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.

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.

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.

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.

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.

Increased risk for non-melanoma skin cancer in patients with inflammatory bowel disease.

BACKGROUND & AIMS: Patients with inflammatory bowel disease (IBD) might be at increased risk for certain malignancies. We evaluated the risk of non-melanoma skin cancer (NMSC) in patients with IBD and determined how immunosuppressive and biologic medications affect this risk. METHODS: We performed retrospective cohort and nested case-control studies by using administrative data from PharMetrics Patient Centric Database. In the cohort study, 26,403 patients with Crohn's disease (CD) and 26,974 patients with ulcerative colitis (UC) were each matched to 3 non-IBD controls. NMSC risk was evaluated by incidence rate ratio (IRR). In the nested case-control study, 387 CD patients and 355 UC patients with NMSC were each matched to 4 IBD patients without NMSC by using incidence density sampling. Conditional logistic regression was used to determine the association between specific IBD medication use and NMSC. RESULTS: In the cohort study, the incidence of NMSC was higher among patients with IBD compared with controls (IRR, 1.64; 95% confidence interval [CI], 1.51-1.78). In the nested-case control study, recent thiopurine use (< or =90 days) was associated with NMSC (adjusted odds ratio [OR], 3.56; 95% CI, 2.81-4.50), as was recent biologic use among patients with CD (adjusted OR, 2.07; 95% CI, 1.28-3.33). Persistent thiopurine use (>365 days) was associated with NMSC (adjusted OR, 4.27; 95% CI, 3.08-5.92), as was persistent biologic use among patients with CD (adjusted OR, 2.18; 95% CI, 1.07-4.46). CONCLUSIONS: Patients with IBD, especially those who receive thiopurines, are at risk for NMSC. Appropriate counseling and monitoring of such patients with IBD are recommended.