TITLE: Association of Alcohol Use, Depression, and Pain among Cancer Patients AUTHOR INFO Nneoma Ubah Manik Ahuja Eugene Annor Author(s) Affiliations: College of Public Health, East Tennessee State University, Johnson City, TN 37614, United States Background: Cancer is often a chronic illness that evolves with pain. Studies have shown that 60% of patients with cancer are burdened with pain, and 25% to 30% have severe pain. Uncontrolled pain has been recognized as one of the significant causes of depression among cancer patients. Depression is a comorbid syndrome that affects 25% of cancer patients, but only 5% see a mental health professional. Major depressive disorders have very high rates of comorbidity, with substance use disorders ranging from 12% to 80%. However, there is limited data on the association of depression, alcohol use disorders, and pain among cancer patients. This study aims to identify this association. Methods: We used cross-sectional data from the 2021 Behavioral Risk Factor Surveillance System, a nationally representative U.S. telephone-based survey of adults aged 18 and above. We also extracted data for cancer patients (n=8,963). Logistic regression analysis was conducted to test the association between pain associated with cancer and two outcomes, depression, and alcohol use. We controlled for income, race, educational status, health insurance status, race/ethnic minority status, and age. Results: Overall, 8.6% (n=843) of patients reported pain from their cancer, while 20.2% reported depression and 44.4% reported alcohol use. Pain from cancer was associated with significantly higher odds of depression (OR=1.75, 95% CI, 1.49, 2.05) along with low income (OR=1.93, 95% CI, 1.73, 2.16) and less than high school education (OR=1.30, 95% CI, 1.02, 1.65). Pain from cancer was not significantly associated with alcohol use, while male gender (OR=1.46, 95% CI, 1.34, 1.58) among cancer patients predicted higher odds of alcohol use. Conclusion: Depression and alcohol use have been identified as significant problems among cancer patients with pain. Among the cancer patients studied, pain from cancer was not significantly associated with alcohol use. However, cancer patients burdened with pain were more likely to suffer depression. This indicates a need to invest more effort in identifying cancer patients with depression and managing their pain appropriately to improve their outcomes. Proper pain management should also be prioritized in cancer care to prevent depression. Keywords: Pain management, Cancer Pain, Alcohol, Depression.

INTRODUCTION: There is uncertainty in the prevalence of chronic non-cancer pain (CNCP) in military veterans. A systematic review and meta-analysis was conducted to elucidate this issue, and examine potential effect modifiers of CNCP prevalence. Additionally, chronic pain is a pervasive and debilitating condition that disproportionately affects military veterans. We recently completed a qualitative study of Canadian veterans living with chronic pain to identify their research priorities; however, the generalizability of our findings was uncertain. METHODS: MEDLINE, EMBASE, PsycINFO, CINAHL, Web of Science were searched from 2013 to January 21, 2021, for observational studies reporting “chronic pain” or pain ≥ 3 months in military veterans. The random-effects meta-analysis was used for pooling data, the Grading of Recommendations, Assessment, Development and Evaluations approach was used for rating quality of evidence, and the Instrument to Assess the Credibility of Effect Modification Analyses was used to rate credibility of the subgroup analyses. Furthermore, from January to March 2021, we emailed a 45-item cross-sectional survey to a list of Canadian veterans that asked about the relative importance of 20 research priorities regarding chronic pain. We explored for statistical significance between male and female responses for any item in which the proportion of endorsement showed a ≥10% difference. RESULTS: 41 observational studies with 5,550,375 military veterans were included. The overall pooled CNCP prevalence is 34% (95% confidence interval (CI) 25% to 45%). However, significant subgroup effect was found for type of prevalence measure (generic or specific) among military veterans (test of interaction p=0.007, moderate subgroup credibility): the pooled generic CNCP prevalence of 43%, 95% CI 29% to 57% (Low-certainty evidence) vs. the pooled specific type of CNCP prevalence of 14%, 95% CI 6.7% to 23% (Moderate-certainty evidence). A multivariable meta-regression model adjusted for proportion lost to follow-up found the type of prevalence measure to be the only significant predictor of CNCP prevalence (p < 0.0001). 313 of 699 Canadian military veterans living with chronic pain completed ≥50% of the survey (45% response rate). Respondents were predominantly male (77%) with a median age of 52 (interquartile range [IQR] 44-58). All 20 research priorities listed in the survey were endorsed as very important by ≥52% of respondents, and three received endorsement by ≥85%: (I) optimizing chronic pain management after release from the military; and (II) identifying and (III) treating mental illness among veterans living with chronic pain. Women were more likely than men to endorse research on post-surgical care for chronic pain prevention or research on holistic care for chronic pain. Men were more likely than women to endorse research on physical activity or exercise for chronic pain. Individuals with higher gross income (≥$80,000) were less likely to endorse research into physiotherapy for chronic pain, or chiropractic for chronic pain compared to those with lower gross income. Individuals with greater age are less likely to endorse research on medical cannabis for chronic pain. CONCLUSIONS: The overall prevalence of CNCP is 34% among military veterans. For generic CNCP, the prevalence is 43%; for a given subtype of CNCP, the prevalence is 11%. Methodologically robust studies are required to more precisely determine CNCP prevalence. The most salient research priorities among our respondents were optimizing chronic pain management during service and after discharge from the military, including co-morbid mental illness. Differences in gender, gross income, and age are implicated in the endorsement of therapy-related priorities, which include surgery, physical activity or exercise, chiropractic, and medical cannabis. Our findings provide insight into the research priorities of Canadian military veterans living with chronic pain. These findings should be considered by granting agencies when formulating calls for proposals, and by researchers who wish to undertake research that will address the needs of military veterans living with chronic pain. / Thesis / Master of Science (MSc)

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National rates of chronic non-cancer pain (CNCP) are rising alongside increasing reports of prescription opioid abuse and mortality. Associations between the rise in CNCP and in opioid abuse seem logical, yet research on CNCP among individuals with opioid dependence is currently limited due to the complicated nature of comorbid conditions in research and treatment. This study aims to expand the CNCP knowledge base by responding to the question: Do individuals with CNCP participating in an opiate treatment program have better or worse treatment outcomes than individuals without CNCP? This study used a secondary dataset including 483 adults from Kentucky’s Opiate Recovery Treatment Outcome Study. Individuals in the sample met DSM-IV-TR criteria for opioid dependence and were in treatment at a licensed opiate treatment program (OTP). Analysis compared cases with and without CNCP on national treatment outcome measures including substance use, recovery support, education, employment, mental health symptoms, and criminal justice system involvement. Results indicated no differences at follow-up between the CNCP (n=163) and non-CNCP (n=320) individuals on substance abstinence, recovery supports, education level, or criminal justice system involvement. At baseline and follow-up there were more unemployed individuals and individuals receiving disability benefits in the CNCP group than the non-CNCP group. Reported anxiety and depression symptoms increased at follow-up, while use of prescription medicine for mental health symptoms declined for both groups (non-significant differences). The only predictors for CNCP cases in this sample were tobacco use and presence of a chronic medical condition. Recommendations include expansion of smoking cessation programs in substance abuse treatment settings. Future research might examine integrated treatment and medical home health models to better address biopsychosocial components of clients with comorbid conditions like opioid dependence and CNCP.

Suffering is a fundamental experience of the human condition. Whereas the arts and humanities have struggled to make sense of this condition, no concerted effort has taken place in nursing. Suffering is painfully absent within the cancer nursing research literature, a place where suffering should be conspicuous. The purpose of this study was to explore suffering inherent in the cancer experience. The concurrent use of Travelbee's Human-To-Human Relationship Model and narrative theory provided the conceptual underpinning for this prospective ethnography. Narratives of suffering were explored among seven patients diagnosed with cancer (breast, n = 4; brain; malignant melanoma; and ovarian cancer). Five women and two men were interviewed weekly (N = 89 interviews) for a period of up to five months. Participant observation supplemented the interview data. Seven richly textured narratives revealed the suffering endured in the living-of-cancer. The narratives also detailed the informant as person, the cancer trajectory, and explanatory models of cancer causation. A second level analysis of the narratives provided an intra-group comparison of suffering. "Cascade of losses" was the overarching theme. The undermining of personhood, and a loss of faith and trust in the medical system characterized this cascade of losses. Losses were further encountered: the dismissal of symptoms presented to physicians, the failure of treatment as cure, the death of other cancer patients, and the false reassurance that "cancer can be beaten". The remaining themes were "cancer as torture" and "the work of suffering--the beauty of cancer". The findings of this study suggest that nurses may not be capable of alleviating patient suffering. Patients' lives intersect at the suffering experience; their suffering is shaped by the past, present, and future. Nurses may influence these intersections of suffering to some extent, however, it is the individual who ultimately determines the living and outcome (if any) of their suffering. In the lives of the informants, it was the love of spouses and children, faith and trust in God, and satisfaction with life's accomplishments which permitted the endurance of suffering. Competent, comfort-care provided by compassionate nurses is needed by patients who suffer with cancer.

Dans le présent travail, le rôle de la glie dans l’expression de la douleur cancéreuse et de la douleur neuropathique a été étudié de façon comparative. Le modèle animal de douleur cancéreuse a été obtenu par injection osseuse dans le tibia, chez la rate Sprague-Dawley, de cellules de carcinome mammaire de type MRMT-1. Le modèle de douleur neuropathique a été obtenu chez le rat Wistar par ligature des nerfs spinaux L5 et L6. Les données obtenues par l’analyse du comportement douloureux en réponse à la stimulation par des filaments de von Frey ont permis de quantifier l’allodynie et l’hyperalgésie mécaniques statiques. La douleur chronique, hors stimulation nociceptive, a été mesurée à l’aide d’un test d’impotence. Les agents pharmacologiques ont été administrés par voie intrapéritonéale ou par voie intrathécale, à l’aide d’un cathéter implanté de façon chronique. L’analyse des comportements nociceptifs après stimulation par filaments de von Frey montre que l’inhibition fonctionnelle transitoire de la glie spinale par le fluorocitrate est sans effet sur la douleur dans les deux modèles. Dans les deux modèles, l’expression des réponses douloureuses dépend de l’activation des récepteurs NMDA spinaux. L’administration par voie intrathécale d’une seule dose de D-aminoacide oxydase, qui dégrade la D-sérine, co-agoniste endogène du récepteur NMDA, réduit l’allodynie et l’hyperalgésie chez les rats neuropathiques et l’allodynie chez les rats cancéreux. Les effets d’un traitement chronique par le fluoroacétate chez les rats neuropathiques sont réversés par l’administration intrathécale de D-sérine. La D-sérine altère légèrement le seuil nociceptif chez les rats cancéreux. Aucun des agents pharmacologiques utilisés ne réverse la réduction d’appui du membre lésé chez les rats cancéreux ou neuropathiques. Ces résultats montrent que, chez le rat, la douleur neuropathique comme la douleur osseuse cancéreuse dépend de la co-activation des récepteurs NMDA spinaux par un de ses ligands endogènes, la D-sérine, mais que seule la douleur neuropathique requiert une glie spinale fonctionnelle. Ils suggèrent donc un rôle différentiel de la glie dans la physiopathologie de ces deux types de douleur chronique / The present work has investigated the role of glia upon pain symptoms in a well established peripheral neuropathic pain model and a bone cancer pain model. The neuropathic pain model was obtained by right L5-L6 spinal nerve ligation in male Wistar rats. Bone cancer pain was induced by injecting MRMT-1 rat mammary gland carcinoma cells into the right tibia of Sprague-Dawley female rats. Mechanical allodynia and hyperalgesia were quantified using von Frey hairs and ambulatory incapacitance using dynamic weight bearing. Drugs were administered either acutely or chronically using osmotic pumps, through intrathecal catheters chronically implanted in experimental animals. Using von Frey hair stimuli, we found that transient inhibition of glia metabolism by intrathecal injection of fluorocitrate was ineffective in both models. In both models, pain symptoms required spinal NMDA receptor activation. Intrathecal administration of a single dose of D-aminoacid oxidase, which degrades D-serine, a co-agonist of NMDA receptors, reduced mechanical allodynia and hyperalgesia in neuropathic rats and allodynia in cancer rats. The effect of chronic fluoroacetate in neuropathic rats was reversed by acutely administered intrathecal D-serine, which had only a slight effect in cancer rats. None of these compounds altered the functional disability shown by neuropathic or cancer animals and measured by the dynamic weight bearing apparatus. These results show that neuropathic pain and cancer pains depend upon D-serine co-activation of spinal NMDA receptors but only neuropathic pain requires functional spinal cord glia in the rat. Glia may thus play different roles in the development and maintenance of chronic pain in these two situations.

Bakgrund: Smärta drabbar de flesta cancerpatienter, och är det symtom de fruktar mest med sjukdomen. Smärtan påverkar deras liv lika mycket som själva cancerdiagnosen. Syfte: Syftet med denna litteraturöversikt var att belysa patienters upplevelser av cancerrelaterad smärta och uppmärksamma vilka effekter det kan ha för livskvaliteten, samt uppmärksamma hur vårdpersonalen bemöter patienternas smärta. Metod: En litteraturöversikt har gjorts där elva vetenskapliga artiklar har granskats och analyserats med kvalitativ innehållsanalys. Tre huvudteman har genererats: upplevelsen av smärtan, effekter på livskvaliteten, vårdens bemötande. Resultat: Smärta är en individuell upplevelse som är svår att beskriva för andra. Patienternas livskvalitet påverkades negativt genom att de begränsades fysiskt, psykiskt och socialt. Många var missnöjda med den vård de fick och kände att kommunikationen inte var tillräcklig. Ett dåligt bemötande från vårdpersonalen ledde till att patienterna tappade förtroendet till dem, och bristfällig information till att de tappade hoppet om att bli smärtfria. Slutsats: Att drabbas av en cancerdiagnos innebär en stor påfrestning, och att samtidigt lida av smärta försvårar patientens förmåga att klara av sin livssituation. Vårdpersonalen har en viktig roll för att kunna minska patientens lidande, och kan genom att förbättra kommunikationen och bemötandet göra skillnad hos patienter med cancer som lider av smärta. / Background: Pain affects most cancer patients, and it is what they fear most about the disease. The pain affects their lives as much as the cancer diagnosis itself. Purpose: The purpose of this literature review was to illustrate patients experiences of cancer-related pain and what effects it may have on the quality of life, and to highlight how the healthcare professionals respond to patients’ pain. Method: A literature review has been made where eleven scientific articles have been reviewed and analyzed with qualitative content analysis. This generated tree main themes: the experience of the pain, effects on the quality of life, the treatment of care. Result: Pain is an individual experience which is difficult to describe. The quality of life of the patients was negatively affected because they were physically, mentally and socially limited. Many were dissatisfied with the care they received and felt that communication was not sufficient. A poor response from caregivers has led to patients’ loss of trust, and inadequate information to loss of hope in being painless. Conclusion: Being affected by a cancer diagnosis is hard enough, and at the same time suffer from pain exacerbates the situation. The caregiver has an important role in reducing the patients’ suffering, and by improving the deficiencies, they can make a difference for cancer patients´ suffering from pain.

There is evidence of a relationship between sleep-wake disturbances and pain variables in cancer patients. It is hypothesized that pain affects all aspects of sleep patterns. Pain has been known to affect sleep disturbances; however there are different facets of sleep-disturbances and pain that can be evaluated. These variables include pain distress, pain intensity, pain at its worst, relief from pain, sleep distress, how well the patient sleeps, how tired one feels, and drowsiness distress. Several studies identify relationships between sleep-disturbances and pain. This study using secondary analysis was designed to correlate variables related to sleep-wake disturbance and pain in cancer patients admitted to hospice home care. The study sample included 209 cancer patients from a previously completed clinical trial with various cancer diagnoses. Results of sleep and pain variables were re-analyzed using Pearson correlations. The results showed significant positive relationships between pain distress and sleep distress (p = .000), difficulty sleeping and pain intensity (p = .008), and sleep distress and pain at its worst (p = .008). There were no significant relationships found between sleep distress and relief from pain, pain distress and how well the patient sleeps, pain distress and how tired one feels, and pain distress and drowsiness distress. Sleep-wake disturbances and pain have been studied in cancer patients, but there is little known concerning pain and its correlation to sleep disturbances of cancer patients admitted to hospice home care. This study provided important information on the relationship between sleep-wake disturbance and pain variables in this group of cancer patients. This study provides data to support the necessity to provide complete and accurate assessments of sleep and pain symptoms on admission to hospice home care and throughout the patient's care to aid in improved quality of life.

Inadequate cancer pain management is a global problem. The problem is particularly worse in developing countries where the majority of patients present with advanced stages of the disease. Nurses play an important role in cancer pain management because they spend the majority of their time with patients. The purpose of the study was to examine role of unit cultures on cancer pain management practices among nurses in Kenya. A focused ethnography was used to explore cancer pain management practices of two different units (general and private) within the same institution. Data were collected for four months in a national referral hospital in Nairobi, Kenya. Purposive sampling was used to recruit participants. A total of twenty five nurses and fourteen secondary participants (e.g., nurse managers) participated in this study. Data were collected through semi-structured interviews, observations, and document reviews. Content analysis was used to analyze the data. The study findings show that the unit culture plays a role in cancer pain management practices. For instance, nurses on the oncology unit prioritize pain while nurses on the private unit prioritize overall patient satisfaction. Nurses in both units do not conduct a comprehensive pain assessment and they do not use validated pain assessment tools. Facilitators, such as availability of analgesics and palliative care training, were helpful in managing cancer pain especially in the oncology unit. Barriers such as, negative attitudes towards opioids and doubting patients’ report of pain continue to hinder adequate cancer pain management in the private unit. Other barriers including lack of pain management policies, assessment tools, and workload, influence cancer pain management practices negatively in both units. Understanding the role of unit culture in nursing cancer pain management practices has important implications for policy and practice. Findings in this study show a divergence of the prevailing training of nurses on pain management and practice. Findings could be used to develop pain management policies and protocols for nurses to use as a guide in cancer pain management. Also, nurse managers could use this findings to improve practice for instance, training in cancer pain management could be expanded to include nurses in the private unit. In terms of research, studies could be done to capture patients’ perspectives regarding cancer pain management, or implementation studies could be carried out to alleviate the barriers identified. Lastly, tailored strategies aimed at changing the culture in a unit to enhance change in practice are needed.

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