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Anthony Giuffrida,1 Christy Saia-Owenby,2 Chris Andriano,3,* Douglas Beall,4,* Ashley Bailey-Classen,5,* Patrick Buchanan,6,* Ryan Budwany,7,* Mehul J Desai,8,* Ashley Comer,9,* Andrew Dudas,10,* Vinicius Tieppo Francio,11,* Warren Grace,12,* Benjamin Gill,13,* Betsy Grunch,14,* Andrew Goldblum,13,* Rosa A Garcia,15,* David W Lee,16,* Chad Lavender,17,* Marco Lawandy,18,* Lyric Mandell,2,* Robin Mata,19,* Morteza Rabii,20,* Kiran Patel,21,* Raj G Patel,22,* Ankur A Patel,23,* Dawood Sayed,24,* Gurtej Singh,25,* Natalie Strand,26,* Jordan Tate,27,* Michael E Schatman,28 Timothy Deer29 1Cantor Spine Center, Paley Orthopedic and Spine Institute, Fort Lauderdale, FL, USA; 2MOXY Company, Covington, LA, USA; 3Georgia Pain Care, Stockbridge, GA, USA; 4Oklahoma Spine Hospital, Oklahoma City, OK, USA; 5Trinity Pain Medicine Associates, Fort Worth, TX, USA; 6Spanish Hills Interventional Pain Specialists, Camarillo, CA, USA; 7Center for Pain Relief, Charleston Area Medical Center, Charleston, WV, USA; 8International Spine, Pain, and Performance Center, Washington, DC, USA; 9The Spine and Nerve Centers of the Virginias, Charleston, WV, USA; 10Maya & Schnapp, Neurospine and Pain, Memphis, TN, USA; 11Anesthesiology and Pain Medicine, University of Kansas, Kansas City, KS, USA; 12Redefine Healthcare, Orthopedic Pain and Spine Center, Edison, NJ, USA; 13Physical Medicine and Rehabilitation, University of Missouri, Columbia, MO, USA; 14Longstreet Clinic, Gainesville, GA, USA; 15Larkin Hospital Health Systems, Miami, FL, USA; 16Interventional Pain and Spine, Fullerton Orthopedics, Yorba Linda, CA, USA; 17Department of Orthopaedics, Marshall University, Huntington, WV, USA; 18Physical Medicine and Rehabilitation, Montefiore Medical Center, New York, NY, USA; 19Department of Physical Medicine and Rehabilitation, University of Miami, Miami, FL, USA; 20Crimson Pain Management, Overland Park, KS, USA; 21Pain Medicine and Anesthesiology, Northwell Health, New York, NY, USA; 22Central Texas Interventional Pain Doctor, Capitol Pain Institute, Austin, TX, USA; 23Department of Neurological Surgery, UT Southwestern Medical Center, Dallas, TX, USA; 24Department of Pain Medicine and Neurology, University of Kansas Health System, Kansas City, KS, USA; 25Department of Pain Medicine, Rehabilitation, and Pain Medicine, the Center for Advance Orthopaedics, Cantonsville, MD, USA; 26Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Phoenix, AZ, USA; 27Department of Pain Medicine and Physical Medicine and Rehabilitation, Southern Pain and Spine, Jasper, GA, USA; 28Department of Anesthesiology, Perioperative Care, and Pain Medicine at NYU Grossman School of Medicine, New York, NY, USA; 29Department of Pain Management, Spine and Nerve Centers of the Virginias, Charleston, WV, USA*These authors contributed equally to this workCorrespondence: Lyric Mandell, MOXY Company, Covington, LA, USA, Email lyric@moxycompany.comPurpose: The American Society of Pain and Neuroscience (ASPN) identified a significant gap in resources and guidelines that aim to educate healthcare providers for best practices when engaging on social media. As part of the broader initiatives on Spine and Nerve practice, the executive board of ASPN has decided it would be beneficial to include comprehensive guidance for healthcare providers when engaging on social media.Methods: A panel of experts was chosen based on expertise, publications, diversity, and their social media presence. Along with expert guidance, the committee conducted an extensive analysis of peer-reviewed literature in communication and medical journals to determine best practices for healthcare practitioners on social media.Results: Social media messages significantly impact patients’ and colleagues’ perceptions and actions regarding medical issues. As such, providers and their teams must be aware of legal and ethical considerations in healthcare while maintaining a consistent, educational, and digestible persona online.Conclusion: The advancement of communication and medical technologies and systems necessitates continued education and resources to adapt to our rapidly changing media and medical landscape.Keywords: digital communication, social networking sites, healthcare providers, best practices, physician communication, social media, medical marketing, spine

Scott G Pritzlaff,1 Johnathan H Goree,2 Jonathan M Hagedorn,3 David W Lee,4 Kenneth B Chapman,5 Sandy Christiansen,6 Andrew Dudas,7 Alexander Escobar,8 Christopher J Gilligan,9 Maged Guirguis,10 Amitabh Gulati,11 Jessica Jameson,12 Christopher J Mallard,13 Melissa Murphy,14 Kiran V Patel,15 Raj G Patel,16 Samir J Sheth,17 Stephanie Vanterpool,18 Vinita Singh,19 Gregory Smith,2 Natalie H Strand,20 Chau M Vu,21 Tolga Suvar,22 Krishnan Chakravarthy,23 Leonardo Kapural,24 Michael S Leong,25 Timothy R Lubenow,22 Alaa Abd-Elsayed,26 Jason E Pope,21 Dawood Sayed,27 Timothy R Deer28 1Department of Anesthesiology and Pain Medicine, University of California, Davis, Sacramento, CA, USA; 2Department of Anesthesiology, University of Arkansas for Medical Sciences, Little Rock, AR, USA; 3Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Mayo Clinic, Rochester, MN, USA; 4Fullerton Orthopedic Surgery Medical Group, Fullerton, CA, USA; 5The Spine & Pain Institute of New York, New York, NY, USA; 6Department of Anesthesiology and Perioperative Medicine, Oregon Health & Science University, Portland, OR, USA; 7Mays & Schnapp Neurospine and Pain, Memphis, TN, USA; 8Department of Anesthesiology, University of Toledo, Toledo, OH, USA; 9Division of Pain Medicine, Brigham and Women’s Hospital Harvard Medical School, Boston, MA, USA; 10Division of Pain Management, Ochsner Health, New Orleans, LA, USA; 11Department of Anesthesiology and Critical Care, Memorial Sloan Kettering Cancer Center, New York, NY, USA; 12Axis Spine Center, Coeur D’Alene, ID, USA; 13Department of Anesthesiology, University of Kentucky, Lexington, KY, USA; 14North Texas Orthopedics and Spine Center, Grapevine, TX, USA; 15Department of Anesthesiology and Pain Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Northwell Health, Hempstead, NY, USA; 16Capitol Pain Institute, Austin, TX, USA; 17Interventional Pain Management, Sutter Health, Roseville, CA, USA; 18Department of Anesthesiology, University of Tennessee, Knoxville, TN, USA; 19Department of Anesthesiology, Emory University, Atlanta, GA, USA; 20Interventional Pain Management, Mayo Clinic, Scottsdale, AZ, USA; 21Evolve Restorative Center, Santa Rosa, CA, USA; 22Department of Anesthesiology and Pain Medicine, Rush University Medical Center, Chicago, IL, USA; 23Coastal Pain and Spinal Diagnostics Medical Group, San Diego, CA, USA; 24Carolinas Pain Institute, Winston-Salem, NC, USA; 25Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, CA, USA; 26Department of Anesthesiology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; 27Department of Anesthesiology, Pain and Perioperative Medicine, University of Kansas, Kansas City, KS, USA; 28The Spine and Nerve Center of the Virginias, Charleston, WV, USACorrespondence: Scott G Pritzlaff, University of California, Davis, 4860 Y Street, Suite 3020, Sacramento, CA, 95817, USA, Tel +1 916 734-6824, Fax +1 916 734-6827, Email spritzlaff@ucdavis.eduAbstract: The need to be competent in neuromodulation is and should be a prerequisite prior to completing a fellowship in interventional pain medicine. Unfortunately, many programs lack acceptable candidates for these advanced therapies, and fellows may not receive adequate exposure to neuromodulation procedures. The American Society of Pain and Neuroscience (ASPN) desires to create a consensus of experts to set a minimum standard of competence for neurostimulation procedures, including spinal cord stimulation (SCS), dorsal root ganglion stimulation (DRG-S), and peripheral nerve stimulation (PNS). The executive board of ASPN accepted nominations for colleagues with excellence in the subject matter of neuromodulation and physician education. This diverse group used peer-reviewed literature and, based on grading of evidence and expert opinion, developed critical consensus guides for training that all accredited fellowship programs should adopt. For each consensus point, transparency and recusal were used to eliminate bias, and an author was nominated for evidence grading oversight and bias control. Pain Education and Knowledge (PEAK) Consensus Guidelines for Neuromodulation sets a standard for neuromodulation training in pain fellowship training programs. The consensus panel has determined several recommendations to improve care in the United States for patients undergoing neuromodulation. As neuromodulation training in the United States has evolved dramatically, these therapies have become ubiquitous in pain medicine. Unfortunately, fellowship programs and the Accreditation Council for Graduate Medical Education (ACGME) pain program requirements have not progressed training to match the demands of modern advancements. PEAK sets a new standard for fellowship training and presents thirteen practice areas vital for physician competence in neuromodulation.Keywords: neuromodulation, pain education, spinal cord stimulation, dorsal root ganglion stimulation, peripheral nerve stimulation, fellowship training

Background Dydrogesterone, an oral selective progesterone receptor agonist with high bioavailability, has been used since the 1960s to treat various conditions arising due to the deficiency of progesterone. Patients are expected to have additional compliance and reduced pill burden with dydrogesterone 20 mg and 30 mg SR once a day (OD) for conditions requiring 10 mg twice a day (BID) or thrice a day (TID). Methodology A real-world analysis was conducted using the HealthPlix electronic medical records (EMR) database to understand the demography, indications, and prescription patterns of dydrogesterone 20 mg and 30 mg SR, including co-prescriptions. Results The mean age of the female patients prescribed dydrogesterone 20 mg SR was 27.23 ± 4.79 years while those prescribed 30 mg SR had a mean age of 28.56 ± 5.17 years. Common indications for the prescription of dydrogesterone 20 mg SR were pregnancy, infertility, and abortion/miscarriage. Pregnancy, infertility, and amenorrhea were the common conditions for dydrogesterone 30 mg SR prescription. The average duration of prescription of dydrogesterone 20 mg and 30 mg SR was 55.50 ± 31.33 and 79.66 ± 68.38 days, respectively. OD regimen was the preferred regimen for dydrogesterone 20 mg SR (89.48%) and dydrogesterone 30 mg SR (64.06%). Conclusions This analysis suggests dydrogesterone 20 mg and 30 mg SR are being prescribed for various indications in the real world with significant variation in the prescription patterns., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Royal Pune Independent Ethics Committee issued approval RPIEC140824. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Manickavasagam et al.)

Surgical management of the subscapularis tendon is critical to a successful outcome following anatomic total shoulder arthroplasty. However, the optimal surgical technique for adequate exposure of the glenohumeral joint while mini-mizing complications resulting from subscapularis tendon dysfunction continues to be controversial. Common surgical techniques for the management of the subscapularis tendon include tenotomy, peeling, sparing, and lesser tuberosity oste-otomy. Despite a number of published studies comparing these techniques, no consensus has been reached regarding optimal management. This article reviews the extensive literature on the biomechanical, radiologic, and clinical outcomes of each technique, including recently published comparison studies.

Background: Amongst various other factors, oxygen (O2) concentration in embryo culture plays an important role in determining pregnancy outcomes in women undergoing in vitro fertilisation. Some studies have reported that lowering O2 levels in embryo culture provides better results., Aims: To explore the effects of low- and ultra-low- O2 concentrations (5% and 2%, respectively) in extended embryo culture on various outcome parameters of pregnancy., Settings and Design: This was a retrospective cross-sectional study., Materials and Methods: In this study 382 participants had their embryos cultured in varying O2 concentrations (5% or 2%), followed by either a fresh embryo transfer (ET) or frozen embryo transfer (FET). Outcomes such as pregnancy rate, implantation rate, abortion rate, twinning rate, and live birth rate were compared between the groups., Statistical Analysis Used: Chi square test was applied to compare the primary and secondary outcomes between different groups., Results: No significant differences were observed in pregnancy rate and implantation rate between 5% and 2% O2 groups, irrespective of their mode of ET. The abortion rate was significantly higher in 5% O2 group than in 2% group during FET (24.71% vs. 11.49%, P = 0.02). While the proportion of good-quality embryos was higher in 5% O2 group, these did not translate to better pregnancy outcomes. Additionally, embryos cultured in 2% O2 concentration had a significantly better implantation rate when they were transferred fresh rather than frozen (71.34% vs. 61.46%, P = 0.04). There were no other differences observed., Conclusion: Only marginal benefits were observed in switching human embryos to ultra-low O2 concentration after the initial days of culture., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Human Reproductive Sciences.)

Tenosynovial giant cell tumors (TSGCT) are benign tumors originating from the synovial joint, bursa, or tendon sheath. Localized pigmented villonodular synovitis (PVNS), a subtype of TSGCT, commonly affects the hands and feet and has also been reported in the literature in the knee joint. There is sparse literature on localized PVNS arising specifically from meniscal tissue. We present a case report of a 17-year- old male with symptoms and MRI findings consistent with a lateral meniscus tear. Intraoperatively, the patient was found to have a mass originating from the torn meniscal tissue, which was confirmed by pathology to be a TSGCT. We performed a literature review of intra-articular localized PVNS within the knee presenting as a meniscal tear., Competing Interests: None declared., (Thieme. All rights reserved.)

CDK4/6 inhibitors significantly prolong progression-free survival in patients with advanced hormone receptor-positive (HR+) HER2-negative breast cancer. Despite recent successes, patients acquire resistance, necessitating the development of additional novel therapeutic strategies. Bromodomain and extra-terminal domain (BET) proteins are key epigenetic regulators that interact with acetylated lysine (AcLys) residues of histones or transcription factors. BET proteins are directly involved in modulating estrogen receptor (ER) signaling and the cell cycle. Therefore, BET inhibitors can potentially offer new strategies in the treatment of advanced ER+ breast cancer. ZEN-3694 is an orally bioavailable small molecule BET inhibitor currently being evaluated in Phase 1/2 clinical trials (NCT03901469). To assess a potential combination strategy in a CDK4/6i resistant breast cancer population, we investigated the mechanism of action of ZEN-3694 combined with CDK4/6 inhibitors in the ER+ cell lines resistant to palbociclib or abemaciclib. Here, we describe that the combination of ZEN-3694 with CDK4/6i potently inhibits proliferation and induces apoptosis in CDK4/6i resistant cell lines. The resistance to both palbociclib and abemaciclib was associated with the strong upregulation of CDK6 and CCND1 protein levels, which was reversed by the ZEN-3694 treatment. Furthermore, RNAseq data and pathway analysis elucidated the combinatorial effects of ZEN-3694 with CDK4/6 inhibitors through significant downregulation of multiple pathways involved in cell cycle regulation, cellular growth, proliferation, apoptosis, inflammation, and cellular immune response. Our data indicate that ZEN-3694 has therapeutic potential in combination with CDK4/6 inhibitors in patients with advanced ER+ breast resistant to CDK4/6 inhibitors., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Tophaceous gout affecting the olecranon region can result in local discomfort, skin ulceration, secondary infection, and considerable disability if left untreated. However, there are limited reports of outcomes, including postoperative complications and recurrence after surgical excision of tophaceous gout deposits at the elbow. The aim of this study is to present our surgical technique and minimum one-year outcomes after surgical excision of tophaceous gout involving the elbow., Methods: A retrospective chart review was performed on all patients from a single surgeon's practice who underwent surgical excision of gouty tophi of the elbow between January 2016 and December 2019. The indications for surgical excision of tophi included failure of medical management, presence of skin ulceration, and/or large gouty tophi. The relevant data pertaining to patient demographics, preoperative findings, intraoperative findings, surgical pathology reports, and short-term postoperative complications were collected through retrospective chart review. Patients were subsequently contacted for a follow-up telehealth visit to assess recurrence of gouty tophi, functional outcomes, and range of motion (ROM) measurements., Results: Six male patients underwent 7 total procedures (1 bilateral elbow) during the study period. The mean age of the cohort at the time of surgery was 56.0 ± 7.1 years (range: 45.3-63.5). The mean size of the swelling in 2 maximum dimensions was 5.8 × 3.4 cm. There were no intraoperative or immediate postoperative wound complications. There was no recurrence of gouty tophi at a mean follow-up time of 30.8 months (range: 14.0-43.5). Patients reported physiologic ROM (mean flexion-extension arc of 2°-134°) with no pain at final follow-up., Conclusion: Surgical treatment of tophaceous gout of the elbow is associated with a low risk of wound complication and recurrence., (© 2022 The Authors.)

Background: The objective of this study was to assess patient satisfaction and preference for telemedicine vs. in-person visits for outpatient shoulder and elbow musculoskeletal consultation during the coronavirus disease 2019 (COVID-19) pandemic and in the future., Methods: Patients who had telemedicine visits for shoulder and elbow musculoskeletal complaints at a single institution from March through June 2020 were invited to respond to a post-visit survey. The survey included a standardized questionnaire that focused on the patient's satisfaction with the telemedicine visits during the pandemic and preference for using the telemedicine platform in the future, following the pandemic. Additional details regarding their virtual visits (severity of medical condition, as well as previous virtual or emergency department visits) were also obtained. Data regarding patient demographic characteristics and visit details (primary diagnosis, type of visit, length of visit, and treating physician) were extracted from the electronic medical records., Results: In total, 153 patients participated in the study. Overall, high satisfaction scores regarding the telemedicine visits were noted: 91% of patients reported that their concerns were adequately addressed, 89% would recommend telemedicine to a friend, and 94% stated that they would use the telemedicine platform again in the presence of a situation similar to the COVID-19 pandemic. However, the majority of patients (76%) reported a preference for in-person visits for the same musculoskeletal complaint if it were not for COVID-19. A telemedicine visit duration > 10 minutes and a first-time telemedicine visit correlated with higher satisfaction rates (P = .037 and P = .001, respectively)., Conclusions: COVID-19 has provided a boost to the use of our telemedicine platform, with a high satisfaction rate among patients with shoulder and elbow musculoskeletal complaints, largely owing to safety reasons and limited access to in-person doctor visits. However, a considerable number of patients would have preferred in-person visits for similar health complaints if there were no pandemic. Further research on optimizing the selection of patients for telemedicine visits and addressing their expectations and concerns regarding their visits will improve patients' preference for future telemedicine visits., (Copyright © 2021 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Sleep is essential for good health however, it is often neglected in medical education. As four students wanting to tackle this unique problem, we realised the necessity of establishing a platform dedicated to teaching about sleep., (© 2020 John Wiley & Sons Ltd and The Association for the Study of Medical Education.)

BET proteins are key epigenetic regulators that regulate transcription through binding to acetylated lysine (AcLys) residues of histones and transcription factors through bromodomains (BDs). The disruption of this interaction with small molecule bromodomain inhibitors is a promising approach to treat various diseases including cancer, autoimmune and cardiovascular diseases. Covalent inhibitors can potentially offer a more durable target inhibition leading to improved in vivo pharmacology. Here we describe the design of covalent inhibitors of BRD4(BD1) that target a methionine in the binding pocket by attaching an epoxide warhead to a suitably oriented noncovalent inhibitor. Using thermal denaturation, MALDI-TOF mass spectrometry, and an X-ray crystal structure, we demonstrate that these inhibitors selectively form a covalent bond with Met149 in BRD4(BD1) but not other bromodomains and provide durable transcriptional and antiproliferative activity in cell based assays. Covalent targeting of methionine offers a novel approach to drug discovery for BET proteins and other targets.

The nose is a complex structure important in facial aesthetics and in respiratory physiology. Nasal defects can pose a challenge to reconstructive surgeons who must re-create nasal symmetry while maintaining nasal function. A basic understanding of the underlying nasal anatomy is thus necessary for successful nasal reconstruction., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Bromodomains are epigenetic readers that specifically bind to the acetyl lysine residues of histones and transcription factors. Small molecule BET bromodomain inhibitors can disrupt this interaction which leads to potential modulation of several disease states. Here we describe the binding properties of a novel BET inhibitor RVX-297 that is structurally related to the clinical compound RVX-208, currently undergoing phase III clinical trials for the treatment of cardiovascular diseases, but is distinctly different in its biological and pharmacokinetic profiles. We report that RVX-297 preferentially binds to the BD2 domains of the BET bromodomain and Extra Terminal (BET) family of protein. We demonstrate the differential binding modes of RVX-297 in BD1 and BD2 domains of BRD4 and BRD2 using X-ray crystallography, and describe the structural differences driving the BD2 selective binding of RVX-297. The isothermal titration calorimetry (ITC) data illustrate the related differential thermodynamics of binding of RVX-297 to single as well as dual BET bromodomains., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Apabetalone (RVX-208) inhibits the interaction between epigenetic regulators known as bromodomain and extraterminal (BET) proteins and acetyl-lysine marks on histone tails. Data presented here supports the manuscript published in Atherosclerosis "RVX-208, a BET-inhibitor for Treating Atherosclerotic Cardiovascular Disease, Raises ApoA-I/HDL and Represses Pathways that Contribute to Cardiovascular Disease" (Gilham et al., 2016) [1]. It shows that RVX-208 and a comparator BET inhibitor (BETi) JQ1 increase mRNA expression and production of apolipoprotein A-I (ApoA-I), the main protein component of high density lipoproteins, in primary human and African green monkey hepatocytes. In addition, reported here are gene expression changes from a microarray-based analysis of human whole blood and of primary human hepatocytes treated with RVX-208.

The relationship between nasal resistance (R) and airspace minimal cross-sectional area (mCSA) remains unclear. After the introduction of acoustic rhinometry, many otolaryngologists believed that mCSA measurements would correlate with subjective perception of nasal airway obstruction (NAO), and thus could provide an objective measure of nasal patency to guide therapy. However, multiple studies reported a low correlation between mCSA and subjective nasal patency, and between mCSA and R. This apparent lack of correlation between nasal form and function has been a long-standing enigma in the field of rhinology. Here we propose that nasal resistance is described by the Bernoulli Obstruction Theory. This theory predicts two flow regimes. For mCSA>Acrit, the constriction is not too severe and there is not a tight coupling between R and mCSA. In contrast, when mCSAAcrit (estimated to be 0.37cm(2)), this theory suggests that airway constrictions are rarely an exclusive contributor to nasal resistance, which may explain the weak correlation between mCSA and subjective nasal patency., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Limited health literacy is a risk factor for poor outcomes in numerous health care settings. Little is known about the impact of instructional modality and health literacy on adherence to emergency department (ED) discharge instructions., Purpose: To examine the impact of instructional modality on 72-hour antibiotic retrieval among ED patients prescribed outpatient antibiotics for infections., Methods: English-speaking ED patients diagnosed as having acute infections and prescribed outpatient antibiotics were randomized to standard discharge instructions, standard instructions plus text-messaged instructions, or standard instructions plus voicemailed instructions targeting ED prescriptions. Health literacy was determined by validated instrument. Seventy-two-hour antibiotic retrieval, 30-day report of prescription completion, and discharge instructional modality preference were assessed., Results: Nearly one-quarter of the 2521 participants demonstrated low health literacy. Low health literacy predicted decreased 72-hour antibiotic retrieval (χ(2) = 9.56, P=.008). No significant association with antibiotic retrieval was noted across the 3 treatment groups (χ(2) = 5.112, P=.078). However, patients randomized to the text message group retrieved antibiotic prescriptions within 72 hours more frequently than did those randomized to the voicemail treatment group (χ(2) = 4.345, P=.037), and patients with low health literacy randomized to voicemailed instructions retrieved their antibiotic prescriptions less frequently than did those randomized to standard of care instructions (χ(2) = 5.526, P=.019). Reported instructional modality preferences were inconsistent with the primary findings of the study., Conclusions: Discharge instructional modality impacts antibiotic retrieval in patients with low health literacy. Preference for discharge instructional modality varies by degree of health literacy, but does not predict which modality will optimize 72-hour antibiotic retrieval., (Copyright © 2016 Elsevier Inc. All rights reserved.)

High density lipoproteins (HDL), through activity of the main protein component apolipoprotein A-I (ApoA-I), can reduce the risk of cardiovascular disease (CVD) by removing excess cholesterol from atherosclerotic plaque. In this study, we demonstrate that the bromodomain and extraterminal domain (BET) inhibitor RVX-208 increases ApoA-I gene transcription and protein production in human and primate primary hepatocytes. Accordingly, RVX-208 also significantly increases levels of ApoA-I, HDL-associated cholesterol, and HDL particle number in patients who received the compound in recently completed phase 2b trials SUSTAIN and ASSURE. Moreover, a post-hoc analysis showed lower instances of major adverse cardiac events in patients receiving RVX-208. To understand the effects of RVX-208 on biological processes underlying cardiovascular risk, we performed microarray analyses of human primary hepatocytes and whole blood treated ex vivo. Overall, data showed that RVX-208 raises ApoA-I/HDL and represses pro-inflammatory, pro-atherosclerotic and pro-thrombotic pathways that can contribute to CVD risk., (Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

Objectives: (1) To develop a method to account for the confounding effect of the nasal cycle when comparing preoperative and postoperative objective measures of nasal patency. (2) To illustrate this method by reporting objective measures derived from computational fluid dynamics (CFD) models spanning the full range of mucosal engorgement associated with the nasal cycle in 2 subjects., Study Design: Retrospective., Setting: Academic tertiary medical center., Subjects and Methods: A cohort of 24 patients with nasal airway obstruction was reviewed to select the 2 patients with the greatest reciprocal change in mucosal engorgement between preoperative and postoperative computed tomography (CT) scans. Three-dimensional anatomic models were created based on the preoperative and postoperative CT scans. Nasal cycling models were also created by gradually changing the thickness of the inferior turbinate, middle turbinate, and septal swell body. Moreover, CFD was used to simulate airflow and to calculate nasal resistance and the average heat flux., Results: Before accounting for the nasal cycle, patient A appeared to have a paradoxical worsening nasal obstruction in the right cavity postoperatively. After accounting for the nasal cycle, patient A had small improvements in objective measures postoperatively. The magnitude of the surgical effect also differed in patient B after accounting for the nasal cycle., Conclusion: By simulating the nasal cycle and comparing models in similar congestive states, surgical changes in nasal patency can be distinguished from physiological changes associated with the nasal cycle. This ability can lead to more precise comparisons of preoperative and postoperative objective measures and potentially more accurate virtual surgery planning., (© American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.)

Pain is a leading public health problem in the United States, with an annual economic burden of more than $630 billion, and is one of the most common reasons that individuals seek emergency department (ED) care. There is a paucity of data regarding sex differences in the assessment and treatment of acute and chronic pain conditions in the ED. The Academic Emergency Medicine consensus conference convened in Dallas, Texas, in May 2014 to develop a research agenda to address this issue among others related to sex differences in the ED. Prior to the conference, experts and stakeholders from emergency medicine and the pain research field reviewed the current literature and identified eight candidate priority areas. At the conference, these eight areas were reviewed and all eight were ratified using a nominal group technique to build consensus. These priority areas were: 1) gender differences in the pharmacological and nonpharmacological interventions for pain, including differences in opioid tolerance, side effects, or misuse; 2) gender differences in pain severity perceptions, clinically meaningful differences in acute pain, and pain treatment preferences; 3) gender differences in pain outcomes of ED patients across the life span; 4) gender differences in the relationship between acute pain and acute psychological responses; 5) the influence of physician-patient gender differences and characteristics on the assessment and treatment of pain; 6) gender differences in the influence of acute stress and chronic stress on acute pain responses; 7) gender differences in biological mechanisms and molecular pathways mediating acute pain in ED populations; and 8) gender differences in biological mechanisms and molecular pathways mediating chronic pain development after trauma, stress, or acute illness exposure. These areas represent priority areas for future scientific inquiry, and gaining understanding in these will be essential to improving our understanding of sex and gender differences in the assessment and treatment of pain conditions in emergency care settings., (© 2014 by the Society for Academic Emergency Medicine.)

We investigated the prevalence and risk factors for preoperative dental clearance failure in joint arthroplasty patients. Over a 5-month period, all patients scheduling total joint arthroplasty completed a dental questionnaire. Data collected included demographics, medical and dental history, dental hygiene practices, frequency of dental care, and results of dental clearance. Of the 300 patients, 35 (12%) failed dental clearance. Risk factors included tobacco use, poor flossing habits, history of tooth extraction, age, narcotic use, and lack of a dentist visit within 12 months. Of 189 patients who lacked the 3 least prevalent risk factors (tobacco use, narcotic use, no dental visit within 12 months), 11 (6%) failed dental clearance. Selective dental clearance based on patient risk stratification may be a reasonable approach., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Bioengineered hydrogels have been explored in cell and tissue engineering applications to support cell growth and modulate its behavior. A rationally designed scaffold should allow for encapsulated cells to survive, adhere, proliferate, remodel the niche, and can be used for controlled delivery of biomolecules. Here we report a microarray of composite bioadhesive microgels with modular dimensions, tunable mechanical properties and bulk modified adhesive biomolecule composition. Composite bioadhesive microgels of maleimide functionalized polyethylene glycol (PEG-MAL) with interpenetrating network (IPN) of gelatin ionically cross-linked with silicate nanoparticles were engineered by integrating microfabrication with Michael-type addition chemistry and ionic gelation. By encapsulating clinically relevant anchorage-dependent cervical cancer cells and suspension leukemia cells as cell culture models in these composite microgels, we demonstrate enhanced cell spreading, survival, and metabolic activity compared to control gels. The composite bioadhesive hydrogels represent a platform that could be used to study independent effect of stiffness and adhesive ligand density on cell survival and function. We envision that such microarrays of cell adhesive microenvironments, which do not require harsh chemical and UV crosslinking conditions, will provide a more efficacious cell culture platform that can be used to study cell behavior and survival, function as building blocks to fabricate 3D tissue structures, cell delivery systems, and high throughput drug screening devices.

Objectives: There are many studies that evaluate the role of surgery in the treatment of complications of pediatric acute sinusitis; however there are few studies, if any that report the incidence of surgery following recovery from acute complicated sinusitis. The goal of this study was to report the incidence and indications for surgical intervention after recovery from complications of pediatric acute sinusitis., Methods: We reviewed the records of all children admitted to a tertiary care children's hospital between January 2005 and September 2010 with a diagnosis of sinusitis and an orbital or intracranial complication. Eighty-six patients met inclusion criteria. Charts were reviewed for type of complication, initial treatment (medical or surgical), type of procedure, secondary procedures, age, and comorbidities. Statistical analysis was completed using independent samples student t-tests and Mann-Whitney tests., Results: A total of 86 patients with a mean age of 6.38 years (2 months to 18 years) were identified. Eighty patients had orbital complications while six presented with intracranial complications. Twenty-seven patients (31%) underwent sinus surgery during the acute phase of their illness whereas 59 patients (69%) were treated medically. After hospitalization and recovery for acute complicated sinusitis, surgery was performed on nine patients (mean age 4.86 years) within 1 month to 2 years post hospitalization. Of the nine patients who required secondary surgery following resolution of the initial complicated sinusitis, four patients were following initial surgical intervention and five patients had initially resolved their complication with medical therapy alone. Indications for subsequent surgery included failure of medical therapy for persistent rhinosinusitis (8 patients) and second complication (1 patient)., Conclusions: This study suggests that following resolution of complicated pediatric rhinosinusitis, very few patients may need further surgical intervention. Subsequent intervention is best guided by clinical judgment, symptoms during outpatient clinic visits, and failure of medical therapy., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

A new series of N-arylamino biquinoline derivatives 5a-x were synthesized by reaction of 2-chloro-3-formyl quinolines 2a-d with malononitrile and various enhydrazinoketones 4a-f in absolute ethanol. The newly synthesized compounds were evaluated for their in vitro antimicrobial activity against a representative panel of pathogenic strains and antituberculosis activity against Mycobacterium tuberculosis H37Rv. Compounds 5h and 5s exhibited excellent antibacterial activity and some of the compounds demonstrated moderate antituberculosis activities compared with the first line drugs. The compounds were evaluated in vitro for their activity against the growth of Plasmodium falciparum, the malaria causing parasite. Some of them showed antimalarial activity with IC(50) values as low as 0.005-0.009 μg/mL., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

A new series of pyrano[4,3-b]pyran 4a-i and pyrano[3,2-c]chromene 6a-r derivatives bearing a 2-thiophenoxyquinoline nucleus were synthesized by reaction of 2-(4-(un)-substituted thiophenoxy)quinoline-3-carbaldehydes 2a-i with 6-methyl-4-hydroxypyran-2-one 3 and 4-hydroxy-6-(un)-substituted-2H-chromen-2-one 5a-b respectively and malononitrile at room temperature in the presence of KOH as a basic catalyst. All the compounds were screened against three Gram-positive bacteria (Streptococcus pneumoniae, Bacillus subtilis, Clostridium tetani), three Gram-negative bacteria (Salmonella typhi, Escherichia coli, Vibrio cholerae) and two fungi (Candida albicans, Aspergillus fumigatus) using the broth microdilution MIC (minimum inhibitory concentration) method. Upon antimicrobial screening, it was observed that the majority of the compounds were found to be active against Bacillus subtilis, Clostridium tetani and Candida albicans as compared to standard drugs., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A new series of fused pyran derivatives 5a-x bearing 2-morpholinoquinoline nucleus has been synthesized under microwave irradiation by a reaction of 2-morpholinoquinoline-3-carbaldehyde 2a-c, malononitrile 3 and compounds 4a-h in presence of NaOH as basic catalyst. All the compounds were screened against three Gram positive bacteria (Streptococcus pneumoniae, Clostridium tetani, Bacillus subtilis), three Gram negative bacteria (Salmonella typhi, Vibrio cholerae, Escherichia coli) and two fungi (Aspergillus fumigatus, Candida albicans) using broth microdilution MIC (Minimum Inhibitory Concentration) method. Of the compounds studied, compounds 5b, 5f, 5k, 5m, 5q, 5s and 5v have found to be most efficient members of the series., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

A new class of β-aryloxyquinolines 3a-i and their pyrano[3,2-c]chromene derivatives 6a-r incorporating a validated molecular target has been synthesized via a nucleophilic displacement and a one-pot multicomponent reaction respectively. In vitro antimicrobial activity of the synthesized compounds were investigated against a representative panel of pathogenic strains specifically Bacillus subtilis, Clostridium tetani, Streptococcus pneumoniae, Escherichia coli, Salmonella typhi, Vibrio cholera, Aspergillus fumigatus and Candida albicans. Compounds 3c, 3e, 3g, 6f, 6l and 6q exhibited excellent antibacterial activity while compound 6p exhibited more potent antifungal activity than that of first line standard drugs. In vitro antituberculosis activity was evaluated against Mycobacterium tuberculosis H37Rv and compound 6f is emerged as the promising antimicrobial member with better antitubercular activity. Majority of the compounds appears to be better antimicrobials but poor antituberculars., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Unlabelled: The aims of this study were to evaluate cardiac involvement, assess risk factors and mortality, and define the outcome of cardiac abnormalities with age in the different types of mucopolysaccharidoses (MPS). The echocardiograms of 99 patients with MPS, aged 1-24 y (median age 10.3 y) were reviewed between 1978 and 2000. Mitral regurgitation (MR) was detected in 29 patients (29%). MR was more frequent in types IH [n = 11 (38%)], II [n = 10 (24%)] and III [n = 4 (20%)]. Sixteen patients (16%) developed aortic regurgitation (AR), seen mostly in types II [n = 9 (56%)] and IV [n = 4 (24%)]. AR and/or MR was detected in 37 patients and 8 had both abnormalities of borderline significance (odds ratio 2.95, 95% confidence interval 1.0-8.85, p = 0.05). Of 99 patients, 47 had a normal study on their first echocardiogram, whereas only 7 had a normal study on subsequent echocardiograms. Fifty-four (54%) had a single echocardiogram. Of these, 27 (50%) were abnormal and 27 normal. Forty-five patients had more than one echocardiogram, of which 25 (56%) were abnormal and 20 normal. In 13/20 (65%) a cardiac abnormality developed on a subsequent echocardiogram which was statistically significant (p = 0.002). Overall mitral and aortic valve abnormalities showed a positive association with age. Univariate analysis of risk factors showed that increasing age, MPS I and ejection fraction were significant risk factors for death. However, left ventricular hypertrophy, mitral valve abnormalities and type II MPS were not significant risk factors for death, with borderline significance for aortic valve abnormalities., Conclusion: This study demonstrates the evaluation of ventricular function, which is a significant risk factor for death, along with increasing age and MPS I, and outlines the borderline significance of aortic valve abnormalities, which has not been mentioned in previous studies. It also shows that mitral valve lesions, commonly seen in MPS, were not a significant risk factor for death. The results emphasize the importance of performing serial echocardiograms in patients with MPS to assess ventricular function and the progression of cardiac abnormalities with age.

Mammalian brain development requires the transmission of electrical signals between neurons via the N-methyl-d-aspartate (NMDA) class of glutamate receptors. However, little is known about how NMDA receptors carry out this role. Here we report the first genes shown to be regulated by physiological levels of NMDA receptor function in developing neurons in vivo: NMDA receptor-regulated gene 1 (NARG1), NARG2, and NARG3. These genes share several striking regulatory features. All three are expressed at high levels in the neonatal brain in regions of neuronal proliferation and migration, are dramatically down-regulated during early postnatal development, and are down-regulated by NMDA receptor function. NARG2 and NARG3 appear to be novel, while NARG1 is the mammalian homologue of a yeast N-terminal acetyltransferase that regulates entry into the G(o) phase of the cell cycle. The results suggest that highly specific NMDA receptor-dependent regulation of gene expression plays an important role in the transition from proliferation of neuronal precursors to differentiation of neurons.

Pulmonary manifestations in sarcoidosis vary, ranging from asymptomatic chest radiographic abnormalities to progressive destruction of lung parenchyma with respiratory insufficiency. We describe a case of sarcoidosis in a patient with bilateral hydropneumothorax, parenchyma infiltrates, and respiratory insufficiency. Hydropneumothorax is extremely rare, and to our knowledge only two cases have been reported.

Introduction: Percutaneous transtracheal jet ventilation (PTJV) with a large-bore angiocath that is inserted through the cricothyroid membrane can provide immediate oxygenation from a high-pressure (50 lb per square inch) oxygen wall outlet, as well as ventilation by means of manual triggering. The objective of this retrospective study is to highlight the potential benefit of PTJV as a temporary lifesaving procedure during difficult situations when oral endotracheal intubation is unsuccessful and bag-valve-mask ventilation is ineffective for oxygenation during acute respiratory failure., Methods: The medical records of 29 consecutive patients who required emergent PTJV within the past 4 years were reviewed. PTJV was required because the pulse O(2) saturation could not be maintained at > 90% with bag-mask-valve ventilation and because the airway could not be secured quickly with direct laryngoscopy., Results: The cricothyroid membrane was cannulated successfully in 23 patients. In these patients, pulse O(2) saturation was raised to > 90% and was maintained with PTJV until the airway was secured. All but 3 of the 23 patients were subsequently intubated orally. In one patient, PTJV maintained adequate gas exchange until an emergent tracheostomy was performed. In two patients, airway exchange catheters were inserted into the trachea due to a small glottic aperture. The endotracheal tube was slid over the catheter. In 6 of the 29 patients, there was difficulty inserting a catheter through the cricothyroid membrane or there was inability to insufflate the oxygen with a jet ventilator. There were no immediate fatalities from the use of PTJV., Conclusion: Based on the subsequent insertion of an endotracheal tube into the trachea, there were two important benefits in the patients who underwent PTJV successfully. First, PTJV provided effective oxygenation, while allowing adequate time for upper airway visualization and possible suctioning of oropharyngeal secretions. Second, tracheal intubation was subsequently easier, possibly because the high tracheal pressure from the gas insufflation opened the collapsed glottis, making visualization of the glottic aperture better. PTJV is safe and quick in providing immediate oxygenation, and therefore should be considered as an alternative to insistent, multiple intubation attempts, when neither bag-mask-valve ventilation nor endotracheal intubation is feasible in providing adequate gas exchange.

A 5 year old girl with a haemodynamically significant mid-muscular ventricular septal defect (VSD) had successful transcatheter closure using the Amplatzer VSD occluder. This device passes through a small diameter sheath and can be easily retrieved or repositioned. These properties may make it a suitable device for closure of large mid-muscular defects in small children.

Human ehrlichiosis is not a common cause of acute respiratory distress syndrome (ARDS). Physicians should be aware of this life-threatening but treatable entity. Progression to ARDS may be related to delay in diagnosis and treatment. Fever, leukopenia, thrombocytopenia, and a history of tick exposure in an endemic area during the spring and summer months should alert the physician to the possibility of human ehrlichiosis, since a definitive diagnosis requires serologic testing that may take weeks to confirm. We describe a case of ARDS resulting from human ehrlichiosis. A unique feature in our case was that despite the early use of doxycycline, the patient had near fatal ARDS that responded dramatically to high doses of steroids.

Background: We sought to determine the relationship among radiographic findings, clinical presentation, and diagnostic testing of pulmonary blastomycosis., Methods: We reviewed the medical records of 100 consecutive patients with pulmonary blastomycosis., Results: Air-space infiltrates were the usual radiographic finding of pulmonary blastomycosis. Mass-like infiltrates were associated more with chronic than acute presentations. Air-space and mass-like infiltrate were predominately involved in the upper lobes. Sputum analysis made the initial diagnosis of blastomycosis most often. Acute and chronic presentations were not different between immunosuppressed patients and the remainder of the patients. In addition, infiltrates on chest radiographs in immunosuppressed patients were similar to the other patients., Conclusions: In an endemic area, pulmonary blastomycosis should be considered for any pulmonary infiltrate, especially in the upper lobes. Sputum analysis in most cases aids in the diagnosis, but bronchoscopy and/or tissue biopsy should be considered if the suspicion of blastomycosis is high and sputum analysis is inconclusive, negative, or not possible. Follow-up with chest radiographs after antifungal therapy is reasonable until complete resolution or fibrotic changes in patients with pulmonary blastomycosis.

Study Objective: Our objective was to compare respiratory muscle performance, pulmonary mechanics, and gas exchange between the BiPAP S/T-D ventilation system (Respironics Inc; Murrysville, PA) and the Servo Ventilator 900C (Siemens-Elma AB; Sweden) with similar inspiratory and expiratory airway pressure in patients who are recovering from acute respiratory failure., Study Design: A prospective, randomized, clinical trial., Setting: Medical ICU., Patients and Methods: We studied 27 medical patients on mechanical ventilators following gradual pressure support weaning. Each patient breathed while in the following equivalent modes: (a) an inspiratory pressure preset (pressure support mode) of 5 cm H2O with an external positive end-expiratory pressure (PEEP) of 5 cm H2O on the Servo Ventilator 900C and (b) an inspiratory pressure preset of 10 cm H2O with an expiratory pressure preset of 5 cm H2O on the BiPAP S/T-D. Using the CP-100 pulmonary monitor, we compared the total work of breathing (WOB), the pressure-time index (PTP), and other pulmonary mechanics and gas exchange parameters between the two modes., Results: The WOB injoules per liter (mean +/- SE) (0.76+/-0.08 vs 0.73+/-0.08, p = 0.70), the WOB in joules per minute (8.62+/-1.06 vs 8.11+/-0.96, p = 0.60), and the PTP in cm H2O/s/min (187+/-18 vs 167+/-18, p = 0.21) between the BiPAP S/T-D and the Servo Ventilator 900C were not statistically different. There were statistically significant differences between the two ventilators in auto-PEEP (1.34+/-0.37 vs 0.88+/-0.30 cm H2O, p = 0.03), duty cycle (0.44+/-0.01 vs 0.37+/-0.01, p < 0.001), and expiratory airway resistance (11.81+/-1.53 vs 8.75+/-1.22 cm H2O/L/s, p < 0.001), but not in respiratory rate (27.48+/-1.54 vs 28.06+/-1.61 breaths/min, p = 0.40) or in minute ventilation (10.43+/-0.59 vs 10.27+/-0.37 L/min, p = 0.66). There was a statistically significant difference in the ratio of Pa(O2) to the fraction of inspired oxygen (F(IO2)) (333+/-21 vs 300+/-22, p < 0.03) but not in Pa(CO2) (48+/-2 vs 47+/-2 mm Hg, p = 0.59) between the BiPAP S/T-D and the Servo Ventilator 900C., Conclusions: Despite differences in initiating and maintaining the inspiratory and expiratory phases, in breathing circuits, and in ventilator circuits between the two ventilators, the performance of the BiPAP S/T-D is equally efficacious to that of a conventional mechanical ventilator in supporting respiratory muscles. Thus, the BiPAP S/T-D is safe and effective when used in mechanically ventilated patients recovering from acute respiratory failure who do not require total ventilatory support.

This is an uncommon case of a patient who developed pneumopericardium while being treated with face-mask continuous positive airway pressure (CPAP) for hypoxic respiratory failure following a coronary artery bypass graft surgery. A pneumopericardium detected by chest radiograph resolved completely after discontinuation of face-mask CPAP. Possible mechanisms that may have been involved in this unusual complication are reviewed.

Objective: To report initial experience with a new occlusion device for native and residual patent ductus arteriosus., Design: Descriptive study of consecutive non-randomised patients undergoing a new method of patent ductus arteriosus closure with detachable coils., Setting: Tertiary centres for paediatric cardiology., Patients: 71 consecutive patients, aged 1.2-22 years, with a patent ductus arteriosus (PDA) underwent elective transcatheter closure. 45 had native PDAs (group A) with a minimum diameter of 1.0 mm-5.0 mm (median 2.0 mm). A further 26 had undergone one or more previous occlusion attempts (group B)., Interventions: A total of 133 detachable (Cook) spring coils were successfully implanted in 70 patients. The procedure was performed transvenously in 51 patients, retrograde arterially in 13, and by both routes in a further 6 patients. One 5 mm coil migrated but was successfully retrieved., Main Outcome Measures: In group A colour flow Doppler echocardiography showed that complete occlusion was achieved in 40/45 (89%) at 24 hours, 41/45 (91%) at 1 month, and 44/45 (98%) by 6 months post procedure. Occlusion rates in residual PDAs were 22/25 (88%) occluded at 24 hours, 23/25 (92%) at 1 month, and 24/25 (96%) at 6 months follow up., Conclusions: Transcatheter occlusion using detachable (Cook) spring coils is a safe and effective alternative to presently available devices. The delivery system allows full retrieval of the coil until a satisfactory position is obtained.

The lack of oral anticoagulant guidelines specific to paediatric practice has led to the adoption of adult regimens, often without scientific evidence of efficacy or safety. A two year prospective study of anticoagulant control was carried out in 45 children aged 9 months to 18 years, the majority of whom were receiving primary prophylactic anticoagulation. The main indication was congenital heart disease, either with (n = 8) or without (n = 34) mechanical valve prosthesis. During a follow up period of 602 patient months the average interval between visits was three weeks. Target international normalised ratios (INRs) were achieved on 62% and 39% of visits for children with low target INR (2.0-3.0) and high target INR (3.0-4.0) respectively. However warfarin dose was altered on only 22% of visits. Warfarin doses required to achieve a stable INR of 2.0-3.0 in 33 children were strongly correlated with weight [dose (mg/d) = 0.07 x weight (kg) + 0.54] but independently influenced by age. No thrombotic complications were recorded, and haemorrhagic events were infrequent (2.1% of visits) and, with one exception, minor. Safe outpatient oral anticoagulation is feasible in children, whose warfarin requirements appear moderately predictable and whose control is no more erratic than that of adults.

Using indices to predict weaning outcome can avoid premature extubation and unnecessary prolongation of ventilatory support. Unfortunately, none of the indices is consistently able to predict outcome. The key to successful weaning is to assess respiratory function repeatedly with several indices, not just one. The patient should be able to sustain spontaneous breathing for at least 24 hours on minimal partial ventilatory support (a pressure support or a continuous positive airway pressure of 5 cm H2O or a T piece, for example). Indices of maximal inspiratory pressure; work of breathing; and rapid, shallow breathing are useful in evaluating a patient's respiratory muscle performance; airway occlusion pressure is helpful as well when increased neuromuscular drive is a problem.

Mucoepidermoid tumors are rare bronchial adenomas whose clinical presentation can mimic that of bronchial asthma. Bronchial adenoma should be included in the differential diagnosis of a patient with a persistent radiographic abnormality and clinical features of bronchial asthma. We present an adolescent female with a history suggestive of bronchial asthma and a persistent left lower lobe atelectasis, who later was found to have a low-grade mucoepidermoid tumor.