Areej El-Jawahri

Video decision support tool for advance care planning in dementia: randomised controlled trial

Objective To evaluate the effect of a video decision support tool on the preferences for future medical care in older people if they develop advanced dementia, and the stability of those preferences after six weeks. Design Randomised controlled trial conducted between 1 September 2007 and 30 May 2008. Setting Four primary care clinics (two geriatric and two adult medicine) affiliated with three academic medical centres in Boston. Participants Convenience sample of 200 older people (≥65 years) living in the community with previously scheduled appointments at one of the clinics. Mean age was 75 and 58% were women. Intervention Verbal narrative alone (n=106) or with a video decision support tool (n=94). Main outcome measures Preferred goal of care: life prolonging care (cardiopulmonary resuscitation, mechanical ventilation), limited care (admission to hospital, antibiotics, but not cardiopulmonary resuscitation), or comfort care (treatment only to relieve symptoms). Preferences after six weeks. The principal category for analysis was the difference in proportions of participants in each group who preferred comfort care. Results Among participants receiving the verbal narrative alone, 68 (64%) chose comfort care, 20 (19%) chose limited care, 15 (14%) chose life prolonging care, and three (3%) were uncertain. In the video group, 81 (86%) chose comfort care, eight (9%) chose limited care, four (4%) chose life prolonging care, and one (1%) was uncertain (χ2=13.0, df=3, P=0.003). Among all participants the factors associated with a greater likelihood of opting for comfort care were being a college graduate or higher, good or better health status, greater health literacy, white race, and randomisation to the video arm. In multivariable analysis, participants in the video group were more likely to prefer comfort care than those in the verbal group (adjusted odds ratio 3.9, 95% confidence interval 1.8 to 8.6). Participants were re-interviewed after six weeks. Among the 94/106 (89%) participants re-interviewed in the verbal group, 27 (29%) changed their preferences (κ=0.35). Among the 84/94 (89%) participants re-interviewed in the video group, five (6%) changed their preferences (κ=0.79) (P<0.001 for difference). Conclusion Older people who view a video depiction of a patient with advanced dementia after hearing a verbal description of the condition are more likely to opt for comfort as their goal of care compared with those who solely listen to a verbal description. They also have more stable preferences over time. Trial registration Clinicaltrials.gov NCT00704886.

3H Dendrimer Nanoparticle Organ/Tumor Distribution

AbstractPurpose. To determine the in vivo biodistribution for differently charged poly(amidoamine) (PAMAM) dendrimers in B16 melanoma and DU145 human prostate cancer mouse tumor model systems. Methods. Neutral (NSD) and positive surface charged (PSD) generation 5 (d =5 nm) PAMAM dendrimers were synthesized by using 3H-labeled acetic anhydride and tested in vivo. Dendrimer derivatives were injected intravenously, and their biodistribution was determined via liquid scintillation counting of tritium in tissue and excretory samples. Mice were also monitored for acute toxicity. Results. Both PSD and NSD localized to major organs and tumor. Dendrimers cleared rapidly from blood, with deposition peaking at 1 h for most organs and stabilizing from 24 h to 7 days postinjection. Maximal excretion occurred via urine within 24 h postinjection. Neither dendrimer showed acute toxicity. Conclusions. Changes in the net surface charge of polycationic PAMAMs modify their biodistribution. PSD deposition into tissues is higher than NSD, although the biodistribution trend is similar. Highest levels were found in lungs, liver, and kidney, followed by those in tumor, heart, pancreas, and spleen, while lowest levels were found in brain. These nanoparticles could have future utility as systemic biomedical delivery devices.

Effects of Early Integrated Palliative Care in Patients With Lung and GI Cancer: A Randomized Clinical Trial

Purpose We evaluated the impact of early integrated palliative care (PC) in patients with newly diagnosed lung and GI cancer. Patients and Methods We randomly assigned patients with newly diagnosed incurable lung or noncolorectal GI cancer to receive either early integrated PC and oncology care (n = 175) or usual care (n = 175) between May 2011 and July 2015. Patients who were assigned to the intervention met with a PC clinician at least once per month until death, whereas those who received usual care consulted a PC clinician upon request. The primary end point was change in quality of life (QOL) from baseline to week 12, per scoring by the Functional Assessment of Cancer Therapy-General scale. Secondary end points included change in QOL from baseline to week 24, change in depression per the Patient Health Questionnaire-9, and differences in end-of-life communication. Results Intervention patients ( v usual care) reported greater improvement in QOL from baseline to week 24 (1.59 v -3.40; P = .010) but not week 12 (0.39 v -1.13; P = .339). Intervention patients also reported lower depression at week 24, controlling for baseline scores (adjusted mean difference, -1.17; 95% CI, -2.33 to -0.01; P = .048). Intervention effects varied by cancer type, such that intervention patients with lung cancer reported improvements in QOL and depression at 12 and 24 weeks, whereas usual care patients with lung cancer reported deterioration. Patients with GI cancers in both study groups reported improvements in QOL and mood by week 12. Intervention patients versus usual care patients were more likely to discuss their wishes with their oncologist if they were dying (30.2% v 14.5%; P = .004). Conclusion For patients with newly diagnosed incurable cancers, early integrated PC improved QOL and other salient outcomes, with differential effects by cancer type. Early integrated PC may be most effective if targeted to the specific needs of each patient population.

Molecular Advances of Brain Tumors in Radiation Oncology

Glioblastoma, grade IV malignant glioma based on the World Health Organization classification, is the most common primary brain tumor in adults. The average survival time of less than 1 year has not improved notably over the last 3 decades. Surgery and radiotherapy, the traditional cornerstones of therapy, provide palliative benefit, whereas the value of chemotherapy has been marginal and controversial. The dismal prognosis of glioblastoma patients is largely caused by the striking radioresistance of these tumors. A better understanding of the molecular mechanisms that underlie the malignant phenotype of glioblastomas and plausible mechanisms of radiation resistance can provide new possibilities in terms of targeted therapeutic strategies. Despite the genetic heterogeneity of malignant gliomas, common aberrations in the signaling elements of the growth and survival pathways are found. New treatments have emerged to target molecules in these signaling pathways with the goal to increase specific efficacy and minimize toxicity. Monoclonal antibodies and low molecular-weight kinase inhibitors are the most common classes of agents in targeted cancer treatment. This review introduces these new targeted therapies in the context of current treatment options for patients with glioblastoma. It is hoped that this combined approach will overcome the current limitations in the treatment of patients with glioblastoma and result in a better prognosis for these patients.

Effect of Inpatient Palliative Care on Quality of Life 2 Weeks After Hematopoietic Stem Cell Transplantation: A Randomized Clinical Trial.

Importance During hospitalization for hematopoietic stem cell transplantation (HCT), patients receive high-dose chemotherapy before transplantation and experience significant physical and psychological symptoms and poor quality of life (QOL). Objective To assess the effect of inpatient palliative care on patient- and caregiver-reported outcomes during hospitalization for HCT and 3 months after transplantation. Design, Setting, and Participants Nonblinded randomized clinical trial among 160 adults with hematologic malignancies undergoing autologous/allogeneic HCT and their caregivers (n = 94). The study was conducted from August 2014 to January 2016 in a Boston hospital; follow-up was completed in May 2016. Interventions Patients assigned to the intervention (n=81) were seen by palliative care clinicians at least twice a week during HCT hospitalization; the palliative intervention was focused on management of physical and psychological symptoms. Patients assigned to standard transplant care (n=79) could be seen by palliative care clinicians on request. Main Outcomes and Measures Primary: change in patient QOL from baseline to week 2; secondary: patient-assessed mood, fatigue, and symptom burden scores at baseline, 2 weeks, and 3 months after HCT and caregiver-assessed QOL and mood at baseline and 2 weeks after HCT. Results Among 160 enrolled patients (mean age, 60 [SD, 13.3] years; 91 women [56.9%]; median hospital stay, 21 days) and 94 caregivers, 157 (98.1%) and 89 (94.7%), respectively, completed 2-week follow-up, and 149 patients (93.1%) completed 3-month follow-up. Patients in the intervention group reported a smaller decrease in QOL from baseline to week 2 (mean baseline score, 110.26; week 2 score, 95.46; mean change, -14.72) compared with patients in the control group (mean baseline score, 106.83; week 2 score, 85.42; mean change, -21.54; difference between groups, -6.82; 95% CI, -13.48 to -0.16; P = .045). Among the secondary outcomes, from baseline to week 2, patients in the intervention group vs those in the control group had less increase in depression (mean, 2.43 vs 3.94; mean difference, 1.52; 95% CI, 0.23-2.81; P = .02), lower anxiety (mean, -0.80 vs 1.12; mean difference, 1.92; 95% CI, 0.83-3.01; P < .001), no difference in fatigue (mean, -10.30 vs -13.65; mean difference, -3.34; 95% CI, -7.25 to 0.56; P = .09), and less increase in symptom burden (mean, 17.35 vs 23.14; mean difference, 5.80; 95% CI, 0.49-11.10; P = .03). At 3 months after HCT, intervention patients vs control patients had higher QOL scores (mean, 112.00 vs 106.66; mean difference, 5.34; 95% CI, 0.04-10.65; P = .048) and less depression symptoms (mean, 3.49 vs 5.19; mean difference, -1.70; 95% CI, -2.75 to -0.65; P = .002) but no significant differences in anxiety, fatigue, or symptom burden. From baseline to week 2 after HCT, caregivers of patients in the intervention group vs caregivers of patients in the control group reported no significant differences in QOL or anxiety but had a smaller increase in depression (mean, 0.25 vs 1.80; mean difference, 1.55; 95% CI, 0.14-2.96; P = .03). Conclusions and Relevance Among adults at a single institution undergoing HCT for hematologic malignancy, the use of inpatient palliative care compared with standard transplant care resulted in a smaller decrease in QOL 2 weeks after transplantation. Further research is needed for replication and to assess longer-term outcomes and cost implications. Trial Registration clinicaltrials.gov Identifier: NCT02207322.

Haematopoietic cell transplantation with and without sorafenib maintenance for patients with FLT3-ITD acute myeloid leukaemia in first complete remission

We performed a retrospective study analysing the effect of sorafenib, an oral fms‐Like Tyrosine Kinase 3 (FLT3)/multikinase inhibitor, as post‐transplant maintenance in adult patients with FLT3‐internal tandem duplication (ITD) acute myeloid leukaemia (AML). We identified consecutive patients with FLT3‐ITD AML diagnosed between 2008 and 2014 who received haematopoietic cell transplantation (HCT) in first complete remission (CR1). Post‐HCT initiation of sorafenib (yes/no) was evaluated as a time‐varying covariate in the overall survival/progression‐free survival (OS/PFS) analysis and we performed a landmark analysis of controls alive without relapse at the median date of sorafenib initiation. We identified 26 sorafenib patients and 55 controls. Median follow‐up was 27·2 months post‐HCT for sorafenib survivors, and 38·4 months for controls (P = 0·021). The median time to initiating sorafenib was 68 days post‐HCT; 43 controls were alive without relapse at this cut‐off. Sorafenib patients had improved 2‐year OS in the d+68 landmark analysis (81% vs. 62%, P = 0·029). Sorafenib was associated with improved 2‐year PFS (82% vs. 53%, P = 0·0081) and lower 2‐year cumulative incidence of relapse (8·2% vs. 37·7%, P = 0·0077). In multivariate analysis, sorafenib significantly improved OS [Hazard ratio (HR) 0·26, P = 0·021] and PFS (HR 0·25, P = 0·016). There was no difference in 2‐year non‐relapse mortality (9·8% vs. 9·3%, P = 0·82) or 1‐year chronic graft‐versus‐host disease (55·5% vs. 37·2%, P = 0·28). These findings suggest potential benefit of post‐HCT sorafenib in FLT3‐ITD AML, and support further evaluation of post‐HCT FLT3 inhibition.

Quality of life and mood of patients and family caregivers during hospitalization for hematopoietic stem cell transplantation

We conducted a study to investigate the impact of hospitalization for hematopoietic stem cell transplantation (HCT) on the quality of life (QOL) and mood of patients and family caregivers (FC).

Augmenting Communication and Decision Making in the Intensive Care Unit with a Cardiopulmonary Resuscitation Video Decision Support Tool: A Temporal Intervention Study

OBJECTIVE Effective communication between intensive care unit (ICU) providers and families is crucial given the complexity of decisions made regarding goals of therapy. Using video images to supplement medical discussions is an innovative process to standardize and improve communication. In this six-month, quasi-experimental, pre-post intervention study we investigated the impact of a cardiopulmonary resuscitation (CPR) video decision support tool upon knowledge about CPR among surrogate decision makers for critically ill adults. METHODS We interviewed surrogate decision makers for patients aged 50 and over, using a structured questionnaire that included a four-question CPR knowledge assessment similar to those used in previous studies. Surrogates in the post-intervention arm viewed a three-minute video decision support tool about CPR before completing the knowledge assessment and completed questions about perceived value of the video. RESULTS We recruited 23 surrogates during the first three months (pre-intervention arm) and 27 surrogates during the latter three months of the study (post-intervention arm). Surrogates viewing the video had more knowledge about CPR (p=0.008); average scores were 2.0 (SD 1.1) and 2.9 (SD 1.2) (out of a total of 4) in pre-intervention and post-intervention arms. Surrogates who viewed the video were comfortable with its content (81% very) and 81% would recommend the video. CPR preferences for patients at the time of ICU discharge/death were distributed as follows: pre-intervention: full code 78%, DNR 22%; post-intervention: full code 59%, DNR 41% (p=0.23).

Health care utilization and end‐of‐life care for older patients with acute myeloid leukemia

Health care utilization in older adults (age ≥60 years) with acute myeloid leukemia (AML) has not been well studied.

The relationship between coping strategies, quality of life, and mood in patients with incurable cancer.

Patients with incurable cancer face many physical and emotional stressors, yet little is known about their coping strategies or the relationship between their coping strategies, quality of life (QOL), and mood.