Risk factors for exacerbations and pneumonia in patients with chronic obstructive pulmonary disease: a pooled analysis.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) are at risk of exacerbations and pneumonia; how the risk factors interact is unclear. METHODS: This post-hoc, pooled analysis included studies of COPD patients treated with inhaled corticosteroid (ICS)/long-acting β2 agonist (LABA) combinations and comparator arms of ICS, LABA, and/or placebo. Backward elimination via Cox's proportional hazards regression modelling evaluated which combination of risk factors best predicts time to first (a) pneumonia, and (b) moderate/severe COPD exacerbation. RESULTS: Five studies contributed: NCT01009463, NCT01017952, NCT00144911, NCT00115492, and NCT00268216. Low body mass index (BMI), exacerbation history, worsening lung function (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage), and ICS treatment were identified as factors increasing pneumonia risk. BMI was the only pneumonia risk factor influenced by ICS treatment, with ICS further increasing risk for those with BMI <25 kg/m2. The modelled probability of pneumonia varied between 3 and 12% during the first year. Higher exacerbation risk was associated with a history of exacerbations, poorer lung function (GOLD stage), female sex and absence of ICS treatment. The influence of the other exacerbation risk factors was not modified by ICS treatment. Modelled probabilities of an exacerbation varied between 31 and 82% during the first year. CONCLUSIONS: The probability of an exacerbation was considerably higher than for pneumonia. ICS reduced exacerbations but did not influence the effect of risks associated with prior exacerbation history, GOLD stage, or female sex. The only identified risk factor for ICS-induced pneumonia was BMI <25 kg/m2. Analyses of this type may help the development of COPD risk equations

The Human Factor: The Behavioral Drivers and Operational Impact of Discretion

Aim: Recent operations research acknowledges that agents in our operational systems have discretion to make decisions. Modeling this behavior requires assumptions, but these assumptions may induce gaps between models and real-world observations. In the end, these decisions coalesce firm-level outputs, both for good and ill. Despite this, deliberate system design can transform problematic deviance into productive discretion. In this dissertation, I detail three explorations of system design and the operational impact of human discretion. Background: The operations literature has a rich history of applying formal mathematical models to explain and study both product and service settings. Operational systems matter, but wherever these systems contain human discretion, people matter too. Context and Methodology: I primarily focus on the operational effects of discretion in the healthcare setting, where the literature frequently examines how providers shape a service system. My research empirically responds to each of my research questions with modern econometric and machine learning methods. In the first essay, I designed and implemented a field experiment among 145 healthcare clinics. In the second and third essays, I leverage archival data analysis methods. Conclusion: Operations research considers many facets of work: “What work should we do? When should we do it? How should we do it? And who should be doing it?” Given my focus on the role of people within the system, my work provides valuable clarity into how human discretion affects operational outcomes, and my insights empower future operations research to better understand the full spectrum of worker behavior.Doctor of Philosoph

Estimating the Subsonic Aerodynamic Center and Moment Components for Swept Wings

An improved method is presented for estimating the subsonic location of the semispan aerodynamic center of a swept wing and the aerodynamic moment components about that aerodynamic center. The method applies to wings with constant linear taper and constant quarter-chord sweep. The results of a computational fluid dynamics study for 236 wings show that the position of the semispan aerodynamic center of a wing depends primarily on aspect ratio, taper ratio, and quarter-chord sweep angle. Wing aspect ratio was varied from 4.0 to 20, taper ratios from 0.25 to 1.0 were investigated quarter-chord sweep angles were varied from 0 to 50 deg. and linear geometric washout was varied from -4.0 to +8.0 deg. All wings and airfoil sections from the NACA 4-digit airfoil sweries with camber varied from 0 to 4% and thickness ranging from 6 to 18%. Within the range of parameters studied, wing camber, thickness and twist were shown to have significant effect on the position of the semispan aerodynamic center. The results of this study provide improved resolution of the semispan aerodynamic center and moment componennts for conceptual designs and analysis

Pitch Dynamics of Unmanned Aerial Vehicles

Dynamic stability requirements for manned aircraft have been in place for many years. However, we cannot expect stability constraints for UAVs to match those for manned aircraft; and dynamic stability requirements specific to UAVs have not been developed. The boundaries of controllability for both remotely-piloted and auto-piloted aircraft must be established before UAV technology can reach its full potential. The development of dynamic stability requirements specific to UAVs could improve flying qualities and facilitate more efficient UAV designs to meet specific mission requirements. As a first step to developing UAV stability requirements in general, test techniques must be established that will allow the stability characteristics of current UAVs to be quantified. This paper consolidates analytical details associated with procedures that could be used to experimentally determine the pitch stability boundaries for good UAV flying qualities. The procedures require determining only the maneuver margin and pitch radius of gyration and are simple enough to be used in an educational setting where resources are limited. The premise is that these procedures could be applied to UAVs now in use, in order to characterize the longitudinal flying qualities of current aircraft. This is but a stepping stone to the evaluation of candidate metrics for establishing flying-quality constraints for unmanned aircraft

Impact of Agricultural Communication Interventions on Improving Agricultural Productivity in Malawi

Agricultural communication (AGCOM) has been known to aid in disseminating research-based agricultural information among Malawian farmers. In 1958 the Malawi Government, via the Ministry of Agriculture, established the Agricultural Communications Branch (ACB) in an attempt to increase access to and adoption of scientifically-proven technologies among farmers. Moreover, in 2000 the Malawi Government started implementing an agricultural extension policy that promoted pluralistic demand-driven extension, which led to the increased availability of non-governmental organizations providing AGCOM services to farmers. However, after several decades of using different communication tools to promote new technologies, low productivity in most small holder farms remains a challenge, with limited adoption of improved technology as one of the contributing factors. In this exploratory, convergent, mixed methods study, 30 Malawian farmers and six AGCOM officers who were selected using convenient and snow ball sampling respectively participated in key informant interviews. In addition, 64 AGCOM officers who were selected using simple random sampling were involved in a survey. The findings of the study revealed that information delivered to farmers does not address farmer needs in most cases. Specifically, existing policies, source and availability of funding, and the agricultural calendar influenced choice of information that was disseminated. For example,the existing policy does not allow AGCOM officers to disseminate local and innovative farmer practices unless they are tested and approved by scientists. Such policies, perpetuates a mindset among farmers that innovations originate from outside their communities, thereby making it hard for them to share their local, indigenous ideas with their colleagues. Moreover, it has contributed to the inability of AGCOM to be used as an innovation creation tool, hence AGCOMs’ limited impact

Beryllium increases the CD14^dimCD16+ subset in the lung of chronic beryllium disease

CD14dimCD16+ and CD14brightCD16+ cells, which compose a minor population of monocytes in human peripheral blood mononuclear cells (PBMC), have been implicated in several inflammatory diseases. The aim of this study was to investigate whether this phenotype was present as a subset of lung infiltrative alveolar macrophages (AMs) in the granulomatous lung disease, chronic beryllium disease (CBD). The monocytes subsets was determined from PBMC cells and bronchoalveolar lavage (BAL) cells from CBD, beryllium sensitized Non-smoker (BeS-NS) and healthy subjects (HS) using flow cytometry. The impact of smoking on the AMs cell phenotype was determined by using BAL cells from BeS smokers (BeS-S). In comparison with the other monocyte subpopulations, CD14dimCD16+ cells were at decreased frequency in PBMCs of both BeS-NS and CBD and showed higher HLA-DR expression, compared to HS. The AMs from CBD and BeS-NS demonstrated a CD14dimCD16+phenotype, while CD14brightCD16+ cells were found at increased frequency in AMs of BeS, compared to HS. Fresh AMs from BeS-NS and CBD demonstrated significantly greater CD16, CD40, CD86 and HLA-DR than HS and BeS-S. The expression of CD16 on AMs from both CBD and BeS-NS was downregulated significantly after 10μM BeSO4 stimulation. The phagocytic activity of AMs decreased after 10μM BeSO4 treatment in both BeS-NS and CBD, although was altered or reduced in HS and BeS-S. These results suggest that Be increases the CD14dimCD16+ subsets in the lung of CBD subjects. We speculate that Be-stimulates the compartmentalization of a more mature CD16+ macrophage phenotype and that in turn these macrophages are a source of Th1 cytokines and chemokines that perpetuate the Be immune response in CBD. The protective effect of cigarette smoking in BeS-S may be due to the low expression of co-stimulatory markers on AMs from smokers as well as the decreased phagocytic function

Correlating changes in lung function with patient outcomes in chronic obstructive pulmonary disease: a pooled analysis

Background Relationships between improvements in lung function and other clinical outcomes in chronic obstructive pulmonary disease (COPD) are not documented extensively. We examined whether changes in trough forced expiratory volume in 1 second (FEV1) are correlated with changes in patient-reported outcomes. Methods Pooled data from three indacaterol studies (n = 3313) were analysed. Means and responder rates for outcomes including change from baseline in Transition Dyspnoea Index (TDI), St. George's Respiratory Questionnaire (SGRQ) scores (at 12, 26 and 52 weeks), and COPD exacerbation frequency (rate/year) were tabulated across categories of ΔFEV1. Also, generalised linear modelling was performed adjusting for covariates such as baseline severity and inhaled corticosteroid use. Results With increasing positive ΔFEV1, TDI and ΔSGRQ improved at all timepoints, exacerbation rate over the study duration declined (P < 0.001). Individual-level correlations were 0.03-0.18, but cohort-level correlations were 0.79-0.95. At 26 weeks, a 100 ml increase in FEV1 was associated with improved TDI (0.46 units), ΔSGRQ (1.3-1.9 points) and exacerbation rate (12% decrease). Overall, adjustments for baseline covariates had little impact on the relationship between ΔFEV1 and outcomes. Conclusions These results suggest that larger improvements in FEV1 are likely to be associated with larger patient-reported benefits across a range of clinical outcomes

Effect of Fluticasone Furoate and Vilanterol on Exacerbations of COPD in Patients with Moderate Airflow Obstruction

BACKGROUND: Inhaled corticosteroids have been shown to decrease exacerbations in COPD patients with moderate to severe COPD. Their effect in patients with milder airflow obstruction remains unclear.OBJECTIVE: This was an analysis of exacerbations in the Study to Understand Mortality and MorbidITy (SUMMIT) study.DESIGN: In a double-blind randomized controlled trial, once daily inhaled placebo, fluticasone furoate (FF, 100 μg), vilanterol (VI, 25 μg) or the combination (FF/VI) was administered. The primary outcome was all-cause mortality. Exacerbations of COPD were an additional pre-defined endpoint.SETTING: 1,368 centers in 43 countries.PARTICIPANTS: 16,485 patients with moderate COPD and heightened cardiovascular risk.RESULTS: Compared with placebo, FF/VI reduced the rate of moderate/severe exacerbations by 29% (95% CI 22, 35; p&lt;0.001) and the rate of hospitalized exacerbations by 27 % (95% CI 13, 39; p&lt;0.001). These relative effects were similar regardless of whether subjects had a history of exacerbation in the year prior to the study or an FEV1 less than or ≥ 60% predicted. The number needed to treat was not influenced by baseline FEV1 but was influenced by the prior history of exacerbations. FF/VI also reduced the rate of exacerbations treated with corticosteroids alone or with corticosteroids and antibiotics but not those treated with antibiotics alone.CONCLUSIONS: Patients with moderate chronic airflow obstruction experienced a reduction in exacerbations with FF/VI, compared with placebo, irrespective of a prior history of exacerbations or baseline FEV1. Clinical trial registration available at www.clinicaltrials.gov, ID NCT01313676.</p

Budesonide/formoterol as effective as prednisolone plus formoterol in acute exacerbations of COPD A double-blind, randomised, non-inferiority, parallel-group, multicentre study

<p>Abstract</p> <p>Background</p> <p>Oral corticosteroids and inhaled bronchodilators with or without antibiotics represent standard treatment of COPD exacerbations of moderate severity. Frequent courses of oral steroids may be a safety issue. We wanted to evaluate in an out-patient setting whether a 2-week course of inhaled budesonide/formoterol would be equally effective for treatment of acute COPD exacerbations as standard therapy in patients judged by the investigator not to require hospitalisation.</p> <p>Methods</p> <p>This was a double-blind, randomised, non-inferiority, parallel-group, multicentre study comparing two treatment strategies; two weeks' treatment with inhaled budesonide/formoterol (320/9 μg, qid) was compared with prednisolone (30 mg once daily) plus inhaled formoterol (9 μg bid) in patients with acute exacerbations of COPD attending a primary health care centre. Inclusion criteria were progressive dyspnoea for less than one week, FEV₁30–60% of predicted normal after acute treatment with a single dose of oral corticosteroid plus nebulised salbutamol/ipratropium bromide and no requirement for subsequent immediate hospitalisation, i.e the clinical status after the acute treatment allowed for sending the patient home.</p> <p>A total of 109 patients (mean age 67 years, 33 pack-years, mean FEV₁45% of predicted) were randomized to two weeks' double-blind treatment with budesonide/formoterol or prednisolone plus formoterol and subsequent open-label budesonide/formoterol (320/9 μg bid) for another 12 weeks. Change in FEV₁was the primary efficacy variable. Non-inferiority was predefined.</p> <p>Results</p> <p>Non-inferiority of budesonide/formoterol was proven because the lower limit of FEV₁-change (97.5% CI) was above 90% of the efficacy of the alternative treatment. Symptoms, quality of life, treatment failures, need for reliever medication (and exacerbations during follow-up) did not differ between the groups. No safety concerns were identified.</p> <p>Conclusion</p> <p>High dose budesonide/formoterol was as effective as prednisolone plus formoterol for the ambulatory treatment of acute exacerbations in non-hospitalized COPD patients. An early increase in budesonide/formoterol dose may therefore be tried before oral corticosteroids are used.</p> <p>Clinical trial registration</p> <p>NCT00259779</p