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

Realising the right to data portability for the domestic Internet of Things

There is an increasing role for the IT design community to play in regulation of emerging IT. Article 25 of the EU General Data Protection Regulation (GDPR) 2016 puts this on a strict legal basis by establishing the need for information privacy by design and default (PbD) for personal data-driven technologies. Against this backdrop, we examine legal, commercial and technical perspectives around the newly created legal right to data portability (RTDP) in GDPR. We are motivated by a pressing need to address regulatory challenges stemming from the Internet of Things (IoT). We need to find channels to support the protection of these new legal rights for users in practice. In Part I we introduce the internet of things and information PbD in more detail. We briefly consider regulatory challenges posed by the IoT and the nature and practical challenges surrounding the regulatory response of information privacy by design. In Part II, we look in depth at the legal nature of the RTDP, determining what it requires from IT designers in practice but also limitations on the right and how it relates to IoT. In Part III we focus on technical approaches that can support the realisation of the right. We consider the state of the art in data management architectures, tools and platforms that can provide portability, increased transparency and user control over the data flows. In Part IV, we bring our perspectives together to reflect on the technical, legal and business barriers and opportunities that will shape the implementation of the RTDP in practice, and how the relationships may shape emerging IoT innovation and business models. We finish with brief conclusions about the future for the RTDP and PbD in the IoT

Expression of steroid receptor coactivator 3 in ovarian epithelial cancer is a poor prognostic factor and a marker for platinum resistance

BACKGROUND: Steroid receptor coactivator 3 (SRC3) is an important coactivator of a number of transcription factors and is associated with a poor outcome in numerous tumours. Steroid receptor coactivator 3 is amplified in 25% of epithelial ovarian cancers (EOCs) and its expression is higher in EOCs compared with non-malignant tissue. No data is currently available with regard to the expression of SRC-3 in EOC and its influence on outcome or the efficacy of treatment. METHODS: Immunohistochemistry was performed for SRC3, oestrogen receptor-α, HER2, PAX2 and PAR6, and protein expression was quantified using automated quantitative immunofluorescence (AQUA) in 471 EOCs treated between 1991 and 2006 with cytoreductive surgery followed by first-line treatment platinum-based therapy, with or without a taxane. RESULTS: Steroid receptor coactivator 3 expression was significantly associated with advanced stage and was an independent prognostic marker. High expression of SRC3 identified patients who have a significantly poorer survival with single-agent carboplatin chemotherapy, while with carboplatin/paclitaxel treatment such a difference was not seen. CONCLUSION: Steroid receptor coactivator 3 is a poor prognostic factor in EOCs and appears to identify a population of patients who would benefit from the addition of taxanes to their chemotherapy regimen, due to intrinsic resistance to platinum therapy

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

c-Met overexpression in inflammatory breast carcinomas: automated quantification on tissue microarrays

Inflammatory breast carcinoma (IBC) is a rare but aggressive tumour associated with poor outcome owing to early metastases. Increased expression of c-Met protein correlates with reduced survival and high metastatic risk in human cancers including breast carcinomas and is targetable by specific drugs, that could potentially improve the prognosis. In the present study, we compared c-Met expression in IBC (n=41) and non-IBC (n=480) immunohistochemically (Ventana Benchmark autostainer) in two tissue microarrays (TMA) along with PI3K and E-cadherin. The results were quantified through an automated image analysis device (SAMBA Technologies). We observed that (i) c-Met was significantly overexpressed in IBC as compared with non-IBC (P<0.001), (ii) PI3K was overexpressed (P<0.001) in IBC, suggesting that the overexpressed c-Met is functionally active at least through the PI3K signal transduction pathway; and (iii) E-cadherin was paradoxically also overexpressed in IBC. We concluded that overexpressed c-Met in IBC constitutes a potential target for specific therapy for the management of patients with poor-outcome tumours such as IBC. Automated image analysis of TMA proved to be a valuable tool for high-throughput immunohistochemical quantification of the expression of intratumorous protein markers

Proteome Analysis of Borrelia burgdorferi Response to Environmental Change

We examined global changes in protein expression in the B31 strain of Borrelia burgdorferi, in response to two environmental cues (pH and temperature) chosen for their reported similarity to those encountered at different stages of the organism's life cycle. Multidimensional nano-liquid chromatographic separations coupled with tandem mass spectrometry were used to examine the array of proteins (i.e., the proteome) of B. burgdorferi for different pH and temperature culture conditions. Changes in pH and temperature elicited in vitro adaptations of this spirochete known to cause Lyme disease and led to alterations in protein expression that are associated with increased microbial pathogenesis. We identified 1,031 proteins that represent 59% of the annotated genome of B. burgdorferi and elucidated a core proteome of 414 proteins that were present in all environmental conditions investigated. Observed changes in protein abundances indicated varied replicon usage, as well as proteome functional distributions between the in vitro cell culture conditions. Surprisingly, the pH and temperature conditions that mimicked B. burgdorferi residing in the gut of a fed tick showed a marked reduction in protein diversity. Additionally, the results provide us with leading candidates for exploring how B. burgdorferi adapts to and is able to survive in a wide variety of environmental conditions and lay a foundation for planned in situ studies of B. burgdorferi isolated from the tick midgut and infected animals

Mitochondrial fragmentation and superoxide anion production in coronary endothelial cells from a mouse model of type 1 diabetes

Mitochondria frequently change their shapes by fusion and fission and these morphological dynamics play important roles in mitochondrial function and development as well as programmed cell death. The goal of this study is to investigate whether: (1) mitochondria in mouse coronary endothelial cells (MCECs) isolated from diabetic mice exhibit increased fragmentation; and (2) chronic treatment with a superoxide anion (O2 −) scavenger has a beneficial effect on mitochondrial fragmentation in MCECs. MCECs were freshly isolated and lysed for protein measurement, or cultured to determine mitochondrial morphology and O2 − production. For the ex vivo hyperglycaemia experiments, human coronary endothelial cells were used. Elongated mitochondrial tubules were observed in MCECs isolated from control mice, whereas mitochondria in MCECs from diabetic mice exhibited augmented fragmentation. The level of optic atrophy 1 (OPA1) protein, which leads to mitochondrial fusion, was significantly decreased, while dynamin-related protein 1 (DRP1), which leads to mitochondrial fission, was significantly increased in MCECs from diabetic mice. Diabetic MCECs exhibited significantly higher O2 − concentrations in cytosol and mitochondria than control MCECs. Administration of the O2 − scavenger TEMPOL to diabetic mice for 4 weeks led to a significant decrease in mitochondrial fragmentation without altering the levels of OPA1 and DRP1 proteins in MCECs. High-glucose treatment for 24 h significantly induced mitochondrial fragmentation, which was restored by TEMPOL treatment. In addition, excess O2 − production, either in cytosol or in mitochondria, significantly increased mitochondrial fragmentation. These data suggest that lowering the O2 − concentration can restore the morphological change in mitochondria and may help improve mitochondrial function in diabetic MCECs

Overexpression of Chitinase 3-Like 1/YKL-40 in Lung-Specific IL-18-Transgenic Mice, Smokers and COPD

We analyzed the lung mRNA expression profiles of a murine model of COPD developed using a lung-specific IL-18-transgenic mouse. In this transgenic mouse, the expression of 608 genes was found to vary more than 2-fold in comparison with control WT mice, and was clustered into 4 groups. The expression of 140 genes was constitutively increased at all ages, 215 genes increased gradually with aging, 171 genes decreased gradually with aging, and 82 genes decreased temporarily at 9 weeks of age. Interestingly, the levels of mRNA for the chitinase-related genes chitinase 3-like 1 (Chi3l1), Chi3l3, and acidic mammalian chitinase (AMCase) were significantly higher in the lungs of transgenic mice than in control mice. The level of Chi3l1 protein increased significantly with aging in the lungs and sera of IL-18 transgenic, but not WT mice. Previous studies have suggested Chi3l3 and AMCase are IL-13-driven chitinase-like proteins. However, IL-13 gene deletion did not reduce the level of Chi3l1 protein in the lungs of IL-18 transgenic mice. Based on our murine model gene expression data, we analyzed the protein level of YKL-40, the human homolog of Chi3l1, in sera of smokers and COPD patients. Sixteen COPD patients had undergone high resolution computed tomography (HRCT) examination. Emphysema was assessed by using a density mask with a cutoff of −950 Hounsfield units to calculate the low-attenuation area percentage (LAA%). We observed significantly higher serum levels in samples from 28 smokers and 45 COPD patients compared to 30 non-smokers. In COPD patients, there was a significant negative correlation between serum level of YKL-40 and %FEV1. Moreover, there was a significant positive correlation between the serum levels of YKL-40 and LAA% in COPD patients. Thus our results suggest that chitinase-related genes may play an important role in establishing pulmonary inflammation and emphysematous changes in smokers and COPD patients

Longitudinal proxy measurements in multiple sclerosis: patient-proxy agreement on the impact of MS on daily life over a period of two years

Background: The use of self- report measurements in clinical settings is increasing. However, in patients with limitations that interfere with reliable self- assessment such as cognitive impairment or mood disturbances, as may be the case in multiple sclerosis ( MS), data collection might be problematic. In these situations, information obtained from proxy respondents ( e. g. partners) may replace self- ratings. The aim of this study was to examine the value of proxy ratings at separate points in time and to assess patient- proxy agreement on possible changes in disease impact of MS. Methods: Fifty- six MS patients and their partners completed the Multiple Sclerosis Impact Scale ( MSIS- 29) at baseline and follow- up, two years later. Patient- proxy agreement was assessed at both time points by calculating intraclass correlation coefficients ( ICCs), exact and global agreement and the mean directional differences between groups. Agreement of change over time was assessed by calculating ICCs between change scores. In parallel, global ratings of both patients and proxy respondents of the extent to which the patient had improved or deteriorated over the past two years were collected to validate possible changes on the MSIS- 29. Results: At both time points, agreement on the physical scale was higher than agreement on the psychological scale ( ICCs at baseline were 0.81 for the physical scale and 0.72 for the psychological scale; at follow- up, the ICC values were 0.86 and 0.65 respectively). At follow- up, statistically significant mean differences between patients and proxies were noted for the physical scale (- 4.8 +/- 12.7, p = 0.006) and the psychological scale (- 8.9 +/- 18.8, p = 0.001). Agreement between change scores on the MSIS- 29 was fair ( ICC < 0.60). Our analyses suggest that the validity of measuring changes over time might be better for proxy respondents compared to patients. Conclusion: Proxy respondents could act as a reliable source of information in cross- sectional studies. Moreover, results suggested that agreement on change over time might be better for proxy respondents compared to patients. Although this remarkable finding should be interpreted cautiously because of several limitations of the study, it does plead for further investigation of this important topic