Search

Aim When selecting treatments for type 2 diabetes (T2D), it is important to consider not only efficacy and safety, but also other treatment attributes that have an impact on patient preference. The objective of this study was to examine preference between injection devices used for two weekly GLP‐1 receptor agonists. Materials and Methods The PREFER study was an open‐label, multicentre, randomized, crossover study assessing patient preference for dulaglutide and semaglutide injection devices among injection‐naïve patients receiving oral medication for type 2 diabetes. After being trained to use each device, participants performed all steps of injection preparation and administered mock injections into an injection pad. Time‐to‐train (TTT) for each device was assessed in a subset. Results There were 310 evaluable participants (48.4% female; mean age, 60.0 years; 78 participants in the TTT subgroup). More participants preferred the dulaglutide device than the semaglutide device (84.2% vs. 12.3%; P

IntroductionHealth state utilities associated with weight change are needed as inputs for cost-utility analyses (CUAs) examining the value of treatments for obesity and type 2 diabetes (T2D). Although some pharmaceutical treatments currently in development are associated with substantial weight loss, little is known about the utility impact of weight decreases greater than 10%. The purpose of this study was to estimate utilities associated with body weight decreases up to 20% based on preferences of individuals with obesity, with and without T2D.MethodsHealth state vignettes were developed to represent respondents' own current weight and weight decreases of 2.5%, 5%, 10%, 15%, and 20%. Health state utilities were elicited in time trade-off interviews in two UK locations (Edinburgh and London) with a sample of participants with obesity, with and without T2D. Mean utility increases associated with each amount of weight decrease were calculated. Regression analyses were performed to derive a method for estimating utility change associated with weight decreases.ResultsAnalyses were conducted with data from 405 individuals with obesity (202 with T2D, 203 without T2D). Utility increases associated with various levels of weight decrease ranged from 0.011 to 0.060 in the subgroup with T2D and 0.015 to 0.077 in the subgroup without T2D. All regression models found that the percentage of weight decrease was a highly significant predictor of change in utility (p

Nancy K Leidy,1 Fernando J Martinez,2 Karen G Malley,1 David M Mannino,3 MeiLan K Han,4 Elizabeth D Bacci,5 Randall W Brown,6 Julia F Houfek,7 Wassim W Labaki,4 Barry J Make,8 Catherine A Meldrum,4 Wilson Quezada,9 Stephen Rennard,10 Byron Thomashow,9 Barbara P Yawn11 1Evidera, Patient-Centered Research, Bethesda, MD, USA; 2Weill Cornell Medicine, Joan & Sanford Weill Department of Medicine, New York, NY, USA; 3University of Kentucky, Preventive Medicine & Environmental Health, Lexington, KY, USA; 4University of Michigan, Division of Pulmonary & Critical Care Medicine, Ann Arbor, MI, USA; 5Evidera, Patient-Centered Research, Seattle, WA, USA; 6University of Michigan, Department of Health Behavior & Health Education, School of Public Health, Ann Arbor, MI, USA; 7University of Nebraska Medical Center College of Nursing, Omaha, NE, USA; 8National Jewish Health, Department of Medicine, Division of Pulmonary, Critical Care & Sleep Medicine, Denver, CO, USA; 9Columbia University Medical Center, Division of Pulmonary, Allergy, & Critical Care, New York, NY, USA; 10AstraZeneca, IMED Biotech Unit, Cambridge, UK & University of Nebraska Medical Center, Department of Medicine, Omaha, NE, USA; 11University of Minnesota, Department of Family & Community Health, Minneapolis, MN & COPD Foundation, Miami, FL, USA Background: COPD Assessment in Primary Care To Identify Undiagnosed Respiratory Disease and Exacerbation Risk (CAPTURE™) uses five questions and peak expiratory flow (PEF) thresholds (males ≤350 L/min; females ≤250 L/min) to identify patients with a forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) 2: 37% vs 5%, p10: 86% vs 57%, p

Background This study tested the properties of a Spanish translation of CAPTURE (COPD Assessment in Primary Care To Identify Undiagnosed Respiratory Disease and Exacerbation Risk) with selective use of peak expiratory flow (PEF). Methods : This study comprised analyses of data from the Spanish-speaking cohort of the cross-sectional, case-control study used to develop CAPTURE. Translation procedures included forward and backward translation, reconciliation, and cognitive interviewing to assure linguistic and cultural equivalence, yielding CAPTURE-S. Spanish-speaking participants were recruited through one center and designated as case subjects (clinically significant COPD: FEV 1 ≤ 60% predicted and/or at risk of COPD exacerbation) or control subjects (no or mild COPD). Subjects completed a questionnaire booklet that included 44 candidate items, the COPD Assessment Test (CAT), and the modified Medical Research Council (mMRC) dyspnea question. PEF and spirometry were also performed. Results The study included 30 participants (17 case subjects and 13 control subjects). Their mean (± SD) age was 62.6 (11.49) years, and 33% were male. CAPTURE-S scores were significantly correlated with PEF ( r = –0.78), the FEV 1 /FVC ratio ( r = –0.74), FEV 1 ( r = –0.69), FEV 1 % predicted ( r = –0.69), the CAT score ( r = 0.70), and the mMRC dyspnea question ( r = 0.59) ( P t = 6.16; P 1 ( r = 0.89), FEV 1 % predicted ( r = 0.79), and the FEV 1 /FVC ratio ( r = 0.75) ( P t = 5.08; P Conclusions CAPTURE-S with selective use of PEF seems to be useful for identifying Spanish-speaking patients in need of diagnostic evaluation for clinically significant COPD who may benefit from initiation of COPD treatment. Trial Registry ClinicalTrials.gov; No.: NCT01880177; URL: www.clinicaltrials.gov.

Rationale This study is part of a larger, multi-method project to develop a questionnaire for identifying undiagnosed cases of chronic obstructive pulmonary disease (COPD) in primary care settings, with specific interest in the detection of patients with moderate to severe airway obstruction or risk of exacerbation. Objectives To examine 3 existing datasets for insight into key features of COPD that could be useful in the identification of undiagnosed COPD. Methods Random forests analyses were applied to the following databases: COPD Foundation Peak Flow Study Cohort (N=5761), Burden of Obstructive Lung Disease (BOLD) Kentucky site (N=508), and COPDGene® (N=10,214). Four scenarios were examined to find the best, smallest sets of variables that distinguished cases and controls:(1) moderate to severe COPD (forced expiratory volume in 1 second [FEV1] Results From 4 to 8 variables were able to differentiate cases from controls, with sensitivity ≥73 (range: 73-90) and specificity >68 (range: 68-93). Across scenarios, the best models included age, smoking status or history, symptoms (cough, wheeze, phlegm), general or breathing-related activity limitation, episodes of acute bronchitis, and/or missed work days and non-work activities due to breathing or health. Conclusions Results provide insight into variables that should be considered during the development of candidate items for a new questionnaire to identify undiagnosed cases of clinically significant COPD.

Rationale: Chronic obstructive pulmonary disease (COPD) is often unrecognized and untreated.Objectives: To develop a method for identifying undiagnosed COPD requiring treatment with currently available therapies (FEV1

This study tested the properties of a Spanish translation of CAPTURE (COPD Assessment in Primary Care To Identify Undiagnosed Respiratory Disease and Exacerbation Risk) with selective use of peak expiratory flow (PEF).This study comprised analyses of data from the Spanish-speaking cohort of the cross-sectional, case-control study used to develop CAPTURE. Translation procedures included forward and backward translation, reconciliation, and cognitive interviewing to assure linguistic and cultural equivalence, yielding CAPTURE-S. Spanish-speaking participants were recruited through one center and designated as case subjects (clinically significant COPD: FEVThe study included 30 participants (17 case subjects and 13 control subjects). Their mean (± SD) age was 62.6 (11.49) years, and 33% were male. CAPTURE-S scores were significantly correlated with PEF (r = -0.78), the FEVCAPTURE-S with selective use of PEF seems to be useful for identifying Spanish-speaking patients in need of diagnostic evaluation for clinically significant COPD who may benefit from initiation of COPD treatment.ClinicalTrials.gov; No.: NCT01880177; URL: www.clinicaltrials.gov.

Background: Validated algorithms for identifying progression to metastatic cancer could permit the use of administrative claims databases for research in this area. Objective: To identify simple algorithms that could accurately detect cancer progression to metastatic breast, non-small cell lung, and colorectal cancer using medical and pharmacy claims data. Methods: Adults with stage I–III breast, non-small cell lung cancer (NSCLC), or colorectal cancer (CRC) in the Geisinger Health System from 2004–2011 were selected. Evidence of progression was extracted via manual chart review as the reference standard. In addition to secondary malignancy diagnosis (ICD-9 code for metastases), diagnoses, procedures, and treatments were selected with clinician input as indicators of cancer progression. Random forests models provided variable importance scores. In addition to codes for secondary malignancy, several more complex algorithms were constructed and performance measures calculated. Results: Among those with breast cancer (17/502 [3.4%] progressed), the performance of a secondary malignancy code was suboptimal (sensitivity: 64.7%; specificity: 86.0%; positive predictive value [PPV]: 13.9; negative predictive value [NPV]: 98.6%); requiring malignancy at another site or initiation of immunotherapy increased PPV and specificity but decreased sensitivity. For NSCLC (61/236 [25.8%] progressed) codes for secondary malignancy alone (PPV: 47.4%; NPV: 84.8%; sensitivity: 60.7%; specificity: 76.6%) performed similarly or better than more complex algorithms. For CRC (33/276 [12.0%] progressed), secondary malignancy codes had good specificity (92.7%) and NPV (92.3%) but low sensitivity (42.4%) and PPV (43.8%); an algorithm with change in chemotherapy increased sensitivity but decreased other metrics. Conclusions: Selected algorithms performed similarly to the presence of a secondary tumor diagnosis code, with low sensitivity/PPV and higher specificity/NPV. Accurate identification of cancer progression likely requires verification through chart review.

Louis S Matza,1 Glenn A Phillips,2 Dennis A Revicki,1 Haya Ascher-Svanum,3 Karen G Malley,4 Andrew C Palsgrove,1 Douglas E Faries,3 Virginia Stauffer,3 Bruce J Kinon,3 A George Awad,5 Richard SE Keefe,6 Dieter Naber71Outcomes Research, United BioSource Corporation, Bethesda, MD, 2Formerly with Eli Lilly and Company, Indianapolis, IN, 3Eli Lilly and Company, Indianapolis, IN, 4Malley Research Programming, Inc, Rockville, MD, USA; 5Department of Psychiatry and Behavioral Sciences; University of Toronto, Toronto, Canada; 6Duke University Medical Center, Durham NC, USA; 7Universitaetsklinikum Hamburg-Eppendorf, Hamburg, GermanyIntroduction: The Reasons for Antipsychotic Discontinuation Interview (RAD-I) was developed to assess patients’ perceptions of reasons for discontinuing or continuing an antipsychotic. The current study examined reliability and validity of domain scores representing three factors contributing to these treatment decisions: treatment benefits, adverse events, and distal reasons other than direct effects of the medication.Methods: Data were collected from patients with schizophrenia or schizoaffective disorder and their treating clinicians. For approximately 25% of patients, a second rater completed the RAD-I for assessment of inter-rater reliability.Results: All patients (n = 121; 81 discontinuation, 40 continuation) reported at least one reason for discontinuation or continuation (mean = 2.8 reasons for discontinuation; 3.4 for continuation). Inter-rater reliability was supported (kappas = 0.63–1.0). Validity of the discontinuation domain scores was supported by associations with symptom measures (the Positive and Negative Syndrome Scale for Schizophrenia, the Clinical Global Impression – Schizophrenia Scale; r = 0.30 to 0.51; all P < 0.01), patients’ primary reasons for discontinuation, and adverse events. However, the continuation domain scores were not significantly associated with these other indicators.Discussion: Results support the reliability, convergent validity, and known-groups validity of the RAD-I for assessing patients’ reasons for antipsychotic discontinuation. Further research is needed to examine validity of the RAD-I continuation section.Keywords: discontinuation, antipsychotic, schizophrenia, treatment continuation, patient-reported outcomes, instrument development

Introduction Among researchers and clinicians who treat depression, there is growing interest in treatment of specific residual symptoms such as fatigue. However, there is no available measure that provides a detailed assessment of fatigue associated with depression. Thus, the purpose of the current study was to develop and validate a patient-reported outcome measure designed to assess depression-related fatigue and its impact. Methods The Fatigue Associated with Depression Questionnaire (FAsD) was developed based on literature review, clinician interviews, and focus groups and cognitive debriefing interviews with patients. Then, a draft questionnaire was administered to a sample of patients with depression. Statistical analysis first focused on item reduction and subscale identification, followed by psychometric evaluation of the FAsD. Results The per protocol sample (n = 317) was primarily female (68.1%), with a mean age of 47.0 years. Based on item performance and exploratory factor analysis, three items were dropped from the draft FAsD, yielding a final 13-item questionnaire with two subscales (experience and impact). The FAsD demonstrated good internal consistency reliability (Cronbach's alphas ≥ 0.88) and test–retest reliability (intraclass correlation coefficients ≥ 0.78). The FAsD demonstrated construct validity through strong correlations with measures assessing fatigue/energy and symptoms of depression. The FAsD also discriminated among groups of participants differentiated by clinician ratings of global severity of depression (CGI-S). Limitations Limitations include heterogeneity of current treatments received by the sample, as well as lack of knowledge regarding the extent to which FAsD scores were influenced by patients' treatments rather than the depression itself. Conclusions In this initial psychometric evaluation, the FAsD demonstrated good reliability, validity, and factor structure. This questionnaire may be a useful tool for evaluating treatment interventions that focus specifically on fatigue associated with depression.

The aim of the current study was to identify and evaluate cutoffs for mild, moderate, and severe ranges of Hamilton Anxiety Rating Scale (HAM-A) scores. Data were from a four-week randomized trial of treatment for generalized anxiety disorder. Measures included the HAM-A, SF-36, Hospital Anxiety and Depression Scale (HADS), and Clinical Global Impressions of Severity (CGI-S) scale. HAM-A cutoffs were identified based on literature review, expert panel input, and MANOVA models. The optimal cutoff set was evaluated based on association with clinician CGI-S ratings. The sample included 144 patients (56.3% female; 73.6% white; mean age = 35.7 years; mean baseline HAM-A score = 23.7). The optimal HAM-A score ranges were: mild anxiety = 8-14; moderate = 15-23; severe ≥ 24 (scores ≤ 7 were considered to represent no/minimal anxiety). Analysis of variance (ANOVA) models found statistically significant differences among these groups in the SF-36 and HADS. The HAM-A severity ranges closely corresponded to clinicians' CGI-S ratings. The study represents the first step towards developing severity ranges for the HAM-A. These cutoffs should be used with caution and validated in larger samples. If the proposed cutoffs are accepted for general use, they could make results more meaningful and interpretable for researchers, clinicians, and patients.

This study examined responsiveness of the Adult Attention-Deficit/Hyperactivity Disorder Quality of Life Scale (AAQoL), which was developed to assess health-related quality of life (HRQL) among adults with attention-deficit/hyperactivity disorder (ADHD). Adults with ADHD completed the AAQoL, Conners’ Adult ADHD Rating Scale (CAARS), SF-36, and Endicott Work Productivity Scale (EWPS) at baseline and week 8 of a randomized, placebo-controlled trial of atomoxetine. Clinicians rated symptom severity and improvement (CGI-ADHD-S, CGI-ADHD-I). Responsiveness was examined through effect sizes and association with change in the measures listed previously (Spearman correlations, GLMs). Analyses included 328 patients (58.8% male; mean age = 36.9 years). All AAQoL scales reflected significant improvement from baseline to week 8 (P

This study (1) used patient-reported outcome measures to assess and compare the health status of type 2 diabetes patients with and without obesity and (2) assessed the value of weight change among obese and non-obese subgroups, using standard gamble (SG) utility methodology.Among a sample with type 2 diabetes in the United Kingdom, individuals with obesity (BMIor = 30 kg/m2) were identified and compared to non-obese patients. Patients completed the EQ-5D, Psychological General Well-Being Index, Appraisal of Diabetes Symptoms, and Diabetes Symptom Checklist-Revised (DSC-R). SG interviews assessed the utility of the 'basic' type 2 diabetes health state anchored to respondents' body weight, as well as health states with altered weight.A total of 129 patients (74 obese; 55 non-obese) completed interviews (mean age 55.9 years; 64.3% male). Obese patients reported lower health status (EQ-5D VAS; between-group difference: p0.001) and greater symptom impact (several DSC-R scales, p0.05). Utilities of the basic health state were 0.86 (obese) and 0.91 (non-obese; p = 0.02). Hypothetical health states with higher weight received lower utilities, whereas reduced weight was associated with increased utility. There was a between-group difference in the disutility associated with 5% higher weight (obese 0.068; non-obese 0.051; p = 0.03).Compared with non-obese patients, the obese group reported lower health status and greater symptom impact. SG interviews found an inverse relationship between weight and utility. Furthermore, obese patients with type 2 diabetes may value weight change differently than non-obese patients. Study limitations include the sample size and the use of a patient sample, rather than a sample selected from the general population. Overall, the results demonstrate that utilities can differ by patient subgroups, even among patients with the same diagnosis.

Background: COPD is underdiagnosed, often uncovered during exacerbations or after significant loss of lung function. We are developing a new method (simple questionnaire + peak expiratory flow [PEF]) for identifying patients needing spirometric evaluation for clinically significant COPD (FEV1 Purpose: This study used random forests (RF) to identify the best, smallest set of questions (with and without PEF) capable of case identification. Methods: Prospective, cross-sectional, multi-site, case-control study. Subjects: ≥40 years from US pulmonary and primary care clinics. Cases (clinically significant COPD): ≥1 AECOPD past 12 months or FEV1 60% pred) and AECOPD-free ≥12 months or no COPD. Subjects completed questionnaires, PEF, spirometry (if not on record). Results: N=346; 186 Cases (184 with PEF), 160 Controls. Mean (SD) age=62.7 (10.1) years; 55% female; 86% white; 41% ≤high school; 16% never smoked. Cases: mean (SD) FEV1% pred=42.5(14.2); Controls=82.5(15.7). RF case-control sensitivity/specificity estimates for the final 5-item questionnaire: 83.5/69.7; questionnaire followed by score-driven use of PEF: 90.2/78.8%. Case-no COPD with score-driven PEF: 90.2/92.0. Questions ask about exposure, breathing, tire easily, and acute respiratory illness, and do not ask about smoking, cough, or sputum. Conclusions: These 5 questions + selective use of PEF may be an effective and efficient approach for identifying patients needing diagnostic evaluation for COPD.

The idiopathic inflammatory myopathies (IIM) are systemic connective tissue diseases in which autoimmune pathology is suspected to promote chronic muscle inflammation and weakness. We have performed low to high resolution genotyping to characterize the allelic profiles of HLA-A, -B, -Cw, -DRB1, and -DQA1 loci in a large population of North American Caucasian patients with IIM representing the major clinicopathologic groups (n = 571). We confirmed that alleles of the 8.1 ancestral haplotype were important risk markers for the development of IIM, and a random forests classification analysis suggested that within this haplotype, HLA-B*0801, DRB1*0301 and/ or closely linked genes are the principal HLA risk factors. In addition, we identified several novel HLA factors associated distinctly with 1 or more clinicopathologic groups of IIM. The DQA1*0201 allele and associated peptide-binding motif (KLPLFHRL) were exclusive protective factors for the CD8+ T cell-mediated IIM forms of polymyositis (PM) and inclusion body myositis (IBM) (pc0.005). In contrast, HLA-A*68 alleles were significant risk factors for dermatomyositis (DM) (pc = 0.0021), a distinct clinical group thought to involve a humorally mediated immunopathology. While the DQA1*0301 allele was detected as a possible risk factor for IIM, PM, and DM patients (p0.05), DQA1*03 alleles were protective factors for IBM (pc = 0.0002). Myositis associated with malignancies was the most distinctive group of IIM wherein HLA Class I alleles were the only identifiable susceptibility factors and a shared HLA-Cw peptide-binding motif (AGSHTLQWM) conferred significant risk (pc = 0.019). Together, these data suggest that HLA susceptibility markers distinguish different myositis phenotypes with divergent pathogenetic mechanisms. These variations in associated HLA polymorphisms may reflect responses to unique environmental triggers resulting in the tissue pathospecificity and distinct clinicopathologic syndromes of the IIM.

Objective To determine whether patients in whom myositis develops after they receive silicone breast implants have distinct clinical, serologic, and/or immunogenetic features compared with patients with myositis who do not have silicone implants. Methods A preliminary case series study was followed by a larger, independent, matched case–control study to evaluate women in whom myositis developed after they received silicone implants (MASI patients) compared with healthy women with silicone implants and women with myositis but without silicone implants (idiopathic inflammatory myopathy; IIM patients). Results In a preliminary study, 11 MASI patients differed from 76 IIM patients in having an increased frequency of HLA–DQA1*0102 (odds ratio [OR] 9.8, 95% confidence interval [95% CI] 1.77–96.79) and decreased frequencies of the myositis-associated risk factor DRB1*0301 (OR 0.1 [95% CI 0.002–0.63]) and its linked allele DQA1*0501 (OR 0.2 [95% CI 0.02–0.87]). A subsequent independent, matched case–control study revealed that although clinical features and autoantibodies did not differ significantly between the MASI and IIM groups, MASI patients again had decreased frequencies of DRB1*0301 (OR 0.2 [95% CI 0.07–0.72]) and DQA1*0501 (OR 0.2 [95% CI 0.08–0.84]) compared with IIM patients. Additional comparisons between MASI patients from both studies combined (n = 37) and a larger population of IIM patients (n = 453) suggested that HLA–DQA1*0102 may be uniquely associated with MASI (OR 2.6 [95% CI 1.25–5.46]). Conclusion Women in whom inflammatory myopathy develops after they receive silicone implants constitute an immunogenetically distinct group of patients with myositis. These and other data suggest that autoimmune diseases as now defined may consist of multiple distinct entities, each of which is characterized by different genes and environmental exposures.

Purpose The Fatigue Associated with Depression Questionnaire (FAsD) was developed to assess fatigue and its impact among patients with depression. The purpose of this study was to examine the questionnaire’s responsiveness to change and identify a responder definition for interpretation of treatment-related changes. Methods Data were collected at baseline and at 6 weeks from patients with depression starting treatment with a new antidepressant. Results Of the 96 participants, 55.2% were women, with a mean age of 43.4 years. The total score and both subscales demonstrated statistically significant change with moderate to large effect sizes (absolute values ≥0.76). FAsD change scores were significantly correlated with change on the Brief Fatigue Inventory (r ≥ 0.73; p

The Reasons for Antipsychotic Discontinuation Questionnaire (RAD-Q) was designed to assess clinicians' perceptions of reasons for antipsychotic discontinuation or continuation. The current study examined psychometric properties of this instrument and patterns of antipsychotic discontinuation. The sample of 121 patients (81 discontinuation, 40 continuation) with schizophrenia or schizoaffective disorder was 66.9% male, with a mean age of 41.6 years. Treating clinicians reported a mean of 4.1 reasons for discontinuation and 7.5 reasons for continuation. RAD-Q domain scores were derived to quantify the impact of three factors on the decision to discontinue or continue: treatment benefits, adverse events, and distal reasons other than direct effects of the medication. Analysis of inter-rater reliability indicated an acceptable degree of agreement between clinicians (weighted Kappa for discontinuation scores=0.70-0.78). Correlations with symptom measures (Clinical Global Impression-Schizophrenia Scale (CGI-SCH), Positive and Negative Syndrome Scale (PANSS)) supported convergent validity of the benefits domain score (r=0.28-0.47; all p

Background/Purpose: The myositis syndromes are rare systemic autoimmune diseases with poorly understood etiologies. We present the demographics, illness features and treatments of patients with juvenile dermatomyositis (JDM) who enrolled in a newly created national registry. Methods: Using a patient database from The Myositis Association and supplemental advertisements, a national registry of myositis patients was established. Between December 2010 and July 2012 questionnaires were mailed to 8847 myositis patients in the US and Canada. The questionnaire queried demographics, clinical features, environmental exposures, and quality of life. Descriptive statistics and multivariable logistic regression analysis were computed using GraphPad Prysm and SAS. Results: 1956 patients (22%) returned the questionnaire and consented to participate; 1806 who met probable or definite Bohan and Peter criteria for myositis were included (708 DM, 483 PM, 466 IBM, 139 JDM, 10 JPM); juvenile patients were diagnosed before age 18 years. Of the 139 JDM patients, the median age at diagnosis was 6.9 years and median disease duration at enrollment was 10.3 years. Most JDM patients were female (78%) and Non-Hispanic Caucasian (88%), and the remainder were Hispanic (6.5%), Asian (2.9%), multiple races (2.2%), and Black (0.7%). Patients or their parents often completed a graduate degree (23%) or college degree (29%). JDM patients were primarily diagnosed by a pediatric rheumatologist (48%), with adult and pediatric dermatologists (22%), pediatric neurologists and primary care physicians (11% each) diagnosing most of the remaining patients; 67% were under the care of a pediatric rheumatologist. JDM patients frequently had skin rashes as a major manifestation (86%); arthritis (35%) and dysphagia (32%) were also common, whereas lung disease (12%) was less frequent. An additional autoimmune disease was present in 18% of JDM patients, with JIA (8%) and SLE and celiac disease (3% each) the most frequent. There were no recorded associated malignancies. 98% of JDM patients received prednisone therapy. Methotrexate was the most common steroid-sparing agent (84%), followed by hydroxychloroquine (60%), IV pulse solumedrol (54%), IVIG (48%), cyclosporine (19%), rituximab and anti-TNFs (10% each). Predictors of which agents were received varied among medications, but included age, year of JDM diagnosis, gender, and region of country. Pulse solumedrol and cyclosporine were more likely to be used in JDM patients with dysphagia, hydroxychloroquine in patients with skin rashes and less likely in those with fevers, and azathioprine was less likely in patients with arthritis. Of medications utilized, 45% of JDM patients reported responding best to IVIG, 39% responded best to prednisone, 33% to anti-TNFs, and 29% to cyclophosphamide. Conclusion: A nationwide myositis registry has been established and includes a subsample of JDM patients that appears demographically and clinically representative of other US populations. This registry may help identify environmental exposures associated with myositis, elucidate factors associated with quality of life, and serve as an important resource for future clinical investigations.

Background: The ASK-20 survey is a previously validated patient-report measure of barriers to medication adherence and adherence-related behavior. Objective: To derive and validate a shorter version of the ASK-20 scale. Methods: Patients with asthma, diabetes, and congestive heart failure were recruited from a university medical center. Participants completed the ASK-20 survey and other questionnaires. Approximately one-third of participants were randomized to a 2-week retest administration. Item performance and results of an exploratory factor analysis were examined for item reduction and subscale identification. Subsequent analyses examined reliability and validity of the shorter version of the ASK. Results: A total of 112 patients participated (75.9% female; mean age 46.7 y; 53.6% African American). Eight items were dropped from the ASK-20 based on factor loadings, floor effects, Cronbach's α, and the ability of each item to discriminate between groups of patients differing in self-reported adherence. The new total score (ASK-12) had good internal consistency reliability (Cronbach's α 0.75) and test-retest reliability (intraclass correlation 0.79). Convergent validity was demonstrated through correlations with the Morisky Medication Adherence Scale (r -0.74; p < 0.001), condition-specific measures, the SF-12 Mental Component Score (r –.32; p < 0.01), and proportion of days covered by tilled medication prescriptions in the past 6 months as indicated by pharmacy claims data (r -0.20; p = 0.059). The ASK-12 total score also discriminated among groups of patients who differed in self-reported adherence indicators, including whether a dose was missed in the past week, the number of days medication was not taken as directed, and treatment satisfaction. Three subscales were identified (adherence behavior, health beliefs, inconvenience/forgetfulness), and results provided initial support for their validity. Conclusions: The ASK-12 demonstrated adequate reliability and validity, and it may be a useful brief measure of adherence behavior and barriers to treatment adherence.

Objective To investigate possible associations of GM and KM markers with adult and juvenile forms of the idiopathic inflammatory myopathies (IIMs) in Caucasian and African American patients. Methods We performed serologic analyses of polymorphic determinants associated with immunoglobulin gamma heavy chains (GM) and kappa light chains (KM) in large populations of Caucasian patients (n= 514 [297 adults and 217 children]) and African American patients (n = 123 [73 adults and 50 children]) with IIM representing the major clinical and autoantibody groups. Results For Caucasian patients with dermatomyositis (DM), the Gm 3 23 5,13 phenotype was a risk factor in both adults (odds ratio [OR] 2.2, corrected P [Pcorr] = 0.020) and children (OR 2.2, Pcorr = 0.0013). Of interest, the GM 13 allotype was a risk factor for juvenile DM in both Caucasian subjects (OR 3.9, Pcorr < 0.0001) and African American subjects (OR 4.8, Pcorr = 0.033). However, the Gm 1,3,17 5,13,21 phenotype was a risk factor for juvenile DM in Caucasian subjects but not African American subjects. Among the IIM autoantibody groups, Gm 3 23 5,13 was a risk factor in Caucasian adults with anti–Jo-1 autoantibodies (OR 3.4, Pcorr = 0.0031), while the GM 3 allotype was protective in adults with anti–threonyl–transfer RNA synthetase or anti–U RNP autoantibodies (OR 0.1, Pcorr = 0.047 and OR 0.2, Pcorr = 0.034, respectively). In contrast, GM 6 was a risk factor in African American adults with anti–signal recognition particle autoantibodies (OR 7.5, Pcorr = 0.041). Conclusion These data suggest that polymorphic alleles of GM and KM loci are differentially associated with IIM subgroups defined by age, ethnicity, clinical features, and autoantibody status, and expand the list of immune response genes that are possibly important in the pathogenesis of myositis.

Objective To investigate possible associations of HLA polymorphisms with idiopathic inflammatory myopathy (IIM) in African Americans, and to compare this with HLA associations in European American IIM patients with IIM. Methods Molecular genetic analyses of HLA–A, B, Cw, DRB1, and DQA1 polymorphisms were performed in a large population of African American patients with IIM (n = 262) in whom the major clinical and autoantibody subgroups were represented. These data were compared with similar information previously obtained from European American patients with IIM (n = 571). Results In contrast to European American patients with IIM, African American patients with IIM, in particular those with polymyositis, had no strong disease associations with HLA alleles of the 8.1 ancestral haplotype; however, African Americans with dermatomyositis or with anti–Jo-1 autoantibodies shared the risk factor HLA–DRB1*0301 with European Americans. We detected novel HLA risk factors in African American patients with myositis overlap (DRB1*08) and in African American patients producing anti–signal recognition particle (DQA1*0102) and anti–Mi-2 autoantibodies (DRB1*0302). DRB1*0302 and the European American–, anti–Mi-2–associated risk factor DRB1*0701 were found to share a 4–amino-acid sequence motif, which was predicted by comparative homology analyses to have identical 3-dimensional orientations within the peptide-binding groove. Conclusion These data demonstrate that North American IIM patients from different ethnic groups have both shared and distinct immunogenetic susceptibility factors, depending on the clinical phenotype. These findings, obtained from the largest cohort of North American minority patients with IIM studied to date, add additional support to the hypothesis that the myositis syndromes comprise multiple, distinct disease entities, perhaps arising from divergent pathogenic mechanisms and/or different gene–environment interactions.

Background Patient-reported measures can be used to examine whether drug differences other than clinical efficacy have an impact on outcomes that may be important to patients. Although exenatide and insulin glargine appear to have similar efficacy for treatment of type 2 diabetes, there are several differences between the two treatments that could influence outcomes from the patient's perspective. The purpose of the current study was to examine whether the two drugs were comparable as assessed by patient-reported outcomes using data from a clinical trial in which these injectable medications were added to pre-existing oral treatment regimens. Methods Patients were randomized to either twice daily exenatide or once daily insulin glargine during a 26-week international trial. At baseline and endpoint, five patient-reported outcome measures were administered: the Vitality Scale of the SF-36, The Diabetes Symptom Checklist – Revised (DSC-R), the EuroQol EQ-5D, the Treatment Flexibility Scale (TFS), and the Diabetes Treatment Satisfaction Questionnaire (DTSQ). Change from baseline to endpoint was analyzed within each treatment group. Group differences were examined with General linear models (GLMs), controlling for country and baseline scores. Results A total of 549 patients with type 2 diabetes were enrolled in the trial, and current analyses were conducted with data from the 455 per protocol patients (228 exenatide and 227 insulin glargine). The sample was primarily Caucasian (79.6%), with slightly more men (55.2%) than women, and with a mean age of 58.5 years. Paired t-tests found that both treatment groups demonstrated statistically significant baseline to endpoint change on several of the health outcomes instruments including the DSC-R, DTSQ, and the SF-36 Vitality subscale. GLMs found no statistically significant differences between groups in change on the health outcomes instruments. Conclusion This analysis found that both exenatide and insulin glargine were associated with significant improvements in patient-reported outcomes when added to oral medications among patients with type 2 diabetes. Despite an additional daily injection and a higher rate of gastrointestinal adverse events, treatment satisfaction in the exenatide group was comparable to that of the glargine group, possibly because of weight reduction observed in patients treated with exenatide.

The idiopathic inflammatory myopathies (IIM) are systemic connective tissue diseases defined by chronic muscle inflammation and weakness associated with autoimmunity. We have performed low to high resolution molecular typing to assess the genetic variability of major histocompatibility complex loci (HLA-A, -B, -Cw, -DRB1, and -DQA1) in a large population of European American patients with IIM (n = 571) representing the major myositis autoantibody groups. We established that alleles of the 8.1 ancestral haplotype (8.1 AH) are important risk factors for the development of IIM in patients producing anti-synthetase/anti-Jo-1, -La, -PM/Scl, and -Ro autoantibodies. Moreover, a random forests classification analysis suggested that 8.1 AH-associated alleles B*0801 and DRB1*0301 are the principal HLA risk markers. In addition, we have identified several novel HLA susceptibility factors associated distinctively with particular myositis-specific (MSA) and myositis-associated autoantibody (MAA) groups of the IIM. IIM patients with anti-PL-7 (anti-threonyl-tRNA synthetase) autoantibodies have a unique HLA Class I risk allele, Cw*0304 (pcorr = 0.046), and lack the 8.1 AH markers associated with other anti-synthetase autoantibodies (for example, anti-Jo-1 and anti-PL-12). In addition, HLA-B*5001 and DQA1*0104 are novel potential risk factors among anti-signal recognition particle autoantibody-positive IIM patients (pcorr = 0.024 and p = 0.010, respectively). Among those patients with MAA, HLA DRB1*11 and DQA1*06 alleles were identified as risk factors for myositis patients with anti-Ku (pcorr = 0.041) and anti-La (pcorr = 0.023) autoantibodies, respectively. Amino acid sequence analysis of the HLA DRB1 third hypervariable region identified a consensus motif, 70D (hydrophilic)/71R (basic)/74A (hydrophobic), conferring protection among patients producing anti-synthetase/anti-Jo-1 and -PM/Scl autoantibodies. Together, these data demonstrate that HLA signatures, comprising both risk and protective alleles or motifs, distinguish IIM patients with different myositis autoantibodies and may have diagnostic and pathogenic implications. Variations in associated polymorphisms for these immune response genes may reflect divergent pathogenic mechanisms and/or responses to unique environmental triggers in different groups of subjects resulting in the heterogeneous syndromes of the IIM.

Background This study characterized the degree of change in health-related quality of life (HRQL) associated with change in visual acuity among patients with diabetic retinopathy. Methods Data are from a randomized, placebo-controlled trial of ruboxistaurin for vision loss in patients with diabetic retinopathy. Visual acuity was quantified as letters on the ETDRS visual acuity chart. HRQL was assessed with the 25-Item Visual Function Questionnaire (VFQ-25) and the SF-36. Patients were categorized into groups based on visual acuity change from baseline to month 18. HRQL change of these groups was compared using general linear models. Regression analyses examined visual acuity change defined continuously. Results Patients (N = 535) were primarily Caucasian (81.9%) and male (64.1%); mean age = 59.3 years. Compared to patients whose visual acuity did not change, the group with > 10 letters vision loss had significantly greater decreases in all VFQ-25 subscales except ocular pain. SF-36 change scores did not correspond as closely to change in vision. Change in visual acuity defined continuously was significantly associated with change in all VFQ-25 scales except ocular pain (p < 0.0001). Conclusion Change in visual acuity was associated with corresponding changes in HRQL among patients with diabetic retinopathy. Previous research has often defined vision loss as a loss of at least 15 letters on the ETDRS visual acuity chart. In the current study, however, a loss of at least 10 letters was associated with substantial declines in HRQL domains such as driving, dependency, role limitations, and mental health. These findings suggest that patients who experience vision loss of at least 10 letters may be appropriate targets of future research and clinical intervention.

To investigate the relation between the size of circumoval granulomas and hepatic fibrosis, a variety of mouse strains infected with Schistosoma mansoni were examined and the number of eggs in the tissues, the fibrotic responses to the eggs, and the volume of the granulomas were determined. Marked differences in granuloma volume and in hepatic fibrosis were found between mouse strains, and those strains with the largest granulomas also showed the most hepatic fibrosis. On the other hand no significant correlation between granuloma size and hepatic fibrosis was found in the progeny of the F2 generation and backcrosses between F1 mice and the parental strains when crosses were made between Nmri mice (high granuloma volume and high fibrosis) and C57BL/6 mice (low granuloma volume and low fibrosis). Hepatic fibrosis per egg decreased with increasing infection intensity while granuloma volume was unaffected, indicating that fibrosis and granuloma size are at least in part modulated by different factors. The number of eggs found in the tissues per worm pair and the proportion of eggs in the liver also decreased as infection intensity increased. Some influence of the major histocompatibility complex on both granuloma size and fibrosis was found. Congenic mice on the C57BL/10 and C3H/HeSn backgrounds showed larger granulomas in H-2b than in H-2k mice, but no such correlation was found in comparing C57BL/6 mice with B6.H-2k mice. Less hepatic fibrosis was found in B10.M (H-2f), B10.SM (H-2v), and B10.RIII (H-2r) animals than in C57BL/10 mice. The regulation of granuloma size and of hepatic fibrosis is clearly complex and involves genes both outside of and within the major histocompatibility complex.

Machine learning is a critical component of any biological data mining. Given its established advantages, there remain challenges that need to be addressed before it can be considered practical and persuasive. Thus, not quite The Tempest (Act V, Scene One), above, but Shakespeare would still have understood: learning machines have achieved stunning success in a stunning range of areas, but they are still often—correctly—seen as strange and mysterious. They make predictions {tumor, not tumor} with ease and rapidity, but how do we understand the forecasts? How were the forecasts made, and how do they apply to this patient, with this set of symptoms and exposure factors? How does a low mean square error translate into guidance for patient treatment and care? How is any machine translated?