Prognostic variables and scores identifying the last year of life in COPD: a systematic review protocol

Introduction People living with advanced chronic obstructive pulmonary disease (COPD) suffer from significant morbidity, reduced quality of life and high mortality, and are likely to benefit from many aspects of a palliative care approach. Prognostic estimates are a meaningful part of decision-making and better evidence for such estimates would facilitate advance care planning. We aim to provide quality evidence on known prognostic variables and scores which predict a prognosis in COPD of <12 months for use in the community. Methods and analysis We will conduct a systematic review of randomised or quasi-randomised controlled trials, prospective and retrospective longitudinal cohort and case–control studies on prognostic variables, multivariate scores or models for COPD. The search will cover the period up to April 2016. Study selection will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, with data extraction using fields from the Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies (CHARMS) checklist for multivariate models, and study quality will be assessed using a modified version of the Quality In Prognosis Studies (QUIPS) tool. Ethics and dissemination The results will be disseminated through peer-reviewed publications and national and international conference presentations

Serotype k Streptococcus mutans Binding to Collagen and Fibrinogen in Nicotine

poster abstractBackground: Streptococcus mutans is a gram-positive coccus-shaped, facultatively anaerobic bacterium that is commonly found in the human oral cavity and is a major contributor to tooth decay. The bacterium has the potential to make its way into the blood stream and adhere to endothelial cell proteins such as collagen and fibrinogen in the arteries through specific receptors potentially leading to atherosclerosis. Endothelial cells secrete cell-associated and cell-free collagen and fibrinogen. Specifically, serotype k S. mutans have been associated with atherosclerosis and nicotine has been shown to increase the biofilm formation of S. mutans (serotype k). The focus of this research was to measure S. mutans ability to bind to collagen type I and fibrinogen when the cells were grown in the presence of nicotine. Methods: S. mutans serotype k strains 51, 52, and 89 were cultured in 0–2 mg/mL nicotine. Formaldehyde was added to kill the cells followed by labeling the cells with biotin. Collagen type I and fibrinogen were coated (1 μg/mL) onto 96-well microtiter plates. The plates were washed and 1% BSA was added to block the wells. Then the biotinylated nicotine-treated S. mutans were added, incubated to allow binding to the endothelial cell proteins, and washed. Finally, ExtrAvidin HRP and OPD were added to the plate and the optical density was measured at an absorbance of 490 nm. Results: The optical density was directly related to the relative number of cells bound to collagen type I and fibrinogen. Conclusion: The results demonstrated a significant increase in all three strains of S. mutans binding to the proteins when cultured in 1 and 2 mg/mL concentrations of nicotine compared to the 0 nicotine control. The increased numbers of nicotine-treated S. mutans binding to the endothelial cell proteins may have the ability to contribute to atherosclerosis

Effects of Nicotine on Aerobic and Anaerobic Serotype K Streptococcus mutans Biofilm Formation

poster abstractAtherosclerosis is a specific form of arteriosclerosis where the walls of arteries began to thicken as a result of bacterial invasion and accumulation of inflammatory white blood cells. There could be a direct correlation of atherosclerosis and the intake of nicotine. Nicotine has been reported to increase the amount of the cariogenic oral bacteria known as Streptococcus mutans; thus possibly leading to an increase of dental caries. Serotype K S. mutans has been associated strongly with atherosclerosis. Objective: This study focused on the biofilm formation of S. mutans serotype K when incubated in various dilutions of nicotine. Methods: S. mutans UA159 (stereotype C), and stereotype K strains 89, 52, and 51 were cultured in tryptic soy broth (TSB) overnight and then added to dilutions of TSB with 1% sucrose (TSBS) containing concentrations of nicotine between 0 and 32 mg/ml. Each dilution was added to 96-well microtiter plates, inoculated with bacteria and incubated for 24 hours aerobically at 37oC in 5% CO2 and anaerobically. The plates were treated with formaldehyde, crystal violet, and isopropanol and biofilm formation was measured at an absorbance of 490 nm. Results: Strains UA159, 89, 52, and 51 all demonstrated significantly higher biofilm formation (p<0.05) at a nicotine dilution of 8 mg/ml. When comparing the anaerobic results to the aerobic results, anaerobic incubation increased the overall biofilm formation across the majority of nicotine dilutions. Conclusion: It was established that when S. mutans strains UA159, 89, 52, and 51 were incubated anaerobically and aerobically biofilm formation was enhanced. Smoking can lead to a higher population of S. mutans in the oral cavity that potentially has traits of significantly enhanced biofilm formation when presented with moderately high levels of nicotine which may lead to increased binding to endothelial cells contributing to atherosclerosis

3D tomography of cells in micro-channels

We combine confocal imaging, microfluidics and image analysis to record 3D-images of cells in flow. This enables us to recover the full 3D representation of several hundred living cells per minute. Whereas 3D confocal imaging has thus far been limited to steady specimen, we overcome this restriction and present a method to access the 3D shape of moving objects. The key of our principle is a tilted arrangement of the micro-channel with respect to the focal plane of the microscope. This forces cells to traverse the focal plane in an inclined manner. As a consequence, individual layers of passing cells are recorded which can then be assembled to obtain the volumetric representation. The full 3D information allows for a detailed comparisons with theoretical and numerical predictions unfeasible with e.g.\ 2D imaging. Our technique is exemplified by studying flowing red blood cells in a micro-channel reflecting the conditions prevailing in the microvasculature. We observe two very different types of shapes: `croissants' and `slippers'. Additionally, we perform 3D numerical simulations of our experiment to confirm the observations. Since 3D confocal imaging of cells in flow has not yet been realized, we see high potential in the field of flow cytometry where cell classification thus far mostly relies on 1D scattering and fluorescence signals

Validation of chronic obstructive pulmonary disease recording in the Clinical Practice Research Datalink (CPRD-GOLD)

Objectives: The optimal method of identifying people with chronic obstructive pulmonary disease (COPD) from electronic primary care records is not known. We assessed the accuracy of different approaches using the Clinical Practice Research Datalink, a UK electronic health record database. Setting: 951 participants registered with a CPRD practice in the UK between 1 January 2004 and 31 December 2012. Individuals were selected for ≥1 of 8 algorithms to identify people with COPD. General practitioners were sent a brief questionnaire and additional evidence to support a COPD diagnosis was requested. All information received was reviewed independently by two respiratory physicians whose opinion was taken as the gold standard. Primary outcome measure: The primary measure of accuracy was the positive predictive value (PPV), the proportion of people identified by each algorithm for whom COPD was confirmed. Results: 951 questionnaires were sent and 738 (78%) returned. After quality control, 696 (73.2%) patients were included in the final analysis. All four algorithms including a specific COPD diagnostic code performed well. Using a diagnostic code alone, the PPV was 86.5% (77.5-92.3%) while requiring a diagnosis plus spirometry plus specific medication; the PPV was slightly higher at 89.4% (80.7-94.5%) but reduced case numbers by 10%. Algorithms without specific diagnostic codes had low PPVs (range 12.2-44.4%). Conclusions: Patients with COPD can be accurately identified from UK primary care records using specific diagnostic codes. Requiring spirometry or COPD medications only marginally improved accuracy. The high accuracy applies since the introduction of an incentivised disease register for COPD as part of Quality and Outcomes Framework in 2004

Acute kidney injury in stable COPD and at exacerbation.

BACKGROUND: While acute kidney injury (AKI) alone is associated with increased mortality, the incidence of hospital admission with AKI among stable and exacerbating COPD patients and the effect of concurrent AKI at COPD exacerbation on mortality is not known. METHODS: A total of 189,561 individuals with COPD were identified from the Clinical Practice Research Datalink. Using Poisson and logistic regressions, we explored which factors predicted admission for AKI (identified in Hospital Episode Statistics) in this COPD cohort and concomitant AKI at a hospitalization for COPD exacerbation. Using survival analysis, we investigated the effect of concurrent AKI at exacerbation on mortality (n=36,107) and identified confounding factors. RESULTS: The incidence of AKI in the total COPD cohort was 128/100,000 person-years. The prevalence of concomitant AKI at exacerbation was 1.9%, and the mortality rate in patients with AKI at exacerbation was 521/1,000 person-years. Male sex, older age, and lower glomerular filtration rate predicted higher risk of AKI or death. There was a 1.80 fold (95% confidence interval: 1.61, 2.03) increase in adjusted mortality within the first 6 months post COPD exacerbation in patients suffering from AKI and COPD exacerbation compared to those who were AKI free. CONCLUSION: In comparison to previous studies on general populations and hospitalizations, the incidence and prevalence of AKI is relatively high in COPD patients. Coexisting AKI at exacerbation is prognostic of poor outcome

A compilation, tabulation and analysis of spelling errors made by pupils in grades four, five, and six in free writing of sentences using given stimuli words

Thesis (M.A.)--Boston Universit

Acquired epidermodysplasia verruciformis due to multiple and unusual HPV infection among vertically-infected, HIV-positive adolescents in Zimbabwe.

BACKGROUND: We have previously described the presentation of epidermodysplasia verruciformis (EV)-like eruptions in almost a quarter of hospitalized adolescents with vertically-acquired human immunodeficiency virus (HIV) infection in Harare, Zimbabwe, a region with a high prevalence of HIV infection. METHODS: We performed a clinical case note review and skin biopsy from affected sites in 4 HIV-infected adolescents with EV-like lesions in Harare. Biopsies were processed for histology and for human papillomavirus (HPV) typing. RESULTS: All patients had long-standing skin lesions that pre-dated the diagnosis of HIV by several years. The histology of skin biopsies from all patients was consistent with EV. In each biopsy, EV-associated β-HPV type 5 was identified (additionally, type 19 was found in 1 biopsy). Cutaneous wart-associated HPV types 1 and 2 were detected in all biopsies, together with genital lesion-associated HPV types 6, 16, and 52, (as well as ≥3 other genital lesion-associated HPV types). Despite immune reconstitution with combination antiretroviral therapy (cART), there was no improvement in EV-like lesions in any patient. CONCLUSIONS: EV is a disfiguring and potentially stigmatizing condition among this patient group and is difficult to treat; cART appears to have no impact on the progression of skin disease. Among adolescents with longstanding HIV-induced immunosuppression and with high levels of sun exposure, close dermatological surveillance for potential skin malignancy is required

Artificial neural networks for 3D cell shape recognition from confocal images

We present a dual-stage neural network architecture for analyzing fine shape details from microscopy recordings in 3D. The system, tested on red blood cells, uses training data from both healthy donors and patients with a congenital blood disease. Characteristic shape features are revealed from the spherical harmonics spectrum of each cell and are automatically processed to create a reproducible and unbiased shape recognition and classification for diagnostic and theragnostic use.Comment: 17 pages, 8 figure

COPD disease severity and the risk of venous thromboembolic events: a matched case-control study.

BACKGROUND: It is generally accepted that people with chronic obstructive pulmonary disease (COPD) are at increased risk of vascular disease, including venous thromboembolism (VTE). While it is plausible that the risk of arterial and venous thrombotic events is greater still in certain subgroups of patients with COPD, such as those with more severe airflow limitation or more frequent exacerbations, these associations, in particular those between venous events and COPD severity or exacerbation frequency, remain largely untested in large population cohorts. METHODS: A total of 3,594 patients with COPD with a first VTE event recorded during January 1, 2004 to December 31, 2013, were identified from the Clinical Practice Research Datalink dataset and matched on age, sex, and general practitioner practice (1:3) to patients with COPD with no history of VTE (n=10,782). COPD severity was staged by degree of airflow limitation (ie, GOLD stage) and by COPD medication history. Frequent exacerbators were defined as patients with COPD with ≥ 2 exacerbations in the 12-month period prior to their VTE event (for cases) or their selection as a control (for controls). Conditional logistic regression was used to estimate the association between disease severity or exacerbation frequency and VTE. RESULTS: After additional adjustment for nonmatching confounders, including body mass index, smoking, and heart-related comorbidities, there was evidence for an association between increased disease severity and VTE when severity was measured either in terms of lung function impairment (odds ratio [OR]moderate:mild =1.16; 95% confidence intervals [CIs] =1.03, 1.32) or medication usage (ORsevere:mild/moderate =1.17; 95% CIs =1.06, 1.26). However, there was no evidence to suggest that frequent exacerbators were at greater risk of VTE compared with infrequent exacerbators (OR =1.06; 95% CIs =0.97, 1.15). CONCLUSION: COPD severity defined by airflow limitation or medication usage, but not exacerbation frequency, appears to be associated with VTE events in people with COPD. This finding highlights the disconnect between disease activity and severity in COPD