Tryptophan and Kynurenine Pathway Metabolites and Psychoneurological Symptoms Among Breast Cancer Survivors.

BACKGROUND: Among breast cancer survivors, pain, fatigue, depression, anxiety, and sleep disturbance are common psychoneurological symptoms that cluster together. Inflammation-induced activation of the tryptophan-kynurenine metabolomic pathway may play an important role in these symptoms. AIMS: This study investigated the relationship between the metabolites involved in the tryptophan-kynurenine pathway and psychoneurological symptoms among breast cancer survivors. DESIGN: Cross-sectional study. SETTING: Participants were recruited at the oncology clinic at the University of Illinois Hospital & Health Sciences System. PARTICIPANTS/SUBJECTS: 79 breast cancer survivors after major cancer treatment. METHODS: We assessed psychoneurological symptoms with the PROMIS-29 and collected metabolites from fasting blood among breast cancer survivors after major cancer treatment, then analyzed four major metabolites involved in the tryptophankynurenine pathway (tryptophan, kynurenine, kynurenic acid, and quinolinic acid). Latent profile analysis identified subgroups based on the five psychoneurological symptoms. Mann-Whitney U tests and multivariable logistic regression compared targeted metabolites between subgroups. RESULTS: We identified two distinct symptom subgroups (low, 81%; high, 19%). Compared with participants in the low symptom subgroup, patients in the high symptom subgroup had higher BMI (p = .024) and were currently using antidepressants (p = .008). Using multivariable analysis, lower tryptophan levels (p = .019) and higher kynurenine/tryptophan ratio (p = .028) were associated with increased risk of being in the high symptom subgroup after adjusting for BMI and antidepressant status. CONCLUSION: The tryptophan-kynurenine pathway and impaired tryptophan availability may contribute to the development of psychoneurological symptoms.

Pain Interference in End Stage Kidney Disease is Associated with Changes in Gut Microbiome Features Before and After Kidney Transplantation.

BACKGROUND: Pain, a common debilitating symptom among kidney transplant recipients (KTRs), is among the most common and undertreated symptoms after kidney transplantation. AIMS: Characterize associations between gut microbiome features and pain interference before and after kidney transplantation. DESIGN: Longitudinal, repeated measures study, collecting fecal specimens and pain interference data pretransplant and 3 months posttransplant. SETTING: Participants were recruited at the kidney transplant clinic at the University of Illinois Hospital & Health Sciences System. PARTICIPANTS/SUBJECTS: 19 living donor kidney transplant recipients. METHODS: We assessed fecal microbial community structure with shotgun metagenomic sequencing; we used pain interference scores derived from the Patient-Reported Outcomes Measurement Information System-57. RESULTS: We measured a reduction in the Shannon diversity index in both groups after transplantation but observed no significant differences between groups at either time point. We did observe significant differences in fecal microbial Bray-Curtis similarity index among those reporting pain interference pre- transplant versus no pain interference at 3-months posttransplant (R = .306, p = .022), and between pain interference groups at posttransplant (R = .249, p = .041). Pairwise models showed significant differences between groups posttransplant in relative abundances of several taxa, including a 5-fold reduction.ßin Akkermansia among those with pain interference and a higher relative abundance of taxa associated with chronic inflammation in those with pain interference posttransplant. Functional gene analysis identified two features that were significantly enriched in those with pain interference, including a peptide transport system gene. CONCLUSIONS: Gut microbiota community structure differs between groups with and without pain interference at 3 months after kidney transplantation. Several taxa involved in intestinal barrier integrity and chronic inflammation were associated with posttransplant pain.

Sleep Disturbances in Older Adults Receiving Dialysis.

Sleep disturbances are serious issues in individuals with end stage kidney disease because they are associated with worsening kidney function and other negative health outcomes, especially in older adults. Our analysis aimed to provide clinicians with the conceptual clarity required for managing sleep disturbances in older patients who are receiving dialysis. A literature review revealed three attributes that define this population's sleep disturbances: sleep initiation and maintenance difficulties, restless sleep and short sleep, and abnormal breathing during sleep. Con sidering the serious consequences and correlates of sleep disturbances in older patients who are receiving dialysis, tailored interventions are needed to improve their sleep. Our literature review, concept analysis, and case studies provide key information for designing future mechanistic, clinical-translational, and interventional research.

Novel approach to unpleasant symptom clusters surrounding pruritus in patients with chronic kidney disease and on dialysis therapy.

PURPOSE OF REVIEW: Chronic kidney disease-associated-pruritus (CKD-aP) is a common symptom in patients with end-stage kidney disease (ESKD) undergoing dialysis. CKD-aP typically occurs alongside other debilitating symptoms and may comprise so-called 'symptom clusters' which have synergistic effects that adversely impact patient health-related quality of life (HRQoL). Importantly, symptoms in a cluster may share a common biological mechanism. Here we review the clinical impact of CKD-aP and its association with other symptoms reported by dialysis patients. The clinical benefits of treating pruritus and its potential impact on other symptoms are also addressed. RECENT FINDINGS: Studies have shown CKD-aP significantly impairs HRQoL in patients with ESKD undergoing dialysis and is associated with adverse clinical outcomes, including increased risk of infections, hospitalizations, and mortality. Despite these negative effects, CKD-aP remains underrecognized and undertreated in clinical practice. CKD-aP is frequently associated with other symptoms, including disturbed sleep/poor sleep quality, anxiety, depression, and pain. Clinical studies of antipruritic therapies show that reduction of itch intensity may also alleviate other associated symptoms, such as poor sleep quality. SUMMARY: CKD-aP and its associated symptoms are inadequately managed in clinical practice. Greater understanding and awareness of CKD-aP and its surrounding symptom clusters in dialysis patients may improve their overall symptom management and HRQoL.

Standardized Patient Education for Decompensated Cirrhotic Patients and Impact on Clinician Satisfaction.

The development of ascites in patients with cirrhosis can cause numerous complications including abdominal discomfort, pain, respiratory distress, decreased mobility, diminished quality of life, and contributes to an increased mortality. Symptom self-monitoring that incorporates evidence-based treatments has been effective when used by patients with noncirrhotic chronic diseases. Guided by the theory of Self-Care of Chronic Illness, a self-monitoring guide was adapted from an existing validated tool. In the context of a pilot quality initiative, staff nurses educated patients with ascites and their caregivers, with the adapted symptom self-monitoring guide using a standardized process. Clinicians were surveyed regarding their satisfaction with the patient education pre- and post-implementation. Results indicated improved clinician satisfaction with the education provided to patients and their caregivers during the clinic visit. Implementation of self-monitoring may improve clinician and patient satisfaction and clinic workflows. Additional evaluation of the self-monitoring guide and its effect on patient satisfaction, impact on hospital admissions, and outpatient paracentesis is warranted.

Small-Molecule Antiviral ß-d-N4-Hydroxycytidine Inhibits a Proofreading-Intact Coronavirus with a High Genetic Barrier to Resistance.

Coronaviruses (CoVs) have emerged from animal reservoirs to cause severe and lethal disease in humans, but there are currently no FDA-approved antivirals to treat the infections. One class of antiviral compounds, nucleoside analogues, mimics naturally occurring nucleosides to inhibit viral replication. While these compounds have been successful therapeutics for several viral infections, mutagenic nucleoside analogues, such as ribavirin and 5-fluorouracil, have been ineffective at inhibiting CoVs. This has been attributed to the proofreading activity of the viral 3'-5' exoribonuclease (ExoN). ß-d-N4-Hydroxycytidine (NHC) (EIDD-1931; Emory Institute for Drug Development) has recently been reported to inhibit multiple viruses. Here, we demonstrate that NHC inhibits both murine hepatitis virus (MHV) (50% effective concentration [EC50] = 0.17 µM) and Middle East respiratory syndrome CoV (MERS-CoV) (EC50 = 0.56 µM) with minimal cytotoxicity. NHC inhibited MHV lacking ExoN proofreading activity similarly to wild-type (WT) MHV, suggesting an ability to evade or overcome ExoN activity. NHC inhibited MHV only when added early during infection, decreased viral specific infectivity, and increased the number and proportion of G:A and C:U transition mutations present after a single infection. Low-level NHC resistance was difficult to achieve and was associated with multiple transition mutations across the genome in both MHV and MERS-CoV. These results point to a virus-mutagenic mechanism of NHC inhibition in CoVs and indicate a high genetic barrier to NHC resistance. Together, the data support further development of NHC for treatment of CoVs and suggest a novel mechanism of NHC interaction with the CoV replication complex that may shed light on critical aspects of replication.IMPORTANCE The emergence of coronaviruses (CoVs) into human populations from animal reservoirs has demonstrated their epidemic capability, pandemic potential, and ability to cause severe disease. However, no antivirals have been approved to treat these infections. Here, we demonstrate the potent antiviral activity of a broad-spectrum ribonucleoside analogue, ß-d-N4-hydroxycytidine (NHC), against two divergent CoVs. Viral proofreading activity does not markedly impact sensitivity to NHC inhibition, suggesting a novel interaction between a nucleoside analogue inhibitor and the CoV replicase. Further, passage in the presence of NHC generates only low-level resistance, likely due to the accumulation of multiple potentially deleterious transition mutations. Together, these data support a mutagenic mechanism of inhibition by NHC and further support the development of NHC for treatment of CoV infections.

Physical Symptom Cluster Subgroups in Chronic Kidney Disease.

BACKGROUND: Symptom burden associated with chronic kidney disease can be debilitating, with a negative effect on patient health-related quality of life. Latent class clustering analysis is an innovative tool for classifying patient symptom experience. OBJECTIVES: The aim of the study was to identify subgroups of patients at greatest risk for high symptom burden, which may facilitate development of patient-centered symptom management interventions. METHODS: In this cross-sectional analysis, baseline data were analyzed from 3,921 adults enrolled in the Chronic Renal Insufficiency Cohort Study from 2003 to 2008. Latent class cluster modeling using 11 items on the Kidney Disease Quality of Life symptom profile was employed to identify patient subgroups based on similar observed physical symptom response patterns. Multinomial logistic regression models were estimated with demographic variables, lifestyle and clinical variables, and self-reported measures (Kidney Disease Quality of Life physical and mental component summaries and the Beck Depression Inventory). RESULTS: Three symptom-based subgroups were identified, differing in severity (low symptom, moderate symptom, and high symptom). After adjusting for other variables in multinomial logistic regression, membership in the high-symptom subgroup was less likely for non-Hispanic Blacks and men. Other factors associated with membership in the high-symptom subgroup included lower estimated glomerular filtration rate, history of cardiac/cardiovascular disease, higher Beck Depression Inventory scores, and lower Kidney Disease Quality of Life physical and mental component summaries. DISCUSSION: Three symptom subgroups of patients were identified among patients with mild-to-moderate chronic kidney disease. Several demographic and clinical variables predicted membership in subgroups. Further research is needed to determine if symptom subgroups are stable over time and can be used to predict healthcare utilization and clinical outcomes.

ß-d-N4-Hydroxycytidine Is a Potent Anti-alphavirus Compound That Induces a High Level of Mutations in the Viral Genome.

Venezuelan equine encephalitis virus (VEEV) is a representative member of the New World alphaviruses. It is transmitted by mosquito vectors and causes highly debilitating disease in humans, equids, and other vertebrate hosts. Despite a continuous public health threat, very few compounds with anti-VEEV activity in cell culture and in mouse models have been identified to date, and rapid development of virus resistance to some of them has been recorded. In this study, we investigated the possibility of using a modified nucleoside analog, ß-d-N4-hydroxycytidine (NHC), as an anti-VEEV agent and defined the mechanism of its anti-VEEV activity. The results demonstrate that NHC is a very potent antiviral agent. It affects both the release of genome RNA-containing VEE virions and their infectivity. Both of these antiviral activities are determined by the NHC-induced accumulation of mutations in virus-specific RNAs. The antiviral effect is most prominent when NHC is applied early in the infectious process, during the amplification of negative- and positive-strand RNAs in infected cells. Most importantly, only a low-level resistance of VEEV to NHC can be developed, and it requires acquisition and cooperative function of more than one mutation in nsP4. These adaptive mutations are closely located in the same segment of nsP4. Our data suggest that NHC is more potent than ribavirin as an anti-VEEV agent and likely can be used to treat other alphavirus infections.IMPORTANCE Venezuelan equine encephalitis virus (VEEV) can cause widespread epidemics among humans and domestic animals. VEEV infections result in severe meningoencephalitis and long-term sequelae. No approved therapeutics exist for treatment of VEEV infections. Our study demonstrates that ß-d-N4-hydroxycytidine (NHC) is a very potent anti-VEEV compound, with the 50% effective concentration being below 1 µM. The mechanism of NHC antiviral activity is based on induction of high mutation rates in the viral genome. Accordingly, NHC treatment affects both the rates of particle release and the particle infectivity. Most importantly, in contrast to most of the anti-alphavirus drugs that are under development, resistance of VEEV to NHC develops very inefficiently. Even low levels of resistance require acquisition of multiple mutations in the gene of the VEEV-specific RNA-dependent RNA polymerase nsP4.

Orally Efficacious Broad-Spectrum Ribonucleoside Analog Inhibitor of Influenza and Respiratory Syncytial Viruses.

Morbidity and mortality resulting from influenza-like disease are a threat, especially for older adults. To improve case management, next-generation broad-spectrum antiviral therapeutics that are efficacious against major drivers of influenza-like disease, including influenza viruses and respiratory syncytial virus (RSV), are urgently needed. Using a dual-pathogen high-throughput screening protocol for influenza A virus (IAV) and RSV inhibitors, we have identified N4-hydroxycytidine (NHC) as a potent inhibitor of RSV, influenza B viruses, and IAVs of human, avian, and swine origins. Biochemical in vitro polymerase assays and viral RNA sequencing revealed that the ribonucleotide analog is incorporated into nascent viral RNAs in place of cytidine, increasing the frequency of viral mutagenesis. Viral passaging in cell culture in the presence of an inhibitor did not induce robust resistance. Pharmacokinetic profiling demonstrated dose-dependent oral bioavailability of 36 to 56%, sustained levels of the active 5'-triphosphate anabolite in primary human airway cells and mouse lung tissue, and good tolerability after extended dosing at 800 mg/kg of body weight/day. The compound was orally efficacious against RSV and both seasonal and highly pathogenic avian IAVs in mouse models, reducing lung virus loads and alleviating disease biomarkers. Oral dosing reduced IAV burdens in a guinea pig transmission model and suppressed virus spread to uninfected contact animals through direct transmission. Based on its broad-spectrum efficacy and pharmacokinetic properties, NHC is a promising candidate for future clinical development as a treatment option for influenza-like diseases.

Patient-Reported Barriers to the Prekidney Transplant Evaluation in an At-Risk Population in the United States.

BACKGROUND: Despite our knowledge of barriers to the early stages of the transplant process, we have limited insight into patient-reported barriers to the prekidney transplant medical evaluation in populations largely at-risk for evaluation failure. METHODS: One-hundred consecutive adults were enrolled at an urban, Midwestern transplant center. Demographic, clinical, and quality of life data were collected prior to patients visit with a transplant surgeon/nephrologist (evaluation begins). Patient-reported barriers to evaluation completion were collected using the Subjective Barriers Questionnaire 90-days after the initial medical evaluation appointment (evaluation ends), our center targeted goal for transplant work-up completion. RESULTS: At 90 days, 40% of participants had not completed the transplant evaluation. Five barrier categories were created from the 85 responses to the Subjective Barriers Questionnaire. Patient-reported barriers included poor communication, physical health, socioeconomics, psychosocial influences, and access to care. In addition, determinants for successful evaluation completion included being of white race, higher income, free of dialysis, a lower comorbid burden, and reporting higher scores on the Kidney Disease Quality of Life subscale role-emotional. CONCLUSION: Poor communication between patients and providers, and among providers, was the most prominent patient-reported barrier identified. Barriers were more prominent in marginalized groups such as ethnic minorities and people with low income. Understanding the prevalence of patient-reported barriers may aid in the development of patient-centered interventions to improve completion rates.

Non-Biological Barriers to Referral and the Pre-Kidney Transplant Evaluation Among African Americans in the United States: A Systematic Review.

African Americans face a disproportionate burden related to the incidence of end stage renal disease. A literature search was conducted for research articles published between 2006-2015 to synthesize current literature related to non-biological barriers to early stages of the pre-kidney transplant continuum for African Americans in the United States. Twenty-four articles were included in the final sample. Eleven barriers were identified. Barriers were categorized as socioeconomic-based barriers, culture-based barriers, and knowledge-based barriers. Resources to develop educational interventions for both patients and providers may help reduce existing barriers.

Determinants of frequent Internet use in an urban kidney transplant population in the United States: characterizing the digital divide.

CONTEXT: The Internet is a staple of electronic communication and is essential to the emerging telemonitoring and health information technology interventions for adults with chronic diseases. OBJECTIVE: To identify determinants of frequent Internet use in an urban kidney transplant population in the United States. DESIGN: A single center, cross-sectional survey study. SETTING: An urban Midwestern transplant center. PARTICIPANTS: 78 pretransplant and 177 posttransplant patients. MAIN OUTCOME MEASURES: Frequent Internet use, defined as using the Internet more than 5 hours per week. RESULTS: Only 38% of participants reported being frequent Internet users. Non-Hispanic blacks and participants who reported their race/ethnicity as "other" were significantly less likely than whites to report being frequent Internet users. Women were 59% less likely than men to be frequent users of the Internet. Those who reported having kidney disease for more than 3 years were more likely to report being frequent Internet users. As education increased, Internet use increased. As age increased, Internet use decreased. CONCLUSION: Alternatives to electronic information sources and/or additional resources should be considered for those who may fall in the so-called digital divide.

Critical Realism in Symptom Science - A Scoping Review.

There has been an increasing interest in research positioned within critical realism (CR). This analysis aimed to determine how CR has been applied in symptom science through a scoping review of the literature. Fifty-two articles were identified through searches in seven databases and search engines, and grey literature. Quantitative and qualitative analyses were performed using Excel and ATLAS.ti 8.0. Review findings indicate that CR has been used to examine two key aspects of symptoms - symptom experiences and symptom interventions. The details of how CR was operationalized are presented. This first scoping review highlights how a critical realist lens would help examine individual and contextual factors that influence symptom experiences, response to interventions, and outcomes.

Associations Between Gut Microbial Features and Sickness Symptoms in Kidney Transplant Recipients.

PURPOSE: The study investigated the relationship of gut microbiome features and sickness symptoms in kidney transplant recipients. METHODS: Employing a prospective, longitudinal design, we collected data from 19 participants who had undergone living-donor kidney transplant at three timepoints (pre-transplant and 1 week and 3 months post-transplant). Sickness symptom data and fecal specimens were collected at each timepoint. Participants were grouped either as high or low sickness symptom severity at baseline. Shotgun metagenomics sequencing characterized gut microbial structure and functional gene content. Fecal microbial features, including alpha (evenness and richness within samples) and beta (dissimilarities between samples) diversity and relative abundances, were analyzed using R statistical packages. Cross-sectional and longitudinal analyses examined relationships between gut microbial features and sickness symptoms. RESULTS: Although our exploratory findings revealed no significant differences in alpha and beta diversity between groups, the high-severity group showed lower microbial richness and evenness than the low-severity group. The high-severity group had enriched relative abundance of bacteria from the genera Citrobacter and Enterobacter and reduced relative abundance of bacteria from the genus Akkermansia across timepoints. No functional genes differed significantly between groups or timepoints. CONCLUSIONS: Kidney transplant recipients with high symptom burden displayed increased putative proinflammatory bacteria and decreased beneficial bacteria. This study provides an effect size that future large cohort studies can employ to confirm associations between gut microbial features and sickness symptom experiences in the kidney transplant population. The study findings also have implications for future interventional studies aiming to alleviate the sickness symptom burden in this population.

The Gut Microbiome and Symptom Burden After Kidney Transplantation: An Overview and Research Opportunities.

Many kidney transplant recipients continue to experience high symptom burden despite restoration of kidney function. High symptom burden is a significant driver of quality of life. In the post-transplant setting, high symptom burden has been linked to negative outcomes including medication non-adherence, allograft rejection, graft loss, and even mortality. Symbiotic bacteria (microbiota) in the human gastrointestinal tract critically interact with the immune, endocrine, and neurological systems to maintain homeostasis of the host. The gut microbiome has been proposed as an underlying mechanism mediating symptoms in several chronic medical conditions including irritable bowel syndrome, chronic fatigue syndrome, fibromyalgia, and psychoneurological disorders via the gut-brain-microbiota axis, a bidirectional signaling pathway between the enteric and central nervous system. Post-transplant exposure to antibiotics, antivirals, and immunosuppressant medications results in significant alterations in gut microbiota community composition and function, which in turn alter these commensal microorganisms' protective effects. This overview will discuss the current state of the science on the effects of the gut microbiome on symptom burden in kidney transplantation and future directions to guide this field of study.

Kidney transplant and the digital divide: is information and communication technology a barrier or a bridge to transplant for African Americans?

CONTEXT: Barriers to kidney transplant for African Americans are well documented in the literature. Little information on ownership of information and communication technology and use of such technology in transplant populations has been published. OBJECTIVE: To characterize racial differences related to ownership and use of information and communication technology in kidney transplant patients. DESIGN: A single-center, cross-sectional survey study. SETTING: An urban Midwestern transplant center. PARTICIPANTS: 78 pretransplant patients and 177 transplant recipients. MAIN OUTCOMES MEASURES: The survey consisted of 6 demographic questions, 3 disease-related questions, and 9 technology-related questions. Dichotomous (yes/no) and Likert-scale items were the basis for the survey. RESULTS: Cell phone use was high and comparable between groups (94% in African Americans, 90% in whites, P= .22). A vast majority (75% of African Americans and 74% of whites) reported being "comfortable" sending and receiving text messages. Computer ownership (94.3% vs 79.3%) and Internet access (97.7% vs 80.7%) were greater among whites than African Americans (both P< .01). Fewer African Americans were frequent users of the Internet (27.1% vs 56.3%) and e-mail (61.6% vs 79.3%) than whites (both P<.01). More African Americans than whites preferred education in a classroom setting (77% vs 60%; P< .005) and educational DVDs (66% vs 46%; P< .002). CONCLUSION: The use of cell phone technology and text messaging was ubiquitous and comparable between groups, but computer and Internet access and frequency of use were not. Reaching out to the African American community may best be accomplished by using cell phone/text messaging as opposed to Internet-based platforms.

Asymmetric synthesis of host-directed inhibitors of myxoviruses.

High-throughput screening (HTS) previously identified benzimidazole 1 (JMN3-003) as a compound with broad antiviral activity against different influenza viruses and paramyxovirus strains. In pursuit of a lead compound from this series for development, we sought to increase both the potency and the aqueous solubility of 1. Lead optimization has achieved compounds with potent antiviral activity against a panel of myxovirus family members (EC(50) values in the low nanomolar range) and much improved aqueous solubilities relative to that of 1. Additionally, we have devised a robust synthetic strategy for preparing 1 and congeners in an enantio-enriched fashion, which has allowed us to demonstrate that the (S)-enantiomers are generally 7- to 110-fold more potent than the corresponding (R)-isomers.

Sickness Symptoms in Kidney Transplant Recipients: A Scoping Review.

Sickness symptoms (depressive symptoms, anxiety, and fatigue) are common among people with chronic illness, often presenting as a symptom cluster. Sickness symptoms persist in many patients with chronic kidney disease, even after kidney transplantation (KT); however, little is known about sickness symptom-induced burden in KT recipients. This scoping review synthesizes available evidence for sickness symptoms in KT recipients, including findings on symptom prevalence, predictors, outcomes, interrelationships, and clustering. Among 38 reviewed studies, none identified sickness symptoms as a cluster, but we observed interrelationships among the symptoms examined. Fatigue was the most prevalent sickness symptom, followed by anxiety and depressive symptoms. Predictors of these symptoms included demographic, clinical, and psychosocial factors, and health-related quality of life was the most researched outcome. Future research should use common data elements to phenotype sickness symptoms, include biological markers, and employ sophisticated statistical methods to identify potential clustering of sickness symptoms in KT recipients.

Health Belief Model Constructs Affect Influenza Vaccine Uptake in Kidney Transplant Recipients.

This secondary analysis explored how the constructs of the health belief model affect influenza vaccine uptake in kidney transplant recipients (KTRs). In the parent study, a total of 180 KTRs were recruited at an organ transplant center in South Korea. A nonlinear path analysis using generalized structural equation modeling was performed. Previous influenza vaccination had a direct effect on their behavior, while cues to action alone did not directly affect their behavior. Perceived benefits played a key role as a mediator in improving influenza vaccine uptake in KTRs. This study highlights the need for health professionals to assess perceived benefits at the individual level and provide patient-centered interventions based on a consideration of theoretical mechanisms. As cues to action, recommendations for recipients' first vaccination after kidney transplant should focus on changing patients' perceptions of benefits by emphasizing the positive aspects of the influenza vaccine for immunosuppressed patients.

On a pathway to resigned acceptance: Patients' experiences of living with symptom clusters in oral cancer.

PURPOSE: Patients treated for oral cancer experience multiple concurrent symptoms. A larger mixed-methods study was conducted among patients who were treated with surgery alone or in combination with other modalities. The aim of the qualitative strand was to explore the experiences of living with symptom clusters. METHODS: A phenomenological design was used to explore the lived experiences. Participants were recruited for the larger study from two outpatient units of a tertiary teaching hospital (N = 300). After completion of a survey, a maximum variation purposive subsample of 20 participants was drawn from the larger sample and were interviewed in-depth about their experiences. Thematic analysis was conducted. FINDINGS: All participants experienced multiple concurrent symptoms, commonly including chewing difficulties + dry mouth + speech difficulties; chewing difficulties + dry mouth + diminished taste; and chewing difficulties + dry mouth + speech difficulties + trismus. Analysis of their experiences of living with these symptom clusters revealed six themes: Acknowledged Disruptions, Inner Dialogue, Shifting Expectations, Floods of Emotions, Exercising Control over Life, and Resigned Acceptance. These themes portrayed that time and living with symptom clusters lead to what we describe as a pathway to resigned acceptance. This pathway is intermingled with disruptions, self-reflections on 'why me' and karma, negative emotions, and failed expectations regarding symptom recovery. Attempts to exercise control over their lives were also revealed through coping strategies, watchful living, future planning, and being health advocates. On realizing with time that further symptom alleviation is unlikely, and considering symptom-cluster experiences as being written in their fate, they move towards a state of resigned acceptance. However, unlike passive acceptance, their belief in fate was accompanied with resilience, evidenced by their ongoing efforts to explore pragmatic ways to live with symptom clusters. CONCLUSIONS: Findings provide key insights into patient perspectives which most often remain unexpressed in clinical settings. Further research is required to explore watchful living, fate as a coping strategy, and intertwining of faith, fate, and karma.