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1.
J Hosp Palliat Nurs ; 25(3): 129-136, 2023 06 01.
Article in English | MEDLINE | ID: mdl-36971763

ABSTRACT

Nominal research illustrates the lived experience of intensive care unit registered nurses during the COVID pandemic. Palliative care team leaders and nurse researchers designed this cross-sectional study to discover opportunities for palliative care team members to enhance the experience of nurses who cared for critically ill patients during this challenging time. The study aimed to compare the effect of caring for patients in COVID versus non-COVID units. Surveys were distributed after the area's initial COVID patient influx. Questions included general demographics, the Professional Quality of Life survey instrument (measuring compassion satisfaction, burnout, and secondary traumatic stress), and open-ended questions to identify protective factors and unique challenges. Across 5 care settings with 311 nurses eligible for the study in total, 90 completed the survey. The population consisted of COVID-designated unit nurses (n = 48, 53.33%) and non-COVID unit nurses (n = 42, 46.67%). Analysis between COVID-designated and non-COVID units revealed significantly lower mean compassion scores and significantly higher burnout and stress scores among those working within COVID-designated units. Despite higher levels of burnout and stress and lower levels of compassion, nurses identified protective factors that improved coping and described challenges they encountered. Palliative care clinicians used insights to design interventions to mitigate identified challenges and stressors.


Subject(s)
Burnout, Professional , COVID-19 , Nurses , Humans , Inpatients , Cross-Sectional Studies , Quality of Life , Palliative Care , Pandemics , COVID-19/epidemiology
2.
J Psychosoc Oncol ; 41(6): 732-743, 2023.
Article in English | MEDLINE | ID: mdl-36752067

ABSTRACT

Introduction: Patients undergoing oncology-related gynecologic surgical procedures experience substantial symptom burden and distress. Support from specialist palliative care teams may benefit these patients and their families; however, an evidence-informed approach to the integration of palliative care and gynecologic surgical oncology is needed. To inform such an approach, a scoping review synthesizing current evidence on the palliative care needs of patients and families in gynecologic surgical oncology was conducted.Methods: Reviewers performed a structured search of online databases CINAHL, Scopus, PsycINFO, MEDLINE, and PubMed in addition to the grey literature to identify relevant studies published between 2011 and June 11th, 2021. The original search identified 993 articles, which were dually screened for study inclusion, resulting in a final sample of articles from which data were systematically extracted and synthesized.Results: This review of 59 publications predominantly consisted of European studies (n = 26, 44.1%), described quantitative study methods (n = 47, 79.6%), followed an observational study design (n = 49, 83.1%), and focused on psychological impact of treatment as a major topic of study (n = 21, 35.6%). The dataset also described sexual function of women post treatment (n = 15, 25.4%), quality of life (n = 10, 16.9%), therapeutic decision making (n = 9, 15.2%), pain assessment (n = 2, n = 3.6%), and medication for symptom management (n = 2, 3.6%). Explicit discussion of specialist palliative care involvement was rare.Conclusion: The needs of patients and families in gynecologic surgical oncology are well-suited to palliative care collaboration; however, the body of literature on palliative care services provided to this unique population is underdeveloped.

3.
Am J Hosp Palliat Care ; 40(3): 291-298, 2023 Mar.
Article in English | MEDLINE | ID: mdl-35723043

ABSTRACT

Background: Evidence suggests the usefulness of complementary and alternative medicine approaches, like neurofeedback and virtual reality, for the management of cancer-related pain and mood. It is not well-understood whether neurofeedback delivered through virtual reality is feasible and acceptable to patients actively undergoing cancer treatment. Objective: The purpose of this study was to explore the feasibility and acceptability of a nature-based virtual reality combined with neurofeedback as a non-pharmacologic strategy for managing cancer-related pain and anxiety. Methods: This study utilized a mixed-methods approach. Participants included 15 cancer patients undergoing treatment. Patients engaged in a 22-minute nature-based virtual reality experience, wearing a virtual reality headset with a Brainlink headband measuring EEG activity. Participants were asked to complete the Edmonton Symptom Assessment System revised version (ESAS-r) before (T1) and after (T3) the experience to measure pain and anxiety. They were asked their level of pain midway through the experience (T2) and completed a follow-up interview afterward. Results: This study revealed feasible delivery of a virtual reality intervention combined with neurofeedback for patients seeking cancer treatment. All participants (100%) completed the intervention experience. Patients report this is an acceptable approach to managing cancer-related pain and anxiety. Comparisons between patients' pain scores at T1, T2, and T3 reveal statistically significant reductions in pain (p .001). Patients also report decreased depression and anxiety. Conclusion: This is the first study examining virtual reality combined with neurofeedback as a non-pharmacologic intervention for managing cancer symptoms during treatment. The study reveals it is a promising for managing cancer-symptoms.


Subject(s)
Cancer Pain , Neoplasms , Neurofeedback , Virtual Reality , Humans , Neurofeedback/methods , Feasibility Studies , Pain , Anxiety/etiology , Anxiety/therapy , Neoplasms/complications , Neoplasms/therapy
4.
Nucleic Acid Ther ; 33(1): 35-44, 2023 01.
Article in English | MEDLINE | ID: mdl-36318487

ABSTRACT

Despite wide recognition as a disease of pandemic proportions, effective treatments for nonalcoholic fatty liver disease (NAFLD) remain elusive. Most of the current clinical programs aim to reduce hepatic fat accumulation and, thus, prevent downstream inflammation and fibrosis. To date, this therapeutic approach has helped identify a potential disconnect between steatosis reduction and disease resolution. Mounting preclinical evidence indicates liver inflammation may play a major role in steatosis development and fibrosis but has not garnered the same clinical representation. This may be owing to deficiencies in standard therapeutic modalities that limit their application in NAFLD. RNA interference (RNAi) is an attractive approach to targeting liver inflammation owing to its clinical safety profile, target specificity, and limited biodistribution. In this study, we characterize a simple cholesterol-short-interfering RNA (siRNA) conjugate system targeting Tnf mRNA in liver macrophages for the treatment of NAFLD. First, we observed delivery and anti-inflammatory activity in an acute liver inflammation model. In a follow-up murine NAFLD model, we observed total prevention of nearly all hallmarks of this disease: steatosis, inflammation, and fibrosis. This simple conjugate siRNA delivery system may be the first to show RNAi activity in liver macrophages and provide evidence for a novel therapeutic approach to inflammation in NAFLD.


Subject(s)
Non-alcoholic Fatty Liver Disease , Mice , Animals , Non-alcoholic Fatty Liver Disease/genetics , Non-alcoholic Fatty Liver Disease/therapy , Non-alcoholic Fatty Liver Disease/metabolism , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism , Tissue Distribution , Liver/metabolism , Kupffer Cells , Inflammation/genetics , Inflammation/therapy , Cholesterol , RNA, Double-Stranded/metabolism , Fibrosis
5.
J Pain Symptom Manage ; 63(3): e287-e293, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34826545

ABSTRACT

CONTEXT: Hospitalization provides an opportunity to address end-of-life care (EoLC) preferences if patients at risk of death can be accurately identified while in the hospital. The modified Hospital One-Year Mortality Risk (mHOMR) uses demographic and admission data in a logistic regression algorithm to identify patients at risk of death one year from admission. OBJECTIVES: This project sought to validate mHOMR and identify superior models. METHODS: The mHOMR model was validated using historical data from an academic health system. Alternative logistic regression and random forest (RF) models were developed using the same variables. Receiver operating characteristic (ROC) and precision recall curves were developed, and sensitivity, specificity, and positive and negative predictive values were compared over a range of model thresholds. RESULTS: The RF model demonstrated higher area under the ROC curve (0.950, 95% CI 0.947 - 0.954) as compared to the logistic regression models (0.818 [95% CI 0.812 - 0.825] and 0.841 [95% CI 0.836 - 0.847]). Area under the precision recall curve was higher with the random forest model compared to the logistic regression models (0.863 vs. 0.458 and 0.494, respectively). Across a range of thresholds, the RF model demonstrated superior sensitivity, equivalent specificity, and higher positive and negative predictive values. CONCLUSION: A machine learning RF model, using common demographic and utilization data available on hospital admission, identified inpatients at risk of death more effectively than logistic regression models using the same variables. Machine learning models have promise for identifying admitted patients with elevated one-year mortality risk, increasing opportunities to prompt discussion of EoLC preferences.


Subject(s)
Hospitalization , Machine Learning , Hospital Mortality , Humans , Logistic Models , ROC Curve , Retrospective Studies
6.
Am J Hosp Palliat Care ; 38(5): 467-471, 2021 May.
Article in English | MEDLINE | ID: mdl-32757823

ABSTRACT

The translation of evidence-based interventions into routine hospice care is impeded by numerous barriers, including a disconnect between research priorities and clinical care. To inform the development of a more practice-informed agenda for hospice intervention research, our team conducted a qualitative descriptive study, posing the following research questions: 1) How do hospice staff members describe their most significant work-related challenges? and 2) What regulatory changes do hospice staff members report would most improve hospice care? To answer these research questions, we interviewed 22 hospice staff members and then conducted a template analysis of the interview content. In doing so, we identified themes that described challenges in 5 key areas: time, documentation, professional roles, recruitment and retention, and burn-out. In addition, we identified a perceived need among hospice staff members for more regulatory flexibility and clarity. Based on our findings, we conclude that a practice-informed agenda for hospice intervention research includes the development and testing of interventions that increase efficiency, explicitly speak to the humanity of hospice care, and elevate the roles of all members of the interdisciplinary team.


Subject(s)
Hospice Care , Hospices , Humans , Professional Role , Qualitative Research
7.
Environ Sci Technol ; 54(20): 13016-13025, 2020 10 20.
Article in English | MEDLINE | ID: mdl-32881494

ABSTRACT

The need to characterize and track coastal hypoxia has led to the development of geostatistical models based on in situ observations of dissolved oxygen (DO) and mechanistic models based on a representation of biophysical processes. To integrate the benefits of these two distinct modeling approaches, we develop a space-time geostatistical framework for synthesizing DO observations with hydrodynamic-biogeochemical model simulations and meteorological time series (as covariates). This fusion-based approach is used to estimate hypoxia in the northern Gulf of Mexico across summers from 1985 to 2017. Deterministic trends with dynamic covariates explain over 35% of the variability in DO. Moreover, cross-validation results indicate that 58% of DO variability is explained when combining these trends with spatiotemporal interpolation, which is substantially better than mechanistic or conventional geostatistical hypoxia modeling alone. The fusion-based approach also reduces hypoxic area uncertainties by 11% on average and up to 40% in months with sparse sampling. Moreover, our new estimates of mean summer hypoxic area changed by >10% in a majority of years, relative to previous geostatistical estimates. These fusion-based estimates can be a valuable resource when assessing the influence of hypoxia on the coastal ecosystem.


Subject(s)
Ecosystem , Oxygen , Environmental Monitoring , Gulf of Mexico , Humans , Hypoxia , Oxygen/analysis , Seasons
8.
J Psychosoc Oncol ; 37(6): 777-790, 2019.
Article in English | MEDLINE | ID: mdl-31204604

ABSTRACT

Purpose/Objectives: Family caregivers of individuals living with cancer are often highly involved in communication with healthcare teams, yet little is known about their experiences, needs, and preferences in this role. To address this gap in the knowledge base, researchers sought to explore family caregivers' perspectives on communication with oncology care providers. Design and Methods: Researchers conducted a secondary inductive thematic analysis of qualitative interviews originally collected as part of a randomized clinical trial of a supportive intervention for family caregivers of patients with cancer (N = 63). Participants: Participants were family caregivers of adult patients with cancer. Most were patients' spouses/long-term partners (52.3%) or adult children/grandchildren (29.2%). Caregivers of patients with all cancer types and stages of disease progression were eligible for study enrollment. Findings: Caregivers valued communication with healthcare providers who were attentive, genuine, broadly focused on patients and caregivers' experiences, sensitive to unmet information needs, and responsive to the potentially different communication preferences of patients and caregivers. Interpretation: Family caregivers expressed a strong preference for person-centered communication, conceptualized as communication that helps healthcare providers meet the needs of patients and caregivers both as individuals and as an interdependent unit of care, and that acknowledges individuals' experiences beyond their prescribed roles of "cancer patient" and "caregiver." Implications for Psychosocial Oncology Practice: Psychosocial oncology providers' strong orientation to the biopsychosocial and spiritual aspects of cancer care delivery make them uniquely positioned to support family caregivers. Findings suggest that providers should explicitly communicate their commitment to both patient and family care, involve family caregivers in psychosocial assessment activities and subsequent intervention, and strive to honor patients and caregivers' potentially different communication preferences.


Subject(s)
Attitude to Health , Caregivers/psychology , Communication , Neoplasms/therapy , Professional-Family Relations , Adult , Aged , Caregivers/statistics & numerical data , Female , Humans , Male , Middle Aged , Qualitative Research
9.
Psychopharmacology (Berl) ; 236(8): 2325-2336, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31201476

ABSTRACT

RATIONALE: Patients with obsessive-compulsive disorder (OCD) have been found to show exaggerated error responses and prediction error learning signals in a variety of EEG and fMRI tasks, with data converging on the anterior cingulate cortex as a key locus of dysfunction. Considerable evidence has linked prediction error processing to dopaminergic function. OBJECTIVE: In this study, we investigate potential dopaminergic dysfunction during reward processing in the context of OCD. METHODS: We studied OCD patients (n = 18) and controls (n = 18) whilst they learned probabilistic associations between abstract stimuli and monetary rewards in the fMRI scanner involving administration (on separate visits) of a dopamine receptor agonist, pramipexole 0.5 mg; a dopamine receptor antagonist, amisulpride 400 mg; and placebo. We fitted a Q-learning computational model to fMRI prediction error responses; group differences were examined in anterior cingulate and nucleus accumbens regions of interest. RESULTS: There were no significant group, drug, or interaction effects in the number of correct choices; computational modeling suggested a marginally significant difference in learning rates between groups (p = 0.089, partial ƞ2 = 0.1). In the imaging results, there was a significant interaction of group by drug (p = 0.013, partial ƞ2 = 0.13). OCD patients showed abnormally strong cingulate signaling of prediction errors during omission of an expected reward, with unexpected reduction by both pramipexole and amisulpride (p = 0.014, partial ƞ2 = 0.26, 1-ß error probability = 0.94). Exaggerated cingulate prediction error signaling to omitted reward in placebo was related to trait subjective difficulty in self-regulating behavior in OCD. CONCLUSIONS: Our data support cingulate dysfunction during reward processing in OCD, and bidirectional remediation by dopaminergic modulation, suggesting that exaggerated cingulate error signals in OCD may be of dopaminergic origin. The results help to illuminate the mechanisms through which dopamine receptor antagonists achieve therapeutic benefit in OCD. Further research is needed to disentangle the different functions of dopamine receptor agonists and antagonists during bidirectional modulation of cingulate activation.


Subject(s)
Dopamine Agonists/pharmacology , Dopamine Antagonists/pharmacology , Gyrus Cinguli/drug effects , Gyrus Cinguli/diagnostic imaging , Obsessive-Compulsive Disorder/diagnostic imaging , Reward , Adult , Dopamine/metabolism , Double-Blind Method , Female , Forecasting , Gyrus Cinguli/metabolism , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Nucleus Accumbens/diagnostic imaging , Nucleus Accumbens/drug effects , Nucleus Accumbens/metabolism , Obsessive-Compulsive Disorder/metabolism , Photic Stimulation/methods
10.
Palliat Support Care ; 17(5): 579-583, 2019 10.
Article in English | MEDLINE | ID: mdl-30841945

ABSTRACT

OBJECTIVE: Hospice nurses frequently encounter patients and families under tremendous emotional distress, yet the communication techniques they use in emotionally charged situations have rarely been investigated. In this study, researchers sought to examine hospice nurses' use of validation communication techniques, which have been shown in prior research to be effective in supporting individuals experiencing emotional distress. METHOD: Researchers performed a directed content analysis of audiorecordings of 65 hospice nurses' home visits by identifying instances when nurses used validation communication techniques and rating the level of complexity of those techniques. RESULT: All nurses used validation communication techniques at least once during their home visits. Use of lower level (i.e., more basic) techniques was more common than use of higher level (i.e., more complex) techniques. SIGNIFICANCE OF RESULTS: Although hospice nurses appear to use basic validation techniques naturally, benefit may be found in the use of higher level techniques, which have been shown to result in improved clinical outcomes in other settings.


Subject(s)
Hospice and Palliative Care Nursing/standards , Nurse-Patient Relations , Nurses/psychology , Adult , Aged , Caregivers/psychology , Female , Hospice Care/psychology , Hospice and Palliative Care Nursing/methods , Hospice and Palliative Care Nursing/statistics & numerical data , Hospices/organization & administration , Humans , Male , Middle Aged , Nurses/statistics & numerical data , Patients/psychology , Qualitative Research
11.
Mol Ther ; 26(11): 2567-2579, 2018 11 07.
Article in English | MEDLINE | ID: mdl-30274786

ABSTRACT

Wnt/ß-catenin signaling mediates cancer immune evasion and resistance to immune checkpoint therapy, in part by blocking cytokines that trigger immune cell recruitment. Inhibition of ß-catenin may be an effective strategy for increasing the low response rate to these effective medicines in numerous cancer populations. DCR-BCAT is a nanoparticle drug product containing a chemically optimized RNAi trigger targeting CTNNB1, the gene that encodes ß-catenin. In syngeneic mouse tumor models, ß-catenin inhibition with DCR-BCAT significantly increased T cell infiltration and potentiated the sensitivity of the tumors to checkpoint inhibition. The combination of DCR-BCAT and immunotherapy yielded significantly greater tumor growth inhibition (TGI) compared to monotherapy in B16F10 melanoma, 4T1 mammary carcinoma, Neuro2A neuroblastoma, and Renca renal adenocarcinoma. Response to the RNAi-containing combination therapy was not dependent on Wnt activation status of the tumor. Importantly, this drug combination was associated with elevated levels of biomarkers of T cell-mediated cytotoxicity. Finally, when CTLA-4 and PD-1 antibodies were combined with DCR-BCAT in MMTV-Wnt1 transgenic mice, a genetic model of spontaneous Wnt-driven tumors, complete regressions were achieved in the majority of treated subjects. These data support RNAi-mediated ß-catenin inhibition as an effective strategy to increase response rates to cancer immunotherapy.


Subject(s)
CTLA-4 Antigen/antagonists & inhibitors , Carcinoma, Renal Cell/drug therapy , Melanoma, Experimental/drug therapy , Programmed Cell Death 1 Receptor/antagonists & inhibitors , beta Catenin/genetics , Animals , CTLA-4 Antigen/genetics , CTLA-4 Antigen/immunology , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/immunology , Carcinoma, Renal Cell/pathology , Combined Modality Therapy , Female , Humans , Immunotherapy/methods , Melanoma, Experimental/genetics , Melanoma, Experimental/immunology , Melanoma, Experimental/pathology , Mice , Mice, Transgenic , Programmed Cell Death 1 Receptor/immunology , RNA Interference , RNA, Small Interfering/administration & dosage , RNA, Small Interfering/genetics , T-Lymphocytes/immunology , Wnt Signaling Pathway/genetics , Wnt1 Protein/genetics , beta Catenin/antagonists & inhibitors
12.
Psychooncology ; 27(10): 2494-2499, 2018 10.
Article in English | MEDLINE | ID: mdl-30107070

ABSTRACT

OBJECTIVE: In response to the well-documented need for evidence-based cancer caregiver support, we examined the feasibility of problem-solving therapy for family caregivers of cancer patients receiving outpatient palliative care and investigated the impact of problem-solving therapy on family caregivers' anxiety, depression, and quality of life. METHODS: We conducted a feasibility study of a structured problem-solving therapy intervention delivered to family caregivers of cancer patients receiving outpatient palliative care from an academic health center in the Midwestern United States. Participants (N = 83) were randomly assigned to receive usual care or usual care plus a problem-solving therapy intervention, which was delivered over three sessions via web-based videoconferencing or telephone. Descriptive statistics were used to determine feasibility relative to recruitment, retention, and fidelity to core intervention components. Outcome data were analyzed using ordinary least squares multiple regression. RESULTS: Problem-solving therapy for family caregivers of patients with cancer was found to be highly feasible in the outpatient palliative care setting. Caregivers who received problem-solving therapy reported less anxiety than those who received only usual care (P = 0.03). No statistically significant differences were observed for caregiver depression (P = 0.07) or quality of life (P = 0.06). CONCLUSIONS: Problem-solving therapy is a feasible and promising approach to reducing cancer family caregivers' anxiety in the outpatient palliative care setting. Further testing in multiple sites is recommended.


Subject(s)
Caregivers/psychology , Cognitive Behavioral Therapy/methods , Neoplasms/psychology , Palliative Care/methods , Problem Solving , Ambulatory Care/methods , Family/psychology , Feasibility Studies , Female , Humans , Male , Middle Aged , Neoplasms/therapy , Quality of Life/psychology , Single-Blind Method
13.
Expert Opin Drug Deliv ; 15(6): 629-640, 2018 06.
Article in English | MEDLINE | ID: mdl-29727206

ABSTRACT

INTRODUCTION: Oligonucleotide therapeutics have the potential to change the way disease is treated due to their ability to modulate gene expression of any therapeutic target in a highly specific and potent manner. Unfortunately, this drug class is plagued with inherently poor pharmacological characteristics, which need to be overcome. The development of a chemical modification library for oligonucleotides has addressed many of the initial challenges, but delivery of these payloads across plasma membranes remains difficult. The latest technological advances in oligonucleotide therapeutics utilizes direct conjugation to targeting ligands, which has improved bioavailability and target tissue exposure many-fold. The success of this approach has resulted in numerous clinical programs over the past 5 years. AREAS COVERED: We review the literature on oligonucleotide conjugate strategies which have proven effective preclinically and clinically. We summarize the chemical modifications which allow parenteral administration as well as evaluate the efficacy of a multitude of conjugate approaches including lipids, peptides, carbohydrates, and antibodies. EXPERT OPINION: The success of future conjugate strategies will likely rely on the effective combination of characteristics from earlier technologies. High-affinity ligand-receptor interactions can be critical to achieving meaningful accumulation in target tissues, but pharmacokinetic modulators which increase the circulating half-life may also be necessary. Synthesis of these approaches has the potential to bring the next breakthrough in oligonucleotide therapeutics.


Subject(s)
Oligonucleotides, Antisense/administration & dosage , Oligonucleotides/administration & dosage , Animals , Carbohydrates/chemistry , Humans , Ligands , Lipids/chemistry , Peptides/chemistry
14.
Mol Cancer Ther ; 17(2): 544-553, 2018 02.
Article in English | MEDLINE | ID: mdl-29282298

ABSTRACT

Colorectal carcinomas harbor well-defined genetic abnormalities, including aberrant activation of Wnt/ß-catenin and MAPK pathways, often simultaneously. Although the MAPK pathway can be targeted using potent small-molecule drugs, including BRAF and MEK inhibitors, ß-catenin inhibition has been historically challenging. RNAi approaches have advanced to the stage of clinical viability and are especially well suited for transcriptional modulators, such as ß-catenin. In this study, we report therapeutic effects of combined targeting of these pathways with pharmacologic agents. Using a recently described tumor-selective nanoparticle containing a ß-catenin-targeting RNAi trigger, in combination with the FDA-approved MEK inhibitor (MEKi) trametinib, we demonstrate synergistic tumor growth inhibition in in vivo models of colorectal cancer, melanoma, and hepatocellular carcinoma. At dose levels that were insufficient to significantly impact tumor growth as monotherapies, combination regimens resulted in synergistic efficacy and complete tumor growth inhibition. Importantly, dual MEKi/RNAi therapy dramatically improved survival of mice bearing colorectal cancer liver metastases. In addition, pharmacologic silencing of ß-catenin mRNA was effective against tumors that are inherently resistant or that acquire drug-induced resistance to trametinib. These results provide a strong rationale for clinical evaluation of this dual-targeting approach for cancers harboring Wnt/ß-catenin and MAPK pathway mutations. Mol Cancer Ther; 17(2); 544-53. ©2017 AACR.


Subject(s)
Colorectal Neoplasms/therapy , MAP Kinase Kinase Kinases/antagonists & inhibitors , Pyridones/pharmacology , Pyrimidinones/pharmacology , RNA, Messenger/genetics , RNA, Small Interfering/administration & dosage , beta Catenin/genetics , Animals , Cell Line, Tumor , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Drug Synergism , Gene Silencing , Heterografts , Humans , Liver Neoplasms, Experimental/secondary , MAP Kinase Kinase Kinases/metabolism , MAP Kinase Signaling System/drug effects , Mice , Mice, Nude , Nanoparticles/administration & dosage , Protein Kinase Inhibitors/pharmacology , RNA, Messenger/metabolism , RNA, Small Interfering/genetics , Wnt Signaling Pathway/drug effects , beta Catenin/metabolism
15.
J Pain Symptom Manage ; 55(3): 922-929, 2018 03.
Article in English | MEDLINE | ID: mdl-29128433

ABSTRACT

CONTEXT: Shared decisions between health care providers and patients and families are replacing the traditional physician-driven plans of care. Hospice philosophy recognizes the patient and family as a unit of care and embraces their role in decision making. OBJECTIVE: The goal of this study was to evaluate the shared decisions between hospice nurses and patients and family members. METHODS: A secondary analysis of audio recordings of 65 home hospice nurse visits from 65 home hospice nurse visits in 11 different U.S. hospice programs. RESULTS: To varying degrees, hospice nurses used all the recommended elements of shared decision making during home visits with patients and families; however, not all elements were used in every visit. The most commonly used element was defining a problem, and the least used element was the assessment of patient and family understanding. CONCLUSIONS: Hospice staff can benefit from a more purposeful shared decision-making process and a greater focus on assessment of patient and family understanding and ability to implement plans of care.


Subject(s)
Decision Making , Home Care Services , House Calls , Nurses/psychology , Adult , Aged , Caregivers/psychology , Family/psychology , Female , Health Communication , Hospice and Palliative Care Nursing , Humans , Male , Middle Aged , Nurse-Patient Relations , Qualitative Research
16.
Palliat Support Care ; 16(2): 127-136, 2018 04.
Article in English | MEDLINE | ID: mdl-28137342

ABSTRACT

ABSTRACTObjective:Researchers sought to determine the extent to which burden related to patients' symptom subtypes could predict informal hospice caregiver depression, and to illustrate the differences between caregivers who experience suicidal ideation and those who do not. METHOD: Informal caregivers recruited from a not-for-profit community-based hospice agency participated in a cross-sectional survey. Self-report questionnaires assessed caregiver burden associated with patient symptomatology (via a modified version of the Memorial Symptom Assessment Scale-Short Form) and caregiver depressive symptoms, including suicidal ideation (measured by the Patient Health Questionnaire-9). Multiple regressions evaluated the unique predictability of patients' symptom subtypes on caregiver depression. Exploratory analyses examined mean differences of study variables between participants who did and did not endorse suicidal ideation. RESULTS: Caregiver burden related to patients' psychological symptoms accounted for significant variance in caregiver depression scores when controlling for burden related to physical symptoms. Among 229 caregivers (M age = 61.4 years), 12 reported suicidal ideation, where 6 of the 12 were male, despite male caregivers comprising less than 20% of the total sample. SIGNIFICANCE OF RESULTS: Burden associated with patients' psychological symptoms uniquely contributed to caregiver depression, further highlighting the clinical utility and necessity for hospice providers to address the emotional needs of patients and their caregivers alike. Developing clinical procedures to identify and respond to such needs would not only behoove hospice agencies, but it would likely enhance the caregiving experience holistically, which might be particularly imperative for male caregivers.


Subject(s)
Caregivers/psychology , Cost of Illness , Depression/etiology , Syndrome , Aged , Depression/psychology , Female , Hospice Care/psychology , Humans , Male , Middle Aged , Psychometrics/instrumentation , Psychometrics/methods , Quality of Life/psychology , Self Report , Stress, Psychological/complications , Stress, Psychological/etiology , Stress, Psychological/psychology , Suicidal Ideation , Surveys and Questionnaires , Workforce
17.
Br J Pain ; 11(2): 87-96, 2017 May.
Article in English | MEDLINE | ID: mdl-28491301

ABSTRACT

The aim of this retrospective study was to determine whether an inpatient approach and the use of regional anaesthesia techniques can accelerate the recovery to normal functions in children with Complex Regional Pain Syndrome (CRPS). This study looked at the data of patients admitted to the rehabilitation unit with a diagnosis of CRPS from January 2010 to April 2015. Variables such as hospital stay, medications administered, regional anaesthesia procedures, changes in functional status prior to treatment and at the time of discharge, psychological evaluation and diagnosis were evaluated. A total of 31 patients (21 females and 10 males) were admitted with a diagnosis of CRPS 1 and 2. In all, 97% of the patients received a peripheral or central nerve catheter for an average of 4 days with pain scores of Verbal Numeric Scale (VNS) score = 1.0 ± 0.7 and an average length of hospital stay of 8.2 ± 2.6 days. The modified Functional Independence Measure for Children (WeeFIM) scores and Canadian Association of Occupational Therapists tests significantly improved at the time of hospital discharge, as well as their pain scores, which decreased from 8.2 ± 2 to 1.6 ± 3. In conclusion, these data suggest that the use of regional anaesthesia techniques and an intensive inpatient rehabilitation programme could accelerate the recovery of children with CRPS.

18.
Mol Cancer Ther ; 15(9): 2143-54, 2016 09.
Article in English | MEDLINE | ID: mdl-27390343

ABSTRACT

The Wnt/ß-catenin pathway is among the most frequently altered signaling networks in human cancers. Despite decades of preclinical and clinical research, efficient therapeutic targeting of Wnt/ß-catenin has been elusive. RNA interference (RNAi) technology silences genes at the mRNA level and therefore can be applied to previously undruggable targets. Lipid nanoparticles (LNP) represent an elegant solution for the delivery of RNAi-triggering oligonucleotides to disease-relevant tissues, but have been mostly restricted to applications in the liver. In this study, we systematically tuned the composition of a prototype LNP to enable tumor-selective delivery of a Dicer-substrate siRNA (DsiRNA) targeting CTNNB1, the gene encoding ß-catenin. This formulation, termed EnCore-R, demonstrated pharmacodynamic activity in subcutaneous human tumor xenografts, orthotopic patient-derived xenograft (PDX) tumors, disseminated hematopoietic tumors, genetically induced primary liver tumors, metastatic colorectal tumors, and murine metastatic melanoma. DsiRNA delivery was homogeneous in tumor sections, selective over normal liver and independent of apolipoprotein-E binding. Significant tumor growth inhibition was achieved in Wnt-dependent colorectal and hepatocellular carcinoma models, but not in Wnt-independent tumors. Finally, no evidence of accelerated blood clearance or sustained liver transaminase elevation was observed after repeated dosing in nonhuman primates. These data support further investigation to gain mechanistic insight, optimize dose regimens, and identify efficacious combinations with standard-of-care therapeutics. Mol Cancer Ther; 15(9); 2143-54. ©2016 AACR.


Subject(s)
Neoplasms/genetics , RNA Interference , RNA, Small Interfering/genetics , beta Catenin/genetics , Animals , Apolipoproteins E/chemistry , Apolipoproteins E/metabolism , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/metabolism , Cell Line, Tumor , Disease Models, Animal , Gene Expression Regulation, Neoplastic , Gene Silencing , Humans , Lipids/chemistry , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , Male , Melanoma, Experimental , Mice , Nanoparticles/chemistry , Neoplasm Metastasis , Neoplasms/metabolism , RNA, Small Interfering/administration & dosage , RNA, Small Interfering/chemistry , Structure-Activity Relationship , Wnt Signaling Pathway , Xenograft Model Antitumor Assays , beta Catenin/metabolism , ras Proteins/genetics , ras Proteins/metabolism
19.
Eur Neuropsychopharmacol ; 26(6): 994-1003, 2016 06.
Article in English | MEDLINE | ID: mdl-27133029

ABSTRACT

Intravenous infusion of lanicemine (formerly AZD6765), a low trapping non-selective N-methyl-D-aspartate (NMDA) receptor antagonist, induces antidepressant effects with a similar time course to ketamine. We investigated whether a single dose lanicemine infusion would reproduce the previously reported decrease in subgenual anterior cingulate cortex (sgACC) activity evoked by ketamine, a potential mechanism of antidepressant efficacy. Sixty un-medicated adults meeting the criteria for major depressive disorder were randomly assigned to receive constant intravenous infusions of ketamine, lanicemine or saline during a 60min pharmacological magnetic resonance imaging (phMRI) scan. Both ketamine and lanicemine gradually increased the blood oxygen level dependent signal in sgACC and rostral ACC as the primary outcome measure. No decreases in signal were seen in any region. Interviewer-rated psychotic and dissociative symptoms were minimal following administration of lanicemine. There was no significant antidepressant effect of either infusion compared to saline. The previously reported deactivation of sgACC after ketamine probably reflects the rapid and pronounced subjective effects evoked by the bolus-infusion method used in the previous study. Activation of the ACC was observed following two different NMDA compounds in both Manchester and Oxford using different 3T MRI scanners, and this effect predicted improvement in mood 1 and 7 days post-infusion. These findings suggest that the initial site of antidepressant action for NMDA antagonists may be the ACC (NCT01046630. A Phase I, Multi-centre, Double-blind, Placebo-controlled Parallel Group Study to Assess the pharmacoMRI Effects of AZD6765 in Male and Female Subjects Fulfilling the Criteria for Major Depressive Disorder; http://clinicaltrials.gov/show/NCT01046630).


Subject(s)
Antidepressive Agents/therapeutic use , Depressive Disorder, Major/drug therapy , Excitatory Amino Acid Antagonists/therapeutic use , Gyrus Cinguli/drug effects , Ketamine/therapeutic use , Phenethylamines/therapeutic use , Pyridines/therapeutic use , Adolescent , Adult , Affect , Antidepressive Agents/administration & dosage , Antidepressive Agents/adverse effects , Cross-Over Studies , Depressive Disorder, Major/diagnostic imaging , Double-Blind Method , Excitatory Amino Acid Antagonists/administration & dosage , Excitatory Amino Acid Antagonists/adverse effects , Female , Humans , Ketamine/administration & dosage , Ketamine/adverse effects , Magnetic Resonance Imaging , Male , Middle Aged , Phenethylamines/administration & dosage , Phenethylamines/adverse effects , Psychiatric Status Rating Scales , Pyridines/administration & dosage , Pyridines/adverse effects , Treatment Outcome , Young Adult
20.
Am J Hosp Palliat Care ; 32(7): 745-9, 2015 Nov.
Article in English | MEDLINE | ID: mdl-24982302

ABSTRACT

A family member or friend is often a hospice patient's primary caregiver and, as such, may face a significant number of stressors, including challenges related to managing patient symptoms. This study investigated the most stressful patient symptoms as reported by 111 hospice family caregivers of cancer (n=66) and cardiopulmonary (n=45) patients. Researchers calculated the mean level of stress caregivers attributed to 32 different patient symptoms commonly encountered at end of life. They found the symptoms perceived as most stressful for caregivers were psychological in nature. Study findings suggest that members of the hospice interdisciplinary team should connect patients and their caregivers to various types of support to address psychological symptoms, benefitting patients and caregivers alike.


Subject(s)
Cardiovascular Diseases/psychology , Caregivers/psychology , Family/psychology , Grief , Neoplasms/psychology , Stress, Psychological/epidemiology , Adaptation, Psychological , Adult , Aged , Aged, 80 and over , Cardiovascular Diseases/therapy , Female , Hospice Care , Humans , Male , Middle Aged , Neoplasms/therapy , United States/epidemiology
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