Using Electrolyte Repletion Guidelines to Improve the Rate of Oral Potassium and Magnesium Delivery

Introduction: Evidence-based guidelines for electrolyte replacement that safely encourage oral (PO) and/or intravenous (IV) dosing more successfully attain goal levels than standard care. However, the Thomas Jefferson University Hospital (TJUH) electrolyte replacement guidelines (JG 11-1296), approved in 2002 and last updated in 2008, provide guidance for IV repletion not PO. Between 5/2017-11/2017, TJUH dosed potassium and magnesium in a 2.30 and 4.24 IV:PO ratio, respectively. If 50% of doses were given PO, we anticipate ~$800,000 annual TJUH savings. Methods: We created a multidisciplinary team and completed a literature review to inform the creation of updated TJUH guidelines for potassium and magnesium repletion. We attained updated guideline approval from the TJUH Pharmacy & Therapeutics Committee followed by the Medical Executive Board. We are working on an Epic order-set to ease clinician use of guideline-based therapy; an institutional Epic build “Freeze” is delaying progress. We will study the impact of updated guidelines with a pre-post design; using a two-tailed Welch’s t-test to test for significance. Results: We hypothesize that the updated guidelines will reduce the ratio of IV:PO doses, increase the percent of patients within normal limits after repletion, decrease time to repletion, and reduce the average hospital cost for electrolyte repletion per patient/day. We additionally anticipate improved patient comfort and convenience of repletion though we will not study for significance. Conclusion: We anticipate that the creation of an easily-accessible evidence-based TJUH electrolyte repletion guideline will improve quality of repletion and patient comfort while decreasing TJUH electrolyte repletion cost

The “OK” Guideline: Implementing an Electronic Electrolyte Repletion Guideline for Improving Rates of Oral Potassium and Magnesium Delivery

Nearly 500,000 doses of potassium (K) and magnesium (Mg) are given at Thomas Jefferson University Hospital (TJUH) each year. More than 80% of these doses are given intravenously. Guidelines that encourage both intravenous and oral (PO) repletion options increase rates of PO dosing and more successfully attain goal levels than standard care. Our goal was to increase the percent of K and Mg doses delivered by oral route to \u3e50% of total doses distributed at TJUH within one year of implementation of an Epic-based electronic order set

A Case Control Study of Nutrient Intake Deficiencies in Patients Taking Warfarin

Introduction We previously published the case of a woman taking warfarin who was found to have scurvy, a disease caused by a deficiency of vitamin C. This led us to hypothesize that patients taking warfarin who consume a diet limited in vitamin K rich foods may be at risk for other nutrient deficiencies. To test our hypothesis, we studied dietary nutrient intake in patients taking warfarin compared to patients with heart disease not taking warfarin. Methods The warfarin (n=59) and control groups (n=24) comprised convenience samples of patients with heart disease over age 60 years. Patients completed a three-day food diary and reported use of supplements. Results Based on diet history, the most common deficiencies were vitamin D (100% both groups), vitamin E (93% warfarin, 92% control), vitamin A (71% warfarin, 71% control), vitamin K (66% warfarin, 58% control), vitamin C (58 % warfarin, 46% control) and pantothenic acid (69% warfarin, 71% control) with no significant differences in intake deficiencies between warfarin and control groups. Conclusion All of our patients had nutritional intake deficiencies. This may be due to Appalachian dietary habits and not the low vitamin K diet. It seems prudent to recommend multivitamins, however, universal multivitamin supplementation has not been supported by randomized controlled trials. More study is needed to determine the reason for poor nutritional intake in our Appalachian population and to determine whether similar results are evident in a larger sample

Association of maternal serum PAPP-A levels, nuchal translucency and crown rump length in first trimester with adverse pregnancy outcomes: Retrospective cohort study.

OBJECTIVE: Are first trimester serum pregnancy-associated plasma protein-A (PAPP-A), nuchal translucency (NT) and crown rump length (CRL) prognostic factors for adverse pregnancy outcomes? METHOD: Retrospective cohort women, singleton pregnancies (UK 2011-2015). Unadjusted and multivariable logistic regression, outcomes: small for gestational age (SGA), pre-eclampsia (PE), pre-term birth (PTB), miscarriage, stillbirth, perinatal mortality and neonatal death (NND). RESULTS: 12,592 pregnancies: 852 (6.8%) PTB, 352 (2.8%) PE, 1824 (14.5%) SGA, 73 (0.6%) miscarriages, 37(0.3%) stillbirths, 73 perinatal deaths (0.6%) and 38 (0.30%) NND. Multivariable analysis: lower odds of SGA [adjusted odds ratio (aOR) 0.88 (95% CI 0.85,0.91)], PTB [0.92 (95%CI 0.88,0.97)], PE [0.91 (95% CI 0.85,0.97)] and stillbirth [ 0.71 (95% CI 0.52,0.98)] as PAPP-A increases. Lower odds of SGA [aOR 0.79 (95% CI 0.70,0.89)] but higher odds of miscarriage [aOR 1.75 95% CI (1.12,2.72)] as NT increases, and lower odds of stillbirth as CRL increases [aOR 0.94 95% CI (0.89,0.99)]. Multivariable analysis of three factors together demonstrated strong associations: a) PAPP-A, NT, CRL and SGA, b) PAPP-A and PTB, c) PAPP-A, CRL and PE, d) NT and miscarriage. CONCLUSIONS: PAPP-A, NT and CRL independent prognostic factor for adverse pregnancy outcomes, especially PAPP-A and SGA with lower PAPP-A associated with increased risk

Gene expression and matrix turnover in overused and damaged tendons

Chronic, painful conditions affecting tendons, frequently known as tendinopathy, are very common types of sporting injury. The tendon extracellular matrix is substantially altered in tendinopathy, and these changes are thought to precede and underlie the clinical condition. The tendon cell response to repeated minor injuries or “overuse” is thought to be a major factor in the development of tendinopathy. Changes in matrix turnover may also be effected by the cellular response to physical load, altering the balance of matrix turnover and changing the structure and composition of the tendon. Matrix turnover is relatively high in tendons exposed to high mechanical demands, such as the supraspinatus and Achilles, and this is thought to represent either a repair or tissue maintenance function. Metalloproteinases are a large family of enzymes capable of degrading all of the tendon matrix components, and these are thought to play a major role in the degradation of matrix during development, adaptation and repair. It is proposed that some metalloproteinase enzymes are required for the health of the tendon, and others may be damaging, leading to degeneration of the tissue. Further research is required to investigate how these enzyme activities are regulated in tendon and altered in tendinopathy. A profile of all the metalloproteinases expressed and active in healthy and degenerate tendon is required and may lead to the development of new drug therapies for these common and debilitating sports injuries

PONV Prophylaxis Failure Disproportionately Affects Female Patients, Despite Intraoperative Computerized Decision Support Guidance

Objectives: To compare postoperative nausea and vomiting (PONV) prophylaxis treatment and outcomes based on patients’ sex, using a retrospective cohort. The setting was the operating room and post-anesthesia care unit of a tertiary care university medical center. Patients: A total of 678 adult male and female patients with American Society of Anesthesiologist (ASA) scores of 1-4 underwent surgery with general anesthesia. All patients received preoperative PONV risk assessment. PONV prophylaxis was administered at the discretion of the anesthesia care team members with guidance from a computerized decision support system. Measurements: Adequacy of prophylaxis was retrospectively determined based on individual patient risk factors and the observed treatment received, compared with guideline-based prophylaxis recommendations. Patient outcome was measured by diagnosis of PONV in recovery. Results: Comparing patients who received fewer than the guideline-recommended number of prophylactic antiemetics by sex, 94.6% were female and 5.4% were males (p \u3c 0.001). Patients who received fewer than guideline-recommended number of antiemetics had significantly higher rates of nausea or vomiting in the post-anesthesia care unit (30.4% vs 17.5%, p \u3c 0.001). Conclusion: This retrospective cohort study shows that female patients receiving general anesthesia are disproportionately affected by failure to adhere to PONV prevention guidelines

Potential for airborne transmission of infection in the waiting areas of healthcare premises: stochastic analysis using a Monte Carlo model

BACKGROUND: Although many infections that are transmissible from person to person are acquired through direct contact between individuals, a minority, notably pulmonary tuberculosis (TB), measles and influenza are known to be spread by the airborne route. Airborne infections pose a particular threat to susceptible individuals whenever they are placed together with the index case in confined spaces. With this in mind, waiting areas of healthcare facilities present a particular challenge, since large numbers of people, some of whom may have underlying conditions which predispose them to infection, congregate in such spaces and can be exposed to an individual who may be shedding potentially pathogenic microorganisms. It is therefore important to understand the risks posed by infectious individuals in waiting areas, so that interventions can be developed to minimise the spread of airborne infections. METHOD: A stochastic Monte Carlo model was constructed to analyse the transmission of airborne infection in a hypothetical 132 m3 hospital waiting area in which occupancy levels, waiting times and ventilation rate can all be varied. In the model the Gammaitoni-Nucci equation was utilized to predict probability of susceptible individuals becoming infected. The model was used to assess the risk of transmission of three infectious diseases, TB, influenza and measles. In order to allow for stochasticity a random number generator was applied to the variables in the model and a total of 10000 individual simulations were undertaken. The mean quanta production rates used in the study were 12.7, 100 and 570 per hour for TB, influenza and measles, respectively. RESULTS: The results of the study revealed the mean probability of acquiring a TB infection during a 30-minute stay in the waiting area to be negligible (i.e. 0.0034), while that for influenza was an order of magnitude higher at 0.0262. By comparison the mean probability of acquiring a measles infection during the same period was 0.1349. If the duration of the stay was increased to 60 minutes then these values increased to 0.0087, 0.0662 and 0.3094, respectively. CONCLUSION: Under normal circumstances the risk of acquiring a TB infection during a visit to a hospital waiting area is minimal. Likewise the risks associated with the transmission of influenza, although an order of magnitude greater than those for TB, are relatively small. By comparison, the risks associated with measles are high. While the installation of air disinfection may be beneficial, when seeking to prevent the transmission of airborne viral infection it is important to first minimize waiting times and the number of susceptible individuals present before turning to expensive technological solutions

Ebola virus glycoprotein stimulates IL-18 dependent natural killer cell responses

BACKGROUND: NK cells are activated by innate cytokines and viral ligands to kill virus-infected cells; these functions are enhanced during secondary immune responses and after vaccination by synergy with effector T cells and virus-specific antibodies. In human Ebola virus infection, clinical outcome is strongly associated with the initial innate cytokine response, but the role of NK cells has not been thoroughly examined. METHODS: The novel 2-dose heterologous Adenovirus type 26.ZEBOV (Ad26.ZEBOV) and modified vaccinia Ankara-BN-Filo (MVA-BN-Filo) vaccine regimen is safe and provides specific immunity against Ebola glycoprotein, and is currently in phase 2 and 3 studies. Here, we analysed NK cell phenotype and function in response to Ad26.ZEBOV, MVA-BN-Filo vaccination regimen, and in response to in vitro Ebola glycoprotein stimulation of PBMC isolated before and after vaccination. RESULTS: We show enhanced NK cell proliferation and activation after vaccination compared with baseline. Ebola glycoprotein-induced activation of NK cells was dependent on accessory cells and TLR-4-dependent innate cytokine secretion (predominantly from CD14+ monocytes) and enriched within less differentiated NK cell subsets. Optimal NK cell responses were dependent on IL-18 and IL-12, whilst IFN-γ secretion was restricted by high concentrations of IL-10. CONCLUSION: This study demonstrates the induction of NK cell effector functions early after Ad26.ZEBOV, MVA-BN-Filo vaccination and provides a mechanism for the activation and regulation of NK cells by Ebola GP. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02313077. FUNDING: U.K. Medical Research Council Studentship in Vaccine Research, Innovative Medicines Initiative 2 Joint Undertaking, EBOVAC (Grant 115861) and Crucell Holland (now Janssen Vaccines & Prevention B.V.), European Union’s Horizon 2020 research and innovation programme and European Federation of Pharmaceutical Industries and Associations (EFPIA)

Tendinopathy—from basic science to treatment

Chronic tendon pathology (tendinopathy), although common, is difficult to treat. Tendons possess a highly organized fibrillar matrix, consisting of type I collagen and various 'minor' collagens, proteoglycans and glycoproteins. The tendon matrix is maintained by the resident tenocytes, and there is evidence of a continuous process of matrix remodeling, although the rate of turnover varies at different sites. A change in remodeling activity is associated with the onset of tendinopathy. Major molecular changes include increased expression of type III collagen, fibronectin, tenascin C, aggrecan and biglycan. These changes are consistent with repair, but they might also be an adaptive response to changes in mechanical loading. Repeated minor strain is thought to be the major precipitating factor in tendinopathy, although further work is required to determine whether it is mechanical overstimulation or understimulation that leads to the change in tenocyte activity. Metalloproteinase enzymes have an important role in the tendon matrix, being responsible for the degradation of collagen and proteoglycan in both healthy patients and those with disease. Metalloproteinases that show increased expression in painful tendinopathy include ADAM (a disintegrin and metalloproteinase)-12 and MMP (matrix metalloproteinase)-23. The role of these enzymes in tendon pathology is unknown, and further work is required to identify novel and specific molecular targets for therapy