A Randomized Trial of Enteral Glutamine for Treatment of Burn Injuries.

BACKGROUND: Glutamine is thought to have beneficial effects on the metabolic and stress response to severe injury. Clinical trials involving patients with burns and other critically ill patients have shown conflicting results regarding the benefits and risks of glutamine supplementation. METHODS: In a double-blind, randomized, placebo-controlled trial, we assigned patients with deep second- or third-degree burns (affecting ≥10% to ≥20% of total body-surface area, depending on age) within 72 hours after hospital admission to receive 0.5 g per kilogram of body weight per day of enterally delivered glutamine or placebo. Trial agents were given every 4 hours through a feeding tube or three or four times a day by mouth until 7 days after the last skin grafting procedure, discharge from the acute care unit, or 3 months after admission, whichever came first. The primary outcome was the time to discharge alive from the hospital, with data censored at 90 days. We calculated subdistribution hazard ratios for discharge alive, which took into account death as a competing risk. RESULTS: A total of 1209 patients with severe burns (mean burn size, 33% of total body-surface area) underwent randomization, and 1200 were included in the analysis (596 patients in the glutamine group and 604 in the placebo group). The median time to discharge alive from the hospital was 40 days (interquartile range, 24 to 87) in the glutamine group and 38 days (interquartile range, 22 to 75) in the placebo group (subdistribution hazard ratio for discharge alive, 0.91; 95% confidence interval [CI], 0.80 to 1.04; P = 0.17). Mortality at 6 months was 17.2% in the glutamine group and 16.2% in the placebo group (hazard ratio for death, 1.06; 95% CI, 0.80 to 1.41). No substantial between-group differences in serious adverse events were observed. CONCLUSIONS: In patients with severe burns, supplemental glutamine did not reduce the time to discharge alive from the hospital. (Funded by the U.S. Department of Defense and the Canadian Institutes of Health Research; RE-ENERGIZE ClinicalTrials.gov number, NCT00985205.).

Cardiac timing and threatening stimuli influence response inhibition and ex-Gaussian parameters of reaction time in a Go/No-go task.

Sensorimotor responses vary as a function of the cardiac cycle phase. These effects, known as cardiac cycle time effects, have been explained by the inhibition of cardiac afferent signals on information processing. However, the validity of cardiac cycle time effects is challenged by mixed findings. Factors such as current information processing and affective context may modulate cardiac cycle time effects and account for inconsistencies in the literature. The current study examines the influence of cardiac cycle time and threatening stimuli on two aspects of sensorimotor processing, response speed and inhibition. Thirty-four participants (Mage  = 19.35 years; 29 female) completed an auditory Go/No-go task in no face, neutral face, and fearful face conditions. Faces were presented at either cardiac diastole or systole. Participants' reaction times (RTs) during Go trials and failures in response inhibition during No-go trials were recorded. The ex-Gaussian model was fit to RT data in each condition deriving the parameters, mu (µ) and tau (τ), that indicate response speed and attentional lapses, respectively. Repeated measures ANOVA were used to analyze behavioral data. Results showed that cardiac systole prolonged µ but decreased τ, and that cardiac diastole reduced inhibition errors in the fearful face condition but not in other conditions. These findings indicate that cardiac timing differentially modulates sensory-perceptual and top-down attentional processes and cardiac timing interacts with threatening contexts to influence response inhibition. These results highlight the specificity of cardiac cycle time effects on sensorimotor processing.

"Generalized unsafety" as fear inhibition to safety signals in adults with and without childhood trauma.

The Generalized Unsafety Theory of Stress posits that low heart rate variability contributes to a perception of "generalized unsafety" (i.e., constantly perceiving oneself to be unsafe), independent of stressful events or stress-related symptomatology. We tested this claim by examining if resting heart rate variability, trait worry, posttraumatic stress symptoms, trauma history, and age of onset predicted fear inhibition, a measure of generalized unsafety. A Pavlovian discriminant conditioning paradigm was used to assess fear inhibition level by comparing eyeblink startle potentiation to a threat cue (presented with air blast) with startle potentiation to a safety signal (never presented with air blast). Survey and laboratory responses were collected from 42 adults who were 20 years old on average, 86% Women, and 76% White. Heart rate variability did not independently predict variation in fear inhibition, as hypothesized. Rather, higher levels of posttraumatic stress symptoms and greater cumulative interpersonal trauma predicted lower fear inhibition. Individuals reporting childhood trauma had higher trait worry, which predicted more severe posttraumatic stress symptoms. These findings highlight the role of attenuated inhibitory learning in stress-related symptomatology and developmentally disruptive trauma. Ability to distinguish threat from safety is a plausible biobehavioral mechanism by which adversity impacts development.

Treatment With Angiotensin II Is Associated With Rapid Blood Pressure Response and Vasopressor Sparing in Patients With Vasoplegia After Cardiac Surgery: A Post-Hoc Analysis of Angiotensin II for the Treatment of High-Output Shock (ATHOS-3) Study.

OBJECTIVE: The present study investigated outcomes in patients with vasoplegia after cardiac surgery treated with angiotensin II plus standard-of-care vasopressors. Vasoplegia is a common complication in cardiac surgery with cardiopulmonary bypass and is associated with significant morbidity and mortality. Approximately 250,000 cardiac surgeries with cardiopulmonary bypass are performed in the United States annually, with vasoplegia occurring in 20%to-27% of patients. DESIGN: Post-hoc analysis of the Angiotensin II for the Treatment of High-Output Shock (ATHOS-3) study. SETTING: Multicenter, multinational study. PARTICIPANTS: Sixteen patients with vasoplegia after cardiac surgery with cardiopulmonary bypass were enrolled. INTERVENTIONS: Angiotensin II plus standard-of-care vasopressors (n = 9) compared with placebo plus standard-of-care vasopressors (n = 7). MEASUREMENTS AND MAIN RESULTS: The primary endpoint was mean arterial pressure response (mean arterial pressure ≥75 mmHg or an increase from baseline of ≥10 mmHg at hour 3 without an increase in the dose of standard-of-care vasopressors). Vasopressor sparing and safety also were assessed. Mean arterial pressure response was achieved in 8 (88.9%) patients in the angiotensin II group compared with 0 (0%) patients in the placebo group (p = 0.0021). At hour 12, the median standard-of-care vasopressor dose had decreased from baseline by 76.5% in the angiotensin II group compared with an increase of 7.8% in the placebo group (p = 0.0013). No venous or arterial thrombotic events were reported. CONCLUSION: Patients with vasoplegia after cardiac surgery with cardiopulmonary bypass rapidly responded to angiotensin II, permitting significant vasopressor sparing.

Understanding the evolving phenotype of vascular complications in telomere biology disorders.

Vascular complications such as bleeding due to gastrointestinal telangiectatic anomalies, pulmonary arteriovenous malformations, hepatopulmonary syndrome, and retinal vessel abnormalities are being reported in patients with telomere biology disorders (TBDs) more frequently than previously described. The international clinical care consortium of telomere-associated ailments and family support group Dyskeratosis Congenita Outreach, Inc. held a workshop on vascular abnormalities in the TBDs at the National Cancer Institute in October 2017. Clinicians and basic scientists reviewed current data on vascular complications, hypotheses for the underlying biology and developed new collaborations to address the etiology and clinical management of vascular complications in TBDs.

Transfusion Requirement in Burn Care Evaluation (TRIBE): A Multicenter Randomized Prospective Trial of Blood Transfusion in Major Burn Injury.

OBJECTIVE: Our objective was to compare outcomes of a restrictive to a liberal red cell transfusion strategy in 20% or more total body surface area (TBSA) burn patients. We hypothesized that the restrictive group would have less blood stream infection (BSI), organ dysfunction, and mortality. BACKGROUND: Patients with major burns have major (>1 blood volume) transfusion requirements. Studies suggest that a restrictive blood transfusion strategy is equivalent to a liberal strategy. However, major burn injury is precluded from these studies. The optimal transfusion strategy in major burn injury is thus needed but remains unknown. METHODS: This prospective randomized multicenter trial block randomized patients to a restrictive (hemoglobin 7-8 g/dL) or liberal (hemoglobin 10-11 g/dL) transfusion strategy throughout hospitalization. Data collected included demographics, infections, transfusions, and outcomes. RESULTS: Eighteen burn centers enrolled 345 patients with 20% or more TBSA burn similar in age, TBSA burn, and inhalation injury. A total of 7054 units blood were transfused. The restrictive group received fewer blood transfusions: mean 20.3 ±â€Š32.7 units, median = 8 (interquartile range: 3, 24) versus mean 31.8 ±â€Š44.3 units, median = 16 (interquartile range: 7, 40) in the liberal group (P < 0.0001, Wilcoxon rank sum). BSI incidence, organ dysfunction, ventilator days, and time to wound healing (P > 0.05) were similar. In addition, there was no 30-day mortality difference: 9.5% restrictive versus 8.5% liberal (P = 0.892, χ test). CONCLUSIONS: A restrictive transfusion strategy halved blood product utilization. Although the restrictive strategy did not decrease BSI, mortality, or organ dysfunction in major burn injury, these outcomes were no worse than the liberal strategy (Clinicaltrials.gov identifier NCT01079247).

Incidence, prevalence, and management of MRSA bacteremia across patient populations-a review of recent developments in MRSA management and treatment.

Methicillin-resistant Staphylococcus aureus (MRSA) infection is still a major global healthcare problem. Of concern is S. aureus bacteremia, which exhibits high rates of morbidity and mortality and can cause metastatic or complicated infections such as infective endocarditis or sepsis. MRSA is responsible for most global S. aureus bacteremia cases, and compared with methicillin-sensitive S. aureus, MRSA infection is associated with poorer clinical outcomes. S. aureus virulence is affected by the unique combination of toxin and immune-modulatory gene products, which may differ by geographic location and healthcare- or community-associated acquisition. Management of S. aureus bacteremia involves timely identification of the infecting strain and source of infection, proper choice of antibiotic treatment, and robust prevention strategies. Resistance and nonsusceptibility to first-line antimicrobials combined with a lack of equally effective alternatives complicates MRSA bacteremia treatment. This review describes trends in epidemiology and factors that influence the incidence of MRSA bacteremia. Current and developing diagnostic tools, treatments, and prevention strategies are also discussed.

Update on Severe Burn Management for the Intensivist.

Thermal injury of humans causes arguably the most severe perturbations in physiology that can be experienced. These physiologic derangements start immediately and can persist in some form until months or even years after the burn wounds are healed. Burn shock, marked activation of the systemic inflammatory response, multiple-organ failure, infection, and wound failure are just a few of the insults that may require management by the intensivist. The purpose of this article is to review recent advances in the critical care management of thermally injured patients.

Gender differences in the relationship between resting heart rate variability and 24-hour blood pressure variability.

The study explored the relationship between time- and frequency-domain indices of cardiac autonomic control and 24 h blood pressure variability (BPV) in a sample of healthy men and women. Vagally mediated cardiac control was inversely related to 24 h BPV, and measures of cardiac autonomic control were better predictors of systolic BPV in men and better predictors of diastolic BPV in women. These findings may help researchers to understand the disparity in cardiovascular disease morbidity and mortality between men and women.

Evaluation of geriatric home healthcare depression assessment and care management: are OASIS-C depression requirements enough?

OBJECTIVE: Research is scarce on how depression is identified and treated among Medicare home healthcare (HHC) patients age 65+ with disability. The Centers for Medicare & Medicaid Services (CMS) recently incorporated depression screening into the OASIS-C HHC assessment. Our study objectives were to evaluate and characterize depression care management (DCM) in an HHC agency after CMS increased its depression requirements and to determine if there was an association of DCM with disability (activities of daily living [ADLs]) outcomes. METHODS: The authors conducted a retrospective chart review of 100 new Medicare HHC admissions patients age 65+ (mean age: 81.7) who screened positive for depression and had disability and multimorbidity. Clinical and administrative records were examined and descriptive analyses used. Multivariate regression analyses investigated the association of six DCM components with ADLs improvement. RESULTS: Depression was recognized in care plans of 60% of patients. Documentation of only one nurse care management activity, antidepressant use, indicated the use of evidence-based standards of depression assessment and DCM. Depression measures were not administered at discharge, recertification, or transfer. Forty percent of patients had a formal depression diagnosis by the referring physician in the chart, and 65% were receiving an antidepressant. Having a depression care plan and depression medication were significantly associated with a large ADLs improvement. CONCLUSION: Despite the association of depression care plans with patient disability improvement, inadequate compliance to evidence-based DCM was found. Medicare and HHC agencies must ensure compliance to DCM, including follow-up depression assessment for patients with positive screens.

Older Adults with Mental Disorders: What Factors Distinguish Those Who Present to Emergency Departments for Mental Health Reasons from Those Who Do Not?

OBJECTIVE: To identify among older adults with mental disorders factors associated with those who present to emergency departments (EDs) for mental health reasons versus those who do not. METHODS: The authors conducted a secondary, cross-sectional analysis of the Medical Expenditure Panel Survey (MEPS), which comprises a representative sample of the U.S. civilian noninstitutionalized population. Of the MEPS participants ages 66 and older on December 31 of the survey years 2000-2005, the analysis sample (2,757) included the 177 persons with at least one mental health ED visit and the 2,580 persons with mental disorders without such a visit. The three categories of the Andersen behavioral model for healthcare services utilization-predisposing, enabling, and need factors-were used as the theoretical framework for the independent variables. RESULTS: Logistic regression analysis indicated that four need factors (adjustment disorder [OR: 3.42], psychosis [OR: 2.68], fair perceived physical health status [OR: 2.24], and anxiety disorder [OR: 1.85]) and two predisposing characteristics (widowed and living alone [OR: 1.68] and female [OR: 1.56]) were significantly associated with older adults with mental disorders who present to an ED for mental health reasons. Good perceived mental health status (OR: 0.55) was protective against presenting to an ED. CONCLUSION: EDs that serve populations with higher proportions of older persons that are women, widowed and living alone, with adjustment disorder, psychosis, anxiety disorders, or fair perceived physical health should expect to have a greater likelihood of older persons visiting the ED for mental health reasons.

An open-label, pragmatic, randomized controlled clinical trial to evaluate the comparative effectiveness of daptomycin versus vancomycin for the treatment of complicated skin and skin structure infection.

BACKGROUND: Treatment of complicated skin and skin structure infection (cSSSI) places a tremendous burden on the health care system. Understanding relative resource utilization associated with different antimicrobials is important for decision making by patients, health care providers, and payers. METHODS: The authors conducted an open-label, pragmatic, randomized (1:1) clinical study (N = 250) to compare the effectiveness of daptomycin with that of vancomycin for treatment of patients hospitalized with cSSSI caused by suspected or documented methicillin-resistant Staphylococcus aureus infection. The primary study end point was infection-related length of stay (IRLOS). Secondary end points included health care resource utilization, cost, clinical response, and patient-reported outcomes. Patient assessments were performed daily until the end of antibiotic therapy or until hospital discharge, and at 14 days and 30 days after discharge. RESULTS: No difference was found for IRLOS, total LOS, and total inpatient cost between cohorts. Hospital LOS contributed 85.9% to the total hospitalization cost, compared with 6.4% for drug costs. Daptomycin showed a nonsignificant trend toward a higher clinical success rate, compared with vancomycin, at treatment days 2 and 3. In the multivariate analyses, vancomycin was associated with a lower likelihood of day 2 clinical success (odds ratio [OR] = 0.498, 95% confidence interval [CI], 0.249-0.997; P < 0.05). CONCLUSION: This study did not provide conclusive evidence of the superiority of one treatment over the other in terms of clinical, economic, or patient outcomes. The data suggest that physician and patient preference, rather than drug acquisition cost, should be the primary driver of initial antibiotic selection for hospitalized patients with cSSSI. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01419184 (Date: August 16, 2011).

Evaluation of filtering methods for acquiring radial intra-artery blood pressure waveforms.

The methods for evaluating noninvasive blood pressure (NIBP) monitors using an intra-arterial reference are detailed in the ANSI/AAMI/ISO 81060-2:2009 standard. In a recent study, GE Healthcare obtained invasive radial arterial blood pressure waveforms. The work presented here describes the development of filtering strategies for obtaining high fidelity intra-arterial pressure waveforms for NIBP accuracy testing using the 81060-2 standard. The natural frequency and damping factor of each subject-catheter-transducer system was computed from fast-flush transients. These parameters were used to construct filters for removing or reducing resonance artifacts. Additionally, new optimal damping factors were evaluated for designing compensation filters. Theoretical measurement systems using actual damping factors (< 0.4) and natural frequencies were found capable of generating significant systolic resonance artifacts (≥ 8 mmHg). Typical filters that may be standardly available in monitoring equipment were observed to be potentially inadequate in removing resonance artifact. Filters with particular optimal damping factors (0.6-0.7) were effective in removing resonance artifact. Clinicians need to understand that resonance artifacts potentially exist in intra-arterial waveforms and that the adjustments of monitoring systems may not be adequate. Optimal filters for obtaining intra-arterial waveforms should take into account the damping factor and natural frequency of the measuring system. In research and device evaluation studies it is necessary that optimal filtering be done to minimize the effects of under-damping.

Using Rasch Analysis to Evaluate Accuracy of Individual Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) for Disability Measurement.

Our study objectives were to examine the accuracy of individual activities of daily living (ADLs) and instrumental ADLs (IADLs) for disability measurement, and determine whether dependence or difficulty is more useful for disability measurement. We analyzed data from 499 patients with 2+ ADLs or 3+ IADLs who participated in a home visiting nurse intervention study, and whose function had been assessed at study baseline and 22 months. Rasch analysis was used to evaluate accuracy of 24 individual ADL and IADL items. The individual items differed in the amount of information provided in measuring functional disability along the range of disability, providing much more information in (usually) one part of the range. While nearly all of the Item Information Curves (IICs) for the ADL dependence, IADL difficulty, and IADL dependence items were unimodal with one information peak each, the IICs for ADL difficulty exhibited a bimodal pattern with two peaks. Which of the individual items performed better in disability measurement varied by the extent of functional disability (i.e., by how disabled the patients were). The information peaks of most ADLs and many IADLs rise or drop steeply in a relatively short distance. Thus, whether dependence or difficulty is superior often changes very quickly along the disability continuum. There was considerable heterogeneity in which individual items provided the most and the least information at the three points of interest examined across the disability range (-2 SD units, mean, +2 SD units). While the disability region (low, medium, and high disability) for which each individual item provided the most information remained quite stable between baseline and 22 months for ADL difficulty, IADL difficulty, and IADL dependence, relatively large shifts occurred for ADL dependence items. At the disability mean dependence items offered more information for assessment than difficulty. While ADLs also provided more information at -2 and +2 SD units, there was more heterogeneity at these points for IADLs, with little difference between dependence and difficulty assessment for some IADLs.

Longitudinal prevalence and correlates of elder mistreatment among older adults receiving home visiting nursing.

The objectives of this study were to identify elder mistreatment (EM) prevalence among a cohort of older adults receiving visiting nurse care in their homes, determine EM subtypes, and identify factors associated with EM. EM data were collected by nurses during monthly home visits for up to 24 months. It took the nurses a mean of 10.5 visits to discern EM. Fifty-four (7.4%) of 724 patients were identified as mistreated, of which 33 had enough information to subtype the EM. Of these 33, 27 were victims of neglect, 16 of psychological abuse, and 10 of financial exploitation, and 17 suffered more than one type. Among the entire sample, 11 variables were positively correlated with EM presence. Nurses visiting older adults in their homes should be aware that their patients are, as a group, vulnerable to EM, and that the factors identified here may be specific markers of greater risk.

Do disabled elderly Medicare beneficiaries with major depression make less use of a consumer-directed home care voucher benefit?

Older adults with major depression may underutilize consumer-directed long-term care. Systematic underutilization would create disparities in outcomes, undermining program effectiveness. The Medicare Primary and Consumer-Directed Care Demonstration included a consumer-directed indemnity benefit that paid for goods and services not financed by traditional Medicare. Overall and for most categories of goods and services there was little difference in use and expenditures between those with and without major depression. However, among those using the benefit to hire in-home workers, arguably the most important consumer-directed purchase, average spending for workers was about 30% lower for depressed persons. While our findings are generally reassuring for public policy, future research is needed to verify that major depression is associated with less spending on in-home workers.

Personality facets and all-cause mortality among Medicare patients aged 66 to 102 years: a follow-on study of Weiss and Costa (2005).

OBJECTIVE: To investigate associations between personality facets and survival during an 8-year follow-up. METHODS: In 597 Medicare recipients (age, 66-102 years) followed up for approximately 8 years, personality domains and facets were assessed using the Revised NEO Personality Inventory (NEO-PI-R). This study builds on a previous study which used proportional hazards regression to test whether the NEO-PI-R factor and selected facet scores were associated with mortality risk. That study revealed that the neuroticism facet impulsiveness, agreeableness facet straightforwardness, and conscientiousness facet self-discipline were related to lower risk during 4 years of follow-up. We extended the follow-up period by 4 years, examined all 30 facets, and used accelerated failure time modeling as an additional analytic approach. Unlike proportional hazards regression, accelerated failure time modeling permits inferences about the median survival length conferred by predictors. Each facet was tested in a model that included health-related covariates and NEO-PI-R factor scores for dimensions that did not include that facet. RESULTS: Over the 8-year follow-up period, impulsiveness was not significant, each standard deviation of straightforwardness was associated with an 11% increase in median survival time and, when dichotomized, higher self-discipline was associated with a 34% increase in median survival time. Each standard deviation of altruism, compliance, tender-mindedness, and openness to fantasy was associated with a 9% to 11% increase in median survival time. CONCLUSIONS: After extending the follow-up period from 4 to 8 years, self-discipline remained a powerful predictor of survival and facets associated with imagination, generosity, and higher-quality interpersonal interactions become increasingly important.

Effects of a home visiting nurse intervention versus care as usual on individual activities of daily living: a secondary analysis of a randomized controlled trial.

BACKGROUND: Home visiting nurses (HVNs) have long been part of home and community-based care interventions designed to meet the needs of functionally declining older adults. However, only one of the studies including HVNs that have demonstrated successful impacts on Activities of Daily Living (ADL) has reported how those interventions affected individual ADLs such as bathing, instead reporting the effect on means of various ADL indices and scales. Reporting impacts on means is insufficient since the same mean can consist of many different combinations of individual ADL impairments. The purpose of our study was to identify which individual ADLs were affected by a specific HVN intervention. METHODS: This is a secondary analysis comparing two arms of a randomized controlled study that enrolled Medicare patients (mean age = 76.8 years; 70% female) with considerable ADL impairment. At baseline difficulty with individual ADLs ranged from a low of 16.0% with eating to a high of 78.0% with walking. Through monthly home visits, the HVN focused on empowering patients and using behavior change approaches to facilitate chronic disease self-management. Three categories of analyses were used to compare difficulty with and dependence in 6 individual ADLs between the HVN (n = 237) and care as usual (n = 262) groups (total N = 499) at 22 months after study entry: (1) unadjusted analyses that strictly depend on random assignment, (2) multinomial logistic regression analyses adjusting for baseline risk factors, and (3) multinomial regression analyses that include variables reporting post-randomization healthcare use as well as the baseline risk factors. RESULTS: Compared to care as usual, patients receiving the HVN intervention had less difficulty performing bathing at 22 months. However, there were no effects for difficulty performing the other 5 ADLs. While no effects were found for lower levels of dependence for any ADLs, impacts were detected for the most dependent levels of 4 ADLs: patients experienced less dependence in walking and transferring, a substitution effect for toileting, and more dependence in eating. CONCLUSIONS: Future research is needed to confirm these findings and determine how HVN interventions affect individual ADLs of older adults with multiple ADLs.

Medicare home health care patient case-mix before and after the Balanced Budget Act of 1997: effect on dual eligible beneficiaries.

The Balanced Budget Act (BBA) of 1997 changed the payment system for Medicare home health care (HHC) from cost-based to prospective reimbursement. We used Medical Expenditure Panel Survey data to assess the impact of the BBA on Medicare HHC patient case-mix measured by the Centers for Medicare and Medicaid Services Hierarchical Condition Categories (CMS-HCC) model. There was a significant increase in Medicare HHC patient case-mix between the pre-BBA and Prospective Payment System (PPS) periods. The increase in the standardized-predicted risk score from the Interim Payment System period to PPS was nearly 4 times greater for the dual eligibles (Medicare-Medicaid) than for the Medicare-only population. This significantly greater rise in the HHC resources required by dual eligibles as compared to nonduals could be due to a shift in HHC payers from Medicare only to Medicaid rather than be an actual increase in case-mix per se.