Harborview Medical Center

BACKGROUND: Non-fatal outcomes of disease and injury increasingly detract from the ability of the world's population to live in full health, a trend largely attributable to an epidemiological transition in many countries from causes affecting children, to non-communicable diseases (NCDs) more common in adults. For the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015), we estimated the incidence, prevalence, and years lived with disability for diseases and injuries at the global, regional, and national scale over the period of 1990 to 2015. METHODS: We estimated incidence and prevalence by age, sex, cause, year, and geography with a wide range of updated and standardised analytical procedures. Improvements from GBD 2013 included the addition of new data sources, updates to literature reviews for 85 causes, and the identification and inclusion of additional studies published up to November, 2015, to expand the database used for estimation of non-fatal outcomes to 60 900 unique data sources. Prevalence and incidence by cause and sequelae were determined with DisMod-MR 2.1, an improved version of the DisMod-MR Bayesian meta-regression tool first developed for GBD 2010 and GBD 2013. For some causes, we used alternative modelling strategies where the complexity of the disease was not suited to DisMod-MR 2.1 or where incidence and prevalence needed to be determined from other data. For GBD 2015 we created a summary indicator that combines measures of income per capita, educational attainment, and fertility (the Socio-demographic Index [SDI]) and used it to compare observed patterns of health loss to the expected pattern for countries or locations with similar SDI scores. FINDINGS: We generated 9·3 billion estimates from the various combinations of prevalence, incidence, and YLDs for causes, sequelae, and impairments by age, sex, geography, and year. In 2015, two causes had acute incidences in excess of 1 billion: upper respiratory infections (17·2 billion, 95% uncertainty interval [UI] 15·4-19·2 billion) and diarrhoeal diseases (2·39 billion, 2·30-2·50 billion). Eight causes of chronic disease and injury each affected more than 10% of the world's population in 2015: permanent caries, tension-type headache, iron-deficiency anaemia, age-related and other hearing loss, migraine, genital herpes, refraction and accommodation disorders, and ascariasis. The impairment that affected the greatest number of people in 2015 was anaemia, with 2·36 billion (2·35-2·37 billion) individuals affected. The second and third leading impairments by number of individuals affected were hearing loss and vision loss, respectively. Between 2005 and 2015, there was little change in the leading causes of years lived with disability (YLDs) on a global basis. NCDs accounted for 18 of the leading 20 causes of age-standardised YLDs on a global scale. Where rates were decreasing, the rate of decrease for YLDs was slower than that of years of life lost (YLLs) for nearly every cause included in our analysis. For low SDI geographies, Group 1 causes typically accounted for 20-30% of total disability, largely attributable to nutritional deficiencies, malaria, neglected tropical diseases, HIV/AIDS, and tuberculosis. Lower back and neck pain was the leading global cause of disability in 2015 in most countries. The leading cause was sense organ disorders in 22 countries in Asia and Africa and one in central Latin America; diabetes in four countries in Oceania; HIV/AIDS in three southern sub-Saharan African countries; collective violence and legal intervention in two north African and Middle Eastern countries; iron-deficiency anaemia in Somalia and Venezuela; depression in Uganda; onchoceriasis in Liberia; and other neglected tropical diseases in the Democratic Republic of the Congo. INTERPRETATION: Ageing of the world's population is increasing the number of people living with sequelae of diseases and injuries. Shifts in the epidemiological profile driven by socioeconomic change also contribute to the continued increase in years lived with disability (YLDs) as well as the rate of increase in YLDs. Despite limitations imposed by gaps in data availability and the variable quality of the data available, the standardised and comprehensive approach of the GBD study provides opportunities to examine broad trends, compare those trends between countries or subnational geographies, benchmark against locations at similar stages of development, and gauge the strength or weakness of the estimates available. FUNDING: Bill & Melinda Gates Foundation.

Journal of Bone and Mineral ResearchVolume 2, Issue 6 p. 595-610 Article Bone histomorphometry: Standardization of nomenclature, symbols, and units: Report of the asbmr histomorphometry nomenclature committee A. Michael Parfitt M.D., Corresponding Author A. Michael Parfitt M.D. Chairman Bone and Mineral Research Laboratory, Department of Medicine, Henry Ford Hospital, Detroit, MIBone and Mineral Research Laboratory Henry Ford Hospital 2799 West Grand Boulevard Detroit, MI 48202Search for more papers by this authorMarc K. Drezner, Marc K. Drezner Bone and Mineral Metabolism Section, Division of Metabolism, Endocrinology and Genetics, Department of Medicine, Duke University Medical Center, Durham, NCSearch for more papers by this authorFrancis H. Glorieux, Francis H. Glorieux Genetics Unit, Shriners Hospital for Crippled Children, Montreal, Quebec, CanadaSearch for more papers by this authorJohn A. Kanis, John A. Kanis Department of Human Metabolism and Clinical Biochemistry, University of Sheffield, Sheffield, UKSearch for more papers by this authorHartmut Malluche, Hartmut Malluche Department of Medicine, Division of Nephrology, Bone and Mineral Metabolism, University of Kentucky College of Medicine, Lexington, KTSearch for more papers by this authorPierre J. Meunier, Pierre J. Meunier INSERM Unit 234, Faculte Alexis Carrel, Lyon, FranceSearch for more papers by this authorSusan M. Ott, Susan M. Ott Department of Medicine, Harborview Medical Center, University of Washington, Seattle, WASearch for more papers by this authorRobert R. Recker, Robert R. Recker Metabolic Research Unit, Department of Internal Medicine, Creighton University School of Medicine, Omaha, NBSearch for more papers by this author A. Michael Parfitt M.D., Corresponding Author A. Michael Parfitt M.D. Chairman Bone and Mineral Research Laboratory, Department of Medicine, Henry Ford Hospital, Detroit, MIBone and Mineral Research Laboratory Henry Ford Hospital 2799 West Grand Boulevard Detroit, MI 48202Search for more papers by this authorMarc K. Drezner, Marc K. Drezner Bone and Mineral Metabolism Section, Division of Metabolism, Endocrinology and Genetics, Department of Medicine, Duke University Medical Center, Durham, NCSearch for more papers by this authorFrancis H. Glorieux, Francis H. Glorieux Genetics Unit, Shriners Hospital for Crippled Children, Montreal, Quebec, CanadaSearch for more papers by this authorJohn A. Kanis, John A. Kanis Department of Human Metabolism and Clinical Biochemistry, University of Sheffield, Sheffield, UKSearch for more papers by this authorHartmut Malluche, Hartmut Malluche Department of Medicine, Division of Nephrology, Bone and Mineral Metabolism, University of Kentucky College of Medicine, Lexington, KTSearch for more papers by this authorPierre J. Meunier, Pierre J. Meunier INSERM Unit 234, Faculte Alexis Carrel, Lyon, FranceSearch for more papers by this authorSusan M. Ott, Susan M. Ott Department of Medicine, Harborview Medical Center, University of Washington, Seattle, WASearch for more papers by this authorRobert R. Recker, Robert R. Recker Metabolic Research Unit, Department of Internal Medicine, Creighton University School of Medicine, Omaha, NBSearch for more papers by this author First published: December 1987 https://doi.org/10.1002/jbmr.5650020617Citations: 4,046AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume2, Issue6December 1987Pages 595-610 RelatedInformation

OBJECTIVE: To update and expand the 2013 Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the ICU. DESIGN: Thirty-two international experts, four methodologists, and four critical illness survivors met virtually at least monthly. All section groups gathered face-to-face at annual Society of Critical Care Medicine congresses; virtual connections included those unable to attend. A formal conflict of interest policy was developed a priori and enforced throughout the process. Teleconferences and electronic discussions among subgroups and whole panel were part of the guidelines' development. A general content review was completed face-to-face by all panel members in January 2017. METHODS: Content experts, methodologists, and ICU survivors were represented in each of the five sections of the guidelines: Pain, Agitation/sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption). Each section created Population, Intervention, Comparison, and Outcome, and nonactionable, descriptive questions based on perceived clinical relevance. The guideline group then voted their ranking, and patients prioritized their importance. For each Population, Intervention, Comparison, and Outcome question, sections searched the best available evidence, determined its quality, and formulated recommendations as "strong," "conditional," or "good" practice statements based on Grading of Recommendations Assessment, Development and Evaluation principles. In addition, evidence gaps and clinical caveats were explicitly identified. RESULTS: The Pain, Agitation/Sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption) panel issued 37 recommendations (three strong and 34 conditional), two good practice statements, and 32 ungraded, nonactionable statements. Three questions from the patient-centered prioritized question list remained without recommendation. CONCLUSIONS: We found substantial agreement among a large, interdisciplinary cohort of international experts regarding evidence supporting recommendations, and the remaining literature gaps in the assessment, prevention, and treatment of Pain, Agitation/sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption) in critically ill adults. Highlighting this evidence and the research needs will improve Pain, Agitation/sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption) management and provide the foundation for improved outcomes and science in this vulnerable population.

BACKGROUND: Acute lung injury is a critical illness syndrome consisting of acute hypoxemic respiratory failure with bilateral pulmonary infiltrates that are not attributed to left atrial hypertension. Despite recent advances in our understanding of the mechanism and treatment of acute lung injury, its incidence and outcomes in the United States have been unclear. METHODS: We conducted a prospective, population-based, cohort study in 21 hospitals in and around King County, Washington, from April 1999 through July 2000, using a validated screening protocol to identify patients who met the consensus criteria for acute lung injury. RESULTS: A total of 1113 King County residents undergoing mechanical ventilation met the criteria for acute lung injury and were 15 years of age or older. On the basis of this figure, the crude incidence of acute lung injury was 78.9 per 100,000 person-years and the age-adjusted incidence was 86.2 per 100,000 person-years. The in-hospital mortality rate was 38.5 percent. The incidence of acute lung injury increased with age from 16 per 100,000 person-years for those 15 through 19 years of age to 306 per 100,000 person-years for those 75 through 84 years of age. Mortality increased with age from 24 percent for patients 15 through 19 years of age to 60 percent for patients 85 years of age or older (P<0.001). We estimate that each year in the United States there are 190,600 cases of acute lung injury, which are associated with 74,500 deaths and 3.6 million hospital days. CONCLUSIONS: Acute lung injury has a substantial impact on public health, with an incidence in the United States that is considerably higher than previous reports have suggested.

This document presents guidelines for developing institutional programs to enhance antimicrobial stewardship, an activity that includes appropriate selection, dosing, route, and duration of antimicrobial therapy. The multifaceted nature of antimicrobial stewardship has led to collaborative review and support of these recommendations by the following organizations: American Academy of Pediatrics, American Society of Health-System Pharmacists, Infectious Diseases Society for Obstetrics and Gynecology, Pediatric Infectious Diseases Society, Society for Hospital Medicine, and Society of Infectious Diseases Pharmacists. The primary goal of antimicrobial stewardship is to optimize clinical outcomes while minimizing unintended consequences of antimicrobial use, including toxicity, the selection of pathogenic organisms (such as Clostridium difficile), and the emergence of resistance. Thus, the appropriate use of antimicrobials is an essential part of patient safety

A cornerstone of modern biomedical research is the use of mouse models to explore basic pathophysiological mechanisms, evaluate new therapeutic approaches, and make go or no-go decisions to carry new drug candidates forward into clinical trials. Systematic studies evaluating how well murine models mimic human inflammatory diseases are nonexistent. Here, we show that, although acute inflammatory stresses from different etiologies result in highly similar genomic responses in humans, the responses in corresponding mouse models correlate poorly with the human conditions and also, one another. Among genes changed significantly in humans, the murine orthologs are close to random in matching their human counterparts (e.g., R(2) between 0.0 and 0.1). In addition to improvements in the current animal model systems, our study supports higher priority for translational medical research to focus on the more complex human conditions rather than relying on mouse models to study human inflammatory diseases.

The recently discovered orexigenic peptide ghrelin is produced primarily by the stomach and circulates in blood at levels that increase during prolonged fasting in rats. When administered to rodents at supraphysiological doses, ghrelin activates hypothalamic neuropeptide Y/agouti gene-related protein neurons and increases food intake and body weight. These findings suggest that ghrelin may participate in meal initiation. As a first step to investigate this hypothesis, we sought to determine whether circulating ghrelin levels are elevated before the consumption of individual meals in humans. Ghrelin, insulin, and leptin were measured by radioimmunoassay in plasma samples drawn 38 times throughout a 24-h period in 10 healthy subjects provided meals on a fixed schedule. Plasma ghrelin levels increased nearly twofold immediately before each meal and fell to trough levels within 1 h after eating, a pattern reciprocal to that of insulin. Intermeal ghrelin levels displayed a diurnal rhythm that was exactly in phase with that of leptin, with both hormones rising throughout the day to a zenith at 0100, then falling overnight to a nadir at 0900. Ghrelin levels sampled during the troughs before and after breakfast correlated strongly with 24-h integrated area under the curve values (r = 0.873 and 0.954, respectively), suggesting that these convenient, single measurements might serve as surrogates for 24-h profiles to estimate overall ghrelin levels. Circulating ghrelin also correlated positively with age (r = 0.701). The clear preprandial rise and postprandial fall in plasma ghrelin levels support the hypothesis that ghrelin plays a physiological role in meal initiation in humans.

Foreword Dear Colleague We would like to introduce you to the 2018 OTA/AO (or AO/OTA) Fracture and Dislocation Classification Compendium. This is the second revision of the compendium which was first published in 1996 as a cooperative effort of the AO Foundation and the Orthopaedic Trauma Association (OTA). Both organizations were committed to assuring that there was a standardized and rational methodology of describing fractures and dislocation as well as a mechanism to code data for future recall. These principles were absolutely necessary to establish a consistent system for clinical interaction and research. After 20 years of use, the current revision addresses the many suggestions to help improve the application of the system, correct errors, and add new classifications. The process was under the direction of a committee of four individuals representing both organizations, with experience in the day to day application of the compendium and fracture coding. The process was supervised and funded by the Classification Committee of the OTA and AOTrauma International Board (AOTIB). An ongoing agreement between both organizations to assure the ongoing collaborative support of the revision process of the compendium was also developed. Importantly, copyright will remain with both organizations so that its reproduction and promulgation will be unencumbered. This establishes not only mutual ownership but also responsibility and ensures continued collaboration and support. We believe that this is an important step forward in the process of clinical research as well as standardizing day to day clinical communication. However, change is inevitable and both the OTA and the AOTIB encourage comment and criticisms so that the next revision process can continue to improve the compendium. John H. Wilber MD Chairman, AOTrauma International Board Professor and Chair Department of Orthopaedic Surgery MetroHealth Medical Center Hansjoerg Wyss Professor Orthopaedic Trauma Case Western Reserve University Cleveland, Ohio William M. Ricci MD President, Orthopaedic Trauma Association Chief, Combined HSS/NYP Trauma Service Hospital for Special Surgery New York Presbyterian Hospital New York, NY Compedium introduction The AO Foundation/Orthopaedic Trauma Association (AO/OTA) fracture classification was published as a compendium to the Journal of Orthopaedic Trauma (JOT) in 1996.1 Using the principles of the Comprehensive Classification of Fractures of the Long Bones (CCF) developed by Müller and collaborators, the OTA classification committee classified and coded the remaining bones.2,3 This helped bring order to the state of fracture classification with its multiple systems that had thwarted any possibility of a standardized language and accumulation of uniform data. Since the compendium was published in 1996, the classification has resided on the OTA and AO Foundation websites and has been regularly used in trauma databases, scientific journals, and textbooks worldwide. It is the official classification of the OTA, the AO, and JOT. It has gained wide acceptance and its use has dramatically improved the way information about fractures is communicated, stored, and used to advance knowledge. In some anatomical areas, this classification has largely supplanted multiple options achieving one of the original intentsion.1,2,3 The classification is intended to be a flexible evolving system in which changes are made based on user feedback, criticism, and appropriate clinical research, thus serving the needs of the orthopedic community for both clinical practice and research. In 2007, the AO and OTA classification committees undertook a revision to address issues of reliability, reproducibility, and need. This revision was based on the premise that changes needed to be validated prior to being implemented. The validation process was expensive and not practical so a decision was made to not validate all edits. The 2007 revision standardized the two different alphanumeric codes into one agreed-upon scheme, thus developing an internationally recognized uniform system for clinical research on fractures and dislocations. The validated AO Pediatric Classification of Fractures developed by Slongo was also included in the compendium.4,5 The two committees confirmed the original premise that the revision process needed to be undertaken every 10 years. Ongoing concerns about terminology, the relevancy of certain classification schemes, and the need to streamline codes provided the impetus to undertake the 2018 review.6–12 To make this an effective, economical, and efficient process, the AOTrauma International Board (AOTIB) and OTA appointed five persons to form the International Comprehensive Classification of Fractures and Dislocations Committee (ICCFC). The process began with the aims to address editorial errors, criticisms of the proximal humerus and proximal femur classification, and to simplify the coding process based on fracture pattern occurrence and complexity using a modified Delphi approach. A priority for this revision was to maintain the original principles of the CCF with regard to definitions and the basic coding system. It became apparent that many of the fracture patterns occurred so infrequently that there was no need to have a unique code for them, as they could easily be coded by a shortened generic system. Frequency plots of a large registry that uses these codes confirmed this. It became evident that it would be more accurate to code radius and ulna fractures separately and to align the system with ICD-10 terminology.13 The same was done for the other two-bone system by adding a new coding system for fibula fractures. The former editions had many qualifications and sub-qualifications for each fracture pattern, many of which were duplications. The committee decided to group these into a universal modifier list that could be applied to every fracture as desired by the end user, who codes the fracture. All fracture specific modifiers were maintained with their specific fracture or dislocation. As this classification system provides standard terminology and codes, it also felt appropriate to combine, insert, or reference other commonly accepted classifications (eg, Neer) into the AO/OTA descriptions and codes. This would assure consistency and greater clinical utility in fracture and dislocation classification. The 2018 compendium revision The compendium is branded as the AO/OTA or OTA/AO Fracture and Dislocation Classification Compendium. In publications, it will be cited as Meinberg E, Agel J, Roberts C, et al. Fracture and Dislocation Classification Compendium–2018, Journal of Orthopaedic Trauma. Volume 32: Number 1; Supplement, January 2018. Future publications related to the revised Compendium will be authored and referenced as determined by the International Comprehensive Classification of Fractures and Dislocations Committee (ICCFC), irrespective of its member composition. The mandates for the 2018 revision are the following: a) Editorial, terminology, and typographical changes and corrections: i. The terms "complex” and "multifragmentary” have created confusion in their application. The term "complex” did not describe a fracture pattern consisting of many fragments while "multifragmentary” does. Multifragmentary was previously used generically to refer to diaphyseal type B and C and did not have a specific alphanumeric code so was rarely used. Consequently, the committee felt that it is more concise to have three types of diaphyseal fractures: simple, wedge, and multifragmentary. "Multifragmentary” will no longer be used as a generic term for diaphyseal types B and C. A multifragmentary diaphyseal or end segment extraarticular fracture is one with many fracture fragments and after reduction there is no contact between the main fragments. A multifragmentary complete articular fracture is one with more than two fracture fragments of the articular surface. ii. The diaphyseal fracture classification has been made consistent for all bones. The diaphysis is defined as that part of the bone between the two end segments and is divided into three equal parts defining the location of the diaphyseal fracture. The fracture location within the diaphysis is a qualification as follows: a Proximal 1/3 b Middle 1/3 c Distal 1/3 iii. A more precise description of the intraarticular portion of proximal tibia fractures has been recommended.14,15 A modification to the proximal tibia classification as recommended by Mauricio Kfuri and Joseph Schaztker to better define the significant joint fragmentation or displacement is added as qualifications for type B and C proximal tibial intraarticular fractures.16 iv. The written description of fractures has been standardized so that each fracture is presented in a similar order highlighting the specific region or fracture morphology. v. To facilitate data entry and lessen the error rate in coding, the hyphen in the code has been removed. vi. A code for fibula fractures based on the principles of the CCF has been added. vii. The Neer classification has been integrated into the fracture description for proximal humeral fractures to facilitate the clinician comprehension of the terms unifocal and bifocal fractures. viii. The proximal femoral classification terminology has been a source of confusion as a variety of descriptive terms have been used to describe similar fractures. There has also been a problem defining fractures for group 31A2. Definitions have been added to help classify these fractures and the codes reorganized to better represent these fractures. The femoral neck fractures have been organized to better align the fracture types. By adding the Pauwels classification as a qualification for femoral neck fractures a more detailed evaluation of high-energy fractures is available. ix. The Young-Burgess Classification of Pelvic Ring Injuries has been integrated into the AO/OTA pelvic fracture classification. b) Addition of recently published validated classifications: i. OTA Open Fracture Classification17 ii. AO/OTA Scapular Fracture Classification18,19 iii. Unified Classification of Periprosthetic Fractures20 iv. AOSpine Subaxial Cervical and Thoracolumbar spine injury classification21 v. AOSpine Sacral Fracture Classification22 c) At the request of the AOTK Thoracic Surgery Expert Group, a preliminary classification of rib and sternal fractures has been included. Publication of this classification will allow interested groups to assess its validity and reproducibility so in the next revision, a validated modification will be available. d) Review of the codes with regards to frequency and applicability: i. Many of the qualifications and subqualifications of the first two compendiums were repetitious and on a survey of users were not routinely used. To simplify the usage, the common modifiers were placed in a list called Universal Modifiers. This simplifies the presentation of the codes and allows each clinician to use these as they see fit for their circumstances. ii. Certain qualifications were fracture-specific and were left as qualifications within the specific fracture types and groups. iii. Complex injuries such as the terrible triad of the elbow and a transolecranon fracture dislocation are difficult to code related to the fact that fractures of radius and ulna were placed into one code. The committee decided to separate the radius and ulna and classify fractures in each bone. This simplifies the process and when combined with the universal modifiers makes classification of complex injuries about the elbow more consistent and accurate. It also follows the ICD-10 system where each bone is coded separately. It was recognized by the committee that this revision must maintain the principles and definitions of the CCF and the prior two compendiums. This revision represents a streamlining of the 2007 version. The aim was to assure that the majority of fracture patterns were represented. This revision provides a more concise and clinically relevant compendium. The user will be able to choose the code that best meets their needs. It is hoped that with the recognition of other standard classifications being integrated into the codes that this compendium will be of increasing value to many other orthopedic subspecialities. Fundamentals of fracture classification Classification is the process by which related groups are organized based on similarities and differences.5 It provides the language necessary to convey information among individuals to ensure standardization. This classification process may be looked upon as the systematic methodology of describing a fracture or dislocation. It is critical to note that a fracture should be coded only after all the information is obtained. It must be remembered that if there is doubt, then waiting until the complete information is available is mandatory before determining the final classification.23–28 The final classification may be delayed until the operative procedure is completed and the fracture fully visualized. This system provides the clinician with standardized definitions so the verbal fracture description is precise and consistent from bone to bone and fracture to fracture. These standard definitions and guidelines for application assure consistency in the classification process.16,24–37 With the improved consistency of fracture descriptions, future investigations assessing treatment guidelines, prognosis, and risk of complications will be more reliable and meaningful. The system also provides a mechanism to convert the verbal description into an alphanumeric code to allow for data storage and future recall. The use of this alphanumeric coding scheme is absolutely necessary for multicenter collaboration, retrospective comparison of results, international communication, and to standardize recording information about all fractures in a trauma database. The classification offers several other benefits. It provides a hierarchy of severity as the descriptions generally proceed from simple to multifragmentary fractures. This hierarchy is based on the energy of injury or potential complexity of treatment. Ease of use is also an important aspect for a classification. This system allows the clinician to be as general or detailed as necessary according to their clinical or research needs. The classification is logical, comprehensible, and does not contain an unmanageable number of categories, a problem that ensures poor reliability. Principles of fracture and dislocation classification The principles of classification2 are based on understanding and applying standardized definitions. These definitions are universal and allow consistency in classification and communication. Although clinical decisions are sometimes made on incomplete information, this should be avoided as much as possible when classifying a fracture–the more precise the description the better the data recorded. Attention should be paid to upper-case versus lower-case letters and ( ) versus [ ] as this will aid in accurate fracture pattern retrieval from databases. Fracture localization–bones and segments The bone is identified (Fig 1).Fig 1: Designation of bone location.Next, it is necessary to determine where in the bone the fracture is located. This requires precise definitions of the parts of a bone. The proximal and distal end segments of the long bones are defined by a square whose sides are the same length as the widest part of the epiphysis/metaphysis in question (Heim's system of squares).23 Each bone has a proximal and distal end segment, between which the diaphysis or shaft is located. These definitions apply to any bone with articulations at both ends and a segment of cortical bone between the articulations, for example, a femur, or a metacarpal, or a phalanx. With the two bone systems now having separate codes, it was decided to maintain the standard definition of the end segments with bones not separated (Fig 2).Fig 2: Determine the location of the end segment.Two exceptions are the proximal femur, defined as being above a line that passes transversely through the inferior edge of the lesser trochanter and the malleolar segment of the distal tibia. The bone segments are numbered as: Proximal end segment = 1 Diaphyseal segment = 2 Distal end segment = 3 The location of the fracture is determined by finding its center. This is defined as follows: In a simple fracture, the center of the fracture is obvious (Fig 3). In a wedge fracture, the center is at the level of the broadest part of the wedge (Fig 4). In a fragmentary wedge and a multifragmentary fracture, the center can be determined only after reduction (Fig 4). Any diaphyseal fracture associated with a displaced articular component is considered an articular fracture. If a fracture is associated with an undisplaced fissure that reaches the joint, it is classified as a metaphyseal or diaphyseal fracture depending on its center. If one bone has two completely separate fractures, one in the diaphysis and one in the proximal or distal end segments (eg, a femoral diaphysis and a femoral neck fracture), each fracture must be classified separately. Fig 3: Simple fractures. The dot represents the center of the fracture.Fig 4: Wedge fractures. The dot represents the center of the fracture.Fracture morphology: types, groups, subgroups, qualifications, and universal modifiers The type (upper-case letter) is a general description of fracture patterns while the group (numerals) is a more specific description based on the individual bone or specific fracture pattern. The morphology of the diaphyseal fracture is defined as: Simple–Type A fractures have a single circumferential disruption of the diaphysis. An oblique fracture forms an angle ≥30° to a line perpendicular to the long axis of the bone. (Fig 3). Wedge–Type B fractures are characterized by contact between the main fragments after reduction usually restoring the length of the bone. The wedge may be or in multiple fragments fragmentary The between and wedge is and not easily determined so these terms were to the universal modifiers (Fig 4). C fractures of many fracture and fracture fragments. These fractures were as wedge or complex fractures in the Müller classification. is a term that confusion it is and is in the 2018 by the term many fracture and not a wedge fracture. In the diaphyseal segment, the segment is or in many fragments so that after reduction if the were there would be no contact between the proximal and distal fragments. is used to describe fragmentation of a wedge or segment (Fig Multifragmentary morphology for end segment fractures is based on they are extraarticular into the articular or intraarticular an into the articular The fracture line may be metaphyseal or but it the articular it may be The fracture part of the articular while the of the joint and is to the and diaphysis. There is a disruption of the articular and the articular is completely separated from the diaphysis. description of fracture morphology at the articular or use the previously defined terms of simple disruption of the joint and multifragmentary of the joint fractures are classified as extraarticular simple fractures (Fig segments fractures are divided into three The proximal end segment of the humerus and femur are Simple proximal humeral fractures one or the or Neer and proximal femoral fractures the are type A The articular type does not in the humerus or Proximal humeral fracture one and the or Neer and the proximal femoral fracture the femoral neck are type Proximal humeral articular fractures the anatomical neck of the humerus and fractures the femoral are type C. The definitions or description of groups and are fracture Universal modifiers The universal modifiers are descriptive terms of fracture associated or location that are to fractures. that are for Universal modifiers may be added to the end of the fracture code within square universal modifiers may be within the same of and separated by a A proximal humerus with and = proximal end segment, articular or fracture, with multifragmentary metaphyseal fracture and articular fracture with an dislocation = Dislocation is also is also Diaphyseal 1 and and 2 to of 3 with of to to bone but not included through bone bone associated with a fracture with a type fracture type fracture system is used with the of the International The fracture qualifications are descriptive terms of fracture morphology or location that are specific to each fracture. All fracture classification qualifications are lower-case letters to from the fracture which is an upper-case All fracture qualifications are in of the in the fracture code as a lower-case within a appropriate in the classification the qualification that to an the is proximal end segment, articular or fracture, with multifragmentary metaphyseal fracture and simple articular fracture with an dislocation process of classification and coding a diaphyseal process of classification and coding an of the AO/OTA classification Since the original of the AO/OTA Fracture Classification in the 1996 Journal of Orthopaedic Trauma there has been important in fracture classification the of a accepted fracture The years of use of the AO/OTA compendium has its and Although the process of classification validation has been and expensive and generally not practical in a retrospective for accepted classifications. With the use of validated a standardized classification of injury is The AOTIB and OTA Classification Committee through the International Comprehensive Classification of Fractures and Dislocations Committee the need to make the compendium as and standardized as This compendium addresses many of the prior criticisms as well as the prior editions and adding new published classifications. These changes in and presentation should make the compendium more universal and to These standardized classification systems should make injury description more standardized and so improve research and fracture The collaboration of the AOTIB and the OTA through their classification committees has in the of the compendium copyright to both organizations so it is available for any clinician to use This collaboration has its in both and The organizations are committed to to the compendium and as

Before publication of the original version of this report in 1987, practitioners of bone histomorphometry communicated with each other in a variety of arcane languages, which in general were unintelligible to those outside the field. The need for standardization of nomenclature had been recognized for many years,1 during which there had been much talk but no action. To satisfy this need, B Lawrence Riggs (ASBMR President, 1985 to 1986) asked A Michael Parfitt to convene an ASBMR committee to develop a new and unified system of terminology, suitable for adoption by the Journal of Bone and Mineral Research (JBMR) as part of its Instructions to Authors. The resulting recommendations were published in 19872 and were quickly adopted not only by JBMR but also by all respected journals in the bone field. The recommendations improved markedly the ability of histomorphometrists to communicate with each other and with nonhistomorphometrists, leading to a broader understanding and appreciation of histomorphometric data. In 2012, 25 years after the development of the standardized nomenclature system, Thomas L Clemens (Editor in Chief of JBMR) felt that it was time to revise and update the recommendations. The original committee was reconvened by David W Dempster, who appointed one new member, Juliet E Compston. The original document was circulated to the committee members and was extensively revised according to their current recommendations. The key revisions include omission of terminology used before 1987, recommendations regarding the parameters and technical information that should be included in all histomorphometry articles, recommendations on how to handle dynamic parameters of bone formation in settings of low bone turnover, and updating of references. It is generally agreed that a bone is an individual organ of the skeletal system, but the term “bone” has at least three meanings. The first is mineralized bone matrix excluding osteoid; this usage conforms rigorously to the definition of bone as a hard tissue. Osteoid is bone matrix that will be (but is not yet) mineralized, and is sometimes referred to as pre-bone. The second meaning of “bone,” and the one we have adopted, is bone matrix, whether mineralized or not, ie, including both mineralized bone and osteoid. The third meaning of “bone” is a tissue including bone marrow and other soft tissue, as well as bone as just defined. We refer to the combination of bone and associated soft tissue or marrow as “bone tissue.” “Tissue” is defined3 as “an aggregation of similarly specialized cells united in the performance of a particular function.” In this sense, bone, bone marrow, and the contents of osteonal canals are certainly not the same tissue, but in a more general sense, most textbooks of histology recognize only four fundamental tissues—epithelium, nerve, muscle, and connective tissue4—of which the last-named includes bone and all its accompanying nonmineralized tissue. In current clinical and radiologic parlance, “trabecular” and “cortical” refer to contrasting structural types of bone. But “trabecular” does not appear in any standard textbook of anatomy or histology as a name for a type of bone; rather, “spongy” or “cancellous” is used. “Spongiosa” (primary or secondary) is best restricted to the stages of endochondral ossification; “cancellous” is most commonly used in textbooks4, 5 and is the term we have chosen. We retain the noun “trabecula” and its associated adjective “trabecular” to refer to an individual structural element of cancellous bone, in accordance with current practice in histology,4 pathology,6 and biomechanics.7 Etymologically, a trabecula is a beam or rod, and in young people plates rather than rods are the predominant structural elements, both in the spine8 and in the ilium,9 but no convenient alternative is available. The size, shape, and orientation of trabeculae (as just defined) vary considerably between different types of cancellous bone.9, 10 “Density” is a frequent source of confusion in discussions about bone. We propose that the term should be restricted as far as possible to its primary meaning in physics of mass per unit volume,11, 12 with a subsidiary meaning analogous to population density, which is applied mainly to cells. This precludes the use of “density” in its stereologic sense, as will be to the the to which mass is referred be of mineralized bone, bone, bone tissue or or a bone. bone is than bone density, which the of and This is and generally be but is to Bone the of osteoid; bone matrix excluding and has been referred to as bone Bone tissue the of soft tissue, or bone density, referred to as bone density, the of bone tissue, cancellous bone tissue, and marrow a bone, the organ of which is by is in the clinical and In most bone are or formation and all cells on the are or but in the most bone are with to bone We refer to the cells that bone as cells and the term to cells that are bone matrix or with only rather than including all cells that are not cells are of and are to have The term is restricted to cells and are have only one or no for of and whether or should be or A of types of primary be on of a or between or between and histomorphometrists report all only in the for to three be to and the of the or the of an are not this is a but bone be in In other of that as an the is to by the of which is the We that this also should be the of bone are for between between and between different types of bone, for element of bone for of and for many of bone as the of and the of individual But as a it is to on adoption of a stereologic that be and a only in bone the is to the bone its before In the the use of a in the was a convenient of of but this for at an the of the of to most stereologic also that the be meaning that a to any element of has an of in any in not for all cancellous bone, in the there is only and stereologic be used with 25 But it is more to the of a is which is with the use of a but there is no other of canals generally not the by more than stereologic in bone are but of the stereologic to bone has not been we that histomorphometric should one of all and in the and or (as by the only the the and with the an is for each type of of how it was the primary as A of and should not be used in the same The only is the type of primary for which there is no convenient of to three the of the of in three is possible the same be in of and but this has not been applied to bone. as also be The original committee not to the terminology of the of as was at the on Bone use the term “density” in a general to any referred to that is and per unit is the of terminology is in the the of “density” in different the all to at the of bone histomorphometry will need to be with the of many to bone are published in the Journal of which is the of the of of and are of the of tissue and be between only to a which will be or the and in have no and in three but it is convenient to refer to as and to as the is the of and of individual have meaning in and are the only type that not a different and to different that use of is and it is to between used include tissue bone bone and and their or of the the use of as a term The of the is not commonly used as a at but is for with of bone for the of and cancellous bone of or for the of different types of bone and different to as of and of and for in the between and of bone of the as a the possible an to the in of to bone as an be as of the the of the to the mainly on the of the bone at the of be with a the but the of and cancellous tissue in the bone be with type of the be by the of and cancellous bone tissue in the The same be applied to and to bone by the by the as the The individual are in in of their or general are in a the is to be rather than the use of is mainly to time or there is a more for as for other their use in other but confusion is with that be with is not to or the use of and but to that the same are used by To this we have the to and the of new with different meanings. We have included in bone their and commonly used in and as well as for all the structural of bone and of and for of bone with are and in to their one the and in of only is it is and used and a suitable The most commonly used are a have an in many to the second or and the second of the by the are used for that are in to for the primary of and and for in its used in should be by a in the of each is to be as an individual In this any combination of be to which are included in the Bone histomorphometry be applied to many types of but the most are of of bone and of we first the terminology for to the the between and is it is to the of the bone at the for the the term is more is and cancellous for on the their are but it is possible to of their and In this the are generally by their of the and that one be in by or at the time of the but this is The generally has more and tissue than the The other of the is referred to as only the of the have the same as the the more term is the of the is to the of the its are It is convenient to as and of for and cancellous for are by the between and in the to of bone different on on by and with of of of on on cancellous to cancellous the and not and their is used for for the the by the and are the be used to and the of bone bone is similarly and cancellous for or marrow for The between and bone and cancellous or marrow on the of the be at in to the in both and bone it is for to recognize a between and cancellous bone tissue and in and This is not in or of its are not A has been used to this in This be to bone but this has not been all all in with bone marrow are referred to as and are cancellous bone and the is the of the between is to in accordance with and will also on whether the is not in with bone marrow are generally referred to as with as the also be referred to as the or osteonal of the of a bone; is on the and is on the the cancellous bone of the is not bone cancellous marrow The standard and for all should be that the of to as well as to the and are used only as and are used only as to the on which the was whether this was a particular or a particular type of tissue. of the commonly used have been many are by the are restricted to of a as the of a or the of cancellous the same be but the should be in the of on the the source is as it will not be to the source each time a particular is referred only one source is used in an it need only be are their be used as for of in or and in most will need to be only are that confusion between is as only one source is possible and its is The three and the are the key to one to is to in stereologic terminology, and and are to in stereologic are the and by which is for or by which has been for cancellous The with that the be and and to in stereologic terminology and are with the and a of the bone is as a and are to and it be to to the mineralized as an alternative to the more bone and of bone formation be to the or to the of as well as to or bone it be to use the between mineralized bone and or bone as a for the of or of the is are In many as only one is used for each the need only be and not each time the is more than one is with the same be to are with in both and in have been but need is used for of mineralized bone and is by Osteoid need to be as or as the in the between which to a and which to a for all are with the is a general term to all tissue that is not and includes marrow in cancellous bone and and canals in bone. both types of tissue, with on individual as cells or The be as an of tissue, by use of the is the of all referred to the of tissue and in The also be as individual by of a is the of individual confusion is the term be as or in be to in the are in be used to but it is to this as Osteoid not that should be for of We the formation and the of current be and for the same we the is with or and the and the individual also be as or cells and are for and the cells on the or cells. is with or the term that will at The of connective tissue the cells on should not be referred to as It is possible that by cells should be as rather than as In all be in by at or by of and The is more and a and a standard as well as a but that be The is and to The is used for between and and and the is used for and are used for and The is for the the between individual at particular and at particular during the The by in an individual be the in a of is the the to the between bone and It is used in and in different types of and different stages of in the should be to the between and is on an individual it has been used in the for of the of and in as an of in is the between on of a as for the is an of bone the but is of the of bone to the most of the but that are the of be restricted to the of the of are but to and need for a be In most the will be an or but of also be per is the of per to bone in cancellous bone tissue, a that with as and as are are and are in a that has been to of its The of to in a is an of be structural or of the are on that are but not rigorously and individual to use or of the that we have is with and time are L and but have other in the according to the as which is to of for cancellous the alternative is with by To between the alternative this is to the with It should be that there is in the term which has been a different by the ASBMR with with the it as the between rather than between is according to the as or as This by is an of the marrow to the and a is by but be in any to the of the marrow as the between is by and also be The of in at a particular time is by the of the resulting at that The of the of is to the of the first and second the of the of are available. of the term or a between the of the the second it is in time to the the only one was in of the or after the the and of the and of the of are the of the and should be be in to a variety of is to the of during which It should be that of individual on the Parfitt and that were than of the in which were This should be in the of and and it is to a is used to in bone formation in a Mineral is the between the or between the of by the time between the of the the of for and the of the vary with the of the which be and We the and to confusion between and and are used in to refer to the bone formation is no convenient of between the and by different that the is it is that the be used is as and the or the bone formation the It is analogous to the and is with formation and “bone formation but of alternative is The is in a and in the of the is the best a of the of the of formation of mineralized bone and of bone matrix, the including of and are their are of and the term be used. We refer to and as rather than as formation to the that an has meaning at a on the a formation has meaning only in to of tissue, or in the of a of but a formation is by the of and on the of as well as on their The rather than the is as the unit the of the on the of its members as well as on their individual Mineral formation is the of mineralized bone per unit as the of and as this term be as to the of the more term mineralized bone formation be used. In a and in the of the formation is with the bone formation and the is the and more term should be used. is a bone formation to each possible for and Bone formation the is to the as bone formation per unit of bone most on bone Bone formation per unit of bone is to the bone which bone and of Bone formation per unit of tissue most of bone the tissue is and its to the The of the was Bone be by histomorphometry but be as the bone formation or by an or of of bone that all are in to the same or of bone a be by and and osteonal with in but it be that bone formation at the current the time which the of bone of the of bone turnover, most the that and formation are is than the of but it is more to that mineralized in to or of bone alternative is to use to the in bone which is for a of but to in a it is be in to a variety of different including time is the time between and of any of matrix, the of the and is by The is in the understanding of and the of it be that to the and of individual of has been as for and be time which is the time between the of matrix and the of at each The name that the of the matrix, as In the and are but in is and than be as and has also been referred to as rather than but it is more to by the of than but it be more convenient for use it is in that be applied to as and information about the of which be with and dynamic of bone is the time to a new bone structural unit or the to the bone at a and is by It includes or or other to the between and that be to and be as by or by or of a that to a between and is the of during the of bone formation is low to of or of of to its has also been referred to as is the key for of all other of the In a of are to of that is any other than including and but will the in are and their of their current and in the by be used to The of the and formation is the which is the of a of bone at any on a bone is a of or than the of bone that a of the for a the bone or the many are much than a including both and and the of many is much than the of a or a not commonly it is this that is the for of a new after any or it is used and in key an for this is an alternative that the and use of The of the and the is the which is the time between the of at the same on the The of is the which is the that a new of will at any on the by the of also be in the more as the of of or and in to the in the is that current does not of the in cancellous bone. It be that which is be as the of bone per were first for of parameters of bone of low were in bone in with the and use of are in which are low that there are no or only in cancellous for of is that the was not or This sometimes be by the of in in the or on the The that a of a low be by low for parameters of bone as or a for the and of the and a In there are no in an we that be as a and that the of in a be in the of the In this it is to a of for and to include in the of for In only or are to be and in the be as a or one has the of a to have been or on the for in the first or the in the The for in the the is also be used. are in of the the the for in that be used or one use the for for the to which the In any of is in three the should be applied The of a to only are is that a of be used to for and parameters as with the that for and the parameters be of will have the The key is that all the of in a with the with only and the and the of with is to the both have applied to for the this a to be on the of in a that have it does not the and the be to the information are low or in an it is that will be low or in the of the The or of and should be for and cancellous The recommendations for and also in the in which only one is primary of and and primary of and should be with the on and the of the most information in of rather than after the are for and and for the between in different and we rather than in this the be used to the and unit of are not used for the be by the type of only We as their with to three 10 also not to the and it more to that the is should be in all primary and in or and all in should be in with as an alternative for should be as and formation with as and should be in or years as most and in We recognize that many who bone histomorphometry or its will on most need to use only a of the we a of its most but this is not to on its to the of the We also a of parameters that should be included in all histomorphometry are in only the most are The term “bone” to bone matrix whether mineralized or not and “bone to bone as with its associated marrow or other soft tissue. Bone tissue is or the between which is the of the is referred to as A trabecula is an individual structural element of cancellous bone tissue, whether or in The term to bone matrix that in the of will mineralized, and does not include the of connective tissue that bone cells on all The between and mineralized bone is referred to as the “bone more The term is restricted to cells that are to be bone and does not refer to all cells with The and are not are that as and are the and are used. The of is referred to as of how it is The used for its be and A the whether or is referred to as a and the term is generally used only are on the be use of only or only terminology and the same or the same are referred to as and in and as and in three the type of primary be only are is the of should be and its The terminology and of the of will not be used. the term “density” its primary meaning in physics of mass per unit this in no the of stereologic for and or is only as an of the of tissue for which should be the term is not used in any other the four types of primary only be a which will be and or in the are possible for all the be and this is as and are and should not be used. only one is or with the same are the need to be only but it be each time there is any of of the first in the same as the in the or has only one as in and no in the of is are used for the most frequent a and an for frequent and a for that are in to be by in the of each is to be as a The same is used for all The source is the type of or a on which the was and will most commonly be bone tissue cancellous bone tissue or but many other are in use or be the in which the source be the name are in the of the practice is in this have only been on cancellous bone tissue, the source is for bone and for and The need for and the to were The most commonly used are tissue bone bone and bone but many other be for particular The are by the to in stereologic and in stereologic we a type with an of at least for and information be with and with rather than but the of that be is more The tissue to be is and the bone is We that be at least three the at about the and by to the tissue and bone The of and the tissue and bone should be in all The committee that a of be used to be with but in that the of used to in a of should be 5 a of and should be and in all histomorphometry with their and that the are on for and and for time and and that is for It is to between and dynamic the not but it is more to between primary and primary is not the but the use of no more of the than is to in of a or to by a as the time between more and on one or more that should be should not be the primary which are that have no of the first of the other and revised this and

A concerted effort to tackle the global health problem posed by traumatic brain injury (TBI) is long overdue. TBI is a public health challenge of vast, but insufficiently recognised, proportions. Worldwide, more than 50 million people have a TBI each year, and it is estimated that about half the world's population will have one or more TBIs over their lifetime. TBI is the leading cause of mortality in young adults and a major cause of death and disability across all ages in all countries, with a disproportionate burden of disability and death occurring in low-income and middle-income countries (LMICs). It has been estimated that TBI costs the global economy approximately $US400 billion annually. Deficiencies in prevention, care, and research urgently need to be addressed to reduce the huge burden and societal costs of TBI. This Commission highlights priorities and provides expert recommendations for all stakeholders—policy makers, funders, health-care professionals, researchers, and patient representatives—on clinical and research strategies to reduce this growing public health problem and improve the lives of people with TBI.

The purpose of this new classification compendium is to republish the Orthopaedic Trauma Association's (OTA) classification. The OTA classification was originally published in a compendium of the Journal of Orthopaedic Trauma in 1996. It adopted The Comprehensive Classification of the Long Bones developed by Müller and colleagues and classified the remaining bones. In this compendium, the introductory chapter reviews new scientific information about classifying fractures that has been published in the last 11 years. The classification is presented in a revised format that is easier to follow. The OTA and AO classification will now have a unified alpha-numeric code eliminating the differences that have existed between the 2 codes. The code was significantly revised for the clavicle and scapula, foot and hand, and patella. Dislocations have been expanded on an anatomic basis and for most joints will be coded separately. This publication should stimulate new developments and interest in a unified language to code and classify fractures. Further improvements in classification will result in better patient care and clinical research.

BACKGROUND: Cardiac-resynchronization therapy (CRT) benefits patients with left ventricular systolic dysfunction and a wide QRS complex. Most of these patients are candidates for an implantable cardioverter-defibrillator (ICD). We evaluated whether adding CRT to an ICD and optimal medical therapy might reduce mortality and morbidity among such patients. METHODS: We randomly assigned patients with New York Heart Association (NYHA) class II or III heart failure, a left ventricular ejection fraction of 30% or less, and an intrinsic QRS duration of 120 msec or more or a paced QRS duration of 200 msec or more to receive either an ICD alone or an ICD plus CRT. The primary outcome was death from any cause or hospitalization for heart failure. RESULTS: We followed 1798 patients for a mean of 40 months. The primary outcome occurred in 297 of 894 patients (33.2%) in the ICD-CRT group and 364 of 904 patients (40.3%) in the ICD group (hazard ratio in the ICD-CRT group, 0.75; 95% confidence interval [CI], 0.64 to 0.87; P<0.001). In the ICD-CRT group, 186 patients died, as compared with 236 in the ICD group (hazard ratio, 0.75; 95% CI, 0.62 to 0.91; P = 0.003), and 174 patients were hospitalized for heart failure, as compared with 236 in the ICD group (hazard ratio, 0.68; 95% CI, 0.56 to 0.83; P<0.001). However, at 30 days after device implantation, adverse events had occurred in 124 patients in the ICD-CRT group, as compared with 58 in the ICD group (P<0.001). CONCLUSIONS: Among patients with NYHA class II or III heart failure, a wide QRS complex, and left ventricular systolic dysfunction, the addition of CRT to an ICD reduced rates of death and hospitalization for heart failure. This improvement was accompanied by more adverse events. (Funded by the Canadian Institutes of Health Research and Medtronic of Canada; ClinicalTrials.gov number, NCT00251251.).

BACKGROUND: Persistent acute respiratory distress syndrome (ARDS) is characterized by excessive fibroproliferation, ongoing inflammation, prolonged mechanical ventilation, and a substantial risk of death. Because previous reports suggested that corticosteroids may improve survival, we performed a multicenter, randomized controlled trial of corticosteroids in patients with persistent ARDS. METHODS: We randomly assigned 180 patients with ARDS of at least seven days' duration to receive either methylprednisolone or placebo in a double-blind fashion. The primary end point was mortality at 60 days. Secondary end points included the number of ventilator-free days and organ-failure-free days, biochemical markers of inflammation and fibroproliferation, and infectious complications. RESULTS: At 60 days, the hospital mortality rate was 28.6 percent in the placebo group (95 percent confidence interval, 20.3 to 38.6 percent) and 29.2 percent in the methylprednisolone group (95 percent confidence interval, 20.8 to 39.4 percent; P=1.0); at 180 days, the rates were 31.9 percent (95 percent confidence interval, 23.2 to 42.0 percent) and 31.5 percent (95 percent confidence interval, 22.8 to 41.7 percent; P=1.0), respectively. Methylprednisolone was associated with significantly increased 60- and 180-day mortality rates among patients enrolled at least 14 days after the onset of ARDS. Methylprednisolone increased the number of ventilator-free and shock-free days during the first 28 days in association with an improvement in oxygenation, respiratory-system compliance, and blood pressure with fewer days of vasopressor therapy. As compared with placebo, methylprednisolone did not increase the rate of infectious complications but was associated with a higher rate of neuromuscular weakness. CONCLUSIONS: These results do not support the routine use of methylprednisolone for persistent ARDS despite the improvement in cardiopulmonary physiology. In addition, starting methylprednisolone therapy more than two weeks after the onset of ARDS may increase the risk of death. (ClinicalTrials.gov number, NCT00295269.).

OBJECTIVE: To provide clinicians with evidence-based strategies to optimize the support of the family of critically ill patients in the ICU. METHODS: We used the Council of Medical Specialty Societies principles for the development of clinical guidelines as the framework for guideline development. We assembled an international multidisciplinary team of 29 members with expertise in guideline development, evidence analysis, and family-centered care to revise the 2007 Clinical Practice Guidelines for support of the family in the patient-centered ICU. We conducted a scoping review of qualitative research that explored family-centered care in the ICU. Thematic analyses were conducted to support Population, Intervention, Comparison, Outcome question development. Patients and families validated the importance of interventions and outcomes. We then conducted a systematic review using the Grading of Recommendations, Assessment, Development and Evaluations methodology to make recommendations for practice. Recommendations were subjected to electronic voting with pre-established voting thresholds. No industry funding was associated with the guideline development. RESULTS: The scoping review yielded 683 qualitative studies; 228 were used for thematic analysis and Population, Intervention, Comparison, Outcome question development. The systematic review search yielded 4,158 reports after deduplication and 76 additional studies were added from alerts and hand searches; 238 studies met inclusion criteria. We made 23 recommendations from moderate, low, and very low level of evidence on the topics of: communication with family members, family presence, family support, consultations and ICU team members, and operational and environmental issues. We provide recommendations for future research and work-tools to support translation of the recommendations into practice. CONCLUSIONS: These guidelines identify the evidence base for best practices for family-centered care in the ICU. All recommendations were weak, highlighting the relative nascency of this field of research and the importance of future research to identify the most effective interventions to improve this important aspect of ICU care.

BACKGROUND AND AIMS: Acute appendicitis (AA) is among the most common causes of acute abdominal pain. Diagnosis of AA is still challenging and some controversies on its management are still present among different settings and practice patterns worldwide. In July 2015, the World Society of Emergency Surgery (WSES) organized in Jerusalem the first consensus conference on the diagnosis and treatment of AA in adult patients with the intention of producing evidence-based guidelines. An updated consensus conference took place in Nijemegen in June 2019 and the guidelines have now been updated in order to provide evidence-based statements and recommendations in keeping with varying clinical practice: use of clinical scores and imaging in diagnosing AA, indications and timing for surgery, use of non-operative management and antibiotics, laparoscopy and surgical techniques, intra-operative scoring, and peri-operative antibiotic therapy. METHODS: This executive manuscript summarizes the WSES guidelines for the diagnosis and treatment of AA. Literature search has been updated up to 2019 and statements and recommendations have been developed according to the GRADE methodology. The statements were voted, eventually modified, and finally approved by the participants to the consensus conference and by the board of co-authors, using a Delphi methodology for voting whenever there was controversy on a statement or a recommendation. Several tables highlighting the research topics and questions, search syntaxes, and the statements and the WSES evidence-based recommendations are provided. Finally, two different practical clinical algorithms are provided in the form of a flow chart for both adults and pediatric (< 16 years old) patients. CONCLUSIONS: The 2020 WSES guidelines on AA aim to provide updated evidence-based statements and recommendations on each of the following topics: (1) diagnosis, (2) non-operative management for uncomplicated AA, (3) timing of appendectomy and in-hospital delay, (4) surgical treatment, (5) intra-operative grading of AA, (6) ,management of perforated AA with phlegmon or abscess, and (7) peri-operative antibiotic therapy.

BACKGROUND: Intracranial-pressure monitoring is considered the standard of care for severe traumatic brain injury and is used frequently, but the efficacy of treatment based on monitoring in improving the outcome has not been rigorously assessed. METHODS: We conducted a multicenter, controlled trial in which 324 patients 13 years of age or older who had severe traumatic brain injury and were being treated in intensive care units (ICUs) in Bolivia or Ecuador were randomly assigned to one of two specific protocols: guidelines-based management in which a protocol for monitoring intraparenchymal intracranial pressure was used (pressure-monitoring group) or a protocol in which treatment was based on imaging and clinical examination (imaging-clinical examination group). The primary outcome was a composite of survival time, impaired consciousness, and functional status at 3 months and 6 months and neuropsychological status at 6 months; neuropsychological status was assessed by an examiner who was unaware of protocol assignment. This composite measure was based on performance across 21 measures of functional and cognitive status and calculated as a percentile (with 0 indicating the worst performance, and 100 the best performance). RESULTS: There was no significant between-group difference in the primary outcome, a composite measure based on percentile performance across 21 measures of functional and cognitive status (score, 56 in the pressure-monitoring group vs. 53 in the imaging-clinical examination group; P=0.49). Six-month mortality was 39% in the pressure-monitoring group and 41% in the imaging-clinical examination group (P=0.60). The median length of stay in the ICU was similar in the two groups (12 days in the pressure-monitoring group and 9 days in the imaging-clinical examination group; P=0.25), although the number of days of brain-specific treatments (e.g., administration of hyperosmolar fluids and the use of hyperventilation) in the ICU was higher in the imaging-clinical examination group than in the pressure-monitoring group (4.8 vs. 3.4, P=0.002). The distribution of serious adverse events was similar in the two groups. CONCLUSIONS: For patients with severe traumatic brain injury, care focused on maintaining monitored intracranial pressure at 20 mm Hg or less was not shown to be superior to care based on imaging and clinical examination. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT01068522.).

OBJECTIVES: The authors test the reliability and validity of the Medical Outcomes Study Short Form 36-Item Health Survey (SF-36) as a written, self-administered survey in outpatients with chronic schizophrenia. METHODS: Thirty-six schizophrenic outpatients completed a written and oral form of the SF-36. A psychiatrist rated the patients using the Brief Psychiatric Rating Scale to determine severity of psychopathology. Cognitive functioning and academic achievement were also assessed. Internal consistency, test-retest reliability, concurrent and discriminative validity of the oral and written versions were determined. RESULTS: The SF-36 in both forms was shown to have good internal consistency, stability, and concurrent validity. The mental health SF-36 subscales had poor discriminant validity, compared with the physical functioning scale that demonstrated good discriminant validity. CONCLUSIONS: The validity of using the written form of the SF-36 on a sample of patients with chronic mental illness was demonstrated. The SF-36 appears to be an appropriate outcome measure for changes in physical and role functioning in consumers of outpatient mental health programs.

The accurate quantitation of high density lipoproteins has recently assumed greater importance in view of studies suggesting their negative correlation with coronary heart disease. High density lipoproteins may be estimated by measuring cholesterol in the plasma fraction of d > 1.063 g/ml. A more practical approach is the specific precipitation of apolipoprotein B (apoB)-containing lipoproteins by sulfated polysaccharides and divalent cations, heparin-Mn(2+) being the most commonly used combination. The present heparin-Mn(2+) procedure was found to be reasonably specific and not often subject to large errors; however, 9% (primarily hypertriglyceridemic samples) of the 966 plasma samples treated with heparin-Mn(2+) had obvious supernatant turbidity, indicating incomplete sedimentation of apoB-associated lipoproteins. Furthermore, 48% of the nonturbid supernates contained more than 1 mg/dl (mean 2.5 mg/dl) of apoB-associated cholesterol when measured by a radial immunodiffusion procedure, indicating slight overestimation of HDL cholesterol. Determination of the extent of the unprecipitated apoB-associated lipoproteins by sensitive radioimmunoassay and of the amount of precipitated high density lipoprotein by radial immunodiffusion assay of apolipoproteins A-I and A-II at various heparin and Mn(2+) concentrations indicated that the usual heparin level (approximately 1.3 mg/ml) was adequate. However, a twofold increase in Mn(2+) concentration to 0.092 M improved precipitation of the apoB-associated lipoproteins without excessive precipitation of high density lipoprotein from plasma. This increased Mn(2+) level also provided improved sedimentation of the apoB-associated lipoproteins from hypertriglyceridemic plasma. Additional observations suggested that, for convenience, the heparin and Mn(2+) can be added simultaneously as a combined reagent, that samples can be incubated for 10 minutes at room temperature before centrifugation, and that turbid supernates from hypertriglyceridemic samples can usually be made free of apoB-associated lipoproteins by centrifugation at 12,000 g for 10 minutes.

Human survival from injury requires an appropriate inflammatory and immune response. We describe the circulating leukocyte transcriptome after severe trauma and burn injury, as well as in healthy subjects receiving low-dose bacterial endotoxin, and show that these severe stresses produce a global reprioritization affecting >80% of the cellular functions and pathways, a truly unexpected "genomic storm." In severe blunt trauma, the early leukocyte genomic response is consistent with simultaneously increased expression of genes involved in the systemic inflammatory, innate immune, and compensatory antiinflammatory responses, as well as in the suppression of genes involved in adaptive immunity. Furthermore, complications like nosocomial infections and organ failure are not associated with any genomic evidence of a second hit and differ only in the magnitude and duration of this genomic reprioritization. The similarities in gene expression patterns between different injuries reveal an apparently fundamental human response to severe inflammatory stress, with genomic signatures that are surprisingly far more common than different. Based on these transcriptional data, we propose a new paradigm for the human immunological response to severe injury.

OBJECTIVE: Despite concern over the appropriateness and quality of care provided in an intensive care unit (ICU) at the end of life, the number of Americans who receive ICU care at the end of life is unknown. We sought to describe the use of ICU care at the end of life in the United States using hospital discharge data from 1999 for six states and the National Death Index. DESIGN: Retrospective analysis of administrative data to calculate age-specific rates of hospitalization with and without ICU use at the end of life, to generate national estimates of end-of-life hospital and ICU use, and to characterize age-specific case mix of ICU decedents. SETTING: All nonfederal hospitals in the states of Florida, Massachusetts, New Jersey, New York, Virginia, and Washington. PATIENTS: All inpatients in nonfederal hospitals in the six states in 1999. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: We found that there were 552,157 deaths in the six states in 1999, of which 38.3% occurred in hospital and 22.4% occurred after ICU admission. Using these data to project nationwide estimates, 540,000 people die after ICU admission each year. The age-specific rate of ICU use at the end of life was highest for infants (43%), ranged from 18% to 26% among older children and adults, and fell to 14% for those >85 yrs. Average length of stay and costs were 12.9 days and $24,541 for terminal ICU hospitalizations and 8.9 days and $8,548 for non-ICU terminal hospitalizations. CONCLUSIONS: One in five Americans die using ICU services. The doubling of persons over the age of 65 yrs by 2030 will require a system-wide expansion in ICU care for dying patients unless the healthcare system pursues rationing, more effective advanced care planning, and augmented capacity to care for dying patients in other settings.