Semantically oriented EHR navigation with a patient specific knowledge base and a clinical context ontology.

Widespread adoption of electronic health records (EHR) in the U.S. has been followed by unintended consequences, overexposing clinicians to widely reported EHR limitations. As an attempt to fixing the EHR, we propose the use of a clinical context ontology (CCO), applied to turn implicit contextual statements into formally represented data in the form of concept-relationship-concept tuples. These tuples form what we call a patient specific knowledge base (PSKB), a collection of formally defined tuples containing facts about the patient's care context. We report the process to create a CCO, which guides annotation of structured and narrative patient data to produce a PSKB. We also present an application of our PSKB using real patient data displayed on a semantically oriented patient summary to improve EHR navigation. Our approach can potentially save precious time spent by clinicians using today's EHRs, by showing a chronological view of the patient's record along with contextual statements needed for care decisions with minimum effort. We propose several other applications of a PSKB to improve multiple EHR functions to guide future research.

Contribution of warm habitat to cold-water fisheries.

A central tenet of landscape ecology is that mobile species depend on complementary habitats, which are insufficient in isolation, but combine to support animals through the full annual cycle. However, incorporating the dynamic needs of mobile species into conservation strategies remains a challenge, particularly in the context of climate adaptation planning. For cold-water fishes, it is widely assumed that maximum temperatures are limiting and that summer data alone can predict refugia and population persistence. We tested these assumptions in populations of redband rainbow trout (Oncorhynchus mykiss newberrii) in an arid basin, where the dominance of hot, hyperproductive water in summer emulates threats of climate change predicted for cold-water fish in other basins. We used telemetry to reveal seasonal patterns of movement and habitat use. Then, we compared contributions of hot and cool water to growth with empirical indicators of diet and condition (gut contents, weight-length ratios, electric phase angle, and stable isotope signatures) and a bioenergetics model. During summer, trout occurred only in cool tributaries or springs (<20 °C) and avoided Upper Klamath Lake (>25 °C). During spring and fall, ≥65% of trout migrated to the lake (5-50 km) to forage. Spring and fall growth (mean [SD] 0.58% per day [0.80%] and 0.34 per day [0.55%], respectively) compensated for a net loss of energy in cool summer refuges (-0.56% per day [0.55%]). In winter, ≥90% of trout returned to tributaries (25-150 km) to spawn. Thus, although perennially cool tributaries supported thermal refuge and spawning, foraging opportunities in the seasonally hot lake ultimately fueled these behaviors. Current approaches to climate adaptation would prioritize the tributaries for conservation but would devalue critical foraging habitat because the lake is unsuitable and unoccupied during summer. Our results empirically demonstrate that warm water can fuel cold-water fisheries and challenge the common practice of identifying refugia based only on summer conditions.

RESUMEN: Un principio central de la ecología de paisaje es que las especies ambulantes dependen de hábitats complementarios, los cuales son insuficientes en aislamiento, pero al combinarse mantienen a los animales durante el ciclo anual completo. Sin embargo, la incorporación de las necesidades dinámicas de las especies ambulantes dentro de las estrategias de conservación todavía es un reto, particularmente en el contexto de la planeación de la adaptación climática. Para los peces de agua fría, generalmente se asume que las temperaturas máximas son limitantes y que los datos estivales son suficientes para predecir refugios y la persistencia poblacional. Pusimos a prueba estas suposiciones en poblaciones de trucha arcoíris (Oncorhynchus mykiss newberrii) de una cuenca árida, en donde el dominio de aguas cálidas e hiperproductivas durante el verano emula las amenazas del cambio climático pronosticadas para los peces de agua fría en otras cuencas. Usamos telemetría para descubrir los patrones estacionales de movimiento y uso de hábitat. Después, comparamos las contribuciones que tienen las aguas cálidas y frías al crecimiento con indicadores empíricos de dieta y condición (contenidos intestinales, proporciones peso-longitud, ángulo de fase eléctrica y huellas de isotopos estables) y un modelo bioenergético. Durante el verano, las truchas sólo estuvieron presentes en manantiales o afluentes fríos (<20°C) y evitaron el Lago Klamath Superior (>25°C). Durante la primavera y el otoño, ≥65% de las truchas migraron al lago (5-50 km) para procurar alimento. El crecimiento durante la primavera y el otoño (media [SD] 0.58% día-1 [0.80%] y 0.34 día-1 [0.55%], respectivamente) compensaron la pérdida neta de energía en los refugios fríos durante el verano (-0.56% día-1 [0.55%]). En el invierno, ≥90% de las truchas regresaron a los afluentes (25-150 km) para desovar. Entonces, mientras que los afluentes perennemente fríos fomentaron los refugios termales y el desove, fueron las oportunidades de alimentación en el lago cálido estacional las que finalmente alentaron estos comportamientos. Las estrategias actuales de adaptación climática pondrían como prioridad de conservación a los afluentes, pero devaluarían el hábitat crítico de alimentación porque el lago está desocupado y no es apto durante el verano. Nuestros resultados demuestran empíricamente que las aguas cálidas pueden promover las pesquerías de aguas frías y desafiar la práctica común de identificar refugios basándose solamente en las condiciones estivales.

The University of Alabama at Birmingham COVID-19 Collaborative Outcomes Research Enterprise: Developing an institutional learning health system in response to the global pandemic.

Introduction: As a local response to the COVID-19 global pandemic, the University of Alabama at Birmingham (UAB) established the UAB COVID-19 Collaborative Outcomes Research Enterprise (CORE), an institutional learning health system (LHS) to achieve an integrated health services outcomes and research response. Methods: We developed a network of expertise and capabilities to rapidly develop and deploy an institutional-level interdisciplinary LHS. Based upon a scoping review of the literature and the Knowledge to Action Framework, we adopted a LHS framework identifying contributors and components necessary to developing a system within and between the university academic and medical centers. We used social network analysis to examine the emergence of informal work patterns and diversified network capabilities based on the LHS framework. Results: This experience report details three principal characteristics of the UAB COVID-19 CORE LHS development: (a) identifying network contributors and components; (b) building the institutional network; and (c) diversifying network capabilities. Contributors and committees were identified from seven components of LHS: (a) collaborative and executive leadership committee, (b) research coordinating committee, (c) oversight and ethics committee, (d) thematic scientific working groups, (e) programmatic working groups, (f) informatics capabilities, and (g) patient advisory groups. Evolving from the topical interests of the initial CORE participants, scientific working groups emerged to support the learning system network. Programmatic working groups were charged with developing a comprehensive and mutually accessible COVID-19 database. Discussion: Our LHS framework allowed for effective integration of multiple academic and medical centers into a cohesive institutional-level learning system. Network analysis indicated diversity of institutional disciplines, professional rank, and topical focus pertaining to COVID-19, with each center leveraging existing institutional responsibilities to minimize gaps in network capabilities. Conclusion: Incorporating an adapted LHS framework designed for academic medical centers served as a foundational resource supporting further institutional-level efforts to develop agile and responsive learning networks.

Development of a Coronavirus Disease 2019 (COVID-19) Application Ontology for the Accrual to Clinical Trials (ACT) network.

Clinical data networks that leverage large volumes of data in electronic health records (EHRs) are significant resources for research on coronavirus disease 2019 (COVID-19). Data harmonization is a key challenge in seamless use of multisite EHRs for COVID-19 research. We developed a COVID-19 application ontology in the national Accrual to Clinical Trials (ACT) network that enables harmonization of data elements that are critical to COVID-19 research. The ontology contains over 50 000 concepts in the domains of diagnosis, procedures, medications, and laboratory tests. In particular, it has computational phenotypes to characterize the course of illness and outcomes, derived terms, and harmonized value sets for severe acute respiratory syndrome coronavirus 2 laboratory tests. The ontology was deployed and validated on the ACT COVID-19 network that consists of 9 academic health centers with data on 14.5M patients. This ontology, which is freely available to the entire research community on GitHub at https://github.com/shyamvis/ACT-COVID-Ontology, will be useful for harmonizing EHRs for COVID-19 research beyond the ACT network.

Development of a COVID-19 Application Ontology for the ACT Network.

Clinical data networks that leverage large volumes of data in electronic health records (EHRs) are significant resources for research on coronavirus disease 2019 (COVID-19). Data harmonization is a key challenge in seamless use of multisite EHRs for COVID-19 research. We developed a COVID-19 application ontology in the national Accrual to Clinical Trials (ACT) network that enables harmonization of data elements that that are critical to COVID-19 research. The ontology contains over 50,000 concepts in the domains of diagnosis, procedures, medications, and laboratory tests. In particular, it has computational phenotypes to characterize the course of illness and outcomes, derived terms, and harmonized value sets for SARS-CoV-2 laboratory tests. The ontology was deployed and validated on the ACT COVID-19 network that consists of nine academic health centers with data on 14.5M patients. This ontology, which is freely available to the entire research community on GitHub at https://github.com/shyamvis/ACT-COVID-Ontology, will be useful for harmonizing EHRs for COVID-19 research beyond the ACT network.

Rapid implementation and improvement of a virtual student placement model in response to the COVID-19 pandemic.

Practice-based learning via clinical placement is a core part of a physiotherapy degree with the Chartered Society of Physiotherapy requiring completion of 1000 placement hours over a preregistration degree programme. In April 2020, as a result of the COVID-19 pandemic and subsequent lockdown Connect Health had to cancel 10 student placements as we transitioned to virtual consultations for all clinics. This cancellation of student placements was replicated across the nation with many Higher Education Institutes reporting a backlog of student placements. Without the requisite placement hours students are unable to progress into the next academic year or are unable to graduate. This then reduces the flow of new-graduate physiotherapists into the workforce at a time when there is a plan to grow the physiotherapy workforce to meet primary care demand. In response to this problem a novel placement model to facilitate virtual student placements ('virtual placements') was developed, tested and then rolled out across Connect Health using the Plan-Do-Study-Act quality improvement methodology. The model combines shadowing a broad range of virtual clinics with delivery of patient-facing online exercise classes via the Facebook Live platform and completion of virtual projects to support knowledge consolidation. This virtual student placement model enabled an increase in student capacity of over 400% compared with 2018-2019 with 182 students starting between May and August 2020. The model runs using widely available technology, requires no additional investment and has enabled these students to continue their studies and progress towards qualifying as physiotherapists.

Emotional exhaustion among anesthesia providers at a tertiary care center assessed using the MBI burnout survey.

Burnout is characterized by three components: emotional exhaustion, depersonalization, and low personal accomplishment. Burnout in health professionals results in reduced job satisfaction, decreased mental health and decreased quality of care, with rates ranging from 30-65% across medical specialties. The purpose of this study was to evaluate the prevalence of burnout components and identify factors associated with these components in physicians, residents, and certified nurse anesthetists (CRNAs) in a large academic anesthesiology department. A survey consisting of the Maslach Burnout Inventory-Human Services Survey and additional demographic questions was distributed via email at 7-day intervals over 4 weeks to all anesthesia providers. Scores from individual questions on each of the three subscales were summed and sorted into low, medium, and high levels of each outcome variable. Fisher's exact chi-square tests were used for categorical data. Eighteen residents, 39 staff anesthesiologists, and 32 CRNAs comprised a total of 89 survey respondents. Rates of emotional exhaustion varied by provider types. Residents reported higher levels of emotional exhaustion than staff anesthesiologists and CRNAs. As a system, it is vital for leaders to identify those with or at risk for burnout, their risk factors, and strategies to mitigate risk. The goals of the healthcare system should aim to maintain both quality patient care and healthcare provider wellness.

Utilizing transesophageal echocardiography for placement of pulmonary artery catheters.

OBJECTIVE: Pulmonary artery catheters (PACs) have routinely been positioned by wedging into the pulmonary artery before pulling back 1-2 centimeters or advancing the PAC several centimeters after achieving a pulmonary artery waveform. A rare, major complication is pulmonary artery rupture. This study presents transesophageal echocardiography (TEE) for PAC placement by leaving the catheter tip at the one o'clock position, upper window short-axis view of the ascending aorta at the bifurcation of the pulmonary artery (TEE distance). DESIGN: Prospective observational cohort study. SETTING: Large urban academic medical center. PARTICIPANTS: 30 males and 30 females undergoing cardiac surgery requiring cardiopulmonary bypass. INTERVENTION: TEE was utilized to obtain an upper esophageal short-axis view of the aorta with long-axis view of the main and right pulmonary arteries. MEASUREMENTS AND RESULTS: The distance between TEE position and wedge position was recorded along with patients' gender, height, and weight. A correlation was found between TEE and wedge distances (P < .0001). There were significant gender differences in TEE distance, with a mean of 43.6 cm in females and 46.5 cm in males (P = .0004). The mean wedge distance was 47.5 cm in females and 51.9 cm in males (P < .0001). The differences between distances of wedge and TEE positions (5.39 cm, males; 3.93 cm, females) were also significant (P < .0001). CONCLUSIONS: By securing the PAC at the one o'clock TEE position, physicians are assured of a safety margin of several centimeters. This direct visualization method for PAC placement may decrease the risk for accidental wedging intraoperatively.

Reducing Postoperative Bleeding After Craniosynostosis Repair Utilizing a Low-Dose Transexamic Acid Infusion Protocol.

BACKGROUND: Craniosynostosis surgery is associated with large volume blood loss and the need for blood transfusion. Recently, the use of tranexamic acid (TXA) has been demonstrated to be helpful in reducing perioperative blood loss in many pediatric procedures. This study used a low-dose pharmacokinetic TXA dosing protocol and assessed its ability to limit perioperative blood loss for craniosynostosis repairs. METHODS: A retrospective chart review was conducted of pediatric craniosynostosis surgeries performed at our institution between September 2011 and December 2014. Outcome measures included comparisons of perioperative blood loss and transfusion rates in patients who had surgery with or without TXA. RESULTS: Twenty-five patients met inclusion criteria. Nine patients had craniosynostosis surgery without TXA (no-TXA group) and 16 patients received TXA (TXA group). The TXA group had significantly higher postoperative hemoglobin levels than the no-TXA group (P = 0.009). This finding was supported by significantly higher postoperative estimated red cell volume in the TXA group (P = 0.017). Postoperative 24-hour drain output was significantly lower in the TXA group (P = 0.042). The volume of packed red blood cells transfused perioperatively was not significantly different between groups. CONCLUSIONS: Patients who received TXA during craniosynostosis surgery at our institution had higher postoperative hemoglobin levels and lower 24-hour drain output. However, TXA was not associated with lower perioperative blood transfusion rates.

Classifying Clinical Trial Eligibility Criteria to Facilitate Phased Cohort Identification Using Clinical Data Repositories.

A major challenge in using electronic health record repositories for research is the difficulty matching subject eligibility criteria to query capabilities of the repositories. We propose categories for study criteria corresponding to the effort needed for querying those criteria: "easy" (supporting automated queries), mixed (initial automated querying with manual review), "hard" (fully manual record review), and "impossible" or "point of enrollment" (not typically in health repositories). We obtained a sample of 292 criteria from 20 studies from ClinicalTrials.gov. Six independent reviewers, three each from two academic research institutions, rated criteria according to our four types. We observed high interrater reliability both within and between institutions. The analysis demonstrated typical features of criteria that map with varying levels of difficulty to repositories. We propose using these features to improve enrollment workflow through more standardized study criteria, self-service repository queries, and analyst-mediated retrievals.

Sedation and Analgesia for Dressing Change: A Survey of American Burn Association Burn Centers.

Pain and sedation management for patients undergoing burn dressing change can be challenging. Variations appear to exist in the selection of medications before and during burn dressing change. To determine if institutional variations exist in pain and sedation management for burn dressing change, an online survey was sent to ABA Burn Center nurses and physicians. Three hundred seventy-eight anonymous responses were received from nurses (72%), nurse practitioners (10%), and physicians (18%). Burn centers had adult (22%), pediatric (12%), or pediatric and adult (66%) patients. Eighty percentage of centers had >200 patients/year. Sixty-eight percentage always used a premedication. Oxycodone and morphine or fentanyl was the most frequently used per oral (PO) and intravenous (IV) opioid premedication, respectively. The most common IV premedication anxiolytic were benzodiazepines. Sixty-eight percentage always used a long-acting opioid. Anesthetic regimen was decided case-by-case (47%) or specific protocol (24%). Protocol was followed always (18%) or mostly (55%). Patients' procedural pain could be better controlled 20% of the time. Pain regimen was altered most of the time (25%). Providers differed rarely (39%) and sometimes (44%) regarding preferred regimen. Ketamine was the most common deep sedative. A dedicated anesthesiologist was rarely (33%) consulted, determined case-by-case (33%) or prior failure/excess pain (19%). Acute pain service was never (51%) or rarely (35%) consulted. Pain and sedation management for burn dressing change is difficult and variations in approach exist among burn centers. Such management needs individualized care. Providers must be responsive to pain alterations. Consultation with anesthesia providers may be needed in specific cases. Further studies need to be completed to demonstrate the most effective means of controlling burn pain and evaluating patient outcomes.

Efficient identification of nationally mandated reportable cancer cases using natural language processing and machine learning.

OBJECTIVE: To help cancer registrars efficiently and accurately identify reportable cancer cases. MATERIAL AND METHODS: The Cancer Registry Control Panel (CRCP) was developed to detect mentions of reportable cancer cases using a pipeline built on the Unstructured Information Management Architecture - Asynchronous Scaleout (UIMA-AS) architecture containing the National Library of Medicine's UIMA MetaMap annotator as well as a variety of rule-based UIMA annotators that primarily act to filter out concepts referring to nonreportable cancers. CRCP inspects pathology reports nightly to identify pathology records containing relevant cancer concepts and combines this with diagnosis codes from the Clinical Electronic Data Warehouse to identify candidate cancer patients using supervised machine learning. Cancer mentions are highlighted in all candidate clinical notes and then sorted in CRCP's web interface for faster validation by cancer registrars. RESULTS: CRCP achieved an accuracy of 0.872 and detected reportable cancer cases with a precision of 0.843 and a recall of 0.848. CRCP increases throughput by 22.6% over a baseline (manual review) pathology report inspection system while achieving a higher precision and recall. Depending on registrar time constraints, CRCP can increase recall to 0.939 at the expense of precision by incorporating a data source information feature. CONCLUSION: CRCP demonstrates accurate results when applying natural language processing features to the problem of detecting patients with cases of reportable cancer from clinical notes. We show that implementing only a portion of cancer reporting rules in the form of regular expressions is sufficient to increase the precision, recall, and speed of the detection of reportable cancer cases when combined with off-the-shelf information extraction software and machine learning.

Federated Aggregate Cohort Estimator (FACE): an easy to deploy, vendor neutral, multi-institutional cohort query architecture.

Cross-institutional data sharing for cohort discovery is critical to enabling future research. While particularly useful in rare diseases, the ability to target enrollment and to determine if an institution has a sufficient number of patients is valuable in all research, particularly in the initiation of projects and collaborations. An optimal technology solution would work with any source database with minimal resource investment for deployment and would meet all necessary security and confidentiality requirements of participating organizations. We describe a platform-neutral reference implementation to meet these requirements: the Federated Aggregate Cohort Estimator (FACE). FACE was developed and implemented through a collaboration of The University of Alabama at Birmingham (UAB), The Ohio State University (OSU), the University of Massachusetts Medical School (UMMS), and the Denver Health and Hospital Authority (DHHA) a clinical affiliate of the Colorado Clinical and Translational Sciences Institute. The reference implementation of FACE federated diverse SQL data sources and an i2b2 instance to estimate combined research subject availability from three institutions. It used easily-deployed virtual machines and addressed privacy and security concerns for data sharing.

Distributed Health Outcome Monitoring and Evaluation Using i2b2.

There is a pressing need for better tools to support comparative effectiveness research (CER) on a national scale. In addition, little is known about within-class outcome disparities for commonly used cardiovascular and diabetes medications. In this presentation, we will describe our experience implementing a new i2b2 cell, the Health Outcome Monitoring and Evaluation Cell (HOME), at 5 collaborating Clinical Translational Science Award sites (CTSAs) in the U.S. We will also describe the motivations to developing a common query framework, and findings related to the implementation and use of the HOME cell, to perform distributed CER queries. Our focus is on the assessment of race, gender, and location-based disparities in outcomes for patients treated with similar mediations for hypertension, dyslipidemias, and diabetes.

Supervised exercise plus acupuncture for moderate to severe knee osteoarthritis: a small randomised controlled trial.

OBJECTIVES: Although total knee replacement (TKR) is cost effective and successful in most cases, patient-reported outcome measures demonstrate 20% of people remain unsatisfied at 1 year after a technically successful procedure. Our group has previously shown that patients with severe knee osteoarthritis (OA) awaiting surgery can achieve a short-term reduction in symptom severity when treated with acupuncture, and that a trend towards improved walking distance, as a measure of function, is achieved with preoperative supervised exercise. The aim of this study was to evaluate the effect of combined acupuncture and physiotherapy on preoperative and postoperative pain and function. METHODS: A total of 56 patients awaiting TKR surgery were randomised to receive either combined physiotherapy and acupuncture or a standardised exercise and advice leaflet. Pain and function were measured primarily using the Oxford Knee Score (OKS), with assessments at baseline prior to intervention, 6 and 12 weeks after intervention and at 3 months postoperatively. RESULTS: Due to the introduction of the 18-week waiting times target during this study, the required sample size was not achieved. There were no significant differences demonstrated between the control and treatment groups for OKS. Seven patients withdrew from surgery because of symptomatic improvement in their knees: six from the treatment group and one from the control group (OR 7.64, 95% CI 0.86 to 68.20). CONCLUSIONS: This study demonstrated that the use of combined acupuncture and physiotherapy in the treatment of patients with moderate to severe knee OA preoperatively did not improve patient outcome postoperatively. As the study was underpowered, a larger trial is required to examine this result further.

Development and validation of a pictorial nausea rating scale for children.

OBJECTIVE: The lack of a widely used, validated measure limits pediatric nausea management. The goal of this study was to create and validate a pictorial scale with regular incremental levels between scores depicting increasing nausea intensity. METHODS: A pictorial nausea scale of 0 to 10 with 6 faces (the Baxter Retching Faces [BARF] scale) was developed in 3 stages. The BARF scale was validated in emergency department patients with vomiting and in healthy patients undergoing day surgery procedures. Patients were presented with visual analog scales for nausea and pain, the pictorial Faces Pain Scale-Revised, and the BARF scale. Patients receiving opioid analgesics or antiemetic agents had their pain and nausea assessed before and 30 minutes after therapy. Spearman's ρ correlation coefficients were calculated. A Wilcoxon matched-pair rank test compared pain and nausea scores before and after antiemetic therapy. RESULTS: Thirty oncology patients and 15 nurses participated in the development of the scale, and 127 patients (52, emergency department; 75, day surgery) ages 7 to 18 years participated in the validation. The Spearman ρ correlation coefficient of the first paired BARF and visual analog scale for nausea scores was 0.93. Visual analog scales for nausea and BARF scores were significantly higher in patients requiring antiemetic agents (P = .0001) and decreased significantly after treatment (P = .0002), while posttreatment VAS (P = .20) and FPSR scores (P =.47) for patients receiving only antiemetic agents did not [corrected]. CONCLUSIONS: We describe the development of a pictorial scale with beginning evidence of construct validity for a self-report assessment of the severity of pediatric nausea. The scale had convergent and discriminant validity, along with an ability to detect change after treatment.

Direct delivery of MIF morpholinos into the zebrafish otocyst by injection and electroporation affects inner ear development.

In recent years, electroporation has become a popular technique for in vivo transfection of DNA, RNA, and morpholinos into various tissues, including the eye, brain, and somites of zebrafish. The advantage of electroporation over other methods of genetic manipulation is that specific tissues can be targeted, both spatially and temporally, for the introduction of macromolecules by the application of electrical current. Here we describe the use of electroporation for transfecting mif and mif-like morpholinos into the tissues of the developing inner ear of the zebrafish. In past studies, mif morpholino injected into embryos at the 1- to 8-cell stage resulted in widespread morphological changes in the nervous system and eye, as well as the ear. By targeting the tissues of the inner ear at later stages in development, we can determine the primary effects of MIF in the developing inner ear, as opposed to secondary effects that may result from the influence of other tissues. By using phalloidin and acetylated tubulin staining to study the morphology of neurons, neuronal processes, and hair cells associated with the posterior macula, we were able to assess the efficacy of electroporation as a method for targeted transfection in the zebrafish inner ear. The otic vesicles of 24hpf embryos were injected with morpholinos and electroporated and were then compared to embryos that had received no treatment or had been only injected or electroporated. Embryos that were injected and electroporated showed a decrease in hair cell numbers, decreased innervation by the statoacoustic ganglion (SAG) and fewer SAG neurons compared with control groups. Our results showed that direct delivery of morpholinos into otocysts at later stages avoids the non-specific nervous system and neural crest effects of morpholinos delivered at the 1-8 cell stage. It also allows examination of effects that are directed to the inner ear and not secondary effects on the ear from primary effects on the brain, neural crest or periotic mesenchyme.

Uniform cell seeding and generation of overlapping gradient profiles in a multiplexed microchamber device with normally-closed valves.

Generation of stable soluble-factor gradients in microfluidic devices enables studies of various cellular events such as chemotaxis and differentiation. However, many gradient devices directly expose cells to constant fluid flow and that can induce undesired responses from cells due to shear stress and/or wash out of cell-secreted molecules. Although there have been devices with flow-free gradients, they typically generate only a single condition and/or have a decaying gradient profile that does not accommodate long-term experiments. Here we describe a microdevice that generates several chemical gradient conditions on a single platform in flow-free microchambers which facilitates steady-state gradient profiles. The device contains embedded normally-closed valves that enable fast and uniform seeding of cells to all microchambers simultaneously. A network of microchannels distributes desired solutions from easy-access open reservoirs to a single output port, enabling a simple setup for inducing flow in the device. Embedded porous filters, sandwiched between the microchannel networks and cell microchambers, enable diffusion of biomolecules but inhibit any bulk flow over the cells.

The effect of intraoperative dexmedetomidine on postoperative analgesia and sedation in pediatric patients undergoing tonsillectomy and adenoidectomy.

BACKGROUND: The immediate postoperative period after tonsillectomy and adenoidectomy, one of the most common pediatric surgical procedures, is often difficult. These children frequently have severe pain but postoperative airway edema along with increased sensitivity to the respiratory-depressant effects of opioids may result in obstructive symptoms and hypoxemia. Opioid consumption may be reduced by nonsteroidal antiinflammatory drugs, but these drugs may be associated with increased bleeding after this operation. Dexmedetomidine has mild analgesic properties, causes sedation without respiratory depression, and does not have an effect on coagulation. We designed a prospective, double-blind, randomized controlled study to determine the effects of intraoperative dexmedetomidine on postoperative recovery including pain, sedation, and hemodynamics in pediatric patients undergoing tonsillectomy and adenoidectomy. METHODS: One hundred nine patients were randomized to receive a single intraoperative dose of dexmedetomidine 0.75 microg/kg, dexmedetomidine 1 microg/kg, morphine 50 microg/kg, or morphine 100 microg/kg over 10 minutes after endotracheal intubation. RESULTS: There were no significant differences among the 4 groups in patient demographics, ASA physical status, postoperative opioid requirements, sedation scores, duration of oxygen supplementation in the postanesthetic care unit, and time to discharge readiness. The median time to first postoperative rescue analgesic was similar in patients receiving dexmedetomidine 1 microg/kg and morphine 100 microg/kg, but significantly longer compared with patients receiving dexmedetomidine 0.75 microg/kg or morphine 50 microg/kg (P < 0.01). In addition, the number of patients requiring >1 rescue analgesic dose was significantly higher in the dexmedetomidine 0.75 microg/kg group compared with the dexmedetomidine 1 microg/kg and morphine 100 microg/kg groups, but not the morphine 50 microg/kg group. Patients receiving dexmedetomidine had significantly slower heart rates in the first 30 minutes after surgery compared with those receiving morphine (P < 0.05). There was no significant difference in sedation scores among the groups. CONCLUSIONS: The total postoperative rescue opioid requirements were similar in tonsillectomy patients receiving intraoperative dexmedetomidine or morphine. However, the use of dexmedetomidine 1 microg/kg and morphine 100 microg/kg had the advantages of an increased time to first analgesic and a reduced need for additional rescue analgesia doses, without increasing discharge times.