Sleep, Fatigue, and Inflammatory Biomarkers in Older Adults with Chronic Venous Leg Ulcers Receiving Intensive Outpatient Wound Care.

Objective: Chronic venous ulcers are a relatively common and distressing condition that disproportionately affects older individuals. Along with multiple concomitant issues such as wound drainage, pain, and mobility impairments, individuals with chronic venous leg ulcers (CVLUs) commonly report sleep disturbances and fatigue; however, limited research has examined these symptoms in relation to inflammatory biomarkers in this population over the intensive wound care treatment trajectory. This study aimed at describing the symptoms of sleep and fatigue in older adults with CVLUs receiving intensive wound treatment with weekly debridement and exploring the relationships between these symptoms and tumor necrosis factor-alpha (TNF-α), c-reactive protein (CRP), and interleukin (IL)-6. Approach: Demographics, clinical characteristics, Pittsburgh Sleep Quality Index (PSQI) scores, Brief Fatigue Inventory (BFI), TNF-α, CRP, and IL-6 levels were collected from 84 older adults with CVLUs at three time points (baseline, week 4, and week 8). Data analysis included descriptive statistics and Bayesian estimation of associations. Results: Findings showed a consistent pattern of poor sleep quality and mild fatigue among these individuals. Lower IL-6 levels at week 4 and higher CRP levels at week 8 were linked to poor sleep quality. Higher CRP levels were linked to greater fatigue at baseline and week 8. Sleep and fatigue were correlated at all time points. Innovation and Conclusion: This study highlights the importance of clinicians evaluating sleep and fatigue in those with CVLUs. Further research is needed to validate circulating inflammatory biomarkers to enhance our understanding of sleep and fatigue's role in wound healing.

Biomarkers of sleep disturbance in adults with chronic illness: A scoping review.

OBJECTIVES: The purpose of this scoping review was to identify which biomarkers for sleep disturbance were the most prevalent and significant in the literature across chronic illnesses. METHODS: A scoping review was conducted, following Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines, to provide a map of the existing literature on the biomarkers of sleep disturbance in adults with chronic illness. Peer-reviewed articles published between 2010-2020 were included if they measured a biomarker and discussed sleep deprivation, disturbance, or dysfunction secondary to a chronic illness. RESULTS: A total of 21 articles were included and synthesized using data charting. There were 24 different biomarkers identified, most commonly collected through serum. Biomarkers were grouped, then biomarkers and correlations with sleep were identified and mapped. DISCUSSION: Overall, the most common biomarkers studied were interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), c-reactive protein (CRP), and interleukin-1 beta (IL-1ß). Cytokines were the most commonly studied biomarkers, with a majority of studies focusing on pro-inflammatory cytokines. Based on the results of this review, CRP, IL-6, TNF-α, and erythrocyte sedimentation rate (ESR) showed themost significant correlations with sleep across all chronic illnesses. Future research is still needed to identify an ideal biomarker for sleep disturbance that can be used across chronic illnesses.

Biobehavioral Mechanisms Associated With Nonhealing Wounds and Psychoneurologic Symptoms (Pain, Cognitive Dysfunction, Fatigue, Depression, and Anxiety) in Older Individuals With Chronic Venous Leg Ulcers.

The prevalence and incidence of chronic venous leg ulcers (CVLUs) are increasing worldwide, as are the associated financial costs. Although it has long been known that their underlying etiology is venous insufficiency, the molecular aspects of healing versus nonhealing, as well as the psychoneurologic symptoms (PNS; pain, cognitive dysfunction, fatigue, depression, and anxiety) associated with CVLUs remain understudied. In this biobehaviorally focused review, we aim to elucidate the complex mechanisms that link the biological and molecular aspects of CLVUs with their PNS. Innovations in "omics" research have increased our understanding of important wound microenvironmental factors (e.g., inflammation, microbial pathogenic biofilm, epigenetic processes) that may adversely alter the wound bed's molecular milieu so that microbes evade immune detection. Although these molecular factors are not singularly responsible for wound healing, they are major components of wound development, nonhealing, and PNS that, until now, have not been amenable to systematic study, especially over time. Further, this review explores our current understanding of the molecular mechanisms by which the immune activation that contributes to the development and persistence of CVLUs also leads to the development, persistence, and severity of wound-related PNS. We also make recommendations for future research that will expand the field of biobehavioral wound science. Biobehavioral research that focuses on the interrelated mechanisms of PNS will lead to symptom-management interventions that improve quality of life for the population burdened by CVLUs.

Enhancing Braden pressure ulcer risk assessment in acutely ill adult veterans.

This study sought to determine if a parsimonious pressure ulcer (PU) predictive model could be identified specific to acute care to enhance the current PU risk assessment tool (Braden Scale) utilized within veteran facilities. Factors investigated include: diagnosis of gangrene, anemia, diabetes, malnutrition, osteomyelitis, pneumonia/pneumonitis, septicemia, candidiasis, bacterial skin infection, device/implant/graft complications, urinary tract infection, paralysis, senility, respiratory failure, acute renal failure, cerebrovascular accident, or congestive heart failure during hospitalization; patient's age, race, smoking status, history of previous PU, surgery, hours in surgery; length of hospitalization, and intensive care unit days. Retrospective chart review and logistic regression analyses were used to examine Braden scores and other risk factors in 213 acutely ill veterans in North Florida with (n = 100) and without (n = 113) incident PU from January-July 2008. Findings indicate four medical factors (malnutrition, pneumonia/pneumonitis, candidiasis, and surgery) have stronger predictive value (sensitivity 83%, specificity 72%, area under receiver operating characteristic [ROC] curve 0.82) for predicting PUs in acutely ill veterans than Braden Scale total scores alone (sensitivity 65%, specificity 70%, area under ROC curve 0.70). In addition, accounting for four medical factors plus two Braden subscores (activity and friction) demonstrates better overall model performance (sensitivity 80%, specificity 76%, area under ROC curve 0.88).

Understanding the role of nutrition and wound healing.

Optimal wound healing requires adequate nutrition. Nutrition deficiencies impede the normal processes that allow progression through stages of wound healing. Malnutrition has also been related to decreased wound tensile strength and increased infection rates. Malnourished patients can develop pressure ulcers, infections, and delayed wound healing that result in chronic nonhealing wounds. Chronic wounds are a significant cause of morbidity and mortality for many patients and therefore constitute a serious clinical concern. Because most patients with chronic skin ulcers suffer micronutrient status alterations and malnutrition to some degree, current nutrition therapies are aimed at correcting nutrition deficiencies responsible for delayed wound healing. This review provides current information on nutrition management for simple acute wounds and complex nonhealing wounds and offers some insights into innovative future treatments.

Arginine metabolites in wound fluids from pressure ulcers: a pilot study.

Compelling evidence suggests that nitric oxide (NO*), a metabolite of arginine, plays an important role in wound healing. Arginine is a semi-essential amino acid that is metabolized by nitric oxide synthase and arginase. One model for wound-healing regulation suggests the importance of strict reciprocal control of these enzymes in wounds. The purpose of this pilot study was to investigate arginine metabolism in wound fluids from patients with Stage III or IV pressure ulcers receiving negative pressure wound therapy (NPWT). Wound fluids were collected from 8 patients, aged 31-79 years, before and after initiation of NPWT on Days 1, 3, and 7. Wound fluids were analyzed for nitrates/nitrites (NOx), arginine, citrulline, proline, and ornithine. There were no significant differences between NOx, arginine, citrulline, proline, and ornithine concentrations before and after initiation of NPWT among the various timepoints. However, we observed a downward trend of NO* levels from baseline to Day 7 of NPWT treatment. Furthermore, we detected a decrease in arginine levels over the study period, suggesting that the iNOS/citrulline pathway predominated during the first 72 hr of treatment, and the arginase/ ornithine pathway dominated thereafter. Arginine and its metabolites are detectable in wound fluids from patients with Stage III or IV pressure ulcers on NPWT. Further studies on chronic wounds are warranted to correlate wound-healing outcomes with arginine metabolites at the cellular and molecular level over a longer period of time.

Nutritional formula improved immune profiles of seniors living in nursing homes.

OBJECTIVES: To assess whether an experimental nutritional formula (EXP) supports immune function in seniors living in long-term care facilities. DESIGN: Prospective, randomized, double-blind, controlled trial conducted September 2002 through January 2003. SETTING: North central Florida nursing homes. PARTICIPANTS: Subjects aged 65 and older (n = 157). INTERVENTION: Subjects received 240 mL/d of EXP or standard liquid nutrition (CON) for 4 weeks before and 6 weeks after an influenza vaccination. MEASUREMENTS: Influenza vaccine antibody responses, immunophenotyping, lymphocyte activation, cytokines, and clinical measures (fever, number of prescribed antibiotics). RESULTS: Ninety-two subjects (n = 40, CON; n = 52, EXP) completed the study. Geometric mean antibody titers were similar between groups, yet the percentage of subjects with H1N1 antibody titers greater than 100 postvaccination was higher in the EXP group than in the CON group (43% vs 23%, P=.047). Similar trends were found for the percentage of subjects (intent to treat) with fourfold increases against the B/Hong Kong component (64% vs 46%, P = .09) or with H3N2 antibody titers of 40 or more (97% vs 89%, P=.06). EXP subjects had higher levels of influenza-activated lymphocytes (CD69+ and CD25+). Cytokine production after mitogen activation was lower in EXP than CON subjects (interleukin (IL)-6: 20+/-3 vs 29+/-3 ng/mL, P = .045; IL-10: 310+/-60 vs 603+/-140 pg/mL, P = .06). Fewer EXP subjects were treated for fever (5% vs 16%, P = .02) or prescribed antibiotics (7 vs 11 new antibiotics/100 days of study, P = .06). CONCLUSION: Seniors consuming the EXP formula demonstrated enhanced immune function, indicated by increased influenza vaccine response and lymphocyte activation, less fever, and fewer newly prescribed antibiotics than those consuming a standard ready-to-drink nutritional supplement.

Arginine supplementation and wound healing.

Modern advances in nutritional therapies have led to the specific use of arginine supplementation for protein synthesis, cell signaling through the production of nitric oxide, and cell proliferation through its metabolism to ornithine and to polyamines. Arginine is classified as a nonessential amino acid that becomes a conditionally essential substrate in stressed adults. Arginine has been shown to enhance wound strength and collagen deposition in artificial incisional wounds in rodents and humans. A role for dietary intervention in the form of arginine supplementation has been proposed to normalize or enhance wound healing in humans. Although this hypothesis is frequently discussed, the therapeutic effect of arginine supplementation on chronic wound healing in humans is still undetermined and requires further objective evidence. Well-designed clinical trials are required to determine whether arginine supplementation is effective in enhancing healing of acute and chronic wounds in humans and how much arginine is recommended to meet metabolic needs during the phases of wound healing.

Mini nutritional assessment and screening scores are associated with nutritional indicators in elderly people with pressure ulcers.

OBJECTIVE: To determine the association between the Mini Nutritional Assessment (MNA) or MNA Screening Form and standard indicators of nutritional status in male elders with pressure ulcers. DESIGN: Cross-sectional study. MNA and MNA Screening Form scores were related to nutritional indicators using the Pearson correlation. SUBJECTS/SETTING: Residents (79+/-1 years, N=23 men) of Veterans Affairs medical center nursing home care units with stage I to IV pressure ulcers were enrolled. MAIN OUTCOME MEASURES: Correlation coefficients were obtained from correlations between the MNA or MNA Screening Form scores and biochemical and anthropometric indices of nutritional status or measures of body composition normalized for height by dividing by height in meters(2). RESULTS: Hemoglobin (106+/-4 g/L; r=0.43, P=.0409, mean, standard error of the mean, Pearson's r, P value), hematocrit (0.32+/-0.01; r=0.44, P=.0358), body mass index (23.1+/-1.0; r=0.66, P=.0006), calf circumference (30.4+/-1.1 cm; r=0.46, P=.0286), fat-free mass index (18.3+/-0; r=0.60, P=.0063), body cell mass index (8.3+/-0.5; r=0.64, P=.0033), and fat mass index (3.7+/-0.4; r=0.50, P=.0275) positively correlated with MNA score. Serum albumin (31+/-1 g/L) and prealbumin (180+/-17 mg/L) did not correlate with MNA, but prealbumin inversely correlated with erythrocyte sedimentation rate (r=-0.52, P=.0134), a marker of inflammation. The inverse correlation between albumin and erythrocyte sedimentation rate approached statistical significance (r=-0.42, P=.0542). The MNA Screening Form showed similar correlations or lack of correlations observed with the MNA with the exception of hemoglobin and hematocrit. CONCLUSIONS: The MNA and MNA Screening Form provide advantages over using visceral proteins in screening and assessing nutritional status of elderly people with pressure ulcers.

Arginine supplementation does not enhance serum nitric oxide levels in elderly nursing home residents with pressure ulcers.

The purpose of this study was to determine whether arginine supplementation enhances in vitro (neutrophil burst and mitogen-induced lymphocyte proliferation) and in vivo (delayed-type hypersensitivity [DTH] and serum nitric oxide) measures of immune function in nursing home elders with pressure ulcers. Twenty-six elders, 65 years of age or older, with one or more pressure ulcers, were randomized to receive 8.5 g of arginine or an isonitrogenous supplement for 4 weeks. Immune function studies and serum arginine, ornithine, citrulline, and nitric oxide were measured at baseline, 4 weeks postsupplementation (Week 4) and after a 6-week washout (Week 10). At Week 4, serum ornithine increased (p = .01) and arginine trended to increase (p = .055), but there was no increase in citrulline or nitric oxide with arginine supplementation. There were no differences in neutrophil burst or DTH responses between groups. Whole blood mitogen-induced proliferation decreased significantly at Week 10 in the isonitrogenous but not in the arginine-supplemented group. There is mounting concern that arginine supplementation during an inflammatory state could be detrimental due to overwhelming nitric oxide production. A key finding of this study is that arginine supplementation did not increase serum nitric oxide levels over that observed in elders with pressure ulcers given an isonitrogenous supplement.

Immune function is impaired with a mini nutritional assessment score indicative of malnutrition in nursing home elders with pressure ulcers.

BACKGROUND: Malnutrition is prevalent in elders with pressure ulcers and is associated with increased morbidity and mortality. This study compared nutritional status, assessed by the Mini Nutrition Assessment (MNA), to immune function in nursing home elders with pressure ulcers. METHODS: Nutritional status was assessed in nursing home residents (>65 years) with a stage II or more severe pressure ulcer. Subjects were classified as well nourished, at risk of malnutrition, or malnourished according to MNA score. Blood was drawn to assess whole blood mitogen-induced lymphocyte proliferation and neutrophil respiratory burst. Delayed-type hypersensitivity to 3 antigens was measured. MNA status was compared with immune parameters using the Kruskall-Wallis test. RESULTS: Of the 24 subjects (23 men, 1 woman) who completed the study protocol, only 4 (17%) were classified as well nourished, whereas 7 (29%) were at risk and 13 (54%) were malnourished according to MNA score. Whole blood lymphocyte proliferation was significantly lower in the malnourished vs at risk subjects with both pokeweed (median [25th, 75th percentile], 0.6 [0.3, 0.9] vs 1.8 [1.2, 2.1] disintegrations per minute [dpm]/cell, p < .05); and concanavalin A (1.7 [0.9, 2.0] vs 2.8 [2.6, 3.9] dpm/cell, p < .05) mitogens. Neutrophil respiratory burst normalized to a young control was significantly lower in malnourished subjects vs well-nourished subjects (0.8 [0.5, 0.9] vs 1.4 [1.0, 1.7], p < .05). Total induration to 3 skin-test antigens was 13.4 +/- 4.6, 3.5 +/- 2.6, and 3.8 +/- 1.8 (mean +/- SEM) for well-nourished, at risk, and malnourished, respectively (p = .059). CONCLUSIONS: Immune function is impaired with an MNA score indicative of malnutrition in nursing home elders with pressure ulcers.

Arginine immunonutrition in critically ill patients: a clinical dilemma.

Commercial enteral nutritional formulas for enhancement of the immune system are widely used in critical care. Immunonutrition with arginine can enhance inflammatory and immunologic responses in animal models and in humans. Although clinical improvements in surgical patients have been reported, benefits in critically ill patients with systemic inflammatory response syndrome, sepsis, or organ failure are less clear. Recent meta-analyses on the use of immunonutrition with arginine in critically ill and surgical patients revealed methodological weaknesses in most published studies. Specifically, a meta-analysis indicated that critically ill patients with preexisting severe sepsis may have an increased mortality rate when fed an immunonutritional enteral formula that contains arginine. These findings brought about confusion and controversy over the use of immunonutritional formulas in subsets of critically ill patients. A review of the literature on the function of arginine, its effect on the immune system, its roles in immunonutrition and in the clinical outcomes of critically ill patients, and the implications for nursing practice indicated that the benefits of immunonutrition with arginine in critically ill patients are unproven and warrant further study. Until more information is available, nutritional support should focus primarily on preventing nutritional deficiencies rather than on immunomodulation.

Nutritional formula enhanced immune function and reduced days of symptoms of upper respiratory tract infection in seniors.

OBJECTIVES: To assess whether an experimental nutritional formula, given as a supplement, would reduce days of symptoms of upper respiratory tract infection (URTI) and affect antibody and lymphocyte proliferative responses to influenza vaccine. DESIGN: A prospective, randomized, double-blind, controlled trial was conducted between October 1999 and April 2000. SETTING: Assisted- and independent-living facilities in North Central Florida. PARTICIPANTS: Sixty-six individuals, aged 65 and older. INTERVENTION: Subjects received 8 oz/d of an experimental formula containing antioxidants, zinc, selenium, fermentable oligosaccharides, and structured triacylglycerol or an isoenergetic, isonitrogenous control formula for 183 days. MEASUREMENTS: Subjects recorded daily symptoms of URTI. Antibody titers and lymphocyte proliferation to three influenza vaccine components were measured on Days 57 and 183. RESULTS: Eighteen subjects in the control group and 16 subjects in the experimental group consumed an average of 7 ounces of formula daily and completed the 183-day study. Median days of symptoms of URTI were 3 (range 0-69, total days=156) and 0 (range 0-49, total days=78) for the control and experimental groups, respectively (P=.049). On Day 57, seven of 17 (41%) subjects in the control group and 13 of 15 (87%) subjects in the experimental group achieved a fourfold or greater increase in serum antibody titer to A/Beijing (P=.012). Lymphocyte proliferation to influenza vaccine components was greater in the experimental (median=1,365 cpm, range=0-14,955 cpm) than the control group (median=136 cpm, range=0-4,270 cpm) (P=.013). CONCLUSION: Subjects consuming an experimental nutritional formula experienced enhanced immune function and fewer days of URTI symptoms.

Early nutritional screening of older adults: review of nutritional support.

Protein-energy malnutrition and its consequences can have considerable impact on the quality of life of the elderly. Healthcare providers working with older adults are challenged to recognize individuals at risk for undernutrition and to initiate early nutritional assessment and intervention strategies to prevent malnutrition. In so doing, they can assist in improving the quality of life for the older adult and decrease healthcare costs associated with serious outcomes of malnutrition. Current knowledge about the nutritional needs of the elderly, definition of malnutrition, age-related risk factors, and causes of malnutrition in the elderly are presented in this article. A practical approach to preventing the occurrence of malnutrition is suggested through the use of a quick and easy nutritional screening assessment tool, the Mini Nutritional Assessment (MNA). Recommendations for specialized nutritional support, as well as its role in wound healing and immune enhancement, are discussed. Where available, scientific data supporting its use are included.

The nursing shortage in acute and critical care settings.

The nursing shortage is seriously challenging hospitals to provide safe, quality care to acute and critically ill patients. Most frequently reported are the registered nurse (RN) shortages in intensive care units (ICUs) and step-down units. Issues surrounding the nursing shortage are multifaceted and require comprehensive solutions. Although work place conditions are typically cited as the leading cause of the shortages, other factors, including a rapidly aging RN workforce, have been implicated. Furthermore, fewer young people are choosing nursing as a career and graduating classes of RNs are decreasing in size. Remedies for the acute and critical care nursing shortage will require highly innovative initiatives and multiple long-term strategies focused on forces driving the growing nursing shortage. One solution to workplace issues may lie in the philosophy of the Magnet Hospital program. The advanced practice nurse can play a significant role in providing leadership in addressing factors and designing comprehensive and innovative strategies directed at recruitment and retention of RNs in acute and critical care settings.

Role of nitric oxide in wound healing.

Chronic wounds mainly affect elderly individuals and persons with comorbid diseases due to a compromised immune status. An age-related decline in immune function deters proper healing of wounds in an orderly and timely manner. Thus, older adults with 1 or more concomitant illnesses are more likely to experience and sufferfrom a nonhealing wound, which may drastically decrease their quality of life and financial resources. Novel therapies in wound care management rely heavily on our current knowledge of wound healing physiology. It is well established that normal wound healing occurs sequentially and is strictly regulated by pro-inflammatory cytokines and growth factors. A multitude of commercial products such as growth factors are available; however, their effectiveness in healing chronic wounds has yet to be proven. Recently, investigators have implicated nitric oxide (NO) in the exertion of regulatoryforces on various cellular activities of the inflammatory and proliferative phases of wound healing. Gene therapy in animal studies has shown promising results and is furthering our understanding of impaired wound healing. The purpose of this article is to review the literature on NO and its role in wound healing. A discussion of the physiology of normal healing and the pathophysiology of chronic wounds is provided.