Showing papers by "Lenox Hill Hospital published in 2017"

Official ERS/ATS clinical practice guidelines: noninvasive ventilation for acute respiratory failure

Abstract: Noninvasive mechanical ventilation (NIV) is widely used in the acute care setting for acute respiratory failure (ARF) across a variety of aetiologies. This document provides European Respiratory Society/American Thoracic Society recommendations for the clinical application of NIV based on the most current literature. The guideline committee was composed of clinicians, methodologists and experts in the field of NIV. The committee developed recommendations based on the GRADE (Grading, Recommendation, Assessment, Development and Evaluation) methodology for each actionable question. The GRADE Evidence to Decision framework in the guideline development tool was used to generate recommendations. A number of topics were addressed using technical summaries without recommendations and these are discussed in the supplementary material. This guideline committee developed recommendations for 11 actionable questions in a PICO (population–intervention–comparison–outcome) format, all addressing the use of NIV for various aetiologies of ARF. The specific conditions where recommendations were made include exacerbation of chronic obstructive pulmonary disease, cardiogenic pulmonary oedema, de novo hypoxaemic respiratory failure, immunocompromised patients, chest trauma, palliation, post-operative care, weaning and post-extubation. This document summarises the current state of knowledge regarding the role of NIV in ARF. Evidence-based recommendations provide guidance to relevant stakeholders.

Cancer-Associated Mutations in Endometriosis without Cancer

Abstract: BackgroundEndometriosis, defined as the presence of ectopic endometrial stroma and epithelium, affects approximately 10% of reproductive-age women and can cause pelvic pain and infertility. Endometriotic lesions are considered to be benign inflammatory lesions but have cancerlike features such as local invasion and resistance to apoptosis. MethodsWe analyzed deeply infiltrating endometriotic lesions from 27 patients by means of exomewide sequencing (24 patients) or cancer-driver targeted sequencing (3 patients). Mutations were validated with the use of digital genomic methods in microdissected epithelium and stroma. Epithelial and stromal components of lesions from an additional 12 patients were analyzed by means of a droplet digital polymerase-chain-reaction (PCR) assay for recurrent activating KRAS mutations. ResultsExome sequencing revealed somatic mutations in 19 of 24 patients (79%). Five patients harbored known cancer driver mutations in ARID1A, PIK3CA, KRAS, or PPP2R1A, which were validated by Safe...

Responsible, Safe, and Effective Prescription of Opioids for Chronic Non-Cancer Pain: American Society of Interventional Pain Physicians (ASIPP) Guidelines.

Abstract: Background Opioid use, abuse, and adverse consequences, including death, have escalated at an alarming rate since the 1990s. In an attempt to control opioid abuse, numerous regulations and guidelines for responsible opioid prescribing have been developed by various organizations. However, the US opioid epidemic is continuing and drug dose deaths tripled during 1999 to 2015. Recent data show a continuing increase in deaths due to natural and semisynthetic opioids, a decline in methadone deaths, and an explosive increase in the rates of deaths involving other opioids, specifically heroin and illicit synthetic fentanyl. Contrary to scientific evidence of efficacy and negative recommendations, a significant proportion of physicians and patients (92%) believe that opioids reduce pain and a smaller proportion (57%) report better quality of life. In preparation of the current guidelines, we have focused on the means to reduce the abuse and diversion of opioids without jeopardizing access for those patients suffering from non-cancer pain who have an appropriate medical indication for opioid use. Objectives To provide guidance for the prescription of opioids for the management of chronic non-cancer pain, to develop a consistent philosophy among the many diverse groups with an interest in opioid use as to how appropriately prescribe opioids, to improve the treatment of chronic non-cancer pain and to reduce the likelihood of drug abuse and diversion. These guidelines are intended to provide a systematic and standardized approach to this complex and difficult arena of practice, while recognizing that every clinical situation is unique. Methods The methodology utilized included the development of objectives and key questions. The methodology also utilized trustworthy standards, appropriate disclosures of conflicts of interest, as well as a panel of experts from various specialties and groups. The literature pertaining to opioid use, abuse, effectiveness, and adverse consequences was reviewed, with a best evidence synthesis of the available literature, and utilized grading for recommendation as described by the Agency for Healthcare Research and Quality (AHRQ).Summary of Recommendations:i. Initial Steps of Opioid Therapy 1. Comprehensive assessment and documentation. (Evidence: Level I; Strength of Recommendation: Strong) 2. Screening for opioid abuse to identify opioid abusers. (Evidence: Level II-III; Strength of Recommendation: Moderate) 3. Utilization of prescription drug monitoring programs (PDMPs). (Evidence: Level I-II; Strength of Recommendation: Moderate to strong) 4. Utilization of urine drug testing (UDT). (Evidence: Level II; Strength of Recommendation: Moderate) 5. Establish appropriate physical diagnosis and psychological diagnosis if available. (Evidence: Level I; Strength of Recommendation: Strong) 6. Consider appropriate imaging, physical diagnosis, and psychological status to collaborate with subjective complaints. (Evidence: Level III; Strength of Recommendation: Moderate) 7. Establish medical necessity based on average moderate to severe (≥ 4 on a scale of 0 - 10) pain and/or disability. (Evidence: Level II; Strength of Recommendation: Moderate) 8. Stratify patients based on risk. (Evidence: Level I-II; Strength of Recommendation: Moderate) 9. Establish treatment goals of opioid therapy with regard to pain relief and improvement in function. (Evidence: Level I-II; Strength of Recommendation: Moderate) 10. Obtain a robust opioid agreement, which is followed by all parties. (Evidence: Level III; Strength of Recommendation: Moderate)ii. Assessment of Effectiveness of Long-Term Opioid Therapy 11. Initiate opioid therapy with low dose, short-acting drugs, with appropriate monitoring. (Evidence: Level II; Strength of Recommendation: Moderate) 12. Consider up to 40 morphine milligram equivalent (MME) as low dose, 41 to 90 MME as a moderate dose, and greater than 91 MME as high dose. (Evidence: Level II; Strength of Recommendation: Moderate) 13. Avoid long-acting opioids for the initiation of opioid therapy. (Evidence: Level I; Strength of Recommendation: Strong) 14. Recommend methadone only for use after failure of other opioid therapy and only by clinicians with specific training in its risks and uses, within FDA recommended doses. (Evidence: Level I; Strength of Recommendation: Strong) 15. Understand and educate the patients of the effectiveness and adverse consequences. (Evidence: Level I; Strength of Recommendation: Strong) 16. Similar effectiveness for long-acting and short-acting opioids with increased adverse consequences of long-acting opioids. (Evidence: Level I-II; Strength of recommendation: Moderate to strong) 17. Periodically assess pain relief and/or functional status improvement of ≥ 30% without adverse consequences. (Evidence: Level II; Strength of recommendation: Moderate) 18. Recommend long-acting or high dose opioids only in specific circumstances with severe intractable pain. (Evidence: Level I; Strength of Recommendation: Strong)iii. Monitoring for Adherence and Side Effects 19. Monitor for adherence, abuse, and noncompliance by UDT and PDMPs. (Evidence: Level I-II; Strength of Recommendation: Moderate to strong) 20. Monitor patients on methadone with an electrocardiogram periodically. (Evidence: Level I; Strength of Recommendation: Strong). 21. Monitor for side effects including constipation and manage them appropriately, including discontinuation of opioids when indicated. (Evidence: Level I; Strength of Recommendation: Strong)iv. Final Phase 22. May continue with monitoring with continued medical necessity, with appropriate outcomes. (Evidence: Level I-II; Strength of Recommendation: Moderate) 23. Discontinue opioid therapy for lack of response, adverse consequences, and abuse with rehabilitation. (Evidence: Level III; Strength of Recommendation: Moderate) CONCLUSIONS: These guidelines were developed based on comprehensive review of the literature, consensus among the panelists, in consonance with patient preferences, shared decision-making, and practice patterns with limited evidence, based on randomized controlled trials (RCTs) to improve pain and function in chronic non-cancer pain on a long-term basis. Consequently, chronic opioid therapy should be provided only to patients with proven medical necessity and stability with improvement in pain and function, independently or in conjunction with other modalities of treatments in low doses with appropriate adherence monitoring and understanding of adverse events.Key words: Chronic pain, persistent pain, non-cancer pain, controlled substances, substance abuse, prescription drug abuse, dependency, opioids, prescription monitoring, drug testing, adherence monitoring, diversionDisclaimer: The guidelines are based on the best available evidence and do not constitute inflexible treatment recommendations. Due to the changing body of evidence, this document is not intended to be a "standard of care."

The Polyanalgesic Consensus Conference (PACC): Recommendations on Intrathecal Drug Infusion Systems Best Practices and Guidelines

Abstract: Introduction Pain treatment is best performed when a patient-centric, safety-based philosophy is used to determine an algorithmic process to guide care. Since 2007, the International Neuromodulation Society has organized a group of experts to evaluate evidence and create a Polyanalgesic Consensus Conference (PACC) to guide practice. Methods The current PACC update was designed to address the deficiencies and innovations emerging since the previous PACC publication of 2012. An extensive literature search identified publications between January 15, 2007 and November 22, 2015 and authors contributed additional relevant sources. After reviewing the literature, the panel convened to determine evidence levels and degrees of recommendations for intrathecal therapy. This meeting served as the basis for consensus development, which was ranked as strong, moderate or weak. Algorithms were developed for intrathecal medication choices to treat nociceptive and neuropathic pain for patients with cancer, terminal illness, and noncancer pain, with either localized or diffuse pain. Results The PACC has developed an algorithmic process for several aspects of intrathecal drug delivery to promote safe and efficacious evidence-based care. Consensus opinion, based on expertise, was used to fill gaps in evidence. Thirty-one consensus points emerged from the panel considerations. Conclusion New algorithms and guidance have been established to improve care with the use of intrathecal drug delivery.

Inflammatory biomarkers of low back pain and disc degeneration: a review

Abstract: Biomarkers are biological characteristics that can be used to indicate health or disease. This paper reviews studies on biomarkers of low back pain (LBP) in human subjects. LBP is the leading cause of disability, caused by various spine-related disorders, including intervertebral disc degeneration, disc herniation, spinal stenosis, and facet arthritis. The focus of these studies is inflammatory mediators, because inflammation contributes to the pathogenesis of disc degeneration and associated pain mechanisms. Increasingly, studies suggest that the presence of inflammatory mediators can be measured systemically in the blood. These biomarkers may serve as novel tools for directing patient care. Currently, patient response to treatment is unpredictable with a significant rate of recurrence, and, while surgical treatments may provide anatomical correction and pain relief, they are invasive and costly. The review covers studies performed on populations with specific diagnoses and undefined origins of LBP. Since the natural history of LBP is progressive, the temporal nature of studies is categorized by duration of symptomology/disease. Related studies on changes in biomarkers with treatment are also reviewed. Ultimately, diagnostic biomarkers of LBP and spinal degeneration have the potential to shepherd an era of individualized spine medicine for personalized therapeutics in the treatment of LBP.

Germline Loss-of-Function Mutations in EPHB4 Cause a Second Form of Capillary Malformation-Arteriovenous Malformation (CM-AVM2) Deregulating RAS-MAPK Signaling

Abstract: BACKGROUND: Most arteriovenous malformations (AVMs) are localized and occur sporadically. However, they also can be multifocal in autosomal-dominant disorders, such as hereditary hemorrhagic telangiectasia and capillary malformation (CM)-AVM. Previously, we identified RASA1 mutations in 50% of patients with CM-AVM. Herein we studied non-RASA1 patients to further elucidate the pathogenicity of CMs and AVMs. METHODS: We conducted a genome-wide linkage study on a CM-AVM family. Whole-exome sequencing was also performed on 9 unrelated CM-AVM families. We identified a candidate gene and screened it in a large series of patients. The influence of several missense variants on protein function was also studied in vitro. RESULTS: We found evidence for linkage in 2 loci. Whole-exome sequencing data unraveled 4 distinct damaging variants in EPHB4 in 5 families that cosegregated with CM-AVM. Overall, screening of EPHB4 detected 47 distinct mutations in 54 index patients: 27 led to a premature stop codon or splice-site alteration, suggesting loss of function. The other 20 are nonsynonymous variants that result in amino acid substitutions. In vitro expression of several mutations confirmed loss of function of EPHB4. The clinical features included multifocal CMs, telangiectasias, and AVMs. CONCLUSIONS: We found EPHB4 mutations in patients with multifocal CMs associated with AVMs. The phenotype, CM-AVM2, mimics RASA1-related CM-AVM1 and also hereditary hemorrhagic telangiectasia. RASA1-encoded p120RASGAP is a direct effector of EPHB4. Our data highlight the pathogenetic importance of this interaction and indicts EPHB4-RAS-ERK signaling pathway as a major cause for AVMs.

Ozone therapy: An overview of pharmacodynamics, current research, and clinical utility

Abstract: The use of ozone (O3) gas as a therapy in alternative medicine has attracted skepticism due to its unstable molecular structure However, copious volumes of research have provided evidence that O3's dynamic resonance structures facilitate physiological interactions useful in treating a myriad of pathologies Specifically, O3 therapy induces moderate oxidative stress when interacting with lipids This interaction increases endogenous production of antioxidants, local perfusion, and oxygen delivery, as well as enhances immune responses We have conducted a comprehensive review of O3 therapy, investigating its contraindications, routes and concentrations of administration, mechanisms of action, disinfectant properties in various microorganisms, and its medicinal use in different pathologies We explore the therapeutic value of O3 in pathologies of the cardiovascular system, gastrointestinal tract, genitourinary system, central nervous system, head and neck, musculoskeletal, subcutaneous tissue, and peripheral vascular disease Despite compelling evidence, further studies are essential to mark it as a viable and quintessential treatment option in medicine

Neurovascular Unit Dysfunction and Blood–Brain Barrier Hyperpermeability Contribute to Schizophrenia Neurobiology: A Theoretical Integration of Clinical and Experimental Evidence

Abstract: Schizophrenia is a psychotic disorder characterized by delusions, hallucinations, negative symptoms, as well as behavioral and cognitive dysfunction. It is a pathoetiologically heterogeneous disorder involving complex inter-related mechanisms that include oxidative stress and neuroinflammation. Neurovascular endothelial dysfunction and blood–brain barrier (BBB) hyperpermeability are established mechanisms in neurological disorders with comorbid psychiatric symptoms, such as epilepsy, traumatic brain injury, and Alzheimer’s disease. Schizophrenia is frequently comorbid with medical conditions associated with peripheral vascular endothelial dysfunction, such as metabolic syndrome, cardiovascular disease, and diabetes mellitus. However, the existence and etiological relevance of neurovascular endothelial dysfunction and BBB hyperpermeability in schizophrenia are still not well recognized. Here, we review the growing clinical and experimental evidence indicating that neurovascular endotheliopathy and BBB hyperpermeability occur in schizophrenia patients. We present a theoretical integration of human and animal data linking oxidative stress and neuroinflammation to neurovascular endotheliopathy and BBB breakdown in schizophrenia. These abnormalities may contribute to the cognitive and behavioral symptoms of schizophrenia via several mechanisms involving reduced cerebral perfusion and impaired homeostatic processes of cerebral microenvironment. Furthermore, BBB disruption can facilitate interactions between brain innate and peripheral adaptive immunity, thereby perpetuating harmful neuroimmune signals and toxic neuroinflammatory responses, which can also contribute to the symptoms of schizophrenia. Taken together, these findings support the “mild encephalitis” hypothesis of schizophrenia. If neurovascular abnormalities prove to be etiologically relevant to the neurobiology of schizophrenia, then targeting these abnormalities may represent a promising therapeutic strategy.

Annotating pathogenic non-coding variants in genic regions

Abstract: Identifying the underlying causes of disease requires accurate interpretation of genetic variants. Current methods ineffectively capture pathogenic non-coding variants in genic regions, resulting in overlooking synonymous and intronic variants when searching for disease risk. Here we present the Transcript-inferred Pathogenicity (TraP) score, which uses sequence context alterations to reliably identify non-coding variation that causes disease. High TraP scores single out extremely rare variants with lower minor allele frequencies than missense variants. TraP accurately distinguishes known pathogenic and benign variants in synonymous (AUC = 0.88) and intronic (AUC = 0.83) public datasets, dismissing benign variants with exceptionally high specificity. TraP analysis of 843 exomes from epilepsy family trios identifies synonymous variants in known epilepsy genes, thus pinpointing risk factors of disease from non-coding sequence data. TraP outperforms leading methods in identifying non-coding variants that are pathogenic and is therefore a valuable tool for use in gene discovery and the interpretation of personal genomes.While non-coding synonymous and intronic variants are often not under strong selective constraint, they can be pathogenic through affecting splicing or transcription. Here, the authors develop a score that uses sequence context alterations to predict pathogenicity of synonymous and non-coding genetic variants, and provide a web server of pre-computed scores.

Systematic review with meta-analysis: enteral nutrition therapy for the induction of remission in paediatric Crohn's disease.

Abstract: Background Despite potential adverse-events in a paediatric population, corticosteroids are used to induce remission in paediatric Crohn's disease. Exclusive enteral nutrition also induces remission, but is infrequently used in the USA because corticosteroids are considered the superior therapy. New data have become available since the publication of the most recent meta-analysis in 2007. Aim To see if current literature supports the use of EEN versus CS in paediatric populations. Methods All studies with comparator arms of exclusive enteral nutrition and an exclusive corticosteroids, with remission clearly defined were identified by searching eight online databases. Results Of 2795 identified sources, nine studies met our inclusion criteria. Eight of these (n = 451), had data that could be abstracted into our meta-analysis. Exclusive enteral nutrition was as effective as corticosteroids in inducing remission (OR = 1.26 [95% CI 0.77, 2.05]) in paediatric Crohn's disease. There was no difference between Exclusive enteral nutrition and corticosteroids efficacy when comparing newly diagnosed Crohn's (OR = 1.61 [95% CI .87, 2.98]) or relapsed (OR = 0.76 [95% CI .29-1.98]). Intestinal healing was significantly more likely among patients receiving Exclusive enteral nutrition compared to corticosteroids (OR = 4.5 [95% CI 1.64, 12.32]). There was no difference in the frequency of biomarker normalisation including CRP (OR = 0.85 [95% CI .44, 1.67]) and faecal calprotectin (OR 2.79 [95% CI .79-10.90]). Conclusions There is no difference in efficacy between Exclusive enteral nutrition and corticosteroids in induction of remission in Crohn's disease in a paediatric population. Exploratory analyses suggest that a greater proportion of patients treated with exclusive enteral nutrition achieved mucosal healing.

Treatment Guidelines for Rheumatologic Manifestations of Sjögren's Syndrome: Use of Biologic Agents, Management of Fatigue, and Inflammatory Musculoskeletal Pain

Abstract: Objective The Sjogren's Syndrome Foundation clinical practice guidelines (CPGs) are designed to improve quality and consistency of care in Sjogren's syndrome by offering recommendations for management. Methods Management questions for the systemic manifestations of Sjogren's syndrome were posed by the CPG committee with input from patients and rheumatologists. Clinical questions were assigned to a topic review group that performed systematic reviews and data extraction and drafted guidelines. Quality of evidence and strength of recommendation were rated using the American Society of Clinical Oncology's modification of the Grading of Recommendations Assessment, Development, and Evaluation. Guideline recommendations were reviewed by a consensus expert panel (CEP) composed of 30–40 clinicians from academia and community practices, as well as registered nurses and patients, using a modified Delphi process. A CEP agreement level of 75% was set as a minimum for adoption of a guideline recommendation. Results Consensus was achieved for 19 recommendations; for 11 additional modules, available data were insufficient to allow a recommendation to be formulated. Of the 19 recommendations, 15 required 1 Delphi round, 2 required 2 rounds, and 2 required 3 rounds. Conclusion Key recommendations include a decision tree for the use of oral disease-modifying antirheumatic drugs for inflammatory musculoskeletal pain, use of self-care measures and advice regarding exercise to reduce fatigue, and the use of rituximab in selected clinical settings for oral and ocular dryness and for certain extraglandular manifestations, including vasculitis, severe parotid swelling, inflammatory arthritis, pulmonary disease, and mononeuritis multiplex. The CPG committee strongly discouraged the use of tumor necrosis factor inhibitors for sicca symptoms and for the majority of clinical contexts in primary Sjogren's syndrome.

Clinical Practice Guideline: Evaluation of the Neck Mass in Adults:

Abstract: ObjectiveNeck masses are common in adults, but often the underlying etiology is not easily identifiable. While infections cause most of the neck masses in children, most persistent neck masses in adults are neoplasms. Malignant neoplasms far exceed any other etiology of adult neck mass. Importantly, an asymptomatic neck mass may be the initial or only clinically apparent manifestation of head and neck cancer, such as squamous cell carcinoma (HNSCC), lymphoma, thyroid, or salivary gland cancer. Evidence suggests that a neck mass in the adult patient should be considered malignant until proven otherwise. Timely diagnosis of a neck mass due to metastatic HNSCC is paramount because delayed diagnosis directly affects tumor stage and worsens prognosis. Unfortunately, despite substantial advances in testing modalities over the last few decades, diagnostic delays are common. Currently, there is only 1 evidence-based clinical practice guideline to assist clinicians in evaluating an adult with a neck mass. Addition...

Adoption of Robotic vs Fluoroscopic Guidance in Total Hip Arthroplasty: Is Acetabular Positioning Improved in the Learning Curve?

Abstract: Background Acetabulum positioning affects dislocation rates, component impingement, bearing surface wear rates, and need for revision surgery. Novel techniques purport to improve the accuracy and precision of acetabular component position, but may have a significant learning curve. Our aim was to assess whether adopting robotic or fluoroscopic techniques improve acetabulum positioning compared to manual total hip arthroplasty (THA) during the learning curve. Methods Three types of THAs were compared in this retrospective cohort: (1) the first 100 fluoroscopically guided direct anterior THAs (fluoroscopic anterior [FA]) done by a surgeon learning the anterior approach, (2) the first 100 robotic-assisted posterior THAs done by a surgeon learning robotic-assisted surgery (robotic posterior [RP]), and (3) the last 100 manual posterior (MP) THAs done by each surgeon (200 THAs) before adoption of novel techniques. Component position was measured on plain radiographs. Radiographic measurements were taken by 2 blinded observers. The percentage of hips within the surgeons' "target zone" (inclination, 30°-50°; anteversion, 10°-30°) was calculated, along with the percentage within the "safe zone" of Lewinnek (inclination, 30°-50°; anteversion, 5°-25°) and Callanan (inclination, 30°-45°; anteversion, 5°-25°). Relative risk (RR) and absolute risk reduction (ARR) were calculated. Variances (square of the standard deviations) were used to describe the variability of cup position. Results Seventy-six percentage of MP THAs were within the surgeons' target zone compared with 84% of FA THAs and 97% of RP THAs. This difference was statistically significant, associated with a RR reduction of 87% (RR, 0.13 [0.04-0.40]; P P P Conclusion Adoption of robotic techniques delivers significant and immediate improvement in the precision of acetabular component positioning during the learning curve. While fluoroscopy has been shown to be beneficial with experience, a learning curve exists before precision improves significantly.

ISSVA Classification of Vascular Anomalies

Abstract: Although the existence of vascular anomalies is far from a new discovery, misconceptions regarding diagnosis and management persist. Fundamental to clarifying this misinformation is a comprehension of the categorization of diagnoses. Throughout many years, classification schemas have evolved. Since the 1980s, resulting from Mulliken’s insight, it has been generally accepted that the partition of vascular anomalies into those that proliferate (“tumors”) and those that are developmental aberrations (vascular malformations) provides a functional taxonomic separation [1]. Although vascular anomalies represent a spectrum of disorders, with some overlap, this partitioning into two separate groups serves as a functional division and can assist in the overall management plan and realistic conversation with patients and their families.

The Kynurenine Pathway: A Primary Resistance Mechanism in Patients with Glioblastoma.

Abstract: The failure of chemotherapy and radiation therapy to achieve long-term remission or cure in patients with glioblastoma (GBM) is, in a large part, due to the suppression of the immune system induced by the tumors themselves. These tumors adapt to treatment with chemotherapy or radiation therapy by stimulating secretion of molecules that cause tryptophan metabolism to be disrupted. Indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) are produced, accelerating metabolism along the kynurenine pathway and resulting in excess levels of quinolinic acid, 3-hydroxyanthranilic acid and other neurotoxic molecules. IDO and TDO also act as checkpoint molecules that suppress T-cell function. GBM is particularly associated with severe immunosuppression, and this tumor type might be thought to be the ideal candidate for checkpoint inhibitor therapy. However, treatment with checkpoint inhibitors now in clinical use for peripheral solid tumors, such as those inhibiting cytotoxic T-lymphocyte-associated protein-4 (CTLA4) or programmed cell death-1 (PD1) receptors, results in further abnormalities of tryptophan metabolism. This implies that to obtain optimal results in the treatment of GBM, one may need to add an inhibitor of the kynurenine pathway to therapy with a CTLA4 or PD1 inhibitor, or use agents which can suppress multiple checkpoint molecules.

The Perioperative Anticoagulant Use for Surgery Evaluation (PAUSE) Study for Patients on a Direct Oral Anticoagulant Who Need an Elective Surgery or Procedure: Design and Rationale

Abstract: Background The perioperative management of patients who take a direct oral anticoagulant (DOAC) for atrial fibrillation and require treatment interruption for an elective surgery/procedure is a common clinical scenario for which best practices are uncertain. The Perioperative Anticoagulant Use for Surgery Evaluation (PAUSE) study is designed to address this unmet clinical need. We discuss the rationale for the PAUSE design and analysis plan as well as the rationale supporting the perioperative DOAC protocol. Methods PAUSE is a prospective study with three parallel cohorts, one for each DOAC, to assess a standardized but patient-specific perioperative management protocol for DOAC-treated patients with atrial fibrillation. The perioperative protocol accounts for DOAC type, patient's renal function and surgery/procedure-related bleeding risk. The primary study aim is to demonstrate the safety of the PAUSE protocol for the perioperative management of each DOAC. The secondary aim is to determine the effect of the pre-procedure interruption on residual anticoagulation when measured by the dilute thrombin time for dabigatran and anti-factor Xa levels for rivaroxaban and apixaban. The study hypothesis is that the perioperative management protocol for each DOAC is safe for patient care, defined by expected risks for major bleeding of 1% (80% power to exclude 2%), and for arterial thromboembolism of 0.5% (80% power to exclude 1.5%) in each DOAC group. Conclusion The PAUSE study has the potential to establish a standard-of-care approach for the perioperative management of DOAC-treated patients. The PAUSE management protocol is designed to be easily applied in clinical practice, as it is standardized and also patient specific.

Risk Prediction Models in Psychiatry: Toward a New Frontier for the Prevention of Mental Illnesses.

Abstract: Objective We conducted a systematic, qualitative review of risk prediction models designed and tested for depression, bipolar disorder, generalized anxiety disorder, posttraumatic stress disorder, and psychotic disorders. Our aim was to understand the current state of research on risk prediction models for these 5 disorders and thus future directions as our field moves toward embracing prediction and prevention. Data sources Systematic searches of the entire MEDLINE electronic database were conducted independently by 2 of the authors (from 1960 through 2013) in July 2014 using defined search criteria. Search terms included risk prediction, predictive model, or prediction model combined with depression, bipolar, manic depressive, generalized anxiety, posttraumatic, PTSD, schizophrenia, or psychosis. Study selection We identified 268 articles based on the search terms and 3 criteria: published in English, provided empirical data (as opposed to review articles), and presented results pertaining to developing or validating a risk prediction model in which the outcome was the diagnosis of 1 of the 5 aforementioned mental illnesses. We selected 43 original research reports as a final set of articles to be qualitatively reviewed. Data extraction The 2 independent reviewers abstracted 3 types of data (sample characteristics, variables included in the model, and reported model statistics) and reached consensus regarding any discrepant abstracted information. Results Twelve reports described models developed for prediction of major depressive disorder, 1 for bipolar disorder, 2 for generalized anxiety disorder, 4 for posttraumatic stress disorder, and 24 for psychotic disorders. Most studies reported on sensitivity, specificity, positive predictive value, negative predictive value, and area under the (receiver operating characteristic) curve. Conclusions Recent studies demonstrate the feasibility of developing risk prediction models for psychiatric disorders (especially psychotic disorders). The field must now advance by (1) conducting more large-scale, longitudinal studies pertaining to depression, bipolar disorder, anxiety disorders, and other psychiatric illnesses; (2) replicating and carrying out external validations of proposed models; (3) further testing potential selective and indicated preventive interventions; and (4) evaluating effectiveness of such interventions in the context of risk stratification using risk prediction models.

Intracardiac Echocardiography for Structural Heart and Electrophysiological Interventions

Abstract: With an increasing number of interventional procedures performed for structural heart disease and cardiac arrhythmias each year, echocardiographic guidance is necessary for safe and efficient results. The purpose of this review article is to overview the principles of intracardiac echocardiography (ICE) and describes the peri-interventional role of ICE in a variety of structural heart disease and electrophysiological interventions. Both transthoracic (TTE) and transesophageal echocardiography have limitations. ICE provides the advantage of imaging from within the heart, providing shorter image distances and higher resolution. ICE may be performed without sedation and avoids esophageal intubation as with transesophageal echocardiography (TEE). Limitations of ICE include the need for additional venous access with possibility of vascular complications, potentially higher costs, and a learning curve for new operators. Data supports the use of ICE in guiding device closure of interatrial shunts, transseptal puncture, and electrophysiologic procedures. This paper reviews the more recent reports that ICE may be used for primary guidance or as a supplement to TEE in patients undergoing left atrial appendage (LAA) closure, interatrial shunt closure, transaortic valve implantation (TAVI), percutaneous mitral valve repair (PMVR), paravalvular leak (PVL) closure, aortic interventions, transcatheter pulmonary valve replacement (tPVR), ventricular septal defect (VSD), and patent ductus arteriosus (PDA) closure. ICE imaging technology will continue to expand and help improve structural heart and electrophysiology interventions.

Pin Site Complications Associated With Computer-Assisted Navigation in Hip and Knee Arthroplasty

Abstract: Background There has been a great increase in the use of navigation technology in joint arthroplasty. In most types of navigation-assisted surgery, several temporary navigation pins are placed in the patient. Goals of this study are (1) to identify complications and (2) risk factors associated with placement of these pins. Methods This is a retrospective cohort study of all navigation-assisted hip and knee arthroplasty performed a single institution over a 3-year period. Records were reviewed and outcome measures were tabulated in a database. Complications included in the database were pin site infection, deep prosthetic joint infection, neurologic injury, vascular injury, and fracture through a pin site. Results A total of 3136 pin sites in 839 patients were included in the study. Five pin site complications were reported with a complication rate of 0.16% per pin site and 0.60% per patient. The complications-per-procedure were slightly higher for unicondylar knee arthroplasty (0.64%) compared with patellofemoral arthroplasty (0%) and total hip arthroplasty (0.46%), but not statistically significant. There were three infections, one neuropraxia, and one suture abscess. No periprosthetic fractures through a pin site were reported. All complications were resolved with nonoperative treatment. The infections required oral antibiotics, and were associated with transcortical drilling in two cases and juxtacortical drilling in the third. Conclusion Pins required for navigation-assisted arthroplasty have a low complication rate. Transcortical or juxtacortical drilling may be a risk factor for pin site infection; future studies should be directed at quantifying this effect.

Reversal of Growth of Utilization of Interventional Techniques in Managing Chronic Pain in Medicare Population Post Affordable Care Act.

Abstract: Background Over the past 2 decades, the increase in the utilization of interventional techniques has been a cause for concern. Despite multiple regulations to reduce utilization of interventional techniques, growth patterns continued through 2009. A declining trend was observed in a previous evaluation; however, a comparative analysis of utilization patterns of interventional techniques has not been performed showing utilization before and after the enactment of the Affordable Care Act (ACA). Objectives Our aim is to assess patterns of utilization and variables of interventional techniques in chronic pain management in the fee-for-service (FFS) Medicare population, with a comparative analysis of pre- and post-ACA. Study design Utilization patterns and variables of interventional techniques were assessed from 2000 to 2009 and from 2009 to 2016 in the FFS Medicare population of the United States in managing chronic pain. Methods The master data from the Centers for Medicare & Medicaid Services (CMS) physician/supplier procedure summary from 2000 to 2016 was utilized to assess overall utilization and comparative utilization at various time periods. Results The analysis of Medicare data from 2000 to 2016 showed an overall decrease in utilization of interventional techniques 0.6% per year from 2009 to 2016, whereas from 2000 to 2009, there was an increase of 11.8% per year per 100,000 individuals of the Medicare population. In addition, the United States experienced an increase of 0.7% per year of population growth, 3.2% of those 65 years or older and a 3% annual increase in Medicare participation from 2009 to 2016. Further analysis also showed a 1.7% annual decrease in the rate of utilization of epidural and adhesiolysis procedures per 100,000 individuals of the Medicare population, with a 2.2% decrease for disc procedures and other types of nerve blocks, whereas there was an increase of 0.8% annually for facet joint interventions and sacroiliac joint blocks from 2009 to 2016. Epidural and adhesiolysis procedures showed an 8.9% annual increase, facet joint interventions and sacroiliac joint blocks showed a 17.6% increase, and disc procedures and other types of nerve blocks showed a 7.2% increase annually per 100,000 individuals of the Medicare population from 2000 to 2009. Limitations The limitations of this assessment include lack of analysis of individual procedures. Additional limitations include lack of inclusion of patients from Medicare Advantage plans and lack of complete and accurate data for statewide utilization. Conclusion From 2009 to 2016, interventional techniques decreased at an annual rate of 0.6% with an overall decrease of 3.9%, compared to an overall increase of 173.6% from 2000 to 2009 with an annual increase of 11.8%. An additional analysis of data with individual procedures is essential to gain further insights into utilization patterns. Key words Interventional pain management, chronic spinal pain, interventional techniques, epidural injections, adhesiolysis, facet joint interventions, sacroiliac joint injections, disc procedures, other types of nerve blocks.