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Emergency departments (EDs) are an important potential site for public health screening programs, although implementation of such programs can be challenging. Potential barriers include system-level issues (e.g., funding and time pressures) and individual provider-level issues (e.g., awareness and acceptance). This cross-sectional evaluation of a nurse-driven, triage-based hepatitis C virus (HCV) screening program in an urban, academic ED assessed variation in nurse participation from April to November 2017. For this program, electronic health record (EHR) prompts for HCV screening were integrated into nurses' triage workflow. Process measures evaluating HCV screening participation were abstracted from the EHR for all ED encounters with patient year of birth between 1945 and 1965. Registered nurses who routinely worked in triage and were full-time employees throughout the study period were included for analysis. The primary outcome was the proportion of eligible ED encounters with completed HCV screening, by nurse. Of 14,375 ED encounters, 3,375 (23.5%, 95% confidence interval [CI]: 22.8, 24.2) had completed HCV screening and 1,408 (9.8%, 95% CI: 3.9, 10.3) had HCV screening EHR sections opened by the triage nurse but closed without action; the remainder of encounters had no activity in HCV screening EHR sections. Among the 93 eligible nurses, 22 nurses (24%, 95% CI: 16, 34) completed HCV screening for more than 70% of encounters, whereas 10 nurses (11%, 95% CI: 6, 19) never completed HCV screening. The proportion of eligible encounters with completed HCV screening was 11.0% higher (95% CI: 9.8, 12.6) for encounters seen between 7 a.m. and 7 p.m. than between 7 p.m. and 7 a.m. (27.5% and 16.3%, respectively). In conclusion, wide variation in individual nurse participation in HCV screening suggests individual-level barriers are a more significant barrier to ED screening than previously recognized. Implementation research should expand beyond questions of resource availability and procedural streamlining to evaluate and address staff knowledge, beliefs, attitudes, and motivation. [ABSTRACT FROM AUTHOR] more...

Context: Overdosing on opioids is a national epidemic and the number one cause of death from unintentional injury in the United States. Poison control centers (PCCs) may be a source of timely data that can track opioid exposure cases, identify clusters of opioid exposure cases by geographic region, and capture opioid exposure cases that may not seek medical attention from health care facilities., Objective: The objectives were to (a) identify data requirements for opioid overdose case ascertainment and classification and visualization in a dashboard, and (b) assess the availability and quality of the relevant PCC data for state-based opioid overdose surveillance., Design: We identified types of opioid exposure, demographic characteristics, and other features that may be relevant for public health officials to monitor and respond to opioid overdose events in the community. We operationalized case definitions for an opioid overdose event based on the Centers for Disease Control and Prevention case classification definitions. We assessed the PCC database for concepts and metrics needed to operationalize case definitions for opioid overdose events to determine the feasibility of using the PCC for automated surveillance., Main Outcome Measure: Quality and availability of required concepts to operationalize metrics and case definitions using PCC data., Results: A subset of the probable case definition may be used for automated surveillance with available structured PCC data. In contrast, logic for confirmed, suspected, and part of the probable case definitions requires additional structured data or analysis of narrative text, which may not contain needed concepts. For example, the confirmed case definition currently requires evidence from narrative text of laboratory confirmation of an opioid in a clinical specimen or diagnosis of opioid overdose in a health care record., Conclusion: PCC data are a timely and potentially useful source for automated surveillance of a subset of opioid overdose events, but additional structured and/or coded data are required., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.) more...

Rationale: Downregulation of the pacemaking ion channel, HCN4 (hyperpolarization-activated cyclic nucleotide gated channel 4), and the corresponding ionic current, I f , underlies exercise training-induced sinus bradycardia in rodents. If this occurs in humans, it could explain the increased incidence of bradyarrhythmias in veteran athletes, and it will be important to understand the underlying processes., Objective: To test the role of HCN4 in the training-induced bradycardia in human athletes and investigate the role of microRNAs (miRs) in the repression of HCN4., Methods and Results: As in rodents, the intrinsic heart rate was significantly lower in human athletes than in nonathletes, and in all subjects, the rate-lowering effect of the HCN selective blocker, ivabradine, was significantly correlated with the intrinsic heart rate, consistent with HCN repression in athletes. Next-generation sequencing and quantitative real-time reverse transcription polymerase chain reaction showed remodeling of miRs in the sinus node of swim-trained mice. Computational predictions highlighted a prominent role for miR-423-5p. Interaction between miR-423-5p and HCN4 was confirmed by a dose-dependent reduction in HCN4 3'-untranslated region luciferase reporter activity on cotransfection with precursor miR-423-5p (abolished by mutation of predicted recognition elements). Knockdown of miR-423-5p with anti-miR-423-5p reversed training-induced bradycardia via rescue of HCN4 and I f . Further experiments showed that in the sinus node of swim-trained mice, upregulation of miR-423-5p (intronic miR) and its host gene, NSRP1, is driven by an upregulation of the transcription factor Nkx2.5., Conclusions: HCN remodeling likely occurs in human athletes, as well as in rodent models. miR-423-5p contributes to training-induced bradycardia by targeting HCN4. This work presents the first evidence of miR control of HCN4 and heart rate. miR-423-5p could be a therapeutic target for pathological sinus node dysfunction in veteran athletes., (© 2017 The Authors.) more...

The aim of this paper is to estimate the relative cost-effectiveness of treatment regimens for managing patients with sciatica. A deterministic model structure was constructed based on information from the findings from a systematic review of clinical effectiveness and cost-effectiveness, published sources of unit costs, and expert opinion. The assumption was that patients presenting with sciatica would be managed through one of 3 pathways (primary care, stepped approach, immediate referral to surgery). Results were expressed as incremental cost per patient with symptoms successfully resolved. Analysis also included incremental cost per utility gained over a 12-month period. One-way sensitivity analyses were used to address uncertainty. The model demonstrated that none of the strategies resulted in 100% success. For initial treatments, the most successful regime in the first pathway was nonopioids, with a probability of success of 0.613. In the second pathway, the most successful strategy was nonopioids, followed by biological agents, followed by epidural/nerve block and disk surgery, with a probability of success of 0.996. Pathway 3 (immediate surgery) was not cost-effective. Sensitivity analyses identified that the use of the highest cost estimates results in a similar overall picture. While the estimates of cost per quality-adjusted life year are higher, the economic model demonstrated that stepped approaches based on initial treatment with nonopioids are likely to represent the most cost-effective regimens for the treatment of sciatica. However, development of alternative economic modelling approaches is required., (Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.) more...

Background: This study aims to describe the healthcare resource utilization and costs of managing renal posttransplant patients over 3 years posttransplant in nine European countries and to stratify them by year 1 glomerular filtration rate (GFR)., Methods: A retrospective observational and database analysis of renal transplant patients and a physician questionnaire study were conducted to collect recipient and donor characteristics, posttransplant events, and healthcare resource utilization related to these posttransplant events. In each country, local published costs were applied to the resource use identified. The results were stratified by the patient GFR reading at a time point 1 year after renal transplant., Results: The database study identified 3,181 patients who met the inclusion criteria, along with 2,818 transplants carried out in the centers surveyed by questionnaire. Total 3-year costs derived from the questionnaire analysis vary depending on local treatment practices, from a minimum of &OV0556;33,602 per patient in the Czech Republic to &OV0556;77,461 per patient in the Netherlands. Consistently across countries, estimated costs appear to decrease with improved graft functioning status (increased GFR) at 1 year. The average 3-year costs, discounting immunosuppression therapy and certain posttransplant events, per patient with a GFR greater than or equal to 60 at 1 year are estimated to be around 35% lower than those with 15≤GFR<30., Conclusion: This study demonstrates that in Europe, worsening posttransplant renal function may contribute to substantive increases in resource use, with some variation across regions. Therefore, management strategies that promote renal function after transplantation have the potential to provide important resource savings. more...

Rationale: The organization of the transverse-tubular (t-t) system and relationship to the sarcoplasmic reticulum (SR) underpins cardiac excitation-contraction coupling. The architecture of the SR, and relationship with the t-ts, is not well characterized at the whole-cell level. Furthermore, little is known regarding changes to SR ultrastructure in heart failure., Objective: The aim of this study was to unravel interspecies differences and commonalities between the relationship of SR and t-t networks within cardiac myocytes, as well as the modifications that occur in heart failure, using a novel high-resolution 3-dimensional (3D) imaging technique., Methods and Results: Using serial block face imaging coupled with scanning electron microscopy and image analysis, we have generated 3D reconstructions of whole cardiomyocytes from sheep and rat left ventricle, revealing that the SR forms a continuous network linking t-ts throughout the cell in both species. In sheep, but not rat, the SR has an intimate relationship with the sarcolemma forming junctional domains. 3D reconstructions also reveal details of the sheep t-t system. Using a model of tachypacing-induced heart failure, we show that there are populations of swollen and collapsed t-ts, patches of SR tangling, and disorder with rearrangement of the mitochondria., Conclusions: We provide the first high-resolution 3D structure of the SR network showing that it forms a cell-wide communication pipeline facilitating Ca(2+) diffusion, buffering, and synchronicity. The distribution of the SR within the cell is related to interspecies differences in excitation-contraction coupling, and we report the first detailed analysis of SR remodeling as a result of heart failure. more...

A low approach to the interscalene block (LISB) deposits local anesthetic farther caudad on the brachial plexus compared with the conventional interscalene block (ISB). We compared the efficacy of LISB and ISB in achieving anesthesia of the distal extremity in 254 patients having upper extremity surgery. The most frequent elicited motor response was the deltoid for ISB and wrist for LISB. There was significantly greater sensory-motor block of regions below the elbow with the LISB compared with ISB (P < 0.001 for both sensory and motor coverage). Our data indicate that LISB results in a higher incidence of distal elicited motor response and greater sensory-motor blockage of the wrist and hand. more...

During orthotopic liver transplantation a patient received epsilon-aminocaproic acid and clotting factors. Shortly after hepatic artery clamping the patient developed a massive intracardiac/intravascular thrombosis that resulted in cardiac arrest. After diagnosis by transesophageal echocardiography, the patient was treated with recombinant tissue plasminogen activator through a central venous catheter advanced into the right atrium. After treatment with recombinant tissue plasminogen activator, the patient's hemodynamic status improved, permitting the liver transplant to be completed. The patient was ultimately discharged to home. We report the successful intraoperative resuscitation of a patient with acute intracardiac/intravascular thrombosis during an orthotopic liver transplantation using thrombolytic therapy. more...

Introduction: Physical activity has been identified as an important predictor of chronic disease risk in numerous studies in which activity levels were measured by questionnaire. Although the validity of physical activity questionnaires has been documented in a number of studies of U.S. adults, few have included a validation analysis among blacks. We have examined the validity and reliability of a physical activity questionnaire that was administered to 165 black Seventh-day Adventists from Southern California., Methods: Subjects completed a self-administered physical activity questionnaire and then "reference" measures of activity (7-d activity recalls, pedometer readings) and fitness (treadmill test) were completed in subsets of this population., Results: The authors found that 7-d recall activity levels correlated well with the corresponding questionnaire indices among women (total activity, r = 0.65; vigorous, r = 0.85; moderate, r = 0.44; inactivity, r = 0.59; sleep duration, r = 0.52) and men (total activity, r = 0.51; vigorous, r = 0.65; moderate, r = 0.53; inactivity, r = 0.69; sleep duration, r = 0.39). Vigorous activity from 7-d recalls was best measured by gender-specific indices that included only recreational activities among men and emphasized nonrecreational activities among women. Correlations between questionnaire data and the other "reference" measures were lower. Test-retest correlations of questionnaire items over a 6-wk interval were high (r = 0.4-0.9)., Conclusion: Simple questions can measure activities of different intensity with good validity and reliability among black Adventist men and women. more...

In order to identify the mechanisms that would lead to increased levels of the inhibitory neuromodulator adenosine in the brain, we tested metabotropic glutamate receptor agonists for their ability to increase extracellular adenosine in the cortex of unanesthetized rat using in vivo microdialysis. The group I/II metabotropic glutamate receptor agonist trans-(+/-)- 1-amino-(1S,3R)-cyclopenyanedicarboxylic acid (I mM) increased extracellular adenosine as did the specific group I agonist (S)- 3,5-dihydroxyphenylglycine (DHPG; 1 mM). The evoked increase of adenosine by 1 mM DHPG was reduced by the group I antagonist (RS)- 1-aminoindan-1,5,-dicarboxylic acid. Activation of group II or III metabotropic receptors did not affect extracellular adenosine. These results suggest that activation of group I metabotropic receptors contributes to elevated extracellular adenosine levels in vivo. more...

The staging of dementia is ideally based on both an examination of the patient and a history taken from an informant. However, in some circumstances, only an informant history is possible. The aim of this study was to assess the validity of the Clinical Dementia Rating (CDR) when the rating is based solely on informant data. The CDR was used in a study of 360 persons aged 78 or older who were participants in a community survey, the Sydney Older Persons Study. The CDR was completed in two ways: (1) a social scientist made the ratings based on an informant interview; and (2) a physician made the ratings after an examination of the subject. All CDRs were scored in the conventional way, as well as by the revised method proposed by Gelb and St. Laurent (Alzheimer Dis Assoc Disord 1993;4:202-11). The informant CDR showed moderate agreement with the clinician CDR, showing that it would be a valid substitute in situations in which the subject could not be examined. The revised scoring method was slightly easier to implement than the conventional method. more...

Whether anesthetized patients register emotionally charged information remains controversial. We tested this possibility using subanesthetic concentrations of propofol or desflurane. Twenty-two volunteers (selected for hypnosis susceptibility) received propofol and desflurane (on separate occasions, and in a random order) at a concentration 1.5-2 times each individual's minimum alveolar anesthetic concentration (MAC)-awake (or equivalent for propofol). We gave vecuronium, intubated the trachea of each volunteer, controlled ventilation, and then presented a neutral (control) drama or a "crisis" drama stating that the oxygen delivery system had failed, assigning crisis and control dramas in a blinded, randomized, and balanced manner. One day later, interviewers blinded to the assigned drama conducted a 2-h structured interview (including hypnosis) to determine whether the contents of the interviews after crisis and control dramas differed. In addition, messages permitting subsequent assessment of learning of matter-of-fact information (Trivial Pursuit-type question task and a behavior task) were presented at the anesthetic concentration just sufficient to prevent response to command in each volunteer. No analyses of the tasks involving matter-of-fact information revealed learning except one which correlated hypnosis susceptibility with behavior task performance. Both propofol and desflurane suppressed memory of the crisis. Consistent with previous findings for isoflurane and nitrous oxide, propofol and desflurane suppressed learning of matter-of-fact information at concentrations just above MAC-awake, except that volunteers' susceptibility to hypnosis correlated with performance of a behavior suggested during anesthesia. Propofol and desflurane suppressed learning of emotionally charged information at anesthetic concentrations 1.5-2 times MAC-awake (less than MAC), a different result from that previously reported for ether. more...

The capacity of desflurane to suppress learning is unknown. We investigated whether a subanesthetic concentration of desflurane (0.6 minimum alevolar anesthetic concentration [MAC]) suppressed learning as much as the same concentration of isoflurane, and whether such suppression differed with increasing duration of anesthesia and intervening changes in anesthetic concentration. Using a cross-over-design study in 18-30 yr-old human volunteers, we supplied answers to Trivial Pursuit (Selchow & Righter Co., Bay Shore, NY)-like questions at 0.6 MAC desflurane and isoflurane before and after imposing a half-hour period at 1.7 MAC of each anesthetic, and behavioral directions and a category-example task at 0.6 MAC after the period at 1.7 MAC. These volunteers had a third anesthesia in which no information was supplied (control). After anesthesia, we tested whether the provision of answers during anesthesia increased the number of correct answers to Trivial Pursuit questions. We tested for the number of correct answers for information presented before versus after the 1.7-MAC period, for increased evocation of examples of categories presented during anesthesia, and for exhibition of a behavior suggested during anesthesia. We found that 0.6 MAC of both anesthetics prevented explicit and implicit learning before and after the period at 1.7 MAC. more...

Background: The power spectrum of the electroencephalogram (EEG) may be analyzed to provide quantitative measures of EEG activity (e.g., spectral edge, which defines the highest EEG frequency at which significant activity is found). The current study tested the hypothesis that spectral edge and similar measures distinguish different functional depths of anesthesia in humans., Methods: Three groups were studied. Group 1 consisted of 34 surgical patients (ASA physical status 1 or 2) who received 0.6, 1.0 and 1.4 MAC isoflurane anesthesia. A subgroup (group 2) of group 1 was tested during 1.0 MAC isoflurane anesthesia at surgical incision. Group 3 consisted of 16 volunteers who listened to an audiotape while receiving 0.15, 0.3, and 0.45 MAC isoflurane or 0.3, 0.45, and 0.6 MAC nitrous oxide in oxygen. The audiotape contained information designed to test implicit and explicit memory formation. We tested the ability of six EEG parameters (spectral-edge, 95th percentile power frequency, median power, and zero crossing frequencies and total power in the alpha- [8-13 Hz] and delta- [< 4 Hz] power ranges) to predict movement after surgical incision, purposeful response to command, or memory of information presented during anesthetic administration., Results: Isoflurane decreased EEG activity in group 1 in a dose-related fashion. The 55% of group 2 who made purposeful movements in response to incision did not differ in their EEG from nonresponders (e.g., spectral edge 19.8 +/- 3.1 vs. 19.3 +/- 2.6 Hz, mean +/- SD). In group 3, memory of the information presented did not correlate with values of any EEG parameter. Response to verbal command was associated with lower anesthetic concentrations and with smaller alpha- and delta-band power (298 +/- 66 vs. 401 +/- 80 watts; and 75 +/- 20 vs. 121 +/- 49 watts, mean +/- SD), but there was no difference in values for other parameters., Conclusions: We conclude that our EEG measures do not predict depth of anesthesia as defined by the response to surgical incision, the response to verbal command or the development of memory. more...

Background: A greater MAC fraction of nitrous oxide than isoflurane is required to prevent response to verbal commands and suppress the capacity to learn. Speculating that this difference between these agents may be caused by nitrous oxide's capacity to increase sympathetic activity, we tested the hypothesis that nitrous oxide may antagonize the suppression of learning found with isoflurane., Methods: We administered a combination of isoflurane and nitrous oxide at three subanesthetic test concentrations (0.43, 0.56, and 0.68 MAC) to 24 healthy male volunteers. Assuming additivity of the anesthetics, the first test concentration was selected to suppress learning of new information by 50% (ED50 for suppression of learning); the second concentration, to suppress the ability to respond appropriately to verbal command by 50% (MAC-awake); and the third, to provide 1.4 times MAC-awake. Three tests of learning were applied. At each test concentration, we provided 7 answers to "trivial pursuit"-type questions, resulting in a set of 21 answered questions for each volunteer; an additional 7 unanswered questions served as controls. At the highest test concentration, each volunteer also heard two examples from each of two categories (4 words) repeated 30 times (the category-example task), and a message instructing them to touch either their nose or their ear during a specified interval in the postanesthetic interview (the behavior task)., Results: The MAC-awake value for the combination of isoflurane and nitrous oxide was 118 +/- 4% of the expected value (i.e., the two anesthetics were antagonistic for this effect). Consistent with antagonism, the anesthetic concentration predicted to suppress learning by 50% permitted significantly more learning, and the ED50 was 105 +/- 2% of that predicted. Neither the category task nor the behavior task demonstrated evidence of learning at 1.4 times MAC-awake., Conclusions: Our results are consistent with an antagonism between nitrous oxide and isoflurane; however, the degree of antagonism is small. more...

Background: Previously, we found unconscious (implicit) learning in subjects given subanesthetic, but not anesthetic, concentrations of isoflurane. Other investigators, using different learning tasks, have reported implicit learning at anesthetic concentrations. We investigated whether one of these tasks might provide a more sensitive test of implicit learning. In addition, to determine whether suppression of explicit or implicit learning is dose-dependent, we studied one of the tasks at three subanesthetic concentrations., Methods: We applied a category-example task at 0.15, 0.28, and 0.4 minimum alveolar concentration (MAC) of isoflurane, and a behavior task only at 0.4 MAC. After anesthesia, we determined whether volunteers more frequently listed an example of a category (e.g., flute as an example of musical instrument) presented during anesthesia and/or demonstrated a behavior (touching ear, chin, or knee) suggested to them at 0.4 MAC., Results: Results from the category task indicated implicit learning only at 0.15 MAC, a concentration that also permitted significant explicit learning. Explicit learning was demonstrated at 0.28 but not at 0.4 MAC (ED50 of 0.20 MAC and ED95 of 0.4 MAC). Results from the behavior task revealed neither implicit nor explicit learning., Conclusions: The ED50 that suppressed explicit learning in our volunteers equaled that previously reported (0.2 MAC) for implicit learning in volunteers measured using a different task. Combined, these results suggest that less than 0.45 MAC isoflurane suppresses learning in volunteers. more...

Awareness, defined as conscious memory during anesthesia, has been a problem in anesthesia practice. To determine the effect of isoflurane and nitrous oxide (N2O) on memory, 17 healthy adult volunteers were randomly assigned to receive isoflurane or N2O and received the alternate agent 1-2 weeks later. Each volunteer was studied at four end-tidal concentrations of each agent, consecutively 0.15, 0.3, 0.45, and 0.15 times the minimum alveolar concentration (MAC) for isoflurane or 0.3, 0.45, 0.6, and 0.3 times MAC for N2O. After 15-min equilibration at each end-tidal concentration, volunteers were tested for voluntary response to command and were presented with verbal information to be recalled after anesthesia. Volunteers were interviewed on the day after the study and tested for conscious and unconscious memory of the information presented during anesthetic administration. MAC-awake (the end-tidal concentration preventing voluntary response in 50% of volunteers) was 0.38 (0.35-0.42) times MAC for isoflurane and 0.64 (0.61-0.68) MAC for N2O (means, 95% confidence limits), indicating isoflurane to be more potent than N2O in suppressing voluntary response (P = .0001). Memory data were analyzed in 12 volunteers who completed the study and in whom the allocation of information to be recalled was counterbalanced among agents and concentrations of agents. Memory was decreased by increasing concentrations of both agents. Conscious memory of the information presented during anesthetic administration was prevented by 0.45 MAC isoflurane but not completely prevented by 0.6 MAC N2O. Unconscious memory (defined as memory of information without conscious recognition) occurred during administration of both agents and was prevented by 0.45 MAC isoflurane but not by 0.6 MAC N2O. Isoflurane was more potent in suppressing memory than MAC-equivalent concentrations of N2O. Using models of the relationship between dose of agent and suppression of memory, a dose of both agents was estimated that suppressed memory by 50% (ED50). The ED50 was 0.20 MAC for isoflurane (95% confidence intervals, 0.15-0.25), and 0.50 MAC for N2O (95% confidence intervals 0.43-0.55). We conclude that isoflurane and N2O suppress memory in a dose-dependent manner, and that isoflurane is more potent in preventing memory and voluntary response to command than MAC-equivalent concentrations of N2O. more...