Reba Umberger

Nursing Genomics: Practice Implications Every Nurse Should Know

Twenty-first century nurse clinicians, scientists, and educators must be informed of and become proficient in genetic competencies to provide the best available evidenced-based patient care. This article presents a historical context and basic applications of genetics, along with the attendant legal and ethical issues, to provide a framework for understanding genetics and the genomics applications used in clinical nursing practice. The implications of genomics are relevant to all areas of nursing practice, including risk assessment, education, clinical management, and future research.

Inter-individual variability of plasma PAF-acetylhydrolase activity in ARDS patients and PAFAH genotype

Background:  Platelet activating factor (PAF), a pro‐inflammatory phospholipid, stimulates cytokine secretion from polymorphonuclear leukocytes expressing the transmembrane G‐protein coupled PAF receptor. Elevated PAF levels are associated with acute respiratory distress syndrome (ARDS) and sepsis severity. The pro‐inflammatory effects of PAF are terminated by PAF acetylhydrolase (PAF‐AH).

Corticosteroid treatment in severe community-acquired pneumonia: duration of treatment affects control of systemic inflammation and clinical improvement

Dear Editor, In a preliminary randomized trial of patients with severe communityacquired pneumonia (CAP), we reported that glucocorticoid treatment was associated with attenuation of systemic inflammation and improvement in pulmonary and extrapulmonary organ dysfunction [1]. Response to glucocorticoid treatment—ineffective, effective, or toxic—is influenced by drug dosage and duration of administration. In CAP, the effect of duration of glucocorticoid treatment on systemic inflammation and clinical outcome is unknown. We hypothesized that longer duration of treatment prevents rebound systemic inflammation and clinical deterioration. We conducted a post hoc analysis of 51 patients meeting American Thoracic Society criteria for severe pneumonia [2] recruited in two separate randomized trials [3, 4]. CAP patients with acute respiratory distress syndrome (ARDS) received methylprednisolone (1 mg/kg/day) for more than 21 days [3], patients without ARDS received hydrocortisone (240 mg/day) for 7 days [4]. Patients receiving glucocorticoids [methyprednisolone (n = 18) and hydrocortisone (n = 15)] were compared to placebo (n = 18). Baseline characteristics were similar between the two groups, with the exception of a higher proportion of patients requiring mechanical ventilation in the steroid group (97 vs. 78%; p = 0.05). As shown in Fig. 1, by study day 7, those randomized to glucocorticoids had significant improvements in C-reactive protein (CRP) levels, a higher proportion of extubated patients (64 vs. 28%; p = 0.02), a lower multiple organ dysfunction syndrome (MODS) score (0.66 ± 1 vs. 1.4 ± 1; p = 0.05), and a non-significant change in mortality (7 vs. 22%; p = 0.17). The extubation rate was similar in the methylprednisolone and hydrocortisone group (61 vs. 67%). After discontinuation of hydrocortisone treatment, 7 (44%) patients had rebound systemic inflammation (threeto fivefold increase in CRP) and associated clinical deterioration (3 had worsening MODS and 3 required re-intubation). To the contrary, continuation of methylprednisolone treatment was associated with a sustained antiinflammatory effect without re-exacerbation of respiratory failure. Overall treatment was associated with reduction in median (IQR) duration of mechanical ventilation [5.5 (4.5) vs. 10.0 (6.0); p = 0.05] but no significant change in duration of hospital stay [11.0 (9.0) vs. 15.5 (16.0); p = 0.43] or intensive care unit (ICU) survival (82 vs. 72%; p = 0.49). Our findings, in agreement with the recent literature for patients without CAP [5], indicate that the initial biological and physiological benefits observed during glucocorticoid administration may be lost if discontinuation of treatment is not preceded by slow tapering. For this reason a recent consensus statement [5] recommended that glucocorticoid

Effect of Zafirlukast on Methacholine and Ultrasonically Nebulized Distilled Water Challenge in Patients with Mild Asthma

Background: Bronchial asthma is a chronic inflammatory disease characterized by airway inflammation and hyperresponsiveness due to the release of multiple mediators, such as cysteinyl-leukotrienes (cys-LTs). Objective: Our study was designed to investigate whether oral pretreatment with zafirlukast (a cys-LTs receptor antagonist) reduces bronchoconstriction against methacholine (MC) and ultrasonically nebulized distilled water (UNDW) challenge in patients with mild asthma. Methods: Fourteen non-atopic patients (8 males, 20–42 years, forced expiratory volume in 1 s (FEV1) 97% SD ± 0.4) with mild, intermittent bronchial asthma performed a sequential weekly pulmonary function test following challenge with MC or UNDW 2 h after zafirlukast or placebo administration, according to a single-blind method. Results: We found that pretreatment with zafirlukast significantly decreased bronchoconstriction MC (maximum FEV1 drop –10.75% SD ± 1.89, p < 0.001) and UNDW induced (maximum FEV1 drop –12% SD ± 0.15, p < 0.001), while pretreatment with placebo did not protect patients against FEV1 drop following MC (maximum FEV1 drop –33.22% SD ± 1.42, p < 0.001) and UNDW challenge (maximum FEV1 drop –30.02% SD ± 0.4, p < 0.001). Conclusions: Pretreatment with zafirlukast significantly reduced bronchoconstriction against MC and UNDW challenge in individuals with mild intermittent asthma, indicating that cys-LTs receptor antagonists might be useful as preventive therapy in these patients population.

Exaggerated plasma interleukin 6, interleukin 10, and subsequent development of health care-associated infections in patients with sepsis

Background: Health care–associated infections (HAIs) are the target of many well-known preventive measures in the intensive care unit (ICU); however, little is known about post–sepsis-induced immunosuppression. Objectives: This study explores the relationship between baseline plasma levels of inflammatory cytokines interleukin 6 (IL-6), IL-10, and IL-6:IL-10 and subsequent development of HAIs in patients with admitted with sepsis. Methods: Prospective observational study was conducted among veterans admitted to the ICU with sepsis and monitored daily through ICU discharge (up to 28 days) to investigate HAI development. Baseline plasma IL-6 and IL-10 levels were measured with a multiplex bead based assay. Exaggerated systemic inflammation was defined as the fourth quartile (IL-6 and IL-10) compared with other quartiles. Results: We recruited 78 patients over 18 months, primarily older (65.5 ± 12.6 years) men (94.9%) with underlying comorbidities (93.9%) and a high severity of illness (Acute Physiologic and Chronic Health Evaluation II score 20.6 ± 6.4). Seventeen patients (21.7%) developed at least 1 HAI, and candidemia was the leading infection. Patients with exaggerated baseline systemic inflammation developed a nonsignificantly higher proportion of HAI as compared with those not developing HAI (IL-6: 31.6% vs 18.6%, P = .55; IL-10: 26.3% vs 20.3%, P = .43). Discussion: Patients with exaggerated systemic inflammation had a higher severity of illness, but not a statistically significant higher incidence of HAI. A larger, more adequately powered sample with serial cytokine measures is needed. Routine surveillance cultures are needed. Health care–associated infection may occur in the absence of fever, and the emerging incidence of Candida is a concern. Immune suppression after sepsis should be recognized as a risk for HAI development. Antibiotic therapy should be targeted with prompt de-escalation of empiric therapy per established guidelines to preserve normal flora.

Severe sepsis in older adults.

Severe sepsis may be underrecognized in older adults. Therefore, the purpose of this article is to review special considerations related to early detection of severe sepsis in older adults. Normal organ changes attributed to aging may delay early detection of sepsis at the time when interventions have the greatest potential to improve patient outcomes. Systems are reviewed for changes. For example, the cardiovascular system may have a limited or absent compensatory response to inflammation after an infectious insult, and the febrile response and recruitment of white blood cells may be blunted because of immunosenescence in aging. Three of the 4 hallmark responses (temperature, heart rate, and white blood cell count) to systemic inflammation may be diminished in older adults as compared with younger adults. It is important to consider that older adults may not always manifest the typical systemic inflammatory response syndrome. Atypical signs such as confusion, decreased appetite, and unsteady gait may occur before sepsis related organ failure. Systemic inflammatory response syndrome criteria and a comparison of organ failure criteria were reviewed. Mortality rates in sepsis and severe sepsis remain high and are often complicated by multiple organ failures. As the numbers of older adults increase, early identification and prompt treatment is crucial in improving patient outcomes.

Collection and storage of human blood and adipose for genomic analysis of clinical samples

In this methods article, we describe collection and storage of clinically acquired blood and adipose samples for transcript analysis in an ongoing study exploring obesity in renal transplant recipients. Total ribonucleic acid (RNA) was isolated from whole blood using the LeukoLOCK™ Total RNA Isolation System (n = 4), and comparisons between fresh and frozen samples were made. Abdominal subcutaneous adipose samples (n = 4) were obtained during kidney transplantation, flash frozen, and stored at -80°C. Adipose RNA was extracted using either the STAT-60 method modified for lipids or Trizol plus RNeasy extraction. Affymetrix HG-U133 plus 2.0 arrays and Affymetrix Human Gene 1.0 ST arrays were used for both blood and adipose transcriptome analysis. Purity, quality, and quantity of RNA were high with comparable results using both array platforms.

The Effect of Physical Activity on PTSD

ABSTRACT Although physical activity (PA) is known to reduce anxiety and depression, less is known about the effects of PA on post-traumatic stress disorder (PTSD). The author examined the state of the science regarding the effect of PA on PTSD. Three themes emerged: PA characteristics, added benefits of PA as a PTSD intervention, and theories on the method of action. Physical activity seems to be an effective adjunct therapy to reduce PTSD symptom severity. Findings are inconsistent between observational and controlled studies. More research is needed to identify the most effective type, dose, and duration of exercise. The primary author is responsible for review, synthesis, and analysis of the literature as well as preparation of the manuscript. The corresponding author is responsible for reviewing and editing the manuscript. All authors have reviewed the submitted manuscript and approve the manuscript for submission. SUMMARY STATEMENT Why is this review needed? • Post-traumatic stress disorder is a debilitating condition that is growing in prevalence and, if untreated or undertreated, can have significant impact on individuals, families, and ultimately the society at large.• Traditional treatment includes psychotherapy and pharmacotherapy; however, many who suffer from post-traumatic stress disorder have limited access to these treatment modalities.• The Institute of Medicine has called for research into cost-effective, complementary treatments to potentiate the traditional method of combined psychotherapy and pharmacotherapy. What are the key findings? • Physical activity has been shown to reduce symptoms of post-traumatic stress disorder in persons with subsyndromal symptoms and persons resistant to standard treatment.• Physical activity has also been shown to improve health conditions that may accompany PTSD (e.g., anxiety, depression, sleep disturbances, and cardiovascular disease). How should the findings be used to influence policy/practice/research/education? • Clinicians should include patient-specific exercise prescriptions in their plan of care for treating those with PTSD (e.g., walking program, aerobic activity, or yoga).• Interventions for persons with PTSD should extend beyond the relationship with the clinician, and include methods that motivate continued exercise.• Research should focus on the type and amount of activity that is most effective for treating persons with PTSD, including the length of time needed for optimal improvements to be maintained.

The Utility of the Candida Score in Patients With Sepsis.

Background:Candida is a leading cause of infection in the intensive care unit. Colonization versus infection remains a challenge. A Candida Score (CS) of 3 or greater has been used to target antifungal therapy in surgical patients at risk of candidemia but has not been well evaluated in medical patients with sepsis. Objectives:The aim of this study was to assess utility of the CS in detecting candidemia early in patients with sepsis. Methods:This was a secondary analysis of patients with sepsis (n = 77) who were followed up for development of new infections. Patients with known fungal infection at admission were excluded. Candida colonization was defined as Candida cultured from any baseline culture, except blood, as a part of routine clinical care. Results:Candidemia was detected in 8 of 77 participants (10.4%; 4 [15.4%] with a CS ≥3 and 4 [7.8%] with a CS <3). Demographic variables (age, race, sex) were similar among those who did and did not develop candidemia. Using the recommended CS of 3 or greater, sensitivity was (4/8) 50%, specificity was (47/69) 68.1%, positive predictive value was (4/26) 15.4%, and negative predictive value was (47/51) 92.2%. Baseline colonization was significantly higher among those who developed candidemia (50% vs 11.6%; P = .02), but no significant differences were observed among CS components or total scores. Conclusions:Despite a relatively poor sensitivity, a reasonable specificity with a strong negative predictive value makes this tool a viable option for screening medically ill patients who may require antifungal agents. The CS should be evaluated in a larger, more inclusive, medical population.

Unit-level changes in central line-associated bloodstream infection before and after implementation of the affordable care act and mandatory reporting legislation

Background: Central line–associated bloodstream infection (CLABSI) prevention efforts have increased over the past decade because of implications of the Affordable Care Act and mandatory reporting laws. These legislative measures allow for reduced reimbursement to hospitals with high level of CLABSIs and other health care–associated infections. Objective: The aim of this study was to explore the impact of legislation and mandatory reporting on CLABSI rates and reporting. Methods: The study team performed a retrospective review of medical intensive care unit patients in January 2008, 2012, and 2015 to examine changes in CLABSI reporting by 2 methods (International Classification of Diseases [ICD] by providers and Centers for Disease Control by infection prevention [IP]), as well as changes in central line use over time. Data were summarized and compared. Percent agreement and &kgr; statistics were calculated for ICD- and IP-coded CLABSIs. Results: Among 465 intensive care unit patients, most were white (89.9%), males (52.0%), aged 58.7 ± 17.1 years. Only 3 new CLABSIs were reported during the study period: 2 by ICD and IP in 2008, 1 by ICD in 2012, and 0 by either method in 2015. The percent agreement (99.6%) and &kgr; (0.799) represent excellent agreement. Central line usage was similar for each time period. Discussion: The number of CLABSIs decreased over time; however, the findings were limited, and a larger sample over a longer period is needed to draw conclusions about the influence of legislative changes. One discrepancy was observed between the 2 reporting methods, which is consistent with other studies. More research is needed to understand the complexity of provider coding practices and changes in central line use (eg, duration, type, location) over time.