Debra Lynch Kelly

A Systematic Review of Effects of Waterpipe Smoking on Cardiovascular and Respiratory Health Outcomes

Background Waterpipe smoking (WPS) is a social custom common in many Middle Eastern, North African, and Asian countries and has become increasingly popular in the US, especially among youth; however, WPS smoking may be increasing in the US adult population as well. There is a common belief among waterpipe (WP) smokers that WPS is less harmful than smoking cigarettes. Thus, this review aims to systematically explore the literature on the effects of WP tobacco smoking with a particular focus on cardiovascular and respiratory health outcomes as well as on oxidative stress, immunity, and cell cycle interference health outcomes. Methodology We conducted a systematic review, guided by the criteria of The Preferred Reporting Items for Systematic Reviews and Meta-Analyses, using the following online databases MEDLINE, CINAHL, ScienceDirect, PMC, and Cochrane Library. Results were summarized qualitatively. Results Forty studies met the inclusion criteria established for this review. Based on the existing evidence, several cardiovascular and respiratory physiologic health indicators and conditions have been shown to be negatively affected by WPS. In addition to the effects of nicotine and chemical toxicant exposures, WPS was significantly associated with an increase in heart rate, blood pressure, and lower pulmonary function test results, as well as a number of health conditions such as lung cancer, alterations in oxidative stress, immunity, and cell cycle interference. Conclusion The current literature provides evidence that WPS is associated with a number of negative health indicators and outcomes. There is need for more research related to WPS and its effects on health so that appropriate campaigns and prevention interventions can be implemented to control the epidemic increase of WPS in the US.

Relationship of systemic cytokine concentrations to cognitive function over two years in women with early stage breast cancer

Cancer and its treatment are frequently associated with cancer-related cognitive impairment (CRCI). While CRCI has been associated with linked to chemotherapy, there is increasing evidence that the condition may start prior to treatment and for some, remain unresolved after active treatment and into survivorship. Although the pathophysiology of the condition is complex, alterations in systemic cytokines, signaling molecules activated in response to infection or injury that trigger inflammation, are a possible mechanism linked to cognitive dysfunction in breast cancer and other conditions. Given the conflicting results in the literature, the lack of focus on domain specific cognitive testing, and the need for a longer time period given the multiple modalities of standard treatments for early-stage breast cancer, this longitudinal study was conducted to address these gaps. METHODS We assessed 75 women with early-stage breast cancer at five points over two years, starting prior to the initial chemotherapy through 24months after chemotherapy initiation. Measures included a validated computerized evaluation of domain-specific cognitive functioning and a 17-plex panel of plasma cytokines. Linear mixed-effects models were applied to test the relationships of clinical variables and cytokine concentrations to each cognitive domain. RESULTS Levels and patterns of cytokine concentrations varied over time: six of the 17 cytokines (IL-6, IL-12, IL-17, G-CSF, MIPS-1β, and MCP-1) had the most variability. Some cytokine levels (e.g., IL-6) increased during chemotherapy but then decreased subsequently, while others (e.g., IL-17) consistently declined from baseline over time. There were multiple relationships among cytokines and cognition, which varied over time. At baseline, elevated concentrations of G-CSF and reduced concentrations of IL-17 were associated with faster psychomotor speed. At the second time-point (prior to the mid-chemotherapy), multiple cytokines had significant associations with psychomotor speed, complex attention, executive function, verbal memory, cognitive flexibility, composite memory and visual memory. Six months after chemotherapy initiation and at the one-year point, there were multiple, significant relationships among cytokines and multiple cognitive. At two years, fewer significant relationships were noted; however, lower concentrations of IL-7, a hematopoietic cytokine, were associated with better psychomotor speed, complex attention, and memory (composite, verbal and visual). MCP-1 was inversely associated with psychomotor speed and complex attention and higher levels of MIP-1β were related to better complex attention. CONCLUSION Levels and patterns of cytokines changed over time and demonstrated associations with domain-specific cognitive functioning that varied over time. The observed associations between cytokines and cognitive performance provides evidence that not only prototypical cytokines (i.e., IL-6, TNF-α, and IL1-β) but also cytokines from multiple classes may contribute to the inflammatory environment that is associated with cognitive dysfunction. Future studies to better delineate the cytokine changes, both individually and in networks, are needed to precisely assess a mechanistic link between cytokines and cognitive function in women receiving treatments for breast cancer.

The Microbiome and Cancer: Implications for Oncology Nursing Science.

Background: Approximately 1.6 million Americans were diagnosed with cancer in 2014. To combat their disease, many individuals received either curative or palliative treatments that produced undesired symptoms. These symptoms, which often cause significant distress for individuals coping with cancer, may share biologic underpinnings such as epigenetic changes and immune dysregulation. Alterations in the normal flora of the gut may also influence cancer symptoms. Objective: The aim of this review is to describe the emerging role for the gut microbiome in cancer research, especially the potential relationship between the gut microbiome and cancer symptoms. Methods: Extant literature was reviewed and synthesized. Results: The majority of studies linking the gut microbiota and cancer are animal models and focus on the relationship between dysbiosis and colorectal cancer. Emerging evidence supports that the “gut-brain” connection is a plausible mechanism for “psychoneurological” cancer symptoms such as depression, pain, and fatigue. Conclusions: There is compelling evidence that the gut microbiota affects cancer via several mechanisms, including microbial diversity and number, metabolism, and/or immune initiation. However, more research is necessary to elucidate these mechanisms, particularly among a variety of cancers and cancer-related symptoms. Implications for Practice: A better understanding of the role of the gut microbiota in cancer symptoms may lead to the development of targeted individualized interventions affecting the gut microbiota that prevent or ameliorate dysbiosis, thereby reducing symptoms. These interventions may emphasize self-care management strategies essential for wellness, such as diet, nutrition, and stress reduction.

Symptoms, Cytokines, and Quality of Life in Patients Diagnosed With Chronic Graft-Versus-Host Disease Following Allogeneic Hematopoietic Stem Cell Transplantation

PURPOSE/OBJECTIVES To describe associations among symptoms, cytokines, and quality of life (QOL) of patients with chronic graft-versus-host disease (cGVHD). DESIGN Prospective, cross-sectional, cohort. SETTING The bone marrow transplantation unit at a National Cancer Institute-designated cancer center in Virginia.
 SAMPLE 24 adults diagnosed with cGVHD. METHODS Data were collected for demographic factors, symptoms, and QOL from medical record and validated questionnaires. Serum was analyzed for cytokine levels. MAIN RESEARCH VARIABLES cGVHD, symptoms, cytokines, C-reactive protein, and QOL.
 FINDINGS Participants reported multiple, concurrent symptoms. Cytokine levels were higher in participants with symptoms versus those without symptoms. Cytokine interleukin-6 correlated with lack of energy and dry mouth. Negative correlations were noted between QOL and symptoms. CONCLUSIONS Findings demonstrated multiple concurrent symptoms present in this sample and significant relationships among symptoms, cytokines, and QOL. IMPLICATIONS FOR NURSING cGVHD is a serious condition affecting QOL in many individuals after bone marrow transplantation for many different cancers. Results from this pilot study indicate that patients experience multiple symptoms, including sexual dysfunction, that adversely affect QOL. Better understanding of the interrelated symptoms of cGVHD and the biomarkers associated with these symptoms may lead to targeted symptom management interventions.

Health Promoting Life-Style Behaviors and Systemic Inflamma­tion in African American and Caucasian Women Prior to Chemo­therapy for Breast Cancer

BACKGROUND Racial disparities in breast cancer outcomes persist, with differential adverse outcomes in African American women. Although research has ex-amined possible genetic differences, there has been little research on potentially modifiable characteristics such as health promoting behaviors. The purpose of this article is to describe the characteristics and to compare the differences by race in lifestyle factors and inflammatory biomarkers in African American and Caucasian women with breast cancer. METHODS This is a baseline descriptive analysis from an ongoing randomized controlled trial that includes 124 women diagnosed with early stage breast cancer prior to chemotherapy. Data sources included medical records, self-re-port questionnaires and a blood sample for measures of inflammation. The sta-tistical analysis included descriptive statistics and ANOVA models to determine differences between the two groups. RESULTS Overall, both groups had low levels of health promoting behaviors. African Americans had a significantly higher body mass index. Caucasian women consumed more alcohol. Levels of C-reactive protein and MIP-1β were significantly higher in African Americans. CONCLUSION Potentially modifiable factors such as nutrition, physical activity and levels of inflammation warrant further attention.

Variations in COMT and NTRK2 Influence Symptom Burden in Women Undergoing Breast Cancer Treatment

Women with breast cancer frequently report distressing symptoms during and after treatment that can significantly erode quality of life (QOL). Symptom burden among women with breast cancer is of complex etiology and is likely influenced by disease, treatment, and environmental factors as well as individual genetic differences. The purpose of the present study was to examine the relationships between genetic polymorphisms within Neurotrophic tyrosine kinase receptor 1 (NTRK1), Neurotrophic tyrosine kinase receptor 2 (NTRK2), and catechol-O-methyltransferase (COMT) and patient symptom burden of QOL, pain, fatigue, anxiety, depression, and sleep disturbance before, during, and after treatment for breast cancer in a subset of participants (N = 51) in a randomized clinical trial of a novel symptom-management modality for women with breast cancer undergoing chemotherapy. Patients were recruited at the time of initial breast cancer diagnosis and completed all survey measures at the time of recruitment, after the initiation of treatment (surgery and/or chemotherapy), and then following treatment conclusion. Multiple linear regression analyses revealed significant associations between NTRK2 and COMT single nucleotide polymorphism (SNP) genotype and symptom burden. Two COMT variants were associated with the specific symptoms of anxiety and QOL measures prior to the initiation of chemotherapy as well as pain interference and severity during and after treatment. Genotype at the NTRK2 SNP rs1212171 was associated with both sleep disturbance and fatigue. These findings, while exploratory, indicate that the genotypes of NTRK2 and COMT may contribute to relative risk for symptom burden during and shortly after the period of chemotherapy in women with early stage breast cancer.

Fall Risk in Adult Inpatients With Leukemia Undergoing Induction Chemotherapy

Falls are a major concern for patients with acute myeloid leukemia who are admitted to the hospital for induction chemotherapy. Patients with cancer are at risk for rapidly changing health status and, therefore, need a different kind of fall surveillance than those in other inpatient units. Fall risk most likely will change throughout an inpatients stay. Oncology nurses can start addressing this issue by reviewing the documented data of falls in this patient population.

Neurocognitive dysfunction in hematopoietic cell transplant recipients: expert review from the late effects and Quality of Life Working Committee of the CIBMTR and complications and Quality of Life Working Party of the EBMT

Hematopoietic cell transplantation (HCT) is a potentially curative treatment for children and adults with malignant and non-malignant diseases. Despite increasing survival rates, long-term morbidity following HCT is substantial. Neurocognitive dysfunction is a serious cause of morbidity, yet little is known about neurocognitive dysfunction following HCT. To address this gap, collaborative efforts of the Center for International Blood and Marrow Transplant Research and the European Society for Blood and Marrow Transplantation undertook an expert review of neurocognitive dysfunction following HCT. In this review, we define what constitutes neurocognitive dysfunction, characterize its risk factors and sequelae, describe tools and methods to assess neurocognitive function in HCT recipients, and discuss possible interventions for HCT patients with this condition. This review aims to help clinicians understand the scope of this health-related problem, highlight its impact on well-being of survivors, and to help determine factors that may improve identification of patients at risk for declines in cognitive functioning after HCT. In particular, we review strategies for preventing and treating neurocognitive dysfunction in HCT patients. Lastly, we highlight the need for well-designed studies to develop and test interventions aimed at preventing and improving neurocognitive dysfunction and its sequelae following HCT.

Pilot Study of Metabolomics and Psychoneurological Symptoms in Women With Early Stage Breast Cancer

Many women with breast cancer experience symptoms of pain, fatigue, and depression, collectively known as psychoneurologic (PN) symptoms, during and after chemotherapy treatment. Evidence that inflammatory dysfunction related to cancer and its treatments contributes to the development and persistence of PN symptoms through several interrelated pathways is accumulating. However, a major limiting factor in more precisely identifying the biological mechanisms underlying these symptoms is the lack of biological measures that represent a holistic spectrum of biological responses. Metabolomics allows for examination of multiple, co-occurring metabolic pathways and provides a systems-level perspective on biological mechanisms that may contribute to PN symptoms. Methods: In this pilot study, we performed serum metabolome analysis using liquid chromatography high-resolution mass spectrometry of global and targeted metabolomics from the tryptophan pathway from archived samples from 19 women with early-stage breast cancer. We used paired t tests to compare metabolite concentrations and Pearson’s correlation coefficients to examine concomitant changes in metabolite concentrations and PN symptoms before and after chemotherapy. Results: Levels of pain, fatigue, and depression increased after chemotherapy. Compared with pre-chemotherapy, global metabolites post-chemotherapy were characterized by higher concentrations of acetyl-l-alanine and indoxyl sulfate and lower levels of 5-oxo-l-proline. Targeted analysis indicated significantly higher kynurenine levels and kynurenine/tryptophan ratios post-chemotherapy. Symptoms of pain and fatigue had strong associations with multiple global and several targeted metabolites. Conclusion: Results demonstrated that metabolomics may be useful for elucidating biological mechanisms associated with the development and severity of PN symptoms, specifically pain and fatigue, in women with early-stage breast cancer.

Systematic review of genetic polymorphisms associated with psychoneurological symptoms in breast cancer survivors.

PurposePsychoneurological (PN) symptoms, such as anxiety, cognitive impairment, depression, fatigue, sleep disturbances, and pain, are highly prevalent in breast cancer patients undergoing cancer treatment. Emerging evidence suggests that genetic polymorphisms may contribute to differential symptom susceptibility. We aimed to systematically review associations between genetic polymorphisms and PN symptoms during or after cancer treatment for early-stage breast cancer.MethodsTwenty-six eligible articles published until October 2017 were identified in PubMed, PsycINFO, Web of Science, and additional records. Information on study characteristics, genetic polymorphisms, and PN symptoms was extracted. Study quality was evaluated by the STrengthening the REporting of Genetic Association (STREGA) guideline. Genes included in the analysis were categorized by biological pathways based on the Reactome database.ResultsA total of 54 single nucleotide polymorphisms and haplotypes that are significantly associated with PN symptoms were identified; half of them were associated with increased severity of PN symptoms, while the other half contributed to the decrease of PN symptoms. Pain has the known highest number of associated genetic polymorphisms reported, followed by fatigue, cognitive impairment, depressive symptoms, sleep disturbances, and anxiety. The majority of genetic polymorphisms were involved in immune system and neuronal system pathways. Most studies were unsuccessful in meeting the STREGA guideline, which requires transparent reporting of methods and results.ConclusionsThis review provides comprehensive evidence of genetic polymorphisms underlying PN symptoms, which may pave the way for the development of personalized therapeutics targeting these symptoms. More well-designed genome-wide association studies are required to validate and replicate these findings.