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ContextPalliative care offers patient and family centered approaches that may mitigate risk of caregiver burden and poor mood.ObjectivesTo determine whether a palliative care intervention (CONNECT) improved burden, mood, and self-efficacy among caregivers of patients with advanced cancer.MethodsIn this cluster randomized trial, patients and their caregivers were recruited from 17 Oncology clinics in Pennsylvania. Participants attended nurse-led monthly visits, addressing patient symptoms, goals of care, and advance care planning. At baseline and three months, we measured caregiver burden using Zarit Burden Interview (ZBI-12; range 0-48), caregiver anxiety and depression using Hospital Anxiety and Depression Scales (HADS-A, range 0-21; HADS-D, range 0-21). We measured caregiver self-efficacy at three months using Caregiver Inventory (CGI; range 0-189).ResultsWe enrolled 441 caregivers and 381 completed three-month assessments. We found no significant differences in caregiver burden (adjusted mean difference -0.39; 95% CI -1.07-0.29, P=0.90), depression (adjusted mean difference -0.22, 95% CI -0.97-0.55, P=0.26), or anxiety (adjusted mean difference 0.09; 95% CI -1.25-1.43, P=0.58), between the intervention and standard care at three months. Caregiver self-efficacy was higher at three months in the intervention compared to standard care (adjusted mean difference 9.36; 95% CI 0.95-17.77, P=0.030).ConclusionCaregivers in CONNECT did not experience improved burden or mood, however, they reported higher self-efficacy compared to caregivers receiving standard care. This study highlights the need for strategies to optimize caregiver outcomes in palliative care interventions.

BACKGROUND: Telenovelas show significant promise as a mode of education that could potentially enhance hospice family caregivers' (HFCG) ability to manage distress or pain for themselves and the care recipient. OBJECTIVES: We sought to understand HFCGs' perceived benefits and challenges of NOVELA using the Levels of Kirkpatrick as a conceptual framework. SETTING/SUBJECTS: HFCGs from two hospices in the Mid-Atlantic region of the United States. MEASUREMENTS: Semistructured interviews were conducted to understand perceptions of HFCGs on the benefits and challenges of the NOVELA intervention. RESULTS: Participants (N = 20) in our study were mainly homebound, well educated, White female, and adult children of people with advanced cancer who reported mild anxiety and moderate self-efficacy at baseline. Three unique themes were identified: acceptability of NOVELA, usability and relevance of NOVELA, and the effect of NOVELA. According to our conceptual model, the intervention positively affects all three adult learning categories: reaction, learning, and behavior. CONCLUSION: Our findings suggest that HFCGs support the proposed NOVELA intervention and it appears to be an acceptable educational tool during hospice care (NCT04533594).

PURPOSE: Patients with advanced cancer often have unrealistic expectations about prognosis and treatment. This study assessed the effect of an oncology nurse-led primary palliative care intervention on illness expectations among patients with advanced cancer. METHODS: This study is a secondary analysis of a cluster-randomized trial of primary palliative care conducted at 17 oncology clinics. Adult patients with advanced solid tumors for whom the oncologist would not be surprised if died within 1 year were enrolled. Monthly visits were designed to foster realistic illness expectations by eliciting patient concerns and goals for their medical care and empowering patients and families to engage in discussions with oncologists about treatment options and preferences. Baseline and 3-month questionnaires included questions about life expectancy, treatment intent, and terminal illness acknowledgment. Odds of realistic illness expectations at 3 months were adjusted for baseline responses, patient demographic and clinical characteristics, and intervention dose. RESULTS: Among 457 primarily White patients, there was little difference in realistic illness expectations at 3 months between intervention and standard care groups: 12.8% v 11.4% for life expectancy (adjusted odds ratio [aOR] = 1.15; 95% CI, 0.59 to 2.22; P = .684); 24.6% v 33.3% for treatment intent (aOR = 0.76; 95% CI, 0.44 to 1.27; P = .290); 53.6% v 44.7% for terminal illness acknowledgment (aOR = 1.28; 95% CI, 0.81 to 2.00; P = .288). Results did not differ when accounting for variation in clinic sites or intervention dose. CONCLUSION: Illness expectations are difficult to change among patients with advanced cancer. Additional work is needed to identify approaches within oncology practices that foster realistic illness expectations to improve patient decision making.

In the management of symptomatic bone metastases, current practice guidelines do not provide clear methodology for selecting palliative radiotherapy (RT) regimens based on specific patient and disease features. Decision support aids may offer an effective means for translating the complex data needed to render individualised treatment decisions, yet no such tools are available for use in this setting. Thus, we describe the development of the Bone Metastases Ensemble Trees for Survival-Decision Support Platform (BMETS-DSP), which aims to optimise selection of evidence-based, individualised palliative RT regimens.The Ottawa Decision Support Framework was used as the theoretical basis for development of BMETS-DSP. First, we utilised stakeholder input and review of the literature to assess determinants underlying the provider decision. Based on this assessment and iterative stakeholder feedback, we developed the web-based, provider-facing BMETS-DSP. Consistent with the underlying theoretical framework, our design also included assessment of decision quality using the International Patient Decision Aids Standards (IPDAS) certification checklist.Stakeholder input and review of 54 evidence-based publications identified the following determinants of the provider decision: estimated prognosis, characteristics of the target symptomatic lesion and the primary cancer type, consideration of alternative interventions, access to patient-specific recommendations, and patient preferences. Based on these determinants, we developed the BMETS-DSP that (1) collects patient-specific data, (2) displays an individualised predicted survival curve, and (3) provides case-specific, evidence-based recommendations regarding RT, open surgery, systemic therapy, and hospice referral to aid in the decision-making process. The finalised tool met IPDAS quality requirements. Preliminary results of a pilot assessment suggest impact of clinical outcomes.We describe the successful development of a provider-facing decision support platform to aid in the provision of palliative RT in better alignment with patient and disease features. Impact of the BMETS-DSP on decision outcomes will be further assessed in a randomised, controlled study.

First-line medications for the treatment of painful diabetic neuropathy (PDN) are associated with a substantial rate of discontinuation due to adverse effects or insufficient efficacy. Neuromodulation techniques have been used for PDN, but a comprehensive review of the literature that incorporates several distinct device categories has yet to be undertaken.We aimed to summarize the evidence regarding 4 major types of neuromodulation devices for the treatment of PDN. We focused on spinal cord stimulators (SCS), peripheral nerve stimulators (PNS), transcutaneous electrical nerve stimulators (TENS), and scrambler therapy devices (ST) because they are often used for refractory neuropathic pain.Narrative Review.A comprehensive and reproducible literature search was performed using PubMed with no search restrictions applied. The available Medical Subject Headings were used. Inclusion criteria included prospective studies, retrospective studies, case series, and case reports indexed from database inception to the search date (September 14, 2021).Seventeen studies met inclusion criteria, 10 of which were regarding SCS. Only 3 of the 10 were randomized controlled trials. We found no studies assessing contemporary PNS. Four studies assessed TENS, but the devices varied widely in voltages and waveforms. Two case reports described ST.Potential selection bias due to the nature of a narrative review, although a reproducible search strategy was utilized. Several neuromodulation modalities have minimal published evidence available.The evidence for neuromodulation devices for the treatment of PDN mostly comprises open-label prospective trials or case reports. SCS has the most volume of evidence for efficacy. Studies regarding TENS show mixed results, possibly due to numerous device varieties. PNS and ST may hold promise based on their proposed mechanisms of action, but prospective controlled trials are needed.

Corticosteroids are used for a multitude of indications in palliative patients. In this narrative review, we aim to review literature on the treatment and prevention of neuropsychiatric complications of steroids. For prevention, only lamotrigine had a positive effect in a small number of studies. For treatment, olanzapine appears to be nearly universally effective at low doses, but randomized trial evidence is lacking. Further randomized clinical trials are necessary to elucidate data-driven guidelines for prevention and treatment of corticosteroid-induced neuropsychiatric symptoms. Until further data are available, it is reasonable to consider low dose olanzapine for any patient taking 40 mg of prednisone or its equivalent, especially those with a history of depression or neuropsychiatric symptoms.

Palliative care clinicians display less burnout than oncology clinicians. Little is known about the impact of providing both oncology care and primary palliative care in the same setting.The aim was to determine whether nurses providing primary palliative care in addition to oncology care would experience less burnout over time than nurses providing oncology care only.The authors performed secondary analysis of the CONNECT study. Three groups of nurses were evaluated: primary palliative care, non-primary palliative care, and standard care. On study enrollment and after one year, nurses completed the Maslach Burnout Inventory. Multivariable regression analyses were performed to test differences in follow-up burnout scores between groups.Overall burnout rates were low at enrollment for all groups. There were no differences in burnout scores at one year between nurses who provided palliative care and nurses in the other two groups.nbsp.

Background: Phase 1 clinical trials remain vital for oncology care. Patients on these trials require supportive care for quality-of-life (QOL) concerns. Objective: To test a Palliative Care Intervention (PCI) for patients with solid tumors enrolled in Phase I therapeutic trials with a priori hypothesis that psychological distress, QOL, satisfaction, symptoms, and resource utilization would be improved in the PCI group. Design: This unblinded randomized trial compared the PCI with usual care in patients accrued to Phase I Clinical Trials. Subjects (n = 479) were followed for 24 weeks, with 12 weeks as the primary outcome. Setting: Two Comprehensive Cancer Centers in the United States. Subjects: A consecutive sample, 21 years or older, English fluency, with solid tumors initiating a Phase 1 trial. Measurements: Psychological Distress (Distress Thermometer), QOL total and subscales (FACT-G), satisfaction (FAM-CARE), survival, and resource utilization (chart audit). Results: PCI subjects showed improved Psychological Distress (−0.47, p = 0.015) and Emotional Well-Being (0.81, p = 0.045), with differences on variables of QOL and distress between sites. High rates of symptom-management admissions (41.3%) and low rates of Advance Directive completion (39.0%), and hospice enrollment (30.7%), despite a median survival in both groups of 10.1 months from initiating a Phase 1 study. Conclusions: A nurse-delivered PCI can improve some QOL outcomes and distress for patients participating in Phase 1 trials. Greater integration of PC is needed to provide quality care to these patients and to support transitions from treatment to supportive care, especially at the end of life. ClinicalTrials.gov Identifier: NCT01612598.

ObjectivesFamily caregiver burden among older adults with advanced cancer remains poorly understood. We sought to (1) identify patient factors associated with caregiver burden and (2) examine how amount of time caregiving modifies these relationships.MethodsCross-sectional analysis of baseline data from a cluster-randomized palliative care intervention trial including patients with advanced cancer and their family caregivers, recruited from 17 oncology practices in Pennsylvania. Caregiver burden was measured using Zarit Burden Interview (ZBI-12; range 0-48). Patient factors included functional status (Eastern Cooperative Oncology Group), symptom burden (Edmonton Symptom Assessment Scale), anxiety and depression (Hospital Anxiety and Depression Scale), and quality of life (Functional Assessment of Chronic Illness Therapy - Palliative Care). Using adjusted multivariable regression, we analyzed (1) independent associations between patient factors and caregiver burden and (2) how weekly caregiving hours modified these relationships.ResultsAmong 441 patient-caregiver dyads, mean patient age was 70±10 and caregiver age was 62±13years. Most caregivers (59%) were patients' partners. Caregivers reported 44.5±53.5 average hours spent caregiving weekly; mean ZBI-12 scores were 10.3±7.3. Worse patient functional status (β=4.20, p&nbsp

PURPOSE: Hope is a modifiable entity that can be augmented. We evaluated the feasibility, acceptability, and efficacy of a short intervention to increase hopefulness in patients with advanced breast cancer and oncologists. METHODS: We enrolled eligible participants to two cohorts: one for patients with metastatic breast cancer and one for medical, radiation, or surgical oncologists. The intervention, a half-day hope enhancement workshop, included groups of 10-15 participants within each cohort. Participants in both cohorts completed preworkshop, postworkshop, and 3-month evaluations, which included the Adult Hope Scale (AHS), Herth Hope Index (HHI), and Patient-Reported Outcomes Measurement Information System-Global Health (PROMIS-GH) measures in patients, and the AHS, HHI, and a burnout self-assessment tool in physicians. RESULTS: We consented 13 patients and 26 oncologists for participation in the workshop and 76.9% (n = 10) of consented patients and 100% (n = 26) of consented physicians participated. Postworkshop, all participants planned to incorporate what they learned into their daily lives. In patients, AHS scores increased from preworkshop to postworkshop, and the mean change of 5.90 was significant (range 0-15, SD: 4.7, t = 3.99, P = .0032). HHI scores also increased, although the mean change was not significant. AHS and HHI scores did not significantly change in oncologists from preworkshop to postworkshop. At 3 months, less than half of the participants responded to the evaluation. CONCLUSION: We found that conducting a hope-enhancement workshop for patients with metastatic breast cancer and oncologists was feasible, generally acceptable to both populations, and associated with increased hopefulness in patients. Next steps should focus on confirming this effect in a randomized study and maintaining this effect in the postworkshop interval.

The past 25 years have proved that palliative care is effective in improving care of seriously ill patients. Research attention must pivot to focus on policy changes and systems and models of care that ensure easy access to quality palliative care to all patients who need it. Education, alone, has not worked. Leaving it to individual organizations to decide has not worked. The question of whether incentives should be used has arisen. Should we design treatment algorithms, such as for cardiopulmonary resuscitation, where palliative care is part of standard care and requires an “opt out”? Should payers pay more to health care organizations who demonstrate they provide universal access to palliative care and how can we control for unintended consequences? Should provision of specialist palliative care be required for a health care organization to be accredited? How can we advance the state of the science and best support the workforce?

BACKGROUND: Place of death is important to patients and caregivers, and often a surrogate measure of health care disparities. While recent trends in place of death suggest an increased frequency of dying at home, data is largely unknown for older adults with cancer. METHODS: Deidentified death certificate data were obtained via the National Center for Health Statistics. All lung, colon, prostate, breast, and pancreas cancer deaths for older adults (defined as >65 years of age) from 2003 to 2017 were included. Multinomial logistic regression was used to test for differences in place of death associated with sociodemographic variables. RESULTS: From 2003 through 2017, a total of 3,182,707 older adults died from lung, colon, breast, prostate and pancreas cancer. During this time, hospital and nursing home deaths decreased, and the rate of home and hospice facility deaths increased (all p

OBJECTIVE: Patient–oncologist therapeutic alliance is a foundation of quality cancer care, although there is limited research demonstrating its relationship with patient outcomes. We investigated the relationship between therapeutic alliance and patient quality of life with a secondary goal of determining whether the association varied by patients’ baseline level of psychological distress. METHODS: Cross-sectional analysis of baseline data from a randomized clinical trial of 672 patients with advanced cancer participating in a primary palliative care intervention trial. Patients completed baseline self-reported measures of therapeutic alliance (The Human Connection Scale, range: 16–64), overall quality of life (Functional Assessment of Cancer Therapy—Palliative Care, range: 0–184), and psychological distress (Hospital Anxiety and Depression Scale, range: 0–42). First, we determined the relationship between therapeutic alliance and quality of life using multivariable regression adjusting for confounders. We then examined if psychological distress was an effect modifier in this relationship by adding interaction effects of depression and anxiety symptoms on therapeutic alliance into the regression model. RESULTS: Patients reported high levels of therapeutic alliance (56.4 ± 7.4) and moderate quality of life (130.3 ± 25.5). Stronger therapeutic alliance was associated with better quality of life after adjusting for other confounding factors (β = 3.7, 95% confidence interval = 2.1, 5.3, p < 0.01). The relationship between therapeutic alliance and quality of life was generally consistent regardless of psychological distress. CONCLUSIONS: Collaborative, trusting relationships between patients with advanced cancer and their oncologists are associated with better patient quality of life. Future research should investigate the causal, longitudinal nature of these relationships.

PURPOSE:African American patients with cancer underutilize advance care planning (ACP) and palliative care (PC). This feasibility study investigated whether community health workers (CHWs) could improve ACP and PC utilization for African American patients with advanced cancer.METHODS:African American patients diagnosed with an advanced solid organ cancer (stage IV or stage III disease with a palliative performance score < 60%) were enrolled. Patients completed baseline surveys that assessed symptom burden and distress at baseline and 3 months post-CHW intervention. The CHW intervention consisted of a comprehensive assessment of multiple PC domains and social determinants of health. CHWs provided tailored support and education on the basis of iterative assessment of patient needs. Intervention feasibility was determined by patient and caregiver retention rate above 50% at 3 months.RESULTS:Over a 12-month period, 24 patients were screened, of which 21 were deemed eligible. Twelve patients participated in the study. Patient retention was high at 3 months (75%) and 6 months (66%). Following the CHW intervention, symptom assessment as measured by Edmonton Symptom Assessment System improved from 33.8 at baseline to 18.8 ( P = .03). Psychological distress improved from 5.5 to 4.7 ( P = .36), and depressive symptoms from 42.2 to 33.6 ( P = .09), although this was not significant. ACP documentation improved from 25% at baseline to 75% at study completion. Sixty-seven percentage of patients were referred to PC, with 100% of three decedents using hospice.CONCLUSION:Utilization of CHWs to address PC domains and social determinants of health is feasible. Although study enrollment was identified as a potential barrier, most recruited patients were retained on study.

PURPOSE: Hospice utilization metrics are essential for any serious effort to improve end-of-life care in oncology. However, oncologists do not routinely receive these personalized reports. We evaluated whether a behavioral science intervention, using peer comparisons coupled with social norms, was associated with improvements in hospice use. METHODS: Oncologists at two academic practices of Johns Hopkins Medicine were randomly assigned to receive a peer comparison report by e-mail displaying individual hospice utilization metrics compared with top-performing peers or to receive no report. The data accrued for the intervention represented hospice utilization for the previous calendar year. The intervention period was from June 1, 2020, to December 30, 2020, and included oncologists from both the solid and hematologic malignancies programs. The primary outcome was the proportion of patients between groups with short hospice length of stay (LOS; defined as ≤ 7 days) after 6 months. Secondary outcomes included hospice referral rate, enrollment rate, and median LOS. RESULTS: Forty-seven oncologists participated. The percent of patients with a short hospice stay in the intervention group was lower (17.4%) compared with patients treated by physicians in the usual care group (46.3%, difference = 21.8%; 95% CI, 16.0 to 41.6; P < .001). Receipt of peer comparisons was associated with a greater likelihood of enrolling in hospice (73.7% v 42.8%; difference = 31.1%; 95% CI, 20.4 to 41.7; P < .001) and a longer hospice LOS (37.2 v 18.3 days; difference = 17.2; 95% CI, 8.8 to 25.7 days; P < .001). CONCLUSION: Peer comparisons improved hospice utilization metrics among a group of academic oncologists. Behavioral science offers one pragmatic strategy to overcome suboptimal oncologist decision-making biases related to hospice use.

The disruption to patient and family well-being introduced by the rising costs of cancer care is a growing clinical problem. In addition to logistical questions, there is a compelling, existential one: “How should healthcare teams address patient and caregiver distress and uncertainty from financial toxicity?” We argue that the principles and practice of palliative care can help alleviate this element and often unaddressed component of human suffering.

Background Malaria programmes in countries with low transmission levels require evidence to optimize deployment of current and new tools to reach elimination with limited resources. Recent pilots of elimination strategies in Ethiopia, Senegal, and Zambia produced evidence of their epidemiological impacts and costs. There is a need to generalize these findings to different epidemiological and health systems contexts. Methods Drawing on experience of implementing partners, operational documents and costing studies from these pilots, reference scenarios were defined for rapid reporting (RR), reactive case detection (RACD), mass drug administration (MDA), and in-door residual spraying (IRS). These generalized interventions from their trial implementation to one typical of programmatic delivery. In doing so, resource use due to interventions was isolated from research activities and was related to the pilot setting. Costing models developed around this reference implementation, standardized the scope of resources costed, the valuation of resource use, and the setting in which interventions were evaluated. Sensitivity analyses were used to inform generalizability of the estimates and model assumptions. Results Populated with local prices and resource use from the pilots, the models yielded an average annual economic cost per capita of $0.18 for RR, $0.75 for RACD, $4.28 for MDA (two rounds), and $1.79 for IRS (one round, 50% households). Intervention design and resource use at service delivery were key drivers of variation in costs of RR, MDA, and RACD. Scale was the most important parameter for IRS. Overall price level was a minor contributor, except for MDA where drugs accounted for 70% of the cost. The analyses showed that at implementation scales comparable to health facility catchment area, systematic correlations between model inputs characterizing implementation and setting produce large gradients in costs. Conclusions Prospective costing models are powerful tools to explore resource and cost implications of policy alternatives. By formalizing translation of operational data into an estimate of intervention cost, these models provide the methodological infrastructure to strengthen capacity gap for economic evaluation in endemic countries. The value of this approach for decision-making is enhanced when primary cost data collection is designed to enable analysis of the efficiency of operational inputs in relation to features of the trial or the setting, thus facilitating transferability.

Objective: Hospice family caregivers are seeking additional information related to patient care, pain and symptom management, and self-care. This study interviewed hospice staff about the potential dissemination of bilingual telenovelas to address these caregiver needs. Methods: Qualitative structured phone interviews were conducted with 22 hospice professionals from 17 different hospice organizations in 3 different Midwest states. The interviews were conducted from October to December 2019. Hospice staff volunteers were recruited from conferences, then individual interviews were audio-recorded, transcribed, and thematic analysis was conducted to gain an in-depth understanding of how to best implement telenovela video education into hospice care. Results: Most participants were hospice nurses (36%) located primarily in Missouri (91%), with a mean of 9 years of experience. Three discrete themes emerged, the educational resources currently provided to patient/families, perceptions of the usefulness of telenovelas for education, and practical suggestions regarding the dissemination of telenovelas. The development of 4 telenovela videos covering different topics is described. Conclusion: Hospice staff responded favorably to the concept of telenovelas and identified important keys for dissemination.

Context Opportunities for the use of palliative care services are missed in African American (AA) communities, despite Level I evidence demonstrating their benefits. Objectives Single-institution and stakeholder-engaged study to design an intervention to increase palliative care use in AA communities. Methods Two-phased qualitative research design guided by the Behavior Change Wheel and Theoretical Domains Framework models. In Phase 1, focus group sessions were conducted to identify barriers and facilitators of palliative care use and the viability of community health workers (CHWs) as a solution. After applying the Behavior Change Wheel and Theoretical Domains Framework to data gathered from Phase 1, Phase 2 consisted of a stakeholder meeting to select intervention content and prioritize modes of delivery. Results A total of 15 stakeholders participated in our study. Target behaviors identified were for patients to gain knowledge about benefits of palliative care, physicians to begin palliative care discussions earlier in treatment, and to improve patient-physician interpersonal communication. The intervention was designed to improve patient capability, physician capability, patient motivation, physician motivation, and increase patient opportunities to use palliative care services. Strategies to change patient and physician behaviors were all facilitated by CHWs and included creation and dissemination of brochures about palliative care to patients, empowerment and activation of patients to initiate goals-of-care discussions, outreach to community churches, and expanding patient social support. Conclusion Use of a theory-based approach to facilitate the implementation of a multi-component strategy provided a comprehensive means of identifying relevant barriers and enablers of CHWs as an agent to increase palliative care use in AA communities.

Context: Increasing emphasis on patient-centered care has led to highlighted importance of shared decision making, which better aligns medical decisions with patient care preferences. Effective shared decision making in metastatic breast cancer (MBC) treatment requires prognostic understanding, without which patients may receive treatment inconsistent with personal preferences. Objectives: To assess MBC patient and provider perspectives on the role of prognostic information in treatment decision making. Methods: We conducted semi-structured interviews with MBC patients and community oncologists and separate focus groups involving lay navigators, nurses, and academic oncologists. Qualitative analysis utilized a content analysis approach that included a constant comparative method to generate themes. Results: Of 20 interviewed patients with MBC, 30% were African American. Academic oncologists were mostly women (60%), community oncologists were all Caucasian, and nurses were all women and 28% African American. Lay navigators were all African American and predominately women (86%). Five emergent themes were identified. (1) Most patients wanted prognostic information but differed in when they wanted to have this conversation, (2) Emotional distress and discomfort was a critical reason for not discussing prognosis, (3) Religious beliefs shaped preferences for prognostic information, (4) Health care professionals differed on prognostic information delivery timing, and (5) Providers acknowledged that an individualized approach taking into account patient values and preferences would be beneficial. Conclusion: Most MBC patients wanted prognostic information, yet varied in when they wanted this information. Understanding why patients want limited or unrestricted prognostic information can inform oncologists' efforts toward shared decision making.

ObjectiveTo determine whether Scrambler therapy is an effective, acceptable, and feasible treatment of persistent central neuropathic pain in patients with neuromyelitis optica spectrum disorder (NMOSD) and to explore the effect of Scrambler therapy on co-occurring symptoms.MethodsWe conducted a randomized single-blind, sham-controlled trial in patients with NMOSD who have central neuropathic pain using Scrambler therapy for 10 consecutive weekdays. Pain severity, pain interference, anxiety, depression, and sleep disturbance were assessed at baseline, at the end of treatment, and at the 30- and 60-day follow-up.ResultsTwenty-two patients (11 per arm) were enrolled in and completed this trial. The median baseline numeric rating scale (NRS) pain score decreased from 5.0 to 1.5 after 10 days of treatment with Scrambler therapy, whereas the median NRS score did not significantly decrease in the sham arm. Depression was also reduced in the treatment arm, and anxiety was decreased in a subset of patients who responded to treatment. These symptoms were not affected in the sham arm. The safety profiles were similar between groups.ConclusionsScrambler therapy is an effective, feasible, and safe intervention for central neuropathic pain in patients with NMOSD. Decreasing pain with Scrambler therapy may additionally improve depression and anxiety.Clinicaltrials.gov identifierNCT03452176.Classification of evidenceThis study provides Class II evidence that Scrambler therapy significantly reduces pain in patients with NMOSD and persistent central neuropathic pain.

Objectives Patients with cancer who are at a transition to Phase I investigational treatments have been identified as an underserved population with regard to palliative care. This disease transition is often accompanied by spiritual and existential concerns. The study objective was to conduct a secondary analysis of data from a larger study testing a palliative care intervention. This paper reports the findings of this secondary focus on the spiritual needs of this population. Methods Patients (n = 479) were accrued to this study prior to initiating a Phase I clinical trial with data collected at baseline, and 4, 12, and 24 week follow-up. Results Qualitative data revealed that the transition to Phase 1 trial participation is a time of balancing hope for extended life with the reality of advancing disease. Quantitative results demonstrated increased spirituality over time in both religious- and non-religious-affiliated patients. Conclusions Patients entering Phase I trials have important spiritual needs as they face treatment decisions, advancing disease, and often mortality. Spiritual care should be provided to seriously ill patients as a component of quality care.

Palliative care began in academic centers with specialty consultation services, and its value to patients, families, and health systems has been evident. The demand for palliative care to be integrated throughout the cancer trajectory, combined with a limited palliative care workforce, means that new models of care are needed. This review discusses evidence regarding the need for integration of palliative care into routine oncology care and describes best practices recognized for dissemination of palliative care. The available evidence suggests that palliative care be widely adopted by clinicians in all oncology settings to benefit patients with cancer and their families. Efforts are needed to adapt and integrate palliative care into community practice. Limitations of these models are discussed, as are future directions to continue implementation efforts. The benefits of palliative care can only be realized through effective dissemination of these principles of care, with more primary palliative care delivered by oncology clinicians.

Using a stigma-based bullying framework, the current study investigated how (a) disability status was related to bullying-related behaviors when controlling for gender, grade level, and free or reduced lunch status; (b) gender, grade level, and free or reduced lunch status moderated the associations of disability status with bullying-related behaviors; and (c) classification in specific disability categories was associated with bullying-related behaviors with a sample of 10,483 students (47.8% female) in elementary, middle, and high school. School records data were collected on grade level, gender, free or reduced lunch price status, disability status, and disability category. Students completed the Bullying Participant Behaviors Questionnaire (BPBQ), rating five types of bully role behaviors (bullying behavior, assistant behavior, victimization, defending behavior, and outsider behavior). Findings indicated that having a disability was associated with increased victimization, assisting, and defending behavior. Furthermore, disability status interacted in meaningful ways with several demographic factors: (a) females with a disability reported more victimization and reported engaging in more outsider behaviors than females without a disability, (b) elementary students with a disability reported more assisting and less defending behaviors than those without a disability, (c) high school students with a disability reported less bullying and assisting behaviors and more defending behaviors than those without a disability, and (d) students with a disability from low socioeconomic backgrounds reported more bullying and outsider behaviors than students not from lower socioeconomic family backgrounds. When comparing students from specific disability categories to those with no disability, students with an emotional disability reported more assisting, victimization, and outsider behaviors; students with other health impairment reported more assisting, victimization, and defending; students with autism reported less defending and outsider behaviors; and students with a learning disability reported more defending behavior. Exploratory analyses of the effects of school-level factors found that school size (enrollment) was positively related to prevalence of assisting and outsider behavior. The percentage of low-income students in a school was positively associated with the extent of victimization and defending behaviors reported, but negatively associated with the extent of outsider behaviors reported.

Communications biology 5(1), 563 (2022). doi:10.1038/s42003-022-03497-4, Norovirus capsids are icosahedral particles composed of 90 dimers of the major capsid protein VP1. The C-terminus of the VP1 proteins forms a protruding (P)-domain, mediating receptor attachment, and providing a target for neutralizing antibodies. NMR and native mass spectrometry directly detect P-domain monomers in solution for murine (MNV) but not for human norovirus (HuNoV). We report that the binding of glycochenodeoxycholic acid (GCDCA) stabilizes MNV-1 P-domain dimers (P-dimers) and induces long-range NMR chemical shift perturbations (CSPs) within loops involved in antibody and receptor binding, likely reflecting corresponding conformational changes. Global line shape analysis of monomer and dimer cross-peaks in concentration-dependent methyl TROSY NMR spectra yields a dissociation rate constant k$_{off}$ of about 1 s$^{−1}$ for MNV-1 P-dimers. For structurally closely related HuNoV GII.4 Saga P-dimers a value of about 10$^{−6}$ s$^{−1}$ is obtained from ion-exchange chromatography, suggesting essential differences in the role of GCDCA as a cofactor for MNV and HuNoV infection., Published by Springer Nature, London

CONTEXT: Little attention has been given to social environmental factors associated with advance care planning (ACP) among African Americans or persons living with advanced Human Immunodeficiency Virus (PLHIVs). OBJECTIVES: The present study aimed to identify support network factors that affect the likelihood of naming a decision-maker and of talking to family/friends and doctors about ACP among vulnerable PLHIVs. METHODS: PLHIV were recruited from a large urban HIV clinic. A social support network inventory was used to calculate numbers of persons available for various types of support. Characteristics of network members were also collected. Multivariable logistic regression models were fit to examine associations between social network factors and ACP discussion, adjusting for age, sex, education and total number of network members. RESULTS: The sample (N=370) was mostly African American (95%), male (56%) and 48% had less than a high school education. Almost half the sample (48%) had talked to their family/friends or doctor about ACP and 34% had named a medical decision-maker. Adjusted analysis revealed that talking about ACP with family/friends was associated with female sex and a larger, closer support network who provided health information and physical assistance. Talking to doctors about ACP was associated with larger support networks who provided physical assistance but lower numbers from whom emotional support was received. Naming a decision-maker was associated with greater numbers of network members who provided emotional support, health information, and medication adherence reminders. CONCLUSION: The findings revealed aspects of family/ support network structures and caregiving function associated with ACP in a population with often vital yet vulnerable networks.

In Ghana, surveillance efforts on antibiotic resistance so far have not covered carbapenem resistance. In this study, our aim was to apply phenotypic and genotypic methods to identify and characterize carbapenem-resistant (CR) Gram-negative bacteria from the hospital environment in Ghana. A collection of 3840 isolates of Gram-negative bacilli infections from various clinical specimens was screened for carbapenem resistance by disc diffusion for imipenem, meropenem, and doripenem. Minimum Inhibitory Concentration (MIC) of the CR isolates was determined by E-test for the three carbapenems. All the CR isolates were further screened for carbapenemase activity by modified Hodge and boronic acid disc synergy tests. The CR isolates were investigated for the presence of carbapenemase and extended-spectrum beta-lactamase genes by PCR and confirmed by sequencing. The overall prevalence of CR isolates was 2.9% (111/3840). Based on the disc diffusion test, prevalence of resistance to carbapenems were doripenem (75%), imipenem (66.7%), and meropenem (58%). The highest measurable MIC levels (≥32 μg/mL) were observed in 56.8% of CR isolates with the nonfermenters, Pseudomonas aeruginosa (24.3%) and Acinetobacter species (18.9%), disproportionately represented. Phenotypic identification of carbapenamase activity occurred in 18.9% of the CR isolates by the modified Hodge test and 2.7% by Boronic acid disc synergy test; 21.6% exhibited carbapenemase production by both methods. All the CR isolates carried ESBL genes (blaTEM and blaSHV), whereas 23.4% were carriers of carbapenemase genes, of which 14.4% were blaNDM-1, 7.2% blaVIM-1, and 1.8% blaOXA-48. Phylogenetically, the CR isolates were diverse and showed limited relatedness to isolates from other geographical regions.

Students with mental health difficulties are at increased risk for victimization, and this risk may be exacerbated during the transition to middle school, when there is an increase in bullying behaviors. Through a social-ecological lens, the present study investigated how internalizing and externalizing problems in the fall of fifth grade were associated with bullying role behaviors in the fall of sixth grade and whether these associations differed by gender. This study expanded prior research by examining not only bullying and victimization, but also bystander behaviors (i.e., assisting, defending, or outsider behavior). Participants were students attending fifth grade at one of 13 elementary schools at Time 1, and later attending sixth grade at one of five middle schools at Time 2 (N = 1,139). Structural equation modeling results indicated that externalizing problems in fifth grade were positively associated with bullying (B = .25, p < .001), assisting (B = .08, p = .024), and victimization (B = .30, p = .010) in sixth grade; further, internalizing problems in fifth grade were significantly positively associated with victimization (B = .43, p < .001) and defending (B = .33, p = .002) in sixth grade. There were no significant gender differences in these associations. Implications for social-emotional screening and intervention are discussed. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Background: Pancreatic cancer patients often present with complications, which can impact treatment tolerance. Thus, symptom management is a vital component of treatment in addition to traditional chemotherapeutics. Concurrent palliative care with an emphasis on aggressive symptom management may sustain both clinical and patient-centered outcomes during treatment. The purpose of this article is to explore the impact of a concurrent palliative care intervention in patients with pancreatic cancer treated on phase I clinical trials. Materials and Methods: This is a secondary analysis of a National Cancer Institute (NCI)-funded randomized trial of an advanced practice nurse driven palliative care intervention for solid tumor patients treated on phase I clinical trials. Only pancreatic cancer patients were included in the analysis. Patients received two educational sessions around the quality of life (QOL) domains and completed the Functional Assessment of Cancer Therapy-General (FACT-G), patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE), and the psychological distress thermometer at baseline, 4 and 12 weeks. Mixed model with repeated measures analysis was used to explore outcomes by study arm. Results: Of the 479 patients accrued to the study, 42 were diagnosed with pancreatic cancer (26 intervention, 16 usual care). A trend toward improvement in the physical, social, emotional, and functional FACT-G QOL subscales and psychological distress (baseline to 12 weeks) were observed for the intervention arm. Patients reported moderate severity in psychological and physical stress. Conclusions: In this secondary analysis, a nurse-led palliative care intervention may improve the QOL and psychological distress of pancreatic cancer patients. A phase III trial focused on patients with pancreatic cancer is needed to determine the effectiveness of the intervention.

Human norovirus is the leading cause of gastroenteritis worldwide, with no approved vaccine or antiviral treatment to mitigate infection. These plus-strand RNA viruses have T = 3 icosahedral protein capsids with 90 pronounced protruding (P) domain dimers, to which antibodies and cellular receptors bind. We previously demonstrated that bile binding to the capsid of mouse norovirus (MNV) causes several major conformational changes; the entire P domain rotates by ∼90° and contracts onto the shell, the P domain dimers rotate about each other, and the structural equilibrium of the epitopes at the top of the P domain shifts toward the closed conformation, which favors receptor binding while blocking antibody binding. Here, we demonstrate that MNV undergoes reversible conformational changes at pH 5.0 that are nearly identical to those observed when bile binds. Notably, at low pH or when metals bind, a cluster of acidic resides in the G′-H′ loop interact and distort the G′-H′ loop, and this may drive C′-D′ loop movement toward the closed conformation. Enzyme-linked immunosorbent assays with infectious virus particles at low pH or in the presence of metals demonstrated that all tested antibodies do not bind to this contracted form, akin to what was observed with the MNV-bile complex. Therefore, low pH, cationic metals, and bile salts are physiological triggers in the gut for P domain contraction and structural rearrangement, which synergistically prime the virus for receptor binding while blocking antibody binding. IMPORTANCE The protruding domains on the calicivirus capsids are recognized by cell receptors and antibodies. We demonstrated that MNV P domains are highly mobile, and bile causes contraction onto the shell surface while allosterically blocking antibody binding. We present the near-atomic cryo-electron microscopy structures of infectious MNV at pH 5.0 and pH 7.5. Surprisingly, low pH is sufficient to cause the same conformational changes as when bile binds. A cluster of acidic residues on the G′-H′ loop were most likely involved in the pH effects. These residues also bound divalent cations and had the same conformation as observed here at pH 5. Binding assays demonstrated that low pH and metals block antibody binding, and thus the G′-H′ loop might be driving the conformational changes. Therefore, low pH, cationic metals, and bile salts in the gut synergistically prime the virus for receptor binding while blocking antibody binding.

Background In cluster randomized trials (CRTs) or stepped wedge cluster randomized trials (SWCRTs) of malaria interventions, mosquito movement leads to contamination between trial arms unless buffer zones separate the clusters. Contamination can be accounted for in the analysis, yielding an estimate of the contamination range, the distance over which contamination measurably biases the effectiveness. Methods A previously described analysis for CRTs is extended to SWCRTs and estimates of effectiveness are provided as a function of intervention coverage. The methods are applied to two SWCRTs of malaria interventions, the SolarMal trial on the impact of mass trapping of mosquitoes with odor-baited traps and the AvecNet trial on the effect of adding pyriproxyfen to long-lasting insecticidal nets. Results For the SolarMal trial, the contamination range was estimated to be 146 m ($$95\%$$ 95 % credible interval $$[0.052,\,0.923]$$ [ 0.052 , 0.923 ] km), together with a $$31.9\%$$ 31.9 % ($$95\%$$ 95 % credible interval $$[15.3,\,45.8]\%$$ [ 15.3 , 45.8 ] % ) reduction of Plasmodium infection, compared to the $$30.0\%$$ 30.0 % reduction estimated without accounting for contamination. The estimated effectiveness had an approximately linear relationship with coverage. For the AvecNet trial, estimated contamination effects were minimal, with insufficient data from the cluster boundary regions to estimate the effectiveness as a function of coverage. Conclusions The contamination range in these trials of malaria interventions is much less than the distances Anopheles mosquitoes can fly. An appropriate analysis makes buffer zones unnecessary, enabling the design of more cost-efficient trials. Estimation of the contamination range requires information from the cluster boundary regions and trials should be designed to collect this.

Importance Guidelines recommend early specialty palliative care for all patients with advanced cancer, but most patients lack access to such services. Objective To assess the effect of CONNECT (Care Management by Oncology Nurses to Address Supportive Care Needs), a primary palliative care intervention delivered by oncology nurses, on patient outcomes. Design, setting, and participants This cluster randomized clinical trial of the CONNECT intervention vs standard care was conducted from July 25, 2016, to October 6, 2020. Participants were adult patients with metastatic solid tumors who were undergoing oncological care and for whom an oncologist would agree with the statement "would not be surprised if the patient died in the next year." The trial was conducted at 17 community oncology practices in western Pennsylvania. Data analyses adhered to the intention-to-treat principle. Interventions The CONNECT intervention included 3 monthly visits with an existing infusion room nurse who was trained to address symptoms, provide emotional support, engage in advance care planning, and coordinate care. Main outcomes and measures The primary outcome was quality of life. At baseline and 3 months, participants completed assessments of quality of life (Functional Assessment of Chronic Illness Therapy-Palliative care: score range, 0-184, with higher scores indicating better quality of life), symptom burden (Edmonton Symptom Assessment Scale: score range, 0-90, with higher scores indicating greater symptom burden), and mood symptoms (Hospital Anxiety and Depression Scale [HADS]: score range, 0-21, with higher scores indicating substantial anxiety and depression). Linear mixed-effects models were used to estimate adjusted mean differences in 3-month outcomes. Preplanned, intensity-adjusted analyses were conducted. Results A total of 672 patients were enrolled (mean [SD] age, 69.3 [10.2] years; 360 women [53.6%]). The mean (SD) number of CONNECT visits completed was 2.2 (1.0). At 3 months, no difference in mean (SD) quality-of-life score was found between the CONNECT and standard care groups (130.7 [28.2] vs 134.1 [28.1]; adjusted mean difference, 1.20; 95% CI, -2.75 to 5.15; P = .55). Similarly, there was no difference between groups in 3-month mean (SD) symptom burden (23.2 [16.6] vs 24.0 [16.1]; adjusted mean difference, -2.64; 95% CI, -5.85 to 0.58; P = .11) or mood symptoms (HADS depression subscale score: 5.1 [3.4] vs 4.8 [3.7], adjusted mean difference, -0.08 [95% CI, -0.71 to 0.57], P = .82; HADS anxiety subscale score: 5.7 [3.9] vs 5.4 [4.2], adjusted mean difference, -0.31 [95% CI, -0.96 to 0.33], P = .34). Intensity-adjusted analyses revealed a larger estimated treatment effect for patients who received a full dose (3 visits) of the CONNECT intervention. Conclusions and relevance This cluster randomized clinical trial found that a primary palliative care intervention that was delivered by oncology nurses did not improve patient-reported outcomes at 3 months. Primary palliative care interventions with a higher dose intensity may be beneficial for most patients with advanced cancer who lack access to palliative care specialists. Trial registration ClinicalTrials.gov Identifier: NCT02712229.

Examining and addressing unmet care needs is integral to improving the provision and quality of cancer services. This review explored the prevalence of unmet supportive care needs, and factors associated with unmet need, in adults with advanced cancers (solid and hematological malignancies) and their caregivers. Electronic databases (PubMed, CINAHL, EMBASE) were searched, producing 85 papers representing 81 included studies. People with advanced cancer reported the highest unmet needs in financial, health system and information, psychological, and physical and daily living domains, whereas caregivers reported the highest unmet needs in psychological, and patient care and support domains. Distress, depression, and anxiety were associated with higher unmet needs across all unmet need domains for people with advanced cancer and their caregivers. Substantial heterogeneity in study populations and methods was observed. Findings from this review can inform targeted strategies and interventions to address these unmet needs in people with advanced cancer.

Background: Scrambler therapy (ST) is a relatively new neuromodulation technique that is useful in treatment of medication-resistant pain syndromes, including chemotherapy-induced peripheral neuropathy and other chronic pain syndromes. Amyloidosis commonly leads to peripheral neuropathy, and although the mechanism is unclear, it is possibly related to amyloid deposits on the nerve. Case Presentation: In this case presentation, we describe the novel use of ST for a patient with 13 years of neuropathic pain related to amyloidosis and worsened by chemotherapy. The patient reported bilateral hand pain with burning and aching and bilateral numbness on the soles of her feet. Her upper extremities were treated with 4 days of 40 minute ST treatment sessions providing reduction in her pain scores to zero. Discussion: Current therapy for amyloid peripheral neuropathy aims at treating the underlying condition, and then medical management with gabapentinoids. This is first case presentation showing successful treatment with ST.

The provision of specialty palliative care alongside oncology care is now recommended by the American Society of Clinical Oncology (ASCO) on the basis of multiple randomized trials showing that it leads to better symptom control, less depression and anxiety, improved quality of life, improved caregiver quality of life, and even longer survival. That said, simply not enough palliative care specialists are available to provide concurrent care, so oncologists are tasked with providing the greatest part of primary palliative care. It is useful to think of primary palliative care as comprising 2 skill sets, or "bundles": the first symptom assessment and management, and the second communication. Symptom assessment begins with the use of a standardized scale that emphasizes the assessment of anxiety, depression, physical symptoms, and coping strategies. Communication requires knowing how much information the patient and family want, especially about prognosis, and involves shared decision making. It also encompasses advance care planning, starting with the identification of a medical power of attorney and proceeding to a discussion about hospice and end-of-life treatment choices. The communication skill set includes providing caregiver support and spiritual care referral, making culturally appropriate decisions, and providing a specific statement of non-abandonment near the end of life. If specialty palliative care is involved, data show that the effect on quality of life and end-of-life choices is most meaningful if consultation is started at least 3 months before death. In this article, we provide a brief overview of the benefits of incorporating palliative care into routine oncologic practice and offer clinical pearls on how best to deliver the tenets of palliative care in the outpatient and inpatient settings.

This commentary discusses evidence supporting the importance of full palliative care dose intensity in outcomes for patients with cancer.

Glutamate dehydrogenase (GDH) is a homohexameric enzyme that catalyzes the reversible oxidative deamination of l-glutamate. While GDH is found in all living organisms, only that from animals is highly allosterically regulated by a wide array of metabolites. Because only animal GDH has a 50-residue antenna domain, we hypothesized that it was critical for allostery. To this end, we previously replaced the antenna with the loop found in bacteria, and the resulting chimera was no longer regulated by purine nucleotides. Hence, it seemed logical that the purpose of the antenna is to exert the subunit communication necessary for heterotrophic allosteric regulation. Here, we revisit the antenna deletion studies by retaining 10 more of the human GDH (hGDH) residues without adding the bacterial loop. Unexpectedly, the results were profoundly different than before. The basal activity of the mutant is only ∼13% of that of the wild type but ∼100 times more sensitive to all allosteric activators. In contrast, the mutant is still affected by all of the tested inhibitors to approximately the same degree. The resulting antenna-less mutant retained its negative cooperativity with respect to the coenzyme, again suggesting that intersubunit communication is intact. Finally, the mutant still exhibits substrate inhibition, albeit there are differences in the details. We present a model in which the majority of the antenna is not directly involved in allosteric regulation per se but rather may be responsible for improving enzymatic efficiency by acting as a conduit for substrate binding energy between subunits.

In the era of effective antiretroviral therapy, persons living with HIV/AIDS (PLWHA) are living longer, transforming HIV from a universally fatal disease to a serious chronic illness, warranting discussions between patients and their loved ones about advance care planning (ACP). Evidence is needed on factors associated with patients' likelihood to discuss ACP with loved ones.To further characterize factors associated with successful ACP in PLWHAs with their loved ones, we examined associations between patients having ACP discussions with the need for assistance with personal care, chronic pain, life satisfaction, prior family disagreements over health care decisions, sex, age, and interference in daily routines due to memory problems.Data were from the Affirm Care study (N = 370), which examined social and environmental factors associated with health outcomes among PLWHAs and their informal caregivers.Slightly more than half of respondents discussed ACP with loved ones (57%). In adjusted analysis, higher levels of chronic pain (odds ratio [OR] = 2.09, P = 0.045), needing assistance with personal care (OR = 1.63, P = 0.023), greater life satisfaction (OR = 1.02, P = 0.002), prior family arguments over health care decisions (OR = 2.80, P 0.001), and female sex (OR = 2.22, P = 0.001) were associated with higher odds of discussing ACP with loved ones, whereas age, drug use, education level, depression, and memory problems were nonsignificant.These results suggest that interventions to increase ACP among PLWHAs and their loved ones should target males. The findings also suggest PLWHAs with chronic pain, the need for assistance with personal care, and those with a history of prior family arguments over health care decisions may be primed for ACP.

Nurses play an integral role in high-quality patient care. Thus, their skills in providing end-of-life care should be assessed and continually enhanced. Education intended to improve end-of-life skills must address the affective/emotional component of nursing care. Evidence demonstrates that emotional engagement and resilience among health care providers are correlated with improved quality outcomes and, conversely, that burnout and stress negatively affect patient safety. Addressing the emotional needs of health care providers is critical to improving quality throughout the health care system. An evidence-based workshop was implemented among direct care staff on a hospital-based palliative care unit, with the goal of fostering emotional engagement to improve staff perceptions and attitudes about caring for patients at or near the end of life. Although perceptions about quality of death were not affected by this intervention, there was a significant improvement in attitudes about end-of-life nursing care. Qualitative feedback also reflected appreciation for small group discussions and opportunities to debrief with peers away from the unit. This intervention reflected the value of emotional engagement in educational efforts to improve end-of-life nursing care.

Background: African Americans in the United States have worse end-of-life care and cancer outcomes than whites. Palliative care may improve this disparity. Community Health Workers may provide a means to improve palliative care disparities. Methods: Semistructured in-depth interviews (five) and stakeholder focus groups (four) were conducted with cancer patients, caregivers, health care administrators, oncologists, and community health workers (CHWs). Patients were recruited through snowball sampling. Three raters coded interviews independently. Data were analyzed using interpretative phenomenological analysis. Results: Seventy-one individuals were contacted to participate with 24 stakeholders (34%) participating in individual interviews or across 4 stakeholder engagements. Eleven constructs were identified and grouped in three broader themes: “hub of the wheel,” understanding palliative care, and patient–provider relationships. Participants felt that the role of a CHW should be central, bridging patients with their providers, information, and resources, including psychosocial support and advance care planning documents. They also placed an emphasis on the background of CHWs, saying individuals selected should be familiar with the history, culture, and norms of the communities from which they operate. Stakeholders reported that a CHW could activate a patient to contact their primary care physician or oncologist who may refer to or provide palliative care. Stakeholders reported that given the barriers to palliative care, a CHW could contribute to patient-centered multidisciplinary care while addressing palliative care domains with patients and families in a culturally sensitive manner. Conclusion: Based on feedback from patients, caregivers, and providers, a culturally adapted CHW intervention may improve palliative care use for African American patients with advanced malignancies.

NSCLC treatment includes targeting of EGFR with tyrosine kinase inhibitors (TKIs) such as Erlotinib; however, resistance to TKIs is commonly acquired through T790M EGFR mutations or overexpression of vascular endothelial growth factor receptor-2 (VEGFR-2). We investigated the mechanisms of EGFR-TKI resistance in NSCLC cell lines with EGFR mutations or acquired resistance to Erlotinib. These studies showed upregulated gene and protein expression of VEGF, VEGFR-2, and a VEGF co-receptor neuropilin-1 (NP-1) in Erlotinib-resistant (1.4–5.3-fold) and EGFR double-mutant (L858R and T790M; 4.1–8.3-fold) NSCLC cells compared to parental and EGFR single-mutant (L858R) NSCLC cell lines, respectively. Immunofluorescence and FACS analysis revealed increased expression of VEGFR-2 and NP-1 in EGFR-TKI-resistant cell lines compared to TKI-sensitive cell lines. Cell proliferation assays showed that treatment with a VEGFR-2 inhibitor combined with Erlotinib lowered cell survival in EGFR double-mutant NSCLC cells to 9% compared to 72% after treatment with Erlotinib alone. Furthermore, Kaplan–Meier analysis revealed shorter median survival in late-stage NSCLC patients with high vs. low VEGFR-2 expression (14 mos vs. 21 mos). The results indicate that VEGFR-2 may play a key role in EGFR-TKI resistance and that combined treatment of Erlotinib with a VEGFR-2 inhibitor may serve as an effective therapy in NSCLC patients with EGFR mutations.

Background Inpatient palliative care is associated with lower inpatient costs; however, this has yet to be studied using a more nuanced, multi-tiered measure of inpatient palliative care and a national population-representative dataset. Using a population-based cohort of Canadians who died in hospital, our objectives were to: describe patients’ receipt of palliative care and active interventions in their terminal hospitalization; and examine the relationship between inpatient palliative care and hospitalization costs. Methods Retrospective cohort study using data from the Discharge Abstract Database in Canada between fiscal years 2012 and 2015. The cohort were Canadian adults (age ≥ 18 years) who died in hospital between April 1st, 2012 and March 31st, 2015 (N = 250,640). The exposure was level of palliative care involvement defined as: medium-high, low, or no palliative care. The main measure was acute care costs calculated using resource intensity weights multiplied by the cost of standard hospital stay, represented in 2014 Canadian dollars (CAD). Descriptive statistics were represented as median (IQR), and n(%). We modelled cost as a function of palliative care using a gamma generalized estimating equation (GEE) model, accounting for clustering by hospital. Results There were 250,640 adults who died in hospital. Mean age was 76 (SD 14), 47% were female. The most common comorbidities were: metastatic cancer (21%), heart failure (21%), and chronic obstructive pulmonary disease (16%). Of the decedents, 95,450 (38%) had no palliative care involvement, 98,849 (38%) received low involvement, and 60,341 (24%) received medium to high involvement. Controlling for age, sex, province and predicted hospital mortality risk at admission, the cost per day of a terminal hospitalization was: $1359 (95% CI 1323: 1397) (no involvement), $1175 (95% CI 1146: 1206) (low involvement), and $744 (95% CI 728: 760) (medium-high involvement). Conclusions Increased involvement of palliative care was associated with lower costs. Future research should explore whether this relationship holds for non-terminal hospitalizations, and whether palliative care in other settings impacts inpatient costs.

PURPOSE The Bone Metastases Ensemble Trees for Survival (BMETS) model uses a machine learning algorithm to estimate survival time following consultation for palliative radiation therapy for symptomatic bone metastases (SBM). BMETS was developed at a tertiary-care, academic medical center, but its validity and stability when applied to external data sets are unknown. PATIENTS AND METHODS Patients treated with palliative radiation therapy for SBM from May 2013 to May 2016 at two hospital-based community radiation oncology clinics were included, and medical records were retrospectively reviewed to collect model covariates and survival time. The Kaplan-Meier method was used to estimate overall survival from consultation to death or last follow-up. Model discrimination was estimated using time-dependent area under the curve (tAUC), which was calculated using survival predictions from BMETS based on the initial training data set. RESULTS A total of 216 sites of SBM were treated in 182 patients. Most common histologies were breast (27%), lung (23%), and prostate (23%). Compared with the BMETS training set, the external validation population was older (mean age, 67 v 62 years; P < .001), had more primary breast (27% v 19%; P = .03) and prostate cancer (20% v 12%; P = .01), and survived longer (median, 10.7 v 6.4 months). When the BMETS model was applied to the external data set, tAUC values at 3, 6, and 12 months were 0.82, 0.77, and 0.77, respectively. When refit with data from the combined training and external validation sets, tAUC remained > 0.79. CONCLUSION BMETS maintained high discriminative ability when applied to an external validation set and when refit with new data, supporting its generalizability, stability, and the feasibility of dynamic modeling.

Background Quorum sensing is an extracellular bacterial communication system used in the density-dependent regulation of gene expression and development of biofilms. Biofilm formation has been implicated in the establishment of catheter-associated urinary tract infections and therefore quorum sensing inhibitors (QSIs) have been suggested as anti-biofilm catheter coating agents. The long-term effects of QSIs in uropathogens is, however, not clearly understood. Objectives We evaluated the effects of repeated exposure to the QSIs cinnamaldehyde, (Z)-4-bromo-5(bromomethylene)-2(5H)-furanone-C30 (furanone-C30) and 4-fluoro-5-hydroxypentane-2,3-dione (F-DPD) on antimicrobial susceptibility, biofilm formation and relative pathogenicity in eight uropathogenic Escherichia coli (UPEC) isolates. Methods MICs, MBCs and minimum biofilm eradication concentrations and antibiotic susceptibility were determined. Biofilm formation was quantified using crystal violet. Relative pathogenicity was assessed in a Galleria mellonella model. To correlate changes in phenotype to gene expression, transcriptomic profiles were created through RNA sequencing and variant analysis of genomes was performed in strain EC958. Results Cinnamaldehyde and furanone-C30 led to increases in susceptibility in planktonic and biofilm-associated UPEC. Relative pathogenicity increased after cinnamaldehyde exposure (4/8 isolates), decreased after furanone-C30 exposure (6/8 isolates) and varied after F-DPD exposure (one increased and one decreased). A total of 9/96 cases of putative antibiotic cross-resistance were generated. Exposure to cinnamaldehyde or F-DPD reduced expression of genes associated with locomotion, whilst cinnamaldehyde caused an increase in genes encoding fimbrial and afimbrial-like adhesins. Furanone-C30 caused a reduction in genes involved in cellular biosynthetic processes, likely though impaired ribonucleoprotein assembly. Conclusions The multiple phenotypic adaptations induced during QSI exposure in UPEC should be considered when selecting an anti-infective catheter coating agent.

Background In cluster randomized trials (CRTs) of interventions against malaria, mosquito movement between households ultimately leads to contamination between intervention and control arms, unless they are separated by wide buffer zones. Methods This paper proposes a method for adjusting estimates of intervention effectiveness for contamination and for estimating a contamination range between intervention arms, the distance over which contamination measurably biases the estimate of effectiveness. A sigmoid function is fitted to malaria prevalence or incidence data as a function of the distance of households to the intervention boundary, stratified by intervention status and including a random effect for the clustering. The method is evaluated in a simulation study, corresponding to a range of rural settings with varying intervention effectiveness and contamination range, and applied to a CRT of insecticide treated nets in Ghana. Results The simulations indicate that the method leads to approximately unbiased estimates of effectiveness. Precision decreases with increasing mosquito movement, but the contamination range is much smaller than the maximum distance traveled by mosquitoes. For the method to provide precise and approximately unbiased estimates, at least 50% of the households should be at distances greater than the estimated contamination range from the discordant intervention arm. Conclusions A sigmoid approach provides an appropriate analysis for a CRT in the presence of contamination. Outcome data from boundary zones should not be discarded but used to provide estimates of the contamination range. This gives an alternative to “fried egg” designs, which use large clusters (increasing costs) and exclude buffer zones to avoid bias.