Problem Alcohol Use Among Rural Head and Neck Cancer Patients at Diagnosis: Associations with Health-related Quality of Life

OBJECTIVE: Problem alcohol use in persons with head and neck cancer (HNC) is associated with poor outcomes, including survival. Some evidence suggests that individuals living in rural areas may be at greater risk of problem alcohol use. The present exploratory cross-sectional study sought to examine problem alcohol use at diagnosis in a sample of HNC patients by rural vs urban status. METHODS: Self-reported problem alcohol use as measured by the Short Michigan Alcoholism Screening Test (SMAST) was examined in rural and urban HNC patients at diagnosis (N=454). Multivariable linear regression analysis was conducted to examine correlates of problem alcohol use. Subgroup analyses examined HNC-specific health-related quality of life (HRQOL) by problem drinking status at diagnosis and 3- and 12-months postdiagnosis in rural patients. RESULTS: Multivariable linear regression analysis controlling for age, cancer site, cancer stage, depressive symptoms at diagnosis, and tobacco use at diagnosis indicated that rural residence was significantly associated with SMAST scores at diagnosis such that rural patients were more likely to report higher scores (ß=.095, sr(2)=.010, p=.04). Covariate-adjusted subgroup analyses suggest that rural patients with self-reported problem alcohol use may exhibit deficits in HNC-specific HRQOL at diagnosis and 3- and 12-months postdiagnosis. CONCLUSIONS: HNC patients should be screened for problem alcohol use at diagnosis and counseled regarding the deleterious effects of continued drinking during treatment and beyond. Because access to treatment and referral options may be lacking in rural areas, additional ways of connecting rural patients to specialty care should be explored

The lived experience of head and neck cancer patients receiving curative radiotherapy: A systematic review and meta‐ethnography

Objective: This review aims to explore, appraise, and synthesise the existing evidence of the meaning that head and neck cancer (HNC) patients assign to the experience of receiving curative radiotherapy. Methods: Qualitative evidence synthesis was undertaken using meta‐ethnography. Published literature was identified using 7 databases: AMED, ASSIA, CINAHL, EMBASE, MEDLINE, PubMed, and PsycINFO. Databases were searched from January 2005 to April 2017. The strategy was supplemented by grey literature and citation searches. Results: Out of 1403 titles, 57 abstracts and 35 full texts were screened. Ultimately, 8 studies were eligible for inclusion. The evidence base was moderate to strong in quality. Most of the studies showed that HNC patients undergoing radiotherapy have unmet needs. Four related concepts were identified: the disruption to life that the disease and radiotherapy treatment cause, patients' feelings of isolation, the need for patients to make sense of their situation, and the waiting and uncertainty that radiotherapy creates. Conclusions: The current literature suggests that both HNC and radiotherapy cause disruption in patients' lives. Radiotherapy causes many unpleasant side effects, and in this difficult treatment period, HNC patients feel isolated, uncertain, and in need of coping strategies. Therapeutic radiographers are ideally placed to offer a supportive relationship. By having a deeper understanding of patients' lived experience, radiographers may form stronger relationships and more effectively help patients through their radiotherapy

Depression phenotype, inflammation and the brain: implications for future research

Inflammation is implicated in the etiology of Major Depressive Disorder (MDD). Human neuroimaging techniques are increasingly used to characterize the neural circuitry mediating actions of inflammation on mood, motivation and cognition and its relationship to MDD. In this issue, Byrne and colleagues report the first systematic review of these studies. The systematic review provides a much-needed synthesis of current research findings and highlights the role of cortical and subcortical brain structure and function. In this accompanying commentary, we highlight further points of particular relevance to future studies, including the potential advantages of functional phenotype models rather than the emphasis on mutually exclusive diagnostic categories in describing MDD and other psychiatric disorders. Novel imaging techniques will further enhance possibilities to clarify the link between inflammation and depression. New research challenges are described regarding the relationships between behavioural phenotype, brain structure and function, and peripheral inflammation

Differential effect of interferon-alpha treatment on AEA and 2-AG levels.

The endocannabinoid (eCB) system is one of the key players in immunoregulation, and reduced activity of the eCB system has been linked with depressive-like behaviours in animal studies and depression in clinical samples. There is a well-established link between immune activation and depression, such as following the administration of the pro-inflammatory cytokine, interferon-α (IFN-α), used to treat hepatitis C viral (HCV) infection. However, the role of peripheral endocannabinoids (eCBs), anandamide (AEA) and 2-arachidonoylglycerol (2-AG), following immunotherapy with IFN-α and in IFN-α -induced depression, have not been examined yet. In this study, we investigated whether circulating AEA and 2-AG were modified by treatment with IFN-α and whether they were involved in the development of IFN-α-induced depression. We also explored whether circulating eCBs were associated with peripheral cytokines during and after IFN-α treatment. We measured serum concentrations of AEA and 2-AG using High Performance Liquid Chromatography with Tandem Mass Spectrometry, and serum concentrations of cytokines using Meso Scale Discovery electrochemiluminescence V-PLEX assay, in 70 patients with HCV infection and 41 healthy subjects. We assessed HCV patients at baseline, IFN-α-treatment weeks (TW) 4 and 24, end of treatment (END) and at six months follow-up (FU). We assessed depression using M.I.N.I. International Neuropsychiatric Interview. We found a different pattern of change in peripheral AEA and 2-AG during and after IFN-α treatment. Whilst 2-AG increased earlier in immunotherapy (TW4), remained elevated throughout treatment, and reduced at six months follow-up (FU), AEA increased later in treatment (TW24) and remained elevated six months post-treatment. We also found that baseline levels of AEA were lower in HCV patients compared with healthy controls, whereas there were no differences in 2-AG levels. Interestingly, AEA, but not 2-AG, was significantly, negatively correlated with interleukin (IL)-2 and IL-17a at six months follow-up. We did not find any difference in both eCBs between patients with and without IFN-α-induced depression, at any time point. Our findings suggest that AEA and 2-AG are involved in different stages of immunoregulation following IFN-α treatment, where AEA might be involved in chronic inflammation. Lack of association between peripheral eCBs and IFN-α-induced depression suggests that different biological mechanisms may underpin inflammation-induced depression compared with classic "psychiatric" depression, or that any changes in the eCB system in depression may not be captured by peripheral AEA and 2-AG

Illness Schema Activation and the Effects of Illness Seasonality on Accessibility of Implicit Illness-Related Information

The Common-Sense Model (CSM) of illness self-regulation is a leading theoretical framework describing the process by which an individual recognizes that he or she is physically ill and subsequently attempts to manage that illness state. The CSM proposes that people possess schematically organized implicit cognitive representations of health threats comprising information about illness such as symptoms, causes, label, duration, consequences, and procedures for managing threat [1, 2, 3, 4]. The proposed function of these stored knowledge structures is to activate a self-regulation process that might protect or restore a state of well-being [5]. The CSM proposes that the schematic representation is centrally activated by detection of deviations from the normal functioning self (i.e., experienced symptoms). The identification of illness and the initiation of self-management attempts follow from the search for illness-relevant cognitive structures and the matching of the content of illness schema to the symptomatic experience. For example, a headache (a symptomatic deviation from normal somatic experience) might activate illness schemata containing the cognitive representation of “headache” such as “hangover,” “dehydration,” or “flu.” The matching of the symptom to a particular illness schema will follow from the search and match to other aspects of plausible illness representations, such as its probable cause or duration (timeline).Full Tex

Depression and sickness behavior are Janus-faced responses to shared inflammatory pathways

It is of considerable translational importance whether depression is a form or a consequence of sickness behavior. Sickness behavior is a behavioral complex induced by infections and immune trauma and mediated by pro-inflammatory cytokines. It is an adaptive response that enhances recovery by conserving energy to combat acute inflammation. There are considerable phenomenological similarities between sickness behavior and depression, for example, behavioral inhibition, anorexia and weight loss, and melancholic (anhedonia), physio-somatic (fatigue, hyperalgesia, malaise), anxiety and neurocognitive symptoms. In clinical depression, however, a transition occurs to sensitization of immuno-inflammatory pathways, progressive damage by oxidative and nitrosative stress to lipids, proteins, and DNA, and autoimmune responses directed against self-epitopes. The latter mechanisms are the substrate of a neuroprogressive process, whereby multiple depressive episodes cause neural tissue damage and consequent functional and cognitive sequelae. Thus, shared immuno-inflammatory pathways underpin the physiology of sickness behavior and the pathophysiology of clinical depression explaining their partially overlapping phenomenology. Inflammation may provoke a Janus-faced response with a good, acute side, generating protective inflammation through sickness behavior and a bad, chronic side, for example, clinical depression, a lifelong disorder with positive feedback loops between (neuro)inflammation and (neuro)degenerative processes following less well defined triggers

Monocyte Chemotactic Protein-1 (MCP-1) and Growth Factors Called into Question as Markers of Prolonged Psychosocial Stress

BACKGROUND:Psychosocial stress is becoming a major contributor to increased mental ill-health and sick leave in many countries. Valid markers of chronic stress would be valuable for diagnostic and prognostic purposes. A recent study suggested monocyte chemotactic protein-1 (MCP-1), epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) as markers of chronic stress. We aimed to confirm these potential biomarkers of prolonged psychosocial stress in female patients. METHODOLOGY/PRINCIPAL FINDINGS:Circulating levels of MCP-1, EGF and VEGF, along with several other cytokines, were measured in plasma from 42 female patients suffering from exhaustion due to prolonged psychosocial stress and 42 control subjects, using a protein biochip immunoassay. There were no significant differences between patients and controls in any of the cytokines or growth factors analyzed. Furthermore, when using a different protein bioassay and reanalyzing MCP-1 and VEGF in the same samples, markedly different levels were obtained. To further explore if inflammation is present in patients with exhaustion, the classical inflammatory marker C-reactive protein (CRP) was measured in another group of patients (n=89) and controls (n=88) showing a small but significant increase of CRP levels in the patients. CONCLUSIONS/SIGNIFICANCE:MCP-1, EGF and VEGF may not be suitable markers of prolonged psychosocial stress as previously suggested. Furthermore, significant differences were obtained when using two different protein assays measuring the same samples, indicating that comparing studies where different analytic techniques have been used might be difficult. Increased levels of CRP indicate that low-grade inflammation might be present in patients with exhaustion due to prolonged stress exposure but this inflammation does not seem to be reflected by increase in circulating MCP-1 or other cytokines measured

Interleukin-6 promoter polymorphism interacts with pain and life stress influencing depression phenotypes

Interleukin-6 (IL-6) has emerged as a potent biomarker for depression as its elevated plasma levels in patients with clinical depression have been confirmed by meta-analyses. Increased plasma IL-6 concentration was associated with various psychological stress factors and physical disorders accompanied by pain. Another modulator of the IL-6 level is rs1800795, a promoter polymorphism in the IL-6 gene which is able to influence its expression rate. Therefore, we examined in a Hungarian population sample of 1053 volunteers with European origins if rs1800795 polymorphism can affect depression symptoms measured by Zung Self-rating Depression Scale (ZSDS), and Brief Symptom Inventory (BSI). We also investigated the interactions of the polymorphism with reported painful physical conditions and Recent Negative Life Events (RLE) measured by the List of Life Threatening Experiences. Rs1800795 significantly interacted with both RLE and painful condition on depressive symptoms measured by ZSDS and BSI using different heritability models, while no main effects of the polymorphism were identified. After correction for multiple testing only the rs1800795 x RLE interaction effect (recessive model) remained significant on the BSI score, while both RLE and painful conditions significantly interacted on the ZSDS. In conclusion, the functional IL-6 rs1800795 polymorphism in interaction with various stress factors increases the risk of depression and has a greater impact on symptoms measured by the ZSDS. Thus, IL-6 and other cytokines may be more relevant in the development of somatic symptoms compared to affective signs of depression, delineating a specific genotype-phenotype relationship in this heterogeneous disorder