dental health issues and shoulder-neck dysfunction. The questionnaires were scored and univariate analyses were performed using the variables of age, radiation dosage, definitive radiation + neck dissection versus definitive surgery + postoperative radiation, and chemotherapy. Results Median follow-up was 2.5 years. Of 58 patients, 35% reported having more problems with their general dental health as compared to before treatment and 38% reported having pain at night in the neck/shoulder after treatment. With regard to pretreatment counseling, 79% of patients reported being counseled about their dental health prior to treatment, while 31% reported being counseled about possible shoulder-neck dysfunction. Patients younger than 65, patients receiving higher doses of radiation, and patients undergoing definitive surgery + postoperative radiation reported more functional and symptomatic issues. Conclusion Patients treated with radiation for head and neck cancer face a number of survivorship issues, including problems with dental health and shoulder-neck dysfunction, and are not necessarily thoroughly counseled about these issues prior to treatment. Patients younger than 65, patients receiving higher doses of radiation, and patients undergoing definitive surgery + postoperative radiation may experience more survivorship issues. Level of evidence IV.

Practice guidelines recommend palliative care for patients with advanced cancer, but gaps in access and quality of care persist.To increase goals-of-care (GOC) communication for hospitalized patients with Stage IV cancer.An interdisciplinary team designed a quality improvement intervention to enhance oncology palliative care, including training in communication skills and triggers for palliative care consults.All adult inpatients with Stage IV cancer and unplanned admission at an 804-bed hospital affiliated with a National Cancer Institute (NCI) Comprehensive Cancer Center.The primary quality measure was the percentage of patients with Stage IV cancer who had a GOC discussion during hospitalization; secondary measures included screening for pain, dyspnea, spiritual needs, and outcomes of intensive care, hospice, and 30-day readmission.In the 11-month study period, n = 330, Stage IV cancer patients were hospitalized. Comparing the first three months with the final three months, rates of GOC discussion increased from 29% to 48% (p = 0.013), and specialty palliative care consultation increased from 18% to 33%, (p = 0.026). Rates of symptom screening, intensive care unit transfer, hospice, and 30-day re-admission did not change overall. However, patients with specialty palliative care more frequently had pain screening (91% vs. 81%, p = 0.020), spiritual assessment (48% vs. 10%, p 0.001), and hospice referral (39% vs. 9%, p 0.001), and they were less likely to be re-admitted within 30 days (12% vs. 21%, p = 0.059).Interdisciplinary quality improvement was effective to increase GOC discussions and palliative care consults for patients with Stage IV cancer.

Purpose Appropriate use of oral chemotherapy is a challenge for patients and clinicians. The purpose of this study was to analyze cancer patients’ use of oral chemotherapies and identify opportunities to improve adherence. Methods We developed a 30-question survey to address frequency and reasons for reducing/skipping doses; sources of information for oral chemotherapy use; perceived importance of food–drug effects; and ease of understanding labeling directions. Results Ninety-three patients taking oral chemotherapies with chronic myeloid leukemia, renal cell carcinoma, breast cancer, and colorectal cancer completed the survey. This was a well-educated population with 69% (n = 62) having completed some college; 51% (n = 47) female and 59% (n = 54) older than 50 years of age. Thirty percent of patients reported forgetting to take their oral chemotherapy at least “sometimes”. Younger patients (Conclusion There are three main barriers associated with appropriate use of oral chemotherapies: misunderstanding about the timing of drug with food; stopping drug without informing physicians; and difficulty understanding labeling directions. A multipronged approach is needed to optimize communication of directions for optimal oral chemotherapy use.

Malignant pleural effusions (MPEs) are common complications that occur with advanced stages of cancer. In general, they indicate a poor prognosis and greatly affect quality of life (QOL). The treatment goal of MPEs is to provide relief of symptoms. The standard treatment for MPEs is talc pleurodesis; however, indwelling pleural catheters have become more frequently used. This article focuses on current management strategies for MPEs and assesses their influence on QOL.At a GlanceSymptoms of malignant pleural effusions (MPEs), which involve the accumulation of fluid in the pleural space, include dyspnea, shortness of breath, chest pain, and other issues that decrease functional status.Treatment for MPEs should be palliative, achieving immediate symptom relief and improved quality of life.The optimal treatment strategy for MPEs should have minimal side effects, require minimal or no hospitalization, and have low rates of recurrence.

Cancer patients have a high rate of emergency department (ED) visits and inpatient hospitalizations (IHs) that may be reduced by use of outpatient palliative care services.To determine whether the outpatient adult palliative care service at the University of North Carolina (UNC) Hospital, begun in 2008, reduced the frequency of ED visits and IH during a two-year period.The charts of patients with lung cancer or head and neck cancer seen by the supportive care service from 2010 to 2011, and of a contemporaneous set of potential consults that were not seen, were retrospectively reviewed to determine the impact of this care delivery model.The number of individuals with lung cancer and head cancer seen during this two-year period was 24 and 23, respectively, permitting a statistical analysis from which meaningful conclusions could be drawn.The frequency of ED visits and IHs for each patient was reviewed. Descriptive statistics were used. Fisher's exact test was used for data categorized into two by two contingency tables. The nonparametric Jonckheere-Terpstra method was used to test for ordered differences across categories.Consultation with supportive care did not decrease overall use of ED visits. Patients with head and neck cancer showed an increase in ED visits (p = 0.08) but a reduction in inpatient admissions (p = 0.0004). In patients with lung cancer, the opposite effect was seen-an increase in inpatient visits (p = 0.02) but a decrease in ED visits. The frequency of ED visits was correlated with distance to the ED (p = 0.02), a finding that has not been noted before.Further work is needed to define the best model for outpatient palliative care.

The optimal staffing model during the inter-hospital transfer of patients on extracorporeal membrane oxygenation (ECMO) is not known. We report the complications and outcomes of patients who were commenced on ECMO at a referring hospital by intensive care physicians and compare these findings with patients who had ECMO established at an ECMO center in Australia. This was a single center, retrospective observational study based on a prospectively collected ECMO database from Melbourne, Australia. Patients with severe cardiac and/or respiratory failure failing conventional supportive treatment between 2007-2013 were placed on ECMO via a physician-led model of ECMO retrieval, including two intensivists in a four person team, using percutaneous ECMO cannulation. Patients (198) underwent ECMO over the study period, of which 31% were retrieved. Veno-venous (VV)-ECMO and veno-arterial (VA)-ECMO accounted for 27 and 73% respectively. The VA-ECMO patients had more intra-transport interventions compared with VV-ECMO transported patients, but none resulting in serious morbidity or death. There was no overall difference in survival at 6 months between retrieved and ECMO center patients: VV-ECMO (75 vs. 70%, P = 0.690) versus VA-ECMO (70 vs. 68%, P = 1.000). An intensive care physician-led team was able to safely place all critically ill patients on ECMO and retrieve them to an ECMO center. This may be an appropriate staffing model for ECMO retrieval.

The bulk nanostructure of several inorganic salt solutions in protic ionic liquids is elucidated using neutron diffraction and empirical potential structure refinement modeling. The protic ionic liquids studied are ethylammonium nitrate (EAN) and ethanolammonium nitrate (EtAN), which are mixed with either LiNO3, Mg(NO3)2, Ca(NO3)2, or Al(NO3)3 at 1:10 or 1:30 solute:solvent mol:mol ratios. The models show inorganic metal ions are solvated within the polar domains of the nanostructure and can induce significant differences in bulk solvent nanostructure from that of the pure ionic liquids. For EtAN, the uncharged groups aggregate and form an apolar domain in spite of the cation’s reduced amphiphilicity because the trans rotamer is favored when an inorganic salt is added.

Major depressive disorder (MDD) is a common and debilitating illness in patients with cancer. However, the optimal treatment of depression in these patients remains uncertain, with limited evidence to support the use of pharmacologic therapy. We conducted a pilot study to evaluate the feasibility of an antidepressant clinical trial in the oncology population and the process of symptom-oriented selection of antidepressants (citalopram or mirtazapine) in patients with cancer and MDD.This was a single center, two-arm, nonrandomized, open-label, nine-week pilot study of mirtazapine or citalopram in cancer patients with MDD. The primary endpoint was the feasibility to recruit and to retain patients. Secondary outcomes included changes in Patient Health Questionnaire-9 (PHQ-9) (depression), Functional Assessment of Cancer Therapy-General (FACT-G) (quality of life), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) (fatigue), and Pittsburgh Sleep Quality Index (PSQI) (sleep). We conducted descriptive statistics and responder analyses.Of 21 patients, 18 (86%) successfully completed the study. An average of 2.8 subjects were enrolled per month. Mean scores on the PHQ-9 improved overall by 6.4 points (95% confidence interval [CI] 3.6-9.2). Additionally, mean FACT-G, FACIT-Fatigue, and PSQI scores improved in both study arms.Conducting antidepressant clinical trials is challenging in the oncology population. We approached but did not meet our feasibility goals. Depression and quality of life (QOL) scores improved with both mirtazapine and citalopram, but evidence-based pharmacologic treatments for depression in cancer patients are needed.

e23064 Background: The current exploratory cross-sectional study was designed to better characterize survivorship issues among patients treated with radiation for head and neck cancer with regard to dental health, shoulder-neck dysfunction, and overall quality of life. Methods: Patients (n = 58) being seen for follow-up at a radiation oncology clinic at least one year beyond the end of treatment completed three survey questionnaires: the EORTC Core Quality of Life Questionnaire (EORTC QLQ-C30), the EORTC Head and Neck module (EORTC QLQ-H&N35), and an original 18-item Dental Health and Shoulder Function questionnaire. The questionnaires were scored and univariate analyses were performed using the variables of age, radiation dosage, definitive radiation + neck dissection vs. definitive surgery + postoperative radiation, and chemotherapy. Results: Median follow-up was 2.5 years. Of patients surveyed, 35% reported having more problems with their general dental health as compared to before treatment and 38% reported having pain at night in the neck and shoulder; 79% of patients reported being counseled about their dental health prior to treatment while 31% reported being counseled about possible shoulder-neck dysfunction. Patients younger than 65, patients receiving higher doses of radiation, and patients undergoing definitive surgery + postoperative radiation reported a higher burden of functional and symptomatic issues. Conclusions: Patients treated with radiation for head and neck cancer face a number of survivorship issues, including problems with dental health and shoulder-neck dysfunction, and many do not feel that they are adequately counseled about these issues prior to treatment. Subsets of patients who may experience a higher burden of functional and symptomatic issues include patients younger than 65, patients receiving higher doses of radiation, and patients undergoing definitive surgery + postoperative radiation. Increasing pre-treatment counseling for all patients and placing a particular emphasis on supportive care for these subsets of patients may allow us to better support this growing population of cancer survivors.

Objectives Gemcitabine is a potent radiosensitizer. When combined with standard radiotherapy (XRT) the gemcitabine dose must be reduced to about 10% of its conventional dose. Oxaliplatin and erlotinib also have radiosensitizing properties. Oxaliplatin and gemcitabine have demonstrated synergy in vitro. We aimed to determine the maximum tolerated dose of oxaliplatin and gemcitabine with concurrent XRT, then oxaliplatin, gemcitaibine, and erlotinib with XRT in the treatment of locally advanced and low-volume metastatic pancreatic or biliary cancer. Methods A modified 3+3 dose-escalation design was used for testing 4 dose levels of oxaliplatin and gemcitabine given once weekly for a maximum of 6 weeks with daily XRT in fractions of 1.8 Gy to a total dose of 50.4 Gy. Dose-limiting toxicity (DLT) was defined as any grade 4 toxicity or grade 3 toxicity resulting in a treatment delay of >1 week. In addition, dose reduction in 2 of the 3 patients in a given cohort was counted as a DLT in dose escalation-deescalation rule in the modified 3+3 design. Results Eighteen patients were enrolled, all with pancreatic cancer. Grade 4 transaminitis in a patient in cohort 3 resulted in cohort expansion. Cohort 4, the highest planned dose cohort, had no DLTs. The recommended phase II dose is oxaliplatin 50 mg/m(2)/wk with gemcitabine 200 mg/m(2)/wk and 50.4 Gy XRT. The most prevalent grade 3 toxicities were nausea (22%), elevated transaminases (17%), leucopenia (17%), and hyperglycemia (17%). Median progression-free survival was 7.1 months (95% confidence interval, 4.6-11.1 mo) and median overall survival was 10.8 months (95% confidence interval, 7.1-16.7 mo). The addition of erlotinib was poorly tolerated at the first planned dose level, but full study of the combination was hindered by early closure of the study. Conclusions Weekly oxaliplatin 50 mg/m/wk combined with gemcitabine 200 mg/m/wk and XRT for pancreatic cancer has acceptable toxicity and interesting activity.

Background Embolizing branches of the hepatic artery lengthens survival for patients with unresectable hepatocellular carcinoma (HCC), but the benefit of combining chemotherapy with the embolizing particles remains controversial. Methods A retrospective review was undertaken of sequential patients with advanced HCC undergoing embolization in the past 10 years at 2 neighboring institutions and with 2 years of follow-up data. TACE was generally performed with doxorubicin plus mitomycin C. Results: One hundred twenty-four patients were included; 77 received TACE and 47 received TAE. On multivariable analysis stratified by institution, type of embolization and CLIP score significantly predicted PFS and time to progression (TTP), whereas CLIP score and AFP independently predicted overall survival (OS). TACE significantly prolonged PFS and TTP (P = .0004 and P = .001, respectively), but not OS (P = .83). Conclusions The addition of chemotherapy to TAE prolongs PFS and TTP. Future efforts should focus on adjunctive therapies after the embolization to increase survival.

First published in 1702, Edward Bysshe's The Art of English Poetry presents us with the reading and associational world of an almost unknown man. Coming in three parts: "Rules," "A Dictionary," and "A Collection," The Art of English Poetry was the pre-eminent prosodic handbook, rhyming dictionary and dictionary of quotations of the eighteenth century, being expanded and reprinted nine times. This essay focuses in particular on "A Collection"—a commonplace book of literary quotations—showing its history, construction, and what it has to tell us about the reading habits of the 1690s and the early decades of the eighteenth century.

Purpose Rectal cancer is often clinically resistant to radiotherapy (RT) and identifying molecular markers to define the biologic basis for this phenomenon would be valuable. The nuclear factor κ-light chain-enhancer of activated B cells (NF-κB) is a potential anti-apoptotic transcription factor that has been associated with resistance to RT in model systems. The present study was designed to evaluate NF-κB activation in patients with rectal cancer undergoing chemoradiotherapy to determine whether NF-κB activity correlates with the outcome in rectal cancer patients. Methods and Materials A total of 22 patients underwent biopsy at multiple points in a prospective study and the data from another 50 were analyzed retrospectively. The pretreatment tumor tissue was analyzed for multiple NF-κB subunits by immunohistochemistry. Serial tumor biopsy cores were analyzed for NF-κB–regulated gene expression using reverse transcriptase polymerase chain reaction and for NF-κB subunit nuclear localization using immunohistochemistry. Results Several NF-κB target genes (Bcl-2, cellular inhibitor of apoptosis protein [cIAP]2, interleukin-8, and tumor necrosis factor receptor-associated-1) were significantly upregulated by a single fraction of RT at 24 h, demonstrating for the first time that NF-κB is activated by RT in human rectal tumors. The baseline NF-κB p50 nuclear expression did not correlate with the pathologic response to RT. However, an increasing baseline p50 level was prognostic for overall survival (hazard ratio, 2.15; p = .040). Conclusion NF-κB nuclear expression at baseline in rectal cancer was prognostic for overall survival but not predictive of the response to RT. Larger patient numbers are needed to assess the effect of NF-κB target gene upregulation on the response to RT. Our results suggest that NF-κB might play an important role in tumor metastasis but not to the resistance to chemoradiotherapy.

Purpose: To describe a pharmacist-led, interdisciplinary method of care delivery begun at the University of North Carolina. We describe the characteristics of the population seen and the role of the individual members of the interdisciplinary team, and provide an early analysis of the program’s impact on symptom improvement. Methods: A supportive care consultation service was begun at the University of North Carolina Hospitals to serve adult outpatients with cancer undergoing treatment or follow-up. Patients data were entered into an institutional review board–approved database to permit detailed assessments over time. Patient demographics were analyzed using descriptive statistics, medications used and changes made were noted, and symptom scores from a previously described instrument were captured and compared over time. Results: Patients were seen from all adult oncology services, includinggynecologic,radiation,medical,andsurgical.Thecharacteristics of the population seen were similar to those of the hospital population as a whole. Most of the patients were seen for pain management, and many required a medication change. Symptom scores improved by the second visit, and the improvement was maintained. Conclusion: We are able to demonstrate that the use of a pharmacist-led, interdisciplinary team produced an improvement in symptom scores comparable to what has been seen in the inpatient palliative care service within our institution. Projected shortages of oncology providers may be mitigated by pharmacists working in collaborative practices, with prescriptive authority, in the ambulatory oncology setting.

Although diabetic patients with rectal cancer have poorer outcomes than their nondiabetic counterparts, few studies have looked at diabetics’ response to therapy as an explanation for this disparity. This study compares the neoadjuvant chemoradiotherapy (CRT) response in diabetic and nondiabetic patients with locally advanced rectal cancers. This is a single-institution, retrospective review of rectal cancer patients who received CRT followed by resection from 1995 to 2006. Pretreatment tumor–node–metastasis (TNM) staging was determined using endorectal ultrasound, computed tomography (CT) scan, and magnetic resonance imaging (MRI); post-treatment staging was determined by pathological review. 110 patients were included; seventeen had diabetes and 93 were nondiabetics. Pretreatment staging was similar in both groups. Sixteen of the diabetics (94%) completed CRT compared to 92% (86/93) of the nondiabetics. Tumor downstaging rates were similar in the two groups (53% in diabetics, 52% in nondiabetics). Nondiabetic patients had a higher rate of nodal downstaging although not statistically significant (67% versus 27%, P = 0.80). While none of the diabetics patients achieved a pathologic complete response (pCR), 23% (21/93) of the nondiabetics did (P = 0.039). Local progression rates were higher in the diabetic group (24% versus 5%, P = 0.046). Our study shows that neoadjuvant chemoradiotherapy in rectal cancer is less effective in diabetic patients than in nondiabetics. While minimal differences are found in the rate of downstaging, the rate of achieving a complete pathologic response was significantly higher in nondiabetic patients, and in fact was not seen in any of our diabetic patients. This may explain the poorer outcomes seen in diabetic patients with rectal cancer.

Background Oxaliplatin combined with 5-fluorouracil (5-FU), with or without leucovorin (LV), is effective and well tolerated for first-line therapy of advanced colorectal cancer (CRC). However, there is no consensus as to which oxaliplatin/5-FU–containing regimen is superior in the first-line setting. This randomized, multicenter phase II trial was designed to evaluate and compare the efficacy of 4 different oxaliplatin/5-FU regimens. Patients and Methods Patients with previously untreated metastatic CRC (mCRC; n = 129) were randomized to 1 of 4 treatment regimens: (1) continuous 5-FU infusion plus oxaliplatin (n = 23); (2) weekly 5-FU bolus with LV plus oxaliplatin (n = 40); (3) oxaliplatin with 2-day infusion 5-FU/LV (FOLFOX4, n = 41); and (4) chronomodulated 5-FU plus oxaliplatin (n = 25). Results Overall response rates, after expert assessment, ranged from 24% to 34%, and median progression-free survival (PFS) ranged from 6 months to 8 months. Although no significant differences in efficacy were detected in pairwise comparisons of the 4 different regimens, patients randomized to FOLFOX4 had the highest response rate and longest PFS. The FOLFOX4 regimen was also associated with the lowest incidence of severe (grade 3/4) toxicity, with the exception of cumulative peripheral neurotoxicity. Conclusion This randomized phase II trial provides evidence that oxaliplatin/5-FU regimens are effective and well tolerated for first-line therapy of previously untreated mCRC. The FOLFOX regimens are now an established standard for CRC.

Milataxel is a novel taxane analog, with evidence of enhanced preclinical activity compared to paclitaxel and docetaxel, especially in cell lines that over express P-glycoprotein. Based on preclinical data that milataxel may be active in colorectal cancer (CRC), a phase II study was performed in patients with advanced previously treated CRC.Forty-four eligible patients were entered. Milataxel was administered intravenously every 3 weeks at the dose of 35 mg/m(2). No objective responses were noted, stable disease was seen in three patients. The median time to progression was 1.4 months (95% CI of 1.2-2.4 months). Three subjects developed neutropenic sepsis and two died. The most frequent grade 3/4 adverse events were neutropenia (57%), leukopenia (27%), dehydration (14%), neuropathy (16%), diarrhea (14%) and thrombocytopenia (14%). The pharmacokinetics of milataxel was assessed in five subjects. The mean milataxel elimination half-life was 64 h and the mean area under the plasma concentration-time curve was 1,708 ng h/ml.A syndrome of neutropenic sepsis and diarrhea can be life threatening and close surveillance is needed in patients treated with milataxel at the dose of 35 mg/m(2) every 3 weeks. Clinical activity was not demonstrated in patients with advanced previously treated CRC.

As palliative care expands into the outpatient clinic, the potential for drug interactions increases as patients that are on active treatment for their cancer are also receiving coordinated management for symptoms such as pain, depression, and nausea and vomiting. The drugs used in inpatient palliative care for patients with advanced illness but not on active management of their malignancy must now be reviewed for potential interactions with both older and newer oncology drugs. Reported frequencies of drug interactions in oncology range from 12 to 63 %; and in palliative care they range from 31 to 43 %. Among the drugs which are most likely to cause interactions, nonsteroidal anti-inflammatories, warfarin, antiemetics, and antipsychotics still account for the largest proportion of reports in survey literature. Many of these interactions are pharmacodynamic. Recently, prolongation of the QT interval has become a pharmacodynamic effect of increasing concern with antidepressants, methadone, and many of the newer oral oncology agents.

DNA polymorphisms have been identified in the genes encoding a number of the cytochrome P450 (CYP) enzymes, leading to wide interindividual variation in drug clearance. CYP2D6 metabolizes a significant number of clinically used medications, and genetic variants of the CYP2D6 isozyme that result in varying levels of metabolic activity are of clinical importance in some settings. The exact nature of the clinical effect caused by polymorphisms of the gene depends on the drug in question and the specific variant alleles expressed, as individual variants result in differing phenotypes with a range of levels of enzymatic activity. Compromised drug efficacy due to CYP2D6 variation has been documented with a variety of agents, and this review considers a number of examples, including the 5-HT(3)-receptor antagonists, which are used in oncology supportive care for the prophylaxis of nausea and vomiting. CYP2D6 is involved in the metabolism of all of the most commonly available agents, except granisetron, and their efficacy and side effects may therefore be affected by the CYP2D6 polymorphism. Significant interethnic differences in CYP2D6 allele frequencies have been demonstrated from studies across many countries. However, incidences of polymorphisms in the U.S. population have been challenging to characterize because of the country's wide ethnic diversity. The CYP2D6 polymorphism may become more important as robust clinical tests become widely available and as the use of multiple medications and the attendant risk for drug-drug interactions increases.

The purpose of this article is to assess the comparative antiemetic efficacy of prochlorperazine, ondansetron, and dexamethasone in the prevention of delayed chemotherapy-induced nausea and vomiting (CINV) after moderately high to highly emetogenic chemotherapy. Cancer patients (n = 232) receiving moderately high to highly emetogenic chemotherapy were randomized to 1 of 3 treatments: 15 mg prochlorperazine spansules twice daily; 8 mg ondansetron tablets twice daily; or 8 mg dexamethasone tablets twice daily on days 2 through 5. All patients received 24 mg ondansetron and 20 mg dexamethasone orally before chemotherapy. Daily assessment (days 1 through 5) included the number of episodes of retching and vomiting, severity of nausea, restlessness, difficulty concentrating and fatigue, treatment satisfaction, and overall quality of life (measured using a 10-cm VAS). The Functional Living Index-Emesis (FLIE) was completed on day 5. Other side effects attributed to antiemetic therapy were recorded daily. For acute CINV, total control, defined as no vomiting, retching, nausea

This phase I study investigated the safety, dose-limiting toxicity, and efficacy in three cohorts all treated with the mTOR inhibitor everolimus that was delivered (1) in combination with 5-fluorouracil with leucovorin (5-FU/LV), (2) with mFOLFOX6 (5-FU/LV + oxaliplatin), and (3) with mFOLFOX6 + panitumumab in patients with refractory solid tumors. Patients were accrued using a 3-patient cohort design consisting of two sub-trials in which the maximum tolerated combination (MTC) and dose-limiting toxicity (DLT) of everolimus and 5-FU/LV was established in Sub-trial A and of everolimus in combination with mFOLFOX6 and mFOLFOX6 plus panitumumab in Sub-trial B. Thirty-six patients were evaluable for toxicity, 21 on Sub-trial A and 15 on Sub-trial B. In Sub-trial A, DLT was observed in 1/6 patients enrolled on dose level 1A and 2/3 patients in level 6A. In Sub-trial B, 2/3 patients experienced DLT on level 1B and subsequent patients were enrolled on level 1B-1 without DLT. Three of six patients in cohort 2B-1 experienced grade 3 mucositis, and further study of the combination of everolimus, mFOLFOX6 and panitumumab was aborted. Among the 24 patients enrolled with refractory metastatic colorectal cancer, the median time on treatment was 2.7 months with 45 % of patients remaining on treatment with stable disease for at least 3 months. While a regimen of everolimus in addition to 5-FU/LV and mFOLFOX6 appears safe and tolerable, the further addition of panitumumab resulted in an unacceptable level of toxicity that cannot be recommended for further study. Further investigation is warranted to better elucidate the role which mTOR inhibitors play in patients with refractory solid tumors, with a specific focus on mCRC as a potential for the combination of this targeted and cytotoxic therapy in future studies.

A phase I study of a 96 h paclitaxel infusion with filgrastim support was performed to determine the toxicity, maximum-tolerated dose (MTD) and pharmacokinetics in patients with refractory solid tumors. In this phase I trial, the initial paclitaxel dose was 140 mg/m2/96 h followed by filgrastim (5 microg/kg/day s.c.) beginning 24 h after the paclitaxel and continued until granulocyte recovery. Cycles were repeated every 21 days. Patients with refractory solid tumors were eligible; however, only one previous chemotherapy regimen was allowed. The dose of paclitaxel was escalated by 20 mg/m2/96 h in subsequent cohorts until dose-limiting toxicity (DLT) occurred. Pharmacokinetic analysis was performed by quantitating paclitaxel concentrations at baseline, 24, 48, 72 and 96 h after the start of the paclitaxel infusion. Twenty-one patients were entered into this trial of which 19 were evaluable. A total of 52 treatment cycles were administered. DLT was seen in two of four patients at 200 mg/m2/96 h, and consisted of diarrhea, mucositis and granulocytopenic infection. The MTD of the 96 h paclitaxel infusion was 180 mg/m2 with filgrastim support. Mucosal and granulocyte toxicity were correlated with steady-state paclitaxel concentrations (Css) greater than 0.100 micromol/l. In the presence of liver function test 1.5 times or lower than normal, metastatic liver disease did not alter paclitaxel Css. Objective responses were observed in non-small cell lung cancer, small cell lung cancer and melanoma. The recommended phase II dose of paclitaxel infused over 96 h with filgrastim support is 180 mg/m2. Paclitaxel Css correlate with mucosal and granulocyte toxicity. In the presence of normal enzymatic function, metastatic liver disease does not affect paclitaxel clearance.

It is widely believed that patients' reluctance to report pain and adhere to treatment recommendations are significant barriers to cancer pain control. However, few investigators have examined barriers to cancer pain management from the cancer patient's perspective. Ambulatory patients with cancer who had experienced cancer-related pain in the previous month or were currently taking analgesics for cancer pain control were asked to participate in this study. Information regarding (a) pain assessment, (b) pain medication use, (c) concerns and barriers to compliance, (d) communication patterns regarding pain and pain control, and (e) demographics were collected during a 10-min structured interview. Approximately 20% of patients with a current cancer diagnosis who were approached reported that they had experienced pain or taken analgesic drugs during the preceding month. Eighty-eight percent of these patients ranked their pain as five or greater (scale, 0-10), and 81% reported impaired function due to pain. Major barriers to effective treatment included forgetfulness, the belief that pain should be tolerated, concerns about side effects, and fear and disdain of dependence, addiction, and tolerance. One-third of patients felt that their pain could not be better controlled than it currently was. Patients reported frequent communication regarding pain and pain control with physicians (52%), nurses (41%), and pharmacists (17%). The low pain prevalence, coupled with high pain intensity and associated dysfunction, appears to be a reflection of patient's unwillingness to report pain of mild to moderate intensity. In addition to previously recognized factors, stoicism and fatalism represent significant barriers to cancer pain control.

Purpose The purpose of this evaluation is to examine the relationship among nurses' pain management attitudes and pain management practices and to begin to explore the theoretical underpinnings that may influence this relationship. Description of study A convenience sample of 29 female registered nurses working in hospice or home health settings participated in an educational program 1 day per week for 6 weeks. All participants were asked to complete the Cancer Pain Knowledge Inventory and Survey of Expectations and Pain Assessment Questionnaire 5 weeks before, immediately before, immediately after, 6 months after, and 12 months after the program. Seventeen participants completed all questionnaires at the 6-month follow-up; 16 participants completed all questionnaires at the 1-year follow-up. Personal beliefs about pain were evaluated in relation to the dimensions and treatment of pain. Intentions and expectations to perform specific activities were evaluated in relation to in-depth assessments, equianalgesic conversions, demonstration of new ideas, and communication. Results Nurses' attitudes, beliefs, intentions, and expectations about pain and pain management influenced nurses' patient care and educational activities. Nurses who believed that patients should be pain free and nurses who focused on both the dimensions and treatment of pain implemented more pain management activities. In general, nurses who had high intentions and expectations performed more pain management activities. Clinical implications Although nurses reported change in attitude, and high expectancy for change, feelings of increased credibility, and increased motivation as advocates for new approaches to practice, nurses sometimes found it difficult to implement new practices because of constraints in time and collaborative efforts. To implement new knowledge and achieve individualized goals for change, nurses must be allowed adequate time to analyze the relationships between their beliefs about pain and the ways that they solve patients' pain problems. In addition, more support for multidisciplinary collaboration is needed.

Objective The aim of this report is to discuss the design of an antidepressant clinical trial and discuss the challenges and potential solutions to these challenges to successful recruitment of oncology patients for psychopharmacology trials. Method We utilize meeting minutes and investigator discussions to identify the modifiable and nonmodifiable variables that affected successful subject recruitment for this study. Results No subjects were enrolled in our placebo-controlled antidepressant trial. After study modification to remove the placebo arm, we enrolled 21 subjects with depression and cancer. We identified the following recruitment difficulties during the study: diagnostic ambiguity in patients with depression and cancer, lowered subject retention in a medically ill population, patient reluctance to enroll in placebo-controlled studies and lack of a standardized referral processes for antidepressant studies in oncology at our institution. Conclusion Our experience provides guidance on specific factors that future clinicians and researchers can consider when implementing psychopharmacologic trials in the medically ill.

Background: Converting between the various opioid agents continues to be challenge for many practitioners. Specifically, variable recommendations for converting to the transdermal fentanyl patch may lead to confusion among clinicians and errors in dosing. Objective: Our aim was to describe the inconsistencies among available opioid conversions with regard to transdermal fentanyl and to provide recommendations for safe and effective utilization of this product in patients with chronic pain. Results: Available reports support the use of the morphine intravenous to oral ratio of 1:3 during the conversion to transdermal fentanyl product. Conclusions: Underdosing is an often overlooked complication of switching to transdermal fentanyl. Current recommendations for converting to transdermal fentanyl do not reflect contemporary clinical practice and should be reevaluated.

An educational program designed to change knowledge in order to change pain management practices and patient outcomes was offered to nurses who provide day-to-day care to patients with cancer in communities in a predominately rural state. A quasi-experimental time-series design was used to measure the effectiveness of the program in changing nurse knowledge, attitude and behavior, and to evaluate the relationships between the outcomes. Data were collected from nurses ( N = 29) and patient charts before ( N = 209) and after ( N = 163) the program. Nurses' knowledge increased, but the change was not statistically significant; the mean percent of correct answer on the three subtests were different and differences persisted throughout the study. Nurses believed that patients should be "pain free". Documentation of behaviors, for example, practice activities, occurred infrequently and showed little change until 6 months after the program. Increase in documentation of pain-intensity ratings, pain location, number of sites of pain, presence of confusion, anxious or depressed mood, sleep, nausea and vomiting, constipation, and general activity were noted. Documentation of the use of a propoxyphene-containing analgesic decreased; increase in the use of hydromorphone methadone and transdermal fentanyl was noted. Analysis of the relationships between correct responses to nurse knowledge questions and documentation of behavior provided interesting, statistically insignificant results that need to be reexamined in future research. Future programs should emphasize analgesic dosing and calculation of equianalgesic doses. Current practices in chart documentation may provide incomplete information regarding change in practice behaviors; more detailed documentation of pain management practices is needed. Nurses who participated in the program anecdotally reported feelings of increased credibility and effectiveness. Although change in behavior is slow to occur, education does make a difference.

Hospice and palliative care providers need ways to measure and improve care processes. We tested feasibility, usability, reliability, and validity of Prepare, Embrace, Attend, Communicate, Empower (PEACE) quality measures for palliative care.Trained research nurses abstracted data from medical records to generate quality measures for a random sample of 460 seriously ill patients without, and 102 patients with, specialty palliative care (SPC) services.Patient age ranged from 16 to 99 years, 50% were women, and 24% were African American. Of 34 PEACE quality measures, 17 were feasible for hospital palliative care. Inter-rater reliability was high (κ0.80) for all but two quality measures. Face validity was endorsed by clinical service leaders, and construct validity was established by higher scores for patients receiving SPC. Comprehensive palliative care assessment was completed for only 10% of seriously ill hospitalized patients, compared with 56% of patients with SPC (p0.001). Patients with moderate or severe pain were more likely to have a clinical assessment with SPC (67% versus 42%, p=0.002). Patients with SPC more often received attention for their emotional and spiritual needs (64% versus 40%, p0.001) and documentation of preferences for life-sustaining treatments (91% versus 59%, p0.001). Usability was endorsed by service leaders, who initiated two practice improvement projects.PEACE quality measures are feasible and reliable, and may be useful to examine and improve the quality of palliative care for seriously ill hospitalized patients as well as for patients in hospice. Research is needed to test measures for actionability and responsiveness to intervention.

To evaluate the effects on temperature and outcome at hospital discharge of a pre-hospital rapid infusion of large volume, ice-cold intravenous Hartmann's solution in patients with out-of-hospital cardiac arrest and an initial cardiac rhythm of asystole or pulseless electrical activity.Prospective, randomized, controlled clinical trial.Pre-hospital emergency medical service and 12 critical care units in Melbourne, Australia.One hundred and sixty three patients who had been resuscitated from cardiac arrest with an initial cardiac rhythm of asystole or pulseless electrical activity.: Patients were randomized to either pre-hospital cooling using a rapid infusion of up to two litres ice-cold Hartmann's solution (82 patients) or cooling after hospital admission (81 patients). The planned duration of therapeutic hypothermia (32 °C-34 °C) in both groups was 24 hrs.Patients allocated to pre-hospital cooling received a median of 1500 ml of ice-cold fluid. This resulted in a mean decrease in core temperature of 1.4 °C compared with 0.2 °C in hospital cooled patients (p.001). The time to therapeutic hypothermia (34 °C) was 3.2 hrs in the pre-hospital cooled group compared with 4.8 hrs in the hospital cooled group (p = .0328). Both groups received a mean of 15 hrs cooling in the hospital and only 7 patients in each group were cooled for 24 hrs. Overall, there was no difference in outcomes at hospital discharge with favorable outcome (discharge from hospital to home or rehabilitation) in 10 of 82 (12%) in the pre-hospital cooled patients, compared with 7 of 81 (9%) in the hospital cooled patients (p = .50). In the patients with a cardiac cause of the arrest, 8 of 47 patients (17%) who received pre-hospital cooling had a favorable outcome at hospital discharge compared with 3 of 43 (7%) in the hospital cooled group (p = .146).In adults who have been resuscitated from out-of-hospital cardiac arrest with an initial cardiac rhythm of asystole or pulseless electrical activity, pre-hospital cooling using a rapid infusion of large-volume, ice cold intravenous Hartmann's solution decreases core temperature at hospital arrival and decreases the time to therapeutic hypothermia. In patients with a cardiac cause of the arrest, this treatment may increase the rate of favorable outcome at hospital discharge. Further larger studies should evaluate the effects of pre-hospital cooling when the initial cardiac rhythm is asystole or pulseless electrical activity, particularly in patients with a cardiac cause of the arrest.

Purpose The development, implementation, and early experience with a program providing clinical pharmacist services at the hematology–oncology clinics of a university teaching hospital are described. Summary With funding from a university research grant and other sources, a pharmacist was hired to launch a new program addressing four goals identified in a needs assessment: (1) improved management of supportive care, (2) enhanced education of patients receiving complicated chemotherapy regimens, (3) improved efficiency in the chemotherapy infusion unit, and (4) development of an experiential learning opportunity for pharmacy students and residents. The pharmacist hired to lead the ongoing program was a state-approved clinical pharmacist practitioner (CPP) who had authority to prescribe with physician oversight under established protocols. Experience An oncology supportive care consultation service implemented by the CPP in collaboration with a nurse and a physician served 89 new patients in its first 18 months of operation; during that period the CPP made 186 interventions and wrote 136 prescriptions. The CPP also established a chemotherapy counseling service that provided more than 900 bill-able patient education sessions over 18 months. In addition, the CPP launched an effort to increase use of a rituximab rapid-infusion protocol among eligible patients. The creation of the new oncology pharmacist position has given dozens of pharmacy students and residents a new opportunity for interaction with oncology clinic patients and other health care team members. Conclusion Integration of the services of a CPP into the hematology–oncology clinics has helped achieve goals set by physician, nursing, and pharmacy leaders.

Sorafenib has demonstrated single agent activity in non-small cell (NSCLC) and small cell lung cancer (SCLC). Carboplatin/pemetrexed (CbP) and cisplatin/etoposide (PE) are commonly used in the treatment of these diseases.A phase I trial escalating doses of sorafenib in combination with fixed doses of PE (Arm A) or CbP (Arm B) was performed using a 3-patient cohort design to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT); DLT were assessed in the first cycle. The trial was subsequently amended with closure of Arm B and to include Arm C with a reduced dose of carboplatin.Between 9/2007 and 9/2008, 20 pts were treated on the trial; median age 62 (range 42-73), male/female ratio 12/8, PS 0/1 ratio 6/14, and median number of prior therapies 2 (range 1-4). The most common tumor types were NSCLC and SCLC. On Arm A at dose level 0 (sorafenib 200 mg BID), 2 of 4 patients experienced DLT; 2 patients were enrolled at dose level -1 (sorafenib 200 mg QD) without DLT, but this arm was closed due to slow accrual. On Arm B, 2 of 3 patients experienced DLT at dose level 0 (sorafenib 200 mg BID). On Arm C at dose level 0 (sorafenib 200 mg BID), 1 of 6 patients experienced DLT, and at dose level +1 (sorafenib 400 mg BID) 2 of 5 patients experienced a DLT.The MTD of sorafenib was 200 mg BID continuously in combination with carboplatin (AUC of 5) and pemetrexed 500 mg/m² every 3 weeks. However, only 6 patients were treated at this dose level, and the results should be interpreted cautiously.

Standard therapy for stage II/III rectal cancer consists of a fluoropyrimidine and radiation therapy followed by surgery. Preclinical data demonstrated that bortezomib functions as a radiosensitizer in colorectal cancer models. The purpose of this study was to determine the maximum tolerated dose (MTD) of bortezomib in combination with chemotherapy and radiation.Patients with locally advanced rectal adenocarcinomas, as staged by endoscopic ultrasound, were eligible. Bortezomib was administered on days 1, 4, 8, and 11 every 21 days for 2 cycles with 5-fluorouracil at 225 mg/m2/day continuously and 50.4 Gy of radiation. Dose escalation of bortezomib was conducted via a standard 3 + 3 dose escalation design. A subset of patients underwent serial tumor biopsies for correlative studies.Nine patients in 2 dose cohorts were enrolled. Diarrhea was the principal dose-limiting toxicity and occurred at the 1.0-mg/m2 dose level. There was no clear evidence of suppression of nuclear factor-kappaB target gene expression in biopsy samples.The MTD of bortezomib in combination with chemotherapy and radiation may be below a clinically relevant dose, limiting the clinical applicability of this combination. Performing biopsies before and during irradiation for determining gene expression in response to radiation therapy is feasible.

Purpose Edrecolomab (ED) is a murine monoclonal antibody targeting the EpCam antigen. This phase III randomized multicenter trial investigated the benefit of adding ED to fluorouracil (FU) based therapy in patients with stage III colorectal cancer. Patients and Methods Patients with stage III colon cancer were randomly assigned to one of two treatments after curative surgery. Patients in arm 1 received five infusions of ED together with FU-based chemotherapy; patients in arm 2 received FU-based chemotherapy alone. The primary end point was overall survival (OS). Results One thousand eight hundred thirty-nine patients were randomly assigned; results were analyzed on an intent-to-treat basis. Patient characteristics were well-balanced across treatment arms. Five-year follow-up has been completed. Patients randomly assigned to ED plus FU-based therapy showed a 5-year survival rate of 69.6% while for patients receiving FU-based therapy, the rate was 68.2%. The hazard ratio for death with ED plus FU-based therapy compared to FU-based therapy was 0.896 (95% CI, 0.752 to 1.068), which was not statistically significant (P = .220). The adverse effect profiles of the two treatment arms were similar, with the main adverse effects being diarrhea, abdominal pain, and nausea. Anaphylaxis occurred in fewer than 1% of patients receiving ED. Conclusion For patients with stage III colon cancer, the addition of ED to FU-based therapy had no statistically significant effect on OS.

Purpose Patients with portal vein thrombosis (PVT) and hepatocellular carcinoma (HCC) have limited treatment options because of increased disease burden and diminished hepatic perfusion. Yttrium-90 ( 90 Y) microspheres may be better tolerated than chemoembolization in these patients. The present study reviews the safety and efficacy of 90 Y microspheres in HCC with major PVT. Materials and Methods A retrospective review of HCC with main ( n = 10) or first-branch ( n = 12) PVT treated with 90 Y microspheres ( N = 22) was conducted. Cancer of the Liver Italian Program (CLIP) scores ranged from 2 to 5, with 18% of patients having a score of 4 or greater. Imaging response at 8–12 was based on Response Evaluation Criteria In Solid Tumors. Overall survival (OS) was estimated by the Kaplan-Meier method. Results A total of 32 microsphere treatments (26 glass, six resin) were administered to 22 patients. Common grade 1/2 toxicities included abdominal pain (38%), nausea (28%), and fatigue (22%). Four posttreatment hospitalizations occurred, all less than 48 hours in duration. One death occurred 10 days after therapy. The partial response rate was 8% and progressive disease was seen in 42% of patients. Stable disease was achieved in 50% of treatments. Median OS was 7 months from initial treatment. Patients with Child-Pugh class A disease had a median OS of 7.7 months; those with class B/C disease had an OS of 2.7 months ( P = .01). Median OS for patients with CLIP scores of 2/3 was 7 months, versus 1.3 months for those with scores of 4/5 ( P = .04). Conclusions Yttrium-90 microspheres are tolerated in patients with HCC and major PVT. Compared with chemoembolization, rates of severe adverse events appear low. Radiographic response rates are low. The median OS of 7 months is promising and warrants further study versus systemic therapy.

To determine a dose-response relationship of ondansetron for the prevention of emesis induced by high-dose cisplatin and to study the efficacy of the extended dosing schedule of ondansetron during 20 hours after cisplatin administration, 36 patients with malignant neoplasms who had not previously received chemotherapy but who were currently receiving cisplatin were treated. These patients received a six-dose regimen of 0.01 mg/kg (low dose) or 0.18 mg/kg (high dose) of ondansetron. Seven (41%) patients in the high-dose group had no emesis and four (24%) patients had one or two episodes. One (5%) patient in the low-dose group had no emesis and four (21%) patients had one or two episodes. The difference in the number of emetic episodes was significant (P less than 0.02). Fifty percent of the high-dose patients reported no nausea or mild nausea, compared with 11% of the low-dose patients. Clinical adverse events included mild, transient headache and dizziness in the high-dose group and headache and diarrhea in the low-dose group, with no significant laboratory abnormalities. There is a parallel relationship between the ondansetron doses and the antiemetic efficacy. The response rate for the six-dose regimen of 0.18 mg/kg was not superior to that for the previously reported 0.18 mg/kg regimen given in a three-dose schedule in a similar clinical setting.

Physicians are often asked to prognosticate patient survival. However, prediction of survival is difficult, particularly with critically ill and dying patients within the hospitals. The Palliative Performance Scale (PPS) was designed to assess functional status and measure progressive decline in palliative care patients, yet it has not been validated within hospital health care settings.This study explores the application of the PPS for its predictive ability related to length of survival. Other variables examined were correlates of symptom distress in a tertiary academic setting.Patients were assigned a score on the PPS ranging from 0% to 100% at initial consultation. Standardized symptom assessments were carried out daily, and survival was determined by medical record review and search of the National Death Index.Of 261 patients seen since January 2002, 157 had cancer and 104 had other diagnoses. PPS scores ranged from 10% to 80% with 92% of the scores between 10% and 40%. Survival ranged from 0 to 30 months, with a median of 9 days. By 90 days, 83% of patients had died. Proportional hazards regression estimates showed that a 10% decrement in PPS score was associated with a hazard ratio of 1.65 (95% confidence interval [CI]: 1.42-1.92). Proportional odds regression models showed that a lower PPS was significantly associated with higher levels of dyspnea.The PPS correlated well with length of survival and with select symptom distress scores. We consider it to be a useful tool in predicting outcomes for palliative care patients.

Palliative care consultation is the most common model of hospital-based services in the United States, but few studies examine the impact of this model. In a prospective study, we describe the impact of palliative care consultation on symptoms, treatment, and hospital costs. Patients receiving interdisciplinary palliative care consultations from 2002 to 2004 were approached for enrollment; 304 of 395 (77%) patients participated. Measures included diagnosis, treatment decisions, and symptom scores. To test impact on costs, a one-year subset of cases with lengths of stay4 days (n=104) was compared to all available controls (n=1,813) matched on the 3Mtrade mark All Patients Refined Diagnosis Related Group, Version 20, and mortality risk scores. Half of the patients were younger than 65 years, 28% were African American, and 61% had cancer. Median Palliative Performance score was 20 (range, 10-100). Recommendations were implemented in 88% of cases; new "do not resuscitate/do not intubate" orders were written for 34% of patients, new comfort care orders for 44%, and 27% were referred for hospice care. Symptom scores improved from Day 1 to Day 3, with greatest improvement in pain (2.6-1.4, P0.001). Compared to matched controls without palliative care consultation, palliative care cases had lower cost per day ($897 vs. $1004, P=0.03). Per diem variable costs were 10.7% less for all palliative care cases and 20.5% less for those with50% hospital days with palliative care consultation. Palliative care consultation is followed by decisions to forego costly treatment and improved symptom scores, and earlier palliative care intervention results in greater cost-savings.

ContextPrehospital hypertonic saline (HTS) resuscitation of patients with traumatic brain injury (TBI) may increase survival but whether HTS improves neurological outcomes is unknown.ObjectiveTo determine whether prehospital resuscitation with intravenous HTS improves long-term neurological outcome in patients with severe TBI compared with resuscitation with conventional fluids.Design, Setting, and PatientsDouble-blind, randomized controlled trial of 229 patients with TBI who were comatose (Glasgow Coma Scale score