Digitally enabled hemovigilance allows real time response to transfusion reactions.

BACKGROUND: Transfusion carries a risk of transfusion reaction that is often underdiagnosed due to reliance on passive reporting. The study investigated the utility of digital methods to identify potential transfusion reactions, thus allowing real-time intervention for affected patients. METHOD: The hemovigilance unit monitored 3856 patients receiving 43,515 transfusions under the hemovigilance program. Retrospective comparison data included 298,498 transfusions. Transfusion medicine physicians designed and validated algorithms in the electronic health record that analyze discrete data, such as vital sign changes, to assign a risk score during each transfusion. Dedicated hemovigilance nurses remotely monitor all patients and perform real-time chart reviews prioritized by risk score. When a reaction is suspected, a hemovigilance trained licensed clinician responds to manage the patient and ensure data collection. Board-certified transfusion medicine physicians reviewed data and classified transfusion reactions under various categories according to the Centers for Disease Control hemovigilance definitions. RESULTS: Transfusion medicine physicians diagnosed 564 transfusion reactions (1.3% of transfusions)-a 524% increase compared to the previous passive reporting. The rapid response provider reached the bedside on average at 12.4 min demonstrating logistic feasibility. While febrile reactions were most diagnosed, recognition of transfusion-associated circulatory overload demonstrated the greatest relative increase. Auditing and education programs further enhanced transfusion reaction awareness. DISCUSSION: The model of digitally-enabled expert real-time review of clinical data that prompts rapid response improved recognition of transfusion reactions. This approach could be applied to other patient deterioration events such as early identification of sepsis.

Nanosecond-Timescale Dynamics and Conformational Heterogeneity in Human GCK Regulation and Disease.

Human glucokinase (GCK) is the prototypic example of an emerging class of proteins with allosteric-like behavior that originates from intrinsic polypeptide dynamics. High-resolution NMR investigations of GCK have elucidated millisecond-timescale dynamics underlying allostery. In contrast, faster motions have remained underexplored, hindering the development of a comprehensive model of cooperativity. Here, we map nanosecond-timescale dynamics and structural heterogeneity in GCK using a combination of unnatural amino acid incorporation, time-resolved fluorescence, and 19F nuclear magnetic resonance spectroscopy. We find that a probe inserted within the enzyme's intrinsically disordered loop samples multiple conformations in the unliganded state. Glucose binding and disease-associated mutations that suppress cooperativity alter the number and/or relative population of these states. Together, the nanosecond kinetics characterized here and the millisecond motions known to be essential for cooperativity provide a dynamical framework with which we address the origins of cooperativity and the mechanism of activated, hyperinsulinemia-associated, noncooperative variants.

Postoperative Urinary Tract Infection Quality Assessment and Improvement: The S.T.O.P. UTI Program and Its Impact on Hospitalwide CAUTI Rates.

BACKGROUND: Postoperative urinary tract infection (UTI) is a frequent complication that diminishes patient experience and incurs substantial costs. The purpose of this project was to develop a urinary tract care assessment tool that would lead to actionable quality improvement initiatives. METHODS: Multidisciplinary teams at a single institution developed the S.T.O.P. UTI algorithm to assess elements related to urinary catheter care: Sterile catheter placement, Timely catheter removal, Optimal collection bag position, and Proper urine sampling for urinalysis and culture. Based on this evaluation, a targeted intervention was applied to address deficient areas in surgical patients. UTI rates were monitored. RESULTS: The assessment revealed that best practice for sterile placement was being performed but that time to removal, optimal positioning, and proper sampling could be improved. Providers were educated on best practice for catheter removal, nurses placed a reminder note on the chart, personnel were taught about optimal catheter positioning, and nursing assistants were educated on best practices for collection of urine. From 2012 to 2015, non-risk-adjusted UTI rates in surgical patients decreased from 2.90% to 0.46% (p = 0.0003), and the American College of Surgeons National Surgical Quality Improvement Program risk-adjusted comparison improved from the 8th to the 4th decile. Simultaneously, hospitalwide catheter-associated UTI rates also decreased, from 2.24/1,000 catheter-days in 2014 to 0.70/1,000 catheter-days in 2016 (p < 0.001). CONCLUSION: The S.T.O.P. UTI algorithm is a tool that hospitals can use to systematically assess UTI processes. The program can identify areas for improvement specific to an institution, directing the allocation of quality improvement resources to decrease both surgical and medical UTIs.

Use of laboratory test results in patient management by clinicians in Malawi.

BACKGROUND: Malawi has a high burden of infectious disease. The expansion of programmes targeting these diseases requires a strong laboratory infrastructure to support both diagnosis and treatment. OBJECTIVES: To assess the use of laboratory test results in patient management and to determine the requirements for improving laboratory services. METHODS: A cross-sectional study was conducted in 2012 to survey practising clinicians. Two hospitals were purposively selected for observations of clinicians ordering laboratory tests. Twelve management-level key informants were interviewed. Descriptive statistics were conducted. RESULTS: A total of 242 clinicians were identified and 216 (89%) were interviewed. Of these, 189 (87%) reported doubting laboratory test results at some point. Clinicians most often doubted the quality of haematology (67%), followed by malaria (53%) and CD4 (22%) test results. A total of 151 (70%) clinicians reported using laboratory tests results in patient management. Use of laboratory test results at all times in patient management varied by the type of health facility (P < 0.001). Ninety-one percent of clinicians reported that laboratories required infrastructure improvement. During 97 observations of clinicians' use of laboratory test results, 80 tests were ordered, and 73 (91%) of these were used in patient management. Key informants reported that the quality of laboratory services was good and useful, but that services were often unavailable. CONCLUSION: Gaps in the public laboratory system were evident. Key recommendations to enhance the use of laboratory test results in patient management were to strengthen the supply chain, reduce turn-around times, improve the test menu and improve the laboratory infrastructure.

Use of laboratory test results in patient management by clinicians in Malawi

Background: Malawi has a high burden of infectious disease. The expansion of programmes targeting these diseases requires a strong laboratory infrastructure to support both diagnosis and treatment.Objectives: To assess the use of laboratory test results in patient management and to determine the requirements for improving laboratory services. Methods: A cross-sectional study was conducted in 2012 to survey practising clinicians.Two hospitals were purposively selected for observations of clinicians ordering laboratory tests. Twelve management-level key informants were interviewed. Descriptive statistics were conducted. Results: A total of 242 clinicians were identified and 216 (89%) were interviewed. Of these; 189 (87%) reported doubting laboratory test results at some point. Clinicians most often doubted the quality of haematology (67%); followed by malaria (53%) and CD4 (22%) test results. A total of 151 (70%) clinicians reported using laboratory tests results in patient management. Use of laboratory test results at all times in patient management varied by the type of health facility (P 0.001). Ninety-one percent of clinicians reported that laboratories required infrastructure improvement. During 97 observations of clinicians' use of laboratory test results; 80 tests were ordered; and 73 (91%) of these were used in patient management. Key informants reported that the quality of laboratory services was good and useful; but that services were often unavailable. Conclusion: Gaps in the public laboratory system were evident. Key recommendations to enhance the use of laboratory test results in patient management were to strengthen the supply chain; reduce turn-around times; improve the test menu and improve the laboratory infrastructure

Role of connecting loop I in catalysis and allosteric regulation of human glucokinase.

Glucokinase (GCK, hexokinase IV) is a monomeric enzyme with a single glucose binding site that displays steady-state kinetic cooperativity, a functional characteristic that affords allosteric regulation of GCK activity. Structural evidence suggests that connecting loop I, comprised of residues 47-71, facilitates cooperativity by dictating the rate and scope of motions between the large and small domains of GCK. Here we investigate the impact of varying the length and amino acid sequence of connecting loop I upon GCK cooperativity. We find that sequential, single amino acid deletions from the C-terminus of connecting loop I cause systematic decreases in cooperativity. Deleting up to two loop residues leaves the kcat value unchanged; however, removing three or more residues reduces kcat by 1000-fold. In contrast, the glucose K0.5 and KD values are unaffected by shortening the connecting loop by up to six residues. Substituting alanine or glycine for proline-66, which adopts a cis conformation in some GCK crystal structures, does not alter cooperativity, indicating that cis/trans isomerization of this loop residue does not govern slow conformational reorganizations linked to hysteresis. Replacing connecting loop I with the corresponding loop sequence from the catalytic domain of the noncooperative isozyme human hexokinase I (HK-I) eliminates cooperativity without impacting the kcat and glucose K0.5 values. Our results indicate that catalytic turnover requires a minimal length of connecting loop I, whereas the loop has little impact upon the binding affinity of GCK for glucose. We propose a model in which the primary structure of connecting loop I affects cooperativity by influencing conformational dynamics, without altering the equilibrium distribution of GCK conformations.

Enteral nutritional intake in adult korean intensive care patients.

BACKGROUND: Nutritional support is important for maximizing clinical outcomes in critically ill patients, but enteral nutritional intake is often inadequate. OBJECTIVE: To assess the nutritional intake of energy and protein during the first 4 days after initiation of enteral feeding and to examine the relationship between intake and interruptions of enteral feeding in Korean patients in intensive care. METHODS: A cohort of 34 critically ill adults who had a primary medical diagnosis and received bolus enteral feeding were studied prospectively. Energy and protein requirements were determined by using the Harris-Benedict equation and the American Dietetic Association equation. Energy and protein intake prescribed and received and the reasons for and lengths of feeding interruptions were recorded for 4 consecutive days immediately after enteral feeding began. RESULTS: Although the differences between requirements and intakes of energy and protein decreased significantly, patients did not receive required energy and protein intake during the 4 days of the study. Energy intake prescribed was consistently less than required on each of the 4 days. Enteral nutrition was withheld for a mean of 6 hours per patient for the 4 days. Prolonged feeding interruptions due to gastrointestinal intolerance (r= -0.874; P < .001) and procedures (r= -0.839; P = .005) were negatively associated with the percentage of prescribed energy received. CONCLUSIONS: Enteral nutritional intake was insufficient in bolus-fed Korean intensive care patients because of prolonged feeding interruptions and underprescription of enteral nutrition. Feeding interruptions due to gastrointestinal intolerance and procedures were the main contributors to inadequate energy intake.

Data-driven interdisciplinary interventions to improve inpatient pain management.

Pain during hospitalization and dissatisfaction with pain management are common. This project consisted of 4 phases: identifying a pain numeric rating scale (NRS) metric associated with patient satisfaction, identifying independent predictors of maximum NRS, implementing interventions, and evaluating trends in NRS and satisfaction. Maximum NRS was inversely associated with favorable pain satisfaction for both efficacy (n = 4062, χ(2) = 66.2, P < .001) and staff efforts (n = 4067, χ(2) = 30.3, P < .001). Independent predictors of moderate-to-severe maximum NRS were younger age, female sex, longer hospital stay, admitting department, psychoactive medications, and 10 diagnostic codes. After interventions, moderate-to-severe maximum NRS declined by 3.6% per quarter in 2010 compared with 2009. Satisfaction data demonstrated improvements in nursing units meeting goals (5.3% per quarter, r (2) = 0.67) and favorable satisfaction answers (0.36% per quarter, r (2) = 0.31). Moderate-to-severe maximum NRS was an independent predictor of lower likelihood of hospital discharge (likelihood ratio = 0.62; 95% confidence interval = 0.61-0.64). Targeted interventions were associated with improved inpatient pain management.

Why patients in critical care do not receive adequate enteral nutrition? A review of the literature.

Enteral nutrition is frequently used to provide nutrients for critically ill patients. However, only about half of critically ill enterally fed patients receive their energy requirements. Underfeeding is associated with detrimental clinical outcomes including infection, pressure ulcers, impaired wound healing, prolonged hospital stays, and increased morbidity and mortality. This literature review was conducted to identify major barriers to adequate enteral nutrition intake in critically ill adults and to identify gaps in the research literature. Studies (n = 30) reviewed addressed adult patients in critical care, published since 1999, and written in English. Findings showed that factors that explain inadequate enteral nutritional intake include delayed initiation of enteral nutrition and slow advancement of infusion rate, underprescription, incomplete delivery of prescribed nutrition, and frequent interruption of enteral nutrition. Frequent interruption was caused by diagnostic tests, surgical procedures, gastrointestinal intolerance, feeding tube problems, and routine nursing procedures. There are no standardized protocols that address these barriers to receiving adequate enteral intake. Such protocols must be developed, implemented, and tested to address undernutrition and mitigate the negative consequences of inadequate enteral intake.

Adequacy of early enteral nutrition in adult patients in the intensive care unit.

AIMS AND OBJECTIVES: To evaluate the adequacy of energy and protein intake of patients in a Korean intensive care unit in the first four days after initiation of enteral feeding and to investigate the factors that had impact on adequate intake. BACKGROUND: Underfeeding is a common problem for patients hospitalised in the intensive care unit and is associated with severe negative consequences, including increased morbidity and mortality. DESIGN: A prospective, cohort study was conducted in a medical intensive care unit of a university hospital in Korea. METHODS: A total of 34 adult patients who had a primary medical diagnosis and who had received bolus enteral nutrition for the first four days after initiation of enteral nutrition were enrolled in this study. The data on prescription and intake of energy and protein, feeding method and feeding interruption were recorded during the first four days after enteral feeding initiation. Underfeeding was defined as the intake <90% of required energy and protein. RESULTS: Most patients (62%) received insufficient energy, although some (29%) received adequate energy. More than half of patients (56%) had insufficient protein intake during the first four days after enteral feeding was initiated. Logistic regression analysis showed that the factors associated with underfeeding of energy were early initiation of enteral nutrition, under-prescription of energy and prolonged interruption of prescribed enteral nutrition. CONCLUSION: Underfeeding is frequent in Korean critically ill patients owing to early initiation, under-prescription and prolonged interruption of enteral feeding. RELEVANCE TO CLINICAL PRACTICE: Interventions need to be developed and tested that address early initiation, under-prescription and prolonged interruption of enteral nutrition. Findings from this study are important as they form the foundation for the development of evidence-based care that is badly needed to eliminate underfeeding in this large vulnerable Korean intensive care unit population.

Prevalence of transmitted HIV drug resistance among newly diagnosed antiretroviral therapy-naive pregnant women in Lilongwe and Blantyre, Malawi.

In 2006, a survey of transmitted human immunodeficiency virus (HIV) drug resistance (TDR) was conducted in Lilongwe, Malawi. The survey followed the World Health Organization method to classify TDR to nucleoside reverse transcriptase inhibitors (NRTIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs) among primigravid women aged <25 years. Results of the 2006 survey showed <5% TDR in all drug classes. In 2009, TDR surveys using the same method were repeated in Lilongwe and expanded to Blantyre. Findings show that in Lilongwe TDR to NRTIs and PIs was <5%, whereas TDR to NNRTIs was 5%-15%. In Blantyre, TDR was <5% to all drug classes. Observed moderate TDR in Lilongwe is cause for concern and signals the need for closer monitoring of Malawi's antiretroviral therapy program.

A retrospective survey of HIV drug resistance among patients 1 year after initiation of antiretroviral therapy at 4 clinics in Malawi.

In 2004, Malawi began scaling up its national antiretroviral therapy (ART) program. Because of limited treatment options, population-level surveillance of acquired human immunodeficiency virus drug resistance (HIVDR) is critical to ensuring long-term treatment success. The World Health Organization target for clinic-level HIVDR prevention at 12 months after ART initiation is ≥ 70%. In 2007, viral load and HIVDR genotyping was performed in a retrospective cohort of 596 patients at 4 ART clinics. Overall, HIVDR prevention (using viral load ≤ 400 copies/mL) was 72% (95% confidence interval [CI], 67%-77%; range by site, 60%-83%) and detected HIVDR was 3.4% (95% CI, 1.8%-5.8%; range by site, 2.5%-4.7%). Results demonstrate virological suppression and HIVDR consistent with previous reports from sub-Saharan Africa. High rates of attrition because of loss to follow-up were noted and merit attention.

Prevalence of HIV drug resistance before and 1 year after treatment initiation in 4 sites in the Malawi antiretroviral treatment program.

Since 2004, the Malawi antiretroviral treatment (ART) program has provided a public health-focused system based on World Health Organization clinical staging, standardized first-line ART regimens, limited laboratory monitoring, and no patient-level monitoring of human immunodeficiency virus drug resistance (HIVDR). The Malawi Ministry of Health conducts periodic evaluations of HIVDR development in prospective cohorts at sentinel clinics. We evaluated viral load suppression, HIVDR, and factors associated with HIVDR in 4 ART sites at 12-15 months after ART initiation. More than 70% of patients initiating ART had viral suppression at 12 months. HIVDR prevalence (6.1%) after 12 months of ART was low and largely associated with baseline HIVDR. Better follow-up, removal of barriers to on-time drug pickups, and adherence education for patients 16-24 years of age may further prevent HIVDR.

Cooperativity in monomeric enzymes with single ligand-binding sites.

Cooperativity is widespread in biology. It empowers a variety of regulatory mechanisms and impacts both the kinetic and thermodynamic properties of macromolecular systems. Traditionally, cooperativity is viewed as requiring the participation of multiple, spatially distinct binding sites that communicate via ligand-induced structural rearrangements; however, cooperativity requires neither multiple ligand binding events nor multimeric assemblies. An underappreciated manifestation of cooperativity has been observed in the non-Michaelis-Menten kinetic response of certain monomeric enzymes that possess only a single ligand-binding site. In this review, we present an overview of kinetic cooperativity in monomeric enzymes. We discuss the primary mechanisms postulated to give rise to monomeric cooperativity and highlight modern experimental methods that could offer new insights into the nature of this phenomenon. We conclude with an updated list of single subunit enzymes that are suspected of displaying cooperativity, and a discussion of the biological significance of this unique kinetic response.

Use of dolls as a therapeutic intervention: relationship to previous negative behaviors and pro re nata (prn) Haldol use among geropsychiatric inpatients.

This exploratory study was conducted to determine the effects of use of dolls as a therapeutic intervention with geriatric inpatients. The sample included 115 patients, 29 of whom had an order for prn Haldol. Among patients who had previous negative behaviors, there was a lower average number of prn Haldol doses with those who had dolls. Recommendations for practice and future research are included.

Association of paediatric inflammatory bowel disease with other immune-mediated diseases.

BACKGROUND: Associations between inflammatory bowel diseases (IBDs) and other immune-mediated diseases have been described in adult populations. Whether such associations exist in childhood-onset disease remains unknown. OBJECTIVES: The authors sought to evaluate whether paediatric IBD is associated with the occurrence of other immune-mediated diseases. STUDY DESIGN: The authors identified cases of Crohn's disease (CD) and ulcerative colitis (UC), ≤20 years of age, using administrative data from 87 health plans. Each case was matched to three controls, on the basis of age, gender, and geographical region. The authors used logistic regression to compare the prevalence of various immune-mediated diseases (identified by International Classification of Diseases, ninth revision codes) in cases versus controls. RESULTS: The study included 737 children with CD (1997 controls) and 488 with UC (1310 controls). CD was associated with a higher prevalence of rheumatoid arthritis (OR 15.7, 95% CI 4.6 to 53.7), lupus (OR 41.0, 95% CI 2.3 to 719.1) and hypothyroidism (OR 2.9, 95% CI 1.4 to 6.1), with a trend toward an increased prevalence of asthma, eczema, allergic rhinitis and diabetes. UC was associated with a higher prevalence of diabetes (OR 2.7, 95% CI 1.1 to 6.6), with a trend towards increased prevalence of asthma, eczema, allergic rhinitis, hypothyroidism, rheumatoid arthritis and lupus. DISCUSSION: Children with IBD, particularly CD, have an elevated risk for immune-mediated conditions. This comorbidity adds to the burden of paediatric IBD, and suggests common aetiologic mechanisms.

Global nursing leadership: a practical guide.

Nursing leaders of today must be prepared for a nursing practice environment inclusive of local, national, and global work and issues. The educational preparation of nursing leaders should incorporate a fundamental curriculum that offers a broad preparation and basic leadership skills along with guidelines and experiences to support global outreach and collaboration with many cultures and health care environments. This article provides a practical guide on entry into Global Nursing Leadership for nursing leaders from the nurse executive including all levels of nursing management.

Risk of diagnosed fractures in children with inflammatory bowel diseases.

BACKGROUND: Decreased bone mass is common in children with inflammatory bowel disease (IBD); however, fracture risk is unknown. We sought to evaluate fracture risk in children with IBD as compared to unaffected controls and determine whether this risk is affected by geographical region (a proxy for sun/vitamin D exposure) and oral steroid use. METHODS: We identified cases of Crohn's disease (CD) and ulcerative colitis (UC), less than 20 years of age, using administrative data from 87 health plans. Each case was matched to three controls on the basis of age, gender, and geographical region. We identified fractures in cases and controls using ICD-9 diagnosis codes and measured oral steroid exposure using NDC codes. RESULTS: The study included 733 children with CD, 488 with UC, and 3287 controls (mean age 15 years). IBD was not associated with a higher risk of fracture at any site (CD odds ratio [OR] 0.8, 95% confidence interval [CI] 0.6-1.1; UC OR 1.4, 95% CI 1.0-2.1) or at multiple sites (CD OR 0.8, 95% CI 0.4-1.7; UC OR 0.4, 95% CI 0.1-1.4). Among IBD patients we did not identify any significant differences in the fracture rate between those residing in the Northeast/Midwest versus the South (OR 1.3, 95% CI 0.8-2.2). Steroid exposure was not associated with the occurrence of fractures (P = 0.6). CONCLUSIONS: Children with IBD are no more likely to have experienced a diagnosed fracture than age-, sex-, and gender-matched controls.

Thiazolidinedione use and ulcerative colitis-related flares: an exploratory analysis of administrative data.

BACKGROUND: Recent animal studies and clinical trials suggest that thiazolidinediones, a class of oral antidiabetic agents, are efficacious in reducing inflammation, yet no studies have evaluated their effectiveness in preventing flares. We examined the association between thiazolidinedione use and ulcerative colitis (UC)-related flares. METHODS: We conducted a retrospective cohort study using administrative data from 87 health plans across 33 states. Individuals with both UC and diabetes were identified using administrative definitions. Exposure to thiazolidinediones or other oral antidiabetic agents was ascertained through outpatient pharmacy claims. The primary outcome was occurrence of a UC flare defined by: 1) a new prescription for oral steroids, infliximab, or oral/rectal salicylates, or 2) a claim for colectomy. Secondary analyses analyzed outcomes separately. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression after matching each thiazolidinedione user to a comparable oral antidiabetic user on propensity score. RESULTS: This study included 142 thiazolidinedione and 468 other oral antidiabetic users with a mean follow-up of 7.3 and 6.2 months, respectively. Thiazolidinedione use was not associated with UC-related flares as measured by the composite outcome (HR = 1.05, 95% CI: 0.66, 1.68). However, thiazolidinedione use was associated with a nonsignificant reduction in risk of oral steroid use when analyzed as a separate outcome (HR = 0.53, 95% CI: 0.20, 1.44). CONCLUSIONS: Thiazolidinediones do not provide any benefit over other oral antidiabetics in preventing UC-related flares as measured by our primary composite outcome. However, thiazolidinedione use may reduce the risk of more significant disease flares requiring oral steroid treatment.