State of Science in Alarm System Safety: Implications for Researchers, Vendors, and Clinical Leaders.

Alarm fatigue is a complex phenomenon that needs to be assessed within the context of the clinical setting. Considering that complexity, the available information on how to address alarm fatigue and improve alarm system safety is relatively scarce. This article summarizes the state of science in alarm system safety based on the eight dimensions of a sociotechnical model for studying health information technology in complex adaptive healthcare systems. The summary and recommendations were guided by available systematic reviews on the topic, interventional studies published between January 2019 and February 2022, and recommendations and evidence-based practice interventions published by professional organizations. The current article suggests implications to help researchers respond to the gap in science related to alarm safety, help vendors design safe monitoring systems, and help clinical leaders apply evidence-based strategies to improve alarm safety in their settings. Physiologic monitors in intensive care units-the devices most commonly used in complex care environments and associated with the highest number of alarms and deaths-are the focus of the current work.

Improving the Safety, Effectiveness, and Efficiency of Clinical Alarm Systems: Simulation-Based Usability Testing of Physiologic Monitors.

BACKGROUND: Clinical alarm system safety is a national patient safety goal in the United States. Physiologic monitors are associated with the highest number of device alarms and alarm-related deaths. However, research involving nurses' use of physiologic monitors is rare. Hence, the identification of critical usability issues for monitors, especially those related to patient safety, is a nursing imperative. OBJECTIVE: This study examined nurses' usability of physiologic monitors in intensive care units with respect to the effectiveness and efficiency of monitor use. METHODS: In total, 30 nurses from 4 adult intensive care units completed 40 tasks in a simulation environment. The tasks were common monitoring tasks that were crucial for appropriate monitoring and safe alarm management across four categories of competencies: admitting, transferring, and discharging patients using the monitors (7 tasks); managing measurements and monitor settings (23 tasks); performing electrocardiogram (ECG) analysis (7 tasks); and troubleshooting alarm conditions (3 tasks). The nurse-monitor interaction was video-recorded. The principal investigator and two expert intensive care units nurse educators identified, classified, and validated task success (effectiveness) and the time of task completion (efficiency). RESULTS: Among the 40 tasks, only 2 (5%) were successfully completed by all the nurses. At least 1-27 (3%-90%) nurses abandoned or did not correctly perform 38 tasks. The task with the shortest completion time was "take monitor out of standby" (mean 0:02, SD 0:01 min:s), whereas the task "record a 25 mm/s ECG strip of any of the ECG leads" had the longest completion time (mean 1:14, SD 0:32 min:s). The total time to complete 37 navigation-related tasks ranged from a minimum of 3 min 57 s to a maximum of 32 min 42 s. Regression analysis showed that it took 6 s per click or step to successfully complete a task. To understand the nurses' thought processes during monitor navigation, the authors analyzed the paths of the 2 tasks with the lowest successful completion rates, where only 13% (4/30) of the nurses correctly completed these 2 tasks. Although 30% (9/30) of the nurses accessed the correct screen first for task 1 and task 2, they could not find their way easily from there to successfully complete the 2 tasks. CONCLUSIONS: Usability testing of physiologic monitors revealed major ineffectiveness and inefficiencies in the current nurse-monitor interactions. The results indicate the potential for safety and productivity issues in completing routine tasks. Training on monitor use should include critical monitoring functions that are necessary for safe, effective, efficient, and appropriate monitoring to include knowledge of the shortest navigation path. It is imperative that vendors' future monitor designs mimic clinicians' thought processes for successful, safe, and efficient monitor navigation.

"Getting to Know Them": Person-Centered Care for Patients With Dementia in Acute Care.

Older adults with dementia are reported to have twice as many hospital stays as their age-matched counterparts without dementia. Acute care hospitals are generally not equipped to provide best care for persons with dementia. The purpose of the current qualitative study was to gain an understanding of the needs and perspectives of nursing staff and patient care technicians regarding delivering person-centered care (PCC) to patients with dementia. Nine focus groups (N = 49) were conducted. Participants discussed the importance of "getting to know them" as the basis for their care. Several themes emerged that served to support or detract from providing PCC: (a) communication, (b) education, and (c) care environment. Findings from this study support the desire of nurses and patient care technicians to provide PCC, highlight challenges, and indicate needed system-level changes to education, communication, and the care environment to support best practices. [Journal of Gerontological Nursing, 47(5), 37-44.].

Surgical Inpatient's Attitudes Toward Resident Participation: All About Expectations.

OBJECTIVE: Determine whether an educational video can improve surgical inpatients' attitudes toward resident participation in their care. METHODS: Patients admitted to the Trauma/Emergency General Surgery Service at University Hospital (San Antonio, Texas) were randomly divided into control and intervention groups. Patients in the intervention group viewed a short educational video about the role and responsibilities of medical students, residents, and attending surgeons. All patients then completed a previously published survey. RESULTS: A total of 140 patients responded to the survey (control = 81 and intervention = 59 patients). Overall, 86.4% of patients were welcoming of resident participation. Patients who were expecting residents to be involved in their care had attitudes that are more favorable on almost all survey questions regardless of their study condition. However, patients in the intervention group who expected resident involvement in their care had more favorable attitudes about senior residents (postgraduate year 3-5) assisting in routine or complicated surgery than those in the control group who were expecting resident involvement (both p ≤ 0.001). This same group of patients also had more favorable attitudes about surgical outcomes and overall surgical health when residents are involved (p = 0.004, p = 0.001, respectively). Most patients (79%) said they had no residents previously involved in their care, or they were unsure if residents were previously involved. CONCLUSIONS: Patient expectation of resident involvement is one of the most important factors influencing perceptions of inpatients about resident participation in surgery. Our goal should be early and frequent discussion with patients about resident involvement in order to foster an atmosphere of trust, including full transparency regarding resident involvement in surgical procedures. An educational video may help introduce the roles of trainees and attending surgeons but should not be used in lieu of direct discussion with patients.

Synthetic nucleic acid antibody prophylaxis confers rapid and durable protective immunity against Zika virus challenge.

Significant concerns have arisen over the past 3 y from the increased global spread of the mosquito-borne flavivirus, Zika. Accompanying this spread has been an increase in cases of the devastating birth defect microcephaly as well as of Guillain-Barré syndrome in adults in many affected countries. Currently there is no vaccine or therapy for this infection; however, we sought to develop a combination approach that provides more rapid and durable protection than traditional vaccination alone. A novel immune-based prophylaxis/therapy strategy entailing the facilitated delivery of a synthetic DNA consensus prME vaccine along with DNA-encoded anti-ZIKV envelope monoclonal antibodies (dMAb) were developed and evaluated for antiviral efficacy. This immediate and persistent protection strategy confers the ability to overcome shortcomings inherent with conventional active vaccination or passive immunotherapy. A collection of novel dMAbs were developed which were potent against ZIKV and could be expressed in serum within 24-48 h of in vivo administration. The DNA vaccine, from a previous development, was potent after adaptive immunity was developed, protecting against infection, brain and testes pathology in relevant mouse challenge models and in an NHP challenge. Delivery of potent dMAbs protected mice from the same murine viral challenge within days of delivery. Combined injection of dMAb and the DNA vaccine afforded rapid and long-lived protection in this challenge model, providing an important demonstration of the advantage of this synergistic approach to pandemic outbreaks.

Developing, Implementing, and Evaluating a Multimedia Patient Decision Aid Program to Reform the Informed Consent Process of a Peripherally Inserted Central Venous Catheter Procedure: Protocol for Quality Improvement.

BACKGROUND: Informed consent has considerable clinical, ethical, and legal implications for patient safety and liability. Little information is available about the use of multimedia patient decision aids (PtDA) in the consent process for therapeutic invasive procedures such as the peripherally inserted central venous catheter (PICC). In addition, none of the available studies have designed their multimedia PtDAs based on the Agency for Healthcare Research and Quality's (AHRQ) comprehensive guide for informed consent. OBJECTIVE: This paper describes a patient-centered, systematic, multidisciplinary approach to develop, implement, and alpha test a multimedia PtDA to reform the informed consent process of a PICC for patients in 10 acute and intensive care units. METHODS: The development, implementation, and evaluation processes of the PtDA followed the phases in the Multimedia Production Framework: preproduction, production, and postproduction. Within this framework, we applied the criteria for judging the quality of PtDAs, the AHRQ's Health Literacy Universal Precautions Toolkit, and the AHRQ's Patient Education Materials Assessment Tool Guide. The methodology was guided by the Interprofessional Shared Decision-Making Model and the AHRQ's Making Informed Consent an Informed Choice guide. In the preproduction phase, we (1) reviewed the current consent form; (2) observed 18 consent processes; (3) surveyed the vascular access team (N=6 nurses) about their perception of the current process; (4) surveyed 30 patients for knowledge recall and retention, overall satisfaction, and attitude toward using a multimedia PtDA; and (5) wrote and reviewed the script for the multimedia program. The production phase focused on filming the PtDA in English and Spanish languages. The postproduction phase included integrating the multimedia programs into the care processes, developing a modified workflow for the consent process, and alpha testing of the English and Spanish PtDAs by (1) a group of 5 patients for clarity and understandability of the information; (2) nurses using the AHRQ's Patient Education Materials Assessment Tool Audio and Video; and (3) by the multidisciplinary change team. RESULTS: Based on the alpha testing, patients indicated that the content was easy to follow and read; nurses provided positive feedback, and their comments were mainly related to the changes in the workflow in the consent process of the PICC after using the PtDA; and the multidisciplinary change team suggested edits related to changing a few scenes. The final multimedia program consisted of 7 min and 37 s demonstrating detailed information about the PICC. CONCLUSIONS: A systematic development of PtDAs for nonurgent invasive procedures may eliminate many limitations of the conventional consent process by ensuring comprehensive, standardized, and easy-to-comprehend information and providing sufficient time for the patients to reflect on the information. To be effective, PtDAs should follow a systematic, patient-centered, evidence-based, and rigorous approach in the development, implementation, and evaluation processes. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/10709.

Video-Based Patient Education Improves Patient Attitudes Toward Resident Participation in Outpatient Surgical Care.

OBJECTIVE: Decipher if patient attitudes toward resident participation in surgical care can be improved with patient education using a video-based modality. DESIGN: A survey using a 5-pt Likert scale was created, piloted, and distributed in general and colorectal surgery outpatient clinics that had residents involved with patient care at 2 facilities, both with control and intervention groups. The intervention group viewed a short video (∼4 min) explaining the role, education, and responsibilities of medical students, residents, and attending surgeons prior to answering the survey. SETTING: General and colorectal surgery outpatient clinics at the University of Texas Health San Antonio, Texas. PARTICIPANTS: A total of 383 responses were collected, all clinic patients were eligible. RESULTS: The majority of patients (82%) welcomed resident participation in their health care. Eighteen percent of patients did not expect residents to be involved in their care. Patients had favorable views of residents participating during their surgical procedures with 77% responding "agree" or "strongly agree" to a senior resident assisting with a complicated procedure. Patients who viewed the video versus control were less concerned with how much of the procedure the resident would perform (76% vs 86%, p = 0.010). Patients who viewed the video felt less inconvenienced (p = 0.004). CONCLUSIONS: The majority of patients are welcoming to resident participation in their surgical care but only 54% were expecting resident involvement at their clinic visit. Early explanation with an educational video of resident roles, education, and responsibilities may help bridge the gap and improve patient experience.

A Synthetic Micro-Consensus DNA Vaccine Generates Comprehensive Influenza A H3N2 Immunity and Protects Mice Against Lethal Challenge by Multiple H3N2 Viruses.

Influenza A H3N2 viruses circulate globally, leading to substantial morbidity and mortality. Commercially available, antigen-matched influenza vaccines must be updated frequently to match dynamic sequence variability in immune epitopes, especially within viral influenza A H3N2 hemagglutinin (H3). In an effort to create comprehensive immune responses against H3N2, four micro-consensus antigens were designed to mimic the sequence and antigenic diversity of H3. Synthetic plasmid DNA constructs were developed to express each micro-consensus immunogen and combined into a multi-antigen DNA vaccine cocktail, pH3HA. Facilitated delivery of pH3HA via intramuscular electroporation in mice induced comprehensive, potent humoral responses against diverse seasonal H3N2 viruses that circulated between 1968 and the present. Vaccination with pH3HA also induced an antigen-specific cellular cytokine response. Mice immunized with pH3HA were protected against lethal challenge using two distinct H3N2 viruses, highlighting the heterologous protection afforded by synthetic micro-consensus immunogens. These findings warrant further study of the DNA vaccine micro-consensus platform for broad protection against influenza viruses.

Rapid response to an emerging infectious disease - Lessons learned from development of a synthetic DNA vaccine targeting Zika virus.

Vaccines are considered one of the greatest advances in modern medicine. The global burden of numerous infectious diseases has been significantly reduced, and in some cases, effectively eradicated through the deployment of specific vaccines. However, efforts to develop effective new vaccines against infectious pathogens such as influenza, Human immunodeficiency virus (HIV), dengue virus (DENV), chikungunya virus (CHIKV), Ebola virus, and Zika virus (ZIKV) have proven challenging. Zika virus is a mosquito-vectored flavivirus responsible for periodic outbreaks of disease in Africa, Southeast Asia, and the Pacific Islands dating back over 50 years. Over this period, ZIKV infections were subclinical in most infected individuals and resulted in mild cases of fever, arthralgia, and rash in others. Concerns about ZIKV changed over the past two years, however, as outbreaks in Brazil, Central American countries, and Caribbean islands revealed novel aspects of infection including vertical and sexual transmission modes. Cases have been reported showing dramatic neurological pathologies including microcephaly and other neurodevelopmental problems in babies born to ZIKV infected mothers, as well as an increased risk of Guillain-Barre syndrome in adults. These findings prompted the World Health Organization to declare ZIKV a public health emergency in 2016, which resulted in expanded efforts to develop ZIKV vaccines and immunotherapeutics. Several ZIKV vaccine candidates that are immunogenic and effective at blocking ZIKV infection in animal models have since been developed, with some of these now being evaluated in the clinic. Additional therapeutics under investigation include anti-ZIKV monoclonal antibodies (mAbs) that have been shown to neutralize infection in vitro as well as protect against morbidity in mouse models of ZIKV infection. In this review, we summarize the current understanding of ZIKV biology and describe our efforts to rapidly develop a vaccine against ZIKV.

Broad cross-protective anti-hemagglutination responses elicited by influenza microconsensus DNA vaccine.

Despite the routine development and distribution of seasonal influenza vaccines, influenza remains an important pathogen contributing to significant human morbidity as well as mortality each year. The seasonal variability of influenza creates a significant issue for vaccine development of seasonal strains that can afford protection from infection or disease based on serotype matching. It is appreciated that the globular head of the HA antigen contained in the vaccines generates antibodies that result in HAI activity that are a major correlates of the protection against a particular strain. Due to seasonal genetic changes in the HA protein, however, new vaccine strains are needed to be developed continually to match the new HA antigen of that seasons virus. A distinct advantage in seasonal vaccine development would be if a small group of antigens could be developed that could span many seasons without needed to be replaced due to this genetic drift. Here we report on a synthetic microconsensus approach that relies on a small collection of 4 synthetic H1HA DNA antigens which together induce broad protective HAI immunity spanning decades of H1 influenza viruses in mice, guinea pigs and non-human primates. The protective HAI titers induced by microconsensus immunogens are fully functional in vivo as immunized ferrets were completely protected from A/Mexico/InDRE4487/2009 virus infection and morbidity associated with lethal challenge. These results are encouraging that a limited easy-to-formulate collection of invariant antigens can be developed which can span seasonal vaccine changes allowing for continued immune protection.

Nurse Competence on Physiologic Monitors Use: Toward Eliminating Alarm Fatigue in Intensive Care Units.

BACKGROUND: Studies on nurse competence on alarm management are a few and tend to be focused on limited skills. In response to Phase II of implementing the National Patient Safety Goal on clinical alarm systems safety, this study assessed nurses' perceived competence on physiologic monitors use in intensive care units (ICUs) and developed and validated a tool for this purpose. METHODS: This descriptive study took place in a Magnet hospital in a Southwestern state of the U.S. A Nurse Competence on Philips Physiologic Monitors Use Survey was created and went through validation by 13 expert ICU nurses. The survey included 5 subscales with 59 rated items and two open-ended questions. Items on the first 4 subscales reflect most common tasks nurses perform using physiologic monitors. Items on the fifth subscale (advanced functions) reflect rarely used skills and were included to understand the scope of utilizing advanced physiologic monitors' features. Thirty nurses from 4 adult ICUs were invited to respond to the survey. RESULTS: Thirty nurses (100%) responded to the survey. The majority of nurses were from Neuro (47%) and Surgical Trauma (37%) ICUs. The data supported the high reliability and construct validity of the survey. At least one (3%) to 8 nurses (27%) reported lack of confidence on each item on the survey. On the first four subscales, 3% - 40% of the nurses reported they had never heard of or used 27 features/functions on the monitors. No relationships were found between subscales' scores and demographic characteristics (p > .05). Nurses asked for training on navigating the central-station monitor and troubleshooting alarms, and the use of unit-specific super users to tailor training to users' needs. CONCLUSION: This is the first study to create and test a list of competencies for physiologic monitors use. Rigorous, periodic and individualized training is essential for safe and appropriate use of physiologic monitors and to decrease alarm fatigue. Training should be comprehensive to include all necessary skills and should not assume proficiency on basic skills. Special attention should be focused on managing technical alarms. Increasing the number of super users is a recommended strategy for individualized and unit-specific training. There is a need for a usability testing of complex IT-equipped medical devices, such as physiologic monitors, for effective, efficient and safe navigation of the monitors.

In vivo protection against ZIKV infection and pathogenesis through passive antibody transfer and active immunisation with a prMEnv DNA vaccine.

Significant concerns have been raised owing to the rapid global spread of infection and disease caused by the mosquito-borne Zika virus (ZIKV). Recent studies suggest that ZIKV can also be transmitted sexually, further increasing the exposure risk for this virus. Associated with this spread is a dramatic increase in cases of microcephaly and additional congenital abnormalities in infants of ZIKV-infected mothers, as well as a rise in the occurrence of Guillain Barre' syndrome in infected adults. Importantly, there are no licensed therapies or vaccines against ZIKV infection. In this study, we generate and evaluate the in vivo efficacy of a novel, synthetic, DNA vaccine targeting the pre-membrane+envelope proteins (prME) of ZIKV. Following initial in vitro development and evaluation studies of the plasmid construct, mice and non-human primates were immunised with this prME DNA-based immunogen through electroporation-mediated enhanced DNA delivery. Vaccinated animals were found to generate antigen-specific cellular and humoral immunity and neutralisation activity. In mice lacking receptors for interferon (IFN)-α/ß (designated IFNAR-/-) immunisation with this DNA vaccine induced, following in vivo viral challenge, 100% protection against infection-associated weight loss or death in addition to preventing viral pathology in brain tissue. In addition, passive transfer of non-human primate anti-ZIKV immune serum protected IFNAR-/- mice against subsequent viral challenge. This study in NHP and in a pathogenic mouse model supports the importance of immune responses targeting prME in ZIKV infection and suggests that additional research on this vaccine approach may have relevance for ZIKV control and disease prevention in humans.

Structure Based Thermostability Prediction Models for Protein Single Point Mutations with Machine Learning Tools.

Thermostability issue of protein point mutations is a common occurrence in protein engineering. An application which predicts the thermostability of mutants can be helpful for guiding decision making process in protein design via mutagenesis. An in silico point mutation scanning method is frequently used to find "hot spots" in proteins for focused mutagenesis. ProTherm (http://gibk26.bio.kyutech.ac.jp/jouhou/Protherm/protherm.html) is a public database that consists of thousands of protein mutants' experimentally measured thermostability. Two data sets based on two differently measured thermostability properties of protein single point mutations, namely the unfolding free energy change (ddG) and melting temperature change (dTm) were obtained from this database. Folding free energy change calculation from Rosetta, structural information of the point mutations as well as amino acid physical properties were obtained for building thermostability prediction models with informatics modeling tools. Five supervised machine learning methods (support vector machine, random forests, artificial neural network, naïve Bayes classifier, K nearest neighbor) and partial least squares regression are used for building the prediction models. Binary and ternary classifications as well as regression models were built and evaluated. Data set redundancy and balancing, the reverse mutations technique, feature selection, and comparison to other published methods were discussed. Rosetta calculated folding free energy change ranked as the most influential features in all prediction models. Other descriptors also made significant contributions to increasing the accuracy of the prediction models.

Improving glycemic control with the adjunct use of a data management software program.

BACKGROUND: Published studies have supported the implementation of tight glucose control (TGC) programs to improve patient outcomes and reduce mortality rates. However, measuring a program's efficiency is challenging, because of a lack of systems that capture data, allow access to data, and support analysis and interpretation in a near prospective time frame. We hypothesized that providing clinicians access to real-time blood glucose (BG) results reports could improve the efficacy of our TGC program. METHODS: We performed a retrospective review of BG data during a 12-month period in a surgical trauma intensive care unit at a level I trauma center. A unit-specific insulin algorithm was used throughout the study. We compared BG values before and after the implementation of a data management software program that allowed clinicians access to real-time BG results reports. Reports were run daily and weekly to monitor the unit's TGC program. RESULTS: A total of 70 616 BG values from 1044 patients were analyzed. An overall decrease was observed in the BG level mean, from 121 mg/dL to 112 mg/dL (P < .001), as well as a decrease in the aggregated mean across patients, from 132 mg/dL to 119 mg/dL (P < .001), after implementation of the software. The percentage of values within the target range of 80 to 110 mg/dL increased from 38.9% to 50.4% (P < .001). The percentage of BG values less than 70 increased from 2.7% to 3.4% (P < .001). However, the percentage of severe hypoglyce-mic episodes (≤ 40 mg/dL) remained unchanged. CONCLUSIONS: Access to real-time aggregated BG data reports through the use of a data management software program improved the efficacy of our TGC program.

Case study: family presence in the OR for donation after cardiac death.

Organ donation after cardiac death is an ethical and acceptable practice of providing organs for transplantation. Organ recovery, the removal of life support, and patient death occur in the OR, and, because family members are not present, some feel that they have abandoned their loved one. This article reports a case study of a young woman brought to a level I trauma center with nonsurvivable injuries from a motor vehicle accident. When clinical examinations revealed no hope of recovery, the family agreed to organ donation if the mother could be present in the OR when life support was terminated. Family member presence during organ donation may provide a sense that some good has come of a personal tragedy. Although family requests may be unsettling, advocating for the patient and family is part of the nurse's role.

Case discussion in blood glucose variability.

Stress-induced hyperglycemia has been associated with poor outcomes and death in critically ill patients. Blood glucose (BG) variability, a component of stress-related hyperglycemia has recently been reported as a significant independent predictor of intensive care unit and hospital mortality. We sought to evaluate three cases in which intensive insulin therapy was administered using a standardized insulin dosing protocol to normalize the BG and reduce glycemic variability. Point-of-care BG values and other clinical measures were obtained from the medical record of three patients who received intensive insulin therapy. This was a convenience sample of three patients where the BG level had stabilized on a consistent intravenous insulin dose rate for up to 20 hours in a surgical trauma intensive care unit. Data were collected manually and electronically using the Remote Automated Laboratory System-Tight Glycemic Control Module (RALS-TGCM) BG management and monitoring system. Each case presentation describes a critically ill, nondiabetic patient, requiring continuous intravenous insulin therapy for hyperglycemia. In each instance, BG variability was present in a worsening patient condition after a period of normalization of hyperglycemia with intensive insulin therapy. Although decreasing BG variability is an important aspect of hyperglycemia management, new onset events of variability may be a sentinel warning or occur as a physiologic response to a worsening patient condition. If so, these events warrant rapid investigation and treatment of the underlying problem.

Case study: creating a healthy workplace in a surgical trauma intensive care unit.

This case study describes the implementation of the Parsons' Healthy Workplace Theory and Intervention in a surgical intensive care unit in a level 1 trauma facility. This intervention and change strategy was the impetus for the creation of a more positive work environment by developing and empowering staff. The process led to shared decision making and development of action planning teams that subsequently became unit-based committees. The committees have focused goals, action plans, and timelines for achieving those goals. Transforming care and the enculturation of shared decision making at the bedside is essential for improving quality of patient care and for recruitment and retention of nurses.

Intensive insulin protocol improves glucose control and is associated with a reduction in intensive care unit mortality.

BACKGROUND: Intensive insulin therapy to maintain serum glucose levels between 80 and 110 mg/dL has previously been shown to reduce mortality in the critically ill; recent data, however, have called this benefit into question. In addition, maintaining uniform, tight glucose control is challenging and resource demanding. We hypothesized that, by use of a protocol, tight glucose control could be achieved in the surgical trauma intensive care unit (STICU), and that improved glucose control would be beneficial. STUDY DESIGN: During the study period, a progressively more rigorous approach to glucose control was used, culminating in an implemented protocol in 2005. We reviewed STICU patients' blood glucose levels, measured by point-of-care testing, from 2003 to 2006. Mortality was tracked over the course of the study, and patient charts were retrospectively reviewed to measure illness and injury severity. RESULTS: Mean blood glucose levels steadily improved (p < 0.01). In addition to absolute improvements in glucose control, total variability of glucose ranges in the STICU steadily diminished. A reduction in STICU mortality was temporally associated with implementation of the protocol (p < 0.01). There were fewer intraabdominal abscesses and fewer postinjury ventilator days after implementation of the protocol. There was a small increase in the incidence of clinically relevant hypoglycemia. CONCLUSIONS: Improvements in glucose control in the ICU can be achieved by using a protocol for intensive insulin therapy. In our ICU, this was temporally associated with a significant reduction in mortality.

Decorin evokes protracted internalization and degradation of the epidermal growth factor receptor via caveolar endocytosis.

Decorin inhibits the epidermal growth factor receptor (EGFR) by down-regulating its tyrosine kinase activity, thereby blocking the growth of a variety of transformed cells and tumor xenografts. In this study we provide evidence that decorin directly binds to the EGFR causing its dimerization, internalization, and ultimately its degradation. Using various pharmacological agents to disrupt clathrin-dependent and -independent endocytosis, we demonstrate that decorin evokes a protracted internalization of the EGFR primarily via caveolar-mediated endocytosis. In contrast to EGF, decorin targets the EGFR to caveolae, but not to early or recycling endosomes. Ultimately, however, both EGF- and decorin-induced pathways converge into late endosomes/lysosomes for final degradation. Thus, we have discovered a novel biological mechanism for decorin that could explain its anti-proliferative and anti-oncogenic mode of action.

A role for decorin in the remodeling of myocardial infarction.

Because the small leucine-rich proteoglycan decorin has been implicated in regulation of collagen fibrillogenesis leading to proper extracellular matrix assembly, we hypothesized it could play a key role in cardiac fibrosis following myocardial infarction. In this study we ligated the left anterior descending coronary artery in wildtype and decorin-null mice to produce large infarcts in the anterior wall of the left ventricle. At early stages post-coronary occlusion the myocardial infarction size did not appreciably differ between the two genotypes. However, we found a wider distribution of collagen fibril sizes with less organization and loose packing in mature scar from decorin-null mice. Thus, we tested the hypothesis that these abnormal collagen fibrils would adversely affect post-infarction mechanics and ventricular remodeling. Indeed, scar size, right ventricular remote hypertrophy, and left ventricular dilatation were greater in decorin-null animals compared with wildtype littermates 14 days after acute myocardial infarction. Echocardiography revealed depressed left ventricular systolic function between 4 and 8 weeks post-ischemia in the decorin-null animals. These changes indicate that decorin is required for the proper fibrotic evolution of myocardial infarctions, and that its absence leads to abnormal scar tissue formation. This might contribute to aneurysmal ventricular dilatation, remote hypertrophy, and depressed ventricular function.