Implementation of a Novel Pathway to Integrate Palliative and Oncology Care for Patients With Acute Myeloid Leukemia in a Community Hospital.

PURPOSE: Historically, patients with hematologic malignancies are referred to palliative care less often and later in the disease trajectory than those with solid tumors. Recent evidence demonstrates the benefit of early, integrated inpatient palliative care (PC) for patients with acute myeloid leukemia (AML) receiving chemotherapy at academic centers. The current study evaluated the feasibility of implementing standardized early palliative care services (PCS) during hospitalization for AML treatment in a community setting. METHODS: Starting June 2018, automated consultations for PCS were incorporated into clinical pathways to encourage early, integrated services for patients receiving chemotherapy for AML with an expected hospital stay of 4-6 weeks. Expectations were established that consultations would be performed within 72 hours of request; patients would have two visits per week by a palliative care clinician and at least one visit by a member of the interdisciplinary team. To measure the feasibility of this intervention, data on number of patients who received palliative care consultation and time to palliative care consultation were compared with institutional historical controls. RESULTS: On the basis of retrospective chart review, the postintervention group (n = 21) had greater PCS compared with historical controls (n = 28; 95% v 36%). The average number of PC team member visits per patient was significantly greater after the intervention: PC clinicians (1.04-8.05, P < .001), chaplains (1.3-3.3, P = .0085), and social workers (1.0-4.3, P < .001). Of those patients who received PCS, 74% had their initial palliative medicine consultation within 3 days of a clinician's order and 100% within 4 days. CONCLUSION: We have demonstrated the feasibility of implementing standardized integration of PCS for patients with AML hospitalized for treatment in a community setting.

Ecological Factors of Telemental Healthcare Utilization Among Adolescents with Increased Substance Use During the COVID-19 Pandemic: The Moderating Effect of Gender.

Background: Adolescent substance use is often associated with concurrent mental health problems (e.g., depression, suicide attempts, parental emotional and physical abuse, not feeling close to people at school, and lower virtual connectedness) at multiple ecological levels. Objective: This study examined whether such risk factors among adolescents were associated with the use of telemental healthcare (TMHC) and whether gender moderated these associations. Methods: Data were drawn from the Adolescent Behaviors and Experiences Survey, collected by the U.S. Centers for Disease Control and Prevention from January to June 2021. A hierarchical multiple logistic regression analysis was conducted using a national sample of 1,460 students in Grades 9-12 in the United States who reported having used more alcohol and/or drugs during the pandemic than before it started. Results: The results showed that only 15.3% of students sought TMHC. Students reporting increased substance use during the pandemic were more likely to use TMHC if they experienced more severe mental health problems (e.g., suicide attempts) compared to other ecological factors, such as issues with their family, school, or community. Analysis of the moderating effect showed that the closer male students felt to people at school, the more likely they were to seek TMHC, whereas the opposite was true for female students. Conclusions: The findings highlighted that feeling close to people at school is an important aspect of understanding the help-seeking behavior of female and male adolescent substance users.

Implementation of a Palliative Oncology Tumor Board.

CONTEXT: The integration of palliative care into standard oncologic care has been shown to improve multiple outcomes in patients with advanced cancer. Ideal methods for integrating these disciplines is an ongoing area of discussion. One method of integration is a palliative oncology tumor board (POTB). OBJECTIVES: To describe the implementation of a POTB in a community cancer center as a method of integrating oncology and palliative care by providing a forum for multidisciplinary discussion of complex cases. METHODS: During development of the POTB, multiple influencing factors and barriers were considered including the setting of implementation, culture prior to implementation, design elements, engagement of stakeholders, and evaluation of implementation. The focus of this POTB was to address the identified communication gap between inpatient and outpatient care teams. Two complex hospitalized oncology patients were selected to be discussed weekly. RESULTS: Conferences were attended by an average of 23 individuals. The highest proportion of attendees were members of oncology support services (including nurse navigators, social workers, chaplains, dietitians, financial counselors; OSS; 31%), followed by medical oncology (25%). The most common theme of discussion was methods of communication with patient and/or family (68% of cases). Thirty days after presentation, a total of 50 new referrals were placed to inpatient palliative care, OSS, and outpatient palliative care and 11 new advance care plans were documented in the electronic medical record. CONCLUSION: This paper describes a sustainable method to implement a POTB in a community cancer center setting, which is one method of integrating palliative care into standard oncologic care.

General practitioner practice-based pharmacist input to medicines optimisation in the UK: pragmatic, multicenter, randomised, controlled trial.

BACKGROUND: Changing demographics across the UK has led to general practitioners (GPs) managing increasing numbers of older patients with multi-morbidity and resultant polypharmacy. Through government led initiatives within the National Health Service, an increasing number of GP practices employ pharmacist support. The purpose of this study is to evaluate the impact of a medicines optimisation intervention, delivered by GP practice-based pharmacists, to patients at risk of medication-related problems (MRPs), on patient outcomes and healthcare costs. METHODS: A multi-centre, randomised (normal care or pharmacist supplemented care) study in four regions of the UK, involving patients (n = 356) from eight GP practices, with a 6-month follow-up period. Participants were adult patients who were at risk of MRPs. RESULTS: Median number of MRPs per intervention patient were reduced at the third assessment, i.e. 3 to 0.5 (p < 0.001) in patients who received the full intervention schedule. Medication Appropriateness Index (MAI) scores were reduced (medications more appropriate) for the intervention group, but not for control group patients (8 [4-13] to 5 [0-11] vs 8 [3-13] to 7 [3-12], respectively; p = 0.001). Using the intention-to-treat (ITT) approach, the number of telephone consultations in intervention group patients was reduced and different from the control group (1 [0-3] to 1 [0-2] vs 1 [0-2] to 1 [0-3], p = 0.020). No significant differences between groups were, however, found in unplanned hospital admissions, length of hospital stay, number of A&E attendances or outpatient visits. The mean overall healthcare cost per intervention patient fell from £1041.7 ± 1446.7 to £859.1 ± 1235.2 (p = 0.032). Cost utility analysis showed an incremental cost per patient of - £229.0 (95% CI - 594.6, 128.2) and a mean QALY gained of 0.024 (95% CI - 0.021 to 0.065), i.e. indicative of a health status gain at a reduced cost (2016/2017). CONCLUSION: The pharmacist service was effective in reducing MRPs, inappropriateness of medications and telephone consultations in general practice in a cost-effective manner. TRIAL REGISTRATION: ClinicalTrials.Gov, NCT03241498. Registered 7 August 2017-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03241498.

Reducing Barriers for RN-BSN Education: The Assessment Competency Evaluation.

The Northeast Team of the Ohio Action Coalition, composed of regional clinical and academic educators, identified a potential barrier for nurses pursuing a baccalaureate degree. Duplication of health assessment content was identified for some associate degree graduates enrolled in RN-BSN programs, thereby adding extra time and cost for attaining the baccalaureate degree. In response, the Northeast Team of the Ohio Action Coalition developed an assessment competency evaluation that, if successfully passed, would grant credit for the health assessment course. The assessment competency evaluation provided the opportunity for students to demonstrate competency in both health assessment and clinical judgment skills.

Differences in treatment goals and perception of symptom burden between patients with myeloproliferative neoplasms (MPNs) and hematologists/oncologists in the United States: Findings from the MPN Landmark survey.

BACKGROUND: This analysis of the myeloproliferative neoplasm (MPN) Landmark survey evaluated gaps between patient perceptions of their disease management and physician self-reported practices. METHODS: The survey included 813 patient respondents who had MPNs (myelofibrosis [MF], polycythemia vera [PV], or essential thrombocythemia [ET]) and 457 hematologist/oncologist respondents who treated patients with these conditions. RESULTS: Greater proportions of physician respondents reported using prognostic risk classifications (MF, 83%; PV, 59%; ET, 77%) compared with patient recollections (MF, 54%; PV, 17%; ET, 31%). Most physician respondents reported that their typical symptom assessments included asking patients about the most important symptoms or a full list of symptoms, whereas many patient respondents reported less specific assessments (eg, they were asked how they were feeling). Many patient respondents did not recognize common symptoms as MPN-related. For example, approximately one-half or more did not believe difficulty sleeping resulted from their MPN (MF, 49%; PV, 64%; ET, 76%). Physician respondents underestimated the proportion of patients who had symptomatic PV or ET at diagnosis compared with patient respondents. There was discordance regarding treatment goals: among patient respondents with MF or PV, "slow/delay progression of condition" was the most important treatment goal, whereas physician respondents reported "symptom improvement" and "prevention of vascular/thrombotic events," respectively. Finally, more than one-third of patient respondents were not "very satisfied" with their physician's overall management/communication. CONCLUSIONS: The care and satisfaction of patients with MPN may be improved with increased patient education and improved patient-physician communication. Cancer 2017;123:449-458. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

Myeloproliferative neoplasms (MPNs) have a significant impact on patients' overall health and productivity: the MPN Landmark survey.

BACKGROUND: The Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) myelofibrosis (MF), polycythemia vera (PV), and essential thrombocythemia (ET) negatively affect patient quality of life (QoL) and are associated with increased risk of mortality. METHODS: The MPN Landmark survey was conducted from May to July 2014 in patients with MF, PV, or ET under active management in the United States. The survey assessed respondent perceptions of disease burden and treatment management and included questions on overall disease burden, QoL, activities of daily living, and work productivity. Outcomes were further analyzed by calculated (ie, not respondent-reported) prognostic risk score and symptom severity quartile. RESULTS: The survey was completed by 813 respondents (MF, n = 207; PV, n = 380; ET, n = 226). The median respondent age in each of the 3 MPN subtypes ranged from 62 to 66 years; median disease duration was 4 to 7 years. Many respondents reported that they had experienced MPN-related symptoms ≥1 year before diagnosis (MF, 49 %; PV, 61 %; ET, 58 %). Respondents also reported that MPN-related symptoms reduced their QoL, including respondents with low prognostic risk scores (MF, 67 %; PV, 62 %; ET, 57 %) and low symptom severity (MF, 51 %; PV, 33 %; ET, 15 %). Many respondents, including those with a low prognostic risk score, reported that their MPN had caused them to cancel planned activities or call in sick to work at least once in the preceding 30 days (cancel planned activities: MF, 56 %; PV, 35 %; ET, 35 %; call in sick: MF, 40 %; PV, 21 %; ET, 23 %). CONCLUSIONS: These findings of the MPN Landmark survey support previous research about the symptom burden experienced by patients with MPNs and are the first to detail the challenges that patients with MPNs experience related to reductions in activities of daily living and work productivity.

Five-group cytogenetic risk classification, monosomal karyotype, and outcome after hematopoietic cell transplantation for MDS or acute leukemia evolving from MDS.

Clonal cytogenetic abnormalities are a major risk factor for relapse after hematopoietic cell transplantation (HCT) for myelodysplastic syndrome (MDS). We determined the impact of the recently established 5-group cytogenetic classification of MDS on outcome after HCT. Results were compared with the impact of the International Prognostic Scoring System (IPSS) 3 cytogenetic risk groups, and the additional effect of a monosomal karyotype was assessed. The study included data on 1007 patients, 1-75 years old (median 45 years), transplanted from related (n = 547) or unrelated (n = 460) donors. Various conditioning regimens were used, and marrow, peripheral blood, or cord blood served as stem cell source. Both IPSS and 5-group cytogenetic risk classifications were significantly associated with post-HCT relapse and mortality, but the 5-group classification discriminated more clearly among the lowest- and highest-risk patients. A monosomal karyotype tended to further increase the rates of relapse and mortality, even after considering the IPSS or 5-group classifications. In addition, the pathologic disease category correlated with both relapse and mortality. Mortality was also impacted by patient age, donor type, conditioning regimen, platelet count, and etiology of MDS. Although mortality declined significantly in recent years, novel strategies are needed to overcome the barrier of high-risk cytogenetics.

Vandetanib for the treatment of symptomatic or progressive medullary thyroid cancer in patients with unresectable locally advanced or metastatic disease: U.S. Food and Drug Administration drug approval summary.

On April 6, 2011, the U.S. Food and Drug Administration approved vandetanib (Caprelsa tablets; AstraZeneca Pharmaceuticals LP) for the treatment of symptomatic or progressive medullary thyroid cancer in patients with unresectable, locally advanced, or metastatic disease. Vandetanib is the first drug approved for this indication, and this article focuses on the basis of approval. Approval was based on the results of a double-blind trial conducted in patients with medullary thyroid carcinoma. Patients were randomized 2:1 to vandetanib, 300 mg/d orally (n = 231), or to placebo (n = 100). The primary objective was demonstration of improvement in progression-free survival (PFS) with vandetanib compared with placebo. Other endpoints included evaluation of overall survival and objective response rate. The PFS analysis showed a marked improvement for patients randomized to vandetanib (hazard ratio = 0.35; 95% confidence interval, 0.24-0.53; P < 0.0001). The objective response rate for the vandetanib arm was 44% compared with 1% for the placebo arm. The most common grade 3 and 4 toxicities (>5%) were diarrhea and/or colitis, hypertension and hypertensive crisis, fatigue, hypocalcemia, rash, and corrected QT interval (QTc) prolongation. This approval was based on a statistically significant and clinically meaningful improvement in PFS. Given the toxicity profile, which includes prolongation of the QT interval and sudden death, only prescribers and pharmacies certified through the vandetanib Risk Evaluation Mitigation Strategy Program are able to prescribe and dispense vandetanib. Treatment-related risks should be taken into account when considering the use of vandetanib in patients with indolent, asymptomatic, or slowly progressing disease.

The Hepatocyte Growth Factor/c-Met Antagonist, Divalinal-Angiotensin IV, Blocks the Acquisition of Methamphetamine Dependent Conditioned Place Preference in Rats.

The use of methamphetamine (MA) is increasing in the U.S. and elsewhere around the world. MA's capacity to cause addiction significantly exceeds other psychostimulant drugs, and its use negatively impacts learning and memory. Recently, attempts have been made to interfere with the presumed mechanism(s) underlying the establishment of drug-induced memory consolidation. The majority of these studies have employed matrix metalloproteinase (MMP) inhibitors to disrupt MMP-induced extracellular matrix molecule dependent synaptic reconfiguration, or GABA receptor agonists. The present investigation utilized an angiotensin IV (AngIV) analogue, Divalinal-AngIV (divalinal), to disrupt acquisition of MA-induced dependence in rats as measured using the conditioned place preference paradigm. Results indicate that both acute and chronic intracerebroventricular infusion of divalinal prior to each daily subcutaneous injection of MA prevented acquisition. However, divalinal was unable to prevent MA-induced reinstatement after prior acquisition followed by extinction trials. These results indicate that prevention of MA dependence can be accomplished by blockade of the brain AT4 receptor subtype. On the other hand, once MA-induced memory consolidation is in place divalinal appears to be ineffective. Mechanistic studies indicated that divalinal is a potent inhibitor of the hepatocyte growth factor (HGF)/c-Met receptor system, and thus it appears that a functional HGF/c-Met system is required for the acquisition of MA-mediated conditioned place preference.

Winter body temperature patterns in free-ranging Cape ground squirrel, Xerus inauris: no evidence for torpor.

The body temperature (T(b)) of Cape ground squirrels (Xerus inauris, Sciuridae) living in their natural environment during winter has not yet been investigated. In this study we measured abdominal T(b) of eight free-ranging Cape ground squirrels over 27 consecutive days during the austral winter. Mean daily T(b) was relatively stable at 37.0 ± 0.2°C (range 33.4 to 40.2°C) despite a marked variation in globe temperature (T(g)) (range -7 to 37°C). Lactating females (n = 2) consistently had a significantly higher mean T (b) (0.7°C) than non-lactating females (n = 3) and males. There was a pronounced nychthemeral rhythm with a mean active phase T(b) of 38.1 ± 0.1°C and a mean inactive phase T(b) of 36.3 ± 0.3°C for non-lactating individuals. Mean daily amplitude of T(b) rhythm was 3.8 ± 0.2°C. T(b) during the active phase closely followed T(g) and mean active phase T(b) was significantly correlated with mean active phase T(g) (r(2) = 0.3-0.9; P < 0.01). There was no evidence for daily torpor or pronounced hypothermia during the inactive phase, and mean minimum inactive phase T(b) was 35.7 ± 0.3°C for non-lactating individuals. Several alternatives (including nocturnal huddling, an aseasonal breeding pattern and abundant winter food resources) as to why Cape ground squirrels do not employ nocturnal hypothermia are discussed.

Allogeneic hematopoietic cell transplantation after conditioning with 131I-anti-CD45 antibody plus fludarabine and low-dose total body irradiation for elderly patients with advanced acute myeloid leukemia or high-risk myelodysplastic syndrome.

We conducted a study to estimate the maximum tolerated dose (MTD) of (131)I-anti-CD45 antibody (Ab; BC8) that can be combined with a standard reduced-intensity conditioning regimen before allogeneic hematopoietic cell transplantation. Fifty-eight patients older than 50 years with advanced acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS) were treated with (131)I-BC8 Ab and fludarabine plus 2 Gy total body irradiation. Eighty-six percent of patients had AML or MDS with greater than 5% marrow blasts at the time of transplantation. Treatment produced a complete remission in all patients, and all had 100% donor-derived CD3(+) and CD33(+) cells in the blood by day 28 after the transplantation. The MTD of (131)I-BC8 Ab delivered to liver was estimated to be 24 Gy. Seven patients (12%) died of nonrelapse causes by day 100. The estimated probability of recurrent malignancy at 1 year is 40%, and the 1-year survival estimate is 41%. These results show that CD45-targeted radiotherapy can be safely combined with a reduced-intensity conditioning regimen to yield encouraging overall survival for older, high-risk patients with AML or MDS. This study was registered at www.clinicaltrials.gov as #NCT00008177.

The role of the AT4 and cholinergic systems in the Nucleus Basalis Magnocellularis (NBM): effects on spatial memory.

The brain AT(4) and cholinergic systems play a pivotal role in learning and memory. Studies have investigated the nootropic and amnesic properties of both systems. The cholinergic system has received the most attention for its contribution to cognitive functioning. For example, one of the best known cognitive disorders, Alzheimer's disease (AD), is treated with cholinergic-directed drugs, and post-mortem studies of AD patient brains show neurodegenerative devastation in cholinergic areas of the brain. Studies suggest that potentiation of cholinergic transmission may be a mechanism by which the AngIV/AT(4) receptor system enhances cognition. Since the Nucleus Basalis Magnocellularis (Meynert in humans and primates) (NBM) is a main source of cholinergic innervation to cognitive areas of the brain, this site was chosen to investigate the role and interaction of the two systems. Rats were fitted with permanent bilateral cannulas targeting the NBM for drug administration. Divalinal-AngIV, an AT(4) receptor antagonist produced profound deficits in performance in the Circular water maze. Nicotine treatment reversed these impairments whereas carbachol did not. Similar to the AT(4) antagonist, scopolamine and mecamylamine prevented acquisition of the water maze. Based on these results, it appears that blocking any one of these systems results in impaired spatial learning, while activating the nicotinic receptor system counteracts the effects of AT(4) receptor blockade. These findings suggest a functional role for both the cholinergic and AT(4) receptor systems in spatial learning, and indicate for the first time a functional role for the AngIV/AT(4) receptor system in the NBM.

Endocrine regulation of cognition and neuroplasticity: our pursuit to unveil the complex interaction between hormones, the brain, and behaviour.

Gonadal and stress hormones modulate neuroplasticity and behaviour. This review focuses on our findings over the past decade on the effects of estrogens and androgens on hippocampal neurogenesis, hippocampus-dependent learning and memory and the effects of reproductive experience in the rodent. Evidence suggests that acute estradiol initially enhances and subsequently suppresses cell proliferation in the dentate gyrus of adult female rodents. Repeated exposure to estradiol modulates hippocampal neurogenesis and cell death in adult female, but not male, rodents while, testosterone and dihydrotestosterone upregulate hippocampal neurogenesis in adult male rodents. Estradiol dose-dependently affects different brain regions involved in working memory (prefrontal cortex, hippocampus), reference memory (hippocampus) and conditioned place preference (amygdala). Pregnancy and motherhood differentially regulate adult hippocampal neurogenesis and spatial working memory in the dam after weaning. These studies and others demonstrate that the female brain responds to steroid hormones differently than the male brain. It is of the upmost importance to investigate the effects on neuroplasticity and behaviour in both the male and the female, particularly when modelling diseases that exhibit sex differences in incidence, etiology or treatment.

Application of phage display to high throughput antibody generation and characterization.

We have created a high quality phage display library containing over 1010 human antibodies and describe its use in the generation of antibodies on an unprecedented scale. We have selected, screened and sequenced over 38,000 recombinant antibodies to 292 antigens, yielding over 7,200 unique clones. 4,400 antibodies were characterized by specificity testing and detailed sequence analysis and the data/clones are available online. Sensitive detection was demonstrated in a bead based flow cytometry assay. Furthermore, positive staining by immunohistochemistry on tissue microarrays was found for 37% (143/381) of antibodies. Thus, we have demonstrated the potential of and illuminated the issues associated with genome-wide monoclonal antibody generation.