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Molecular testing patterns in metastatic non-small cell lung cancer.

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Identification of oncogene mutations and gene rearrangements in individuals with non-small cell lung cancer (NSCLC) can help identify candidates for targeted therapy. This study examined whether clinicians are ordering molecular testing for patients with metastatic NSCLC (mNSCLC) prior to therapy initiation.

STUDY DESIGN: Members from a national health plan with lung cancer and metastatic disease were followed retrospectively.
METHODS: Members were identified in medical claims data from January 1, 2010, to December 31, 2012, if they had 2 or more claims for lung cancer (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 162.xx) and metastatic disease (≥ 1 claim with ICD-9-CM code 196.xx-198.xx) who were continuously enrolled in a fully insured plan 180 days prior to index date. Patients were excluded if they had a history of chemotherapy used primarily in small cell lung cancer, or a medical claim associated with an unrelated malignancy. The timing of molecular testing was compared with the start of chemotherapy and targeted therapy, if applicable.

RESULTS: A total of 2623 patients presumed to have mNSCLC were included for analysis; of whom, 52.5% were male with a mean age of 72.5 years (SD = 8.2 years). A total of 1597 (60.9%) patients had a Current Procedural Terminology code associated with molecular testing at any time in their claims history. Of the 733 patients with molecular testing and chemotherapy or targeted therapy claims, testing occurred prior to systemic therapy initiation in 651 (88.8%; 95% CI, 86.1%-90.9%) patients. The median time between testing and therapy initiation was 38 days (interquartile range = 23-69 days).

CONCLUSIONS: Assessment of oncogene mutations and gene rearrangements in mNSCLC routinely occurs prior to treatment initiation as suggested by analyses of claims data from a large US health plan. Validation using patient medical records is needed.

Allergen immunotherapy for insect venom allergy: protocol for a systematic review.

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The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines for Allergen Immunotherapy (AIT) for the Management of Insect Venom Allergy. We seek to critically assess the effectiveness, cost-effectiveness and safety of AIT in the management of insect venom allergy.

METHODS: We will undertake a systematic review, which will involve searching international biomedical databases for published, in progress and unpublished evidence. Studies will be independently screened against pre-defined eligibility criteria and critically appraised using established instruments. Data will be descriptively and, if possible and appropriate, quantitatively synthesised.

DISCUSSION: The findings from this review will be used to inform the development of recomendations for EAACI's Guidelines on AIT.

Lung-gut crosstalk: evidence, mechanisms and implications for the mucosal inflammatory diseases.

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The mucosal immune system (including airway, intestinal, oral and cervical epithelium) is an integrated network of tissues, cells and effector molecules that protect the host from environmental insults and infections at mucous membrane surfaces. Dysregulation of immunity at mucosal surfaces is thought to be responsible for the alarming global increase in mucosal inflammatory diseases such as those affecting the gastrointestinal (Crohn's disease, ulcerative colitis and irritable bowel syndrome) and respiratory (asthma, allergy and chronic obstructive pulmonary disorder) system. Although immune regulation has been well studied in isolated mucosal sites, the extent of the immune interaction between anatomically distant mucosal sites has been mostly circumstantial and the focus of much debate. With novel technology and more precise tools to examine histological and functional changes in tissues, today there is increased appreciation of the 'common mucosal immunological system' originally proposed by Bienenstock nearly 40 years ago.

Evidence is amounting which shows that stimulation of one mucosal compartment can directly and significantly impact distant mucosal site, however the mechanisms are unknown. Today, we are only beginning to understand the complexity of relationships and communications that exist between different mucosal compartments. A holistic approach to studying the mucosal immune system as an integrated global organ is imperative for future advances in understanding mucosal immunology and for future treatment of chronic diseases.

In this review, we particularly focus on the latest evidence and the mechanisms operational in driving the lung-gut crosstalk. This article is protected by copyright. All rights reserved.

Lung diffusing capacity for nitric oxide as a marker of fibrotic changes in idiopathic interstitial pneumonias.

Lung diffusing capacity for carbon monoxide (DLCO) is decreased in both usual interstitial pneumonia-idiopathic pulmonary fibrosis (UIP-IPF) and nonspecific interstitial pneumonia (NSIP), but is moderately related to computed tomography (CT)-determined fibrotic changes. This may be due to the relative insensitivity of DLCO to changes in alveolar membrane diffusive conductance (DMCO).

The purpose of this study was to determine whether measurement of lung diffusing capacity for nitric oxide (DLNO) better reflects fibrotic changes than DLCO. DLNO-DLCO were measured simultaneously in 30 patients with UIP-IPF and 30 with NSIP. Eighty-one matched healthy subjects served as a control group. The amount of pulmonary fibrosis was estimated by CT volumetric analysis of visually bounded areas showing reticular opacities and honeycombing. DMCO and pulmonary capillary volume (VC) were calculated. DLNO was below the lower limit of normal in all patients irrespective of extent and nature of disease, whereas DLCO was within the normal range in a non-negligible number of patients. Both DLNO and DLCO were significantly correlated with visual assessment of fibrosis but DLNO more closely than DLCO. DMCO was also below the lower limit of normal in all UIP-IPF and NSIP patients and significantly correlated with fibrosis extent in both diseases, whereas VC was weakly correlated with fibrosis in UIP-IPF and uncorrelated in NSIP, with normal values in half of patients.

In conclusion, measurement of DLNO may provide a more sensitive evaluation of fibrotic changes than DLCO in either UIP-IPF or NSIP, because it better reflects DMCO.

Hypoxic pulmonary hypertension in chronic lung diseases: novel vasoconstrictor pathways.

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Pulmonary hypertension is a well recognised complication of chronic hypoxic lung diseases, which are among the most common causes of death and disability worldwide. Development of pulmonary hypertension independently predicts reduced life expectancy. In chronic obstructive pulmonary disease, long-term oxygen therapy ameliorates pulmonary hypertension and greatly improves survival, although the correction of alveolar hypoxia and pulmonary hypertension is only partial. Advances in understanding of the regulation of vascular smooth muscle tone show that chronic vasoconstriction plays a more important part in the pathogenesis of hypoxic pulmonary hypertension than previously thought, and that structural vascular changes contribute less. Trials of existing vasodilators show that pulmonary hypertension can be ameliorated and systemic oxygen delivery improved in carefully selected patients, although systemic hypotensive effects limit the doses used.

Vasoconstrictor pathways that are selective for the pulmonary circulation can be blocked to reduce hypoxic pulmonary hypertension without causing systemic hypotension, and thus provide potential targets for novel therapeutic strategies.

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