Publications by authors named "Thomas J Smith"

494 Publications

Lessons from spending on megestrol for cancer cachexia.

Support Care Cancer 2021 Apr 24. Epub 2021 Apr 24.

Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.

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http://dx.doi.org/10.1007/s00520-021-06240-7DOI Listing
April 2021

The association between varying levels of palliative care involvement on costs during terminal hospitalizations in Canada from 2012 to 2015.

BMC Health Serv Res 2021 Apr 13;21(1):331. Epub 2021 Apr 13.

Bruyère Research Institute, 43 Bruyère St, Office 264J-G, Ottawa, ON, K1N 5C8, Canada.

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.
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http://dx.doi.org/10.1186/s12913-021-06335-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045222PMC
April 2021

A norovirus uses bile salts to escape antibody recognition while enhancing receptor binding.

J Virol 2021 Apr 7. Epub 2021 Apr 7.

University of Texas Medical Branch at Galveston, Department of Biochemistry and Molecular Biology, Galveston, Texas, USA.

Noroviruses, members of the family, are the major cause of epidemic gastroenteritis in humans, causing ∼20 million cases annually. 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. In the case of mouse norovirus (MNV), bile salts have been shown to enhance receptor (CD300lf) binding to the P domain. We previously demonstrated that the P domains of several genotypes are markedly flexible and 'float' over the shell, but the role of this flexibility was unclear. Recently, we demonstrated that bile causes a 90° rotation and collapse of the P domain on to the shell surface. Since bile binds distal to the P/shell interface, it was not at all clear how it could cause such dramatic changes. Here we present the near-atomic resolution cryo-EM structure of the protruding MNV complexed with a neutralizing Fab. Combined with previous results, we show here that bile salts cause allosteric conformational changes in the P domain that block antibody recognition to the top of the P domain. In addition, bile also causes a major rearrangement of the P domain dimers that are likely responsible for the bile-induced collapse of the P domain onto the shell. In the contracted shell conformation, antibodies to the P1 and shell domains are not expected to bind. Therefore, at the site of infection in the gut, the host's own bile allows the virus to escape antibody-mediated neutralization while enhancing cell attachment.The major feature of the Calicivirus capsids are the 90 protruding domains (P domains) that are the site of cell receptor(s) attachment and antibody epitopes. We previously demonstrated that these P domains are highly mobile and that bile causes these 'floating' P domains in mouse norovirus (MNV) to contract onto the shell surface. Here, we present the near atomic cryo-EM structure of the isolated MNV P domain complexed with a neutralizing Fab fragment. Together, the data shows that bile causes two sets of changes. First, bile causes allosteric conformational changes in the epitopes at the top of the P domain that block antibody binding. Second, bile causes the P domain dimer subunits to rotate relative to each other, causing contraction of the P domain that buries epitopes at the base of the P and shell domains. Collectively, MNV uses the host's own metabolites to enhance cell receptor binding while simultaneously blocking antibody recognition.
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http://dx.doi.org/10.1128/JVI.00176-21DOI Listing
April 2021

Scrambler therapy for incident pain in bone metastases.

J Osteopath Med 2021 Apr 2. Epub 2021 Apr 2.

Johns Hopkins Medical Institutions, Baltimore, MD, USA.

Incident pain, described as pain induced by bone metastasis and produced by movement, can be devastating. The high doses of opioids needed to control such pain may sedate the patient and cause additional complications. Treatment of incident pain with pharmaceuticals has rarely been studied; only eight patients have been reported in the literature who did not receive additional opioids. We present the case of a 69 year old man with shoulder destruction due to bone metastases who was able to use his arm for normal activities without pain after three sessions of scrambler therapy, a noninvasive form of electrical neuromodulation that requires further study.
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http://dx.doi.org/10.1515/jom-2021-0027DOI Listing
April 2021

Olaparib in Metastatic Castration-Resistant Prostate Cancer.

Authors:
Thomas J Smith

N Engl J Med 2021 03;384(12):1175

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD

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http://dx.doi.org/10.1056/NEJMc2100225DOI Listing
March 2021

External Validation of the Bone Metastases Ensemble Trees for Survival (BMETS) Machine Learning Model to Predict Survival in Patients With Symptomatic Bone Metastases.

JCO Clin Cancer Inform 2021 Mar;5:304-314

Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD.

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 62 years; < .001), had more primary breast (27% 19%; = .03) and prostate cancer (20% 12%; = .01), and survived longer (median, 10.7 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.
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http://dx.doi.org/10.1200/CCI.20.00128DOI Listing
March 2021

Successful Treatment of Diabetic Neuropathy with Scrambler Therapy.

Authors:
Thomas J Smith

J Palliat Med 2021 Mar;24(3):320-321

Johns Hopkins Medical Institutions, Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA.

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http://dx.doi.org/10.1089/jpm.2020.0658DOI Listing
March 2021

Integrated Meditation and Exercise Therapy: A Randomized Controlled Pilot of a Combined Nonpharmacological Intervention Focused on Reducing Disability and Pain in Patients with Chronic Low Back Pain.

Pain Med 2021 Feb;22(2):444-458

Department of Biological Sciences, Duquesne University, Pittsburgh, Pennsylvania, USA.

Objective: This pilot trial examined the effects of a combined intervention of mindfulness meditation followed by aerobic walking exercise compared with a control condition in chronic low back pain patients. We hypothesized that meditation before exercise would reduce disability, pain, and anxiety by increasing mindfulness prior to physical activity compared with an audiobook control group.

Participants: Thirty-eight adults completed either meditation and exercise treatment (MedExT) (n=18) or an audiobook control condition (n=20).

Setting: Duquesne University Exercise Physiology Laboratory.

Design: A pilot, assessor-blinded, randomized controlled trial.

Methods: Over a 4-week period, participants in the MedExT group performed 12-17 minutes of guided meditation followed by 30 minutes of moderate-intensity walking exercise 5 days per week. Measures of disability, pain, mindfulness, and anxiety were taken at baseline and postintervention. Pain perception measurements were taken daily.

Results: Compared with the control group, we observed larger improvements in disability in the MedExT intervention, although the changes were modest and not statistically significant (mean between-group difference, -1.24; 95% confidence interval [CI], -3.1 to 0.6). For secondary outcome measures, MedExT increased mindfulness (within-group) from pre-intervention to postintervention (P=0.0141). Additionally, mean ratings of low back pain intensity and unpleasantness significantly improved with time for the MedExT group compared with that of the control group, respectively (intensity P=0.0008; unpleasantness P=0.0022).

Conclusion: . Overall, 4 weeks of MedExT produced suggestive between-group trends for disability, significant between-group differences for measures of pain, and significant within-group increases in mindfulness.
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http://dx.doi.org/10.1093/pm/pnaa403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901850PMC
February 2021

Developing Workshops to Enhance Hope Among Patients With Metastatic Breast Cancer and Oncologists: A Pilot Study.

JCO Oncol Pract 2021 Feb 17:OP2000744. Epub 2021 Feb 17.

Shaare Zedek Medical Center, Jerusalem, Israel.

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, = 3.99, = .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.
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http://dx.doi.org/10.1200/OP.20.00744DOI Listing
February 2021

The Association Between Area Deprivation Index and Patient-Reported Outcomes in Patients with Advanced Cancer.

Health Equity 2021 19;5(1):8-16. Epub 2021 Jan 19.

Division of General lnternal Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

This analysis describes associations between area deprivation and patient-reported outcomes among patients with advanced cancer. This is a cross-sectional analysis of baseline data from a multisite primary palliative care intervention trial. Participants were adult patients with advanced cancer. Patient-level area deprivation scores were calculated using the Area Deprivation Index (ADI). Quality of life and symptom burden were measured. Uni- and multivariate regressions estimated associations between area deprivation and outcomes of interest. Among 672 patients, ∼0.5 (54%) were women and most (94%) were Caucasian. Mean age was 69.3±10.2 years. Lung (36%), breast (13%), and colon (10%) were the most common malignancies. Mean ADI was 64.0, scale of 1 (low)-100 (high). In unadjusted univariate analysis, Functional Assessment of Cancer Therapy-Palliative (=0.002), Edmonton Symptom Assessment Scale (=0.025) and the Hospital Anxiety and Depression Scale anxiety (=0.003) and depression (=0.029) scores were significantly associated with residence in more deprived areas (=0.003). In multivariate analysis, controlling for patient-level factors, living in more deprived areas was associated with more anxiety (=0.019). Higher ADI was associated with higher levels of anxiety among patients with advanced cancer. Geographic information could assist clinicians with providing geographically influenced social support strategies.
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http://dx.doi.org/10.1089/heq.2020.0037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868579PMC
January 2021

Stronger therapeutic alliance is associated with better quality of life among patients with advanced cancer.

Psychooncology 2021 Feb 5. Epub 2021 Feb 5.

Palliative Research Center (PaRC), University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

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.
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http://dx.doi.org/10.1002/pon.5648DOI Listing
February 2021

Initial Management of Noncastrate Advanced, Recurrent, or Metastatic Prostate Cancer: ASCO Guideline Update.

J Clin Oncol 2021 Apr 26;39(11):1274-1305. Epub 2021 Jan 26.

Nanhealth, Inc, Culver City, CA.

Purpose: Update all preceding ASCO guidelines on initial hormonal management of noncastrate advanced, recurrent, or metastatic prostate cancer.

Methods: The Expert Panel based recommendations on a systematic literature review. Recommendations were approved by the Expert Panel and the ASCO Clinical Practice Guidelines Committee.

Results: Four clinical practice guidelines, one clinical practice guidelines endorsement, 19 systematic reviews with or without meta-analyses, 47 phase III randomized controlled trials, nine cohort studies, and two review papers informed the guideline update.

Recommendations: Docetaxel, abiraterone, enzalutamide, or apalutamide, each when administered with androgen deprivation therapy (ADT), represent four separate standards of care for noncastrate metastatic prostate cancer. Currently, the use of any of these agents in any particular combination or series cannot be recommended. ADT plus docetaxel, abiraterone, enzalutamide, or apalutamide should be offered to men with metastatic noncastrate prostate cancer, including those who received prior therapies, but have not yet progressed. The combination of ADT plus abiraterone and prednisolone should be considered for men with noncastrate locally advanced nonmetastatic prostate cancer who have undergone radiotherapy, rather than castration monotherapy. Immediate ADT may be offered to men who initially present with noncastrate locally advanced nonmetastatic disease who have not undergone previous local treatment and are unwilling or unable to undergo radiotherapy. Intermittent ADT may be offered to men with high-risk biochemically recurrent nonmetastatic prostate cancer. Active surveillance may be offered to men with low-risk biochemically recurrent nonmetastatic prostate cancer. The panel does not support use of either micronized abiraterone acetate or the 250 mg dose of abiraterone with a low-fat breakfast in the noncastrate setting at this time.Additional information is available at www.asco.org/genitourinary-cancer-guidelines.
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http://dx.doi.org/10.1200/JCO.20.03256DOI Listing
April 2021

Poor patient health is associated with higher caregiver burden for older adults with advanced cancer.

J Geriatr Oncol 2021 Jan 18. Epub 2021 Jan 18.

University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Palliative Research Center (PaRC), Section of Palliative Care and Medical Ethics, University of Pittsburgh, Pittsburgh, PA, USA.

Objectives: Family 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.

Methods: Cross-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.

Results: Among 441 patient-caregiver dyads, mean patient age was 70 ± 10 and caregiver age was 62 ± 13 years. 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 < 0.01), poorer quality of life (β = -0.07, p < 0.01), more anxiety (β = 0.33, p < 0.01) and depression (β = 0.33, p < 0.01) were associated with higher caregiver burden; caregiving hours did not affect these relationships.

Conclusions: In advanced cancer, poor patient physical and mental health is associated with higher caregiver burden regardless of hours caregiving; future studies should examine interventions tailored to alleviate caregiver burden for this group.
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http://dx.doi.org/10.1016/j.jgo.2021.01.002DOI Listing
January 2021

Can Community Health Workers Increase Palliative Care Use for African American Patients? A Pilot Study.

JCO Oncol Pract 2021 Feb 21;17(2):e158-e167. Epub 2021 Jan 21.

Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD.

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 ( = .03). Psychological distress improved from 5.5 to 4.7 ( = .36), and depressive symptoms from 42.2 to 33.6 ( = .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.
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http://dx.doi.org/10.1200/OP.20.00574DOI Listing
February 2021

Using Patient-Reported Outcomes to Describe the Patient Experience on Phase I Clinical Trials.

JNCI Cancer Spectr 2020 Dec 14;4(6):pkaa067. Epub 2020 Aug 14.

Johns Hopkins Sidney Kimmel Comprehensive Cancer Institute, Baltimore, MD, USA.

Background: Symptoms are common among patients enrolled in phase I trials. We assessed the validity of Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) items in relation to previously validated assessments of quality of life and psychological distress. We used data from a randomized trial testing a palliative care support intervention for patients enrolled on phase I trials.

Methods: Patients (n = 479) were accrued to the parent study prior to initiating a phase I clinical trial with data collected at baseline, 4, and 12 weeks. We determined the correlation of PRO-CTCAE with distress level, Functional Assessment of Cancer Therapy - General (FACT-G) total, and subscale domain scores.

Results: Patients were predominantly female (56.8%) and older than age 60 years, and 30.7% were from minority populations. The correlation coefficient for distress level for all PRO-CTCAE items was small to moderate (Pearson =0.33-0.46). Pearson correlation coefficient for FACT-G total was moderate ( = -0.45 to -0.69). Stronger associations were noted for mood items of the PRO-CTCAE only (with distress level, =0.55-0.6; with FACT-G, = -0.54 to -0.6). PRO-CTCAE symptom interference scores had the strongest correlation with distress level (Pearson =0.46) and FACT-G total (Pearson = -0.69). Correlations between PRO-CTCAE items and corresponding FACT-G (total and subscales) and distress levels reached statistical significance for all items ( <.001).

Conclusion: Evidence demonstrates validity of PRO-CTCAE in a heterogeneous US sample of patients undergoing cancer treatment on phase I trials, with small to moderate correlations with distress level for all PRO-CTCAE items and moderate correlations with quality of life as measured by FACT-G total.
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http://dx.doi.org/10.1093/jncics/pkaa067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768928PMC
December 2020

Randomized Trial of Scrambler Therapy for Chemotherapy-Induced Peripheral Neuropathy: Crossover Analysis.

J Pain Symptom Manage 2020 Nov 27. Epub 2020 Nov 27.

Department of Oncology, Mayo Clinic, Rochester, Minnesota, USA.

Context: Preliminary trials report that Scrambler Therapy, a form of electroanalgesia, may improve discomfort from chemotherapy-induced peripheral neuropathy (CIPN).

Objective: The objective of this phase II, randomized controlled trial was to evaluate the efficacy of Scrambler therapy vs. transcutaneous electrical nerve stimulation (TENS) in treating CIPN.

Methods: Fifty patients were accrued for the first half of this two-part, crossover trial consisting of a 2-week treatment period with either Scrambler or TENS, followed by an 8-week observation period, and then crossover treatment. Twenty-two patients proceeded to the crossover phase. The primary means of assessment was patient-reported outcomes, including symptom severity scales and Global Impression of Change questionnaires. Symptoms were assessed daily during the treatment period and weekly during an 8-week observation period.

Results: A 50% or greater reduction in primary symptom (pain or tingling) score on the last day of treatment was achieved by 6 of 10 Scrambler-treated patients (60%) and 3 of 12 TENS-treated patients (25%) after crossover (P = 0.11). By day 4 of treatment, the two arms diverged with respect to mean change in primary symptom score; this effect was largely carried through to the end of the two-week treatment period. Similarly, Scrambler therapy appeared better than TENS when assessed by Global Impression of Change for neuropathy, pain, and overall quality of life.

Conclusions: Similar findings from the initial randomization and crossover phases of this study support further evaluation of the efficacy of Scrambler therapy in alleviating CIPN symptoms. Evaluation in a larger, randomized controlled trial with standardized treatment is warranted.
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http://dx.doi.org/10.1016/j.jpainsymman.2020.11.025DOI Listing
November 2020

Detoxification, Active Uptake, and Intracellular Accumulation of Chromium Species by a Methane-Oxidizing Bacterium.

Appl Environ Microbiol 2021 01 4;87(2). Epub 2021 Jan 4.

Biomolecular Sciences Research Centre, Sheffield Hallam University, Sheffield, United Kingdom

Despite the wide-ranging proscription of hexavalent chromium, chromium(VI) remains among the major polluting heavy metals worldwide. Aerobic methane-oxidizing bacteria are widespread environmental microorganisms that can perform diverse reactions using methane as the feedstock. The methanotroph Bath, like many other microorganisms, detoxifies chromium(VI) by reduction to chromium(III). Here, the interaction of chromium species with Bath was examined in detail by using a range of techniques. Cell fractionation and high-performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICP-MS) indicated that externally provided chromium(VI) underwent reduction and was then taken up into the cytoplasmic and membranous fractions of the cells. This was confirmed by X-ray photoelectron spectroscopy (XPS) of intact cultures that indicated negligible chromium on the surfaces of or outside the cells. Distribution of chromium and other elements within intact and sectioned cells, as observed via transmission electron microscopy (TEM) combined with energy-dispersive X-ray spectroscopy (EDX) and electron energy loss spectroscopy (EELS), was consistent with the cytoplasm/membrane location of the chromium(III), possibly as chromium phosphate. The cells could also take up chromium(III) directly from the medium in a metabolism-dependent fashion and accumulate it. These results indicate a novel pattern of interaction with chromium species distinct from that observed previously with other microorganisms. They also suggest that and similar methanotrophs may contribute directly to chromium(VI) reduction and accumulation in mixed communities of microorganisms that are able to perform methane-driven remediation of chromium(VI). Bath is a well-characterized aerobic methane-oxidizing bacterium that has become a model system for biotechnological development of methanotrophs to perform useful reactions for environmental cleanup and for making valuable chemicals and biological products using methane gas. Interest in such technology has increased recently owing to increasing availability of low-cost methane from fossil and biological sources. Here, it is demonstrated that this versatile methanotroph can reduce the toxic contaminating heavy metal chromium(VI) to the less toxic form chromium(III) while accumulating the chromium(III) within the cells. This is expected to diminish the bioavailability of the chromium and make it less likely to be reoxidized to chromium(VI). Thus, has the capacity to perform methane-driven remediation of chromium-contaminated water and other materials and to accumulate the chromium in the low-toxicity chromium(III) form within the cells.
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http://dx.doi.org/10.1128/AEM.00947-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783347PMC
January 2021

Changes in the place of death for older adults with cancer: Reason to celebrate or a risk for unintended disparities?

J Geriatr Oncol 2021 Apr 26;12(3):361-367. Epub 2020 Oct 26.

Department of Biostatistics, Johns Hopkins University, Baltimore, MD, United States of America.

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 < 0.001). In multivariable regression, all assessed variables were found to be associated with place of death. Overall, older age was associated with increased risk of nursing facility death versus home death. Black patients were more likely to experience hospital death (OR 1.7) and Hispanic ethnicity had lower odds of death in a nursing facility (OR 0.55). Since 2003, deaths in hospice facilities rapidly increased by 15%.

Conclusion: Hospital and nursing facility cancer deaths among older adults with cancer decreased since 2003, while deaths at home and hospice facilities increased. Differences in place of death were noted for non-white patients and older adults of advanced age.
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http://dx.doi.org/10.1016/j.jgo.2020.10.008DOI Listing
April 2021

Predictors of academic efficacy and dropout intention in university students: Can engagement suppress burnout?

PLoS One 2020 29;15(10):e0239816. Epub 2020 Oct 29.

Faculty of Pharmaceutical Sciences, Universidade Estadual Paulista, Araraquara, Brazil.

In this study we modelled possible causes and consequences of student burnout and engagement on academic efficacy and dropout intention in university students. Further we asked, can student engagement protect against the effects of burnout? In total 4,061 university students from Portugal, Brazil, Mozambique, the United Kingdom, the United States of America, Finland, Serbia, and Macao SAR, Taiwan participated in this study. With the data collected we analyzed the influence of Social Support, Coping Strategies, and school/course related variables on student engagement and burnout using structural equation modeling. We also analyzed the effect of student engagement, student burnout, and their interaction, on Academic Performance and Dropout Intention. We found that both student engagement and burnout are good predictors of subjective academic performance and dropout intention. However, student burnout suppresses the effect of student engagement on these variables. This result has strong implications for practitioners and administrators. To prevent student dropout, it is not enough to promote student engagement-additionally, and importantly, levels of student burnout must be kept low. Other variables such as social support and coping strategies are also relevant predictors of student engagement and burnout and should be considered when implementing preventive actions, self-help and guided intervention programs for college students.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0239816PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7595383PMC
November 2020

A Palliative Care Intervention for Patients on Phase 1 Studies.

J Palliat Med 2020 Oct 27. Epub 2020 Oct 27.

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA.

Phase 1 clinical trials remain vital for oncology care. Patients on these trials require supportive care for quality-of-life (QOL) concerns. 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. This unblinded randomized trial compared the PCI with usual care in patients accrued to Phase I Clinical Trials. Subjects ( = 479) were followed for 24 weeks, with 12 weeks as the primary outcome. Two Comprehensive Cancer Centers in the United States. A consecutive sample, 21 years or older, English fluency, with solid tumors initiating a Phase 1 trial. Psychological Distress (Distress Thermometer), QOL total and subscales (FACT-G), satisfaction (FAM-CARE), survival, and resource utilization (chart audit). PCI subjects showed improved Psychological Distress (-0.47,  = 0.015) and Emotional Well-Being (0.81,  = 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. 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.
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http://dx.doi.org/10.1089/jpm.2020.0597DOI Listing
October 2020

Primary Palliative Care for Patients with Advanced Hematologic Malignancies: A Pilot Trial of the SHARE Intervention.

J Palliat Med 2020 Oct 19. Epub 2020 Oct 19.

Section of Palliative Care and Medical Ethics, Division of General Internal Medicine, Palliative Research Center (PaRC), University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Develop and pilot-test a nurse-led primary palliative care intervention for patients with advanced hematologic malignancies. Nurse-led primary palliative care interventions may improve outpatient palliative care provision for patients with advanced hematologic malignancies. This two-phase, single-arm pilot study involved patients with recurrent or resistant hematologic malignancies, their caregivers, and oncology clinicians at two US-based urban, university-affiliated oncology clinics. Measurements included feasibility (enrollment rates, intervention fidelity, and outcome assessment rates) and acceptability (patient, caregiver, and clinician surveys). In Phase 1 we developed and implemented an oncology nurse-led primary palliative care intervention for patients with recurrent or resistant hematologic malignancies and their caregivers. In Phase 2, we tested feasibility and acceptability. Twenty-six patient participants enrolled. Consent-to-approach rate was 78% and enrolled-to-consent rate was 84%. All enrolled participants received the intervention per protocol. Sixty-nine percent of patients and 100% of caregivers reported that the intervention helped them better understand the patient's illness and cope. Seventy-five percent of oncologists reported that the intervention improved their patients' quality of care, and 25% reported that it helped them take better care of patients. Although our pilot of oncology nurse-led primary palliative care for patients with advanced hematologic malignancies met some of its secondary feasibility endpoints, it did not meet its primary feasibility endpoint (enrollment) and acceptability was mixed. Protecting nursing staff time, increasing patient and clinician involvement in intervention development, and identifying patients with highest supportive needs may improve feasibility and acceptability of future primary palliative care in hematologic malignancy trials.
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http://dx.doi.org/10.1089/jpm.2020.0407DOI Listing
October 2020

EGFR/c-Met and mTOR signaling are predictors of survival in non-small cell lung cancer.

Ther Adv Med Oncol 2020 14;12:1758835920953731. Epub 2020 Sep 14.

Department of Biomedical Sciences, University of Illinois College of Medicine at Rockford, 1601 Parkview Avenue, Room Number E-632, Rockford, IL 61107, USA.

Background: EGFR/c-Met activation/amplification and co-expression, mTOR upregulation/activation, and Akt/Wnt signaling upregulation have been individually associated with more aggressive disease and characterized as potential prognostic markers for lung cancer patients.

Methods: Tumors obtained from 109 participants with stage I-IV non-small cell lung cancer (NSCLC) were studied for EGFR/c-Met co-localization as well as for total and active forms of EGFR, c-Met, mTOR, S6K, beta-catenin, and Axin2. Slides were graded by two independent blinded pathologists using a validated scoring system. Protein expression profile correlations were assessed using Pearson correlation and Spearman's rho. Prognosis was assessed using Kaplan-Meier analysis.

Results: Protein expression profile analysis revealed significant correlations between EGFR/p-EGFR ( = 0.0412) and p-mTOR/S6K ( = 0.0044). Co-localization of p-EGFR/p-c-Met was associated with increased p-mTOR ( = 0.0006), S6K ( = 0.0018), and p-S6K ( < 0.0001) expression. In contrast, active beta-catenin was not positively correlated with EGFR/c-Met nor any activated proteins. Axin2, a negative regulator of the Wnt pathway, was correlated with EGFR, p-EGFR, p-mTOR, p-S6K, EGFR/c-Met co-localization, and p-EGFR/p-c-Met co-localization (all -values <0.03). Kaplan-Meier analysis revealed shorter median survival in participants with high expression of Axin2, total beta-catenin, total/p-S6K, total/p-mTOR, EGFR, and EGFR/c-Met co-localization compared with low expression. After controlling for stage of disease at diagnosis, subjects with late-stage disease demonstrated shorter median survival when exhibiting high co-expression of EGFR/c-Met (8.1 month 22.3 month,  = 0.050), mTOR (6.7 month 22.3 month,  = 0.002), and p-mTOR (8.1 month 25.4 month,  = 0.004) compared with low levels.

Conclusions: These findings suggest that increased EGFR/c-Met signaling is correlated with upregulated mTOR/S6K signaling, which may in turn be associated with shorter median survival in late-stage NSCLC.
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http://dx.doi.org/10.1177/1758835920953731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493230PMC
September 2020

Relationships Between Advanced Cancer Patients' Worry About Dying and Illness Understanding, Treatment Preferences, and Advance Care Planning.

J Pain Symptom Manage 2021 Apr 12;61(4):723-731.e1. Epub 2020 Sep 12.

Section of Palliative Care and Medical Ethics, Division of General Internal Medicine, Palliative Research Center (PaRC), University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Context: Patients with advanced cancer often worry about dying. Less is known about the role of worry in decision making regarding future care.

Objectives: To explore relationships between patients' worry about dying and their illness understanding, treatment preferences, and advance care planning (ACP).

Methods: This cross-sectional study used baseline data from a primary palliative care intervention trial. All participants had metastatic solid tumors. Using patients' response to I worry about dying from the Functional Assessment of Chronic Illness-Palliative Care survey instrument, univariate and multivariate analyses assessed associations with illness understanding, treatment preferences, and ACP.

Results: Of 672 patients, 47% reported worrying about dying not at all, whereas 9.7% worried quite a bit or very much. In regression analysis, compared with patients who reported not worrying about dying, those who reported high levels of worry were more likely to describe themselves as terminally ill (adjusted odds ratio [AOR] = 1.98; 95% CI = 1.10-3.54; P = 0.021) and prefer life-extending therapy over symptom-focused care (AOR = 2.61; 95% CI = 1.30-5.22; P = 0.007). They were less likely to have completed an advance directive (AOR = 0.49; 95% CI = 0.25-0.94; P = 0.032). The same relationships were seen using patients' response to I feel scared about my future from the Herth Hope Index.

Conclusion: Patients with advanced cancer who worry about dying are more likely to identify as terminally ill and desire life-extending treatment and are less likely to engage in ACP. Understanding how patients cope with worry and make medical decisions is important in providing quality care to these patients.
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http://dx.doi.org/10.1016/j.jpainsymman.2020.09.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952460PMC
April 2021

The Impact of Palliative Care Dose Intensity on Outcomes for Patients with Cancer.

Oncologist 2020 11 1;25(11):913-915. Epub 2020 Sep 1.

Johns Hopkins Sidney Kimmel Comprehensive Cancer Institute, Baltimore, Maryland, USA.

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http://dx.doi.org/10.1634/theoncologist.2020-0551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648340PMC
November 2020

Recovery From Bicalutamide-Associated Pneumonitis in a Patient With -Deficient Prostate Cancer.

JCO Oncol Pract 2020 11 27;16(11):767-770. Epub 2020 Jul 27.

Departments of Urology and Oncology, Sidney Kimmel Comprehensive Cancer Program of Johns Hopkins Medical Institutions, Baltimore, MD.

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http://dx.doi.org/10.1200/OP.20.00219DOI Listing
November 2020

Prevention and Management of Chemotherapy-Induced Peripheral Neuropathy in Survivors of Adult Cancers: ASCO Guideline Update.

J Clin Oncol 2020 10 14;38(28):3325-3348. Epub 2020 Jul 14.

Columbia University Medical Center, New York, NY.

Purpose: To update the ASCO guideline on the recommended prevention and treatment approaches in the management of chemotherapy-induced peripheral neuropathy (CIPN) in adult cancer survivors.

Methods: An Expert Panel conducted targeted systematic literature reviews to identify new studies.

Results: The search strategy identified 257 new references, which led to a full-text review of 87 manuscripts. A total of 3 systematic reviews, 2 with meta-analyses, and 28 primary trials for prevention of CIPN in addition to 14 primary trials related to treatment of established CIPN, are included in this update.

Recommendations: The identified data reconfirmed that no agents are recommended for the prevention of CIPN. The use of acetyl-l-carnitine for the prevention of CIPN in patients with cancer should be discouraged. Furthermore, clinicians should assess the appropriateness of dose delaying, dose reduction, substitutions, or stopping chemotherapy in patients who develop intolerable neuropathy and/or functional impairment. Duloxetine is the only agent that has appropriate evidence to support its use for patients with established painful CIPN. Nonetheless, the amount of benefit from duloxetine is limited.Additional information is available at www.asco.org/survivorship-guidelines.
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http://dx.doi.org/10.1200/JCO.20.01399DOI Listing
October 2020

Integrating Palliative Care for Patients on Clinical Trials: Opportunities for Oncology Nurses.

Asia Pac J Oncol Nurs 2020 Jul-Sep;7(3):243-249. Epub 2020 Jun 26.

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.

The purpose of this article is to describe the lessons learned in the course of a 5-year research study on a palliative care intervention for persons on a Phase 1 clinical trial. Patients who are participating in Phase 1 trials and the families who care for them may be especially vulnerable and require special attention. The patients are generally experiencing the effects of advanced disease, and they also may soon experience unknown side effects, intense treatment regimens, and the emotional stress of an uncertain future as a result of clinical trial participation. Oncology nurses in all roles including clinical trials/research nurses, clinicians, educators, and advanced practice registered nurses play a critical role in addressing the quality-of-life concerns in this population. Palliative care can provide better symptom control and information on treatment options and facilitate a better understanding of patient/family goals. Attending to these factors can ultimately mean improved survival for the advanced cancer patient, and support for these patients can assist in advancing the field of oncology as these investigational therapies hold the promise for enhancing survival.
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http://dx.doi.org/10.4103/apjon.apjon_2_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325778PMC
June 2020

Reflections of Hospice Staff Members About Educating Hospice Family Caregivers Through Telenovela.

Am J Hosp Palliat Care 2021 Feb 8;38(2):161-168. Epub 2020 Jul 8.

Harry J. Duffey Family Professor of Palliative Medicine, JHMI, 1501Johns Hopkins Hospital, Baltimore, MD, USA.

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.
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http://dx.doi.org/10.1177/1049909120936169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752841PMC
February 2021

The Dynamic Life of Virus Capsids.

Viruses 2020 06 5;12(6). Epub 2020 Jun 5.

Department of Biochemistry and Molecular Biology, University of Texas Medical Branch at Galveston, 301 University Boulevard, Route 0645, Galveston, TX 77555, USA.

Protein-shelled viruses have been thought as "tin cans" that merely carry the genomic cargo from cell to cell. However, through the years, it has become clear that viruses such as rhinoviruses and caliciviruses are active and dynamic structures waiting for the right environmental cues to deliver their genomic payload to the host cell. In the case of human rhinoviruses, the capsid has empty cavities that decrease the energy required to cause conformational changes, resulting in the capsids "breathing", waiting for the moment when the receptor binds for it to release its genome. Most strikingly, the buried N-termini of VP1 and VP4 are transiently exposed during this process. A more recent example of a "living" protein capsid is mouse norovirus (MNV). This family of viruses have a large protruding (P) domain that is loosely attached to the shell via a single-polypeptide tether. Small molecules found in the gut, such as bile salts, cause the P domains to rotate and collapse onto the shell surface. Concomitantly, bile alters the conformation of the P domain itself from one that binds antibodies to one that recognizes receptors. In this way, MNV appears to use capsid flexibility to present one face to the immune system and a completely different one to attack the host tissue. Therefore, it appears that even protein-shelled viruses have developed an impressive array of tricks to dodge our immune system and efficiently attack the host.
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http://dx.doi.org/10.3390/v12060618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7354500PMC
June 2020