San Francisco General Hospital

Evidence-based guidelines for the management of patients with methicillin-resistant Staphylococcus aureus (MRSA) infections were prepared by an Expert Panel of the Infectious Diseases Society of America (IDSA). The guidelines are intended for use by health care providers who care for adult and pediatric patients with MRSA infections. The guidelines discuss the management of a variety of clinical syndromes associated with MRSA disease, including skin and soft tissue infections (SSTI), bacteremia and endocarditis, pneumonia, bone and joint infections, and central nervous system (CNS) infections. Recommendations are provided regarding vancomycin dosing and monitoring, management of infections due to MRSA strains with reduced susceptibility to vancomycin, and vancomycin treatment failures.

BACKGROUND: Previous trials have demonstrated that lowering low-density lipoprotein (LDL) cholesterol levels below currently recommended levels is beneficial in patients with acute coronary syndromes. We prospectively assessed the efficacy and safety of lowering LDL cholesterol levels below 100 mg per deciliter (2.6 mmol per liter) in patients with stable coronary heart disease (CHD). METHODS: A total of 10,001 patients with clinically evident CHD and LDL cholesterol levels of less than 130 mg per deciliter (3.4 mmol per liter) were randomly assigned to double-blind therapy and received either 10 mg or 80 mg of atorvastatin per day. Patients were followed for a median of 4.9 years. The primary end point was the occurrence of a first major cardiovascular event, defined as death from CHD, nonfatal non-procedure-related myocardial infarction, resuscitation after cardiac arrest, or fatal or nonfatal stroke. RESULTS: The mean LDL cholesterol levels were 77 mg per deciliter (2.0 mmol per liter) during treatment with 80 mg of atorvastatin and 101 mg per deciliter (2.6 mmol per liter) during treatment with 10 mg of atorvastatin. The incidence of persistent elevations in liver aminotransferase levels was 0.2 percent in the group given 10 mg of atorvastatin and 1.2 percent in the group given 80 mg of atorvastatin (P<0.001). A primary event occurred in 434 patients (8.7 percent) receiving 80 mg of atorvastatin, as compared with 548 patients (10.9 percent) receiving 10 mg of atorvastatin, representing an absolute reduction in the rate of major cardiovascular events of 2.2 percent and a 22 percent relative reduction in risk (hazard ratio, 0.78; 95 percent confidence interval, 0.69 to 0.89; P<0.001). There was no difference between the two treatment groups in overall mortality. CONCLUSIONS: Intensive lipid-lowering therapy with 80 mg of atorvastatin per day in patients with stable CHD provides significant clinical benefit beyond that afforded by treatment with 10 mg of atorvastatin per day. This occurred with a greater incidence of elevated aminotransferase levels.

IMPORTANCE: The human and financial costs of treating surgical site infections (SSIs) are increasing. The number of surgical procedures performed in the United States continues to rise, and surgical patients are initially seen with increasingly complex comorbidities. It is estimated that approximately half of SSIs are deemed preventable using evidence-based strategies. OBJECTIVE: To provide new and updated evidence-based recommendations for the prevention of SSI. EVIDENCE REVIEW: A targeted systematic review of the literature was conducted in MEDLINE, EMBASE, CINAHL, and the Cochrane Library from 1998 through April 2014. A modified Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach was used to assess the quality of evidence and the strength of the resulting recommendation and to provide explicit links between them. Of 5759 titles and abstracts screened, 896 underwent full-text review by 2 independent reviewers. After exclusions, 170 studies were extracted into evidence tables, appraised, and synthesized. FINDINGS: Before surgery, patients should shower or bathe (full body) with soap (antimicrobial or nonantimicrobial) or an antiseptic agent on at least the night before the operative day. Antimicrobial prophylaxis should be administered only when indicated based on published clinical practice guidelines and timed such that a bactericidal concentration of the agents is established in the serum and tissues when the incision is made. In cesarean section procedures, antimicrobial prophylaxis should be administered before skin incision. Skin preparation in the operating room should be performed using an alcohol-based agent unless contraindicated. For clean and clean-contaminated procedures, additional prophylactic antimicrobial agent doses should not be administered after the surgical incision is closed in the operating room, even in the presence of a drain. Topical antimicrobial agents should not be applied to the surgical incision. During surgery, glycemic control should be implemented using blood glucose target levels less than 200 mg/dL, and normothermia should be maintained in all patients. Increased fraction of inspired oxygen should be administered during surgery and after extubation in the immediate postoperative period for patients with normal pulmonary function undergoing general anesthesia with endotracheal intubation. Transfusion of blood products should not be withheld from surgical patients as a means to prevent SSI. CONCLUSIONS AND RELEVANCE: This guideline is intended to provide new and updated evidence-based recommendations for the prevention of SSI and should be incorporated into comprehensive surgical quality improvement programs to improve patient safety.

BACKGROUND: Inhibition of cholesteryl ester transfer protein (CETP) has been shown to have a substantial effect on plasma lipoprotein levels. We investigated whether torcetrapib, a potent CETP inhibitor, might reduce major cardiovascular events. The trial was terminated prematurely because of an increased risk of death and cardiac events in patients receiving torcetrapib. METHODS: We conducted a randomized, double-blind study involving 15,067 patients at high cardiovascular risk. The patients received either torcetrapib plus atorvastatin or atorvastatin alone. The primary outcome was the time to the first major cardiovascular event, which was defined as death from coronary heart disease, nonfatal myocardial infarction, stroke, or hospitalization for unstable angina. RESULTS: At 12 months in patients who received torcetrapib, there was an increase of 72.1% in high-density lipoprotein cholesterol and a decrease of 24.9% in low-density lipoprotein cholesterol, as compared with baseline (P<0.001 for both comparisons), in addition to an increase of 5.4 mm Hg in systolic blood pressure, a decrease in serum potassium, and increases in serum sodium, bicarbonate, and aldosterone (P<0.001 for all comparisons). There was also an increased risk of cardiovascular events (hazard ratio, 1.25; 95% confidence interval [CI], 1.09 to 1.44; P=0.001) and death from any cause (hazard ratio, 1.58; 95% CI, 1.14 to 2.19; P=0.006). Post hoc analyses showed an increased risk of death in patients treated with torcetrapib whose reduction in potassium or increase in bicarbonate was greater than the median change. CONCLUSIONS: Torcetrapib therapy resulted in an increased risk of mortality and morbidity of unknown mechanism. Although there was evidence of an off-target effect of torcetrapib, we cannot rule out adverse effects related to CETP inhibition. (ClinicalTrials.gov number, NCT00134264 [ClinicalTrials.gov].).

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.

A panel of national experts was convened by the Infectious Diseases Society of America (IDSA) to update the 2005 guidelines for the treatment of skin and soft tissue infections (SSTIs). The panel's recommendations were developed to be concordant with the recently published IDSA guidelines for the treatment of methicillin-resistant Staphylococcus aureus infections. The focus of this guideline is the diagnosis and appropriate treatment of diverse SSTIs ranging from minor superficial infections to life-threatening infections such as necrotizing fasciitis. In addition, because of an increasing number of immunocompromised hosts worldwide, the guideline addresses the wide array of SSTIs that occur in this population. These guidelines emphasize the importance of clinical skills in promptly diagnosing SSTIs, identifying the pathogen, and administering effective treatments in a timely fashion.

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

autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

CONTEXT: Health literacy is a measure of patients' ability to read, comprehend, and act on medical instructions. Poor health literacy is common among racial and ethnic minorities, elderly persons, and patients with chronic conditions, particularly in public-sector settings. Little is known about the extent to which health literacy affects clinical health outcomes. OBJECTIVES: To examine the association between health literacy and diabetes outcomes among patients with type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional observational study of 408 English- and Spanish-speaking patients who were older than 30 years and had type 2 diabetes identified from the clinical database of 2 primary care clinics of a university-affiliated public hospital in San Francisco, Calif. Participants were enrolled and completed questionnaires between June and December 2000. We assessed patients' health literacy by using the short-form Test of Functional Health Literacy in Adults (s-TOFHLA) in English or Spanish. MAIN OUTCOME MEASURES: Most recent hemoglobin A(1c) (HbA(1c)) level. Patients were classified as having tight glycemic control if their HbA(1c) was in the lowest quartile and poor control if it was in the highest quartile. We also measured the presence of self-reported diabetes complications. RESULTS: After adjusting for patients' sociodemographic characteristics, depressive symptoms, social support, treatment regimen, and years with diabetes, for each 1-point decrement in s-TOFHLA score, the HbA(1c) value increased by 0.02 (P =.02). Patients with inadequate health literacy were less likely than patients with adequate health literacy to achieve tight glycemic control (HbA(1c) < or = 7.2%; adjusted odds ratio [OR], 0.57; 95% confidence interval [CI], 0.32-1.00; P =.05) and were more likely to have poor glycemic control (HbA(1c) > or = 9.5%; adjusted OR, 2.03; 95% CI, 1.11-3.73; P =.02) and to report having retinopathy (adjusted OR, 2.33; 95% CI, 1.19-4.57; P =.01). CONCLUSIONS: Among primary care patients with type 2 diabetes, inadequate health literacy is independently associated with worse glycemic control and higher rates of retinopathy. Inadequate health literacy may contribute to the disproportionate burden of diabetes-related problems among disadvantaged populations. Efforts should focus on developing and evaluating interventions to improve diabetes outcomes among patients with inadequate health literacy.

The pathogenesis of asthma reflects, in part, the activity of T cell cytokines. Murine models support participation of interleukin-4 (IL-4) and the IL-4 receptor in asthma. Selective neutralization of IL-13, a cytokine related to IL-4 that also binds to the alpha chain of the IL-4 receptor, ameliorated the asthma phenotype, including airway hyperresponsiveness, eosinophil recruitment, and mucus overproduction. Administration of either IL-13 or IL-4 conferred an asthma-like phenotype to nonimmunized T cell-deficient mice by an IL-4 receptor alpha chain-dependent pathway. This pathway may underlie the genetic associations of asthma with both the human 5q31 locus and the IL-4 receptor.

The basal cell nevus syndrome (BCNS) is characterized by developmental abnormalities and by the postnatal occurrence of cancers, especially basal cell carcinomas (BCCs), the most common human cancer. Heritable mutations in BCNS patients and a somatic mutation in a sporadic BCC were identified in a human homolog of the Drosophila patched (ptc) gene. The ptc gene encodes a transmembrane protein that in Drosophila acts in opposition to the Hedgehog signaling protein, controlling cell fates, patterning, and growth in numerous tissues. The human PTC gene appears to be crucial for proper embryonic development and for tumor suppression.

Evidence-based guidelines for the management of patients with methicillin-resistant Staphylococcus aureus (MRSA) infections were prepared by an Expert Panel of the Infectious Diseases Society of America (IDSA). The guidelines are intended for use by health care providers who care for adult and pediatric patients with MRSA infections. The guidelines discuss the management of a variety of clinical syndromes associated with MRSA disease, including skin and soft tissue infections (SSTI), bacteremia and endocarditis, pneumonia, bone and joint infections, and central nervous system (CNS) infections. Recommendations are provided regarding vancomycin dosing and monitoring, management of infections due to MRSA strains with reduced susceptibility to vancomycin, and vancomycin treatment failures.

Soft-tissue infections are common, generally of mild to modest severity, and are easily treated with a variety of agents. An etiologic diagnosis of simple cellulitis is fre-quently difficult and generally unnecessary for patients with mild signs and symptoms of illness. Clinical as-sessment of the severity of infection is crucial, and sev-eral classification schemes and algorithms have been proposed to guide the clinician [1]. However, most clinical assessments have been developed from either retrospective studies or from an author’s own “clinical experience, ” illustrating the need for prospective studies with defined measurements of severity coupled to man-agement issues and outcomes. Until then, it is the recommendation of this com-mittee that patients with soft-tissue infection accom-

OBJECTIVE: To determine if professional medical interpreters have a positive impact on clinical care for limited English proficiency (LEP) patients. DATA SOURCES: A systematic literature search, limited to the English language, in PubMed and PsycINFO for publications between 1966 and September 2005, and a search of the Cochrane Library. STUDY DESIGN: Any peer-reviewed article which compared at least two language groups, and contained data about professional medical interpreters and addressed communication (errors and comprehension), utilization, clinical outcomes, or satisfaction were included. Of 3,698 references, 28 were found by multiple reviewers to meet inclusion criteria and, of these, 21 assessed professional interpreters separately from ad hoc interpreters. Data were abstracted from each article by two reviewers. Data were collected on the study design, size, comparison groups, analytic technique, interpreter training, and method of determining the participants' need for an interpreter. Each study was evaluated for the effect of interpreter use on four clinical topics that were most likely to either impact or reflect disparities in health and health care. PRINCIPAL FINDINGS: In all four areas examined, use of professional interpreters is associated with improved clinical care more than is use of ad hoc interpreters, and professional interpreters appear to raise the quality of clinical care for LEP patients to approach or equal that for patients without language barriers. CONCLUSIONS: Published studies report positive benefits of professional interpreters on communication (errors and comprehension), utilization, clinical outcomes and satisfaction with care.

A panel of national experts was convened by the Infectious Diseases Society of America (IDSA) to update the 2005 guidelines for the treatment of skin and soft tissue infections (SSTIs). The panel's recommendations were developed to be concordant with the recently published IDSA guidelines for the treatment of methicillin-resistant Staphylococcus aureus infections. The focus of this guideline is the diagnosis and appropriate treatment of diverse SSTIs ranging from minor superficial infections to life-threatening infections such as necrotizing fasciitis. In addition, because of an increasing number of immunocompromised hosts worldwide, the guideline addresses the wide array of SSTIs that occur in this population. These guidelines emphasize the importance of clinical skills in promptly diagnosing SSTIs, identifying the pathogen, and administering effective treatments in a timely fashion.

BACKGROUND: Alternative therapies for Staphylococcus aureus bacteremia and endocarditis are needed. METHODS: We randomly assigned 124 patients with S. aureus bacteremia with or without endocarditis to receive 6 mg of daptomycin intravenously per kilogram of body weight daily and 122 to receive initial low-dose gentamicin plus either an antistaphylococcal penicillin or vancomycin. The primary efficacy end point was treatment success 42 days after the end of therapy. RESULTS: Forty-two days after the end of therapy in the modified intention-to-treat analysis, a successful outcome was documented for 53 of 120 patients who received daptomycin as compared with 48 of 115 patients who received standard therapy (44.2 percent vs. 41.7 percent; absolute difference, 2.4 percent; 95 percent confidence interval, -10.2 to 15.1 percent). Our results met prespecified criteria for the noninferiority of daptomycin. The success rates were similar in subgroups of patients with complicated bacteremia, right-sided endocarditis, and methicillin-resistant S. aureus. Daptomycin therapy was associated with a higher rate of microbiologic failure than was standard therapy (19 vs. 11 patients, P=0.17). In 6 of the 19 patients with microbiologic failure in the daptomycin group, isolates with reduced susceptibility to daptomycin emerged; similarly, a reduced susceptibility to vancomycin was noted in isolates from patients treated with vancomycin. As compared with daptomycin therapy, standard therapy was associated with a nonsignificantly higher rate of adverse events that led to treatment failure due to the discontinuation of therapy (17 vs. 8, P=0.06). Clinically significant renal dysfunction occurred in 11.0 percent of patients who received daptomycin and in 26.3 percent of patients who received standard therapy (P=0.004). CONCLUSIONS: Daptomycin (6 mg per kilogram daily) is not inferior to standard therapy for S. aureus bacteremia and right-sided endocarditis. (ClinicalTrials.gov number, NCT00093067 [ClinicalTrials.gov].).

Cigarette smoking remains a leading cause of preventable disease and premature death in the United States and other countries.On average, 435,000 people in the United States die prematurely from smoking-related diseases each year; overall, smoking causes 1 in 5 deaths.The chance that a lifelong smoker will die prematurely from a complication of smoking is approximately 50%. 1 Tobacco use is a major cause of death from cancer, cardiovascular disease, and pulmonary disease.Cigarette smoking is also a risk factor for respiratory tract and other infections, osteoporosis, reproductive disorders, adverse postoperative events and delayed wound healing, duodenal and gastric ulcers, and diabetes.In addition, smoking has a strong association with fire-related and trauma-related injuries.Smoking-caused disease is a consequence of exposure to toxins in tobacco smoke.Although nicotine plays a minor role, if any, in causing smoking-induced diseases, addiction to nicotine is the proximate cause of these diseases.Currently, about 45 million Americans smoke tobacco.Seventy percent of smokers say they would like to quit, and every year, 40% do quit for at least 1 day. 2 Some highly addicted smokers make serious attempts to quit but are able to stop only for a few hours. 3Moreover, the 80% who attempt to quit on their own return to smoking within a month, and each year, only 3% of smokers quit successfully.Unfortunately, the rate at which persons -primarily children and adolescents -become daily smokers nearly matches the quit rate, so the prevalence of cigarette smoking has declined only very slowly in recent years. 2 This article focuses on nicotine as a determinant of addiction to tobacco and the pharmacologic effects of nicotine that sustain cigarette smoking.Tobacco addiction (like all drug addictions) involves the interplay of pharmacology, learned or conditioned factors, genetics, and social and environmental factors (including tobacco product design and marketing) 4 (Fig. 1).The pharmacologic reasons for nicotine use are enhancement of mood, either directly or through relief of withdrawal symptoms, and augmentation of mental or physical functions. BRAIN MECHANISMS NICOTINIC ACETYLCHOLINE RECEPTORSInhalation of smoke from a cigarette distills nicotine from the tobacco in the cigarette.Smoke particles carry the nicotine into the lungs, where it is rapidly absorbed into the pulmonary venous circulation.The nicotine then enters the arterial circulation and moves

BACKGROUND: Combination antiretroviral therapy (ART) has significantly increased survival among HIV-positive adults in the United States (U.S.) and Canada, but gains in life expectancy for this region have not been well characterized. We aim to estimate temporal changes in life expectancy among HIV-positive adults on ART from 2000-2007 in the U.S. and Canada. METHODS: Participants were from the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD), aged ≥20 years and on ART. Mortality rates were calculated using participants' person-time from January 1, 2000 or ART initiation until death, loss to follow-up, or administrative censoring December 31, 2007. Life expectancy at age 20, defined as the average number of additional years that a person of a specific age will live, provided the current age-specific mortality rates remain constant, was estimated using abridged life tables. RESULTS: The crude mortality rate was 19.8/1,000 person-years, among 22,937 individuals contributing 82,022 person-years and 1,622 deaths. Life expectancy increased from 36.1 [standard error (SE) 0.5] to 51.4 [SE 0.5] years from 2000-2002 to 2006-2007. Men and women had comparable life expectancies in all periods except the last (2006-2007). Life expectancy was lower for individuals with a history of injection drug use, non-whites, and in patients with baseline CD4 counts <350 cells/mm(3). CONCLUSIONS: A 20-year-old HIV-positive adult on ART in the U.S. or Canada is expected to live into their early 70 s, a life expectancy approaching that of the general population. Differences by sex, race, HIV transmission risk group, and CD4 count remain.

Strains of methicillin-resistant Staphylococcus aureus (MRSA), which had been largely confined to hospitals and long-term care facilities, are emerging in the community. The changing epidemiology of MRSA bears striking similarity to the emergence of penicillinase-mediated resistance in S. aureus decades ago. Even though the origin (hospital or the community) of the emerging MRSA strains is not known, the prevalence of these strains in the community seems likely to increase substantially.

The alpha chain of the human histocompatibility antigen HLA-G was identified as an array of five 37- to 39-kilodalton isoforms by the use of two-dimensional gel electrophoresis. Both cell-associated and secreted HLA-G antigens are prominent in first trimester villous cytotrophoblasts and are greatly reduced in third trimester cytotrophoblasts. Allelic variation was not detected, an indication that HLA-G is not obviously polymorphic in cytotrophoblasts. Among the following choriocarcinoma cell lines studied, HLA-G is expressed in JEG but not in Jar or BeWo. Expression of endogenous HLA-G genes has not been found in normal lymphoid cells. Thus, HLA-G is subject to both cell type-specific and developmental regulation and is expressed in early gestation human cytotrophoblasts.