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Background: Adult medulloblastoma (MB) is rare, and management guidelines are largely based on pediatric clinical trials and retrospective series. Limited data exist with respect to clinical characteristics, prognostic factors, and outcomes based on first-line treatments., Methods: Two hundred adults with MB seen at a single institution from January 1978 to April 2017 were identified and followed for a median of 8.4 y (7.1, 10.3)., Results: Patient's median age at diagnosis was 29 y (18, 63). One hundred eleven (55.5%) were standard-risk, 59 (29.5%) were high-risk, and 30 (15.0%) were indeterminate. Most received post-operative radiation (RT) (184 [92.0%]), and 105 (52.5%) received first-line chemotherapy. Median overall survival (OS) was 8.8 y (7.2, 12.2) and median progression-free survival (PFS) was 6.6 y (4.9, 11.2). High-risk patients had inferior OS (Hazard ratio [HR] = 2.5 [1.5, 4.2], P = .0006) and PFS (HR = 2.3 [1.3, 3.9], P = .002) compared to standard-risk patients. Age, sex, and metastatic disease were not associated with survival. After adjusting for risk status, those who received RT plus adjuvant chemotherapy had superior PFS compared to RT plus neoadjuvant chemotherapy [HR = 0.46 (0.22, 0.95), P = .0357]. Within a subgroup for whom detailed clinical data were available, those who received RT plus adjuvant chemotherapy had improved PFS compared to RT only [HR = 0.24 (0.074-0.76), P = .016]. The substitution of cisplatin for carboplatin and the elimination of vincristine did not negatively affect outcomes., Conclusion: This is the largest single-institution retrospective study of adult MB to our knowledge and identifies standard-risk status, first-line RT and adjuvant chemotherapy as factors associated with improved outcomes., (© The Author(s) 2021. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Our previous study indicated that a high amount of visceral adipose tissue was associated with poor survival outcomes in patients with early breast cancer who received neoadjuvant chemotherapy. However, inconsistency was observed in the prognostic role of body composition in breast cancer treatment outcomes. In the present study, we aimed to validate our previous research by performing a comprehensive body composition analysis in patients with a standardized clinical background. We included 198 patients with stage III breast cancer who underwent neoadjuvant chemotherapy between January 2007 and June 2015. The impact of body composition on pathologic complete response and survival outcomes was determined. Body composition measurements had no significant effect on pathologic complete response. Survival analysis showed a low ratio of total visceral adipose tissue to subcutaneous adipose tissue (V/S ratio ≤ 34) was associated with shorter overall survival. A changepoint method determined that a V/S ratio cutoff of 34 maximized the difference in overall survival. Our study indicated the prognostic effect of body composition measurements in patients with locally advanced breast cancer compared to those with early breast cancer. Further investigation will be needed to clarify the biological mechanism underlying the association of V/S ratio with prognosis in locally advanced breast cancer.

Context: Limited access to opioids for patients with cancer has been reported as a potential unintended consequence of recent regulations restricting opioid use and prescribing practices. To our knowledge, there are a limited number of peer-reviewed studies that evaluate the perceived difficulties of the patients with cancer when filling their opioid prescription. To understand these difficulties, we surveyed patients receiving opioids in our outpatient supportive care center (SCC)., Objectives: The primary objective of this study was to evaluate cancer patients' perceptions of overall difficulties when filling their opioid prescription. Secondary objectives included determining associations between patient characteristics and difficulty and comparing difficulty between filling opioid and nonopioid prescriptions., Methods: Patients with cancer receiving opioids that had been seen two times or more at our SCC were asked to complete a survey. The information collected included patient demographics, clinical characteristics, and patients' experiences filling their opioid prescription., Results: The patients' median age was 60 years; 54% were female and 69% were white. Forty-four patients (32%) reported that they have experienced difficulty filling their opioid prescription. More than 25% of those 44 patients perceived difficulty from interactions with the pharmacy and/or pharmacist. Forty-six patients (33%) reported more difficulty filling their opioid prescriptions than filling their nonopioid prescriptions., Conclusion: This study provides evidence that patients with cancer visiting our SCC perceived difficulties obtaining their opioid prescriptions. The results suggest that negative interactions with the pharmacy and/or pharmacist contribute to their perceived difficulty. Additional research is needed to further characterize the contributors of the difficulties patients with cancer face in filling their opioid prescriptions., (Published by Elsevier Inc.)

Introduction: Programmed death-ligand 1 (PD-L1) expression may vary in different disease sites and at different time points of the disease course. We aimed to investigate PD-L1 heterogeneity and its usefulness as a predictive value for immune checkpoint inhibitor (ICI) therapy in patients with NSCLC., Methods: PD-L1 expression was analyzed in 1398 patients with NSCLC. The predictive value of PD-L1 for ICIs in 398 patients with metastatic NSCLC was assessed., Results: PD-L1 was significantly associated with biopsy sites (p = 0.004). Adrenal, liver, and lymph node (LN) metastases had the highest PD-L1 expression as a continuous variable and at 1% or 50% cutoff. PD-L1 expression was lower in bone and brain metastases. Among 112 patients with two specimens tested, 55 (49%) had major changes in PD-L1 falling into different clinically relevant categories (<1%, 1%-49%, ≥50%) at different time points. Previous ICI therapy was associated with significant decrease in PD-L1 compared with treatment-naive counterparts (p = 0.015). Patients with metastatic NSCLC treated with ICI (n = 398) were divided into three cohorts on the basis of biopsy sites: lung (n = 252), LN (n = 85), and distant metastasis (n = 61). Higher PD-L1 in lung or distant metastasis specimens was associated with higher response rate, longer progression-free survival, and overall survival. However, PD-L1 in LN biopsies was not associated with either response or survival., Conclusions: PD-L1 varies substantially across different anatomical sites and changes during the clinical course. PD-L1 from different biopsy sites may have different predictive values for benefit from ICIs in NSCLC., (Copyright © 2020 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

With recent developments in computer power the application of exact inferential methods has become more feasible which has resulted in increasing popularity of these approaches. However, there is a lack of such methodology for populations with more complex structure, such as finite populations. When a small sample is drawn from a finite population, the number of individuals with a specific characteristic of interest follows hypergeometric distribution. In order to test for the comparison of two proportions in finite populations we develop an exact unconditional test. We utilize the information gained from the sample to restrict our search for the maximum p -value. Our proposed test has power equal to its competitors while maintains the pre-specified nominal significance level., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2020 Informa UK Limited, trading as Taylor & Francis Group.)

Background: Subtypes of pediatric oncology patients and childhood cancer survivors who are overweight or obese have worse prognosis than their healthy-weighted peers. Several studies have examined weight status in either pediatric patients or survivors with acute leukemia, but few have compared these data across various diagnoses. Objectives: We examined BMI from oncology diagnosis or presentation, through treatment, and into survivorship across the most common cancer types seen in pediatric oncology. Methods: Patients were categorized into three oncologic diagnoses: leukemia and lymphoma ( n  = 69), neural tumors ( n  = 80), and non-neural solid tumors ( n  = 80) at yearly intervals over the course of 11 years. To allow for comparisons across age groups, BMI percentiles were calculated with <5th percentile classified as underweight ( n  = 11), the 5th-84th percentile classified as a healthy weight ( n  = 129), and above the 85th percentile classified as overweight and obese ( n  = 87). Results: At presentation, 45.6% of leukemia and lymphoma patients were overweight or obese, and 44.3% of neural tumor patients were overweight or obese. These high obesity rates persisted into survivorship. Compared to the non-neural tumor group, the leukemia and lymphoma group had a significant increase in BMI percentile over time, while the neural tumor group did not. Conclusions: Pediatric patients with leukemia, lymphoma, and neural tumors and who are overweight or obese at presentation continue this trend into survivorship, indicating a need for management of overweight and obesity through lifestyle interventions concurrent with therapy.

Objective: Evaluate Functional Independence Measure (FIM) changes and incidence of serious medical complications requiring return to the primary acute care service of acute rehabilitation cancer inpatients with leptomeningeal disease (LMD)., Design: Retrospective chart review., Setting: Tertiary referral based comprehensive cancer center acute inpatient rehabilitation unit., Participants: Thirty cancer patients admitted to acute inpatient rehabilitation between 8 January 2014 and 8 August 2018 with pathology confirmed LMD within 6 months., Interventions: Not applicable., Main Outcome Measures: FIM and incidence of return to the primary acute care service., Results: Twenty five of 30 (83.3%) patients were noted to have neurologic impairments and 13/30 (43.3%) were noted to have cognitive impairments. Five of 30 patients (16.7%) received intrathecal chemotherapy and 4/30 (13.3%) received radiation during acute inpatient rehabilitation for LMD treatment. Median days in acute care prior to acute inpatient rehabilitation was 22.5. Median days from acute inpatient rehabilitation admission until death of the 23 deceased patients as of 1 January 2019 was 180.00. Twenty of 30 (66.7%) patients were discharged home, 9/30 (30%) transferred to the primary acute care service, and 1/30 (3.3%) discharged to a skilled nursing facility. Reasons for return to the primary acute care service included additional chemotherapy 3/9 (33%), neurologic decline 2/9 (22%), fever 2/9 (22%), altered mental status 1/9 (11%), and progressive polyarthritis 1/9 (11%). Of the 21 patients who completed acute inpatient rehabilitation without return to the primary acute care service, mean FIM subscore changes from admission to discharge for Activities of Daily Living, Mobility, and Motor were 5.1 (P < .001), 4.8 (P < .001) and 11.7 (P < .001), respectively (Wilcoxon signed rank test, significance P < .05)., Conclusion: LMD patients who completed acute inpatient rehabilitation made statistically significant improvements on the majority of FIM items. Most patients were discharged home. Our data suggest LMD should not be a reason for exclusion from acute inpatient rehabilitation., Level of Evidence: III., (© 2019 American Academy of Physical Medicine and Rehabilitation.)

Background: The concurrent use of opioids with benzodiazepines (BZD) or nonbenzodiazepine sedatives (S) recently was found to be associated with an increased risk of overdose death compared with the use of opioids alone. In the current study, the authors examined the frequency and trend of concurrent opioid/BZD-S use and its associated risk factors among patients with cancer., Methods: Data regarding the frequency and trend of concurrent opioid/BZD-S use were extracted for 1500 randomly selected patients referred to the outpatient palliative care clinic at The University of Texas MD Anderson Cancer Center between the calendar years of 2011 and 2016. To explore associated risk factors, the authors compared the demographic and clinical predictors of 418 patients each in the concurrent opioid/BZD-S group and opioids-only group., Results: In 2011, at the time of referral to the palliative care clinic, 96 of 221 patients with cancer (43%) were prescribed concurrent opioids/BZD-S. This rate progressively declined to 67 of 217 patients (31%) by 2016 (P = .0008). Patients in the concurrent opioid/BZD-S group had a higher percentage of females (233 individuals; 55% [P = .007]) and whites (323 individuals; 77% [P = .002]), and patients reported higher scores regarding depression (P = .0001), anxiety (P ≤ .0001), drowsiness (P = .048), and worst feeling of well-being (P = .001). The morphine equivalent daily dose was significantly higher in concurrent opioid/BZD-S group (median of 67.5 mg/day [interquartile range (IQR), 30-135 mg/day] vs 60 mg/day [IQR, 30-105 mg/day]; P = .034). Multivariate analysis demonstrated that anxiety (P ≤ .0001), white race (P = .0092), and poor Eastern Cooperative Oncology Group performance status (P = .0017) were significantly associated with concurrent use., Conclusions: The concurrent use of opioids with BZD-S has declined but continues to be frequent among patients with cancer. Anxiety, white race, and poor Eastern Cooperative Oncology Group performance status were associated with its use. More research is needed to explore which medications can replace these agents., (© 2019 American Cancer Society.)

Purpose: Music therapy has shown benefits for reducing distress in individuals with cancer. We explore the effects of music therapy on self-reported symptoms of patients receiving inpatient care at a comprehensive cancer center., Methods: Music therapy was available as part of an inpatient integrative oncology consultation service; we examined interventions and symptoms for consecutive patients treated by a board-certified music therapist from September 2016 to May 2017. Patients completed the Edmonton Symptom Assessment Scale (ESAS, 10 symptoms, scale 0-10, 10 most severe) before and after the intervention. Data was summarized by descriptive statistics. Changes in ESAS symptom and subscale scores (physical distress (PHS), psychological distress (PSS), and global distress (GDS)) were evaluated by Wilcoxon signed rank test., Results: Data were evaluable for 96 of 100 consecutive initial, unique patient encounters; 55% were women, average age 50, and majority with hematologic malignancies (47%). Reasons for music therapy referral included anxiety/stress (67%), adjustment disorder/coping (28%), and mood elevation/depression (17%). The highest (worst) symptoms at baseline were sleep disturbance (5.7) and well-being (5.5). We observed statistically and clinically significant improvement (means) for anxiety (- 2.3 ± 1.5), drowsiness (- 2.1 ± 2.2), depression (- 2.1 ± 1.9), nausea (- 2.0 ± 2.4), fatigue (- 1.9 ± 1.5), pain (- 1.8 ± 1.4), shortness of breath (- 1.4 ± 2.2), appetite (- 1.1 ± 1.7), and for all ESAS subscales (all ps < 0.02). The highest clinical response rates were observed for anxiety (92%), depression (91%), and pain (89%)., Conclusions: A single, in-person, tailored music therapy intervention as part of an integrative oncology inpatient consultation service contributed to the significant improvement in global, physical, and psychosocial distress. A randomized controlled trial is justified.

Background: Ambulatory cancer rehabilitation programs vary widely in the types of services offered, and there is a lack of consistency with respect to the coordination of rehabilitation with oncologic treatment plans. There are no guidelines for outpatient interdisciplinary rehabilitation team meetings, and the types and characteristics of recommendations that a physiatrist can provide during these meetings have not been reported., Objective: To identify the frequency and characteristics of different types of recommendations that were derived through monthly interdisciplinary outpatient rehabilitation team meetings involving physiatrists, physical therapists, and occupational therapists., Design: Case series-descriptive study., Setting: Quaternary cancer center., Participants: Outpatient rehabilitation cancer patients discussed during consecutive monthly team meetings., Main Outcome Measure(s): Frequency and characteristics of recommendations., Results: Over a 7-month period, there were 57 potential patients to be discussed, and 42 patients were discussed. Among the 42 patients, 30 received recommendations, which yields 71% of patients receiving at least 1 recommendation. Some patients required repeated discussions in different months; thus, a total of 71 discussions occurred and resulted in 51 recommendations. Out of the 71 discussions, 41 (58%) discussions resulted in recommendations such as coordination of care in 19 (37%) cases, physiatry clinic follow-up in 9 cases (18%), oncology clinic follow-up in 7 cases (14%), and orders for referrals to other health professionals were placed in 5 cases (10%). Thirty discussions (42%) did not result in any recommendations, with the most common reason being stable or having improved functional status., Conclusions: In contrast to acute inpatient rehabilitation interdisciplinary weekly team meetings required by Centers for Medicare and Medicaid Services, there are no guidelines for outpatient interdisciplinary rehabilitation team meetings. Thus, the types and characteristics of recommendations that a physiatrist can provide during these meetings have not been previously reported. Regularly scheduled outpatient interdisciplinary cancer rehabilitation team meetings increase communication among rehabilitation specialists to identify outpatients experiencing barriers to therapy progress, provide recommendations to address those barriers, and reassess rehabilitation goals previously established., Level of Evidence: IV., (© 2018 American Academy of Physical Medicine and Rehabilitation.)

Background: Increased access to complementary therapies such as acupuncture at academic medical centers has created new opportunities for management of cancer and cancer treatment related symptoms. Methods: Patients presenting for acupuncture treatment during calendar year 2016 at an outpatient integrative medicine clinic in a comprehensive cancer center were asked to complete a modified Edmonton Symptom Assessment Scale (ESAS; 16 symptoms, score 0-10, 10 worst possible) before and after each visit. ESAS subscales analyzed included global (GDS; score 0-90), physical (PHS, 0-60) and psychological distress (PSS, 0-20). ESAS symptom score change pre/post acupuncture treatment & from baseline visit to first follow up were evaluated by paired t-test. Results: Of 375 participants [mean age 55.6, 68.3% female, 73.9% white, most common cancer diagnosis of breast (32.8%) and thoracic/head & neck (25.9%)], 73.3% had at least one follow up acupuncture treatment [mean 4.6 (SD 5.1) treatments]. Highest/worst symptoms at baseline were poor sleep (3.92), fatigue (3.43), well-being (3.31), and pain (3.29). Statistically significant reduction/improvement (pre/post) was observed for all ESAS symptoms and subscales for the initial acupuncture treatment (p <0.001). Hot flashes had the highest mean reduction (-1.93), followed by fatigue (-1.72), numbness/tingling (-1.70), and nausea (-1.67). Clinically significant reductions were also observed for ESAS subscales of GDS (-12.2), PHS (-8.5), and PSS (-2.6). For symptom change from initial acupuncture treatment to first follow up (pre/pre), statistically and clinically significant improvement was observed for spiritual pain (-1.10; p<0.001) and ESAS subscale of GDS (-6.09; p=0.048). Clinical response rates (reduction ≥1) on follow up were highest for symptoms of spiritual pain (58.9%), dry mouth (57.8%) and nausea (57.3%). Conclusions: Outpatient acupuncture was associated with immediate & longitudinal significant improvement across a range of symptoms commonly experienced by individuals during cancer care. Further research is needed to better understand frequency of treatments needed in clinical practice to help maintain benefit., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Objective: To identify the frequency and characteristics of bleeding complications during acute inpatient rehabilitation of hematologic malignancy patients with severe thrombocytopenia., Design: Retrospective descriptive analysis., Setting: Comprehensive cancer center acute inpatient rehabilitation unit., Participants: Consecutive hematologic malignancy patients with a platelet count of less than or equal to 20,000/microliter (μL) on the day of acute inpatient rehabilitation admission from 1/1/2005 through 8/31/2016., Interventions: Medical records were retrospectively analyzed for demographic, laboratory, and medical data. Patients were rehabilitated using the institutional exercise guidelines for thrombocytopenic patients., Main Outcome Measures: Bleeding events noted in the medical record., Results: Out of 135 acute inpatient rehabilitation admissions, 133 unique patients were analyzed with a total of 851 inpatient rehabilitation days. The mean platelet count was 14,000/μL on the day of admission and 22,000/μL over the course of the rehabilitation admission. There were 252 days of inpatient rehabilitation where patients had less than 10,000/μL platelets. A total of 97 bleeding events were documented in 77/135 (57%) admissions. Of the 97 bleeding events, 72 (74%), 14 (14%), and 11 (11%) were considered to be of low, medium, and high severity, respectively. There were 4/97 (4%) bleeding events that were highly likely attributable to physical activity but only 1/4 was considered high severity. Bleeding rates were .09, .08, .17, and .37 for > 20,000, 15-20,000, 10-15,000, and < 10,000/μL mean platelet counts respectively (p = .003). Forty-four percent of patients were transferred back to the primary acute care service with infection being the most common reason for transfer., Conclusions: This study is the first to examine exercise-related bleeding complications during acute inpatient rehabilitation in severely thrombocytopenic hematologic cancer patients. Bleeding rates increased with lower platelet counts. However, using the exercise guidelines for severely thrombocytopenic patients, the risk of severe exercise-related bleeding events was low.

Background: The Richmond Agitation-Sedation Scale (RASS) is commonly used to assess psychomotor activity; however, to the authors' knowledge, its minimal clinically important difference (MCID) has not been determined to date. The objective of the current study was to identify the MCID for RASS using 2 anchor-based approaches., Methods: The current study was a secondary analysis of a randomized controlled trial to compare the effect of lorazepam versus placebo as an adjuvant to haloperidol for persistent agitation in patients with delirium. The primary outcome was change in RASS (10-point numeric rating scale ranging from -5 [unarousable] to +4 [combative]) from baseline to 8 hours after treatment administration. The sensitivity-specificity and within-patient change methods were used to identify the MCID, with the anchor being patient comfort after the study intervention as perceived by caregivers and nurses., Results: A total of 90 patients were randomized and 58 (64%) received the study medication for restlessness/agitation (mean baseline RASS, 1.6). A total of 23 caregivers (61%) and 23 nurses (55%) perceived that the patient was more comfortable after treatment. Using the sensitivity-specificity method, the optimal RASS reduction was ≥4 points according to both caregivers (sensitivity of 61% and specificity of 80%; area under the curve, 0.71) and nurses (sensitivity of 73% and specificity of 84%; area under the curve, 0.78). The RASS cutoff value based on the within-patient change method was similar (-4.2 for caregivers and -4.0 for nurses)., Conclusions: For patients with persistent restlessness/agitation, a reduction of ≥4 points in RASS was considered to be the MCID for both nurses and caregivers. These preliminary findings may have implications for sample size calculation and the interpretation of treatment effect in future delirium trials. Cancer 2018;124:2246-52. © 2018 American Cancer Society., (© 2018 American Cancer Society.)

Context: Low-income patients face barriers to palliative care access, which might negatively influence symptom management and advanced care planning., Objective: Our aim was to compare time of referral and characteristics (level of symptom distress) among uninsured (indigent), low-insured (Medicaid), and insured patients presenting to our supportive care center (SCC)., Methods: We conducted a retrospective review of randomly selected 100 indigent, 100 Medicaid, and 300 insured outpatients referred during the same five-year period. We reviewed demographic and clinical characteristics including date of diagnosis of advanced cancer and of first visit to SCC, symptom assessment (Edmonton Symptom Assessment System), type and dose of opioid medication, number of total outpatient visits, and date of last contact with palliative care team., Results: Among 482 evaluable patients, indigent, Medicaid, and insured patients, respectively, had mean (SD) ages of 48 (11), 50 (12), and 63 (13) years (P < 0.001); Edmonton Symptom Assessment System pain scores at first visit of 6.7 (2.5), 5.6 (3.2), and 4.9 (3.2) (P < 0.001); nonwhite race in 60%, 49%, and 25% of cases (P < 0.001); unmarried status in 68%, 64%, and 33% of cases (P < 0.001), while 63%, 87%, and 54% of patients (P < 0.001) were on opioids with median number of encounters per month of 0.6, 0.8, and 0.5 (P = 0.001). Median survival (95% CI) from first visit to last contact was 4.6 (2.8-6.2), 5.4 (3.5-7), and 5.6 (4.7-7.3) months (P = 0.036)., Conclusion: Patients with limited or no insurance had significantly higher pain and were more frequently on opioids, younger, nonwhite, and not married. They required higher number of SCC follow-up visits. Insurance status did not affect timing of SCC referral or follow-ups at our cancer center., (Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Context: Cranial electrotherapy stimulation (CES) is a safe modulation of brain activity for treating depression, anxiety, insomnia, and pain. However, there are no published studies in patients with advanced cancer (ACPs)., Objectives: The aim of the study was to determine the feasibility and preliminary efficacy of a four-week CES intervention on depression, anxiety, sleep disturbance, and pain scores. Concurrent salivary biomarker studies were conducted., Methods: In this one group open label pre- and post-intervention study with a four-week CES intervention, ACPs with one or more of four moderate intensity (≥3/10) Edmonton Symptom Assessment Scale (ESAS) symptoms (depression, anxiety, sleep disturbance, and pain) were eligible. Adherence (0%-100%), satisfaction rates (0-10), and safety were assessed. ESAS, Hospital Anxiety and Depression Scale (HADS), Pittsburgh Sleep Quality Index, Brief Pain Inventory, and salivary levels (cortisol, alpha amylase, C-reactive protein, and interleukin-1β, and interleukin-6) were assessed from baseline to Week 4., Results: Thirty-three of 36 patients (92%) completed the CES. Median (interquartile range) adherence CES use and satisfaction scores were 93% (89-100) and 10% (9-10), respectively, and the adherence criteria was met in the study. CES use was safe (no Grade 3 or higher adverse events). HADS anxiety (P < 0.001), HADS depression (P = 0.024), ESAS anxiety (P = 0.001), ESAS depression (P = 0.025), Brief Pain Inventory pain (P = 0.013), Pittsburgh Sleep Quality Index daytime dysfunction (P = 0.002), and medication use (P = 0.006) scores improved after four-week CES treatment., Conclusion: In this preliminary study, we found that the use of CES was safe and feasible in ACP. The use of CES was associated with significant improvement of depression, anxiety, pain, and sleep scores. These findings support further studies of CES in ACP for symptom control., (Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Importance: The use of benzodiazepines to control agitation in delirium in the last days of life is controversial., Objective: To compare the effect of lorazepam vs placebo as an adjuvant to haloperidol for persistent agitation in patients with delirium in the setting of advanced cancer., Design, Setting, and Participants: Single-center, double-blind, parallel-group, randomized clinical trial conducted at an acute palliative care unit at MD Anderson Cancer Center, Texas, enrolling 93 patients with advanced cancer and agitated delirium despite scheduled haloperidol from February 11, 2014, to June 30, 2016, with data collection completed in October 2016., Interventions: Lorazepam (3 mg) intravenously (n = 47) or placebo (n = 43) in addition to haloperidol (2 mg) intravenously upon the onset of an agitation episode., Main Outcomes and Measures: The primary outcome was change in Richmond Agitation-Sedation Scale (RASS) score (range, -5 [unarousable] to 4 [very agitated or combative]) from baseline to 8 hours after treatment administration. Secondary end points were rescue neuroleptic use, delirium recall, comfort (perceived by caregivers and nurses), communication capacity, delirium severity, adverse effects, discharge outcomes, and overall survival., Results: Among 90 randomized patients (mean age, 62 years; women, 42 [47%]), 58 (64%) received the study medication and 52 (90%) completed the trial. Lorazepam + haloperidol resulted in a significantly greater reduction of RASS score at 8 hours (-4.1 points) than placebo + haloperidol (-2.3 points) (mean difference, -1.9 points [95% CI, -2.8 to -0.9]; P < .001). The lorazepam + haloperidol group required less median rescue neuroleptics (2.0 mg) than the placebo + haloperidol group (4.0 mg) (median difference, -1.0 mg [95% CI, -2.0 to 0]; P = .009) and was perceived to be more comfortable by both blinded caregivers and nurses (caregivers: 84% for the lorazepam + haloperidol group vs 37% for the placebo + haloperidol group; mean difference, 47% [95% CI, 14% to 73%], P = .007; nurses: 77% for the lorazepam + haloperidol group vs 30% for the placebo + haloperidol group; mean difference, 47% [95% CI, 17% to 71%], P = .005). No significant between-group differences were found in delirium-related distress and survival. The most common adverse effect was hypokinesia (3 patients in the lorazepam + haloperidol group [19%] and 4 patients in the placebo + haloperidol group [27%])., Conclusions and Relevance: In this preliminary trial of hospitalized patients with agitated delirium in the setting of advanced cancer, the addition of lorazepam to haloperidol compared with haloperidol alone resulted in a significantly greater reduction in agitation at 8 hours. Further research is needed to assess generalizability and adverse effects., Trial Registration: clinicaltrials.gov Identifier: NCT01949662.