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

External validation of a COPD prediction model using population-based primary care data: a nested case-control study

Emerging models for predicting risk of chronic obstructive pulmonary disease (COPD) require external validation in order to assess their clinical value. We validated a previous model for predicting new onset COPD in a different database. We randomly drew 38,597 case-control pairs (total N = 77,194) of individuals aged ≥35 years and matched for sex, age, and general practice from the United Kingdom Clinical Practice Research Datalink database. We assessed accuracy of the model to discriminate between COPD cases and non-cases by calculating area under the receiver operator characteristic (ROC(AUC)) for the prediction scores. Analogous to the development model, ever smoking (OR 6.70; 95%CI 6.41–6.99), prior asthma (OR 6.43; 95%CI 5.85–7.07), and higher socioeconomic deprivation (OR 2.90; 95%CI 2.72–3.09 for highest vs. lowest quintile) increased the risk of COPD. The validated prediction scores ranged from 0–5.71 (ROC(AUC) 0.66; 95%CI 0.65–0.66) for males and 0–5.95 (ROC(AUC) 0.71; 95%CI 0.70–0.71) for females. We have confirmed that smoking, prior asthma, and socioeconomic deprivation are key risk factors for new onset COPD. Our model seems externally valid at identifying patients at risk of developing COPD. An impact assessment now needs to be undertaken to assess whether this prediction model can be applied in clinical care settings

Overcoming the Challenges Associated with Image-based Mapping of Small Bodies in Preparation for the OSIRIS-REx Mission to (101955) Bennu

The OSIRIS-REx Asteroid Sample Return Mission is the third mission in NASA's New Frontiers Program and is the first U.S. mission to return samples from an asteroid to Earth. The most important decision ahead of the OSIRIS-REx team is the selection of a prime sample-site on the surface of asteroid (101955) Bennu. Mission success hinges on identifying a site that is safe and has regolith that can readily be ingested by the spacecraft's sampling mechanism. To inform this mission-critical decision, the surface of Bennu is mapped using the OSIRIS-REx Camera Suite and the images are used to develop several foundational data products. Acquiring the necessary inputs to these data products requires observational strategies that are defined specifically to overcome the challenges associated with mapping a small irregular body. We present these strategies in the context of assessing candidate sample-sites at Bennu according to a framework of decisions regarding the relative safety, sampleability, and scientific value across the asteroid's surface. To create data products that aid these assessments, we describe the best practices developed by the OSIRIS-REx team for image-based mapping of irregular small bodies. We emphasize the importance of using 3D shape models and the ability to work in body-fixed rectangular coordinates when dealing with planetary surfaces that cannot be uniquely addressed by body-fixed latitude and longitude.Comment: 31 pages, 10 figures, 2 table

IL1RN genetic variations and risk of IPF: a meta-analysis and mRNA expression study

Idiopathic pulmonary fibrosis (IPF) is a rare and devastating lung disease of unknown aetiology. Genetic variations in the IL1RN gene, encoding the interleukin-1 receptor antagonist (IL-1Ra), have been associated with IPF susceptibility. Several studies investigated the variable number tandem repeat (VNTR) or single nucleotide polymorphisms rs408392, rs419598 and rs2637988, with variable results. The aim of this study was to elucidate the influence of polymorphisms in IL1RN on IPF susceptibility and mRNA expression. We performed a meta-analysis of the five case–control studies that investigated an IL1RN polymorphism in IPF in a Caucasian population. In addition, we investigated whether IL1RN mRNA expression was influenced by IL1RN polymorphisms. The VNTR, rs408392 and rs419598 were in tight linkage disequilibrium, with D′ > 0.99. Furthermore, rs2637988 was in linkage disequilibrium with the VNTR (D′ = 0.90). A haploblock of VNTR*2 and the minor alleles of rs408392and rs419598 was constructed. Meta-analysis revealed that this VNTR*2 haploblock is associated with IPF susceptibility both with an allelic model (odds ratio = 1.42, p = 0.002) and a carriership model (odds ratio = 1.60, p = 0.002). IL1RN mRNA expression was significantly influenced by rs2637988, with lower levels found in carriers of the (minor) GG genotype (p < 0.001). From this meta-analysis, we conclude that the VNTR*2 haploblock is associated with susceptibility to IPF. In addition, polymorphisms in IL1RN influence IL-1Ra mRNA expression, suggesting that lower levels of IL-1Ra predispose to developing IPF. Together these findings demonstrate that the cytokine IL-1Ra plays a role in IPF pathogenesis

Anti-cytokine therapy in fibrosing alveolitis: where are we now?

Idiopathic pulmonary fibrosis (IPF) is a condition that has a poor prognosis, with a median survival of 4-5 years irrespective of treatment. Ziesche et al (N Engl J Med 1999, 341: 1264-1269) describe an open randomised trial of 18 patients with IPF, unresponsive to corticosteroid treatment at high dose. Nine patients were treated with continued corticosteroid and nine with prednisolone plus interferon-γ 1b (IFN-γ). Significant benefits in physiological parameters are reported in the IFN-γ-treated group. An analysis of lung tissue by reverse-transcriptase-mediated polymerase chain reaction showed corresponding decreases in the transcription of transforming growth factor-β1 and connective tissue growth factor. This is the first report of treatment showing efficacy in this disease, albeit in a very preliminary study, but the data should be viewed with caution. This study is discussed in the context of other published studies of treatment for IPF and the scientific rationale on which it was based

The Relationship between Telomere Length and Mortality in Chronic Obstructive Pulmonary Disease (COPD)

Some have suggested that chronic obstructive pulmonary disease (COPD) is a disease of accelerated aging. Aging is characterized by shortening of telomeres. The relationship of telomere length to important clinical outcomes such as mortality, disease progression and cancer in COPD is unknown. Using quantitative polymerase chain reaction (qPCR), we measured telomere length of peripheral leukocytes in 4,271 subjects with mild to moderate COPD who participated in the Lung Health Study (LHS). The subjects were followed for approximately 7.5 years during which time their vital status, FEV1 and smoking status were ascertained. Using multiple regression methods, we determined the relationship of telomere length to cancer and total mortality in these subjects. We also measured telomere length in healthy “mid-life” volunteers and patients with more severe COPD. The LHS subjects had significantly shorter telomeres than those of healthy “mid-life” volunteers (p<.001). Compared to individuals in the 4th quartile of relative telomere length (i.e. longest telomere group), the remaining participants had significantly higher risk of cancer mortality (Hazard ratio, HR, 1.48; p = 0.0324) and total mortality (HR, 1.29; p = 0.0425). Smoking status did not make a significant difference in peripheral blood cells telomere length. In conclusion, COPD patients have short leukocyte telomeres, which are in turn associated increased risk of total and cancer mortality. Accelerated aging is of particular relevance to cancer mortality in COPD

What proportion of patients with chronic noncancer pain are prescribed an opioid medicine? Systematic review and meta-regression of observational studies

Guidelines now discourage opioid analgesics for chronic noncancer pain because the benefits frequently do not outweigh the harms. We aimed to determine the proportion of patients with chronic noncancer pain who are prescribed an opioid, the types prescribed and factors associated with prescribing. Database searches were conducted from inception to 29 October 2018 without language restrictions. We included observational studies of adults with chronic noncancer pain measuring opioid prescribing. Opioids were categorized as weak (e.g. codeine) or strong (e.g. oxycodone). Study quality was assessed using a risk of bias tool designed for observational studies measuring prevalence. Individual study results were pooled using a random‐effects model. Meta‐regression investigated study‐level factors associated with prescribing (e.g. sampling year, geographic region as per World Health Organization). The overall evidence quality was assessed using Grading of Recommendations Assessment, Development and Evaluation criteria. Of the 42 studies (5,059,098 participants) identified, the majority (n = 28) were from the United States of America. Eleven studies were at low risk of bias. The pooled estimate of the proportion of patients with chronic noncancer pain prescribed opioids was 30.7% (95% CI 28.7% to 32.7%, n = 42 studies, moderate‐quality evidence). Strong opioids were more frequently prescribed than weak (18.4% (95% CI 16.0–21.0%, n = 15 studies, low‐quality evidence), versus 8.5% (95% CI 7.2–9.9%, n = 15 studies, low‐quality evidence)). Meta‐regression determined that opioid prescribing was associated with year of sampling (more prescribing in recent years) (P = 0.014) and not geographic region (P = 0.056). Opioid prescribing for patients with chronic noncancer pain is common and has increased over time

Association between Variations in Cell Cycle Genes and Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a devastating and progressive lung disease. Its aetiology is thought to involve damage to the epithelium and abnormal repair. Alveolar epithelial cells near areas of remodelling show an increased expression of proapoptotic molecules. Therefore, we investigated the role of genes involved in cell cycle control in IPF. Genotypes for five single nucleotide polymorphisms (SNPs) in the tumour protein 53 (TP53) gene and four SNPs in cyclin-dependent kinase inhibitor 1A (CDKN1A), the gene encoding p21, were determined in 77 IPF patients and 353 controls. In peripheral blood mononuclear cells (PBMC) from 16 healthy controls mRNA expression of TP53 and CDKN1A was determined