Serum Proteomics and Plasma Fibulin-3 in Differentiation of Mesothelioma From Asbestos-Exposed Controls and Patients With Other Pleural Diseases.

INTRODUCTION: Malignant pleural mesothelioma (MPM) is difficult to diagnose. An accurate blood biomarker could prompt specialist referral or be deployed in future screening. In earlier retrospective studies, SOMAscan proteomics (Somalogic, Boulder, CO) and fibulin-3 seemed highly accurate, but SOMAscan has not been validated prospectively and subsequent fibulin-3 data have been contradictory. METHODS: A multicenter prospective observational study was performed in 22 centers, generating a large intention-to-diagnose cohort. Blood sampling, processing, and diagnostic assessment were standardized, including a 1-year follow-up. Plasma fibulin-3 was measured using two enzyme-linked immunosorbent assays (CloudClone [used in previous studies] and BosterBio, Pleasanton, CA). Serum proteomics was measured using the SOMAscan assay. Diagnostic performance (sensitivity at 95% specificity, area under the curve [AUC]) was benchmarked against serum mesothelin (Mesomark, Fujirebio Diagnostics, Malvern, PA). Biomarkers were correlated against primary tumor volume, inflammatory markers, and asbestos exposure. RESULTS: A total of 638 patients with suspected pleural malignancy (SPM) and 110 asbestos-exposed controls (AECs) were recruited. SOMAscan reliably differentiated MPM from AECs (75% sensitivity, 88.2% specificity, validation cohort AUC 0.855) but was not useful in patients with differentiating non-MPM SPM. Fibulin-3 (by BosterBio after failed CloudClone validation) revealed 7.4% and 11.9% sensitivity at 95% specificity in MPM versus non-MPM SPM and AECs, respectively (associated AUCs 0.611 [0.557-0.664], p = 0.0015) and 0.516 [0.443-0.589], p = 0.671), both inferior to mesothelin. SOMAscan proteins correlated with inflammatory markers but not with asbestos exposure. Neither biomarker correlated with tumor volume. CONCLUSIONS: SOMAscan may prove useful as a future screening test for MPM in asbestos-exposed persons. Neither fibulin-3 nor SOMAscan should be used for diagnosis or pathway stratification.

Accelerated, Dose escalated, Sequential Chemoradiotherapy in Non-small-cell lung cancer (ADSCaN): a protocol for a randomised phase II study.

INTRODUCTION: Lung cancer is the most common cause of cancer mortality in the UK, and non-small-cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. Most patients present with inoperable disease; therefore, radiotherapy plays a major role in treatment. However, the majority of patients are not suitable for the gold standard treatment (concurrent chemoradiotherapy) due to performance status and comorbidities. Novel strategies integrating radiotherapy advances and radiobiological knowledge need to be evaluated in patients treated with sequential chemoradiotherapy. Four separate dose escalation accelerated radiotherapy schedules have been completed in UK (CHART-ED, IDEAL-CRT, I-START and Isotoxic IMRT). This study will compare these schedules with a UK standard sequential chemoradiotherapy schedule of 55 Gy in 20 fractions over 4 weeks. As it would be impossible to test all schedules in a phase III study, the aim is to use a combined randomised phase II screening/'pick the winner' approach to identify the best schedule to take into a randomised phase III study against conventionally fractionated radiotherapy. METHODS AND ANALYSIS: Suitable patients will have histologically/cytologically confirmed, stage III NSCLC and are able to undergo chemoradiotherapy treatment. The study will recruit 360 patients; 120 on the standard arm and 60 on each experimental arm. Patients will complete 2-4 cycles of platinum-based chemotherapy before being randomised to one of the radiotherapy schedules. The primary endpoint is progression-free survival, with overall survival, time to local-regional failure, toxicity and cost-effectiveness as secondary objectives. ETHICS AND DISSEMINATION: The study has received ethical approval (research ethics committee (REC) reference: 16/WS/0165) from the West of Scotland REC 1. The trial is conducted in accordance with the Declaration of Helsinki and Good Clinical Practice. Trial results will be published in a peer-reviewed journal and presented internationally. TRIAL REGISTRATION NUMBER: ISRCTN47674500.

A first step in addressing medical education Curriculum gaps in lesbian-, gay-, bisexual-, and transgender-related content: The University of Louisville Lesbian, Gay, Bisexual, and Transgender Health Certificate Program.

BACKGROUND: Individuals who are lesbian, gay, bisexual, transgender (LGBT), gender nonconforming, and/or born with differences of sex development have specific health needs and significant health disparities exacerbated by a lack of training among health professionals. The University of Louisville LGBT Health Certificate Program used an interdisciplinary approach to increase training, potentially enabling future physicians to provide quality healthcare to LGBT patients. METHODS: A pretest-post-test design was used to investigate medical students' (n = 39) attitude and knowledge outcomes after program participation. Attitudinal items with Likert-type responses were analyzed using the Wilcoxon signed-rank test. Baseline frequency and percentage of correct responses were tabulated for knowledge questions. At both pre- and post-test, the 11 knowledge items were summed to establish a total knowledge score, creating two total scores. The paired sample t-test was used to evaluate the pre- and post-change, and Cohen's D was used to assess effect size. All P values were two-tailed. Statistical significance was set by convention at P < 0.05. RESULTS: Students correctly answered 69% or less of the knowledge questions at baseline. Total correct knowledge scores significantly increased post intervention with the effect size being large (Cohen's D = 0.90, P < 0.001). Attitudes significantly increased post intervention on two items (P = 0.019 and P = 0.037). Some attitude items decreased post intervention: students felt it is more challenging to conduct a patient history with a LGB patient (pre-mean agreement = 2.44; post-mean agreement = 2.97, P = 0.018). CONCLUSIONS: Medical educators can play a critical role in decreasing LGBT healthcare disparities. The University of Louisville LGBT Health Certificate Program played an important first step in increasing medical students' knowledge and improving certain attitudes about LGBT patients.

Substance abuse.

Alcohol abuse poses special risks for increased morbidity and mortality among older adults, contributing to the heightened use of medical resources and the related increase in medical costs. Although the prevalance of alcohol use disorders in the older adults is generally less than that found in younger groups, it is expected to increase with the aging of the "baby-boom" generation. In spite of this, little attention has focused on developing, and evaluating the efficacy of, treatment programs for older adults with alcohol related disorders. This article discusses the availability of effective treatment strategies for older alcohol abusers and reviews the epidemiological and outcomes research literatures related to alcohol abuse and older adults. The few empirical studies that examine outcomes associated with the treatment of older substance abusers reveal positive outcomes, especially when "age-specific," cognitive-behavioral, and less confrontational treatment approaches are employed.

Lack of a close confidant: prevalence and correlates in a medically underserved primary care sample.

The present study examined prevalence of lack of a close confidant in a medically underserved primary care sample, and evaluated demographic, medical, and psychological correlates of patients' deficits in close, personal contact. Adult patients (n = 413) reported on confidant status and symptoms of depression and anxiety. Sociodemographic and medical information were obtained through chart review. One-quarter of patients endorsed lack of a close confidant. Past month anxiety and depression symptoms, but not medical status, were associated with unmet socioemotional needs. Implications for primary healthcare interventions are discussed.

Predicting erythroid response to recombinant erythropoietin plus granulocyte colony-stimulating factor therapy following a single subcutaneous bolus in patients with myelodysplasia.

We randomized 21 patients with low-risk myelodysplastic syndromes (MDS) to receive a single subcutaneous bolus of recombinant erythropoietin (epoietin) +/- granulocyte-colony stimulating factor (G-CSF), or placebo and monitored erythropoietic response over 7 days. In this small study, the reticulocyte response at day 7 was highly predictive of subsequent response to a therapeutic trial of epoietin + G-CSF.