The validity of using ICD-9 codes and pharmacy records to identify patients with chronic obstructive pulmonary disease

Background: Administrative data is often used to identify patients with chronic obstructive pulmonary disease (COPD), yet the validity of this approach is unclear. We sought to develop a predictive model utilizing administrative data to accurately identify patients with COPD. Methods: Sequential logistic regression models were constructed using 9573 patients with postbronchodilator spirometry at two Veterans Affairs medical centers (2003-2007). COPD was defined as: 1) FEV1/FVC <0.70, and 2) FEV1/FVC < lower limits of normal. Model inputs included age, outpatient or inpatient COPD-related ICD-9 codes, and the number of metered does inhalers (MDI) prescribed over the one year prior to and one year post spirometry. Model performance was assessed using standard criteria. Results: 4564 of 9573 patients (47.7%) had an FEV1/FVC < 0.70. The presence of ≥1 outpatient COPD visit had a sensitivity of 76% and specificity of 67%; the AUC was 0.75 (95% CI 0.74-0.76). Adding the use of albuterol MDI increased the AUC of this model to 0.76 (95% CI 0.75-0.77) while the addition of ipratropium bromide MDI increased the AUC to 0.77 (95% CI 0.76-0.78). The best performing model included: ≥6 albuterol MDI, ≥3 ipratropium MDI, ≥1 outpatient ICD-9 code, ≥1 inpatient ICD-9 code, and age, achieving an AUC of 0.79 (95% CI 0.78-0.80). Conclusion: Commonly used definitions of COPD in observational studies misclassify the majority of patients as having COPD. Using multiple diagnostic codes in combination with pharmacy data improves the ability to accurately identify patients with COPD.Department of Veterans Affairs, Health Services Research and Development (DHA), American Lung Association (CI- 51755-N) awarded to DHA, the American Thoracic Society Fellow Career Development AwardPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/84155/1/Cooke - ICD9 validity in COPD.pd

Recurrent adamantinomatous craniopharyngiomas show MAPK pathway activation, clonal evolution and rare <i>TP53 </i>-loss-mediated malignant progression

The two types of craniopharyngioma, adamantinomatous (ACP) and papillary (PCP), are clinically relevant tumours in children and adults. Although the biology of primary craniopharyngioma is starting to be unravelled, little is known about the biology of recurrence. To fill this gap in knowledge, we have analysed through methylation array, RNA sequencing and pERK1/2 immunohistochemistry a cohort of paired primary and recurrent samples (32 samples from 14 cases of ACP and 4 cases of PCP). We show the presence of copy number alterations and clonal evolution across recurrence in 6 cases of ACP, and analysis of additional whole genome sequencing data from the Children’s Brain Tumour Network confirms chromosomal arm copy number changes in at least 7/67 ACP cases. The activation of the MAPK/ERK pathway, a feature previously shown in primary ACP, is observed in all but one recurrent cases of ACP. The only ACP without MAPK activation is an aggressive case of recurrent malignant human craniopharyngioma harbouring a CTNNB1 mutation and loss of TP53. Providing support for a functional role of this TP53 mutation, we show that Trp53 loss in a murine model of ACP results in aggressive tumours and reduced mouse survival. Finally, we characterise the tumour immune infiltrate showing differences in the cellular composition and spatial distribution between ACP and PCP. Together, these analyses have revealed novel insights into recurrent craniopharyngioma and provided preclinical evidence supporting the evaluation of MAPK pathway inhibitors and immunomodulatory approaches in clinical trials in against recurrent ACP

Tele-branding in TVIII: the network as brand and the programme as brand

In the era of TVIII, characterized by deregulation, multimedia conglomeration, expansion and increased competition, branding has emerged as a central industrial practice. Focusing on the case of HBO, a particularly successful brand in TVIII, this article argues that branding can be understood not simply as a feature of television networks, but also as a characteristic of television programmes. It begins by examining how the network as brand is constructed and conveyed to the consumer through the use of logos, slogans and programmes. The role of programmes in the construction of brand identity is then complicated by examining the sale of programmes abroad, where programmes can be seen to contribute to the brand identity of more than one network. The article then goes on to examine programme merchandising, an increasingly central strategy in TVIII. Through an analysis of different merchandising strategies the article argues that programmes have come to act as brands in their own right, and demonstrates that the academic study of branding not only reveals the development of new industrial practices, but also offers a way of understanding the television programme and its consumption by viewers in a period when the texts of television are increasingly extended across a range of media platforms

Association of Accelerometry-Measured Physical Activity and Cardiovascular Events in Mobility-Limited Older Adults: The LIFE (Lifestyle Interventions and Independence for Elders) Study.

BACKGROUND:Data are sparse regarding the value of physical activity (PA) surveillance among older adults-particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. METHODS AND RESULTS:Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home-based activity data were collected by hip-worn accelerometers at baseline and at 6, 12, and 24&nbsp;months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500&nbsp;steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96; P=0.001). At baseline, every 30&nbsp;minutes spent performing activities ≥500&nbsp;counts per minute (hazard ratio, 0.75; confidence interval, 0.65-0.89 [P=0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow-up (6, 12, and 24&nbsp;months), both the number of steps per day (per 500&nbsp;steps; hazard ratio, 0.90, confidence interval, 0.85-0.96 [P=0.001]) and duration of activity ≥500&nbsp;counts per minute (per 30&nbsp;minutes; hazard ratio, 0.76; confidence interval, 0.63-0.90 [P=0.002]) were significantly associated with lower cardiovascular event rates. CONCLUSIONS:Objective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score &gt;10 on the Short Physical Performance Battery) both using baseline and longitudinal data. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500

Tumour compartment transcriptomics demonstrates the activation of inflammatory and odontogenic programmes in human adamantinomatous craniopharyngioma and identifies the MAPK/ERK pathway as a novel therapeutic target

Adamantinomatous craniopharyngiomas (ACPs) are clinically challenging tumours, the majority of which have activating mutations in CTNNB1. They are histologically complex, showing cystic and solid components, the latter comprised of different morphological cell types (e.g. β-catenin-accumulating cluster cells and palisading epithelium), surrounded by a florid glial reaction with immune cells. Here, we have carried out RNA sequencing on 18 ACP samples and integrated these data with an existing ACP transcriptomic dataset. No studies so far have examined the patterns of gene expression within the different cellular compartments of the tumour. To achieve this goal, we have combined laser capture microdissection with computational analyses to reveal groups of genes that are associated with either epithelial tumour cells (clusters and palisading epithelium), glial tissue or immune infiltrate. We use these human ACP molecular signatures and RNA-Seq data from two ACP mouse models to reveal that cell clusters are molecularly analogous to the enamel knot, a critical signalling centre controlling normal tooth morphogenesis. Supporting this finding, we show that human cluster cells express high levels of several members of the FGF, TGFB and BMP families of secreted factors, which signal to neighbouring cells as evidenced by immunostaining against the phosphorylated proteins pERK1/2, pSMAD3 and pSMAD1/5/9 in both human and mouse ACP. We reveal that inhibiting the MAPK/ERK pathway with trametinib, a clinically approved MEK inhibitor, results in reduced proliferation and increased apoptosis in explant cultures of human and mouse ACP. Finally, we analyse a prominent molecular signature in the glial reactive tissue to characterise the inflammatory microenvironment and uncover the activation of inflammasomes in human ACP. We validate these results by immunostaining against immune cell markers, cytokine ELISA and proteome analysis in both solid tumour and cystic fluid from ACP patients. Our data support a new molecular paradigm for understanding ACP tumorigenesis as an aberrant mimic of natural tooth development and opens new therapeutic opportunities by revealing the activation of the MAPK/ERK and inflammasome pathways in human ACP. KEYWORDS: Craniopharyngioma; IL1-β; Inflammasome; MAPK/ERK pathway; Odontogenesis; Paracrine signalling; Trametini

Growing cerebellum requiring operative decompression following perinatal ventriculoperitoneal shunting

INTRODUCTION: While cases of acquired Chiari I malformation following ventriculoperitoneal shunting for posthemorrhagic hydrocephalus have been reported, true disproportionate cerebellar growth is rare, with no previous cases requiring posterior fossa decompression reported. CLINICAL PRESENTATION: We present a premature neonate who underwent ventriculoperitoneal shunt placement for suspected posthemorrhagic hydrocephalus. He subsequently developed a symptomatic Chiari I malformation with volumetric measurements demonstrating disproportionate growth of the cerebellum. He did not demonstrate thickening of the supratentorial or posterior fossa cranium. The patient underwent an extradural posterior fossa decompression, with resolution of symptoms. OUTCOME AND CONCLUSIONS: We review the extant literature regarding the development of Chiari malformation type I as a manifestation of craniocerebral disproportion (CCD) following shunt placement for posthemorrhagic hydrocephalus of prematurity. Most previous reports reflect a mechanism that includes underdevelopment of the intracranial posterior fossa (or supratentorial) volume. The case presented in this report, as well as one additional case, indicates that there may exist a variant mechanism, characterized by rapid growth of the cerebellum itself, in the absence of one of the rare syndromes associated with primary macrocerebellum. While this case was effectively managed with extradural posterior fossa decompression, previous reports indicate that supratentorial cranial expansion procedures are preferable in some cases. As such, pediatric neurosurgeons should be able to distinguish the patterns of craniocerebral disproportion when considering treatment options for these patients. Further investigation regarding these uncommon patients may better describe the underlying mechanisms

Survival benefit of postoperative radiation in papillary meningioma: Analysis of the National Cancer Data Base

Aim/BackgroundPapillary meningioma represents a rare subset of World Health Organization (WHO) Grade III meningioma that portends an overall poor prognosis. There is relatively limited data regarding the benefit of postoperative radiation therapy (PORT). We used the National Cancer Data Base (NCDB) to compare overall survival (OS) outcomes of surgically resected papillary meningioma cases undergoing PORT compared to post-operative observation.Materials and methodsThe NCDB was queried for patients with papillary meningioma, diagnosed between 2004 and 2013, who underwent upfront surgery with or without PORT. Overall survival (OS) was determined using the Kaplan–Meier method. Univariate (UVA) and multivariate (MVA) analyses were performed.ResultsIn total, 190 patients were identified; 89 patients underwent PORT, 101 patients were observed. Eleven patients received chemotherapy (6 with PORT, 5 without). 2-Year OS was significantly improved with PORT vs. no PORT (93.0% vs. 74.4%), as was 5-year OS (78.5% vs. 62.5%) (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.27–0.85; p[[ce:hsp sp="0.25"/]]=[[ce:hsp sp="0.25"/]]0.01). On MVA, patients receiving PORT had improved OS compared to observation (HR, 0.41; 95% CI, 0.22–0.76; p[[ce:hsp sp="0.25"/]]=[[ce:hsp sp="0.25"/]]0.005). On subset analysis by age group, the benefit of PORT vs. no PORT was significant in patients ≤18 years (n[[ce:hsp sp="0.25"/]]=[[ce:hsp sp="0.25"/]]13), with 2-year OS of 85.7% vs. 50.0% (HR, 0.08; 95% CI, 0.01–0.80; p[[ce:hsp sp="0.25"/]]=[[ce:hsp sp="0.25"/]]0.032) and for patients >18 years (n[[ce:hsp sp="0.25"/]]=[[ce:hsp sp="0.25"/]]184), with 2-year OS of 94.7% vs. 76.1% (HR, 0.55; 95% CI, 0.31–1.00; p[[ce:hsp sp="0.25"/]]=[[ce:hsp sp="0.25"/]]0.049), respectively.ConclusionsIn this large contemporary analysis, PORT was associated with improved survival for both adult and pediatric patients with papillary meningioma. PORT should be considered in those who present with this rare, aggressive tumor