Showing papers by "University of Colorado Denver published in 2007"

Management of Thyroid Dysfunction during Pregnancy and Postpartum: An Endocrine Society Clinical Practice Guideline

Abstract: Objective: The aim was to update the guidelines for the management of thyroid dysfunction during pregnancy and postpartum published previously in 2007. A summary of changes between the 2007 and 2012 version is identified in the Supplemental Data (published on The Endocrine Society's Journals Online web site at http://jcem.endojournals.org). Evidence: This evidence-based guideline was developed according to the U.S. Preventive Service Task Force, grading items level A, B, C, D, or I, on the basis of the strength of evidence and magnitude of net benefit (benefits minus harms) as well as the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. Consensus Process: The guideline was developed through a series of e-mails, conference calls, and one face-to-face meeting. An initial draft was prepared by the Task Force, with the help of a medical writer, and reviewed and commented on by members of The Endocri...

Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia.

Abstract: Sixty-five boys younger than 30 months of age were randomly assigned to prophylaxis (32 boys) or enhanced episodic therapy (33 boys). When the boys reached 6 years of age, 93% of those in the prophylaxis group and 55% of those in the episodic-therapy group were considered to have normal index-joint structure on MRI (P = 0.006). The relative risk of MRI-detected joint damage with episodic therapy as compared with prophylaxis was 6.1 (95% confidence interval, 1.5 to 24.4). The mean annual numbers of joint and total hemorrhages were higher at study exit in the episodic-therapy group than in the prophylaxis group (P<0.001 for both comparisons). High titers of inhibitors of factor VIII developed in two boys who received prophylaxis; three boys in the episodic-therapy group had a life-threatening hemorrhage. Hospitalizations and infections associated with central-catheter placement did not differ significantly between the two groups. Conclusions Prophylaxis with recombinant factor VIII can prevent joint damage and decrease the frequency of joint and other hemorrhages in young boys with severe hemophilia A. (ClinicalTrials.gov number, NCT00207597.)

Reduction in Weight and Cardiovascular Disease Risk Factors in Individuals With Type 2 Diabetes: One-Year Results of the Look AHEAD Trial

Abstract: Objective: The effectiveness of intentional weight loss in reducing cardiovascular disease (CVD) events in type 2 diabetes is unknown. This report describes one-year changes in CVD risk factors in a trial designed to examine the long-term effects of an intensive lifestyle intervention on the incidence of major CVD events. Research Design and Methods: A multi-centered randomized controlled trial of 5,145 individuals with type 2 diabetes, aged 45-74 years, with body mass index >25 kg/m2 (>27 kg/m2 if taking insulin). An Intensive Lifestyle Intervention (ILI) involving group and individual meetings to achieve and maintain weight loss through decreased caloric intake and increased physical activity was compared to a Diabetes Support and Education (DSE) condition. Results: Participants assigned to ILI lost an average 8.6% of their initial weight versus 0.7% in DSE group (p Conclusions: At 1 year, ILI resulted in clinically significant weight loss in persons with type 2 diabetes. This was associated with improved diabetes control and CVD risk factors and reduced medicine use in ILI versus DSE. Continued intervention and follow-up will determine whether these changes are maintained and will reduce CVD risk. Trial Registration: clinicaltrials.gov Identifier: NCT00017953

An Array of Qualitative Data Analysis Tools: A Call for Data Analysis Triangulation.

Abstract: One of the most important steps in the qualitative research process is analysis of data. The purpose of this article is to provide elements for understanding multiple types of qualitative data analysis techniques available and the importance of utilizing more than one type of analysis, thus utilizing data analysis triangulation, in order to understand phenomenon more fully for school psychology research and beyond. The authors describe seven qualitative analysis tools: methods of constant comparison, keywords-in-context, word count, classical content analysis, domain analysis, taxonomic analysis, and componential analysis. Then, the authors outline when to use each type of analysis. In so doing, the authors use real qualitative data to help distinguish the various types of analyses. Furthermore, flowcharts and tables are provided to help delineate when to choose each type of analysis. Finally, the role of computer-assisted software in the qualitative data-analytic process is discussed. As such, use of the analyses outlined in this article should help to promote rigor in qualitative research.

Evolutionary and biomedical insights from the rhesus macaque genome

Abstract: The rhesus macaque (Macaca mulatta) is an abundant primate species that diverged from the ancestors of Homo sapiens about 25 million years ago. Because they are genetically and physiologically similar to humans, rhesus monkeys are the most widely used nonhuman primate in basic and applied biomedical research. We determined the genome sequence of an Indian-origin Macaca mulatta female and compared the data with chimpanzees and humans to reveal the structure of ancestral primate genomes and to identify evidence for positive selection and lineage-specific expansions and contractions of gene families. A comparison of sequences from individual animals was used to investigate their underlying genetic diversity. The complete description of the macaque genome blueprint enhances the utility of this animal model for biomedical research and improves our understanding of the basic biology of the species.

The Epidemiology of Autism Spectrum Disorders

Abstract: Autism spectrum disorders (ASDs) are complex, lifelong, neurodevelopmental conditions of largely unknown cause. They are much more common than previously believed, second in frequency only to mental retardation among the serious developmental disorders. Although a heritable component has been demonstrated in ASD etiology, putative risk genes have yet to be identified. Environmental risk factors may also play a role, perhaps via complex gene-environment interactions, but no specific exposures with significant population effects are known. A number of endogenous biomarkers associated with autism risk have been investigated, and these may help identify significant biologic pathways that, in turn, will aid in the discovery of specific genes and exposures. Future epidemiologic research should focus on expanding population-based descriptive data on ASDs, exploring candidate risk factors in large well-designed studies incorporating both genetic and environmental exposure data and addressing possible etiologic heterogeneity in studies that can stratify case groups and consider alternate endophenotypes.

Allergen immunotherapy: A practice parameter third update

Abstract: These parameters were developed by the Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma & Immunology (AAAAI); the American Col- lege of Allergy, Asthma & Immunology (ACAAI); and the Joint Council of Allergy, Asthma & Immunology. The American Academy of Allergy, Asthma & Immunology and the American College of Allergy, Asthma & Immunology have jointly accepted responsibility for establishing ''Allergen immunotherapy: A practice parameter third update.'' This is a complete and com- prehensive document at the current time. The medical environ- ment is a changing environment, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single individ- ual, including those who served on the Joint Task Force, is authorizedtoprovideanofficial AAAAIorACAAIinterpretation ofthesepracticeparameters.Anyrequestforinformationaboutor an interpretation of these practice parameters by the AAAAI or the ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma & Immunology. These parameters are not designed for use by pharmaceutical companies in drug promotion. A current list of published practice parameters of the Joint Task Force on Practice ParametersforAllergyandImmunologycanbefoundinTableE1 in this article's Online Repository at www.jacionline.org. Disclosure ofpotentialconflictofinterest:L.Coxisaconsultant forGenentech/Novartis, Hollister-Stier, and Stallergenes; is a speaker for Novartis; has received research support from Stallergenes; is on the Board of Directors for the American Board of Allergy and Immunology; and is on the US Food and Drug Administration (FDA)'s Allergenic Product Advisory Committee. H. Nelson is a consultant for Merck and Planet Biopharmaceuticals, is a Data and Safety Monitoring Board member of DBV Technologies, and has received research support from ALK-AbellM. Nelson has re- ceivedresearchsupportfromtheDepartmentofDefense,isaspeakerfortheAmerican College of Allergy, Asthma & Immunology (ACAAI), and is a member of the FDA's AdvisoryCommitteeonAllergicProducts.R.Weberisonthespeakers'bureauforAs- traZeneca and Genentech, has received research support from Novartis and Glaxo- SmithKline, and is Committee Chair of the ACAAI. D. I. Bernstein is a consultant and on the advisory board for ALK America, is on the advisory board for Merck, and has received research support from Merck and Schering-Plough. J. Blessing- Moore is a speaker for Merck-Schering/AstraZeneca, Novartis, TEVA, and Meda Alcon and has received research support from Meda. D. A. Khan is a speaker for As- traZeneca and Merck, has received research support from the Vanberg Family Foun- dation and the Sellars Family Foundation, is Conjoint Board Review Chair for the ACAAI,andisapastpresidentoftheTexasAllergy,AsthmaandImmunologySociety. D. M. Lang is a speaker and consultant for GlaxoSmithKline; is a speaker for Astra- Zeneca, Merck, TEVA, Sanofi-Aventis, and Genentech/Novartis; and has received re- search support from Genentech/Novartis. R. A. Nicklas is a fellow for the ACAAI. J. Oppenheimer is a consultant and has provided lectures for AstraZeneca, Merck, and GlaxoSmithKline; and has received research support from AstraZeneca, Merck, Glax- oSmithKline, and Genentech. J. M. Portnoy is a speaker for Phadia, Merck, and CSL Behring; hasreceived researchsupportfromtheUSDepartment ofHousingandUrban Development;andisa board memberof theACAAI board of regents.S.L. Spector has received research support from Genentech, GlaxoSmithKline, Schering-Plough, Aventis, Novartis, Pharmaxis, Boehringer Ingelheim, AstraZeneca, Johnson & John- son, Xyzal, Alcon, Centocor, Sepracor, UCB, Amgen, Capnia, and IVAX. S. Tilles isaspeakerforAlcon; isontheadvisoryboard forALK,Ista,Merck,andStallergenes; has received research support from Alcon, Amgen, Amphastar, Astellas, Boehringer Ingelheim,Ception,Genentech,Icagen, MAP Pharma, MEDA, Merck, Novartis, Rox- ane, and Sepracor; is Associate Editor of Allergy Watchand Annals of Allergy; and is a task force member for the Joint Task Force for Practice Parameters. D. Wallace is a speaker and advisor for Alcon, is a speaker for Merck and Sanofi-Aventis, and is President-Elect of the ACAAI. The rest of the authors have declared that they have no conflict of interest.

Primary Prevention of Cardiovascular Diseases in People With Diabetes Mellitus A scientific statement from the American Heart Association and the American Diabetes Association

Abstract: The American Heart Association (AHA) and the American Diabetes Association (ADA) have each published guidelines for cardiovascular disease prevention: the ADA has issued separate recommendations for each of the cardiovascular risk factors in patients with diabetes, and the AHA has shaped primary and secondary guidelines that extend to patients with diabetes. This statement will attempt to harmonize the recommendations of both organizations where possible but will recognize areas in which AHA and ADA recommendations differ.

QM/MM: what have we learned, where are we, and where do we go from here?

Abstract: This paper briefly reviews the current status of the most popular methods for combined quantum mechanical/molecular mechanical (QM/MM) calculations, including their advantages and disadvantages There is a special emphasis on very general link-atom methods and various ways to treat the charge near the boundary Mechanical and electric embedding are contrasted We consider methods applicable to gas-phase organic chemistry, liquid-phase organic and organometallic chemistry, biochemistry, and solid-state chemistry Then we review some recent tests of QM/MM methods and summarize what we learn about QM/MM from these studies We also discuss some available software Finally, we present a few comments about future directions of research in this exciting area, where we focus on more intimate blends of QM with MM

LMSD: LIPID MAPS structure database.

Abstract: The LIPID MAPS Structure Database (LMSD) is a relational database encompassing structures and annotations of biologically relevant lipids. Structures of lipids in the database come from four sources: (i) LIPID MAPS Consortium's core laboratories and partners; (ii) lipids identified by LIPID MAPS experiments; (iii) computationally generated structures for appropriate lipid classes; (iv) biologically relevant lipids manually curated from LIPID BANK, LIPIDAT and other public sources. All the lipid structures in LMSD are drawn in a consistent fashion. In addition to a classification-based retrieval of lipids, users can search LMSD using either text-based or structure-based search options. The text-based search implementation supports data retrieval by any combination of these data fields: LIPID MAPS ID, systematic or common name, mass, formula, category, main class, and subclass data fields. The structure-based search, in conjunction with optional data fields, provides the capability to perform a substructure search or exact match for the structure drawn by the user. Search results, in addition to structure and annotations, also include relevant links to external databases. The LMSD is publicly available at www.lipidmaps.org/data/structure/.

Assessment of Child and Adolescent Overweight and Obesity

Abstract: Accurate appropriate assessment of overweight and obesity in children and adolescents is a critical aspect of contemporary medical care. However, physicians and other health care professionals may find this a somewhat thorny field to enter. The BMI has become the standard as a reliable indicator of overweight and obesity. The BMI is incomplete, however, without consideration of the complex behavioral factors that influence obesity.Because of limited time and resources, clinicians need to have quick, evidence-based interventions that can help patients and their families recognize the importance of reducing overweight and obesity and take action. In an era of fast food, computers, and DVDs, it is not easy to persuade patients to modify their diets and to become more physically active. Because research concerning effective assessment of childhood obesity contains many gaps, this report is intended to provide a comprehensive approach to assessment and to present the evidence available to support key aspects of assessment. The discussion and recommendations are based on 300 studies published since 1995, which examined an array of assessment tools. With this information, clinicians should find themselves better equipped to face the challenges of assessing childhood overweight and obesity accurately.

The cation efflux transporter ZnT8 (Slc30A8) is a major autoantigen in human type 1 diabetes

Abstract: Type 1 diabetes (T1D) results from progressive loss of pancreatic islet mass through autoimmunity targeted at a diverse, yet limited, series of molecules that are expressed in the pancreatic β cell. Identification of these molecular targets provides insight into the pathogenic process, diagnostic assays, and potential therapeutic agents. Autoantigen candidates were identified from microarray expression profiling of human and rodent pancreas and islet cells and screened with radioimmunoprecipitation assays using new-onset T1D and prediabetic sera. A high-ranking candidate, the zinc transporter ZnT8 (Slc30A8), was targeted by autoantibodies in 60–80% of new-onset T1D compared with <2% of controls and <3% type 2 diabetic and in up to 30% of patients with other autoimmune disorders with a T1D association. ZnT8 antibodies (ZnTA) were found in 26% of T1D subjects classified as autoantibody-negative on the basis of existing markers [glutamate decarboxylase (GADA), protein tyrosine phosphatase IA2 (IA2A), antibodies to insulin (IAA), and islet cytoplasmic autoantibodies (ICA)]. Individuals followed from birth to T1D showed ZnT8A as early as 2 years of age and increasing levels and prevalence persisting to disease onset. ZnT8A generally emerged later than GADA and IAA in prediabetes, although not in a strict order. The combined measurement of ZnT8A, GADA, IA2A, and IAA raised autoimmunity detection rates to 98% at disease onset, a level that approaches that needed to detect prediabetes in a general pediatric population. The combination of bioinformatics and molecular engineering used here will potentially generate other diabetes autoimmunity markers and is also broadly applicable to other autoimmune disorders.

Clinical practice guideline: Adult sinusitis

Abstract: Objective This guideline provides evidence-based recommendations on managing sinusitis, defined as symptomatic inflammation of the paranasal sinuses. Sinusitis affects 1 in 7 adults in the United States, resulting in about 31 million individuals diagnosed each year. Since sinusitis almost always involves the nasal cavity, the term rhinosinusitis is preferred. The guideline target patient is aged 18 years or older with uncomplicated rhinosinusitis, evaluated in any setting in which an adult with rhinosinusitis would be identified, monitored, or managed. This guideline is intended for all clinicians who are likely to diagnose and manage adults with sinusitis. Purpose The primary purpose of this guideline is to improve diagnostic accuracy for adult rhinosinusitis, reduce inappropriate antibiotic use, reduce inappropriate use of radiographic imaging, and promote appropriate use of ancillary tests that include nasal endoscopy, computed tomography, and testing for allergy and immune function. In creating this guideline the American Academy of Otolaryngology–Head and Neck Surgery Foundation selected a panel representing the fields of allergy, emergency medicine, family medicine, health insurance, immunology, infectious disease, internal medicine, medical informatics, nursing, otolaryngology–head and neck surgery, pulmonology, and radiology. Results The panel made strong recommendations that 1) clinicians should distinguish presumed acute bacterial rhinosinusitis (ABRS) from acute rhinosinusitis caused by viral upper respiratory infections and noninfectious conditions, and a clinician should diagnose ABRS when (a) symptoms or signs of acute rhinosinusitis are present 10 days or more beyond the onset of upper respiratory symptoms, or (b) symptoms or signs of acute rhinosinusitis worsen within 10 days after an initial improvement (double worsening), and 2) the management of ABRS should include an assessment of pain, with analgesic treatment based on the severity of pain. The panel made a recommendation against radiographic imaging for patients who meet diagnostic criteria for acute rhinosinusitis, unless a complication or alternative diagnosis is suspected. The panel made recommendations that 1) if a decision is made to treat ABRS with an antibiotic agent, the clinician should prescribe amoxicillin as first-line therapy for most adults, 2) if the patient worsens or fails to improve with the initial management option by 7 days, the clinician should reassess the patient to confirm ABRS, exclude other causes of illness, and detect complications, 3) clinicians should distinguish chronic rhinosinusitis (CRS) and recurrent acute rhinosinusitis from isolated episodes of ABRS and other causes of sinonasal symptoms, 4) clinicians should assess the patient with CRS or recurrent acute rhinosinusitis for factors that modify management, such as allergic rhinitis, cystic fibrosis, immunocompromised state, ciliary dyskinesia, and anatomic variation, 5) the clinician should corroborate a diagnosis and/or investigate for underlying causes of CRS and recurrent acute rhinosinusitis, 6) the clinician should obtain computed tomography of the paranasal sinuses in diagnosing or evaluating a patient with CRS or recurrent acute rhinosinusitis, and 7) clinicians should educate/counsel patients with CRS or recurrent acute rhinosinusitis regarding control measures. The panel offered as options that 1) clinicians may prescribe symptomatic relief in managing viral rhinosinusitis, 2) clinicians may prescribe symptomatic relief in managing ABRS, 3) observation without use of antibiotics is an option for selected adults with uncomplicated ABRS who have mild illness (mild pain and temperature <38.3°C or 101°F) and assurance of follow-up, 4) the clinician may obtain nasal endoscopy in diagnosing or evaluating a patient with CRS or recurrent acute rhinosinusitis, and 5) the clinician may obtain testing for allergy and immune function in evaluating a patient with CRS or recurrent acute rhinosinusitis. Disclaimer This clinical practice guideline is not intended as a sole source of guidance for managing adults with rhinosinusitis. Rather, it is designed to assist clinicians by providing an evidence-based framework for decision-making strategies. It is not intended to replace clinical judgment or establish a protocol for all individuals with this condition, and may not provide the only appropriate approach to diagnosing and managing this problem.

Incidence of diabetes in youth in the United States.

Abstract: Context Data on the incidence of diabetes mellitus (DM) among US youth according to racial/ethnic background and DM type are limited. Objective To estimate DM incidence in youth aged younger than 20 years according to race/ethnicity and DM type. Design, setting, and participants A multiethnic, population-based study (The SEARCH for Diabetes in Youth Study) of 2435 youth with newly diagnosed, nonsecondary DM in 2002 and 2003, ascertained at 10 study locations in the United States, covering a population of more than 10 million person-years. Main outcome measure Incidence rates by age group, sex, race/ethnicity, and DM type were calculated per 100,000 person-years at risk. Diabetes mellitus type (type 1/type 2) was based on health care professional assignment and, in a subset, further characterized with glutamic acid decarboxylase (GAD65) autoantibody and fasting C peptide measures. Results The incidence of DM (per 100,000 person-years) was 24.3 (95% confidence interval [CI], 23.3-25.3). Among children younger than 10 years, most had type 1 DM, regardless of race/ethnicity. The highest rates of type 1 DM were observed in non-Hispanic white youth (18.6, 28.1, and 32.9 for age groups 0-4, 5-9, and 10-14 years, respectively). Even among older youth (> or =10 years), type 1 DM was frequent among non-Hispanic white, Hispanic, and African American adolescents. Overall, type 2 DM was still relatively infrequent, but the highest rates (17.0 to 49.4 per 100,000 person-years) were documented among 15- to 19-year-old minority groups. Conclusions Our data document the incidence rates of type 1 DM among youth of all racial/ethnic groups, with the highest rates in non-Hispanic white youth. Overall, type 2 DM is still relatively infrequent; however, the highest rates were observed among adolescent minority populations.

Folic acid for the prevention of colorectal adenomas: a randomized clinical trial.

Abstract: ContextLaboratory and epidemiological data suggest that folic acid may have an antineoplastic effect in the large intestine.ObjectiveTo assess the safety and efficacy of folic acid supplementation for preventing colorectal adenomas.Design, Setting, and ParticipantsA double-blind, placebo-controlled, 2-factor, phase 3, randomized clinical trial conducted at 9 clinical centers between July 6, 1994, and October 1, 2004. Participants included 1021 men and women with a recent history of colorectal adenomas and no previous invasive large intestine carcinoma.InterventionParticipants were randomly assigned in a 1:1 ratio to receive 1 mg/d of folic acid (n = 516) or placebo (n = 505), and were separately randomized to receive aspirin (81 or 325 mg/d) or placebo. Follow-up consisted of 2 colonoscopic surveillance cycles (the first interval was at 3 years and the second at 3 or 5 years later).Main Outcome MeasuresThe primary outcome measure was occurrence of at least 1 colorectal adenoma. Secondary outcomes were the occurrence of advanced lesions (≥25% villous features, high-grade dysplasia, size ≥1 cm, or invasive cancer) and adenoma multiplicity (0, 1-2, or ≥3 adenomas).Results During the first 3 years, 987 participants (96.7%) underwent colonoscopic follow-up, and the incidence of at least 1 colorectal adenoma was 44.1% for folic acid (n = 221) and 42.4% for placebo (n = 206) (unadjusted risk ratio [RR], 1.04; 95% confidence interval [CI], 0.90-1.20; P = .58). Incidence of at least 1 advanced lesion was 11.4% for folic acid (n = 57) and 8.6% for placebo (n = 42) (unadjusted RR, 1.32; 95% CI, 0.90-1.92; P = .15). A total of 607 participants (59.5%) underwent a second follow-up, and the incidence of at least 1 colorectal adenoma was 41.9% for folic acid (n = 127) and 37.2% for placebo (n = 113) (unadjusted RR, 1.13; 95% CI, 0.93-1.37; P = .23); and incidence of at least 1 advanced lesion was 11.6% for folic acid (n = 35) and 6.9% for placebo (n = 21) (unadjusted RR, 1.67; 95% CI, 1.00-2.80; P = .05). Folic acid was associated with higher risks of having 3 or more adenomas and of noncolorectal cancers. There was no significant effect modification by sex, age, smoking, alcohol use, body mass index, baseline plasma folate, or aspirin allocation. ConclusionsFolic acid at 1 mg/d does not reduce colorectal adenoma risk. Further research is needed to investigate the possibility that folic acid supplementation might increase the risk of colorectal neoplasia.Trial Registration clinicaltrials.gov Identifier: NCT00272324

Clomiphene, Metformin, or Both for Infertility in the Polycystic Ovary Syndrome

Abstract: Background The polycystic ovary syndrome is a common cause of infertility. Clomiphene and insulin sensitizers are used alone and in combination to induce ovulation, but it is unknown whether one approach is superior. Methods We randomly assigned 626 infertile women with the polycystic ovary syndrome to receive clomiphene citrate plus placebo, extended-release metformin plus placebo, or a combination of metformin and clomiphene for up to 6 months. Medication was discontinued when pregnancy was confirmed, and subjects were followed until delivery. Results The live-birth rate was 22.5% (47 of 209 subjects) in the clomiphene group, 7.2% (15 of 208) in the metformin group, and 26.8% (56 of 209) in the combination-therapy group (P<0.001 for metformin vs. both clomiphene and combination therapy; P=0.31 for clomiphene vs. combination therapy). Among pregnancies, the rate of multiple pregnancy was 6.0% in the clomiphene group, 0% in the metformin group, and 3.1% in the combination-therapy group. The rates of first...

Validity and Qualitative Research: An Oxymoron?

Abstract: Although the importance of validity has long been accepted among quantitative researchers, this concept has been an issue of contention among qualitative researchers. Thus, the first purpose of the present paper is to introduce the Qualitative Legitimation Model, which attempts to integrate many of the types of validity identified by qualitative researchers. The second purpose of this article is to describe 24 methods for assessing the truth value of qualitative research. Utilizing and documenting such techniques should prevent validity and qualitative research from being seen as an oxymoron.

Characterization of the severe asthma phenotype by the National Heart, Lung, and Blood Institute's Severe Asthma Research Program

Abstract: Background Severe asthma causes the majority of asthma morbidity. Understanding mechanisms that contribute to the development of severe disease is important. Objective The goal of the Severe Asthma Research Program is to identify and characterize subjects with severe asthma to understand pathophysiologic mechanisms in severe asthma. Methods We performed a comprehensive phenotypic characterization (questionnaires, atopy and pulmonary function testing, phlebotomy, exhaled nitric oxide) in subjects with severe and not severe asthma. Results A total of 438 subjects with asthma were studied (204 severe, 70 moderate, 164 mild). Severe subjects with asthma were older with longer disease duration ( P P ≤ .0001). Lung function was lower in severe asthma with marked bronchodilator reversibility ( P P = .0007), but blood eosinophils, IgE, and exhaled nitric oxide levels did not differentiate disease severity. A reduced FEV 1 , history of pneumonia, and fewer positive skin tests were risk factors for severe disease. Early disease onset (age P P = .002). Later disease onset (age ≥ 12 years) was associated with lower lung function and sinopulmonary infections ( P ≤ .02). Conclusion Severe asthma is characterized by abnormal lung function that is responsive to bronchodilators, a history of sinopulmonary infections, persistent symptoms, and increased health care utilization. Clinical implications Lung function abnormalities in severe asthma are reversible in most patients, and pneumonia is a risk factor for the development of severe disease.

Effectiveness of Adjunctive Antidepressant Treatment for Bipolar Depression

Abstract: �Background Episodes of depression are the most frequent cause of disability among patients with bipolar disorder. The effectiveness and safety of standard antidepressant agents for depressive episodes associated with bipolar disorder (bipolar depression) have not been well studied. Our study was designed to determine whether adjunctive antidepressant therapy reduces symptoms of bipolar depression without increasing the risk of mania. Methods In this double-blind, placebo-controlled study, we randomly assigned subjects with bipolar depression to receive up to 26 weeks of treatment with a mood stabilizer plus adjunctive antidepressant therapy or a mood stabilizer plus a matching placebo, under conditions generalizable to routine clinical care. A standardized clinical monitoring form adapted from the mood-disorder modules of the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, was used at all follow-up visits. The primary outcome was the percentage of subjects in each treatment group meeting the criterion for a durable recovery (8 consecutive weeks of euthymia). Secondary effectiveness outcomes and rates of treatment-emergent affective switch (a switch to mania or hypomania early in the course of treatment) were also examined. Results Forty-two of the 179 subjects (23.5%) receiving a mood stabilizer plus adjunctive antidepressant therapy had a durable recovery, as did 51 of the 187 subjects (27.3%) receiving a mood stabilizer plus a matching placebo (P = 0.40). Modest nonsignificant trends favoring the group receiving a mood stabilizer plus placebo were observed across the secondary outcomes. Rates of treatment-emergent affective switch were similar in the two groups. Conclusions The use of adjunctive, standard antidepressant medication, as compared with the use of mood stabilizers, was not associated with increased efficacy or with increased risk of treatment-emergent affective switch. Longer-term outcome studies are needed to fully assess the benefits and risks of antidepressant therapy for bipolar disorder. (ClinicalTrials.gov number, NCT00012558.)

A call for qualitative power analyses.

Abstract: The purpose of this paper is to emphasize the importance of sampling and sample size considerations in all qualitative research. Such considerations would help qualitative researchers to select sample sizes and sampling designs that are most compatible with their research purposes. First, we discuss the importance of sampling in qualitative research. Next, we outline 24 designs for selecting a sample in qualitative research. We then discuss the importance of selecting a sample size that yields data that have a realistic chance of reaching data saturation, theoretical saturation, or informational redundancy. Based on the literature, we then provide sample size guidelines for several qualitative research designs. As such, we provide a framework for making sampling and sample size considerations in interpretive research.

Development and cross-sectional validation of the Childhood Asthma Control Test

Abstract: Background For children younger than 12 years old with asthma, there are several quality-of-life instruments, clinical diaries, and questionnaires assessing symptoms; however, a validated tool for assessing asthma control is currently lacking. Objective To develop and validate the Childhood Asthma Control Test (C-ACT), a self-administered tool for identifying children aged 4-11 years whose asthma is inadequately controlled. Methods A 21-item questionnaire was administered to 343 patients with asthma and their caregivers, randomly assigning 75% (n = 257) for development and cross-sectional validation of the tool and 25% (n = 86) to a confirmatory sample. Stepwise logistic regression was used to reduce the 21 items to those best able to discriminate control as defined by the specialist's rating of asthma control. Results Seven items were selected from regression analyses of the development sample to comprise the C-ACT. The scores of each item were summed for a total score (0-27), with lower scores indicating poorer control. Summed scores discriminated between groups of patients differing in the specialists' rating of asthma control (F = 36.89; P Conclusion The C-ACT is a validated tool to assess asthma control and identify children with inadequately controlled asthma. Clinical implications The C-ACT can be valuable in clinical practice and research based on its validation, ease of use, input from the child and caregiver, and alignment with asthma guidelines.

Recommendations for the management of herpes zoster.

Abstract: The objective of this article is to provide evidence-based recommendations for the management of patients with herpes zoster (HZ) that take into account clinical efficacy, adverse effects, impact on quality of life, and costs of treatment. Systematic literature reviews, published randomized clinical trials, existing guidelines, and the authors' clinical and research experience relevant to the management of patients with HZ were reviewed at a consensus meeting. The results of controlled trials and the clinical experience of the authors support the use of acyclovir, brivudin (where available), famciclovir, and valacyclovir as first-line antiviral therapy for the treatment of patients with HZ. Specific recommendations for the use of these medications are provided. In addition, suggestions are made for treatments that, when used in combination with antiviral therapy, may further reduce pain and other complications of HZ.

Efficacy of communication skills training for giving bad news and discussing transitions to palliative care.

Abstract: Background Few studies have assessed the efficacy of communication skills training for postgraduate physician trainees at the level of behaviors. We designed a residential communication skills workshop (Oncotalk) for medical oncology fellows. The intervention design built on existing successful models by teaching specific communication tasks linked to the patient's trajectory of illness. This study evaluated the efficacy of Oncotalk in changing observable communication behaviors. Methods Oncotalk was a 4-day residential workshop emphasizing skills practice in small groups. This preintervention and postintervention cohort study involved 115 medical oncology fellows from 62 different institutions during a 3-year study. The primary outcomes were observable participant communication skills measured during standardized patient encounters before and after the workshop in giving bad news and discussing transitions to palliative care. The standardized patient encounters were audiorecorded and assessed by blinded coders using a validated coding system. Before-after comparisons were made using each participant as his or her own control. Results Compared with preworkshop standardized patient encounters, postworkshop encounters showed that participants acquired a mean of 5.4 bad news skills (P Conclusion Oncotalk represents a successful teaching model for improving communication skills for postgraduate medical trainees.

Concept Evolution in Sensory Integration: A Proposed Nosology for Diagnosis

Abstract: and growing area of practice in occupational therapy. Debate and discussion with colleagues have led us to develop a proposed taxonomy reflecting a new classification scheme to enhance diagnostic specificity. The nosology proposed here is rooted in empirical data first published by Ayres (Ayres, 1972b, 1989) that has evolved based on empirical and theoretical information. This new nosology provides a viewpoint for discussion and research. Two sociopolitical trends contribute to the timeliness of the ideas presented. First, a call exists throughout health and developmental services for evidence-based practice (Sackett, Richardson, Rosenberg, & Haynes, 1997). Diagnostic precision is crucial for homogeneity of samples in empirical research, affecting the validity of the research findings. Second, the condition of sensory processing disorders (SPD) has recently been acknowledged outside the occupational therapy profession in three diagnostic classification references: the Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood, Revised (known as the DC: 0–3R) (Zero to Three, 2005), the Diagnostic Manual for Infancy and Early Childhood of the Interdisciplinary Council on Developmental and Learning Disorders (ICDL, 2005), and the Psychodynamic Diagnostic Manual (PDM Task Force, 2006). Both manuals include diagnostic taxonomies with subtypes of SPD suggested by a committee of occupational therapists, who assisted in developing guidelines for diagnostic specificity related to sensory-based disorders (Miller, Cermak, Lane, Anzalone, & Koomar, 2004).

Clinical practice guideline: Management of thyroid dysfunction during pregnancy and postpartum: An endocrine society clinical practice guideline

Abstract: Objective: The objective is to provide clinical guidelines for the management of thyroid problems present during pregnancy and in the postpartum. Participants: The Chair was selected by the Clinical Guidelines Subcommittee (CGS) of The Endocrine Society. The Chair requested participation by the Latin American Thyroid Society, the Asia and Oceania Thyroid Society, the American Thyroid Association, the European Thyroid Association, and the American Association of Clinical Endocrinologists, and each organization appointed a member to the task force. Two members of The Endocrine Society were also asked to participate. The group worked on the guidelines for 2 yr and held two meetings. There was no corporate funding, and no members received remuneration. Evidence: Applicable published and peer-reviewed literature of the last two decades was reviewed, with a concentration on original investigations. The grading of evidence was done using the United States Preventive Services Task Force system and, where possible, the GRADE system. Consensus Process: Consensus was achieved through conference calls, two group meetings, and exchange of many drafts by E-mail. The manuscript was reviewed concurrently by the Society’s CGS, Clinical Affairs Committee, members of The Endocrine Society, and members of each of the collaborating societies. Many valuable suggestions were received and incorporated into the final document. Each of the societies endorsed the guidelines. Conclusions: Management of thyroid diseases during pregnancy requires special considerations because pregnancy induces major changes in thyroid function, and maternal thyroid disease can have adverse effects on the pregnancy and the fetus. Care requires coordination among several healthcare professionals. Avoiding maternal (and fetal) hypothyroidism is of major importance because of potential damage to fetal neural development, an increased incidence of miscarriage, and preterm delivery. Maternal hyperthyroidism and its treatment may be accompanied by coincident problems in fetal thyroid function. Autoimmune thyroid disease is associated with both increased rates of miscarriage, for which the appropriate medical response is uncertain at this time, and postpartum thyroiditis. Fine-needle aspiration cytology should be performed for dominant thyroid nodules discovered in pregnancy. Radioactive isotopes must be avoided during pregnancy and lactation. Universal screening of pregnant women for thyroid disease is not yet supported by adequate studies, but case finding targeted to specific groups of patients who are at increased risk is strongly supported. (J Clin Endocrinol Metab 92: S1–S47, 2007)

KRAS Mutation Is an Important Predictor of Resistance to Therapy with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non–Small-Cell Lung Cancer

Abstract: Purpose: EGFR gene mutations and increased EGFR copy number have been associated with favorable response to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKI) in patients with non–small-cell lung cancer (NSCLC). In contrast, KRAS mutation has been shown to predict poor response to such therapy. We tested the utility of combinations of these three markers in predicting response and survival in patients with NSCLC treated with EGFR-TKIs. Experimental Design: Patients with advanced NSCLC treated with EGFR-TKI with available archival tissue specimens were included. EGFR and KRAS mutations were analyzed using PCR-based sequencing. EGFR copy number was analyzed using fluorescence in situ hybridization. Results: The study included 73 patients, 59 of whom had all three potential markers successfully analyzed. EGFR mutation was detected in 7 of 71 patients (9.8%), increased EGFR copy number in 32 of 59 (54.2%), and KRAS mutation in 16 of 70 (22.8%). EGFR mutation ( P EGFR copy number ( P = 0.48) correlated with favorable response. No survival benefit was detected in patients with either of these features. KRAS mutation correlated with progressive disease ( P = 0.04) and shorter median time to progression ( P = 0.0025) but not with survival. Patients with both EGFR mutation and increased EGFR copy number had a >99.7% chance of objective response, whereas patients with KRAS mutation with or without increased EGFR copy number had a >96.5% chance of disease progression. Conclusion: KRAS mutation should be included as indicator of resistance in the panel of markers used to predict response to EGFR-TKIs in NSCLC.

HER2 and Response to Paclitaxel in Node-Positive Breast Cancer

Abstract: BACKGROUND The status of human epidermal growth factor receptor type 2 (HER2) in breast-cancer cells predicts clinical outcomes in women who receive adjuvant anthracycline-based chemotherapy. We hypothesized that HER2 positivity predicts a benefit from adjuvant doxorubicin doses above standard levels, from the addition of paclitaxel after adjuvant chemotherapy with doxorubicin plus cyclophosphamide, or from both. METHODS We randomly selected 1500 women from 3121 women with node-positive breast cancer who had been randomly assigned to receive doxorubicin (60, 75, or 90 mg per square meter of body-surface area) plus cyclophosphamide (600 mg per square meter) for four cycles, followed by four cycles of paclitaxel (175 mg per square meter) or observation. Tissue blocks from 1322 of these 1500 women were available. Immunohistochemical analyses of these tissue specimens for HER2 with the CB11 monoclonal antibody against HER2 or with a polyclonal-antibody assay kit and fluorescence in situ hybridization for HER2 amplification were performed. RESULTS No interaction was observed between HER2 positivity and doxorubicin doses above 60 mg per square meter. HER2 positivity was, however, associated with a significant benefit from paclitaxel. The interaction between HER2 positivity and the addition of paclitaxel to the treatment was associated with a hazard ratio for recurrence of 0.59 (P=0.01). Patients with a HER2-positive breast cancer benefited from paclitaxel, regardless of estrogen-receptor status, but paclitaxel did not benefit patients with HER2-negative, estrogen-receptor-positive cancers. CONCLUSIONS The expression or amplification, or both, of HER2 by a breast cancer is associated with a benefit from the addition of paclitaxel after adjuvant treatment with doxorubicin (<60 mg per square meter) plus cyclophosphamide in node-positive breast cancer, regardless of estrogen-receptor status. Patients with HER2-negative, estrogen-receptor-positive, node-positive breast cancer may gain little benefit from the administration of paclitaxel after adjuvant chemotherapy with doxorubicin plus cyclophosphamide.