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Sample records for acute exacerbation events

  1. Acute exacerbation of COPD.

    PubMed

    Ko, Fanny W; Chan, Ka Pang; Hui, David S; Goddard, John R; Shaw, Janet G; Reid, David W; Yang, Ian A

    2016-10-01

    The literature of acute exacerbation of chronic obstructive pulmonary disease (COPD) is fast expanding. This review focuses on several aspects of acute exacerbation of COPD (AECOPD) including epidemiology, diagnosis and management. COPD poses a major health and economic burden in the Asia-Pacific region, as it does worldwide. Triggering factors of AECOPD include infectious (bacteria and viruses) and environmental (air pollution and meteorological effect) factors. Disruption in the dynamic balance between the 'pathogens' (viral and bacterial) and the normal bacterial communities that constitute the lung microbiome likely contributes to the risk of exacerbations. The diagnostic approach to AECOPD varies based on the clinical setting and severity of the exacerbation. After history and examination, a number of investigations may be useful, including oximetry, sputum culture, chest X-ray and blood tests for inflammatory markers. Arterial blood gases should be considered in severe exacerbations, to characterize respiratory failure. Depending on the severity, the acute management of AECOPD involves use of bronchodilators, steroids, antibiotics, oxygen and noninvasive ventilation. Hospitalization may be required, for severe exacerbations. Nonpharmacological interventions including disease-specific self-management, pulmonary rehabilitation, early medical follow-up, home visits by respiratory health workers, integrated programmes and telehealth-assisted hospital at home have been studied during hospitalization and shortly after discharge in patients who have had a recent AECOPD. Pharmacological approaches to reducing risk of future exacerbations include long-acting bronchodilators, inhaled steroids, mucolytics, vaccinations and long-term macrolides. Further studies are needed to assess the cost-effectiveness of these interventions in preventing COPD exacerbations.

  2. Acute exacerbations of fibrotic interstitial lung disease.

    PubMed

    Churg, Andrew; Wright, Joanne L; Tazelaar, Henry D

    2011-03-01

    An acute exacerbation is the development of acute lung injury, usually resulting in acute respiratory distress syndrome, in a patient with a pre-existing fibrosing interstitial pneumonia. By definition, acute exacerbations are not caused by infection, heart failure, aspiration or drug reaction. Most patients with acute exacerbations have underlying usual interstitial pneumonia, either idiopathic or in association with a connective tissue disease, but the same process has been reported in patients with fibrotic non-specific interstitial pneumonia, fibrotic hypersensitivity pneumonitis, desquamative interstitial pneumonia and asbestosis. Occasionally an acute exacerbation is the initial manifestation of underlying interstitial lung disease. On biopsy, acute exacerbations appear as diffuse alveolar damage or bronchiolitis obliterans organizing pneumonia (BOOP) superimposed upon the fibrosing interstitial pneumonia. Biopsies may be extremely confusing, because the acute injury pattern can completely obscure the underlying disease; a useful clue is that diffuse alveolar damage and organizing pneumonia should not be associated with old dense fibrosis and peripheral honeycomb change. Consultation with radiology can also be extremely helpful, because the fibrosing disease may be evident on old or concurrent computed tomography scans. The aetiology of acute exacerbations is unknown, and the prognosis is poor; however, some patients survive with high-dose steroid therapy.

  3. Acute interstitial pneumonia and acute exacerbations of idiopathic pulmonary fibrosis.

    PubMed

    Swigris, Jeffrey J; Brown, Kevin K

    2006-12-01

    Acute interstitial pneumonia (AIP) and acute exacerbations of idiopathic pulmonary fibrosis (AEIPF) are similar respiratory disorders characterized by the rapid development of progressive dyspnea and cough. Both frequently lead to respiratory failure and death. Pathologically, each is characterized by the presence of a diffuse alveolar damage (DAD) pattern; in AIP, DAD is the sole pattern, whereas in AEIPF DAD is superimposed upon a background usual interstitial pneumonia. They differ in that patients with AEIPF have preexisting idiopathic pulmonary fibrosis, whereas patients with AIP have no predisposing disorders to account for their disease. Because both presentations overlap with multiple other causes of acute lung injury, a comprehensive evaluation is necessary to rule out disorders such as overwhelming infection or congestive heart failure. Although a confident diagnosis can be achieved without it, a surgical lung biopsy is necessary to provide a definitive diagnosis. Despite minimal evidence, glucocorticoids are frequently begun once microbiological evaluation confirms the absence of infection. Despite therapy, the case fatality rate ranges up to 70% for both, with most patients dying in the first 2 weeks. Survivors of the acute event can recover to their previous baseline; however, most AIP survivors will stabilize with some functional impairment, whereas in those with AEIPF, progressive fibrosis with functional deterioration is the rule.

  4. Prevention of Acute Exacerbations of COPD

    PubMed Central

    Bourbeau, Jean; Diekemper, Rebecca L.; Ouellette, Daniel R.; Goodridge, Donna; Hernandez, Paul; Curren, Kristen; Balter, Meyer S.; Bhutani, Mohit; Camp, Pat G.; Celli, Bartolome R.; Dechman, Gail; Dransfield, Mark T.; Fiel, Stanley B.; Foreman, Marilyn G.; Hanania, Nicola A.; Ireland, Belinda K.; Marchetti, Nathaniel; Marciniuk, Darcy D.; Mularski, Richard A.; Ornelas, Joseph; Stickland, Michael K.

    2015-01-01

    BACKGROUND: COPD is a major cause of morbidity and mortality in the United States as well as throughout the rest of the world. An exacerbation of COPD (periodic escalations of symptoms of cough, dyspnea, and sputum production) is a major contributor to worsening lung function, impairment in quality of life, need for urgent care or hospitalization, and cost of care in COPD. Research conducted over the past decade has contributed much to our current understanding of the pathogenesis and treatment of COPD. Additionally, an evolving literature has accumulated about the prevention of acute exacerbations. METHODS: In recognition of the importance of preventing exacerbations in patients with COPD, the American College of Chest Physicians (CHEST) and Canadian Thoracic Society (CTS) joint evidence-based guideline (AECOPD Guideline) was developed to provide a practical, clinically useful document to describe the current state of knowledge regarding the prevention of acute exacerbations according to major categories of prevention therapies. Three key clinical questions developed using the PICO (population, intervention, comparator, and outcome) format addressed the prevention of acute exacerbations of COPD: nonpharmacologic therapies, inhaled therapies, and oral therapies. We used recognized document evaluation tools to assess and choose the most appropriate studies and to extract meaningful data and grade the level of evidence to support the recommendations in each PICO question in a balanced and unbiased fashion. RESULTS: The AECOPD Guideline is unique not only for its topic, the prevention of acute exacerbations of COPD, but also for the first-in-kind partnership between two of the largest thoracic societies in North America. The CHEST Guidelines Oversight Committee in partnership with the CTS COPD Clinical Assembly launched this project with the objective that a systematic review and critical evaluation of the published literature by clinical experts and researchers in

  5. [Management of acute exacerbations of COPD].

    PubMed

    Rabbat, A; Guetta, A; Lorut, C; Lefebvre, A; Roche, N; Huchon, G

    2010-10-01

    Exacerbations of COPD are common and cause a considerable burden to the patient and the healthcare system. To optimize the hospital care of patients with exacerbations of COPD, clinicians should be aware of some key points: management of exacerbations is broadly based on clinical features and severity. Initial clinical evaluation is crucial to define those patients requiring hospital admission and those who could be managed as outpatients. In hospitalized patients, the appropriate level of care should be determined by the initial severity and response to initial medical treatment. Medical treatment should follow recent recommendations, including rest, titrated oxygen therapy, inhaled or nebulized short-acting bronchodilators (Beta2-agonists and anticholinergic agents), DVT prevention with LMWH, steroids in most severely ill patients, unless there are contraindications and antibiotics in the case of a clear bacterial infectious aetiology. Severe exacerbations may lead to acute hypercapnic respiratory failure. Unless contraindicated, non-invasive ventilation (NIV) should be the first line ventilatory support for these patients. NIV should be commenced early, before severe acidosis ensues, to avoid the need for endotracheal intubation and to reduce mortality and treatment failures. Several randomised controlled clinical trials support the use of NIV in the management of acute exacerbations of COPD, demonstrating a decreased need for mechanical ventilation and an improved survival. In most severe cases, NIV should be provided in ICU. Although it has been shown that for less severe patients (with pH values>7.30), NIV can be administered safely and effectively on general medical wards, a lead respiratory consultant and trained nurses are mandatory. Mechanical ventilation through an endotracheal tube should be considered when patients have contraindications to the use of NIV or fail to improve on NIV. The duration of mechanical ventilation should be shortened as much as

  6. Acute Exacerbation of Idiopathic Pulmonary Fibrosis Following Treatment for Cushing's Syndrome.

    PubMed

    Ohara, Nobumasa; Kaneko, Masanori; Sato, Kazuhiro; Usuda, Hiroyuki; Tanaka, Junta; Maekawa, Takashi; Sasano, Hironobu; Katakami, Hideki; Kaneko, Kenzo; Kamoi, Kyuzi

    2016-01-01

    A 64-year-old Japanese man with mild reticular shadows in both lungs developed a lung tumor causing ectopic Cushing's syndrome. He was prescribed an adrenal inhibitor, which controlled his hypercortisolemia. However, he developed acute exacerbation of idiopathic pulmonary fibrosis (IPF) and died within weeks. Previous studies have suggested a dosage reduction of corticosteroids for IPF as a triggering event for acute exacerbation. The present case suggests that IPF coexisting with Cushing's syndrome may have been exacerbated after the correction of hypercortisolemia. Therefore, close monitoring of cortisol levels along with the clinical course of IPF is required in similar cases that require the correction of hypercortisolemia. PMID:26875965

  7. Acute Exacerbation of Idiopathic Pulmonary Fibrosis Following Treatment for Cushing's Syndrome.

    PubMed

    Ohara, Nobumasa; Kaneko, Masanori; Sato, Kazuhiro; Usuda, Hiroyuki; Tanaka, Junta; Maekawa, Takashi; Sasano, Hironobu; Katakami, Hideki; Kaneko, Kenzo; Kamoi, Kyuzi

    2016-01-01

    A 64-year-old Japanese man with mild reticular shadows in both lungs developed a lung tumor causing ectopic Cushing's syndrome. He was prescribed an adrenal inhibitor, which controlled his hypercortisolemia. However, he developed acute exacerbation of idiopathic pulmonary fibrosis (IPF) and died within weeks. Previous studies have suggested a dosage reduction of corticosteroids for IPF as a triggering event for acute exacerbation. The present case suggests that IPF coexisting with Cushing's syndrome may have been exacerbated after the correction of hypercortisolemia. Therefore, close monitoring of cortisol levels along with the clinical course of IPF is required in similar cases that require the correction of hypercortisolemia.

  8. On the Pathogenesis of Acute Exacerbations of Mucoobstructive Lung Diseases.

    PubMed

    Boucher, Richard C

    2015-11-01

    Mucoobstructive lung diseases have highlighted the importance of a proper description of the normal mucus clearance system. A useful description of the normal mucus clearance apparatus requires the presence of two gels on the airway surface (i.e., a mucus layer gel and a periciliary gel). Importantly, most mucoobstructive lung diseases are distributed heterogeneously in the lung, and exacerbations may reflect spread of the disease to previously normal areas. The spread may reflect disturbances in the balance of water between the two gel layers, producing heterogeneous mucus adhesion and infection within the lung. Ultimately, spread can produce losses of lung function that may be associated with acute exacerbation frequency.

  9. On the Pathogenesis of Acute Exacerbations of Mucoobstructive Lung Diseases

    PubMed Central

    2015-01-01

    Mucoobstructive lung diseases have highlighted the importance of a proper description of the normal mucus clearance system. A useful description of the normal mucus clearance apparatus requires the presence of two gels on the airway surface (i.e., a mucus layer gel and a periciliary gel). Importantly, most mucoobstructive lung diseases are distributed heterogeneously in the lung, and exacerbations may reflect spread of the disease to previously normal areas. The spread may reflect disturbances in the balance of water between the two gel layers, producing heterogeneous mucus adhesion and infection within the lung. Ultimately, spread can produce losses of lung function that may be associated with acute exacerbation frequency. PMID:26595733

  10. Endothelial RAGE exacerbates acute postischaemic cardiac inflammation.

    PubMed

    Ziegler, Tilman; Horstkotte, Melanie; Lange, Philipp; Ng, Judy; Bongiovanni, Dario; Hinkel, Rabea; Laugwitz, Karl-Ludwig; Sperandio, Markus; Horstkotte, Jan; Kupatt, Christian

    2016-08-01

    Advanced glycation end-products (AGEs) interact with their receptor RAGE, leading to an inflammatory state. We investigated the role of RAGE in postischaemic leukocyte adhesion after myocardial infarction and its effect on postischaemic myocardial function. Wildtype (WT), ICAM-1-/-, RAGE-/- or ICAM-1/RAGE-/- mice underwent 20 minutes (min) of LAD-occlusion followed by 15 min of reperfusion. We applied in vivo fluorescence microscopy visualising Rhodamine-6G labelled leukocytes. To differentiate between endothelial and leukocyte RAGE, we generated bone marrow chimeric mice. Invasive hemodynamic measurements were performed in mice undergoing 45 min of myocardial ischaemia (via LAD-occlusion) followed by 24 hours of reperfusion. Left-ventricular developed pressure (LVDP) was assessed by insertion of a millar-tip catheter into the left ventricle. In the acute model of myocardial ischaemia, leukocyte retention (WT 68 ± 4 cells/hpf) was significantly reduced in ICAM-1-/- (40 ± 3 cells/hpf) and RAGE-/- mice (38 ± 4 cells/hpf). ICAM-1/RAGE-/- mice displayed an additive reduction of leukocyte retention (ICAM-1/RAGE-/- 15 ± 3 cells/hpf). Ly-6G+ neutrophil were predominantly reduced in ICAM-1/RAGE-/- hearts (28 %), whereas Ly-6C+ proinflammatory monocytes decreased to a lesser extent (55 %). Interestingly, PMN recruitment was not affected in chimeric mice with RAGE deficiency in BM cells (WT mice reconstituted with ICAM-1/RAGE-/- BM: 55 ± 4 cells/hpf) while in mice with global RAGE deficiency (ICAM-1/RAGE-/- mice reconstituted with ICAM-1/RAGE-/- BM) leucocyte retention was significantly reduced (13 ± 1 cells/hpf), similar to non-transplanted ICAM/RAGE-/- mice. Furthermore, postischaemic LVDP increased in ICAM-1/RAGE-/- animals (98 ± 4 mmHg vs 86 ± 4 mmHg in WT mice). In conclusion, combined deficiency of ICAM-1 and RAGE reduces leukocyte influx into infarcted myocardium and improves LV function during the acute phase after myocardial ischaemia and reperfusion

  11. [Perioperative lung injury: acute exacerbation of idiopathic pulmonary fibrosis and acute interstitial pneumonia after pulmonary resection].

    PubMed

    Hoshikawa, Yasushi; Kondo, Takashi

    2004-12-01

    The mortality rate after surgical resection for lung cancer has been reported to range between 1% and 3%, with 30% caused by acute exacerbation of idiopathic pulmonary fibrosis (IPF) or acute interstitial pneumonia (AIP). Approximately 20% of patients with IPF have lung cancer, while 2% to 4% of lung cancer patients have IPF. The incidence of postoperative acute exacerbation of IPF is about 20%. Some investigations in Japan revealed that 10% to 17% of lung cancer patients undergoing lung resection, who have not been diagnosed with IPF preoperatively, have localized-usual interstitial pneumonia (Lo-UIP) lesions. Approximately 20% of patients with Lo-UIP show postoperative acute exacerbation, while about 0.5% of those without Lo-UIP develop AIP after surgery. There is no confirmed treatment or prophylaxis. Most patients who develop postoperative acute exacerbation or AIP are treated with methylpredonisolone (1,000 mg/day x 3 days), but the mortality rate is 50% or greater. We emphasize that more efforts should be made to develop strategies to prevent postoperative acute exacerbation of IPF and AIP.

  12. Tryptophan catabolism in acute exacerbations of chronic obstructive pulmonary disease

    PubMed Central

    Gulcev, Makedonka; Reilly, Cavan; Griffin, Timothy J; Broeckling, Corey D; Sandri, Brian J; Witthuhn, Bruce A; Hodgson, Shane W; Woodruff, Prescott G; Wendt, Chris H

    2016-01-01

    Introduction Exacerbations are a leading cause of morbidity in COPD. The objective of this study was to identify metabolomic biomarkers of acute exacerbations of COPD (AECOPD). Methods We measured metabolites via mass spectrometry (MS) in plasma drawn within 24 hours of admission to the hospital for 33 patients with an AECOPD (day 0) and 30 days later and for 65 matched controls. Individual metabolites were measured via selective reaction monitoring with mass spectrometry. We used a mixed-effect model to compare metabolite levels in cases compared to controls and a paired t-test to test for differences between days 0 and 30 in the AECOPD group. Results We identified 377 analytes at a false discovery rate of 5% that differed between cases (day 0) and controls, and 31 analytes that differed in the AECOPD cases between day 0 and day 30 (false discovery rate: 5%). Tryptophan was decreased at day 0 of AECOPD compared to controls corresponding to an increase in indoleamine 2,3-dioxygenase activity. Conclusion Patients with AECOPD have a unique metabolomic signature that includes a decrease in tryptophan levels consistent with an increase in indoleamine 2,3-dioxygenase activity. PMID:27729784

  13. Fine particulate matter in acute exacerbation of COPD

    PubMed Central

    Ni, Lei; Chuang, Chia-Chen; Zuo, Li

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) is a common airway disorder. In particular, acute exacerbations of COPD (AECOPD) can significantly reduce pulmonary function. The majority of AECOPD episodes are attributed to infections, although environmental stress also plays a role. Increasing urbanization and associated air pollution, especially in developing countries, have been shown to contribute to COPD pathogenesis. Elevated levels of particulate matter (PM) in polluted air are strongly correlated with the onset and development of various respiratory diseases. In this review, we have conducted an extensive literature search of recent studies of the role of PM2.5 (fine PM) in AECOPD. PM2.5 leads to AECOPD via inflammation, oxidative stress (OS), immune dysfunction, and altered airway epithelial structure and microbiome. Reducing PM2.5 levels is a viable approach to lower AECOPD incidence, attenuate COPD progression and decrease the associated healthcare burden. PMID:26557095

  14. Acute Exacerbation of Idiopathic Pulmonary Fibrosis. An International Working Group Report.

    PubMed

    Collard, Harold R; Ryerson, Christopher J; Corte, Tamera J; Jenkins, Gisli; Kondoh, Yasuhiro; Lederer, David J; Lee, Joyce S; Maher, Toby M; Wells, Athol U; Antoniou, Katerina M; Behr, Juergen; Brown, Kevin K; Cottin, Vincent; Flaherty, Kevin R; Fukuoka, Junya; Hansell, David M; Johkoh, Takeshi; Kaminski, Naftali; Kim, Dong Soon; Kolb, Martin; Lynch, David A; Myers, Jeffrey L; Raghu, Ganesh; Richeldi, Luca; Taniguchi, Hiroyuki; Martinez, Fernando J

    2016-08-01

    Acute exacerbation of idiopathic pulmonary fibrosis has been defined as an acute, clinically significant, respiratory deterioration of unidentifiable cause. The objective of this international working group report on acute exacerbation of idiopathic pulmonary fibrosis was to provide a comprehensive update on the topic. A literature review was conducted to identify all relevant English text publications and abstracts. Evidence-based updates on the epidemiology, etiology, risk factors, prognosis, and management of acute exacerbations of idiopathic pulmonary fibrosis are provided. Finally, to better reflect the current state of knowledge and improve the feasibility of future research into its etiology and treatment, the working group proposes a new conceptual framework for acute respiratory deterioration in idiopathic pulmonary fibrosis and a revised definition and diagnostic criteria for acute exacerbation of idiopathic pulmonary fibrosis.

  15. Acute Exacerbation of Idiopathic Pulmonary Fibrosis. An International Working Group Report.

    PubMed

    Collard, Harold R; Ryerson, Christopher J; Corte, Tamera J; Jenkins, Gisli; Kondoh, Yasuhiro; Lederer, David J; Lee, Joyce S; Maher, Toby M; Wells, Athol U; Antoniou, Katerina M; Behr, Juergen; Brown, Kevin K; Cottin, Vincent; Flaherty, Kevin R; Fukuoka, Junya; Hansell, David M; Johkoh, Takeshi; Kaminski, Naftali; Kim, Dong Soon; Kolb, Martin; Lynch, David A; Myers, Jeffrey L; Raghu, Ganesh; Richeldi, Luca; Taniguchi, Hiroyuki; Martinez, Fernando J

    2016-08-01

    Acute exacerbation of idiopathic pulmonary fibrosis has been defined as an acute, clinically significant, respiratory deterioration of unidentifiable cause. The objective of this international working group report on acute exacerbation of idiopathic pulmonary fibrosis was to provide a comprehensive update on the topic. A literature review was conducted to identify all relevant English text publications and abstracts. Evidence-based updates on the epidemiology, etiology, risk factors, prognosis, and management of acute exacerbations of idiopathic pulmonary fibrosis are provided. Finally, to better reflect the current state of knowledge and improve the feasibility of future research into its etiology and treatment, the working group proposes a new conceptual framework for acute respiratory deterioration in idiopathic pulmonary fibrosis and a revised definition and diagnostic criteria for acute exacerbation of idiopathic pulmonary fibrosis. PMID:27299520

  16. Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease

    PubMed Central

    Soler-Cataluna, J; Martinez-Garcia, M; Roman, S; Salcedo, E; Navarro, M; Ochando, R

    2005-01-01

    Background: Patients with chronic obstructive pulmonary disease (COPD) often present with severe acute exacerbations requiring hospital treatment. However, little is known about the prognostic consequences of these exacerbations. A study was undertaken to investigate whether severe acute exacerbations of COPD exert a direct effect on mortality. Methods: Multivariate techniques were used to analyse the prognostic influence of acute exacerbations of COPD treated in hospital (visits to the emergency service and admissions), patient age, smoking, body mass index, co-morbidity, long term oxygen therapy, forced spirometric parameters, and arterial blood gas tensions in a prospective cohort of 304 men with COPD followed up for 5 years. The mean (SD) age of the patients was 71 (9) years and forced expiratory volume in 1 second was 46 (17)%. Results: Only older age (hazard ratio (HR) 5.28, 95% CI 1.75 to 15.93), arterial carbon dioxide tension (HR 1.07, 95% CI 1.02 to 1.12), and acute exacerbations of COPD were found to be independent indicators of a poor prognosis. The patients with the greatest mortality risk were those with three or more acute COPD exacerbations (HR 4.13, 95% CI 1.80 to 9.41). Conclusions: This study shows for the first time that severe acute exacerbations of COPD have an independent negative impact on patient prognosis. Mortality increases with the frequency of severe exacerbations, particularly if these require admission to hospital. PMID:16055622

  17. Viral epidemiology of acute exacerbations of chronic obstructive pulmonary disease.

    PubMed

    Dimopoulos, G; Lerikou, M; Tsiodras, S; Chranioti, Aik; Perros, E; Anagnostopoulou, U; Armaganidis, A; Karakitsos, P

    2012-02-01

    The role of viruses in Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) needs further elucidation. The aim of the present study was to evaluate the molecular epidemiology of viral pathogens in AECOPD. Patients presenting to the Emergency Room with AECOPD needing hospitalization were recruited. Oropharyngeal and sputum samples were collected in order to perform microarrays-based viral testing for the detection of respiratory viruses. A total of 200 (100%) patients were analyzed and from them in 107 (53.5%) a virus was detected. The commonest identified viruses were the human Respiratory Syncytial Virus (subtypes A and B) (40.5%), influenza virus (subtypes A, B, C) (11%), rhinovirus (8%) and human Parainfluenza Virus (subtypes A and B) (7.5%). A bacterial pathogen was isolated in 27 (14%) patients and a dual infection due to a bacterial and a viral pathogen was recognised in 14/107 patients. Patients with AECOPD and a viral infection had a lengthier hospital stay (9.2 ± 4.6 vs 7.6 ± 4.3, p < 0.01) while the severity of the disease was no related with significant differences among the groups of the study population. In conclusion, the isolation of a virus was strongly associated with AECOPD in the examined population. The stage of COPD appeared to have no relation with the frequency of the isolated viruses while dual infection with a viral and a bacterial pathogen was not rare.

  18. Acute exacerbation of COPD: is it the “stroke of the lungs”?

    PubMed Central

    Hillas, Georgios; Perlikos, Fotis; Tzanakis, Nikolaos

    2016-01-01

    Chronic obstructive pulmonary disease (COPD) is one of the top five major causes of morbidity and mortality worldwide. Despite worldwide health care efforts, costs, and medical research, COPD figures demonstrate a continuously increasing tendency in mortality. This is contrary to other top causes of death, such as neoplasm, accidents, and cardiovascular disease. A major factor affecting COPD-related mortality is the acute exacerbation of COPD (AECOPD). Exacerbations and comorbidities contribute to the overall severity in individual patients. Despite the underestimation by the physicians and the patients themselves, AECOPD is a really devastating event during the course of the disease, similar to acute myocardial infarction in patients suffering from coronary heart disease. In this review, we focus on the evidence that supports the claim that AECOPD is the “stroke of the lungs”. AECOPD can be viewed as: a Semicolon or disease’s full-stop period, Triggering a catastrophic cascade, usually a Relapsing and Overwhelming event, acting as a Killer, needing Emergent treatment. PMID:27471380

  19. Viral epidemiology of acute exacerbations of chronic obstructive pulmonary disease.

    PubMed

    Dimopoulos, G; Lerikou, M; Tsiodras, S; Chranioti, Aik; Perros, E; Anagnostopoulou, U; Armaganidis, A; Karakitsos, P

    2012-02-01

    The role of viruses in Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) needs further elucidation. The aim of the present study was to evaluate the molecular epidemiology of viral pathogens in AECOPD. Patients presenting to the Emergency Room with AECOPD needing hospitalization were recruited. Oropharyngeal and sputum samples were collected in order to perform microarrays-based viral testing for the detection of respiratory viruses. A total of 200 (100%) patients were analyzed and from them in 107 (53.5%) a virus was detected. The commonest identified viruses were the human Respiratory Syncytial Virus (subtypes A and B) (40.5%), influenza virus (subtypes A, B, C) (11%), rhinovirus (8%) and human Parainfluenza Virus (subtypes A and B) (7.5%). A bacterial pathogen was isolated in 27 (14%) patients and a dual infection due to a bacterial and a viral pathogen was recognised in 14/107 patients. Patients with AECOPD and a viral infection had a lengthier hospital stay (9.2 ± 4.6 vs 7.6 ± 4.3, p < 0.01) while the severity of the disease was no related with significant differences among the groups of the study population. In conclusion, the isolation of a virus was strongly associated with AECOPD in the examined population. The stage of COPD appeared to have no relation with the frequency of the isolated viruses while dual infection with a viral and a bacterial pathogen was not rare. PMID:21983132

  20. Review of ventilatory techniques to optimize mechanical ventilation in acute exacerbation of chronic obstructive pulmonary disease

    PubMed Central

    Reddy, Raghu M; Guntupalli, Kalpalatha K

    2007-01-01

    Chronic obstructive pulmonary disease (COPD) is a major global healthcare problem. Studies vary widely in the reported frequency of mechanical ventilation in acute exacerbations of COPD. Invasive intubation and mechanical ventilation may be associated with significant morbidity and mortality. A good understanding of the airway pathophysiology and lung mechanics in COPD is necessary to appropriately manage acute exacerbations and respiratory failure. The basic pathophysiology in COPD exacerbation is the critical expiratory airflow limitation with consequent dynamic hyperinflation. These changes lead to further derangement in ventilatory mechanics, muscle function and gas exchange which may result in respiratory failure. This review discusses the altered respiratory mechanics in COPD, ways to detect these changes in a ventilated patient and formulating ventilatory techniques to optimize management of respiratory failure due to exacerbation of COPD. PMID:18268918

  1. Paliperidone Palmitate Once-Monthly Injectable Treatment for Acute Exacerbations of Schizoaffective Disorder

    PubMed Central

    Fu, Dong-Jing; Turkoz, Ibrahim; Simonson, R. Bruce; Walling, David; Schooler, Nina; Lindenmayer, Jean-Pierre; Canuso, Carla; Alphs, Larry

    2016-01-01

    Abstract The optimal treatment for schizoaffective disorder (SCA) is not well established. In this initial 6-month open-label treatment period of a large, multiphase, relapse-prevention study, the efficacy and safety of paliperidone palmitate once-monthly (PP1M) injectable were evaluated in subjects with symptomatic SCA. Subjects with acute exacerbation of SCA (ie, with psychotic and either depressive and/or manic symptoms) were enrolled and treated with PP1M either as monotherapy or in combination with antidepressants or mood stabilizers (combination therapy group). After flexible-dose treatment with PP1M for 13 weeks, stabilized subjects continued into a 12-week fixed-dose PP1M treatment period. A total of 667 subjects were enrolled; 320 received monotherapy and 347 received PP1M as combination therapy; 334 subjects completed the entire 25-week treatment. Statistically significant and clinically meaningful improvements from baseline were observed for all efficacy measures in psychosis (per Positive and Negative Syndrome Scale), mood symptoms (per Young Mania Rating Scale and Hamilton Depression Rating Scale—21 items), and functioning (per Personal and Social Performance Scale) from week 1 to all time points during the 25-week treatment period (P < 0.001). Similar improvements in efficacy measures were observed between subjects receiving monotherapy or combination therapy. Efficacy benefits persisted throughout the 25-week period. The most common adverse events were akathisia (11.1%), injection-site pain (10.6%), and insomnia (10.0%). Paliperidone palmitate once-monthly administered as monotherapy or in combination with mood stabilizers or antidepressants in patients with an acute exacerbation of SCA provided rapid, broad, and persistent reduction in psychotic, depressive, and manic symptoms, as well as improved functioning. PMID:27322760

  2. Paliperidone Palmitate Once-Monthly Injectable Treatment for Acute Exacerbations of Schizoaffective Disorder.

    PubMed

    Fu, Dong-Jing; Turkoz, Ibrahim; Simonson, R Bruce; Walling, David; Schooler, Nina; Lindenmayer, Jean-Pierre; Canuso, Carla; Alphs, Larry

    2016-08-01

    The optimal treatment for schizoaffective disorder (SCA) is not well established. In this initial 6-month open-label treatment period of a large, multiphase, relapse-prevention study, the efficacy and safety of paliperidone palmitate once-monthly (PP1M) injectable were evaluated in subjects with symptomatic SCA. Subjects with acute exacerbation of SCA (ie, with psychotic and either depressive and/or manic symptoms) were enrolled and treated with PP1M either as monotherapy or in combination with antidepressants or mood stabilizers (combination therapy group). After flexible-dose treatment with PP1M for 13 weeks, stabilized subjects continued into a 12-week fixed-dose PP1M treatment period. A total of 667 subjects were enrolled; 320 received monotherapy and 347 received PP1M as combination therapy; 334 subjects completed the entire 25-week treatment. Statistically significant and clinically meaningful improvements from baseline were observed for all efficacy measures in psychosis (per Positive and Negative Syndrome Scale), mood symptoms (per Young Mania Rating Scale and Hamilton Depression Rating Scale-21 items), and functioning (per Personal and Social Performance Scale) from week 1 to all time points during the 25-week treatment period (P < 0.001). Similar improvements in efficacy measures were observed between subjects receiving monotherapy or combination therapy. Efficacy benefits persisted throughout the 25-week period. The most common adverse events were akathisia (11.1%), injection-site pain (10.6%), and insomnia (10.0%). Paliperidone palmitate once-monthly administered as monotherapy or in combination with mood stabilizers or antidepressants in patients with an acute exacerbation of SCA provided rapid, broad, and persistent reduction in psychotic, depressive, and manic symptoms, as well as improved functioning. PMID:27322760

  3. Management of Acute Exacerbation of Asthma and Chronic Obstructive Pulmonary Disease in the Emergency Department.

    PubMed

    Suau, Salvador J; DeBlieux, Peter M C

    2016-02-01

    Acute asthma and chronic obstructive pulmonary disease (COPD) exacerbations are the most common respiratory diseases requiring emergent medical evaluation and treatment. Asthma and COPD are chronic, debilitating disease processes that have been differentiated traditionally by the presence or absence of reversible airflow obstruction. Asthma and COPD exacerbations impose an enormous economic burden on the US health care budget. In daily clinical practice, it is difficult to differentiate these 2 obstructive processes based on their symptoms, and on their nearly identical acute treatment strategies; major differences are important when discussing anatomic sites involved, long-term prognosis, and the nature of inflammatory markers. PMID:26614239

  4. A novel study design for antibiotic trials in acute exacerbations of COPD: MAESTRAL methodology

    PubMed Central

    Wilson, Robert; Anzueto, Antonio; Miravitlles, Marc; Arvis, Pierre; Faragó, Geneviève; Haverstock, Daniel; Trajanovic, Mila; Sethi, Sanjay

    2011-01-01

    Antibiotics, along with oral corticosteroids, are standard treatments for acute exacerbations of chronic obstructive pulmonary disease (AECOPD). The ultimate aims of treatment are to minimize the impact of the current exacerbation, and by ensuring complete resolution, reduce the risk of relapse. In the absence of superiority studies of antibiotics in AECOPD, evidence of the relative efficacy of different drugs is lacking, and so it is difficult for physicians to select the most effective antibiotic. This paper describes the protocol and rationale for MAESTRAL (moxifloxacin in AECBs [acute exacerbation of chronic bronchitis] trial; www.clinicaltrials.gov: NCT00656747), one of the first antibiotic comparator trials designed to show superiority of one antibiotic over another in AECOPD. It is a prospective, multinational, multicenter, randomized, double-blind controlled study of moxifloxacin (400 mg PO [ per os] once daily for 5 days) vs amoxicillin/clavulanic acid (875/125 mg PO twice daily for 7 days) in outpatients with COPD and chronic bronchitis suffering from an exacerbation. MAESTRAL uses an innovative primary endpoint of clinical failure: the requirement for additional or alternate treatment for the exacerbation at 8 weeks after the end of antibiotic therapy, powered for superiority. Patients enrolled are those at high-risk of treatment failure, and all are experiencing an Anthonisen type I exacerbation. Patients are stratified according to oral corticosteroid use to control their effect across antibiotic treatment arms. Secondary endpoints include quality of life, symptom assessments and health care resource use. PMID:21760724

  5. Pathogen-directed Therapy in Acute Exacerbations of Chronic Obstructive Pulmonary Disease

    PubMed Central

    Martinez, Fernando J.

    2007-01-01

    Acute exacerbations of chronic obstructive pulmonary disease (COPD) are important events in the natural history of this chronic lung disorder. These events can be caused by a large number of infectious and noninfectious agents and are associated with an increased local and systemic inflammatory response. Their frequency and severity have been linked to progressive deterioration in lung function and health status. Infectious pathogens ranging from viral to atypical and typical bacteria have been implicated in the majority of episodes. Most therapeutic regimens to date have emphasized broad, nonspecific approaches to bronchoconstriction and pulmonary inflammation. Increasingly, therapy that targets specific etiologic pathogens has been advocated. These include clinical and laboratory-based methods to identify bacterial infections. Further additional investigation has suggested specific pathogens within this broad class. As specific antiviral therapies become available, better diagnostic approaches to identify specific pathogens will be required. Furthermore, prophylactic therapy for at-risk individuals during high-risk times may become a standard therapeutic approach. As such, the future will likely include aggressive diagnostic algorithms based on the combination of clinical syndromes and rapid laboratory modalities to identify specific causative bacteria or viruses. PMID:18073397

  6. Management of chronic obstructive pulmonary disease patients after hospitalization for acute exacerbation.

    PubMed

    Osthoff, Mirjam; Leuppi, Jörg D

    2010-01-01

    The objective of this review is to sum up the literature regarding the management of patients with chronic obstructive pulmonary disease (COPD) after hospitalization for an acute exacerbation. Guidelines recommend a follow-up 4-6 weeks after hospitalization to assess coping strategies, inhaler technique, the need for long-term oxygen therapy and the measurement of FEV(1). This review discusses the follow-up of patients with exacerbations of COPD, the use and value of spirometry in their further management, the potential benefit of home monitoring, the value of long-term oxygen therapy, the value of self-management programs including the use of action plans, the potential benefit of noninvasive ventilation as well as the value of early rehabilitation. There is not enough literature to allow specific recommendations and to define components of a care plan after hospitalization for an acute exacerbation; however, early rehabilitation should be included.

  7. [Acute bacterial exacerbation of chronic obstructive pulmonary disease and biofilm].

    PubMed

    Legnani, Delfino

    2009-07-01

    The lower respiratory tract of patients affected by COPD is constantly colonized by pathogenic microrganisms such as H. influenzae, M. catarrhalis and S. pneumoniae. Role of bacterial colonization of big and small airways in patients affected by COPD is still unclear but it is likely to play a role in directly or indirectly maintaining the vicious circle of infection/inflammation. Colonizer pathogens are capable to stimulate mucus production, to alter the ciliary function by inducing dyskinesia and stasis; in addition, they represent a strong stimulus for neutrophils to come in the airways, which release elastase that, in turn, inhibit the mucus-ciliary function. The same pathogens are responsible for epithelial damage and chronic inflammation, by releasing neutrophilic elastase, leading to the damage progression and obstruction. Recent studies have also shown that infection sustained by H. influenzae is not limited to bronchial mucosa, i.e. surface epithelial cells, but that the pathogen is capable to penetrate cells, so spreading the infection in sub-epithelial cellular layers. In addition, the ability to produce biofilm is another possible defence mechanism which allows them to grow and colonise. Such a mechanism could in part explain the lack of response to antimicrobials and contribute to stimulation of parenchymal inflammatory response, the cause of pathological-anatomic damage which occurs in COPD. The impossibility to eradicate chronic infection and bacterial exacerbations of COPD are likely the elements that promt and worsen obstruction, so determining the disease's progression. PMID:19696555

  8. The inflammasome pathway in stable COPD and acute exacerbations

    PubMed Central

    Faner, Rosa; Sobradillo, Patricia; Noguera, Aina; Gomez, Cristina; Cruz, Tamara; López-Giraldo, Alejandra; Ballester, Eugeni; Soler, Nestor; Arostegui, Juan I.; Pelegrín, Pablo; Rodriguez-Roisin, Roberto; Yagüe, Jordi; Cosio, Borja G.; Juan, Manel

    2016-01-01

    Chronic obstructive pulmonary disease (COPD) is characterised by pulmonary and systemic inflammation that bursts during exacerbations of the disease (ECOPD). The NLRP3 inflammasome is a key regulatory molecule of the inflammatory response. Its role in COPD is unclear. We investigated the NLRP3 inflammasome status in: 1) lung tissue samples from 38 patients with stable COPD, 15 smokers with normal spirometry and 14 never-smokers; and 2) sputum and plasma samples from 56 ECOPD patients, of whom 41 could be reassessed at clinical recovery. We observed that: 1) in lung tissue samples of stable COPD patients, NLRP3 and interleukin (IL)-1β mRNA were upregulated, but both caspase-1 and ASC were mostly in inactive form, and 2) during infectious ECOPD, caspase-1, oligomeric ASC and associated cytokines (IL-1β, IL-18) were significantly increased in sputum compared with clinical recovery. The NLRP3 inflammasome is primed, but not activated, in the lungs of clinically stable COPD patients. Inflammasome activation occurs during infectious ECOPD. The results of this study suggest that the inflammasome participates in the inflammatory burst of infectious ECOPD. PMID:27730204

  9. Postoperative Acute Exacerbation of IPF after Lung Resection for Primary Lung Cancer.

    PubMed

    Watanabe, Atsushi; Kawaharada, Nobuyoshi; Higami, Tetsuya

    2011-01-01

    Idiopathic pulmonary fibrosis (IPF) is characterized by slowly progressive respiratory dysfunction. Nevertheless, some IPF patients experience acute exacerbations generally characterized by suddenly worsening and fatal respiratory failure with new lung opacities and pathological lesions of diffuse alveolar damage. Acute exacerbation of idiopathic pulmonary fibrosis (AEIPF) is a fatal disorder defined by rapid deterioration of IPF. The condition sometimes occurs in patients who underwent lung resection for primary lung cancer in the acute and subacute postoperative phases. The exact etiology and pathogenesis remain unknown, but the condition is characterized by diffuse alveolar damage superimposed on a background of IPF that probably occurs as a result of a massive lung injury due to some unknown factors. This systematic review shows that the outcome, however, is poor, with postoperative mortality ranging from 33.3% to 100%. In this paper, the etiology, risk factors, pathogenesis, therapy, prognosis, and predictors of postoperative AEIPF are described.

  10. Health-related QOL in acute exacerbations of chronic bronchitis and chronic obstructive pulmonary disease: a review of the literature.

    PubMed

    Doll, Helen; Miravitlles, Marc

    2005-01-01

    There is a lack of emphasis on health-related QOL (HR-QOL) changes associated with acute exacerbation of chronic bronchitis (CB) or chronic obstructive pulmonary disease (COPD). The aim of this review is to examine the use of HR-QOL instruments to evaluate acute exacerbation of CB or COPD, so as to form recommendations for future research.A literature search of papers published between 1966 and July 2003 identified more than 300 articles that used acute exacerbation of CB or COPD as the search term. However, only 21 of these studies employed HR-QOL measures as predictors of outcome or in the assessment of the impact, evolution or treatment of acute exacerbations of COPD or CB. A variety of HR-QOL measures were used, both generic and disease specific. The disease-specific St George's Respiratory Questionnaire (SGRQ), devised for patients with stable CB and with a recall period of 1-12 months, was the most widely used measure, with the Chronic Respiratory disease Questionnaire (CRQ) and the Baseline and Transitional Dyspnoea Index (BDI, TDI) being the only other disease-specific measures used. Most measures, both generic and disease specific, performed adequately when used during acute exacerbation of CB or COPD and indicated poor HR-QOL during acute exacerbation, which improved on resolution of the exacerbation. Relationships were evident between HR-QOL during an acute exacerbation and various outcomes, including post-exacerbation functional status, hospital re- admission for acute exacerbation or COPD, and mortality. There is a need for studies of treatments for acute exacerbation of CB or COPD to include an appropriate HR-QOL instrument to aid in the stratification of patients so as to target the right treatment to the right patient group. While a new instrument could be developed to measure HR-QOL during acute exacerbation of CB or COPD, currently available disease-specific measures such as the CRQ and the SGRQ appear to be acceptable to patients during acute

  11. Myofibrillar instability exacerbated by acute exercise in filaminopathy.

    PubMed

    Chevessier, Frédéric; Schuld, Julia; Orfanos, Zacharias; Plank, Anne-C; Wolf, Lucie; Maerkens, Alexandra; Unger, Andreas; Schlötzer-Schrehardt, Ursula; Kley, Rudolf A; Von Hörsten, Stephan; Marcus, Katrin; Linke, Wolfgang A; Vorgerd, Matthias; van der Ven, Peter F M; Fürst, Dieter O; Schröder, Rolf

    2015-12-20

    Filamin C (FLNC) mutations in humans cause myofibrillar myopathy (MFM) and cardiomyopathy, characterized by protein aggregation and myofibrillar degeneration. We generated the first patient-mimicking knock-in mouse harbouring the most common disease-causing filamin C mutation (p.W2710X). These heterozygous mice developed muscle weakness and myofibrillar instability, with formation of filamin C- and Xin-positive lesions streaming between Z-discs. These lesions, which are distinct from the classical MFM protein aggregates by their morphology and filamentous appearance, were greatly increased in number upon acute physical exercise in the mice. This pathology suggests that mutant filamin influences the mechanical stability of myofibrillar Z-discs, explaining the muscle weakness in mice and humans. Re-evaluation of biopsies from MFM-filaminopathy patients with different FLNC mutations revealed a similar, previously unreported lesion pathology, in addition to the classical protein aggregates, and suggested that structures previously interpreted as aggregates may be in part sarcomeric lesions. We postulate that these lesions define preclinical disease stages, preceding the formation of protein aggregates. PMID:26472074

  12. Metallothionein-induced zinc partitioning exacerbates hyperoxic acute lung injury

    PubMed Central

    Lee, Sang-Min; McLaughlin, Joseph N.; Frederick, Daniel R.; Zhu, Lin; Thambiayya, Kalidasan; Wasserloos, Karla J.; Kaminski, Iris; Pearce, Linda L.; Peterson, Jim; Li, Jin; Latoche, Joseph D.; Peck Palmer, Octavia M.; Stolz, Donna Beer; Fattman, Cheryl L.; Alcorn, John F.; Oury, Tim D.; Angus, Derek C.; Pitt, Bruce R.

    2013-01-01

    Hypozincemia, with hepatic zinc accumulation at the expense of other organs, occurs in infection, inflammation, and aseptic lung injury. Mechanisms underlying zinc partitioning or its impact on extrahepatic organs are unclear. Here we show that the major zinc-binding protein, metallothionein (MT), is critical for zinc transmigration from lung to liver during hyperoxia and preservation of intrapulmonary zinc during hyperoxia is associated with an injury-resistant phenotype in MT-null mice. Particularly, lung-to-liver zinc ratios decreased in wild-type (WT) and increased significantly in MT-null mice breathing 95% oxygen for 72 h. Compared with female adult WT mice, MT-null mice were significantly protected against hyperoxic lung injury indicated by reduced inflammation and interstitial edema, fewer necrotic changes to distal airway epithelium, and sustained lung function at 72 h hyperoxia. Lungs of MT-null mice showed decreased levels of immunoreactive LC3, an autophagy marker, compared with WT mice. Analysis of superoxide dismutase (SOD) activity in the lungs revealed similar levels of manganese-SOD activity between strains under normoxia and hyperoxia. Lung extracellular SOD activity decreased significantly in both strains at 72 h of hyperoxia, although there was no difference between strains. Copper-zinc-SOD activity was ∼4× higher under normoxic conditions in MT-null compared with WT mice but was not affected in either group by hyperoxia. Collectively the data suggest that genetic deletion of MT-I/II in mice is associated with compensatory increase in copper-zinc-SOD activity, prevention of hyperoxia-induced zinc transmigration from lung to liver, and hyperoxia-resistant phenotype strongly associated with differences in zinc homeostasis during hyperoxic acute lung injury. PMID:23275622

  13. Antimicrobials in acute exacerbations of chronic obstructive pulmonary disease - An analysis of the time to next exacerbation before and after the implementation of standing orders

    PubMed Central

    Goddard, Rob D; McNeil, Shelly A; Slayter, Kathryn L; McIvor, R Andrew

    2003-01-01

    OBJECTIVE: To compare the mean time to next exacerbation in patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) before and after the implementation of standing orders. SETTING: Tertiary care hospital, Halifax, Nova Scotia, Canada. POPULATION STUDIED: The records of 150 patients were analyzed, 76 were in the preimplementation group, 74 in the postimplementation group. INTERVENTION: The management and outcomes of patients admitted with an acute exacerbation of COPD before and after the implementation of standing orders were compared. DESIGN: A retrospective chart review. MAIN RESULTS: There was no difference in the mean time to next exacerbation between treatment groups (preimplementation group: 310 days, postimplementation group: 289 days, P=0.53). Antibiotics were used in 90% of the cases (preimplementation group: 87%, postimplementation group: 93%). The postimplementation group had a 20% increase in the use of first-line agents over the preimplementation group. Overall, first-line agents represented only 37% of the antibiotic courses. CONCLUSIONS: The implementation of standing orders encouraged the use of first-line agents but did not influence subsequent symptom resolution, length of hospital stay, or the infection-free interval in patients with acute exacerbations of COPD. PMID:18159466

  14. Efficacy and safety of moxifloxacin in acute exacerbations of chronic bronchitis: a prospective, multicenter, observational study (AVANTI)

    PubMed Central

    2013-01-01

    Background Acute exacerbations of chronic bronchitis (AECB), including chronic obstructive pulmonary disease (AECOPD), represent a substantial patient burden. Few data exist on outpatient antibiotic management for AECB/AECOPD in Eastern/South Eastern Europe, in particular on the use of moxifloxacin (Avelox®), although moxifloxacin is widely approved in this region based on evidence from international clinical studies. Methods AVANTI (AVelox® in Acute Exacerbations of chroNic bronchiTIs) was a prospective, observational study conducted in eight Eastern European countries in patients > 35 years with AECB/AECOPD to whom moxifloxacin was prescribed. In addition to safety and efficacy outcomes, data on risk factors and the impact of exacerbation on daily life were collected. Results In the efficacy population (N = 2536), chronic bronchitis had been prevalent for > 10 years in 31.4% of patients and 66.0% of patients had concomitant COPD. Almost half the patients had never smoked, in contrast to data from Western Europe and the USA, where only one-quarter of COPD patients are non-smokers. The mean number of exacerbations in the last 12 months was 2.7 and 26.3% of patients had been hospitalized at least once for exacerbation. Physician compliance with the recommended moxifloxacin dose (400 mg once daily) was 99.6%. The mean duration of moxifloxacin therapy for the current exacerbation (Anthonisen type I or II in 83.1%; predominantly type I) was 6.4 ± 1.9 days. Symptom improvement was reported after a mean of 3.4 ± 1.4 days. After 5 days, 93.2% of patients reported improvement and, in total, 93.5% of patients were symptom-free after 10 days. In the safety population (N = 2672), 57 (2.3%) patients had treatment-emergent adverse events (TEAEs) and 4 (0.15%) had serious TEAEs; no deaths occurred. These results are in line with the known safety profile of moxifloxacin. Conclusions A significant number of patients in this observational study had risk

  15. One Center’s Guide to Outpatient Management of Pediatric Cystic Fibrosis Acute Pulmonary Exacerbation

    PubMed Central

    Muirhead, Corinne A.; Sanford, Jillian N.; McCullar, Benjamin G.; Nolt, Dawn; MacDonald, Kelvin D.

    2016-01-01

    Cystic fibrosis (CF) is a chronic disorder characterized by acute pulmonary exacerbations that comprise increased cough, chest congestion, increased mucus production, shortness of breath, weight loss, and fatigue. Typically, severe episodes are treated in the inpatient setting and include intravenous antimicrobials, airway clearance therapy, and nutritional support. Children with less-severe findings can often be managed as outpatients with oral antimicrobials and increased airway clearance therapy at home without visiting the specialty CF center to begin treatment. Selection of specific antimicrobial agents is dependent on pathogens found in surveillance culture, activity of an agent in patients with CF, and the unique physiology of these patients. In this pediatric review, we present our practice for defining acute pulmonary exacerbation, deciding treatment location, initiating treatment either in-person or remotely, determining the frequency of airway clearance, selecting antimicrobial therapy, recommending timing for follow-up visit, and recognizing and managing treatment failures. PMID:27429564

  16. One Center's Guide to Outpatient Management of Pediatric Cystic Fibrosis Acute Pulmonary Exacerbation.

    PubMed

    Muirhead, Corinne A; Sanford, Jillian N; McCullar, Benjamin G; Nolt, Dawn; MacDonald, Kelvin D

    2016-01-01

    Cystic fibrosis (CF) is a chronic disorder characterized by acute pulmonary exacerbations that comprise increased cough, chest congestion, increased mucus production, shortness of breath, weight loss, and fatigue. Typically, severe episodes are treated in the inpatient setting and include intravenous antimicrobials, airway clearance therapy, and nutritional support. Children with less-severe findings can often be managed as outpatients with oral antimicrobials and increased airway clearance therapy at home without visiting the specialty CF center to begin treatment. Selection of specific antimicrobial agents is dependent on pathogens found in surveillance culture, activity of an agent in patients with CF, and the unique physiology of these patients. In this pediatric review, we present our practice for defining acute pulmonary exacerbation, deciding treatment location, initiating treatment either in-person or remotely, determining the frequency of airway clearance, selecting antimicrobial therapy, recommending timing for follow-up visit, and recognizing and managing treatment failures. PMID:27429564

  17. Use of azithromycin in the treatment of acute exacerbations of COPD

    PubMed Central

    Milstone, Aaron P

    2008-01-01

    Chronic bronchitis is a relatively common entity among patients with underlying chronic obstructive lung disease. Typical treatment includes pulmonary hygiene, bronchodilators, and antimicrobial therapy. In recent years, the duration of antimicrobial therapy in acute exacerbations of COPD has become shorter and shorter. This review summarizes the data on the use of the drug azithromycin for this particular patient population with a focus on 3-day and single-day therapy. PMID:19281070

  18. High-risk patients following hospitalisation for an acute exacerbation of COPD.

    PubMed

    Piquet, Jacques; Chavaillon, Jean-Michel; David, Philippe; Martin, Francis; Blanchon, François; Roche, Nicolas

    2013-10-01

    The aim of this study was to assess long-term mortality and predictive factors of death after hospital admission for acute exacerbation of chronic obstructive pulmonary disease (COPD). 1824 patients (23.2% female; mean age 70.3±11.3 years) consecutively admitted for acute exacerbation of COPD in the respiratory medicine departments of 68 general hospitals between October 2006 and June 2007 were prospectively enrolled in a follow-up cohort. Their vital status was documented between October 2010 and April 2011. Vital status was available for 1750 patients (95.9%), among whom 787 (45%) died during follow-up. Multivariate analysis found that age (60-80 years and ≥80 years versus <60 years, relative risk 2.99, 95% CI 2.31-3.89), lower body mass index (25-30 kg·m(-2) versus ≤20 kg·m(-2), relative risk 0.80, 95% CI 0.66-0.97), lung cancer (relative risk 2.08, 95% CI 1.43-3.01), cardiovascular comorbidity (relative risk 1.35, 95% CI 1.16-1.58), previous hospital admissions for acute exacerbation of COPD (four or more versus none, relative risk 1.91, 95% CI 1.44-2.53), use of accessory respiratory muscles (relative risk 1.19, 95% CI 1.01-1.40) or lower-limb oedema (relative risk 1.74, 95% CI (1.44-2.12)) at admission and treatment by long-term oxygen therapy at discharge (relative risk 2.09, 95% CI 1.79-2.45) were independent risk factors of death. Mortality rate during the 4 years following hospital admission for acute exacerbation of COPD was high (45%). Simple clinical information relating to respiratory and general status can help in identifying high-risk patients and targeting more intensive follow-up and care. Interestingly, cardiovascular comorbidities and past hospitalisations for acute exacerbation of COPD, but not forced expiratory volume in 1 s, independently predicted the risk of death.

  19. Chinese Herbal Medicine (Weijing Decoction) Combined with Pharmacotherapy for the Treatment of Acute Exacerbations of Chronic Obstructive Pulmonary Disease

    PubMed Central

    Yu, Xuhua; Guo, Xinfeng; Xue, Charlie Changli

    2014-01-01

    Objective. To evaluate the efficacy and safety of Weijing decoction combined with routine pharmacotherapy (RP) for the treatment of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Methods. Randomized controlled trials (RCT) evaluating Weijing decoction for AECOPD were included. English, Chinese, and Japanese databases were searched from their respective inceptions to June 2013. The methodological quality was assessed according to the Cochrane Collaboration's risk of bias tool. All data were analyzed and synthesized using RevMan 5.2 software. Results. Fifteen (15) studies involving 986 participants were included. Participants were diagnosed with COPD in the acute exacerbation stage. In addition, most of studies reported that they included participants with the Chinese medicine syndrome, phlegm-heat obstructing the Lung. Weijing decoction combined with RP improved lung function (forced expiratory volume in one second; FEV1), arterial blood gases (PaO2 and PaCO2), clinical effective rate, and reduced inflammatory biomarkers (TNF-α and IL-8) when compared with RP alone. No severe adverse events were reported in these studies. Conclusions. Weijing decoction appeared to be beneficial for AECOPD and well-tolerated when taken concurrently with RP, such as antibiotics, bronchodilators (oral and inhaled), and mucolytics. PMID:25165477

  20. Moxifloxacin versus amoxicillin/clavulanic acid in outpatient acute exacerbations of COPD: MAESTRAL results.

    PubMed

    Wilson, Robert; Anzueto, Antonio; Miravitlles, Marc; Arvis, Pierre; Alder, Jeff; Haverstock, Daniel; Trajanovic, Mila; Sethi, Sanjay

    2012-07-01

    Bacterial infections causing acute exacerbations of chronic obstructive pulmonary disease (AECOPD) frequently require antibacterial treatment. More evidence is needed to guide antibiotic choice. The Moxifloxacin in Acute Exacerbations of Chronic Bronchitis TriaL (MAESTRAL) was a multiregional, randomised, double-blind non-inferiority outpatient study. Patients were aged ≥ 60 yrs, with an Anthonisen type I exacerbation, a forced expiratory volume in 1 s < 60% predicted and two or more exacerbations in the last year. Following stratification by steroid use patients received moxifloxacin 400 mg p.o. q.d. (5 days) or amoxicillin/clavulanic acid 875/125 mg p.o. b.i.d. (7 days). The primary end-point was clinical failure 8 weeks post-therapy in the per protocol population. Moxifloxacin was noninferior to amoxicillin/clavulanic acid at the primary end-point (111 (20.6%) out of 538, versus 114 (22.0%) out of 518, respectively; 95% CI -5.89-3.83%). In patients with confirmed bacterial AECOPD, moxifloxacin led to significantly lower clinical failure rates than amoxicillin/clavulanic acid (in the intent-to-treat with pathogens, 62 (19.0%) out of 327 versus 85 (25.4%) out of 335, respectively; p=0.016). Confirmed bacterial eradication at end of therapy was associated with higher clinical cure rates at 8 weeks post-therapy overall (p=0.0014) and for moxifloxacin (p=0.003). Patients treated with oral corticosteroids had more severe disease and higher failure rates. The MAESTRAL study showed that moxifloxacin was as effective as amoxicillin/clavulanic acid in the treatment of outpatients with AECOPD. Both therapies were well tolerated.

  1. Longitudinal change in quality of life following hospitalisation for acute exacerbations of COPD

    PubMed Central

    Steer, John; Gibson, G John; Bourke, Stephen C

    2015-01-01

    Background Current guidelines for management of patients hospitalised with acute exacerbations of chronic obstructive pulmonary disease (COPD) recommend that clinical decisions, including escalation to assisted ventilation, be informed by an estimate of the patients’ likely postdischarge quality of life. There is little evidence to inform predictions of outcome in terms of quality of life, psychological well-being and functional status. Undue nihilism might lead to denial of potentially life-saving therapy, while undue optimism might prolong suffering when alternative palliation would be more appropriate. This study aimed to detail longitudinal changes in quality of life following hospitalisation for acute exacerbations of COPD. Methods We prospectively recruited two cohorts (exacerbations requiring assisted ventilation during admission and exacerbations not ventilated). Admission clinical data, and mortality and readmission details were collected. Quality of life, psychological well-being and functional status were formally assessed over the subsequent 12 months. Time-adjusted mean change in quality of life was examined. Results 183 patients (82 ventilated; 101 not ventilated) were recruited. On average, overall quality of life improved by a clinically important amount in those not ventilated and did not decline in ventilated patients. Both groups showed clinically important improvements in respiratory symptoms and an individual's sense of control over their condition, despite the tendency for functional status to decline. Conclusions On average, postdischarge quality of life improved in non-ventilated and did not decline in ventilated patients. Certain quality of life domains (ie, symptoms and mastery) improved significantly. Better understanding of longitudinal change in postdischarge quality of life should help to inform decision-making. PMID:25628892

  2. Invasive coronary angiography in patients with acute exacerbated COPD and elevated plasma troponin

    PubMed Central

    Pizarro, Carmen; Herweg-Steffens, Neele; Buchenroth, Martin; Schulte, Wolfgang; Schaefer, Christian; Hammerstingl, Christoph; Werner, Nikos; Nickenig, Georg; Skowasch, Dirk

    2016-01-01

    Background In acute exacerbation of COPD, increased plasma levels of cardiac troponin are frequent and associated with increased mortality. Thus, we aimed at prospectively determining the diagnostic value of coronary angiography in patients with exacerbated COPD and concomitantly elevated cardiac troponin. Patients and methods A total of 88 patients (mean age 72.9±9.2 years, 56.8% male) hospitalized for acute exacerbation of COPD with elevated plasma troponin were included. All patients underwent coronary angiography within 72 hours after hospitalization. Complementary 12-lead electrocardiogram, transthoracic echocardiography, pulmonary function, and angiological testing were performed. Results Coronary angiography objectified the presence of ischemic heart disease (IHD) in 59 patients (67.0%), of whom 34 patients (38.6% of total study population) underwent percutaneous coronary intervention. Among these 34 intervened patients, the vast majority (n=26, 76.5%) had no previously known IHD, whereas only eight out of 34 patients (23.5%) presented an IHD history. Patients requiring coronary intervention showed significantly reduced left ventricular ejection fraction (45.8%±13.1% vs 55.1%±13.3%, P=0.01) and a significantly more frequent electrocardiographic ST-segment depression (20.6% vs 7.4%, P=0.01). Neither additional laboratory parameters for inflammation and myocardial injury nor lung functional measurements differed significantly between the groups. Conclusion Angiographically confirmed IHD that required revascularization occurred in 38.6% of exacerbated COPD patients with elevated cardiac troponin. In this considerable portion of patients, coronary angiography emerged to be of diagnostic and therapeutic value. PMID:27695304

  3. Invasive coronary angiography in patients with acute exacerbated COPD and elevated plasma troponin

    PubMed Central

    Pizarro, Carmen; Herweg-Steffens, Neele; Buchenroth, Martin; Schulte, Wolfgang; Schaefer, Christian; Hammerstingl, Christoph; Werner, Nikos; Nickenig, Georg; Skowasch, Dirk

    2016-01-01

    Background In acute exacerbation of COPD, increased plasma levels of cardiac troponin are frequent and associated with increased mortality. Thus, we aimed at prospectively determining the diagnostic value of coronary angiography in patients with exacerbated COPD and concomitantly elevated cardiac troponin. Patients and methods A total of 88 patients (mean age 72.9±9.2 years, 56.8% male) hospitalized for acute exacerbation of COPD with elevated plasma troponin were included. All patients underwent coronary angiography within 72 hours after hospitalization. Complementary 12-lead electrocardiogram, transthoracic echocardiography, pulmonary function, and angiological testing were performed. Results Coronary angiography objectified the presence of ischemic heart disease (IHD) in 59 patients (67.0%), of whom 34 patients (38.6% of total study population) underwent percutaneous coronary intervention. Among these 34 intervened patients, the vast majority (n=26, 76.5%) had no previously known IHD, whereas only eight out of 34 patients (23.5%) presented an IHD history. Patients requiring coronary intervention showed significantly reduced left ventricular ejection fraction (45.8%±13.1% vs 55.1%±13.3%, P=0.01) and a significantly more frequent electrocardiographic ST-segment depression (20.6% vs 7.4%, P=0.01). Neither additional laboratory parameters for inflammation and myocardial injury nor lung functional measurements differed significantly between the groups. Conclusion Angiographically confirmed IHD that required revascularization occurred in 38.6% of exacerbated COPD patients with elevated cardiac troponin. In this considerable portion of patients, coronary angiography emerged to be of diagnostic and therapeutic value.

  4. Mechanisms of worsening gas exchange during acute exacerbations of chronic obstructive pulmonary disease.

    PubMed

    Barberà, J A; Roca, J; Ferrer, A; Félez, M A; Díaz, O; Roger, N; Rodriguez-Roisin, R

    1997-06-01

    This study was undertaken to investigate the mechanisms that determine abnormal gas exchange during acute exacerbations of chronic obstructive pulmonary disease (COPD). Thirteen COPD patients, hospitalized because of an exacerbation, were studied after admission and 38+/-10 (+/-SD) days after discharge, once they were clinically stable. Measurements included forced spirometry, arterial blood gas values, minute ventilation (V'E), cardiac output (Q'), oxygen consumption (V'O2), and ventilation/perfusion (V'A/Q') relationships, assessed by the inert gas technique. Exacerbations were characterized by very severe airflow obstruction (forced expiratory volume in one second (FEV1) 0.74+/-0.17 vs 0.91+/-0.19 L, during exacerbation and stable conditions, respectively; p=0.01), severe hypoxaemia (ratio between arterial oxygen tension and inspired oxygen fraction (Pa,O2/FI,O2) 32.7+/-7.7 vs 37.6+/-6.9 kPa (245+/-58 vs 282+/-52 mmHg); p=0.01) and hypercapnia (arterial carbon dioxide tension (Pa,CO2) 6.8+/-1.6 vs 5.9+/-0.8 kPa (51+/-12 vs 44+/-6 mmHg); p=0.04). V'A/Q' inequality increased during exacerbation (log SD Q', 1.10+/-0.29 vs 0.96+/-0.27; normal < or = 0.6; p=0.04) as a result of greater perfusion in poorly-ventilated alveoli. Shunt was almost negligible on both measurements. V'E remained essentially unchanged during exacerbation (10.5+/-2.2 vs 9.2+/-1.8 L x min(-1); p=0.1), whereas both Q' (6.1+/-2.4 vs 5.1+/-1.7 L x min(-1); p=0.05) and V'O2 (300+/-49 vs 248+/-59 mL x min(-1); p=0.03) increased significantly. Worsening of hypoxaemia was explained mainly by the increase both in V'A/Q' inequality and V'O2, whereas the increase in Q' partially counterbalanced the effect of greater V'O2 on mixed venous oxygen tension (PV,O2). We conclude that worsening of gas exchange during exacerbations of chronic obstructive pulmonary disease is primarily produced by increased ventilation/perfusion inequality, and that this effect is amplified by the decrease of mixed venous oxygen

  5. Outcomes associated with acute exacerbations of chronic obstructive pulmonary disorder requiring hospitalization

    PubMed Central

    Gaude, Gajanan S; Rajesh, BP; Chaudhury, Alisha; Hattiholi, Jyothi

    2015-01-01

    Background: Acute exacerbations of chronic obstructive pulmonary disorder (AECOPD) are known to be associated with increased morbidity and mortality and have a significant socioeconomic impact. The factors that determine frequent hospital readmissions for AECOPD are poorly understood. The present study was done to ascertain failures rates following AECOPD and to evaluate factors associated with frequent readmissions. Materials and Methods: We conducted a prospective study among 186 patients with COPD with one or more admissions for acute exacerbations in a tertiary care hospital. Frequency of previous re-admissions for AECOPD in the past year, and clinical characteristics, including spirometry were ascertained in the stable state both before discharge and at 6-month post-discharge. Failure rates following treatment were ascertained during the follow-up period. All the patients were followed up for a period of 2 years after discharge to evaluate re-admissions for the AECOPD. Results: Of 186 COPD patients admitted for AECOPD, 54% had one or more readmission, and another 45% had two or more readmissions over a period of 2 years. There was a high prevalence of current or ex-heavy smokers, associated co-morbidity, underweight patients, low vaccination prevalence and use of domiciliary oxygen therapy among COPD patients. A total of 12% mortality was observed in the present study. Immediate failure rates after first exacerbation was observed to be 34.8%. Multivariate analysis showed that duration >20 years (OR = 0.37; 95% CI: 0.10-0.86), use of Tiotropium (OR = 2.29; 95% CI: 1.12-4.69) and use of co-amoxiclav during first admission (OR = 2.41; 95% CI: 1.21-4.79) were significantly associated with higher immediate failure rates. The multivariate analysis for repeated admissions revealed that disease duration >10 years (OR = 0.50; 95% CI: 0.27-0.93), low usage of inhaled ICS + LABA (OR = 2.21; 95% CI: 1.08-4.54), and MRC dyspnea grade >3 (OR = 2.51; 95% CI: 1.08-5.82) were

  6. Thyroid Echography-induced Thyroid Storm and Exacerbation of Acute Heart Failure.

    PubMed

    Nakabayashi, Keisuke; Nakazawa, Naomi; Suzuki, Toshiaki; Asano, Ryotaro; Saito, Hideki; Nomura, Hidekimi; Isomura, Daichi; Okada, Hisayuki; Sugiura, Ryo; Oka, Toshiaki

    2016-01-01

    Hyperthyroidism and thyroid storm affect cardiac circulation in some conditions. Several factors including trauma can induce thyroid storms. We herein describe the case of a 57-year-old woman who experienced a thyroid storm and exacerbation of acute heart failure on thyroid echography. She initially demonstrated a good clinical course after medical rate control for atrial fibrillation; however, thyroid echography for evaluating hyperthyroidism led to a thyroid storm and she collapsed. A multidisciplinary approach stabilized her thyroid hormone levels and hemodynamics. Thus, the medical staff should be prepared for a deterioration in the patient's condition during thyroid echography in heart failure patients with hyperthyroidism.

  7. Thyroid Echography-induced Thyroid Storm and Exacerbation of Acute Heart Failure.

    PubMed

    Nakabayashi, Keisuke; Nakazawa, Naomi; Suzuki, Toshiaki; Asano, Ryotaro; Saito, Hideki; Nomura, Hidekimi; Isomura, Daichi; Okada, Hisayuki; Sugiura, Ryo; Oka, Toshiaki

    2016-01-01

    Hyperthyroidism and thyroid storm affect cardiac circulation in some conditions. Several factors including trauma can induce thyroid storms. We herein describe the case of a 57-year-old woman who experienced a thyroid storm and exacerbation of acute heart failure on thyroid echography. She initially demonstrated a good clinical course after medical rate control for atrial fibrillation; however, thyroid echography for evaluating hyperthyroidism led to a thyroid storm and she collapsed. A multidisciplinary approach stabilized her thyroid hormone levels and hemodynamics. Thus, the medical staff should be prepared for a deterioration in the patient's condition during thyroid echography in heart failure patients with hyperthyroidism. PMID:27522996

  8. Distinct histopathology of acute onset or abrupt exacerbation of hypersensitivity pneumonitis.

    PubMed

    Hariri, Lida P; Mino-Kenudson, Mari; Shea, Barry; Digumarthy, Subba; Onozato, Maristela; Yagi, Yukako; Fraire, Armando E; Matsubara, Osamu; Mark, Eugene J

    2012-05-01

    Hypersensitivity pneumonitis is an inflammatory lung disease that develops in response to exposure to antigen. Cases can be stratified by the duration of exposure and speed of symptom progression into acute, subacute, and chronic hypersensitivity pneumonitis. Although the pathologic features of subacute hypersensitivity pneumonitis are well established and those of chronic hypersensitivity pneumonitis have been reported, little is known about the histopathology of acute hypersensitivity pneumonitis. We evaluated the pathologic features of 5 patients with clinically confirmed hypersensitivity pneumonitis and rapid onset of symptoms and 3 patients with subacute or chronic hypersensitivity pneumonitis with symptom exacerbation. Histopathologic features assessed in each case included those characteristic of subacute hypersensitivity pneumonitis (bronchiolocentric chronic inflammation, histiocytic aggregates, and bronchiolitis obliterans), those associated with acute inflammation (fibrin deposition and neutrophilic infiltrate), and fibrosis. The classic features of hypersensitivity pneumonitis were identified in all 8 cases, with 1 also exhibiting fixed fibrosis confirming underlying chronic hypersensitivity pneumonitis. Fibrin deposition was present in 8 (100%) of 8 cases, and its extent was significant (28% surface area fibrin deposition/total disease area on average). Two had intra-alveolar fibrin so marked that it resembled acute fibrinous and organizing pneumonia. In addition, prominent interstitial neutrophilic infiltrate (≥5 cells/high-power field) was seen in all cases. These features have not been reported as characteristics of subacute or chronic hypersensitivity pneumonitis. Increased fibrin deposition and neutrophilic infiltrate may characterize acute hypersensitivity pneumonitis or abrupt exacerbation of hypersensitivity pneumonitis, and these along with characteristic features of subacute hypersensitivity pneumonitis (granulomatous inflammation and

  9. Autoantibody-Targeted Treatments for Acute Exacerbations of Idiopathic Pulmonary Fibrosis

    PubMed Central

    Donahoe, Michael; Valentine, Vincent G.; Chien, Nydia; Gibson, Kevin F.; Raval, Jay S.; Saul, Melissa; Xue, Jianmin; Zhang, Yingze; Duncan, Steven R.

    2015-01-01

    Background Severe acute exacerbations (AE) of idiopathic pulmonary fibrosis (IPF) are medically untreatable and often fatal within days. Recent evidence suggests autoantibodies may be involved in IPF progression. Autoantibody-mediated lung diseases are typically refractory to glucocorticoids and nonspecific medications, but frequently respond to focused autoantibody reduction treatments. We conducted a pilot trial to test the hypothesis that autoantibody-targeted therapies may also benefit AE-IPF patients. Methods Eleven (11) critically-ill AE-IPF patients with no evidence of conventional autoimmune diseases were treated with therapeutic plasma exchanges (TPE) and rituximab, supplemented in later cases with intravenous immunoglobulin (IVIG). Plasma anti-epithelial (HEp-2) autoantibodies and matrix metalloproteinase-7 (MMP7) were evaluated by indirect immunofluorescence and ELISA, respectively. Outcomes among the trial subjects were compared to those of 20 historical control AE-IPF patients treated with conventional glucocorticoid therapy prior to this experimental trial. Results Nine (9) trial subjects (82%) had improvements of pulmonary gas exchange after treatment, compared to one (5%) historical control. Two of the three trial subjects who relapsed after only five TPE responded again with additional TPE. The three latest subjects who responded to an augmented regimen of nine TPE plus rituximab plus IVIG have had sustained responses without relapses after 96-to-237 days. Anti-HEp-2 autoantibodies were present in trial subjects prior to therapy, and were reduced by TPE among those who responded to treatment. Conversely, plasma MMP7 levels were not systematically affected by therapy nor correlated with clinical responses. One-year survival of trial subjects was 46+15% vs. 0% among historical controls. No serious adverse events were attributable to the experimental medications. Conclusion This pilot trial indicates specific treatments that reduce autoantibodies

  10. Methylprednisolone exacerbates acute critical illness-related corticosteroid insufficiency associated with traumatic brain injury in rats.

    PubMed

    Chen, Xin; Zhang, Bin; Chai, Yan; Dong, Bo; Lei, Ping; Jiang, Rongcai; Zhang, Jianning

    2011-03-25

    consequently exacerbate acute CIRCI and mortality induced by TBI.

  11. COPD exacerbation: lost in translation.

    PubMed

    Makris, Demosthenes; Bouros, Demosthenes

    2009-01-29

    The introduction and acceptance of a standard definition for exacerbations of COPD can be helpful in prompt diagnosis and management of these events. The latest GOLD executive committee recognised this necessity and it has now included a definition of exacerbation in the guidelines for COPD which is an important step forward in the management of the disease. This definition is pragmatic and compromises the different approaches for exacerbation. However, the inclusion of the "healthcare utilisation" approach (".. may warrant a change in regular medication") in the definition may introduce in the diagnosis of exacerbation factors related to the access to health care services which may not be related to the underlying pathophysiological process which characterizes exacerbations. It should be also noted that the aetiology of COPD exacerbations has not yet been included in the current definition. In this respect, the definition does not acknowledge the fact that many patients with COPD may suffer from additional conditions (i.e. congestive cardiac failure or pulmonary embolism) that can masquerade as exacerbations but they should not be considered as causes of them. The authors therefore suggest that an inclusion of the etiologic factors of COPD exacerbations in the definition. Moreover, COPD exacerbations are characterized by increased airway and systemic inflammation and significant deterioration in lung function. These fundamental aspects should be accounted in diagnosis/definition of exacerbations. This could be done by the introduction of a "laboratory" marker in the diagnosis of these acute events. The authors acknowledge that the use of a test or a biomarker in the diagnosis of exacerbations meets certain difficulties related to performing lung function tests or to sampling during exacerbations. However, the introduction of a test that reflects airway or systemic inflammation in the diagnosis of exacerbations might be another step forward in the management of

  12. Computerised Analysis of Telemonitored Respiratory Sounds for Predicting Acute Exacerbations of COPD

    PubMed Central

    Fernandez-Granero, Miguel Angel; Sanchez-Morillo, Daniel; Leon-Jimenez, Antonio

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) is one of the commonest causes of death in the world and poses a substantial burden on healthcare systems and patients’ quality of life. The largest component of the related healthcare costs is attributable to admissions due to acute exacerbation (AECOPD). The evidence that might support the effectiveness of the telemonitoring interventions in COPD is limited partially due to the lack of useful predictors for the early detection of AECOPD. Electronic stethoscopes and computerised analyses of respiratory sounds (CARS) techniques provide an opportunity for substantial improvement in the management of respiratory diseases. This exploratory study aimed to evaluate the feasibility of using: (a) a respiratory sensor embedded in a self-tailored housing for ageing users; (b) a telehealth framework; (c) CARS and (d) machine learning techniques for the remote early detection of the AECOPD. In a 6-month pilot study, 16 patients with COPD were equipped with a home base-station and a sensor to daily record their respiratory sounds. Principal component analysis (PCA) and a support vector machine (SVM) classifier was designed to predict AECOPD. 75.8% exacerbations were early detected with an average of 5 ± 1.9 days in advance at medical attention. The proposed method could provide support to patients, physicians and healthcare systems. PMID:26512667

  13. Bacterial lysate in the prevention of acute exacerbation of COPD and in respiratory recurrent infections

    PubMed Central

    Braido, F; Tarantini, F; Ghiglione, V; Melioli, G; Canonica, G W

    2007-01-01

    Respiratory tract infections (RTIs) represent a serious problem because they are one of the most common cause of human death by infection. The search for the treatment of those diseases has therefore a great importance. In this study we provide an overview of the currently available treatments for RTIs with particular attention to chronic obstructive pulmonary diseases exacerbations and recurrent respiratory infections therapy and a description of bacterial lysate action, in particular making reference to the medical literature dealing with its clinical efficacy. Those studies are based on a very large number of clinical trials aimed to evaluate the effects of this drug in maintaining the immune system in a state of alert, and in increasing the defences against microbial infections. From this analysis it comes out that bacterial lysates have a protective effect, which induce a significant reduction of the symptoms related to respiratory infections. Those results could be very interesting also from an economic point of view, because they envisage a reduction in the number of acute exacerbations and a shorter duration of hospitalization. The use of bacterial lysate could therefore represent an important means to achieve an extension of life duration in patients affected by respiratory diseases. PMID:18229572

  14. High-flow nasal cannula oxygen therapy for acute exacerbation of interstitial pneumonia: A case series.

    PubMed

    Horio, Yukihiro; Takihara, Takahisa; Niimi, Kyoko; Komatsu, Masamichi; Sato, Masako; Tanaka, Jun; Takiguchi, Hiroto; Tomomatsu, Hiromi; Tomomatsu, Katsuyoshi; Hayama, Naoki; Oguma, Tsuyoshi; Aoki, Takuya; Urano, Tetsuya; Takagi, Atsushi; Asano, Koichiro

    2016-03-01

    We report 3 cases (all men, age: 69-81 years) of acute exacerbation of interstitial pneumonia (AEIP) that were successfully treated with a high-flow nasal cannula (HFNC), which delivers heated, humidified gas at a fraction of inspired oxygen (FIO2) up to 1.0 (100%). Oxygenation was insufficient under non-rebreathing face masks; however, the introduction of HFNC with an FIO2 of 0.7-1.0 (flow rate: 40 L/min) improved oxygenation and was well-tolerated until the partial pressure of oxygen in blood/FIO2 ratio increased (between 21 and 26 days). Thus, HFNC might be an effective and well-tolerated therapeutic addition to the management of AEIP. PMID:26879483

  15. Supplemental nasogastric feeding in cystic fibrosis patients during treatment for acute exacerbation of chest disease.

    PubMed

    Daniels, L; Davidson, G P; Martin, A J; Pouras, T

    1989-06-01

    The use of overnight, nasogastric, nutritional supplementation during hospitalization of children with cystic fibrosis (CF) receiving antibiotic therapy for acute exacerbations of respiratory disease was evaluated in 11 children (mean age = 7.75 years). Supplementary feeding significantly increased inpatient energy intake from 116 +/- 30% to 165 +/- 30% (P less than 0.001) of recommended dietary allowance with minimal effect on oral intake. It also resulted in significantly improved weight gains but neither increased energy intakes nor weights were sustained at short-term (mean = 5.7 weeks) or long-term (mean = 21.6 weeks) follow-up. The notion that short bursts of nasogastric feeding for inpatients with CF improve growth status is not supported. However, the study did show that treatment of chest infections alone does not positively affect spontaneous oral energy intake. PMID:2504140

  16. Readmissions after hospital discharge with acute exacerbation of COPD: are we missing something?

    PubMed

    Gaurav, Kumar; Vaid, Urvashi; Sexauer, William; Kavuru, Mani S

    2014-04-01

    Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is an important part of the disease's morbidity, mortality, and progression, and is associated with increasing utilization of health care resources. The concept of integrated care based on a chronic care model is relatively new to chronic obstructive pulmonary disease, but has proved successful in improving clinical outcomes and probably in decreasing health care utilization in other chronic conditions. A comprehensive approach is needed to target a change in behavioral patterns in patients, increase physician's awareness and adherence to evidence-based recommendations, and address system related issues. This article discusses the evidence for various facets of nonpharmacological management of AECOPD and proposes a model of care that might be the missing link for reducing hospital readmissions for AECOPD. This model may decrease the morbidity, slow disease progression, and curb the increasing health care resource utilization without compromising patient care.

  17. Acute exacerbation of combined pulmonary fibrosis and emphysema associated with Hermansky-Pudlak syndrome.

    PubMed

    Sugino, Keishi; Gocho, Kyoko; Kikuchi, Naoshi; Shibuya, Kazutoshi; Uekusa, Toshimasa; Homma, Sakae

    2016-03-01

    A 30-year-old male smoker with congenital amblyopia and oculocutaneous albinism was admitted to our hospital complaining of progressive dyspnea on exertion. Chest computed tomography images revealed diffuse reticular opacities and honeycombing in the bilateral lower lobes with sparing of the subpleural region along with emphysema predominantly in the upper lobes. Lung biopsy specimens showed a mixture of usual interstitial pneumonia and a non-specific interstitial pneumonia pattern with emphysema. Of note, cuboidal epithelial cells with foamy cytoplasm on the alveolar walls and phagocytic macrophages with ceroid pigments in the fibrotic lesions were observed. The patient was diagnosed with Hermansky-Pudlak syndrome (HPS) associated with combined pulmonary fibrosis and emphysema (CPFE). Six years following the patient's initial admission to our hospital, he died from acute exacerbation (AE) of CPFE associated with HPS. This is one of only few reports available on the clinicopathological characteristics of AE in CPFE associated with HPS. PMID:26839694

  18. Acute exacerbation of Hashimoto thyroiditis mimicking anaplastic carcinoma of the thyroid: A complicated case.

    PubMed

    Kanaya, Hiroaki; Konno, Wataru; Fukami, Satoru; Hirabayashi, Hideki; Haruna, Shin-ichi

    2014-12-01

    The fibrous variant of Hashimoto thyroiditis is uncommon, accounting for approximately 10% of all cases of Hashimoto thyroiditis. We report a case of this variant that behaved like a malignant neoplasm. The patient was a 69-year-old man who presented with a right-sided anterior neck mass that had been rapidly growing for 2 weeks. Fine-needle aspiration cytology revealed clusters of large multinucleated cells suggestive of an anaplastic carcinoma. A week after presentation, we ruled out that possibility when the mass had shrunk slightly. Instead, we diagnosed the patient with an acute exacerbation of Hashimoto thyroiditis on the basis of laboratory findings. We performed a right thyroid lobectomy, including removal of the isthmus, to clarify the pathology and alleviate pressure symptoms. The final diagnosis was the fibrous variant of Hashimoto thyroiditis, with no evidence of malignant changes. Physicians should keep in mind that on rare occasions, Hashimoto thyroiditis mimics a malignant neoplasm.

  19. The Most Common Detected Bacteria in Sputum of Patients with the Acute Exacerbation of COPD

    PubMed Central

    Cukic, Vesna

    2013-01-01

    Introduction: Acute exacerbation of COPD (AECOPD) may be triggered by infection with bacteria or viruses or by environmental pollutants; the cause of about one-third of exacerbations cannot be identified. Objective: To determine the most common bacteria in sputum culture of patients with AECOPD hospitalized in Intensive care unit of Clinic for pulmonary disease and TB “Podhrastovi” in the 2012. Material and methods: This is a retrospective analysis of sputum bacterial cultures of patients with AECOPD treated in the Intensive care unit of Clinic for pulmonary disease and TB “Podhrastovi” during 2012 .year. Each patient was required to give two sputum for bacterial examination. Each patient was treated with antibiotics prior to admission in Clinic “Podhrastovi”. The results of sputum bacterial culture findings are expressed in absolute number and percentage of examined patients. Results: In 2012, 75 patients with AECOPD were treated in Intensive care unit of Clinic for pulmonary disease and TB“Podhrastovi”. 44 (58.66%) of patients had normal –nonpathogenic – usual bacterial flora isolated in sputum cultures, 31 (41.34%) had a pathogen bacteria in sputum culture as follows: 7 had Streptoccocus pneumoniae, 8 had Klebsiella pneumoniae (2 with Streptococcus pneumoniae, one with Acinetobacter baumani) ,4 Escherichia colli, others are one or two cases with other bacteria. Conclusion: Bacterial airway infections play a great role in many, but not in all, of cases of AECOPD. So there is the need to do a sputum bacterial culture examination in each patient with AECOPD and with appropriate antibiotics to contribute to curing of them. PMID:24511262

  20. The Belgian trial with azithromycin for acute COPD exacerbations requiring hospitalization: an investigator-initiated study protocol for a multicenter, randomized, double-blind, placebo-controlled trial

    PubMed Central

    Vermeersch, Kristina; Gabrovska, Maria; Deslypere, Griet; Demedts, Ingel K; Slabbynck, Hans; Aumann, Joseph; Ninane, Vincent; Verleden, Geert M; Troosters, Thierry; Bogaerts, Kris; Brusselle, Guy G; Janssens, Wim

    2016-01-01

    Background Long-term use of macrolide antibiotics is effective to prevent exacerbations in chronic obstructive pulmonary disease (COPD). As risks and side effects of long-term intervention outweigh the benefits in the general COPD population, the optimal dose, duration of treatment, and target population are yet to be defined. Hospitalization for an acute exacerbation (AE) of COPD may offer a targeted risk group and an obvious risk period for studying macrolide interventions. Methods/design Patients with COPD, hospitalized for an AE, who have a smoking history of ≥10 pack-years and had ≥1 exacerbation in the previous year will be enrolled in a multicenter, randomized, double-blind, placebo-controlled trial (NCT02135354). On top of a standardized treatment of systemic corticosteroids and antibiotics, subjects will be randomized to receive either azithromycin or placebo during 3 months, at an uploading dose of 500 mg once a day for 3 days, followed by a maintenance dose of 250 mg once every 2 days. The primary endpoint is the time-to-treatment failure during the treatment phase (ie, from the moment of randomization until the end of intervention). Treatment failure is a novel composite endpoint defined as either death, the admission to intensive care or the requirement of additional systemic steroids or new antibiotics for respiratory reasons, or the diagnosis of a new AE after discharge. Discussion We investigate whether azithromycin initiated at the onset of a severe exacerbation, with a limited duration and at a low dose, might be effective and safe in the highest risk period during and immediately after the acute event. If proven effective and safe, this targeted approach may improve the treatment of severe AEs and redirect the preventive use of azithromycin in COPD to a temporary intervention in the subgroup with the highest unmet needs. PMID:27099485

  1. Cigarette smoke causes acute airway disease and exacerbates chronic obstructive lung disease in neonatal mice.

    PubMed

    Jia, Jie; Conlon, Thomas M; Ballester Lopez, Carolina; Seimetz, Michael; Bednorz, Mariola; Zhou-Suckow, Zhe; Weissmann, Norbert; Eickelberg, Oliver; Mall, Marcus A; Yildirim, Ali Önder

    2016-09-01

    Epidemiological evidence demonstrates a strong link between postnatal cigarette smoke (CS) exposure and increased respiratory morbidity in young children. However, how CS induces early onset airway disease in young children, and how it interacts with endogenous risk factors, remains poorly understood. We, therefore, exposed 10-day-old neonatal wild-type and β-epithelial sodium ion channel (β-ENaC)-transgenic mice with cystic fibrosis-like lung disease to CS for 4 days. Neonatal wild-type mice exposed to CS demonstrated increased numbers of macrophages and neutrophils in the bronchoalveolar lavage fluid (BALF), which was accompanied by increased levels of Mmp12 and Cxcl1 BALF from β-ENaC-transgenic mice contained greater numbers of macrophages, which did not increase following acute CS exposure; however, there was significant increase in airway neutrophilia compared with filtered air transgenic and CS-exposed wild-type controls. Interestingly, wild-type and β-ENaC-transgenic mice demonstrated epithelial airway and vascular remodeling following CS exposure. Morphometric analysis of lung sections revealed that CS exposure caused increased mucus accumulation in the airway lumen of neonatal β-ENaC-transgenic mice compared with wild-type controls, which was accompanied by an increase in the number of goblet cells and Muc5ac upregulation. We conclude that short-term CS exposure 1) induces acute airway disease with airway epithelial and vascular remodeling in neonatal wild-type mice; and 2) exacerbates airway inflammation, mucus hypersecretion, and mucus plugging in neonatal β-ENaC-transgenic mice with chronic lung disease. Our results in neonatal mice suggest that young children may be highly susceptible to develop airway disease in response to tobacco smoke exposure, and that adverse effects may be aggravated in children with underlying chronic lung diseases. PMID:27448665

  2. Small pulmonary vascular alteration and acute exacerbations of COPD: quantitative computed tomography analysis

    PubMed Central

    Wang, Zhiyue; Chen, Xuesong; Liu, Kouying; Xie, Weiping; Wang, Hong; Wei, Yongyue; Tang, Lijun; Zhu, Yinsu

    2016-01-01

    The morphologic alterations of pulmonary small vessels measured by computed tomography (CT) have been used to evaluate chronic obstructive pulmonary disease (COPD). However, the relationship between small pulmonary vascular alteration and acute exacerbations of COPD (AECOPD) is not well understood. The aim of this study was to evaluate the cross-sectional area (CSA) of small pulmonary vessel alterations measured on CT images and investigate its relationship with the COPD severity staged by the degree of airflow limitation and the occurrence of AECOPD. We retrospectively reviewed CT scans, clinical characteristics, and pulmonary function test results of 153 patients with COPD. All the patients were divided into AECOPD and non-AECOPD group according to the COPD staging and pulmonary function test results. The percentages of the total CSA less than 5 mm2 and equal to 5–10 mm2 over the lung area (%CSA<5 and %CSA5–10, respectively) were measured. The %CSA<5 steadily decreased in relation to the increase of COPD severity. In addition, %CSA<5 of the AECOPD group was significantly lower than that of the non-AECOPD group (0.41±0.13 versus 0.68±0.18, P<0.001), and the optimal cutoff value was 0.56 (sensitivity, 0.863; specificity, 0.731). Therefore, small pulmonary vascular alteration, as measured by %CSA<5, could indicate not only the degree of COPD severity, but also the occurrence of AECOPD. PMID:27578971

  3. Thromboxane A2 exacerbates acute lung injury via promoting edema formation.

    PubMed

    Kobayashi, Koji; Horikami, Daiki; Omori, Keisuke; Nakamura, Tatsuro; Yamazaki, Arisa; Maeda, Shingo; Murata, Takahisa

    2016-01-01

    Thromboxane A2 (TXA2) is produced in the lungs of patients suffering from acute lung injury (ALI). We assessed its contribution in disease progression using three different ALI mouse models. The administration of hydrochloric acid (HCl) or oleic acid (OA)+ lipopolysaccharide (LPS) caused tissue edema and neutrophil infiltration with TXA2 production in the lungs of the experimental mice. The administration of LPS induced only neutrophil accumulation without TXA2 production. Pretreatment with T prostanoid receptor (TP) antagonist attenuated the tissue edema but not neutrophil infiltration in these models. Intravital imaging and immunostaining demonstrated that administration of TP agonist caused vascular hyper-permeability by disrupting the endothelial barrier formation in the mouse ear. In vitro experiments showed that TP-stimulation disrupted the endothelial adherens junction, and it was inhibited by Ca(2+) channel blockade or Rho kinase inhibition. Thus endogenous TXA2 exacerbates ALI, and its blockade attenuates it by modulating the extent of lung edema. This can be explained by the endothelial hyper-permeability caused by the activation of TXA2-TP axis, via Ca(2+)- and Rho kinase-dependent signaling. PMID:27562142

  4. A case of severe acute exacerbation of Yokkaichi asthma treated with a vibrating mesh nebulizer.

    PubMed

    Yano, Takeshi; Yonaha, Tetsu; Hidaka, Koutaro; Nagahama, Masumi; Koshida, Tomohiro; Matsuoka, Hiroshi; Taniguchi, Masahiko; Tsuneyoshi, Isao

    2016-01-01

    Yokkaichi asthma was one of the most common environmental pollution diseases in Japan in the 1960s and 1970s. The problem of air pollution in Yokkaichi was solved in the 1970s. However, mortality and life expectancy were still affected by the late effects of air pollution in patients with Yokkaichi asthma even in the 2000s. In this case report, we described the experience of successful treatment of a patient with severe asthmatic status due to Yokkaichi asthma. A 40s-year-old man, who was officially certified as a patient with Yokkaichi asthma from his infancy, was admitted to hospital due to acute exacerbation of asthma. Mechanical ventilation, intravenous administration of aminophylline and dexamethasone, enteral administration of montelukast, and a transdermal patch of tulobuterol were started. However, because of the lack of improvement in clinical status, inhalation of procaterol using vibrating mesh nebulizer systems was started. Inhalation of procaterol was used three times a day. After using the vibrating mesh nebulizer, respiratory system compliance and hypercapnia rapidly improved. Bilateral expiratory wheezing was diminished. Weaning from mechanical ventilation was initiated, and on the eighth day of mechanical ventilation, the patient was extubated. Although intractable respiratory failure with decreased respiratory system compliance resulting from the late effects of air pollution and a long-time asthmatic inflammatory condition was observed, the use of a vibrating mesh nebulizer for the inhaled administration of procaterol was useful to relieve severe bronchospasm due to Yokkaichi asthma. PMID:27547723

  5. Clinical features and outcome of acute exacerbation of interstitial pneumonia associated with connective tissue disease.

    PubMed

    Toyoda, Yuko; Hanibuchi, Masaki; Kishi, Jun; Kawano, Hiroshi; Morizumi, Shun; Sato, Seidai; Kondo, Mayo; Takikura, Terumi; Tezuka, Toshifumi; Goto, Hisatsugu; Nishioka, Yasuhiko

    2016-01-01

    Acute exacerbation (AE) of interstitial lung disease is reported to be developed in not only idiopathic pulmonary fibrosis but also connective tissue disease-associated interstitial pneumonia (CTD-IP). As the significance of AE of CTD-IP has not been so widely recognized, its clinical feature is not fully elucidated. In the present study, we investigated the incidence, clinical features and outcome of AE of CTD-IP. We retrospectively reviewed admitted cases in our department with medical record from 2011 to 2015. Among 155 patients with CTD-IP, 10 (6.5%) cases developed AE (6 rheumatoid arthritis, 2 polymyositis/dermatomyositis, 1 systemic lupus erythematosus, 1 Sjögren syndrome), and one died of AE within 30 days. Median survival time after the onset of AE was 169 days in all 10 patients. The treatment with immunosuppressant just before AE onset might improve the prognosis of AE. The median survival time after the onset of AE was significantly longer in patients showing good response to corticosteroid compared with those with poor response to corticosteroid (805 days and 45 days, respectively) (p <0.05), suggesting that there are some cases in CTD-IP, showing the good response to corticosteroid even when AE was complicated. J. Med. Invest. 63: 294-299, August, 2016. PMID:27644575

  6. Small pulmonary vascular alteration and acute exacerbations of COPD: quantitative computed tomography analysis.

    PubMed

    Wang, Zhiyue; Chen, Xuesong; Liu, Kouying; Xie, Weiping; Wang, Hong; Wei, Yongyue; Tang, Lijun; Zhu, Yinsu

    2016-01-01

    The morphologic alterations of pulmonary small vessels measured by computed tomography (CT) have been used to evaluate chronic obstructive pulmonary disease (COPD). However, the relationship between small pulmonary vascular alteration and acute exacerbations of COPD (AECOPD) is not well understood. The aim of this study was to evaluate the cross-sectional area (CSA) of small pulmonary vessel alterations measured on CT images and investigate its relationship with the COPD severity staged by the degree of airflow limitation and the occurrence of AECOPD. We retrospectively reviewed CT scans, clinical characteristics, and pulmonary function test results of 153 patients with COPD. All the patients were divided into AECOPD and non-AECOPD group according to the COPD staging and pulmonary function test results. The percentages of the total CSA less than 5 mm(2) and equal to 5-10 mm(2) over the lung area (%CSA<5 and %CSA5-10, respectively) were measured. The %CSA<5 steadily decreased in relation to the increase of COPD severity. In addition, %CSA<5 of the AECOPD group was significantly lower than that of the non-AECOPD group (0.41±0.13 versus 0.68±0.18, P<0.001), and the optimal cutoff value was 0.56 (sensitivity, 0.863; specificity, 0.731). Therefore, small pulmonary vascular alteration, as measured by %CSA<5, could indicate not only the degree of COPD severity, but also the occurrence of AECOPD. PMID:27578971

  7. Plasma Leptin Is Elevated in Acute Exacerbation of Idiopathic Pulmonary Fibrosis.

    PubMed

    Cao, Mengshu; Swigris, Jeffery J; Wang, Xin; Cao, Min; Qiu, Yuying; Huang, Mei; Xiao, Yonglong; Cai, Hourong

    2016-01-01

    Background. The natural history of idiopathic pulmonary fibrosis (IPF) is very complex and unpredictable. Some patients will experience acute exacerbation (AE) and fatal outcomes. Methods. The study included 30 AE-IPF patients, 32 stable IPF (S-IPF) patients, and 12 healthy controls. We measured the plasma concentrations of leptin and KL-6. Simple correlation was used to assess associations between leptin and other variables. Plasma leptin levels were compared between AE-IPF and S-IPF subjects, decedents, and survivors. Kaplan-Meier curves were used to display survival and Cox proportional hazards regression was used to examine risk factors for survival. Results. In subjects with AE-IPF, plasma leptin was significantly greater than in subjects with S-IPF (p = 0.0003) or healthy controls (p < 0.0001). Plasma leptin was correlated with BMI, KL-6, LDH, CRP, and PaO2/FiO2 (p = 0.007; p = 0.005; p = 0.003; p = 0.033; and p = 0.032, resp.). Plasma leptin was significantly greater in 33 decedents than in the 23 survivors (p = 0.007). Multivariate Cox regression analysis showed leptin (>13.79 ng/mL) was an independent predictor of survival (p = 0.004). Conclusions. Leptin could be a promising plasma biomarker of AE-IPF occurrence and predictor of survival in IPF patients. PMID:27642238

  8. Thromboxane A2 exacerbates acute lung injury via promoting edema formation

    PubMed Central

    Kobayashi, Koji; Horikami, Daiki; Omori, Keisuke; Nakamura, Tatsuro; Yamazaki, Arisa; Maeda, Shingo; Murata, Takahisa

    2016-01-01

    Thromboxane A2 (TXA2) is produced in the lungs of patients suffering from acute lung injury (ALI). We assessed its contribution in disease progression using three different ALI mouse models. The administration of hydrochloric acid (HCl) or oleic acid (OA)+ lipopolysaccharide (LPS) caused tissue edema and neutrophil infiltration with TXA2 production in the lungs of the experimental mice. The administration of LPS induced only neutrophil accumulation without TXA2 production. Pretreatment with T prostanoid receptor (TP) antagonist attenuated the tissue edema but not neutrophil infiltration in these models. Intravital imaging and immunostaining demonstrated that administration of TP agonist caused vascular hyper-permeability by disrupting the endothelial barrier formation in the mouse ear. In vitro experiments showed that TP-stimulation disrupted the endothelial adherens junction, and it was inhibited by Ca2+ channel blockade or Rho kinase inhibition. Thus endogenous TXA2 exacerbates ALI, and its blockade attenuates it by modulating the extent of lung edema. This can be explained by the endothelial hyper-permeability caused by the activation of TXA2-TP axis, via Ca2+- and Rho kinase-dependent signaling. PMID:27562142

  9. Plasma Leptin Is Elevated in Acute Exacerbation of Idiopathic Pulmonary Fibrosis

    PubMed Central

    Wang, Xin; Cao, Min; Qiu, Yuying; Huang, Mei; Xiao, Yonglong

    2016-01-01

    Background. The natural history of idiopathic pulmonary fibrosis (IPF) is very complex and unpredictable. Some patients will experience acute exacerbation (AE) and fatal outcomes. Methods. The study included 30 AE-IPF patients, 32 stable IPF (S-IPF) patients, and 12 healthy controls. We measured the plasma concentrations of leptin and KL-6. Simple correlation was used to assess associations between leptin and other variables. Plasma leptin levels were compared between AE-IPF and S-IPF subjects, decedents, and survivors. Kaplan-Meier curves were used to display survival and Cox proportional hazards regression was used to examine risk factors for survival. Results. In subjects with AE-IPF, plasma leptin was significantly greater than in subjects with S-IPF (p = 0.0003) or healthy controls (p < 0.0001). Plasma leptin was correlated with BMI, KL-6, LDH, CRP, and PaO2/FiO2 (p = 0.007; p = 0.005; p = 0.003; p = 0.033; and p = 0.032, resp.). Plasma leptin was significantly greater in 33 decedents than in the 23 survivors (p = 0.007). Multivariate Cox regression analysis showed leptin (>13.79 ng/mL) was an independent predictor of survival (p = 0.004). Conclusions. Leptin could be a promising plasma biomarker of AE-IPF occurrence and predictor of survival in IPF patients. PMID:27642238

  10. Plasma Leptin Is Elevated in Acute Exacerbation of Idiopathic Pulmonary Fibrosis

    PubMed Central

    Wang, Xin; Cao, Min; Qiu, Yuying; Huang, Mei; Xiao, Yonglong

    2016-01-01

    Background. The natural history of idiopathic pulmonary fibrosis (IPF) is very complex and unpredictable. Some patients will experience acute exacerbation (AE) and fatal outcomes. Methods. The study included 30 AE-IPF patients, 32 stable IPF (S-IPF) patients, and 12 healthy controls. We measured the plasma concentrations of leptin and KL-6. Simple correlation was used to assess associations between leptin and other variables. Plasma leptin levels were compared between AE-IPF and S-IPF subjects, decedents, and survivors. Kaplan-Meier curves were used to display survival and Cox proportional hazards regression was used to examine risk factors for survival. Results. In subjects with AE-IPF, plasma leptin was significantly greater than in subjects with S-IPF (p = 0.0003) or healthy controls (p < 0.0001). Plasma leptin was correlated with BMI, KL-6, LDH, CRP, and PaO2/FiO2 (p = 0.007; p = 0.005; p = 0.003; p = 0.033; and p = 0.032, resp.). Plasma leptin was significantly greater in 33 decedents than in the 23 survivors (p = 0.007). Multivariate Cox regression analysis showed leptin (>13.79 ng/mL) was an independent predictor of survival (p = 0.004). Conclusions. Leptin could be a promising plasma biomarker of AE-IPF occurrence and predictor of survival in IPF patients.

  11. β-Blockers for the prevention of acute exacerbations of chronic obstructive pulmonary disease (βLOCK COPD): a randomised controlled study protocol

    PubMed Central

    Bhatt, Surya P; Connett, John E; Voelker, Helen; Lindberg, Sarah M; Westfall, Elizabeth; Wells, J Michael; Lazarus, Stephen C; Criner, Gerard J; Dransfield, Mark T

    2016-01-01

    Introduction A substantial majority of chronic obstructive pulmonary disease (COPD)-related morbidity, mortality and healthcare costs are due to acute exacerbations, but existing medications have only a modest effect on reducing their frequency, even when used in combination. Observational studies suggest β-blockers may reduce the risk of COPD exacerbations; thus, we will conduct a randomised, placebo-controlled trial to definitively assess the impact of metoprolol succinate on the rate of COPD exacerbations. Methods and analyses This is a multicentre, placebo-controlled, double-blind, prospective randomised trial that will enrol 1028 patients with at least moderately severe COPD over a 3-year period. Participants with at least moderate COPD will be randomised in a 1:1 fashion to receive metoprolol or placebo; the cohort will be enriched for patients at high risk for exacerbations. Patients will be screened and then randomised over a 2-week period and will then undergo a dose titration period for the following 6 weeks. Thereafter, patients will be followed for 42 additional weeks on their target dose of metoprolol or placebo followed by a 4-week washout period. The primary end point is time to first occurrence of an acute exacerbation during the treatment period. Secondary end points include rates and severity of COPD exacerbations; rate of major cardiovascular events; all-cause mortality; lung function (forced expiratory volume in 1 s (FEV1)); dyspnoea; quality of life; exercise capacity; markers of cardiac stretch (pro-NT brain natriuretic peptide) and systemic inflammation (high-sensitivity C reactive protein and fibrinogen). Analyses will be performed on an intent-to-treat basis. Ethics and dissemination The study protocol has been approved by the Department of Defense Human Protection Research Office and will be approved by the institutional review board of all participating centres. Study findings will be disseminated through presentations at national

  12. Comorbidity as a contributor to frequent severe acute exacerbation in COPD patients

    PubMed Central

    Jeong, Suk Hyeon; Lee, Hyun; Carriere, KC; Shin, Sun Hye; Moon, Seong Mi; Jeong, Byeong-Ho; Koh, Won-Jung; Park, Hye Yun

    2016-01-01

    Background Comorbidities have a serious impact on the frequent severe acute exacerbations (AEs) in patients with COPD. Previous studies have used the Charlson comorbidity index to represent a conglomerate of comorbidities; however, the respective contribution of each coexisting disease to the frequent severe AEs remains unclear. Methods A retrospective, observational study was performed in 77 COPD patients who experienced severe AE between January 2012 and December 2014 and had at least 1-year follow-up period from the date of admission for severe AE. We explored the incidence of frequent severe AEs (≥2 severe AEs during 1-year period) in these patients and investigated COPD-related factors and comorbidities as potential risk factors of these exacerbations. Results Out of 77 patients, 61 patients (79.2%) had at least one comorbidity. During a 1-year follow-up period, 29 patients (37.7%) experienced frequent severe AEs, approximately two-thirds (n=19) of which occurred within the first 90 days after admission. Compared with patients not experiencing frequent severe AEs, these patients were more likely to have poor lung function and receive home oxygen therapy and long-term oral steroids. In multiple logistic regression analysis, coexisting asthma (adjusted odds ratio [OR] =4.02, 95% confidence interval [CI] =1.30–12.46, P=0.016), home oxygen therapy (adjusted OR =9.39, 95% CI =1.60–55.30, P=0.013), and C-reactive protein (adjusted OR =1.09, 95% CI =1.01–1.19, P=0.036) were associated with frequent severe AEs. In addition, poor lung function, as measured by forced expiratory volume in 1 second (adjusted OR =0.16, 95% CI =0.04–0.70, P=0.015), was inversely associated with early (ie, within 90 days of admission) frequent severe AEs. Conclusion Based on our study, among COPD-related comorbidities, coexisting asthma has a significant impact on the frequent severe AEs in COPD patients. PMID:27536097

  13. Bacterial flora in the sputum and comorbidity in patients with acute exacerbations of COPD

    PubMed Central

    Boixeda, Ramon; Almagro, Pere; Díez-Manglano, Jesús; Cabrera, Francisco Javier; Recio, Jesús; Martin-Garrido, Isabel; Soriano, Joan B

    2015-01-01

    Objective To determine in patients admitted with an acute exacerbation of chronic obstructive pulmonary disease (AE-COPD) the association between the isolation of potential pathogens in a conventional sputum culture and comorbidities. Patients and methods The ESMI study is a multicenter observational study. Patients with AE-COPD admitted to the Internal Medicine departments of 70 hospitals were included. The clinical characteristics, treatments, and comorbidities were gathered. The results of conventional sputum cultures were recorded. Results A total of 536 patients were included, of which 161 produced valid sputum and a potentially pathogenic microorganism was isolated from 88 subjects (16.4%). The isolation of Pseudomonas aeruginosa (30.7%) was associated with a greater severity of the lung disease (previous admissions [P= 0.026], dyspnea scale [P=0.047], post-broncodilator forced expiratory volume in 1 second (FEV1) [P=0.005], and the BODEx index [P=0.009]); also with higher prevalence of cor pulmonale (P=0.017), heart failure (P=0.048), and cerebrovascular disease (P=0.026). Streptococcus pneumoniae (26.1%) was associated with more comorbidity according to number of diseases (P=0.018); notably, peripheral artery disease (P=0.033), hypertension (P=0.029), dyslipidemia (P=0.039), osteoporosis (P=0.0001), and depression (P=0.005). Conclusion Patients with AE-COPD and P. aeruginosa present higher severity of COPD, while those with S. pneumoniae present greater comorbidity. The potentially pathogenic microorganism obtained in the sputum culture depends on the associated comorbidities. PMID:26664106

  14. Validation of the DECAF score to predict hospital mortality in acute exacerbations of COPD

    PubMed Central

    Echevarria, C; Steer, J; Heslop-Marshall, K; Stenton, SC; Hickey, PM; Hughes, R; Wijesinghe, M; Harrison, RN; Steen, N; Simpson, AJ; Gibson, GJ; Bourke, SC

    2016-01-01

    Background Hospitalisation due to acute exacerbations of COPD (AECOPD) is common, and subsequent mortality high. The DECAF score was derived for accurate prediction of mortality and risk stratification to inform patient care. We aimed to validate the DECAF score, internally and externally, and to compare its performance to other predictive tools. Methods The study took place in the two hospitals within the derivation study (internal validation) and in four additional hospitals (external validation) between January 2012 and May 2014. Consecutive admissions were identified by screening admissions and searching coding records. Admission clinical data, including DECAF indices, and mortality were recorded. The prognostic value of DECAF and other scores were assessed by the area under the receiver operator characteristic (AUROC) curve. Results In the internal and external validation cohorts, 880 and 845 patients were recruited. Mean age was 73.1 (SD 10.3) years, 54.3% were female, and mean (SD) FEV1 45.5 (18.3) per cent predicted. Overall mortality was 7.7%. The DECAF AUROC curve for inhospital mortality was 0.83 (95% CI 0.78 to 0.87) in the internal cohort and 0.82 (95% CI 0.77 to 0.87) in the external cohort, and was superior to other prognostic scores for inhospital or 30-day mortality. Conclusions DECAF is a robust predictor of mortality, using indices routinely available on admission. Its generalisability is supported by consistent strong performance; it can identify low-risk patients (DECAF 0–1) potentially suitable for Hospital at Home or early supported discharge services, and high-risk patients (DECAF 3–6) for escalation planning or appropriate early palliation. Trial registration number UKCRN ID 14214. PMID:26769015

  15. High Prevalence of Acute Exacerbation of Interstitial Lung Disease in Japanese Patients with Systemic Sclerosis.

    PubMed

    Tomiyama, Fumiko; Watanabe, Ryu; Ishii, Tomonori; Kamogawa, Yukiko; Fujita, Yoko; Shirota, Yuko; Sugimura, Koichiro; Fujii, Hiroshi; Harigae, Hideo

    2016-01-01

    Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by extensive fibrosis and autoantibodies. Its clinical manifestations are diverse and include Raynaud's phenomenon, gastrointestinal dysmotility, interstitial lung disease (ILD), pulmonary hypertension, and renal crisis. Among these, ILD is the primary cause of SSc-related death. It has been considered that acute exacerbation of ILD (AE-ILD) is not common in patients with SSc; however, little is known about the prevalence of AE-ILD in Japanese patients with SSc. In this study, we aimed to clarify the prevalence, clinical characteristics, and prognosis of patients with SSc who developed AE-ILD and to identify predictive factors for AE-ILD in our Japanese cohorts. Clinical data of patients who visited our department from 1990 to 2014 and fulfilled the 2013 classification criteria for SSc were retrospectively reviewed. A total of 139 patients were enrolled. The mean age of onset was 49.1 years, and 113 (81.3%) patients were female; 116 (83.5%) had limited cutaneous involvement, and the overall 10-year survival rate was 92.0%. Among 66 (47.5%) patients with ILD, 13 (9.4%) developed AE-ILD. Patients with AE-ILD had a significantly higher incidence of overlap with polymyositis (PM) or dermatomyositis (DM) and lower prevalence of anticentromere antibodies with higher mortality rate compared with those without AE-ILD. Multivariate Cox regression analysis identified that an overlap with PM or DM was the most significant predictive factor for AE-ILD. Our study results suggest that Japanese patients with SSc, particularly patients overlapped with PM or DM, have a high risk of AE-ILD. PMID:27487743

  16. Mechanisms of Chronic Obstructive Pulmonary Disease Exacerbations.

    PubMed

    Wedzicha, Jadwiga A

    2015-11-01

    Chronic obstructive pulmonary disease (COPD) exacerbations are important events that contribute to worsening health status, disease progression, and mortality. They are mainly triggered by respiratory viruses (especially rhinovirus, the cause of the common cold), but airway bacteria are also involved in their pathogenesis. Exacerbations are associated with both airway and systemic inflammation and, this is mainly neutrophilic in origin. Some patients are especially prone to develop exacerbations, and these have been identified as a high-risk group with increased airway inflammation and greater disease progression. Management of acute exacerbations involves therapy with oral corticosteroids and/or antibiotics, and new therapies are needed. A number of interventions may prevent exacerbations, including vaccination, long-acting bronchodilators, antiinflammatory agents, and long-term antibiotic therapy. Understanding of the pathophysiological mechanisms of COPD exacerbations is important to develop novel therapies.

  17. Procalcitonin levels in acute exacerbation of COPD admitted in ICU: a prospective cohort study

    PubMed Central

    Daubin, Cédric; Parienti, Jean-Jacques; Vabret, Astrid; Ramakers, Michel; Fradin, Sabine; Terzi, Nicolas; Freymuth, François; Charbonneau, Pierre; du Cheyron, Damien

    2008-01-01

    Background Antibiotics are recommended for severe acute exacerbation of chronic obstructive pulmonary disease (AECOPD) admitted to intensive care units (ICU). Serum procalcitonin (PCT) could be a useful tool for selecting patients with a lower probability of developing bacterial infection, but its measurement has not been investigated in this population. Methods We conducted a single center prospective cohort study in consecutive COPD patients admitted to the ICU for AECOPD between September 2005 and September 2006. Sputum samples or tracheal aspirates were tested for the presence of bacteria and viruses. PCT levels were measured at the time of admittance, six hours, and 24 hours using a sensitive immunoassay. Results Thirty nine AECOPD patients were included, 31 of which (79%) required a ventilator support at admission. The median [25%–75% interquartile range] PCT level, assessed in 35/39 patients, was: 0.096 μg/L [IQR, 0.065 to 0.178] at the time of admission, 0.113 μg/L [IQR, 0.074 to 0.548] at six hours, and 0.137 μg/L [IQR, 0.088 to 0.252] at 24 hours. The highest PCT (PCTmax) levels were less than 0.1 μg/L in 14/35 (40%) patients and more than 0.25 μg/L in 10/35 (29%) patients, suggesting low and high probability of bacterial infection, respectively. Five species of bacteria and nine species of viruses were detected in 12/39 (31%) patients. Among the four patients positive for Pseudomonas aeruginosa, one had a PCTmax less than 0.25 μg/L and three had a PCTmax less than 0.1 μg/L. The one patient positive for Haemophilus influenzae had a PCTmax more than 0.25 μg/L. The presence or absence of viruses did not influence PCT at time of admission (0.068 vs 0.098 μg/L respectively, P = 0.80). Conclusion The likelihood of bacterial infection is low among COPD patients admitted to ICU for AECOPD (40% with PCT < 0.1 μg/L) suggesting a possible inappropriate use of antibiotics. Further studies are necessary to assess the impact of a procalcitonin

  18. Treatment of acute asthmatic exacerbations with an increased dose of inhaled steroid

    PubMed Central

    Garrett, J; Williams, S; Wong, C; Holdaway, D

    1998-01-01

    OBJECTIVE—To investigate the efficacy of an increased dose of inhaled steroid used within the context of an asthma self management plan for treating exacerbations of asthma.
DESIGN—Randomised, double blind, placebo controlled, crossover trial.
METHODS—Twenty eight children aged 6-14 years with asthma of mild to moderate severity were studied for six months. Eighteen pairs of exacerbations were available for analysis, during which subjects took an increased dose of inhaled steroids or continued on the same dose.
RESULTS—There was no significant difference between increasing inhaled steroids or placebo on morning or evening peak expiratory flow rates (PEFRs), diurnal peak flow variability, or symptom scores in the two weeks following an asthma exacerbation. Difference (95% confidence intervals) in baseline PEFR on days 1-3 were 3.4% (−3.5% to 10.4%) and −0.9% (−4.7% to 2.9%) for inhaled steroid and placebo, respectively. Spirometric function and the parents' opinion of the effectiveness of asthma medications at each exacerbation were also not significantly different between inhaled steroid or placebo.
CONCLUSION—This study suggests that increasing the dose of inhaled steroids at the onset of an exacerbation of asthma is ineffective and should not be included in asthma self management plans.

 PMID:9771245

  19. C-reactive protein in outpatients with acute exacerbation of COPD: its relationship with microbial etiology and severity

    PubMed Central

    Gallego, Miguel; Pomares, Xavier; Capilla, Silvia; Marcos, Maria Angeles; Suárez, David; Monsó, Eduard; Montón, Concepción

    2016-01-01

    Background C-reactive protein (CRP) measurement has proven valuable for detecting exacerbations, but its usefulness in predicting etiology remains controversial. Likewise, its potential value as a marker of severity, which is well established in patients with pneumonia, remains unproven in chronic obstructive pulmonary disease (COPD) exacerbations. Methods A cohort study of 118 patients with severe COPD and acute infectious exacerbations were included and followed up over 1 year. Episodes of exacerbations meeting Anthonisen’s criteria type I–II were evaluated, analyzing the etiology and inflammatory response as measured by CRP in blood. Results A total of 380 episodes were recorded. Full microbiological analysis was available in 265 samples. Haemophilus influenzae was the most commonly isolated bacteria and rhinovirus the most common virus. Median CRP levels from the 265 episodes were higher in the cases with positive cultures for bacteria (58.30 mg/L, interquartile range [IQR] 21.0–28.2) than in episodes only positive for viruses (37.3 mg/L, IQR 18.6–79.1) and cases negative for any microorganism (36.4 mg/L, IQR 10.8–93.7) (P<0.014). H. influenzae and Streptococcus pneumoniae reached the highest CRP levels of 74.5 mg/L (IQR 23.9–167.9) and 74.1 mg/L (IQR 42.0–220.7), respectively. In the 380 exacerbations studied, 227 (~60%) were community-managed, while 153 (~40%) required hospital admission. In the multivariate analysis to assess the influence of inflammatory response on exacerbation severity, baseline hypercapnia (odds ratio [OR]: 2.70, 95% confidence interval [CI]: 1.46–4.9) and CRP levels >100 mg/L (OR: 4.23, 95% CI: 2.12–8.44) were independent predictors after adjustment for baseline characteristics. Conclusion CRP level was higher in bacterial infections, especially when H. influenzae and S. pneumoniae were isolated. CRP values >100 mg/L were associated with a fourfold increased risk of hospital admission. Therefore, CRP blood levels may

  20. Efficacy and Safety of Cariprazine in Acute Exacerbation of Schizophrenia: Results From an International, Phase III Clinical Trial.

    PubMed

    Kane, John M; Zukin, Stephen; Wang, Yao; Lu, Kaifeng; Ruth, Adam; Nagy, Krisztián; Laszlovszky, István; Durgam, Suresh

    2015-08-01

    This phase III study evaluated the efficacy and safety of cariprazine, a dopamine D3 and D2 receptor partial agonist with preferential binding to D3 receptors, in patients with acute exacerbation of schizophrenia. Patients were randomized to 6-week double-blind treatment with placebo, cariprazine 3 to 6 mg/d, or cariprazine 6 to 9 mg/d. Primary and secondary efficacy: change from baseline to week 6 in Positive and Negative Syndrome Scale total and Clinical Global Impressions-Severity scores, respectively, analyzed using a mixed-effects model for repeated measures adjusting for multiple comparisons. Safety included treatment-emergent adverse events, clinical laboratory values, vital signs, electrocardiograms, ophthalmologic examination, Columbia-Suicide Severity Rating Scale, and extrapyramidal symptom scales. In the Safety Population (placebo, n = 147; cariprazine 3-6 mg/d, n = 151; cariprazine 6-9 mg/d, n = 148), 60.5% of patients completed the study. At week 6, statistically significant least squares mean differences in favor of cariprazine versus placebo were observed for Positive and Negative Syndrome Scale total score (3-6 mg/d: -6.8, P = 0.003; 6-9 mg/d: -9.9, P < 0.001) and Clinical Global Impressions-Severity (3-6 mg/d: -0.3, P = 0.012; 6-9 mg/d: -0.5, P < 0.001). Common treatment-emergent adverse events (≥5% and twice the rate of placebo) in both cariprazine groups were akathisia, extrapyramidal disorder, and tremor; most were mild to moderate in severity. Mean changes in metabolic parameters were generally small and similar between groups. Prolactin levels decreased in all groups. In conclusion, cariprazine 3 to 6 and 6 to 9 mg/d versus placebo demonstrated significant improvement on primary and secondary efficacy parameters. Cariprazine was generally well tolerated. These results suggest that cariprazine may be a new and effective treatment for schizophrenia. PMID:26075487

  1. Association of disease activity with acute exacerbation of interstitial lung disease during tocilizumab treatment in patients with rheumatoid arthritis: a retrospective, case-control study.

    PubMed

    Akiyama, Mitsuhiro; Kaneko, Yuko; Yamaoka, Kunihiro; Kondo, Harumi; Takeuchi, Tsutomu

    2016-06-01

    The objective of the study was to identify risk factors for acute exacerbation of interstitial lung disease (ILD) during tocilizumab treatment in patients with rheumatoid arthritis (RA). This is a retrospective, case-control study. We reviewed 395 consecutive RA patients who received tocilizumab. First, we divided the patients according to the presence (RA-ILD) or absence of ILD (non-ILD) assessed by chest X-ray or high-resolution computed tomography, and compared them for characteristics relevant to RA-ILD. Subsequently, focusing on the patients with RA-ILD, we assessed their baseline characteristics and clinical courses comparing patients with acute exacerbation to those without. Comparing 78 with ILD and 317 without ILD, the following were identified as factors related to RA-ILD on multivariate analysis: age 60 years or older (OR 4.5, 95 % CI 2.2-9.4, P < 0.0001), smoking habit (OR 2.9, 95 % CI 1.5-5.5, P = 0.002), and high rheumatoid factor levels (OR 2.8, 95 % CI 1.4-5.5, P = 0.002). Of 78 RA-ILD patients, six developed acute exacerbation during tocilizumab treatment. The median duration between the initiation of tocilizumab treatment and the acute exacerbation occurrence was 48 weeks. While baseline characteristics did not differ between acute exacerbation and non-acute exacerbation groups, patients experiencing acute exacerbation had significantly higher Clinical Disease Activity Index (CDAI) at 24 weeks (20.8 vs. 6.2, P = 0.019). Univariate analysis showed that CDAI > 10 at 24 weeks was a risk factor for acute exacerbation (OR 4.7, 95 % CI 2.1-10.4, P = 0.02). Uncontrolled arthritis activity during tocilizumab treatment may be associated with acute exacerbation of RA-ILD, suggesting post-treatment monitoring of disease activity is important not only with respect to RA itself but also for RA-ILD.

  2. Lower diffusing capacity with chronic bronchitis predicts higher risk of acute exacerbation in chronic obstructive lung disease

    PubMed Central

    Lee, Hwa Young; Kim, Jin Woo; Lee, Sang Haak; Yoon, Hyoung Kyu; Shim, Jae Jeong; Park, Jeong-Woong; Lee, Jae-Hyung; Yoo, Kwang Ha; Jung, Ki-Suck

    2016-01-01

    Background This study was designed to evaluate the effect of chronic bronchitis (CB) symptoms and degree of emphysema in a multicenter Korean cohort. Methods From April 2012 to May 2015, patients diagnosed with chronic obstructive lung disease (COPD) who were aged above 40 years at 46 hospitals throughout Korea were enrolled. All of the patients were classified according to CB symptoms and the diffusing capacity of the lung for carbon monoxide (DLCO); demographic data, symptom scores, and the result of lung function tests and exacerbations were then analyzed. Results A total of 812 patients were enrolled. Among these patients, 285 (35.1%) had CB symptoms. A total of 51% of patients had high DLCO without CB symptoms [CB (−) high DLCO], 24.9% had CB symptoms only [CB (+) high DLCO], 14.2% had low DLCO only [CB (−) low DLCO], and 10.2% had both low DLCO and CB [CB (+) low DLCO]. Patients with CB (+) low DLCO showed a significantly lower post-bronchodilator (BD) forced expiratory volume for 1 second (FEV1) and more severe dyspnea than patients with CB (−) high DLCO. On multivariate analysis, the risk of acute exacerbation was two times higher [odds ratio (OR) 2.06; 95% confidence interval (CI): 1.18–3.62; P=0.01] in the CB (+) low DLCO group than in the CB (−) high DLCO group. Conclusions In this COPD cohort, patients showed distinct clinical characteristics and outcomes according to the presence of CB and degree of DLCO. CB and low DLCO were associated with the risk of acute exacerbation. PMID:27293847

  3. Relevance of serology for Mycoplasma pneumoniae diagnosis compared with PCR and culture in acute exacerbation of bronchial asthma.

    PubMed

    El Sayed Zaki, Maysaa; Raafat, Doaa; El Metaal, Amal Abd

    2009-01-01

    We studied Mycoplasma pneumoniae as the etiologic pathogen in acute exacerbations of asthma and the value of polymerase chain reaction (PCR), culture, and serologic tests for its accurate diagnosis. For the study, 59 nonsmoking patients with asthma (37 females, 22 males; age, 15-50 years) underwent clinical, radiologic, and laboratory examinations. Bacteria isolated from sputum were Streptococcus pneumoniae (32 [54%]), Staphylococcus aureus (23 [39%]), and M pneumoniae (5 [15%]). All M pneumoniae were associated with S pneumoniae (8/32 [25%]) and S aureus (1/23 [4%]). No M pneumoniae were isolated as single pathogens. Serologic testing for M pneumoniae revealed that all samples were positive for specific IgG; 40 (68%) had a high titer, and 19 (32%) had a moderate titer. Of 59 samples, 29 (49%) were positive by Serodia Myco II gelatin particle testing (Fujirebio, Tokyo, Japan). PCR was positive in 25 samples, all of which had a high IgG titer; all culture-positive cases were PCR+. M pneumoniae is a common bacterial pathogen associated with acute exacerbations of asthma in people 15 years or older. Prompt laboratory diagnosis of M pneumoniae requires direct detection by PCR and culture. A high serologic titer can be a clue for the presence of M pneumoniae.

  4. In Vivo Acute on Chronic Ethanol Effects in Liver: A Mouse Model Exhibiting Exacerbated Injury, Altered Metabolic and Epigenetic Responses.

    PubMed

    Shukla, Shivendra D; Aroor, Annayya R; Restrepo, Ricardo; Kharbanda, Kusum K; Ibdah, Jamal A

    2015-11-20

    Chronic alcoholics who also binge drink (i.e., acute on chronic) are prone to an exacerbated liver injury but its mechanism is not understood. We therefore investigated the in vivo effects of chronic and binge ethanol ingestion and compared to chronic ethanol followed by three repeat binge ethanol on the liver of male C57/BL6 mice fed ethanol in liquid diet (4%) for four weeks followed by binge ethanol (intragastric administration, 3.5 g/kg body weight, three doses, 12h apart). Chronic followed by binge ethanol exacerbated fat accumulation, necrosis, decrease in hepatic SAM and SAM:SAH ratio, increase in adenosine levels, and elevated CYP2E1 levels. Histone H3 lysine acetylation (H3AcK9), dually modified phosphoacetylated histone H3 (H3AcK9/PS10), and phosphorylated H2AX increased after binge whereas phosphorylation of histone H3 ser 10 (H3S10) and H3 ser 28 (H3S28) increased after chronic ethanol-binge. Histone H3 lysine 4 and 9 dimethylation increased with a marked dimethylation in H3K9 in chronic ethanol binge group. Trimethylated histone H3 levels did not change. Nuclear levels of histone acetyl transferase GCN5 and histone deacetylase HDAC3 were elevated whereas phospho-CREB decreased in a distinctive manner. Taken together, acute on chronic ethanol ingestion caused amplification of liver injury and elicited characteristic profiles of histone modifications, metabolic alterations, and changes in nuclear protein levels. These findings demonstrate that chronic ethanol exposure renders liver more susceptible to repeat acute/binge ethanol induced acceleration of alcoholic liver disease.

  5. Chronic obstructive pulmonary disease: the clinical management of an acute exacerbation

    PubMed Central

    Hurst, J; Wedzicha, J

    2004-01-01

    Exacerbations of chronic obstructive pulmonary disease impose a considerable burden of morbidity, mortality, and health care cost. Management guidelines outlining best practice, based largely on consensus expert opinion, were produced by a number of organisations during the last decade. Current interest in the field is high. This has resulted in the publication of many further studies which have extended our understanding of the pathology involved and provided, for the first time, an evidence base for many of the therapeutic options. In this review we aim to bring the non-specialist reader up to date with current management principles and the evidence underlying such interventions. PMID:15356350

  6. Prediction of relapse within eight weeks after an acute asthma exacerbation in adults.

    PubMed

    McCarren, M; McDermott, M F; Zalenski, R J; Jovanovic, B; Marder, D; Murphy, D G; Kampe, L M; Misiewicz, V M; Rydman, R J

    1998-02-01

    Associations between historical, presenting, and treatment-related characteristics and relapse within 8 weeks after a moderate to severe asthma exacerbation were studied in a cohort of 284 adult asthmatics. Data were collected prospectively, and a multivariate model was developed and internally validated. Within 10 days, only 8% had relapsed, increasing to 45% by 8 weeks. Three variables that could be identified at the time of discharge were independently associated with relapse. These included: having made three or more visits to an emergency department in the prior 6 months (hazard ratio (HR) = 2.3, 95% CI = 1.6-3.4); difficulty performing work or activities as a result of physical health in the 4 weeks prior (HR = 2.7, 95% CI = 1.6-4.3); discontinuing hospital-based treatment for the exacerbation within 24 hours without having achieved a peak expiratory flow rate of at least 50% of predicted (HR = 2.6, 95% CI = 1.6-4.1). These risk factors may help to identify patients with poorly controlled asthma in need of more intensive and comprehensive management. PMID:9474071

  7. Contribution of influenza to acute exacerbations of chronic obstructive pulmonary disease in Kashmir, India, 2010-2012.

    PubMed

    Koul, Parvaiz A; Khan, Umar H; Asad, Romana; Yousuf, Rubaya; Broor, Shobha; Lal, Renu B; Dawood, Fatimah S

    2015-01-01

    We estimate the contribution of influenza to hospitalizations for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in Kashmir, India. Prospective surveillance for influenza among patients hospitalized with AECOPD was conducted at a tertiary care hospital. Patients had clinical data collected and nasal/throat swabs tested for influenza viruses. Outcomes among patients with and without influenza were compared with logistic regression adjusting for age and underlying conditions. During October 2010-September 2012, 498 patients hospitalized with AECOPD were enrolled, of whom 40 (8%) had received influenza vaccine. Forty (8%) had influenza; influenza virus detection peaked in winter (January-March). Patients with influenza were more likely to die during hospitalization (adjusted OR 3.4, CI 1.0-11.4) than those without.

  8. Clinical efficacy of farcosolvin syrup (ambroxol–theophylline–guaiphenesin mixture) in the treatment of acute exacerbation of chronic bronchitis

    PubMed Central

    Yakoot, Mostafa; Salem, Amel; Omar, Abdel-Mohsen

    2010-01-01

    Background: Acute exacerbations of chronic bronchitis (AECB) are defined as recurrent attacks of worsening bronchial inflammation that are marked by an increase in the volume of daily sputum produced, a change in color of the expectorated sputum, and worsening dyspnea. Farcosolvin® (Pharco Pharmaceuticals, Alexandria, Egypt) is a mixture of ambroxol (15 mg); theophylline (50 mg); and guaiphenesin (30 mg), per 5 mL syrup. Objective: To test the clinical efficacy of Farcosolvin in the treatment of AECB in a randomized, single-blinded, controlled study design. Patients and methods: One hundred patients with AECB were randomized to either Farcosolvin or guaiphenesin treatment groups, in addition to the standard medical treatment for their cases. Baseline clinical symptomatolgy of breathlessness, cough, and sputum severity scoring were compared before and after 3 and 7 days of treatment in both groups and the differences compared between groups. Changes in perceived improvement were also compared between groups using the Clinical Global Impression of Improvement or Change Scale (CGIC). Results: There were statistically significant improvements in breathlessness and cough scores in both groups (pretreatment versus posttreatment at day 3 and at day 7; P < 0.05). There were highly statistically significant differences between groups in improvement in breathlessness and cough scores, after 3 and 7 days treatment, in favor of the Farcosolvin treatment group (P < 0.001). Out of 50 patients, 48 (96%) in the Farcosolvin-treated group rated their improvement on the CGIC scale as “much” and “very much” improved, while only 41 patients (82%) reported such a degree of improvement in the control group. The difference was statistically significant (P < 0.05). Conclusion: We concluded from our study that Farcosolvin syrup might be safe and effective in improving symptoms in cases of acute exacerbation of chronic bronchitis. PMID:20714379

  9. Genome Anatomy of Streptococcus parasanguinis Strain C1A, Isolated from a Patient with Acute Exacerbation of Chronic Obstructive Pulmonary Disease, Reveals Unusual Genomic Features

    PubMed Central

    Ng, Kim Tien; Pang, Yong Kek; Chong, Teik Min; Kamarulzaman, Adeeba; Yin, Wai-Fong; Tee, Kok Keng

    2015-01-01

    Streptococcus parasanguinis causes invasive diseases. However, the mechanism by which it causes disease remains unclear. Here, we describe the complete genome sequence of S. parasanguinis C1A, isolated from a patient diagnosed with an acute exacerbation of chronic obstructive pulmonary disease. Several genes that might be associated with pathogenesis are also described. PMID:26021924

  10. Terbufos-sulfone exacerbates cardiac lesions in diabetic rats: a sub-acute toxicity study.

    PubMed

    Nurulain, Syed M; Shafiullah, Mohamed; Yasin, Javed; Adem, Abdu; Kaabi, Juma Al; Tariq, Saeed; Adeghate, Ernest; Ojha, Shreesh

    2016-06-01

    Organophosphorus compounds (OPCs) have a wide range of applications, from agriculture to warfare. Exposure to these brings forward a varied kind of health issues globally. Terbufos is one of the leading OPCs used worldwide. The present study investigates the cardiac effect of no observable dose of a metabolite of terbufos, terbufos-sulfone (TS), under non-diabetic and streptozotocin-induced diabetic condition. One hundred nanomoles per rat (1/20 of LD50) was administered intraperitoneally to adult male Wister rats daily for fifteen days. The left ventricle was collected for ultrastructural changes by transmission electron microscopy. The blood samples were collected for biochemical tests including RBC acetylcholinesterase, creatinine kinase (CK), lactate dehydrogenase (LDH), cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides, ALT, AST, and GGT. The study revealed about 10 % inhibition of RBC-AChE in two weeks of TS treatment in non-diabetic rats whereas RBC-AChE activity was significantly decreased in diabetic TS treated rats. CK, LDH, and triglycerides were significantly higher in diabetic TS treated rats. Electron microscopy of the heart showed derangement and lesions of the mitochondria of cardiomyocytes in the TS treated groups. The present study concludes that a non-lethal dose of TS causes cardiac lesions which exacerbate under diabetic condition. Biochemical tests confirmed the ultrastructural changes. It is concluded that a non-lethal dose of TS may be a risk factor for a cardiovascular disease, which may be fatal under diabetic condition. PMID:27331300

  11. Exacerbations of COPD

    PubMed Central

    Pavord, Ian D; Jones, Paul W; Burgel, Pierre-Régis; Rabe, Klaus F

    2016-01-01

    Exacerbations of chronic obstructive pulmonary disease (COPD) are defined as sustained worsening of a patient’s condition beyond normal day-to-day variations that is acute in onset, and that may also require a change in medication and/or hospitalization. Exacerbations have a significant and prolonged impact on health status and outcomes, and negative effects on pulmonary function. A significant proportion of exacerbations are unreported and therefore left untreated, leading to a poorer prognosis than those treated. COPD exacerbations are heterogeneous, and various phenotypes have been proposed which differ in biologic basis, prognosis, and response to therapy. Identification of biomarkers could enable phenotype-driven approaches for the management and prevention of exacerbations. For example, several biomarkers of inflammation can help to identify exacerbations most likely to respond to oral corticosteroids and antibiotics, and patients with a frequent exacerbator phenotype, for whom preventative treatment is appropriate. Reducing the frequency of exacerbations would have a beneficial impact on patient outcomes and prognosis. Preventative strategies include modification of risk factors, treatment of comorbid conditions, the use of bronchodilator therapy with long-acting β2-agonists or long-acting muscarinic antagonists, and inhaled corticosteroids. A better understanding of the mechanisms underlying COPD exacerbations will help to optimize use of the currently available and new interventions for preventing and treating exacerbations. PMID:26937187

  12. Pancreatic Protein Tyrosine Phosphatase 1B Deficiency Exacerbates Acute Pancreatitis in Mice.

    PubMed

    Bettaieb, Ahmed; Koike, Shinichiro; Chahed, Samah; Bachaalany, Santana; Griffey, Stephen; Sastre, Juan; Haj, Fawaz G

    2016-08-01

    Acute pancreatitis (AP) is a common and devastating gastrointestinal disorder that causes significant morbidity. The disease starts as local inflammation in the pancreas that may progress to systemic inflammation and complications. Protein tyrosine phosphatase 1B (PTP1B) is implicated in inflammatory signaling, but its significance in AP remains unclear. To investigate whether PTP1B may have a role in AP, we used pancreas PTP1B knockout (panc-PTP1B KO) mice and determined the effects of pancreatic PTP1B deficiency on cerulein- and arginine-induced acute pancreatitis. We report that PTP1B protein expression was increased in the early phase of AP in mice and rats. In addition, histological analyses of pancreas samples revealed enhanced features of AP in cerulein-treated panc-PTP1B KO mice compared with controls. Moreover, cerulein- and arginine-induced serum amylase and lipase were significantly higher in panc-PTP1B KO mice compared with controls. Similarly, pancreatic mRNA and serum concentrations of the inflammatory cytokines IL-1B, IL-6, and tumor necrosis factor-α were increased in panc-PTP1B KO mice compared with controls. Furthermore, panc-PTP1B KO mice exhibited enhanced cerulein- and arginine-induced NF-κB inflammatory response accompanied with increased mitogen-activated protein kinases activation and elevated endoplasmic reticulum stress. Notably, these effects were recapitulated in acinar cells treated with a pharmacological inhibitor of PTP1B. These findings reveal a novel role for pancreatic PTP1B in cerulein- and arginine-induced acute pancreatitis. PMID:27461362

  13. Keep off the grass: marijuana use and acute cardiovascular events.

    PubMed

    Caldicott, David G E; Holmes, James; Roberts-Thomson, Kurt C; Mahar, Leo

    2005-10-01

    Marijuana is one of the most widely used recreational substances in the world, considered by many consumers as a relatively safe drug with few significant side-effects. We report the case of a 21-year-old man who suffered an acute myocardial infarction following the use of marijuana, despite having no other identifiable risk factors for an acute cardiovascular event. We review the published medical literature regarding acute cardiovascular events following marijuana use and postulate a possible mechanism for this unusual pathological consequence of marijuana use.

  14. Differential prognostic utility of NTproBNP and Cystatin C in patients with acute exacerbation of chronic pulmonary disease

    PubMed Central

    Pérez-Calvo, Juan I; Sánchez-Marteles, Marta; Ruiz-Ruiz, Francisco-José; Morales-Rull, José-Luis; Nieto-Rodríguez, José-Antonio

    2010-01-01

    Objectives To determine whether serum Cystatin C (CysC) and NTproBNP have prognostic value among patients with long-standing chronic lung disease. Design Prospective, observational, non-interventional study. Setting CysC and NTproBNP are prognostic markers in several cardiac conditions. In addition, CysC acts as an antiprotease following Cathepsin activation, which has been involved in the pathogenesis of chronic obstructive pulmonary disease. Participants Patients with a basal functional status of II-IV (NYHA), admitted for an acute exacerbation of chronic pulmonary diseases and no previous history of symptoms related to pulmonary hypertension or heart failure. Main outcome measures NTproBNP and CysC were determined at admission in 107 patients with acute exacerbation of chronic lung disease. During 12-month follow-up, mortality, new hospital admissions and prescription of diuretics were recorded. Results During follow-up there were eight patient deaths (7.5%). Mean NTproBNP among the deceased was 1510.20 pg/mL (95% CI 498.44–4628.55) vs 502.70 pg/mL (95% CI 395.44–645.48) among survivors (p = 0.01). Twenty-seven patients (25%) were prescribed loop diuretics. Mean concentration of CysC was 1.45 mg/dL (95% CI 1.21–1.69 mg/dL) vs 1.17 mg/dL (95% IC 1.09–1.25 mg/dL) in those not prescribed (p = 0.004). NTproBNP concentration was 837.14 pg/mL (95% CI 555.57–1274.10 pg/mL) in patients prescribed diuretics vs 473.42 pg/mL (95% CI 357.80–632.70 pg/mL) in those not prescribed (p = 0.03). Kaplan-Meier analysis revealed a significant difference between death and diuretic prescription during follow-up when cut-off value for NTproBNP was 550 pg/mL (p = 0.03 and p = 0.02, respectively). For 1.16mg/dL of CsysC, a significant difference was only observed in diuretic prescription (p = 0.007). Conclusions In patients with chronic respiratory diseases NTproBNP has predictive value in terms of mortality whereas CysC does not. However, it is still possible that both can

  15. A one-year survey on the use of a powder from Rosa canina lito in acute exacerbations of chronic pain.

    PubMed

    Chrubasik, C; Wiesner, L; Black, A; Müller-Ladner, U; Chrubasik, S

    2008-09-01

    This pilot surveillance included 152 patients with acute exacerbations of chronic pain, 124 (Back group) with non-specific low back pain (NSLBP), 20 with NSLBP overridden by osteoarthritic pain (Knee-Hip group), and eight with specific LBP (included in the safety analysis). Patients were recommended the rose hip and seed powder Litozin at a dose providing up to 3 mg of galactolipid/day for up to 54 weeks. Clinical symptoms and well-being were assessed every 6 weeks. The patients also kept a diary of their pain and the requirement for rescue medication. Data were analysed by intention to treat with last observation carried forward. Only 77 patients completed the year of surveillance. Multivariate analysis suggested an appreciable overall improvement during the surveillance, irrespective of group, and this was reflected for most of the individual measures in repeated measures ANOVA. The degree and time-course of improvement echoed that seen in similar surveillances of patients receiving an aqueous extract of Harpagophytum. Multiple regression analyses indicated that percentage changes from baseline tended to be greater in patients with greater degrees of pain and disability, but were otherwise largely unrelated to the patients' characteristics. There were no serious adverse events. The rose hip and seed powder, Litozin, seems to deserve further, more definitive studies as a possible option in long-term management of NSLBP with or without osteoarthritic pain. PMID:18729248

  16. Community-acquired pneumonia and survival of critically ill acute exacerbation of COPD patients in respiratory intensive care units

    PubMed Central

    Lu, Zhiwei; Cheng, Yusheng; Tu, Xiongwen; Chen, Liang; Chen, Hu; Yang, Jian; Wang, Jinyan; Zhang, Liqin

    2016-01-01

    Purpose The aim of this study was to appraise the effect of community-acquired pneumonia (CAP) on inhospital mortality in critically ill acute exacerbation of COPD (AECOPD) patients admitted to a respiratory intensive care unit. Patients and methods A retrospective observational study was performed. Consecutive critically ill AECOPD patients receiving treatment in a respiratory intensive care unit were reviewed from September 1, 2012, to August 31, 2015. Categorical variables were analyzed using chi-square tests, and continuous variables were analyzed by Mann–Whitney U-test. Kaplan–Meier analysis was used to assess the association of CAP with survival of critically ill AECOPD patients for univariate analysis. Cox’s proportional hazards regression model was performed to identify risk factors for multivariate analysis. Results A total of 80 consecutive eligible individuals were reviewed. These included 38 patients with CAP and 42 patients without CAP. Patients with CAP had a higher inhospital rate of mortality than patients without CAP (42% vs 33.3%, P<0.05). Kaplan–Meier survival analysis showed that patients with CAP had a worse survival rate than patients without CAP (P<0.05). Clinical characteristics, including Acute Physiology and Chronic Health Evaluation II (APACHE II) score, C-reactive protein, and CAP, were found to be closely associated with survival of AECOPD individuals. Further multivariate Cox regression analysis confirmed that CAP and APACHE II were independent risk factors for inhospital mortality in critically ill AECOPD patients (CAP: hazard ratio, 5.29; 95% CI, 1.50–18.47, P<0.01 and APACHE II: hazard ratio, 1.20; 95% CI, 1.06–1.37, P<0.01). Conclusion CAP may be an independent risk factor for higher inhospital mortality in critically ill AECOPD patients. PMID:27563239

  17. Severe Acute Asthma Exacerbation in Children: A Stepwise Approach for Escalating Therapy in a Pediatric Intensive Care Unit

    PubMed Central

    Nievas, I. Federico Fernandez; Anand, Kanwaljeet J. S.

    2013-01-01

    OBJECTIVES An increasing prevalence of pediatric asthma has led to increasing burdens of critical illness in children with severe acute asthma exacerbations, often leading to respiratory distress, progressive hypoxia, and respiratory failure. We review the definitions, epidemiology, pathophysiology, and clinical manifestations of severe acute asthma, with a view to developing an evidence-based, stepwise approach for escalating therapy in these patients. METHODS Subject headings related to asthma, status asthmaticus, critical asthma, and drug therapy were used in a MEDLINE search (1980–2012), supplemented by a manual search of personal files, references cited in the reviewed articles, and treatment algorithms developed within Le Bonheur Children's Hospital. RESULTS Patients with asthma require continuous monitoring of their cardiorespiratory status via noninvasive or invasive devices, with serial clinical examinations, objective scoring of asthma severity (using an objective pediatric asthma score), and appropriate diagnostic tests. All patients are treated with β-agonists, ipratropium, and steroids (intravenous preferable over oral preparations). Patients with worsening clinical status should be progressively treated with continuous β-agonists, intravenous magnesium, helium-oxygen mixtures, intravenous terbutaline and/or aminophylline, coupled with high-flow oxygen and non-invasive ventilation to limit the work of breathing, hypoxemia, and possibly hypercarbia. Sedation with low-dose ketamine (with or without benzodiazepines) infusions may allow better toleration of non-invasive ventilation and may also prepare the patient for tracheal intubation and mechanical ventilation, if indicated by a worsening clinical status. CONCLUSIONS Severe asthma can be a devastating illness in children, but most patients can be managed by using serial objective assessments and the stepwise clinical approach outlined herein. Following multidisciplinary education and training, this

  18. Utility of serum procalcitonin values in patients with acute exacerbations of chronic obstructive pulmonary disease: a cautionary note

    PubMed Central

    Falsey, Ann R; Becker, Kenneth L; Swinburne, Andrew J; Nylen, Eric S; Snider, Richard H; Formica, Maria A; Hennessey, Patricia A; Criddle, Mary M; Peterson, Derick R; Walsh, Edward E

    2012-01-01

    Background Serum procalcitonin levels have been used as a biomarker of invasive bacterial infection and recently have been advocated to guide antibiotic therapy in patients with chronic obstructive pulmonary disease (COPD). However, rigorous studies correlating procalcitonin levels with microbiologic data are lacking. Acute exacerbations of COPD (AECOPD) have been linked to viral and bacterial infection as well as noninfectious causes. Therefore, we evaluated procalcitonin as a predictor of viral versus bacterial infection in patients hospitalized with AECOPD with and without evidence of pneumonia. Methods Adults hospitalized during the winter with symptoms consistent with AECOPD underwent extensive testing for viral, bacterial, and atypical pathogens. Serum procalcitonin levels were measured on day 1 (admission), day 2, and at one month. Clinical and laboratory features of subjects with viral and bacterial diagnoses were compared. Results In total, 224 subjects with COPD were admitted for 240 respiratory illnesses. Of these, 56 had pneumonia and 184 had AECOPD alone. A microbiologic diagnosis was made in 76 (56%) of 134 illnesses with reliable bacteriology (26 viral infection, 29 bacterial infection, and 21 mixed viral bacterial infection). Mean procalcitonin levels were significantly higher in patients with pneumonia compared with AECOPD. However, discrimination between viral and bacterial infection using a 0.25 ng/mL threshold for bacterial infection in patients with AECOPD was poor. Conclusion Procalcitonin is useful in COPD patients for alerting clinicians to invasive bacterial infections such as pneumonia but it does not distinguish bacterial from viral and noninfectious causes of AECOPD. PMID:22399852

  19. Morphological changes in small pulmonary vessels are associated with severe acute exacerbation in chronic obstructive pulmonary disease

    PubMed Central

    Yoshimura, Katsuhiro; Suzuki, Yuzo; Uto, Tomohiro; Sato, Jun; Imokawa, Shiro; Suda, Takafumi

    2016-01-01

    Background Pulmonary vascular remodeling is essential for understanding the pathogenesis of chronic obstructive pulmonary disease (COPD). The total cross-sectional area (CSA) of small pulmonary vessels has been reported to correlate with the pulmonary artery pressure, and this technique has enabled the assessment of pulmonary vascular involvements. We investigated the contribution of morphological alterations in the pulmonary vessels to severe acute exacerbation of COPD (AE-COPD). Methods This study enrolled 81 patients with COPD and 28 non-COPD subjects as control and assessed the percentage of CSA (%CSA) less than 5 mm2 (%CSA<5) and %CSA in the range of 5–10 mm2 (%CSA5–10) on high-resolution computed tomography images. Results Compared with the non-COPD subjects, the COPD patients had lower %CSA<5. %CSA<5 was positively correlated with airflow limitation and negatively correlated with the extent of emphysema. COPD patients with lower %CSA<5 showed significantly increased incidences of severe AE-COPD (Gray’s test; P=0.011). Furthermore, lower %CSA<5 was significantly associated with severe AE-COPD (hazard ratio, 2.668; 95% confidence interval, 1.225–5.636; P=0.010). Conclusion %CSA<5 was associated with an increased risk of severe AE-COPD. The distal pruning of the small pulmonary vessels is a part of the risk associated with AE-COPD, and %CSA<5 might be a surrogate marker for predicting AE-COPD. PMID:27418816

  20. Histamine deficiency exacerbates myocardial injury in acute myocardial infarction through impaired macrophage infiltration and increased cardiomyocyte apoptosis.

    PubMed

    Deng, Long; Hong, Tao; Lin, Jinyi; Ding, Suling; Huang, Zheyong; Chen, Jinmiao; Jia, Jianguo; Zou, Yunzeng; Wang, Timothy C; Yang, Xiangdong; Ge, Junbo

    2015-08-17

    Histamine is a biogenic amine that is widely distributed and has multiple functions, but the role it plays in acute myocardial infarction (AMI) remains unclear. In this study, we investigated the origin and contribution of endogenous histamine to AMI. Histidine decarboxylase (HDC) is the unique enzyme responsible for histamine generation. Using HDC-EGFP bacterial artificial chromosome (BAC) transgenic mice in which EGFP expression is controlled by the HDC promoter, we identified HDC expression primarily in CD11b(+)Gr-1(+) immature myeloid cells (IMCs) that markedly increase in the early stages of AMI. Deficiency of histamine in HDC knockout mice (HDC(-/-)) reduced cardiac function and exacerbated the injury of infarcted heart. Furthermore, administering either an H1 receptor antagonist (pyrilamine) or an H2 receptor antagonist (cimetidine) demonstrated a protective effect of histamine against myocardial injury. The results of in vivo and in vitro assays showed that histamine deficiency promotes the apoptosis of cardiomyocytes and inhibits macrophage infiltration. In conclusion, CD11b(+)Gr-1(+) IMCs are the predominant HDC-expressing sites in AMI, and histamine plays a protective role in the process of AMI through inhibition of cardiomyocyte apoptosis and facilitation of macrophage infiltration.

  1. Intensive care unit nurses' perceptions of patient participation in the acute phase of chronic obstructive pulmonary disease exacerbation: an interview study

    PubMed Central

    Kvangarsnes, Marit; Torheim, Henny; Hole, Torstein; Öhlund, Lennart S

    2013-01-01

    Aim To report a study conducted to explore intensive care unit nurses’ perceptions of patient participation in the acute phase of chronic obstructive pulmonary disease exacerbation. Background An acute exacerbation is a life-threatening situation, which patients often consider to be extremely frightening. Healthcare personnel exercise considerable power in this situation, which challenges general professional notions of patient participation. Design Critical discourse analysis. Methods In the autumn of 2009, three focus group interviews with experienced intensive care nurses were conducted at two hospitals in western Norway. Two groups had six participants each, and one group had five (N = 17). The transcribed interviews were analysed by means of critical discourse analysis. Findings The intensive care nurses said that an exacerbation is often an extreme situation in which healthcare personnel are exercising a high degree of control and power over patients. Patient participation during exacerbation often takes the form of non-involvement. The participating nurses attached great importance to taking a sensitive approach when meeting patients. The nurses experienced challenging ethical dilemmas. Conclusion This study shows that patient participation should not be understood in universal terms, but rather in relation to a specific setting and the interactions that occur in this setting. Healthcare personnel must develop skill, understanding, and competence to meet these challenging ethical dilemmas. A collaborative inter-professional approach between physicians and nurses is needed to meet the patients’ demand for involvement. PMID:22512673

  2. Doxapram hydrochloride in the treatment of acute exacerbation of chronic respiratory failure. A patient with four episodes treated without use of a respirator.

    PubMed

    Ohi, M; Nakashima, M; Heki, S; Kato, M; Sagawa, Y

    1978-10-01

    A 51-year-old woman with chronic respiratory failure (status after tuberculosis) was given an infusion of doxapram hydrochloride (1 to 2 mg/kg of body weight per hour) for four episodes of acute exacerbation of her condition. Treatment with the drug prevented worsening of hypercapnia in the four episodes, when administration of 24 percent oxygen had occasioned rises in the arterial carbon dioxide tension of 23, 10, 9, and 7 mm Hg.

  3. Point-of-care procalcitonin test to reduce antibiotic exposure in patients hospitalized with acute exacerbation of COPD

    PubMed Central

    Corti, Caspar; Fally, Markus; Fabricius-Bjerre, Andreas; Mortensen, Katrine; Jensen, Birgitte Nybo; Andreassen, Helle F; Porsbjerg, Celeste; Knudsen, Jenny Dahl; Jensen, Jens-Ulrik

    2016-01-01

    Background This study was conducted to investigate whether point-of-care (POC) procalcitonin (PCT) measurement can reduce redundant antibiotic treatment in patients hospitalized with acute exacerbation of COPD (AECOPD). Methods One-hundred and twenty adult patients admitted with AECOPD were enrolled in this open-label randomized trial. Patients were allocated to either the POC PCT-guided intervention arm (n=62) or the control arm, in which antibiotic therapy followed local guidelines (n=58). Results The median duration of antibiotic exposure was 3.5 (interquartile range [IQR] 0–10) days in the PCT-arm vs 8.5 (IQR 1–11) days in the control arm (P=0.0169, Wilcoxon) for the intention-to-treat population. The proportion of patients using antibiotics for ≥5 days within the 28-day follow-up was 41.9% (PCT-arm) vs 67.2% (P=0.006, Fisher’s exact) in the intention-to-treat population. For the per-protocol population, the proportions were 21.1% (PCT-arm) vs 73.9% (P<0.00001, Fisher’s exact). Within 28-day follow-up, one patient died in the PCT-arm and two died in the control arm. A composite harm end point consisting of death, rehospitalization, or intensive care unit admission, all within 28 days, showed no apparent difference. Conclusion Our study shows that the implementation of a POC PCT-guided algorithm can be used to substantially reduce antibiotic exposure in patients hospitalized with AECOPD, with no apparent harm. PMID:27382274

  4. Non-invasive ventilation: comparison of effectiveness, safety, and management in acute heart failure syndromes and acute exacerbations of chronic obstructive pulmonary disease.

    PubMed

    Pladeck, T; Hader, C; Von Orde, A; Rasche, K; Wiechmann, H W

    2007-11-01

    Continuous positive airway pressure ventilation (CPAP) and non-invasive positive pressure ventilation (NPPV) are accepted treatments in acute cardiogenic pulmonary edema (ACPE) and acute exacerbation of chronic obstructive pulmonary disease (AECOPD). The aim of the study was a comparison of effectiveness, safety, and management of NPPV in ACPE and AECOPD trying to find an approach for standard management in intensive care. Thirty patients with acute respiratory failure (14 due to ACPE, 16 due to AECOPD) were prospectively included into the study. If clinical stability could not be achieved by standard therapy (pharmacological therapy and oxygen) patients were treated by non-invasive ventilation (NPPV) using a BiPAP-Vision device in S/T-mode. During the first 90 min after the onset of NPPV respiratory and vital parameters were documented every 30 min. Additional relevant outcome parameters (need for intubation, duration of ICU stay, complications and mortality) were monitored. We found that 85.7% of the ACPE patients and 50.0% of the AECOPD patients were treated successfully with NPPV. Intubation rate was 31.2% in the AECOPD group and 14.3% in the ACPE group. 78.6% of the ACPE patients and 43.8% of the AECOPD patients were regularly discharged from hospital in a good condition. In the first 90 min of NIV, there was a significant amelioration of respiratory and other vital parameters. In ACPE patients there was a significant increase in PaO2 from 58.9 mmHg to 80.6 mmHg and of oxygen saturation (SaO2) from 85.1% to 93.1% without changing the inspiratory O2 concentration. This effect was comparable in the AECOPD group, but only could be achieved by increasing the inspiratory ventilation pressure. In the ACPE group inspiratory ventilation pressure could be reduced. In conclusion, in acute respiratory failure, ACPE patients comparably profit from NPPV as do patients with AECOPD, but the algorithm of titration for non-invasive ventilation pressure is different.

  5. Worrying About Terrorism and Other Acute Environmental Health Hazard Events

    PubMed Central

    Babcock-Dunning, Lauren

    2012-01-01

    Objectives. To better understand why some people worry more about terrorism compared with others, we measured how much US residents worried about a terrorist event in their area and examined the association of their fears with their concerns about acute and chronic hazards and other correlates. Methods. In 2008 (n = 600) and 2010 (n = 651), we performed a random-digit dialing national landline telephone survey. We asked about worries about terrorism and 5 other environmental health hazard issues. We also collected demographic and socioeconomic data. Results. Only 15% worried “a great deal” about a terrorist event in their area and 18% to 33% were greatly concerned about other environmental issues. Fear about acute hazard events was a stronger predictor of a great deal of concern about terrorism than were age, race/ethnicity, gender, educational achievement, and other correlates. Conclusions. Those who worried most about acute environmental health hazard events were most likely to worry about terrorism. Also, those who were older, poorer, Blacks, or Latinos, or who lived in populous urban areas felt they were most vulnerable to terrorist attacks. We recommend methods to involve US citizens as part of disaster planning. PMID:22397346

  6. The Evidence for Intravenous Theophylline Levels between 10-20mg/L in Children Suffering an Acute Exacerbation of Asthma: A Systematic Review

    PubMed Central

    2016-01-01

    Background Intravenous theophyllines are a second line treatment for children suffering an acute exacerbation of asthma. Various guidelines and formularies recommend aiming for serum theophylline levels between 10-20mg/l. This review aims to assess the evidence underpinning this recommendation. Methods A systematic review comparing outcomes of children who achieved serum theophylline concentrations between 10-20mg/l with those who did not. Primary outcomes were time until resolution of symptoms, mortality and need for mechanical ventilation. Secondary outcomes were date until discharge criteria are met, actual discharge, adverse effects and FEV1. Data sources MEDLINE, CINAHL, CENTRAL and Web of Science. Search performed in October 2015. Eligibility criteria Interventional or observational studies utilizing intravenous theophyllines for an acute exacerbation of asthma in children where serum theophylline levels and clinical outcomes were measured. Findings 10 RCTs and 2 observational studies were included. Children with serum levels between 10-20mg/l did not have a reduction in duration of symptoms, length of hospital stay or need for mechanical ventilation or better spirometric results compared with levels <10mg/l. Levels above 20mg/l are not associated with higher rates of adverse effects. This study is limited due to heterogeneity in the way theophylline levels were reported and poor surveillance of adverse effects across studies. Conclusion Dosing strategies aiming for levels between 10-20mg/l are not associated with better outcomes. Clinicians should rely on clinical outcomes and not serum levels when using intravenous theophyllines in children suffering an acute exacerbation of asthma. PMID:27096742

  7. Juxtarenal Mycotic Aneurysm as a Complication of Acute Exacerbation of Chronic Cholecystitis Treated by Resection and Replacement by a Fresh Allograft.

    PubMed

    Grus, Tomáš; Lambert, Lukáš; Rohn, Vilém; Klika, Tomáš; Grusová, Gabriela; Michálek, Pavel

    2016-01-01

    We present a case of a female patient with infectious (mycotic) juxtarenal abdominal aneurysm with atypical symptoms beginning as acute exacerbation of chronic cholecystitis. Apart from common antibiotic treatment, the patient successfully underwent resection of the diseased segment and replacement by a fresh allograft in order to reduce the risk of infection of the graft, but with the need of subsequent life-long immunosuppressive therapy. Perioperative monitoring of the spinal cord by near infrared spectroscopy was used to identify possible spinal ischemia. The choice of the fresh allograft was based on our experience supported by review of the literature. PMID:26995203

  8. Acute Ozone (O3) Exposure Enhances Aortic Contraction in Healthy Rats while Exacerbating Pulmonary Injury in Diabetics

    EPA Science Inventory

    Air pollution exposure affects health adversely in individuals with type 2 diabetes (T2D) and diet induced obesity (DIO). We hypothesized that T2D and DIO would exacerbate O3 induced pulmonary responses and alter arterial reactivity. Male Wistar and Goto Kakizaki (GK) rats, a l...

  9. Prevalence and Prognostic Significance of Hyponatremia in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease: Data from the Akershus Cardiac Examination (ACE) 2 Study

    PubMed Central

    Brynildsen, Jon; Høiseth, Arne Didrik; Følling, Ivar; Brekke, Pål H.; Christensen, Geir; Hagve, Tor-Arne; Verbalis, Joseph G.; Omland, Torbjørn; Røsjø, Helge

    2016-01-01

    Background Hyponatremia is prevalent and associated with mortality in patients with heart failure (HF). The prevalence and prognostic implications of hyponatremia in acute exacerbation of chronic obstructive pulmonary (AECOPD) have not been established. Method We included 313 unselected patients with acute dyspnea who were categorized by etiology of dyspnea according to established guidelines (derivation cohort). Serum Na+ was determined on hospital admission and corrected for hyperglycemia, and hyponatremia was defined as [Na+]<137 mmol/L. Survival was ascertained after a median follow-up of 816 days and outcome was analyzed in acute HF (n = 143) and AECOPD (n = 83) separately. Results were confirmed in an independent AECOPD validation cohort (n = 99). Results In the derivation cohort, median serum Na+ was lower in AECOPD vs. acute HF (138.5 [135.9–140.5] vs. 139.2 [136.7–141.3] mmol/L, p = 0.02), while prevalence of hyponatremia (27% [22/83] vs. 20% [29/143], p = 0.28) and mortality rate (42% [35/83] vs. 46% [66/143], p = 0.56) were similar. By univariate Cox regression analysis, hyponatremia was associated with increased mortality in acute HF (HR 1.85 [95% CI 1.08, 3.16], p = 0.02), but not in AECOPD (HR 1.00 [0.47, 2.15], p = 1.00). Analogous to the results of the derivation cohort, hyponatremia was prevalent also in the AECOPD validation cohort (25% [25/99]), but not associated with mortality. The diverging effect of hyponatremia on outcome between AECOPD and acute HF was statistically significant (p = 0.04). Conclusion Hyponatremia is prevalent in patients with acute HF and AECOPD, but is associated with mortality in patients with acute HF only. PMID:27529844

  10. A pilot study of a mobile-phone-based home monitoring system to assist in remote interventions in cases of acute exacerbation of COPD.

    PubMed

    Ding, Hang; Karunanithi, Mohan; Kanagasingam, Yogi; Vignarajan, Janardhan; Moodley, Yuben

    2014-04-01

    We conducted a six-month feasibility study of a mobile-phone-based home monitoring system, called M-COPD. Patients with a history of moderate Acute Exacerbation of COPD (AECOPD) were given a mobile phone to record major symptoms (dyspnoea, sputum colour and volume), minor symptoms (cough and wheezing) and vital signs. A care team remotely monitored the recorded data and provided clinical interventions. Eight patients (mean age 65 years) completed the trial. Ten acute exacerbations occurred during the trial and were successfully treated at home. Prior to the AECOPD episode, the combined score of the major symptoms increased significantly (P < 0.05). Following the intervention, it decreased significantly (P < 0.05) within two weeks and returned to the baseline. The score of the minor symptoms also increased significantly (P < 0.05), but the decrease following the intervention was not significant. There were significantly fewer hospital admissions during the trial, fewer ED presentations and fewer GP visits than in a six-month matched period in the preceding year. The results demonstrate the potential of home monitoring for analysing respiratory symptoms for early intervention of AECOPD.

  11. Differences in care between general medicine and respiratory specialists in the management of patients hospitalized for acute exacerbations of chronic obstructive pulmonary disease

    PubMed Central

    Wijayaratne, Kurugamage; Wilson, Jessica; Sivakumaran, Pathmanathan; Sriram, Krishna B.

    2013-01-01

    CONTEXT: Hospitalized patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) may be managed by either respiratory specialists (RS) or general medicine physicians (GMP). While previous studies have audited the hospital AECOPD management of RS, only a small number of studies have evaluated the management of GMP. AIMS: The aims of this study were to firstly examine the differences in AECOPD management of GMP and RS and secondly compare their care to national COPD guidelines. METHODS: A retrospective review was undertaken of consecutive AECOPD patients admitted to two hospitals (one hospital where all AECOPD patients were managed by RS and another where all AECOPD patients were managed by GMP) over a 3-month period. Electronic medical records, medical case notes, pathology and radiology data for the admission were reviewed. RESULTS: There were 201 COPD exacerbations in 169 patients (49.7% male, mean age 72.3). GMP managed 84 (41.7%) exacerbations. In comparison to RS, GMP performed fewer spirometry tests, blood gas analysis and less frequently treated patients with guideline-recommended medications. Referral to pulmonary rehabilitation was poor for both groups of clinicians. Median length of stay was shorter in GMP patients versus RS patients (3 days vs. 5 days, P = 0.001). There were no differences in the 12-month re-admission (41.7% vs. 38.5%, P = 0.664) and mortality rates (10.7% vs. 6%, P = 0.292) between both groups of patients. CONCLUSION: Our study found differences in the hospital AECOPD management of GMP and RS, but these did not translate into different clinical outcomes between their patients. We also found suboptimal adherence to national COPD guidelines, suggesting that there is scope for improvement in the AECOPD management of both groups of clinicians. PMID:24250732

  12. Impact of tornadoes on hospital admissions for acute cardiovascular events

    PubMed Central

    Silva-Palacios, Federico; Casanegra, Ana Isabel; Shapiro, Alan; Phan, Minh; Hawkins, Beau; Li, Ji; Stoner, Julie; Tafur, Alfonso

    2016-01-01

    Background There is a paucity of data describing cardiovascular events after tornado outbreaks. We proposed to study the effects of tornadoes on the incidence of cardiovascular events at a tertiary care institution. Population and methods Hospital admission records from a single center situated in a tornado-prone area three months before and after a 2013 tornado outbreak were abstracted. To control for seasonal variation, we also abstracted data from the same period of the prior year (control). Hospital admissions for cardiovascular events (CVEs) including acute myocardial infarction, stroke and venous thromboembolism (VTE) were summated by zip codes, and compared by time period. Results There were 22,607 admissions analyzed, of which 6,705 (30%), 7,980 (35%), and 7,922 (35%) were during the pre-tornado, post-tornado, and control time frames, respectively. There were 344 CVE in the controls, 317 CVE in pre-tornado and 364 CVEs in post tornado periods. There was no difference in the prevalence of CVE during the post-tornado season compared with the control (PPR = 1.05 95% CI: 0.91 to 1.21, p = 0.50) or the pre-tornado season (PPR= 0.96, 95% CI: 0.83 to 1.21, p = 0.63). Conclusion In conclusion, tornado outbreaks did not increase the prevalence of cardiovascular events. In contrast to the effect of hurricanes, implementation of a healthcare policy change directed toward the early treatment and prevention of cardiovascular events after tornadoes does not seem warranted. PMID:26388119

  13. Optimization of ventilator setting by flow and pressure waveforms analysis during noninvasive ventilation for acute exacerbations of COPD: a multicentric randomized controlled trial

    PubMed Central

    2011-01-01

    Introduction The analysis of flow and pressure waveforms generated by ventilators can be useful in the optimization of patient-ventilator interactions, notably in chronic obstructive pulmonary disease (COPD) patients. To date, however, a real clinical benefit of this approach has not been proven. Methods The aim of the present randomized, multi-centric, controlled study was to compare optimized ventilation, driven by the analysis of flow and pressure waveforms, to standard ventilation (same physician, same initial ventilator setting, same time spent at the bedside while the ventilator screen was obscured with numerical data always available). The primary aim was the rate of pH normalization at two hours, while secondary aims were changes in PaCO2, respiratory rate and the patient's tolerance to ventilation (all parameters evaluated at baseline, 30, 120, 360 minutes and 24 hours after the beginning of ventilation). Seventy patients (35 for each group) with acute exacerbation of COPD were enrolled. Results Optimized ventilation led to a more rapid normalization of pH at two hours (51 vs. 26% of patients), to a significant improvement of the patient's tolerance to ventilation at two hours, and to a higher decrease of PaCO2 at two and six hours. Optimized ventilation induced physicians to use higher levels of external positive end-expiratory pressure, more sensitive inspiratory triggers and a faster speed of pressurization. Conclusions The analysis of the waveforms generated by ventilators has a significant positive effect on physiological and patient-centered outcomes during acute exacerbation of COPD. The acquisition of specific skills in this field should be encouraged. Trial registration ClinicalTrials.gov NCT01291303. PMID:22115190

  14. Readmission for Acute Exacerbation within 30 Days of Discharge Is Associated with a Subsequent Progressive Increase in Mortality Risk in COPD Patients: A Long-Term Observational Study

    PubMed Central

    Guerrero, Mónica; Crisafulli, Ernesto; Liapikou, Adamantia; Huerta, Arturo; Gabarrús, Albert; Chetta, Alfredo; Soler, Nestor; Torres, Antoni

    2016-01-01

    Background and Objective Twenty per cent of chronic obstructive pulmonary disease (COPD) patients are readmitted for acute exacerbation (AECOPD) within 30 days of discharge. The prognostic significance of early readmission is not fully understood. The objective of our study was to estimate the mortality risk associated with readmission for acute exacerbation within 30 days of discharge in COPD patients. Methods The cohort (n = 378) was divided into patients readmitted (n = 68) and not readmitted (n = 310) within 30 days of discharge. Clinical, laboratory, microbiological, and severity data were evaluated at admission and during hospital stay, and mortality data were recorded at four time points during follow-up: 30 days, 6 months, 1 year and 3 years. Results Patients readmitted within 30 days had poorer lung function, worse dyspnea perception and higher clinical severity. Two or more prior AECOPD (HR, 2.47; 95% CI, 1.51–4.05) was the only variable independently associated with 30-day readmission. The mortality risk during the follow-up period showed a progressive increase in patients readmitted within 30 days in comparison to patients not readmitted; moreover, 30-day readmission was an independent risk factor for mortality at 1 year (HR, 2.48; 95% CI, 1.10–5.59). In patients readmitted within 30 days, the estimated absolute increase in the mortality risk was 4% at 30 days (number needed to harm NNH, 25), 17% at 6-months (NNH, 6), 19% at 1-year (NNH, 6) and 24% at 3 years (NNH, 5). Conclusion In conclusion a readmission for AECOPD within 30 days is associated with a progressive increased long-term risk of death. PMID:26943928

  15. Prediction of key genes and miRNAs responsible for loss of muscle force in patients during an acute exacerbation of chronic obstructive pulmonary disease

    PubMed Central

    Duan, Yanhong; Zhou, Min; Xiao, Jian; Wu, Chaomin; Zhou, Lei; Zhou, Feng; Du, Chunling; Song, Yuanlin

    2016-01-01

    The present study aimed to identify genes and microRNAs (miRNAs or miRs) that were abnormally expressed in the vastus lateralis muscle of patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD). The gene expression profile of GSE10828 was downloaded from the Gene Expression Omnibus database, and this dataset was comprised of 4 samples from patients with AECOPD and 5 samples from patients with stable COPD. Differentially expressed genes (DEGs) were screened using the Limma package in R. A protein-protein interaction (PPI) network of DEGs was built based on the STRING database. Module analysis of the PPI network was performed using the ClusterONE plugin and functional analysis of DEGs was conducted using DAVID. Additionally, key miRNAs were enriched using gene set enrichment analysis (GSEA) software and a miR-gene regulatory network was constructed using Cytoscape software. In total, 166 up- and 129 downregulated DEGs associated with muscle weakness in AECOPD were screened. Among them, NCL, GOT1, TMOD1, TSPO, SOD2, NCL and PA2G4 were observed in the modules consisting of upregulated or downregulated genes. The upregulated DEGs in modules (including KLF6 and XRCC5) were enriched in GO terms associated with immune system development, whereas the downregulated DEGs were enriched in GO terms associated with cell death and muscle contraction. Additionally, 39 key AECOPD-related miRNAs were also predicted, including miR-1, miR-9 and miR-23a, miR-16 and miR-15a. In conclusion, DEGs (NCL, GOT1, SOD2, KLF6, XRCC5, TSPO and TMOD1) and miRNAs (such as miR-1, miR-9 and miR-23a) may be associated with the loss of muscle force in patients during an acute exacerbation of COPD which also may act as therapeutic targets in the treatment of AECOPD.

  16. Study of Pre-disposing Factors of Acute Exacerbation of Chronic Obstructive Pulmonary Disease and Antibiotic Prescribing Pattern with Reference to Antibiotic Sensitivity Test.

    PubMed

    Shrestha, R; Shrestha, B; Shakya Shrestha, S; Pant, A; Prajapati, B; Karmacharya, B M

    2015-01-01

    Background Chronic Obstructive Pulmonary Disease (COPD) affects about 329 million people worldwide, which is nearly 5% of the entire global population. In the context of Nepal, COPD accounts for 43% of the non-communicable disease burden and 2.56% of hospitalizations. Various pre-disposing factors like bacterial, viral, fungal, smoking, occupational exposures and genetic factors have been proposed to precipitate COPD and its exacerbation though, the definitive pre-disposing factors and factors related to acute exacerbation have not been determined in the context of Nepal. Objective To find out the pre-disposing factors and the related causative agents for COPD. Method A cross sectional study was conducted in a tertiary care hospital. Patients of all age group who were diagnosed as COPD and admitted in the hospital were included in this study. Patients were interviewed using structured questionnaire. The sociodemographic data including personal and medical history were recorded from those participants. In addition, sputum from those patients was sent for culture to investigate the possible responsible pathogens as well as its antibiotic sensitivity pattern. Result A total of 150 patients having Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD) who have admitted from either emergency or out-patient department of the hospital were included in this study. Among the total number of patients, more than half of them were female (n=82). In addition, analysis of occupations shows that most of them were either farmer (36.0%) or housewife (30.7%). In total studied patients (n=150), most of them were using traditional firewood (83%) for cooking purpose and majority of patients (91%) were smokers. Most of the sputum samples show growth of gram-positive cocci (26.7%) and gram negative bacilli (27.5%). Considering the overall sensitivity pattern, the higher sensitivity was recorded for Co-trimoxazole and Ciprofloxacin while higher rate of resistance was noted

  17. Serum soluble urokinase-type plasminogen activator receptor levels in male patients with acute exacerbation of schizophrenia.

    PubMed

    Genc, Abdullah; Kalelioglu, Tevfik; Karamustafalioglu, Nesrin; Tasdemir, Akif; Genc, Esra Sena; Akkus, Mustafa; Emul, Murat

    2016-02-28

    Inflammatory abnormalities have been shown in the pathogenesis of schizophrenia. Soluble urokinase-type plasminogen activator receptor (suPAR) is a protein that is measurable in the circulating blood and reflects the inflammation in the body. We aimed to investigate serum suPAR levels in patients with schizophrenia who were in acute state and to compare with healthy controls. Forty five patients and 43 healthy controls were included in the study. We found no significant difference in suPAR levels between patients and controls, suggesting that suPAR as an inflammatory marker does not have a role in the inflammatory process of acute schizophrenia.

  18. [EFFICIENCY OF COMBINATION OF ROFLUMILAST AND QUERCETIN FOR CORRECTION OXYGEN- INDEPENDENT MECHANISMS AND PHAGOCYTIC ACTIVITY OF MACROPHAGE CELLS OF PATIENTS WITH ACUTE EXACERBATION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE WHEN COMBINED WITH CORONARY HEART DISEASE].

    PubMed

    Gerych, P; Yatsyshyn, R

    2015-01-01

    Studied oxygen independent reaction and phagocytic activity of macrophage cells of patients with chronic obstructive pulmonary disease (COPD) II-III stage when combined with coronary heart disease (CHD). The increasing oxygen independent reactions monocytes and neutrophils and a decrease of the parameters that characterize the functional state of phagocytic cells, indicating a decrease in the functional capacity of macrophage phagocytic system (MPS) in patients with acute exacerbation of COPD, which runs as its own or in combination with stable coronary heart disease angina I-II. FC. Severity immunodeficiency state in terms of cellular component of nonspecific immunity in patients with acute exacerbation of COPD II-III stage in conjunction with the accompanying CHD increases with the progression of heart failure. Inclusion of basic therapy of COPD exacerbation and standard treatment of coronary artery disease and drug combinations Roflumilastand quercetin causes normalization of phagocytic indices MFS, indicating improved immune status and improves myocardial perfusion in terms of daily ECG monitoring.

  19. The association between glucose levels and hospital outcomes in patients with acute exacerbations of chronic obstructive pulmonary disease

    PubMed Central

    Islam, Ebtesam A.; Limsuwat, Chok; Nantsupawat, Teerapat; Berdine, Gilbert G.; Nugent, Kenneth M.

    2015-01-01

    BACKGROUND: Corticosteroids used for chronic obstructive pulmonary disease (COPD) exacerbations can cause hyperglycemia in hospitalized patients, and hyperglycemia may be associated with increased mortality, length of stay (LOS), and re-admissions in these patients. MATERIALS AND METHODS: We did three retrospective studies using charts from July 2008 through June 2009, January 2006 through December 2010, and October 2010 through March 2011. We collected demographic and clinical information, laboratory results, radiographic results, and information on LOS, mortality, and re-admission. RESULTS: Glucose levels did not predict outcomes in any of the studied cohorts, after adjustment for covariates in multivariable analysis. The first database included 30 patients admitted to non-intensive care unit (ICU) hospital beds. Six of 20 non-diabetic patients had peak glucoses above 200 mg/dl. Nine of the ten diabetic patients had peak glucoses above 200 mg/dl. The maximum daily corticosteroid dose had no apparent effect on the glucose levels. The second database included 217 patients admitted to ICUs. The initial blood glucose was higher in patients who died than those who survived using bivariate analysis (P = 0.015; odds ratio, OR, 1.01) but not in multivariable analysis. Multivariable logistic regression analysis also demonstrated that glucose levels did not affect LOS. The third database analyzing COPD re-admission rates included 81 patients; the peak glucose levels were not associated with re-admission. CONCLUSIONS: Our data demonstrate that COPD patients treated with corticosteroids developed significant hyperglycemia, but the increase in blood glucose levels did not correlate with the maximum dose of corticosteroids. Blood glucose levels were not associated with mortality, LOS, or re-admission rates. PMID:25829959

  20. Early Supported Discharge/Hospital At Home For Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Review and Meta-Analysis.

    PubMed

    Echevarria, Carlos; Brewin, Karen; Horobin, Hazel; Bryant, Andrew; Corbett, Sally; Steer, John; Bourke, Stephen C

    2016-08-01

    A systematic review and meta-analysis was performed to assess the safety, efficacy and cost of Early Supported Discharge (ESD) and Hospital at Home (HAH) compared to Usual Care (UC) for patients with acute exacerbation of COPD (AECOPD). The structure of ESD/HAH schemes was reviewed, and analyses performed assuming return to hospital during the acute period (prior to discharge from home treatment) was, and was not, considered a readmission. The pre-defined search strategy completed in November 2014 included electronic databases (Medline, Embase, Amed, BNI, Cinahl and HMIC), libraries, current trials registers, national organisations, key respiratory journals, key author contact and grey literature. Randomised controlled trials (RCTs) comparing ESD/HAH to UC in patients admitted with AECOPD, or attending the emergency department and triaged for admission, were included. Outcome measures were mortality, all-cause readmissions to 6 months and cost. Eight RCTs were identified; seven reported mortality and readmissions. The structure of ESD/HAH schemes, particularly selection criteria applied and level of support provided, varied considerably. Compared to UC, ESD/HAH showed a trend towards lower mortality (RRMH = 0.66; 95% CI 0.40-1.09, p = 0.10). If return to hospital during the acute period was not considered a readmission, ESD/HAH was associated with fewer readmissions (RRMH = 0.74, 95% CI: 0.60-0.90, p = 0.003), but if considered a readmission, the benefit was lost (RRMH = 0.84; 95% CI 0.69-1.01, p = 0.07). Costs were lower for ESD/HAH than UC. ESD/HAH is safe in selected patients with an AECOPD. Further research is required to define optimal criteria to guide patient selection and models of care. PMID:26854816

  1. A comparison of synchronized intermittent mandatory ventilation and pressure-regulated volume control ventilation in elderly patients with acute exacerbations of COPD and respiratory failure

    PubMed Central

    Chang, Suchi; Shi, Jindong; Fu, Cuiping; Wu, Xu; Li, Shanqun

    2016-01-01

    Background COPD is the third leading cause of death worldwide. Acute exacerbations of COPD may cause respiratory failure, requiring intensive care unit admission and mechanical ventilation. Intensive care unit patients with acute exacerbations of COPD requiring mechanical ventilation have higher mortality rates than other hospitalized patients. Although mechanical ventilation is the most effective intervention for these conditions, invasive ventilation techniques have yielded variable effects. Objective We evaluated pressure-regulated volume control (PRVC) ventilation treatment efficacy and preventive effects on pulmonary barotrauma in elderly COPD patients with respiratory failure. Patients and methods Thirty-nine intubated patients were divided into experimental and control groups and treated with the PRVC and synchronized intermittent mandatory ventilation – volume control methods, respectively. Vital signs, respiratory mechanics, and arterial blood gas analyses were monitored for 2–4 hours and 48 hours. Results Both groups showed rapidly improved pH, partial pressure of oxygen (PaO2), and PaO2 per fraction of inspired O2 levels and lower partial pressure of carbon dioxide (PaCO2) levels. The pH and PaCO2 levels at 2–4 hours were lower and higher, respectively, in the test group than those in the control group (P<0.05 for both); after 48 hours, blood gas analyses showed no statistical difference in any marker (P>0.05). Vital signs during 2–4 hours and 48 hours of treatment showed no statistical difference in either group (P>0.05). The level of peak inspiratory pressure in the experimental group after mechanical ventilation for 2–4 hours and 48 hours was significantly lower than that in the control group (P<0.05), while other variables were not significantly different between groups (P>0.05). Conclusion Among elderly COPD patients with respiratory failure, application of PRVC resulted in rapid improvement in arterial blood gas analyses while maintaining

  2. The Sputum Microbiome in Chronic Obstructive Pulmonary Disease Exacerbations.

    PubMed

    Huang, Yvonne J; Boushey, Homer A

    2015-11-01

    Acute exacerbations of chronic obstructive pulmonary disease (COPD) are thought to be associated with--and perhaps to mediate--accelerated loss of lung function in COPD. Although the application of culture-independent methods for detection of bacteria have shown COPD to be associated with marked differences in the burden, diversity, and composition of the bronchial bacterial microbiome, few studies have examined the changes associated with community-acquired exacerbations of the disease. In a longitudinal cohort study of COPD, the availability of sputum samples from subjects obtained at the onset of an exacerbation and during periods of clinical stability before and after the event enabled us to recently address this gap in knowledge, using culture-independent, 16S rRNA-based analysis methods combined with in silico inference of metagenomic functions. We observed sputum bacterial composition to be generally stable over the preexacerbation period of clinical stability, but to change at the time of exacerbation, with specific enrichment in not only typical COPD-associated bacterial species (e.g., Haemophilus influenzae) but also other phylogenetically related species with pathogenic potential. Concurrently, we observed depleted abundance of other bacteria whose predicted metagenomes suggest functional capacities to produce a variety of antiinflammatory compounds. Most strikingly, we found that resolution of these exacerbation-related changes in sputum microbiota composition differed significantly, depending on the exacerbation treatments prescribed. Treatment with corticosteroids resulted in microbiome enrichment for a number of bacterial communities, mostly members of the Proteobacteria phylum, whereas prolonged suppression of microbiota was seen in those treated with antibiotics alone. Taken together, our findings suggest that exacerbations of COPD are associated with heterogeneous changes in the bronchial microbiome, with increases in the abundance of species

  3. The Sputum Microbiome in Chronic Obstructive Pulmonary Disease Exacerbations.

    PubMed

    Huang, Yvonne J; Boushey, Homer A

    2015-11-01

    Acute exacerbations of chronic obstructive pulmonary disease (COPD) are thought to be associated with--and perhaps to mediate--accelerated loss of lung function in COPD. Although the application of culture-independent methods for detection of bacteria have shown COPD to be associated with marked differences in the burden, diversity, and composition of the bronchial bacterial microbiome, few studies have examined the changes associated with community-acquired exacerbations of the disease. In a longitudinal cohort study of COPD, the availability of sputum samples from subjects obtained at the onset of an exacerbation and during periods of clinical stability before and after the event enabled us to recently address this gap in knowledge, using culture-independent, 16S rRNA-based analysis methods combined with in silico inference of metagenomic functions. We observed sputum bacterial composition to be generally stable over the preexacerbation period of clinical stability, but to change at the time of exacerbation, with specific enrichment in not only typical COPD-associated bacterial species (e.g., Haemophilus influenzae) but also other phylogenetically related species with pathogenic potential. Concurrently, we observed depleted abundance of other bacteria whose predicted metagenomes suggest functional capacities to produce a variety of antiinflammatory compounds. Most strikingly, we found that resolution of these exacerbation-related changes in sputum microbiota composition differed significantly, depending on the exacerbation treatments prescribed. Treatment with corticosteroids resulted in microbiome enrichment for a number of bacterial communities, mostly members of the Proteobacteria phylum, whereas prolonged suppression of microbiota was seen in those treated with antibiotics alone. Taken together, our findings suggest that exacerbations of COPD are associated with heterogeneous changes in the bronchial microbiome, with increases in the abundance of species

  4. The Effect of Cold Temperature on Increased Exacerbation of Chronic Obstructive Pulmonary Disease: A Nationwide Study

    PubMed Central

    Ou, Shuo-Ming; Hsiao, Yi-Han; Li, Szu-Yuan; Wang, Shuu-Jiun; Yang, Albert C.; Chen, Tzeng-Ji; Perng, Diahn-Warng

    2013-01-01

    Background Seasonal variations in the acute exacerbation of chronic obstructive pulmonary disease (COPD) have been reported. However, the influence of air temperature and other meteorological factors on COPD exacerbation remains unclear. Methods National Health Insurance registry data from January 1, 1999 to December 1, 2009 and meteorological variables from the Taiwan Central Weather Bureau for the same period were analyzed. A case-crossover study design was used to investigate the association between COPD exacerbation and meteorological variables. Results A total of 16,254 cases who suffered from COPD exacerbation were enrolled. We found that a 1°C decrease in air temperature was associated with a 0.8% increase in the exacerbation rate on event-days (95% confidence interval (CI), 1.015–1.138, p = 0.015). With a 5°C decrease in mean temperature, the cold temperature (28-day average temperature) had a long-term effect on the exacerbation of COPD (odds ratio (OR), 1.106, 95% CI 1.063–1.152, p<0.001). In addition, elderly patients and those who did not receive inhaled medication tended to suffer an exacerbation when the mean temperature dropped 5°C. Higher barometric pressure, more hours of sunshine, and lower humidity were associated with an increase in COPD exacerbation. Conclusions This study demonstrated the effect of cold temperatures on the COPD exacerbation rate. Elderly patients and those without inhaled medicine before the exacerbation event were affected significantly by lower mean temperatures. A more comprehensive program to prevent cold stress in COPD patients may lead to a reduction in the exacerbations rate of COPD. PMID:23554858

  5. Predictive Factors for the Effect of Treatment by Noninvasive Ventilation in Patients with Respiratory Failure as a Result of Acute Exacerbation of the Chronic Obstructive Pulmonary Disease

    PubMed Central

    Pejkovska, Sava; Kaeva, Biserka Jovkovska; Goseva, Zlatica; Arsovski, Zoran; Janeva, Jelena Jovanovska; Zeynel, Sead

    2015-01-01

    BACKGROUND: Noninvasive mechanical ventilation (NIV) applies ventilator support through the patient’s upper airway using a mask. AIM: The aim of the study is to define factors that will point out an increased risk of NIV failure in patients with exacerbation of Chronic Obstructive Pulmonary Disease (COPD). PATIENTS AND METHODS: Patients over the age of 40, treated with NIV, were prospectively recruited. After data processing, the patients were divided into two groups: 1) successful NIV treatment group; 2) failed NIV treatment group. RESULTS: On admission arterial pH and Glasgow coma scale (GCS) levels were lower (pH: p < 0.05, GCS: p < 0.05), and Acute Physiology and Chronic Health Evaluation II (APACHE) score and PaCO2 were higher (p < 0.05) in the NIV failure group. Arterial pH was lower (p < 0.05) and PaCO2 and respiratory rate were higher (p < 0.05) after 1h, and arterial pH was lower (p < 0.05) and PaCO2 (p < 0.05), respiratory and heart rate were higher (p < 0.05) after 4h in the NIV failure group. CONCLUSION: Measurement and monitoring of certain parameters may be of value in terms of predicting the effectiveness of NIV treatment. PMID:27275303

  6. Sequential Treatments with Tongsai and Bufei Yishen Granules Reduce Inflammation and Improve Pulmonary Function in Acute Exacerbation-Risk Window of Chronic Obstructive Pulmonary Disease in Rats.

    PubMed

    Lu, Xiaofan; Li, Ya; Li, Jiansheng; Wang, Haifeng; Wu, Zhaohuan; Li, Hangjie; Wang, Yang

    2016-01-01

    Background. Sequential treatments of Chinese medicines for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) risk window (RW) have benefits for preventing reoccurrences of AEs; however, the effects on pulmonary function, pulmonary, and systemic inflammatory biomarkers remain unclear. Methods. Cigarette-smoke/bacterial infections induced rats were randomized into Control, COPD, AECOPD, Tongsai Granule/normal saline (TSG/NS), moxifloxacin + salbutamol/NS (MXF+STL/NS), TSG/Bufei Yishen Granule (BYG), MXF+STL/STL, and TSG+MXF+STL/BYG+STL groups and given corresponding medicine(s) in AE- and/or RW phase. Body temperature, pulmonary function, blood cytology, serum amyloid A (SAA) and C-reactive protein (CRP), pulmonary histomorphology and myeloperoxidase (MPO), polymorphonuclear (PMN) elastase, interleukins IL-1β, IL-6, and IL-10, and tumor necrosis factor- (TNF-) α expressions were determined. Results. Body temperature, inflammatory cells and cytokines, SAA, CRP, and pulmonary impairment were higher in AECOPD rats than stable COPD, while pulmonary function declined and recovered to COPD level in 14-18 days. All biomarkers were improved in treated groups with shorter recovery times of 4-10 days, especially in TSG+MXF+STL/BYG+STL group. Conclusion. Sequential treatments with Tongsai and Bufei Yishen Granules, during AECOPD-RW periods, can reduce inflammatory response and improve pulmonary function and shorten the recovery courses of AEs, especially the integrated Chinese and Western medicines. PMID:27563333

  7. Sequential Treatments with Tongsai and Bufei Yishen Granules Reduce Inflammation and Improve Pulmonary Function in Acute Exacerbation-Risk Window of Chronic Obstructive Pulmonary Disease in Rats

    PubMed Central

    Lu, Xiaofan; Li, Ya; Wang, Haifeng; Wu, Zhaohuan; Li, Hangjie; Wang, Yang

    2016-01-01

    Background. Sequential treatments of Chinese medicines for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) risk window (RW) have benefits for preventing reoccurrences of AEs; however, the effects on pulmonary function, pulmonary, and systemic inflammatory biomarkers remain unclear. Methods. Cigarette-smoke/bacterial infections induced rats were randomized into Control, COPD, AECOPD, Tongsai Granule/normal saline (TSG/NS), moxifloxacin + salbutamol/NS (MXF+STL/NS), TSG/Bufei Yishen Granule (BYG), MXF+STL/STL, and TSG+MXF+STL/BYG+STL groups and given corresponding medicine(s) in AE- and/or RW phase. Body temperature, pulmonary function, blood cytology, serum amyloid A (SAA) and C-reactive protein (CRP), pulmonary histomorphology and myeloperoxidase (MPO), polymorphonuclear (PMN) elastase, interleukins IL-1β, IL-6, and IL-10, and tumor necrosis factor- (TNF-) α expressions were determined. Results. Body temperature, inflammatory cells and cytokines, SAA, CRP, and pulmonary impairment were higher in AECOPD rats than stable COPD, while pulmonary function declined and recovered to COPD level in 14–18 days. All biomarkers were improved in treated groups with shorter recovery times of 4–10 days, especially in TSG+MXF+STL/BYG+STL group. Conclusion. Sequential treatments with Tongsai and Bufei Yishen Granules, during AECOPD-RW periods, can reduce inflammatory response and improve pulmonary function and shorten the recovery courses of AEs, especially the integrated Chinese and Western medicines. PMID:27563333

  8. Utility of the combination of serum highly-sensitive C-reactive protein level at discharge and a risk index in predicting readmission for acute exacerbation of COPD*,**

    PubMed Central

    Chang, Chun; Zhu, Hong; Shen, Ning; Han, Xiang; Chen, Yahong; He, Bei

    2014-01-01

    OBJECTIVE: Frequent readmissions for acute exacerbations of COPD (AECOPD) are an independent risk factor for increased mortality and use of health-care resources. Disease severity and C-reactive protein (CRP) level are validated predictors of long-term prognosis in such patients. This study investigated the utility of combining serum CRP level with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) exacerbation risk classification for predicting readmission for AECOPD. METHODS: This was a prospective observational study of consecutive patients hospitalized for AECOPD at Peking University Third Hospital, in Beijing, China. We assessed patient age; gender; smoking status and history (pack-years); lung function; AECOPD frequency during the last year; quality of life; GOLD risk category (A-D; D indicating the greatest risk); and serum level of high-sensitivity CRP at discharge (hsCRP-D). RESULTS: The final sample comprised 135 patients. Of those, 71 (52.6%) were readmitted at least once during the 12-month follow-up period. The median (interquartile) time to readmission was 78 days (42-178 days). Multivariate analysis revealed that serum hsCRP-D ≥ 3 mg/L and GOLD category D were independent predictors of readmission (hazard ratio = 3.486; 95% CI: 1.968-6.175; p < 0.001 and hazard ratio = 2.201; 95% CI: 1.342-3.610; p = 0.002, respectively). The ordering of the factor combinations by cumulative readmission risk, from highest to lowest, was as follows: hsCRP-D ≥ 3 mg/L and GOLD category D; hsCRP-D ≥ 3 mg/L and GOLD categories A-C; hsCRP-D < 3 mg/L and GOLD category D; hsCRP-D < 3 mg/L and GOLD categories A-C. CONCLUSIONS: Serum hsCRP-D and GOLD classification are independent predictors of readmission for AECOPD, and their predictive value increases when they are used in combination. PMID:25410837

  9. Acute Radiation Effects Resulting from Exposure to Solar Particle Event-Like Radiation

    NASA Astrophysics Data System (ADS)

    Kennedy, Ann; Cengel, Keith

    2012-07-01

    A major solar particle event (SPE) may place astronauts at significant risk for the acute radiation syndrome (ARS), which may be exacerbated when combined with other space flight stressors, such that the mission or crew health may be compromised. The National Space Biomedical Research Institute (NSBRI) Center of Acute Radiation Research (CARR) is focused on the assessment of risks of adverse biological effects related to the ARS in animal models exposed to space flight stressors combined with the types of radiation expected during an SPE. As part of this program, FDA-approved drugs that may prevent and/or mitigate ARS symptoms are being evaluated. The CARR studies are focused on the adverse biological effects resulting from exposure to the types of radiation, at the appropriate energies, doses and dose-rates, present during an SPE (and standard reference radiations, gamma rays or electrons). The ARS is a phased syndrome which often includes vomiting and fatigue. Other acute adverse biologic effects of concern are the loss of hematopoietic cells, which can result in compromised bone marrow and immune cell functions. There is also concern for skin damage from high SPE radiation doses, including burns, and resulting immune system dysfunction. Using 3 separate animal model systems (ferrets, mice and pigs), the major ARS biologic endpoints being evaluated are: 1) vomiting/retching and fatigue, 2) hematologic changes (with focus on white blood cells) and immune system changes resulting from exposure to SPE radiation with and without reduced weightbearing conditions, and 3) skin injury and related immune system functions. In all of these areas of research, statistically significant adverse health effects have been observed in animals exposed to SPE-like radiation. Countermeasures for the management of ARS symptoms are being evaluated. New research findings from the past grant year will be discussed. Acknowledgements: This research is supported by the NSBRI Center of Acute

  10. Prevalence of anemia and its impact on mortality in patients with acute exacerbation of chronic obstructive pulmonary disease in a developing country setting.

    PubMed

    Rahimi-Rad, Mohammad Hossein; Sadighi, Tannaz; Rabieepour, Masomeh; Dinparast, Reza; RahimiRad, Shagayegh

    2015-01-01

    Chronic Obstructive Pulmonary Disease (COPD) is going to be the third most common cause of death worldwide. The natural course of COPD is interrupted by acute exacerbations (AECOPD) with an overall mortality rate of 10%. Anemia is a well-known independent predictor of mortality in several chronic diseases. Little is known about the impact of anemia on mortality in AECOPD. The aims of this study were to determine the prevalence of anemia in AECOPD patients and its impact on mortality in a developing country setting. We retrospectively studied 200 hospitalized patients with AECOPD (100 died in hospital and 100 survived) in Imam Khomeini teaching hospital, Urmia, Iran. Prevalence of anemia between deceased and surviving patients compared by using x-square test. Mean admission day Hb and Hct level were compared between the two groups by using Student t-test. Anemia was defined according to WHO criteria: Hb<13 g/dl in males; Hb<12 g/dl in females. The prevalence of anemia was significantly higher in patients who died in hospital compared to those who survived (72% vs. 49%, p=0.001 and OR=2.68). The mean ±SD Hb level was 11.5±2.7 g/dl among deceased patients vs. 13.0±2.0 g/dl among survivors (p value<0.001). The duration of hospitalization was significantly higher (p<0,001) in anemic patients (mean 13.28 days in anemic vs. 7.0 days in non-anemic patients). In bivariate correlation analysis, Hb was positively correlated with FEV1 (r=+0.210, p=0.011) and negatively with duration of hospitalization (r=-0.389, p=0.000). Anemia was common in AECOPD patients in this developing country setting and was significantly associated with in hospital mortality.

  11. Analysis of blood neutrophil elastase, glutathione levels and pathological findings in postoperative acute exacerbation of idiopathic pulmonary fibrosis associated with lung cancer: Two case reports

    PubMed Central

    Sugino, Keishi; Nakamura, Yasuhiko; Muramatsu, Yoko; Hata, Yoshinobu; Shibuya, Kazutoshi; Homma, Sakae

    2016-01-01

    Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) is characterized by severe worsening dyspnea and high mortality. It has been proven that the serum neutrophil elastase (NE) level, in addition to the serum Krebs von den Lungen-6 (KL-6) and surfactant protein-D (SP-D) levels, was elevated in patients with IPF-AE. Glutathione (GSH) is the major antioxidant involved in cell metabolism and survival. It is also known that IPF is characterized by reduced GSH levels in bronchoalveolar lavage fluid and blood. Case 1 was a 67-year-old man who was referred to our hospital complaining of a 2-year history of progressive dyspnea on exertion (DOE). The patient was initially diagnosed with IPF, followed by inhaled N-acetylcysteine monotherapy. Two years later, left upper lobectomy with lymph node dissection was performed due to primary lung cancer, which was large-cell neuroendocrine carcinoma (pT2aN2M0, stage IIIA). Five days after lung surgery, the patient developed AE. Case 2 was a 67-year-old man who was referred to our hospital with suspected lung cancer, complaining of dry cough and DOE. The patient underwent left upper lobectomy with lymph node dissection for primary lung cancer, which was diagnosed as well-differentiated adenocarcinoma (pT2aN2M0, stage IIIA). Ten days after lung surgery, the patient developed AE. The levels of biomarkers, such as serum NE, redox balance [reduced GSH (rGSH)/oxidized GSH (GSSG)] in the blood, as well as the correlation between serial changes of these biomarkers and prognosis, were analyzed in 2 patients with postoperative IPF-AE associated with lung cancer. Interestingly, the serial changes of the serum rGSH/GSSG ratio may suggest the possibility of predicting the onset of postoperative AE and/or survival, along with serum NE levels.

  12. Patterns, Trajectories, and Predictors of Functional Decline after Hospitalization for Acute Exacerbations in Men with Moderate to Severe Chronic Obstructive Pulmonary Disease: A Longitudinal Study

    PubMed Central

    Medina-Mirapeix, Francesc; Bernabeu-Mora, Roberto; García-Guillamón, Gloria; Valera Novella, Elisa; Gacto-Sánchez, Mariano; García-Vidal, José Antonio

    2016-01-01

    Background Hospitalization for acute exacerbations (AE) of chronic obstructive pulmonary disease (COPD) is common, but little is known about the impact of hospitalization on the development of disability. The purpose of this study was to determine the rate and time course of functional changes 3 months after hospital discharge for AE-COPD compared with baseline levels 2 weeks before admission, and to identify predictors of functional decline. Methods This was a prospective study including 103 patients (age mean, 71 years; standard deviation, 9.1 years) who were hospitalized with AE-COPD. Number of dependencies in Activities of Daily Living (ADLs) was measured at the preadmission baseline and at weeks 6 and 12 after discharge. Patterns of improvement, no change, and decline were defined over 3 consecutive intervals (baseline and weeks 6 and 12). Trajectories grouped patients with similar time courses of disability. Recovery was defined as returning to baseline function after functional decline. Univariate and multivariate multiple logistic regression was used to determine predictors of functional decline after week 12. Results Six trajectories of functional changes were found. From baseline to 12 weeks, 50% of patients continued to have the same function whereas 31% experienced functional decline after 6 weeks; 16.7% recovered over subsequent weeks. At week 12, as a consequence of all trajectories, 38% of patients showed functional declines compared with baseline function, 57% had not declined, and 6 improved. Length of stay (odds ratio [OR] = 1.12;95% [confidence interval] CI 1.03–1.22), dyspnea (OR = 1.85; 95% CI 1.05–3.26), and frailty (OR = 3.97; 95% CI 1.13–13.92) were independent predictors of functional decline after 12 weeks. Conclusions Hospitalization for AE-COPD is a risk factor for the progression of disability. More than one third of patients hospitalized for AE-COPD declined during the 12 weeks following discharge, with most of this decline

  13. Different characteristics associated with intensive care unit transfer from the medical ward between patients with acute exacerbations of chronic obstructive pulmonary disease with and without pneumonia

    PubMed Central

    Shin, Hong-Joon; Park, Cheol-Kyu; Kim, Tae-Ok; Ban, Hee-Jung; Oh, In-Jae; Kim, Yu-Il; Kwon, Yong-Soo; Kim, Young-Chul

    2016-01-01

    Background The rate of hospitalization due to acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is increasing. Few studies have examined the clinical, laboratory and treatment differences between patients in general wards and those who need transfer to an intensive care unit (ICU). Methods We retrospectively reviewed clinical, laboratory, and treatment characteristics of 374 patients who were initially admitted to the general ward at Chonnam National University Hospital in South Korea due to AECOPD (pneumonic, 194; non-pneumonic, 180) between January 2008 and March 2015. Of these patients, 325 were managed at the medical ward during their hospitalization period (ward group), and 49 required ICU transfer (ICU group). We compared the clinical, laboratory, and treatment characteristics associated with ICU transfer between patients with AECOPD with and without pneumonia. Results Male patients were 86.5% in the ward group and 79.6% in the ICU group. High glucose levels [median 154.5 mg/dL, interquartile range (IQR) 126.8–218.3 in ICU group vs. median 133.0, IQR 109.8–160.3 in ward group], high pneumonia severity index scores (median 100.5, IQR 85.5–118.5 vs. median 86.0, IQR 75.0–103.5), low albumin levels (median 2.9 g/dL, IQR 2.6–3.6 vs. median 3.4, IQR 3.0–3.7), and anemia (73.3% vs. 43.3%) independently increased the risk of ICU transfer in the pneumonic AECOPD group. High PaCO2 levels (median 53.1 mmHg in ICU group, IQR 38.5–84.6 vs. median 39.7, IQR 34.2–48.6 in ward group) independently increased the risk of ICU transfer in the non-pneumonic AECOPD group. Treatment with systemic corticosteroids (≥30 mg of daily prednisolone) during hospitalization in the medical ward independently reduced the risk of ICU transfer in both groups. Conclusions The characteristics associated with ICU transfer differed between the pneumonic and non-pneumonic AECOPD groups, and systemic corticosteroids use was associated with lower rate of ICU

  14. Automated oxygen titration and weaning with FreeO2 in patients with acute exacerbation of COPD: a pilot randomized trial

    PubMed Central

    Lellouche, François; Bouchard, Pierre-Alexandre; Roberge, Maude; Simard, Serge; L’Her, Erwan; Maltais, François; Lacasse, Yves

    2016-01-01

    Introduction We developed a device (FreeO2) that automatically adjusts the oxygen flow rates based on patients’ needs, in order to limit hyperoxia and hypoxemia and to automatically wean them from oxygen. Objective The aim of this study was to evaluate the feasibility of using FreeO2 in patients hospitalized in the respiratory ward for an acute exacerbation of COPD. Methods We conducted a randomized controlled trial comparing FreeO2 vs manual oxygen titration in the respiratory ward of a university hospital. We measured the perception of appropriateness of oxygen titration and monitoring in both groups by nurses and attending physicians using a Likert scale. We evaluated the time in the target range of oxygen saturation (SpO2) as defined for each patient by the attending physician, the time with severe desaturation (SpO2 <85%), and the time with hyperoxia (SpO2 >5% above the target). We also recorded length of stay, intensive care unit admissions, and readmission rate. Fifty patients were randomized (25 patients in both groups; mean age: 72±8 years; mean forced expiratory volume in 1 second: 1.00±0.49 L; and mean initial O2 flow 2.0±1.0 L/min). Results Nurses and attending physicians felt that oxygen titration and monitoring were equally appropriate with both O2 administration systems. The percentage of time within the SpO2 target was significantly higher with FreeO2, and the time with severe desaturation and hyperoxia was significantly reduced with FreeO2. Time from study inclusion to hospital discharge was 5.8±4.4 days with FreeO2 and 8.4±6.0 days with usual oxygen administration (P=0.051). Conclusion FreeO2 was deemed as an appropriate oxygen administration system by nurses and physicians of a respiratory unit. This system maintained SpO2 at the target level better than did manual titration and reduced periods of desaturation and hyperoxia. Our results also suggest that FreeO2 has the potential to reduce the hospital length of stay. PMID:27601891

  15. Automated oxygen titration and weaning with FreeO2 in patients with acute exacerbation of COPD: a pilot randomized trial

    PubMed Central

    Lellouche, François; Bouchard, Pierre-Alexandre; Roberge, Maude; Simard, Serge; L’Her, Erwan; Maltais, François; Lacasse, Yves

    2016-01-01

    Introduction We developed a device (FreeO2) that automatically adjusts the oxygen flow rates based on patients’ needs, in order to limit hyperoxia and hypoxemia and to automatically wean them from oxygen. Objective The aim of this study was to evaluate the feasibility of using FreeO2 in patients hospitalized in the respiratory ward for an acute exacerbation of COPD. Methods We conducted a randomized controlled trial comparing FreeO2 vs manual oxygen titration in the respiratory ward of a university hospital. We measured the perception of appropriateness of oxygen titration and monitoring in both groups by nurses and attending physicians using a Likert scale. We evaluated the time in the target range of oxygen saturation (SpO2) as defined for each patient by the attending physician, the time with severe desaturation (SpO2 <85%), and the time with hyperoxia (SpO2 >5% above the target). We also recorded length of stay, intensive care unit admissions, and readmission rate. Fifty patients were randomized (25 patients in both groups; mean age: 72±8 years; mean forced expiratory volume in 1 second: 1.00±0.49 L; and mean initial O2 flow 2.0±1.0 L/min). Results Nurses and attending physicians felt that oxygen titration and monitoring were equally appropriate with both O2 administration systems. The percentage of time within the SpO2 target was significantly higher with FreeO2, and the time with severe desaturation and hyperoxia was significantly reduced with FreeO2. Time from study inclusion to hospital discharge was 5.8±4.4 days with FreeO2 and 8.4±6.0 days with usual oxygen administration (P=0.051). Conclusion FreeO2 was deemed as an appropriate oxygen administration system by nurses and physicians of a respiratory unit. This system maintained SpO2 at the target level better than did manual titration and reduced periods of desaturation and hyperoxia. Our results also suggest that FreeO2 has the potential to reduce the hospital length of stay.

  16. Identifying youth at risk for difficulties following a traumatic event: pre-event factors are associated with acute symptomatology.

    PubMed

    Goslin, Megan C; Stover, Carla Smith; Berkowitz, Steven; Marans, Steven

    2013-08-01

    This study examined factors related to children's acute symptoms following a potentially traumatic event (PTE) to more clearly identify domains that should be included in screenings of youth exposed to a PTE. In particular, the authors examined whether trauma category (i.e., sexual abuse/disclosure of abuse, intentionally perpetrated traumas other than sexual abuse, and unintentional traumas) was related to symptoms after controlling for other relevant factors. Participants were 112 youth presenting for clinical evaluation within a month of a PTE and their nonoffending caregivers. Using data from baseline assessments collected as part of a randomized controlled trial of a secondary prevention program, the following factors were tested in 3 hierarchical regression models: index PTE category, history of traumatic exposure, preindex event functioning, and parenting behaviors. Prior trauma exposure, preindex event functioning, and hostile parenting were uniquely related to children's symptoms in the acute posttraumatic period after controlling for time since the event and child age, but trauma category was not. Implications for identifying and referring children at high risk for poor outcomes in the early aftermath of a PTE are discussed. An exclusive focus on the event is insufficient and more comprehensive understanding of the child and family is required. PMID:23861167

  17. High hyperdiploid childhood acute lymphoblastic leukemia: Chromosomal gains as the main driver event.

    PubMed

    Paulsson, Kajsa

    2016-01-01

    High hyperdiploid childhood acute lymphoblastic leukemia is characterized by multiple chromosomal gains. Recent results show that this subtype harbors relatively few genetic abnormalities besides the extra chromosomes, which appear to arise early and are likely the main driver event. Secondary hits primarily target genes in the rat sarcoma (RAS) signaling pathway and histone modifiers. PMID:27308574

  18. Xuan Bai Cheng Qi formula as an adjuvant treatment of acute exacerbation of chronic obstructive pulmonary disease of the syndrome type phlegm-heat obstructing the lungs: a multicenter, randomized, double-blind, placebo-controlled clinical trial

    PubMed Central

    2014-01-01

    Background Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a common cause of morbidity and mortality. Traditional Chinese medicine (TCM) is used to treat AECOPD as adjunctive therapy. This study aimed to evaluate the efficacy and safety of the TCM formula Xuan Bai Cheng Qi as an adjuvant therapy for AECOPD patients with the syndrome type of phlegm-heat obstructing the lungs. Methods A multicenter, randomized, double-blind, placebo-controlled clinical trial was conducted. A total of 244 patients were divided into the intervention group (n = 122, treated with conventional medicine and Xuan Bai Cheng Qi) and the control group (n = 122, treated with conventional medicine and placebo). Total symptom scores (cough, phlegm, wheezing, chest congestion) before treatment and at 3, 5, 7, 10 days post-treatment were recorded. Lung function, arterial blood gas, serum inflammatory cytokines, oxidation/anti-oxidation index were observed before treatment and at the end of the 10-day treatment. Results A total of 242 patients completed the study. The full analysis set (FAS) population was 244 and the per-protocol analysis set (PPS) population was 229. After the 10-day treatment, symptom scores of the Xuan Bai Cheng Qi group were significantly lower over time compared with the control group (FAS: mean difference -1.84, 95% CI -2.66 to -1.03, P < .001; PPS: mean difference -1.87, 95% CI -2.71 to -1.03, P < .001). FEV1, FVC, and FEV1%pred were significantly higher over time in the Xuan Bai Cheng Qi group compared with those in the control group (day 10, FAS and PPS: P < .05). PaO2 and PaCO2 were significantly improved in the Xuan Bai Cheng Qi group (day 10, FAS and PPS: P < .05). Xuan Bai Cheng Qi was also found to ameliorate cytokine levels and oxidation/antioxidant index compared with placebo. There were no differences in safety variables and adverse events between the two groups. Conclusions Xuan Bai Cheng Qi formula appears to be a

  19. Prognostic value of intravenous dipyridamole thallium scintigraphy after an acute myocardial ischemic event

    SciTech Connect

    Younis, L.T.; Byers, S.; Shaw, L.; Barth, G.; Goodgold, H.; Chaitman, B.R.

    1989-07-15

    Seventy-seven patients recovering from an acute coronary event were studied by intravenous dipyridamole thallium scintigraphy to evaluate the prognostic value and safety of the test in this patient subset. Forty-four patients (58%) had unstable angina and 33 (42%) had an acute myocardial infarction. One death occurred within 24 hours of testing. Sixty-eight patients were followed for an average of 12 months; 25, 31 and 23% had a fixed, reversible or combined thallium defect on their predischarge thallium scan. During follow-up, 10 patients died or had a nonfatal myocardial infarction; in each case, a reversible or combined myocardial thallium defect was present. Univariate analysis of 17 clinical, scintigraphic and angiographic variables showed that a reversible thallium defect and the angiographically determined extent of coronary artery disease were predictors of future cardiac events. The extent of coronary disease and global left ventricular ejection fraction were predictors of subsequent reinfarction or death. Logistic regression analyses revealed that a reversible thallium defect (p less than 0.001) and the extent of coronary disease (p less than 0.009) were the only significant predictors of a cardiac event. When death or reinfarction were the outcome variables, the extent of coronary disease (p less than 0.02) and left ventricular ejection fraction (p less than 0.06) were the only variables selected. Thus, intravenous dipyridamole thallium scintigraphy after an acute coronary ischemic syndrome is a useful and relatively safe noninvasive test to predict subsequent cardiac events.

  20. Neuronal antibody biomarkers for Sydenham's chorea identify a new group of children with chronic recurrent episodic acute exacerbations of tic and obsessive compulsive symptoms following a streptococcal infection.

    PubMed

    Singer, Harvey S; Mascaro-Blanco, Adda; Alvarez, Kathy; Morris-Berry, Christina; Kawikova, Ivana; Ben-Pazi, Hilla; Thompson, Carol B; Ali, Syed F; Kaplan, Edward L; Cunningham, Madeleine W

    2015-01-01

    Several autoantibodies (anti-dopamine 1 (D1R) and 2 (D2R) receptors, anti-tubulin, anti-lysoganglioside-GM1) and antibody-mediated activation of calcium calmodulin dependent protein kinase II (CaMKII) signaling activity are elevated in children with Sydenham's chorea (SC). Recognizing proposed clinical and autoimmune similarities between SC and PANDAS (pediatric autoimmune neuropsychiatric disorder associated with a streptococcal infection), we sought to identify serial biomarker changes in a slightly different population. Antineuronal antibodies were measured in eight children (mean 11.3 years) with chronic, dramatic, recurrent tics and obsessive-compulsive disorder (OCD) associated with a group A β-hemolytic streptococcal (GABHS) respiratory tract infection, but differing because they lacked choreiform movements. Longitudinal serum samples in most subjects included two pre-exacerbation samples, Exac), one midst Exac (abrupt recurrence of tic/OCD; temporally association with a GABHS infection in six of eight subjects), and two post-Exac. Controls included four groups of unaffected children (n = 70; mean 10.8 years) obtained at four different institutions and published controls. Clinical exacerbations were not associated with a significant rise in antineuronal antibody titers. CaMKII activation was increased at the GABHS exacerbation point in 5/6 subjects, exceeded combined and published control's 95th percentile at least once in 7/8 subjects, and median values were elevated at each time point. Anti-tubulin and anti-D2R titers did not differ from published or combined control group's 95th percentile or median values. Differences in anti-lysoganglioside-GM1 and anti-D1R titers were dependent on the selected control. Variances in antibody titers and CaMKII activation were identified among the institutional control groups. Based on comparisons to published studies, results identify two groups of PANDAS: 1) a cohort, represented by this study, which lacks choreiform

  1. Rho-Associated Kinase Activity Is an Independent Predictor of Cardiovascular Events in Acute Coronary Syndrome

    PubMed Central

    Kajikawa, Masato; Noma, Kensuke; Nakashima, Ayumu; Maruhashi, Tatsuya; Iwamoto, Yumiko; Matsumoto, Takeshi; Iwamoto, Akimichi; Oda, Nozomu; Hidaka, Takayuki; Kihara, Yasuki; Aibara, Yoshiki; Chayama, Kazuaki; Sasaki, Shota; Kato, Masaya; Dote, Keigo; Goto, Chikara; Liao, James K.; Higashi, Yukihito

    2016-01-01

    Rho-associated kinases play an important role in a variety of cellular functions. Although Rho-associated kinase activity has been shown to be an independent predictor for future cardiovascular events in a general population, there is no information on Rho-associated kinase activity in patients with acute coronary syndrome. We evaluated leukocyte Rho-associated kinase activity by Western blot analysis in 73 patients with acute coronary syndrome and 73 age- and gender-matched control subjects. Rho-associated kinase activity within 2 hours of acute coronary syndrome onset was higher in patients with acute coronary syndrome than in the control subjects (0.95±0.55 versus 0.69±0.31; P<0.001). Rho-associated kinase activity promptly increased from 0.95±0.55 to 1.11±0.81 after 3 hours and reached a peak of 1.21±0.76 after 1 day (P=0.03 and P=0.03, respectively) and then gradually decreased to 0.83±0.52 after 7 days, 0.78±0.42 after 14 days, and 0.72±0.30 after 6 months (P=0.22, P=0.29, and P=0.12, respectively). During a median follow-up period of 50.8 months, 31 first major cardiovascular events (death from cardiovascular causes, myocardial infarction, ischemic stroke, and coronary revascularization) occurred. After adjustment for age, sex, cardiovascular risk factors, and concomitant treatment with statins, increased Rho-associated kinase activity was associated with increasing risk of first major cardiovascular events (hazard ratio, 4.56; 95% confidence interval, 1.98–11.34; P<0.001). These findings suggest that Rho-associated kinase activity is dramatically changed after acute coronary syndrome and that Rho-associated kinase activity could be a useful biomarker to predict cardiovascular events in Japanese patients with acute coronary syndrome. PMID:26283039

  2. Clinical Decision-Making Tool for Safe and Effective Prescription of Exercise in Acute Exacerbations of Chronic Obstructive Pulmonary Disease: Results From an Interdisciplinary Delphi Survey and Focus Groups

    PubMed Central

    Reid, W. Darlene; Chung, Frank; Kirkham, Ashley; Brooks, Dina; Goodridge, Donna; Marciniuk, Darcy D.; Hoens, Alison M.

    2015-01-01

    Background Exercise is recommended for people with an acute exacerbation of chronic obstructive pulmonary disease (AECOPD), yet there is little information to guide safe and effective mobilization and exercise for these patients. Objectives The purpose of this study was to develop a clinical decision-making tool to guide health care professionals in the assessment, prescription, monitoring, and progression of mobilization and therapeutic exercise for patients with AECOPD. Design and Methods A 3-round interdisciplinary Delphi panel identified and selected items based on a preselected consensus of 80%. These items were summarized in a paper-based tool titled Mobilization in Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD-Mob). Focus groups and questionnaires were subsequently used to conduct a sensibility evaluation of the tool. Results Nine researchers, 13 clinicians, and 7 individuals with COPD identified and approved 110 parameters for safe and effective exercise in AECOPD. These parameters were grouped into 5 categories: (1) “What to Assess Prior to Mobilization,” (2) “When to Consider Not Mobilizing or to Discontinue Mobilization,” (3) “What to Monitor During Mobilization for Patient Safety,” (4) “How to Progress Mobilization to Enhance Effectiveness,” and (5) “What to Confirm Prior to Discharge.” The tool was evaluated in 4 focus groups of 18 health care professionals, 90% of whom reported the tool was easy to use, was concise, and would guide a health care professional who is new to the acute care setting and working with patients with AECOPD. Limitations The tool was developed based on published evidence and expert opinion, so the applicability of the items to patients in all settings cannot be guaranteed. The Delphi panel consisted of health care professionals from Canada, so items may not be generalizable to other jurisdictions. Conclusions The AECOPD-Mob provides practical and concise information on safe and

  3. Double-blind randomized study comparing the efficacies and safeties of a short (3-day) course of azithromycin and a 5-day course of amoxicillin in patients with acute exacerbations of chronic bronchitis.

    PubMed Central

    Mertens, J C; van Barneveld, P W; Asin, H R; Ligtvoet, E; Visser, M R; Branger, T; Hoepelman, A I

    1992-01-01

    The efficacies and safeties of a three-dose regimen of azithromycin (500 mg once daily for 3 days) and a 15-dose regimen of amoxicillin (500 mg three times daily for 5 days) were compared in a double-blind manner in patients with an acute exacerbation of chronic bronchitis. A total of 92% of patients suffered a type 1 exacerbation. Treatment success, defined as cure or major improvement, was achieved in all patients in the azithromycin group by day 5, compared with 23 (92%) of 25 patients in the amoxicillin group. On day 12, these data were 24 of 25 (96%) in the azithromycin group and 20 of 25 (80%) in the amoxicillin group (results were not significantly different). Several pathogens were isolated (MIC ranges [micrograms per milliliter] in parentheses): Haemophilus influenzae or Haemophilus parainfluenzae was isolated 23 times (azithromycin, less than or equal to 0.06 to 32; amoxicillin, 0.12 to 2); Streptococcus pneumoniae was isolated from 11 patients (azithromcyin, less than or equal to 0.06 greater than 256; amoxicillin, less than or equal to 0.06 to 0.25); Moraxella (Branhamella) catarrhalis was isolated from eight patients (azithromycin, less than or equal to 0.06; amoxicillin, less than or equal to 0.06 to 16); and other members of the family Enterobacteriaceae were isolated from eight patients. One patient treated with azithromycin had Legionella pneumophila pneumonia, and another in that group had a significant rise in titer of antibody against influenza A virus. One patient treated with amoxicillin also had a significant rise in titer of antibody against influenza A virus. Microbiological response rates were comparable. One patient who received azithromycin developed abnormal liver function. Two patients treated with amoxicillin developed abnormal liver functions, one developed exanthema, and one treatment was stopped because of nausea. It is concluded that a three-dose (3-day) regimen of azithromycin is as effective clinically and microbiologically as a

  4. Inflammatory Cytokines as Risk Factors for Mortality After Acute Cardiac Events

    PubMed Central

    Hamzic-Mehmedbasic, Aida

    2016-01-01

    Introduction: Inflammatory markers have been identified as potential indicators of future adverse outcome after acute cardiac events. Aim: This study aimed to analyze baseline inflammatory cytokines levels in patients with acute heart failure (AHF) and/or acute coronary syndrome (ACS) according to survival. The main objective was to identify risk factors for mortality after an episode of AHF and/or ACS. Methods: In this prospective longitudinal study 75 patients with the diagnosis of AHF and/or ACS were enrolled. Baseline laboratory and clinical data were retrieved. Serum and urine interleukin-6 (IL-6) and interleukin-18 (IL-18) levels, plasma B-type natriuretic peptide (BNP) and serum cystatin C values were determined. The primary outcome was in-hospital mortality while secondary outcome was six-month mortality. Results: Median serum and urine IL-6 levels, serum and urine IL-18 levels, as well as median concentrations of plasma BNP and serum cystatin C, were significantly increased in deceased in comparison to surviving AHF and/or ACS patients. Univariate Cox regression analysis identified serum IL-6, serum IL-18, urine IL-6, urine IL-18 as well as serum cystatin C and Acute Physiology and Chronic Health Evaluation (APACHE) II score as risk factors for mortality after an episode of AHF and/or ACS. Multivariate Cox regression analysis revealed that only serum IL-6 is the independent risk factor for mortality after acute cardiac events (HR 61.7, 95% CI 2.1-1851.0; p=0.018). Conclusion: Present study demonstrated the strong prognostic value of serum IL-6 in predicting mortality of patients with AHF and/or ACS. PMID:27703283

  5. Oral mucolytic drugs for exacerbations of chronic obstructive pulmonary disease: systematic review

    PubMed Central

    Poole, Phillippa J; Black, Peter N

    2001-01-01

    Objective To assess the effects of oral mucolytics in adults with stable chronic bronchitis and chronic obstructive pulmonary disease. Design Systematic review of randomised controlled trials that compared at least two months of regular oral mucolytic drugs with placebo. Studies Twenty three randomised controlled trials in outpatients in Europe and United States. Main outcome measures Exacerbations, days of illness, lung function, adverse events. Results Compared with placebo, the number of exacerbations was significantly reduced in subjects taking oral mucolytics (weighted mean difference −0.07 per month, 95% confidence interval −0.08 to −0.05, P<0.0001). Based on the annualised rate of exacerbations in the control subjects of 2.7 a year, this is a 29% reduction. The number needed to treat for one subject to have no exacerbation in the study period would be 6. Days of illness also fell (weighted mean difference −0.56, −0.77 to −0.35, P<0.0001). The number of subjects who had no exacerbations in the study period was greater in the mucolytic group (odds ratio 2.22, 95% confidence interval 1.93 to 2.54, P<0.0001). There was no difference in lung function or in adverse events reported between treatments. Conclusions In chronic bronchitis and chronic obstructive pulmonary disease, treatment with mucolytics is associated with a reduction in acute exacerbations and days of illness. As these drugs have to be taken long term, they could be most useful in patients who have repeated, prolonged, or severe exacerbations of chronic obstructive pulmonary disease. What is already know on this topicMucolytic drugs have properties that may be beneficial in chronic obstructive pulmonary diseaseThese drugs are not prescribed in the United Kingdom and Australasia, although they are widely used in many other countriesDrugs that reduce exacerbations may reduce the morbidity and healthcare costs associated with progressively severe diseaseWhat this study addsRegular use of

  6. Vaccination for asthma exacerbations.

    PubMed

    Bardin, P G

    2004-06-01

    Most asthma exacerbations are caused by common cold virus infections, predominantly rhinovirus infections. Full protection against repeat infections with the same rhinovirus serotype is given by serum neutralizing antibody, but cross-reactive antibody developed against other serotypes could yield partial protection and result in attenuated cold and airway symptoms. It is proposed that vaccine-mediated induction of cross-reactive antibody might not prevent rhinovirus infections but might reduce severe asthma symptoms and exacerbations.

  7. Incidence of pulmonary embolism during COPD exacerbation*, **

    PubMed Central

    Akpinar, Evrim Eylem; Hoşgün, Derya; Akpýnar, Serdar; Ataç, Gökçe Kaan; Doğanay, Beyza; Gülhan, Meral

    2014-01-01

    OBJECTIVE: Because pulmonary embolism (PE) and COPD exacerbation have similar presentations and symptoms, PE can be overlooked in COPD patients. Our objective was to determine the prevalence of PE during COPD exacerbation and to describe the clinical aspects in COPD patients diagnosed with PE. METHODS: This was a prospective study conducted at a university hospital in the city of Ankara, Turkey. We included all COPD patients who were hospitalized due to acute exacerbation of COPD between May of 2011 and May of 2013. All patients underwent clinical risk assessment, arterial blood gas analysis, chest CT angiography, and Doppler ultrasonography of the lower extremities. In addition, we measured D-dimer levels and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) levels. RESULTS: We included 172 patients with COPD. The prevalence of PE was 29.1%. The patients with pleuritic chest pain, lower limb asymmetry, and high NT-pro-BNP levels were more likely to develop PE, as were those who were obese or immobile. Obesity and lower limb asymmetry were independent predictors of PE during COPD exacerbation (OR = 4.97; 95% CI, 1.775-13.931 and OR = 2.329; 95% CI, 1.127-7.105, respectively). CONCLUSIONS: The prevalence of PE in patients with COPD exacerbation was higher than expected. The association between PE and COPD exacerbation should be considered, especially in patients who are immobile or obese. PMID:24626268

  8. Using Discrete Event Computer Simulation to Improve Patient Flow in a Ghanaian Acute Care Hospital

    PubMed Central

    Best, Allyson M.; Dixon, Cinnamon A.; Kelton, W. David; Lindsell, Christopher J.

    2014-01-01

    Objectives Crowding and limited resources have increased the strain on acute care facilities and emergency departments (EDs) worldwide. These problems are particularly prevalent in developing countries. Discrete event simulation (DES) is a computer-based tool that can be used to estimate how changes to complex healthcare delivery systems, such as EDs, will affect operational performance. Using this modality, our objective was to identify operational interventions that could potentially improve patient throughput of one acute care setting in a developing country. Methods We developed a simulation model of acute care at a district level hospital in Ghana to test the effects of resource-neutral (e.g. modified staff start times and roles) and resource-additional (e.g. increased staff) operational interventions on patient throughput. Previously captured, de-identified time-and-motion data from 487 acute care patients were used to develop and test the model. The primary outcome was the modeled effect of interventions on patient length of stay (LOS). Results The base-case (no change) scenario had a mean LOS of 292 minutes (95% CI 291, 293). In isolation, neither adding staffing, changing staff roles, nor varying shift times affected overall patient LOS. Specifically, adding two registration workers, history takers, and physicians resulted in a 23.8 (95% CI 22.3, 25.3) minute LOS decrease. However, when shift start-times were coordinated with patient arrival patterns, potential mean LOS was decreased by 96 minutes (95% CI 94, 98); and with the simultaneous combination of staff roles (Registration and History-taking) there was an overall mean LOS reduction of 152 minutes (95% CI 150, 154). Conclusions Resource-neutral interventions identified through DES modeling have the potential to improve acute care throughput in this Ghanaian municipal hospital. DES offers another approach to identifying potentially effective interventions to improve patient flow in emergency and acute

  9. Effects of competition on acute phase proteins and lymphocyte subpopulations - oxidative stress markers in eventing horses.

    PubMed

    Valle, E; Zanatta, R; Odetti, P; Traverso, N; Furfaro, A; Bergero, D; Badino, P; Girardi, C; Miniscalco, B; Bergagna, S; Tarantola, M; Intorre, L; Odore, R

    2015-10-01

    The aim of the study was to evaluate markers of the acute phase response (APR) in eventing horses by measuring acute phase proteins (APP) (haptoglobin, Hp, and serum amyloid A, SAA), lysozyme, protein adducts such as pentosidine-like adducts (PENT), malondialdehyde adducts (MDA), hydroxynonenal adducts (HNE) and total advanced glycation/glycoxidation end products (AGEs), complete blood count and lymphocyte subpopulations (CD4+, CD8+ and CD21+) both at rest and at the end of an eventing competition. Blood samples were collected from eight Warmblood horses (medium age 10 ± 3) during an official national 2-day event competition at rest (R) and 10 min after the arrival of the cross-country test on the second day. Exercise caused a significant increase in red blood cell number, haemoglobin, packed cell volume, neutrophils, white blood cell and lymphocyte number; however, these values remained within the normal range. The CD4+ and CD8+ cells significantly increased, whereas the CD21+ lymphocytes decreased; a significant increase in serum SAA, lysozyme and protein carbonyl derivates was also observed. Two-day event causes significant changes in APR markers such as lysozyme, protein carbonyl derivates (HNE, AGEs, PENT) and lymphocyte subpopulations. The data support the hypothesis that 2-day event may alter significantly APR markers. Limitations of the study were the relatively small sample size and sampling time conditioned by the official regulations of the event. Therefore, further studies are needed to investigate the time required for recovery to basal values in order to define the possible effects on the immune function of the athlete horse.

  10. Pulmonary Strongyloidiasis Masquerading as Exacerbation of Chronic Obstructive Pulmonary Disease

    PubMed Central

    Pradhan, Gourahari; Behera, Priyadarshini; Bhuniya, Sourin; Mohapatra, Prasanta Raghab; Turuk, Jyotirmayee; Mohanty, Srujana

    2016-01-01

    Pulmonary strongyloidiasis is an uncommon presentation of Strongyloides infection, usually seen in immunocompromised hosts. The manifestations are similar to that of acute exacerbation of chronic obstructive pulmonary disease (COPD). Therefore, the diagnosis of pulmonary strongyloidiasis could be challenging in a COPD patient, unless a high index of suspicion is maintained. Here, we present a case of Strongyloides hyperinfection in a COPD patient mimicking acute exacerbation, who was on chronic steroid therapy. PMID:27790284

  11. Acute procedural complications and in-hospital events after percutaneous coronary interventions Eptifibatide versus Abciximab

    SciTech Connect

    Ajani, Andrew E.; Waksman, Ron; Gruberg, Luis; Sharma, Arvind K.; Lew, Robert; Pinnow, Ellen; Canos, Daniel A.; Cheneau, Edouard; Castagna, Marco; Satler, Lowell; Pichard, Augusto; Kent, Kenneth M

    2003-03-01

    Background: Glycoprotein IIb/IIIa antagonists reduce peri-angioplasty ischemic complications and improve in-hospital outcome in patients undergoing percutaneous coronary interventions (PCI). Prior studies have demonstrated favorable results with both eptifibatide and abciximab. The purpose of this study was to assess whether there are any differences in rates of acute procedural complications and in-hospital events with the use of these two agents. Methods: A retrospective review of 359 elective PCIs from June 1998 to August 2000 identified 152 PCIs treated with eptifibatide (bolus 180 {mu}g/kg, infusion 2 {mu}g/kg/min for 12-48 h) and 205 PCIs treated with abciximab (bolus 0.25 mg/kg, infusion 10 {mu}g/min for 12 h). All patients received IIb/IIIa antagonists at the initiation of the intervention. Results: The clinical demographics, the angiographic morphology, the indications, and the procedural details were similar in both groups. In the eptifibatide group, the maximum ACT was lower (235{+-}45 vs. 253{+-}40, P<.0001). The incidence of major procedural and in-hospital events was compared. Eptifibatide and abciximab had similar rates of major complications (death or myocardial infarction) (1.4% vs. 2.9%), repeat PTCA (3.4% vs. 1.9%), and major bleeding (3.3% vs. 4.3%). Conclusions: Eptifibatide is comparable to abciximab in regards to acute procedural complications and in-hospital events after PCI.

  12. Clinical outcomes of adverse cardiovascular events in patients with acute dapsone poisoning

    PubMed Central

    Kang, Kyung Sik; Kim, Hyung Il; Kim, Oh Hyun; Cha, Kyoung Chul; Kim, Hyun; Lee, Kang Hyun; Hwang, Sung Oh; Cha, Yong Sung

    2016-01-01

    Objective Adverse cardiovascular events (ACVEs) account for a large proportion of the morbidities and mortalities associated with drug overdose emergencies. However, there are no published reports regarding outcomes of ACVEs associated with acute dapsone poisoning. Here, the authors retrospectively analyzed ACVEs reported within 48 hours of treatment in patients with acute dapsone poisoning and assessed the significance of ACVEs as early predictors of mortality. Methods Sixty-one consecutive cases of acute dapsone poisoning that were diagnosed and treated at a regional emergency center between 2006 and 2014 were included in the study. An ACVE was defined as myocardial injury, shock, ventricular dysrhythmia, cardiac arrest, or any combination of these occurring within the first 48 hours of treatment for acute dapsone poisoning. Results Nineteen patients (31.1%) had evidence of myocardial injury (elevation of serum troponin-I level or electrocardiography signs of ischemia) after dapsone overdose, and there were a total of 19 ACVEs (31.1%), including one case of shock (1.6%). Fourteen patients (23.0%) died from pneumonia or multiple organ failure, and the incidence of ACVEs was significantly higher among non-survivors than among survivors (64.3% vs. 21.3%, P=0.006). ACVE was a significant predictor of mortality (odds ratio, 5.690; 95% confidence interval, 1.428 to 22.675; P=0.014). Conclusion The incidence of ACVE was significantly higher among patients who died after acute dapsone poisoning. ACVE is a significant predictor of mortality after dapsone overdose, and evidence of ACVE should be carefully sought in these patients. PMID:27752614

  13. Pulmonary Exacerbations in Children with Cystic Fibrosis.

    PubMed

    Waters, Valerie; Ratjen, Felix

    2015-11-01

    Pulmonary exacerbations treated with intravenous antibiotics have significant, well-characterized negative consequences on clinical outcomes in cystic fibrosis (CF). The impact of milder exacerbations in children with CF, commonly treated with oral antibiotics, are less well defined. Pulmonary exacerbations have multiple triggers, but viral infections are particularly common in children. Children with CF and healthy control subjects have similar frequencies of viral respiratory infections, but there is evidence of greater virus-related morbidity in patients with CF, likely due to a combination of increased viral load, more pronounced inflammatory response, and more pronounced impairment in mucociliary clearance. In recent clinical trials in children, definitions have been used that are more symptom based rather than intervention based. These studies have demonstrated differences in the spectrum of symptoms between children and older patients but have also shown that, despite low threshold definitions, a considerable number of patients receive treatment for events not fulfilling the pulmonary exacerbation criteria. Additional research is needed to determine the impact of these milder exacerbations on lung function recovery and time to subsequent exacerbation as well as long-term outcomes such as mortality. PMID:26595740

  14. Endothelial Progenitor Cells Predict Cardiovascular Events after Atherothrombotic Stroke and Acute Myocardial Infarction. A PROCELL Substudy

    PubMed Central

    Cuadrado-Godia, Elisa; Regueiro, Ander; Núñez, Julio; Díaz-Ricard, Maribel; Novella, Susana; Oliveras, Anna; Valverde, Miguel A.; Marrugat, Jaume; Ois, Angel; Giralt-Steinhauer, Eva; Sanchís, Juan; Escolar, Ginès; Hermenegildo, Carlos; Roquer, Jaume

    2015-01-01

    Introduction The aim of this study was to determine prognostic factors for the risk of new vascular events during the first 6 months after acute myocardial infarction (AMI) or atherothrombotic stroke (AS). We were interested in the prognostic role of endothelial progenitor cells (EPC) and circulating endothelial cells (CEC) Methods Between February 2009 and July 2012, 100 AMI and 50 AS patients were consecutively studied in three Spanish centres. Patients with previously documented coronary artery disease or ischemic strokes were excluded. Samples were collected within 24h of onset of symptoms. EPC and CEC were studied using flow cytometry and categorized by quartiles. Patients were followed for up to 6 months. NVE was defined as new acute coronary syndrome, transient ischemic attack (TIA), stroke, or any hospitalization or death from cardiovascular causes. The variables included in the analysis included: vascular risk factors, carotid intima-media thickness (IMT), atherosclerotic burden and basal EPC and CEC count. Multivariate survival analysis was performed using Cox regression analysis. Results During follow-up, 19 patients (12.66%) had a new vascular event (5 strokes; 3 TIAs; 4 AMI; 6 hospitalizations; 1 death). Vascular events were associated with age (P = 0.039), carotid IMT≥0.9 (P = 0.044), and EPC count (P = 0.041) in the univariate analysis. Multivariate Cox regression analysis showed an independent association with EPC in the lowest quartile (HR: 10.33, 95%CI (1.22–87.34), P = 0.032] and IMT≥0.9 [HR: 4.12, 95%CI (1.21–13.95), P = 0.023]. Conclusions Basal EPC and IMT≥0.9 can predict future vascular events in patients with AMI and AS, but CEC count does not affect cardiovascular risk. PMID:26332322

  15. Infective Exacerbation of Pasteurella multocida.

    PubMed

    Hamada, Mayumi; Elshimy, Noha; Abusriwil, Hatem

    2016-01-01

    An 89-year-old lady presented with a one-day history of shortness of breath as well as a cough productive of brown sputum. Her medical history was significant for chronic obstructive pulmonary disease (COPD). She was in severe type one respiratory failure and blood tests revealed markedly raised inflammatory markers; however her chest X-ray was clear. On examination there was bronchial breathing with widespread crepitations and wheeze. She was treated as per an infective exacerbation of COPD. Subsequent blood cultures grew Pasteurella multocida, a common commensal in the oropharynx of domesticated animals. The patient was then asked about any contact with animals, after which she revealed she had a dog and was bitten on her left hand the day before admission. We should not forget to enquire about recent history of injuries or animal bites when patients present acutely unwell. She made a complete recovery after treatment with penicillin. PMID:26942025

  16. Infective Exacerbation of Pasteurella multocida

    PubMed Central

    Hamada, Mayumi; Elshimy, Noha; Abusriwil, Hatem

    2016-01-01

    An 89-year-old lady presented with a one-day history of shortness of breath as well as a cough productive of brown sputum. Her medical history was significant for chronic obstructive pulmonary disease (COPD). She was in severe type one respiratory failure and blood tests revealed markedly raised inflammatory markers; however her chest X-ray was clear. On examination there was bronchial breathing with widespread crepitations and wheeze. She was treated as per an infective exacerbation of COPD. Subsequent blood cultures grew Pasteurella multocida, a common commensal in the oropharynx of domesticated animals. The patient was then asked about any contact with animals, after which she revealed she had a dog and was bitten on her left hand the day before admission. We should not forget to enquire about recent history of injuries or animal bites when patients present acutely unwell. She made a complete recovery after treatment with penicillin. PMID:26942025

  17. Walking, cycling, or gardening, with or without seasonal interruption, in relation to acute coronary events.

    PubMed

    Magnus, K; Matroos, A; Strackee, J

    1979-12-01

    The case-referent study reported here investigates the relationship between acute coronary events (ACE) and sustained light physical exercise, mainly leisure-time walking, cycling, or gardening (WCG). These activities are classified as habitual WCG (greater than 8 months/year), seasonal WCG (4--8 months), or occasional WCG (less than 4 months), each category being further subdivided according to the number of hours a week: less than 4 hours, 4--7 hours, or greater than 7 hours. A significant negative association is found between ACE and habitual WCG. No such relationship is evident between ACE and seasonal WCG, however, seasonal WCG being equally frequent (27%) in both cases and referents. These observations may indicate that any effect on the incidence of acute coronary events that is caused by walking, cycling, or gardening is neutralized if these activities are interrupted for several months of the year. The negative association between habitual WCG and ACE does not depend on the number of hours a week devoted to SCG and is not enhanced by more vigorous additional exercise. The fatality of ACE (death rate within 4 weeks) is significantly higher in the least active group (WCG less than 4 months/year).

  18. Effect of acute exercise and cardiovascular fitness on cognitive function: an event-related cortical desynchronization study.

    PubMed

    Chang, Yu-Kai; Chu, Chien-Heng; Wang, Chun-Chih; Song, Tai-Fen; Wei, Gao-Xia

    2015-03-01

    This study aimed to clarify the effects of acute exercise and cardiovascular fitness on cognitive function using the Stroop test and event-related desynchronization (ERD) in an aged population. Old adults (63.10 ± 2.89 years) were first assigned to either a high-fitness or a low-fitness group, and they were then subjected to an acute exercise treatment and a reading control treatment in a counterbalanced order. Alpha ERD was recorded during the Stroop test, which was administered after both treatments. Acute exercise improved cognitive performance regardless of the level of cognition, and old adults with higher fitness levels received greater benefits from acute exercise. Additionally, acute exercise, rather than overall fitness, elicited greater lower and upper alpha ERDs relative to the control condition. These findings indirectly suggest that the beneficial effects of acute exercise on cognitive performance may result from exercise-induced attentional control observed during frontal neural excitation. PMID:25308605

  19. Clinical Risk Factors for In-Hospital Adverse Cardiovascular Events After Acute Drug Overdose

    PubMed Central

    Manini, Alex F.; Hoffman, Robert S.; Stimmel, Barry; Vlahov, David

    2015-01-01

    Objectives It was recently demonstrated that adverse cardiovascular events (ACVE) complicate a high proportion of hospitalizations for patients with acute drug overdoses. The aim of this study was to derive independent clinical risk factors for ACVE in patients with acute drug overdoses. Methods This prospective cohort study was conducted over 3 years at two urban university hospitals. Patients were adults with acute drug overdoses enrolled from the ED. In-hospital ACVE was defined as any of myocardial injury, shock, ventricular dysrhythmia, or cardiac arrest. Results There were 1,562 patients meeting inclusion/exclusion criteria (mean age, 41.8 years; female, 46%; suicidal, 38%). ACVE occurred in 82 (5.7%) patients (myocardial injury, 61; shock, 37; dysrhythmia, 23; cardiac arrests, 22) and there were 18 (1.2%) deaths. On univariate analysis, ACVE risk increased with age, lower serum bicarbonate, prolonged QTc interval, prior cardiac disease, and altered mental status. In a multivariable model adjusting for these factors as well as patient sex and hospital site, independent predictors were: QTc > 500 msec (3.8% prevalence, odds ratio [OR] 27.6), bicarbonate < 20 mEql/L (5.4% prevalence, OR 4.4), and prior cardiac disease (7.1% prevalence, OR 9.5). The derived prediction rule had 51.6% sensitivity, 93.7% specificity, and 97.1% negative predictive value; while presence of two or more risk factors had 90.9% positive predictive value. Conclusions The authors derived independent clinical risk factors for ACVE in patients with acute drug overdose, which should be validated in future studies as a prediction rule in distinct patient populations and clinical settings. PMID:25903997

  20. Modeling Acute Health Effects of Astronauts from Exposure to Large Solar Particle Events

    NASA Technical Reports Server (NTRS)

    Hu, Shaowen; Kim, Myung-Hee Y.; Cucinotta, Francis A.

    2011-01-01

    In space exploration outside the Earth s geomagnetic field, radiation exposure from solar particle events (SPE) presents a health concern for astronauts, that could impair their performance and result in possible failure of the mission. Acute risks are of special concern during extra-vehicular activities because of the rapid onset of SPE. However, most SPEs will not lead to acute risks but can lead to mission disruption if accurate projection methods are not available. Acute Radiation Sickness (ARS) is a group of clinical syndromes developing acutely (within several seconds to 3 days) after high dose whole-body or significant partial-body ionizing radiation exposures. The manifestation of these syndromes reflects the disturbance of physiological processes of various cellular groups damaged by radiation. Hematopoietic cells, skin, epithelium, intestine, and vascular endothelium are among the most sensitive tissues of human body to ionizing radiation. Most ARS symptoms are directly related to these tissues and other systems (nervous, endocrine, and cardiovascular, etc.) with coupled regulations. Here we report the progress in bio-mathematical models to describe the dose and time-dependent early human responses to ionizing radiation. The responses include lymphocyte depression, granulocyte modulation, fatigue and weakness syndrome, and upper gastrointestinal distress. The modest dose and dose-rates of SPEs are predicted to lead to large sparing of ARS, however detailed experimental data on a range of proton dose-rates for organ doses from 0.5 to 2 Gy is needed to validate the models. We also report on the ARRBOD code that integrates the BRYNTRN and SUMDOSE codes, which are used to estimate the SPE organ doses for astronauts under various space travel scenarios, with our models of ARS. The more recent effort is to provide easy web access to space radiation risk assessment using the ARRBOD code.

  1. Impact of Prolonged Exacerbation Recovery in Chronic Obstructive Pulmonary Disease

    PubMed Central

    Law, Martin; Kowlessar, Beverly; Singh, Richa; Brill, Simon E.; Allinson, James P.; Wedzicha, Jadwiga A.

    2015-01-01

    Rationale: Exacerbations are important and heterogeneous events in the natural history of chronic obstructive pulmonary disease (COPD). Objectives: To examine the consequences of prolonged exacerbation recovery in patients with COPD. Methods: A cohort of 384 patients with COPD (FEV1 % predicted 45.8 [SD, 16.6] and a median exacerbation rate of 2.13 per year [interquartile range, 1.0–3.2]) were followed for 1,039 days (interquartile range, 660–1,814) between October 1995 and January 2013. Patients recorded daily worsening of respiratory symptoms and peak expiratory flow (PEF), and when stable underwent spirometry every 3 months, and completed the St. George’s Respiratory Questionnaire annually. Exacerbations were diagnosed as 2 consecutive days with one major symptom plus another respiratory symptom. Exacerbation duration was defined as the time from onset to the day preceding 2 consecutive symptom-free days and recovery in PEF as return to preexacerbation levels. Measurements and Main Results: A total of 351 patients had one or more exacerbations. Patients with a longer symptom duration (mean, 14.5 d) had a worse St. George’s Respiratory Questionnaire total score (0.2 units per 1 day; P = 0.040). A longer symptomatic duration was associated with a shorter interval between exacerbation recovery and onset of the next exacerbation (hazard ratio, 1.004; P = 0.013). For 257 (7.3%) exacerbations, PEF did not recover within 99 days. These exacerbations were associated with symptoms of a viral infection (cold and sore throat). Patients with these nonrecovered exacerbations showed a 10.8 ml/yr (P < 0.001) faster decline in FEV1. Conclusions: Prolonged exacerbation symptomatic duration is associated with poorer health status and a greater risk of a new event. Exacerbations where lung function does not recover are associated with symptoms of viral infections and accelerated decline in FEV1. PMID:26151174

  2. Association of airborne Aspergillus with asthma exacerbation in Southern Pakistan

    PubMed Central

    Zubairi, Ali Bin Sarwar; Azam, Iqbal; Awan, Safia; Zafar, Afia

    2014-01-01

    Background Exposure to airborne fungi has been related with exacerbation of asthma in adults and children leading to increased outpatient, emergency room visits, and hospitalizations. Hypersensitivity to these airborne fungi may be an important initial predisposing factor in the development and exacerbation of asthma. Objective This study was conducted to determine an association between fungal types and spore concentrations with the risk of asthma exacerbation in adults. Methods This cross-sectional study was conducted from May 2008 to August 2009 at the Aga Khan University Hospital Karachi, Pakistan. All adult (age≥16 years) patients presenting to the hospital with acute asthma exacerbation were enrolled after informed consent. A home survey was conducted for each patient to assess their environmental characteristics. Indoor air samples were also obtained from the patient's home to determine the type and spore concentration of fungi within the week of their enrollment in the study. Results Three hundred and ninety-one patients with an acute asthma exacerbation were enrolled during the study period. The mean age of participants was 46 years (standard deviation, ±18 years) and 247 (63.2%) were females. A trend of higher asthma enrollment associated with higher Aspergillus concentrations was found in two consecutive summers. A total of nineteen types of fungi were found in air samples. Aspergillus spp. was the most frequently isolated fungus with acute asthma exacerbation. Conclusion An association of higher concentration of indoor Aspergillus spp. with asthma exacerbation in adults was observed in this study. PMID:24809014

  3. Asthma Exacerbation: An Emergency Medicine Simulation Scenario

    PubMed Central

    Angus, Karen; Parsons, Michael; Cheeseman, Neil

    2015-01-01

    In the practice of emergency medicine, simulation is a valuable tool that allows medical students and postgraduate residents to develop skills in a safe environment at no risk to patients. In this report, we present a case simulation of an acute asthma exacerbation utilizing a human patient simulator. The case is designed such that it can be easily modified to accommodate the trainee’s level of expertise, allowing instructors to challenge both the novice and advanced learner alike. PMID:26180682

  4. Dipyridamole-thallium-201 scintigraphy in the prediction of future cardiac events after acute myocardial infarction

    SciTech Connect

    Leppo, J.A.; O'Brien, J.; Rothendler, J.A.; Getchell, J.D.; Lee, V.W.

    1984-04-19

    To evaluate the safety and usefulness of serial thallium scanning immediately after intravenous dipyridamole, we studied 51 patients recovering from acute myocardial infarction. Eight patients experienced angina during the procedure, but there were no serious complications. Patients were followed for a mean period of 19 months after hospital discharge. Eleven of 12 patients who died during follow-up or had another infarction had shown transient defects (redistribution) on their predischarge scan, as had 22 of the 24 patients who needed readmission for management of angina. Among all the other clinical or scintigraphic criteria tested, the presence of redistribution on the dipyridamole-thallium scan was the only significant predictor of these serious cardiac events. Twenty-six patients were also given a submaximal exercise test before discharge, of whom 13 subsequently had serious cardiac events. The exercise test had been positive in only 6 of these 13 patients, whereas the dipyridamole-thallium scan had shown a redistribution pattern in 12 (P less than 0.001). We conclude from this preliminary study that dipyridamole-thallium scintigraphy after myocardial infraction is relatively safe. It appears to be a more sensitive predictor of subsequent cardiac events than a submaximal exercise test and may therefore prove useful in evaluating patients after recovery from a myocardial infarction.

  5. Quality of Life of Patients After an Acute Coronary Event: Hospital Discharge

    PubMed Central

    Dias, Cristiane Maria Carvalho Costa; Macedo, Luciana Bilitario; Gomes, Lilian Tapioca Jones Cunha; de Oliveira, Paula Luzia Seixas Pereira; Albuquerque, Iana Verena Santana; Lemos, Amanda Queiroz; Brasil, Cristina Aires; Prado, Eloisa Pires Ferreira; Macedo, Pedro Santiago; de Oliveira, Francisco Tiago Oliveira; dos Reis, Helena Franca Correia; Darze, Eduardo Sahade; Guimaraes, Armenio Costa

    2014-01-01

    Background The acute coronary syndrome (ACS) has a high morbi-mortality rate, including physical deficiencies and functional limitations with impact on quality of life. Cardiovascular rehabilitation 1 (CVR1) should begin as early as possible, to enable improvement in functional capacity and quality of life. Previous studies have shown association of cardiovascular diseases with quality of life, in which depression and anxiety are the domains most altered. The aim of the study is to verify the impact of an acute coronary event on quality of life at the moment of hospital discharge. Methodology This was a cross-sectional study, with ACS patients hospitalized in ICU of a private hospital in the city of Salvador, Brazil, submitted to CVR1. The quality of life questionnaire Euroqol-5D was applied on discharge from hospital. Patients included in the study were those with ACV, who had medical permission to walk, had not been submitted to acute surgical treatment, were time and space oriented, and over the age of 18 years. Patients excluded from the study were those with cognitive, orthopedic and neurological problems, who used orthesis on a lower limb, and were in any condition of risk at the time of beginning with CVR1. Data were collected by a previously trained ICU team. Results Data were collected of 63 patients who revealed compromise in the domains of pain/feeling ill (20.63%) and anxiety/depression (38.09%). Statistical significance was observed in the association between sex and pain/feeling ill (P < 0.01), sex and anxiety/depression (P < 0.01), diabetes and mobility (P < 0.01), hereditary factors and anxiety/depression (p < 0.01), BMI and pain/feeling ill (P < 0.01). Conclusion In this sample of patients, on discharge from hospital after ACS, the pain/feeling ill and anxiety/depression domains were shown to be compromised. PMID:25110540

  6. Treatment and outcomes of patients with suspected acute coronary syndromes in relation to initial diagnostic impressions (insights from the Canadian Global Registry of Acute Coronary Events [GRACE] and Canadian Registry of Acute Coronary Events [CANRACE]).

    PubMed

    Bajaj, Ravi R; Goodman, Shaun G; Yan, Raymond T; Bagnall, Alan J; Gyenes, Gabor; Welsh, Robert C; Eagle, Kim A; Brieger, David; Ramanathan, Krishnan; Grondin, Francois R; Yan, Andrew T

    2013-01-15

    The early diagnosis of acute coronary syndrome (ACS) remains challenging, and a considerable proportion of patients are diagnosed with "possible" ACS on admission. The Global Registry of Acute Coronary Events (GRACE/GRACE(2)) and Canadian Registry of Acute Coronary Events (CANRACE) enrolled 16,618 Canadian patients with suspected ACS in 1999 to 2008. We compared the demographic and clinical characteristics, use of cardiac procedures, prognostic accuracy of the GRACE risk score, and in-hospital outcomes between patients given an admission diagnosis of "definite" versus "possible" ACS by the treating physician. Overall, 11,152 and 5,466 patients were given an initial diagnosis of "definite" ACS and "possible" ACS, respectively. Patients with a "possible" ACS had higher GRACE risk score (median 130 vs 125) and less frequently received aspirin, clopidogrel, heparin, or β blockers within the first 24 hours of presentation and assessment of left ventricular function, stress testing, cardiac catheterization, and percutaneous coronary intervention (all p <0.05). Patients with "possible" ACS had greater rates of in-hospital myocardial infarction (9.0% vs 2.0%, p <0.05) and heart failure (12% vs 8.9%, p <0.05). The GRACE risk score demonstrated excellent discrimination for in-hospital mortality in both groups and for the entire study population. In conclusion, compared to patients with "definite" ACS on presentation, those with "possible" ACS had higher baseline GRACE risk scores but less frequently received evidence-based medical therapies within 24 hours of admission or underwent cardiac procedures during hospitalization. The GRACE risk score provided accurate risk assessment, regardless of the initial diagnostic impression.

  7. Imaging Plaques to Predict and Better Manage Patients with Acute Coronary Events

    PubMed Central

    Garcia-Garcia, Hector M.; Jang, Ik-Kyung; Serruys, Patrick W.; Kovacic, Jason C.; Narula, Jagat; Fayad, Zahi A.

    2014-01-01

    Culprit lesions of patients who have had an acute coronary syndrome commonly are ruptured coronary plaques with superimposed thrombus. The precursor of such lesions is an inflamed thin-capped fibroatheroma. These plaques can be imaged by means of invasive techniques such as intravascular ultrasound (and derived techniques), optical coherence tomography and near-infrared spectroscopy. Very often these patients exhibit similar (multiple) plaques beyond the culprit lesion. These remote plaques can be assessed non invasively by computed tomography angiography and magnetic resonance imaging and also using invasive imaging. The detection of these remote plaques is not only feasible, but also in natural history studies have been associated with clinical coronary events. Different systemic pharmacological treatments have been studied (mostly statins) with modest success and therefore newer approaches are being tested. Local treatment for such lesions is in its infancy and larger, prospective and randomized trials are needed. This review will describe the pathological and imaging findings in culprit lesions of patients with acute coronary syndrome and as well as the assessment of remote plaques. In addition, the pharmacological and local treatment options will be reviewed. PMID:24902974

  8. Imaging plaques to predict and better manage patients with acute coronary events.

    PubMed

    Garcia-Garcia, Hector M; Jang, Ik-Kyung; Serruys, Patrick W; Kovacic, Jason C; Narula, Jagat; Fayad, Zahi A

    2014-06-01

    Culprit lesions of patients, who have had an acute coronary syndrome commonly, are ruptured coronary plaques with superimposed thrombus. The precursor of such lesions is an inflamed thin-capped fibroatheroma. These plaques can be imaged by means of invasive techniques, such as intravascular ultrasound (and derived techniques), optical coherence tomography, and near-infrared spectroscopy. Often these patients exhibit similar (multiple) plaques beyond the culprit lesion. These remote plaques can be assessed noninvasively by computed tomographic angiography and MRI and also using invasive imaging. The detection of these remote plaques is not only feasible but also in natural history studies have been associated with clinical coronary events. Different systemic pharmacological treatments have been studied (mostly statins) with modest success and, therefore, newer approaches are being tested. Local treatment for such lesions is in its infancy and larger, prospective, and randomized trials are needed. This review will describe the pathological and imaging findings in culprit lesions of patients with acute coronary syndrome and the assessment of remote plaques. In addition, the pharmacological and local treatment options will be reviewed.

  9. Evidence Report: Risk of Acute Radiation Syndromes Due to Solar Particle Events

    NASA Technical Reports Server (NTRS)

    Carnell, Lisa; Blattnig, Steve; Hu, Shaowen; Huff, Janice; Kim, Myung-Hee; Norman, Ryan; Patel, Zarana; Simonsen, Lisa; Wu, Honglu

    2016-01-01

    Crew health and performance may be impacted by a major solar particle event (SPE), multiple SPEs, or the cumulative effect of galactic cosmic rays (GCR) and SPEs. Beyond low-Earth orbit, the protection of the Earth's magnetosphere is no longer available, such that increased shielding and protective mechanisms are necessary in order to prevent acute radiation sickness and impacts to mission success or crew survival. While operational monitoring and shielding are expected to minimize radiation exposures, there are EVA scenarios outside of low-Earth orbit where the risk of prodromal effects, including nausea, vomiting, anorexia, and fatigue, as well as skin injury and depletion of the blood-forming organs (BFO), may occur. There is a reasonable concern that a compromised immune system due to high skin doses from a SPE or due to synergistic space flight factors (e.g., microgravity) may lead to increased risk to the BFO. The primary data available at present are derived from analyses of medical patients and persons accidentally exposed to acute, high doses of low-linear energy transfer (LET) (or terrestrial) radiation. Data more specific to the space flight environment must be compiled to quantify the magnitude of increase of this risk and to develop appropriate protection strategies. In particular, information addressing the distinct differences between solar proton exposures and terrestrial exposure scenarios, including radiation quality, dose-rate effects, and non-uniform dose distributions, is required for accurate risk estimation.

  10. Low rate of cardiovascular events in patients with acute myocarditis diagnosed by cardiovascular magnetic resonance

    PubMed Central

    De Stefano, Luciano; Yeyati, Ezequiel Levy; Pietrani, Marcelo; Kohan, Andres; Falconi, Mariano; Benger, Juan; Dragonetti, Laura; Garcia-Monaco, Ricardo; Cagide, Arturo

    2014-01-01

    Background Myocarditis is a relatively common inflammatory disease that affects the myocardium. Infectious disease accounts for most of the cases either because of a direct viral infection or post-viral immune-mediated reaction. Cardiovascular magnetic resonance (CMR) has become an established non-invasive diagnosis tool for acute myocarditis. A recent large single centre study with patients with biopsy-proven viral myocarditis undergoing CMR scans found a high rate of mortality. The aim of this study was to assess the rate of clinical events in our population of patients with diagnosed myocarditis by CMR scan. Methods Patients who consulted to the emergency department with diagnosis of myocarditis by CMR were retrospectively included in the study from January 2008 to May 2012. A CMR protocol was used in all patients, and were followed up to assess the rate of the composite endpoint of all-cause death, congestive heart failure, sudden cardiac death, hospitalization for cardiac cause, recurrent myocarditis or need of radiofrequency ablation or implantable cardiac defibrillator (ICD). A descriptive statistical analysis was performed. Results Thirty-two patients with myocarditis were included in the study. The mean age was 42.6±21.2 years and 81.2% were male. In a mean follow up of 30.4±17.8 months, the rate of the composite endpoint of all-cause death, congestive heart failure, sudden cardiac death, hospitalization for cardiac cause, recurrent myocarditis or need of radiofrequency ablation or ICD was 15.6% (n=5). Two patients had heart failure (one of them underwent heart transplant), one patient needed ICD because of ventricular tachycardia and two other patients were re-hospitalized, for recurrent chest pain and for recurrent myocarditis respectively. Conclusions In our series of acute myocarditis diagnosed by CMR we found a low rate of cardiovascular events without mortality. These findings might oppose data from recently published myocarditis trials. PMID

  11. Seasonal Risk Factors for Asthma Exacerbations among Inner City Children

    PubMed Central

    Teach, Stephen J.; Gergen, Peter J.; Szefler, Stanley J.; Mitchell, Herman E.; Calatroni, Agustin; Wildfire, Jeremy; Bloomberg, Gordon; Kercsmar, Carolyn; Liu, Andrew H.; Makhija, Melanie; Matsui, Elizabeth; Morgan, Wayne; O'Connor, George; Busse, William W.

    2015-01-01

    Background Exacerbations of asthma remain common even in children and adolescents despite optimal medical management. Identification of host risk factors for exacerbations is incomplete, particularly for seasonal episodes. Objective Define host risk factors for asthma exacerbations unique to their season of occurrence. Methods This is a retrospective analysis of patients aged 6-20 years who comprised the control groups of the Asthma Control Evaluation trial and the Inner City Anti-IgE Therapy for Asthma trial. Univariate and multivariate models were constructed to determine if patient demographic and historical factors, allergic sensitization, fractional exhaled nitric oxide, spirometric measurements, asthma control, and treatment requirements were associated with seasonal exacerbations. Results The analysis included 400 patients (54.5% male; 59.0% African American; median age 13 years). Exacerbations occurred in 37.5% of participants over the periods of observation and were most common in the fall (28.8% of participants). In univariate analysis, impaired pulmonary function was significantly associated with greater odds of exacerbations for all seasons, as was an exacerbation in the previous season for all seasons except spring. In multivariate analysis, exacerbation in the previous season was the strongest predictor in fall and winter while a higher requirement for inhaled corticosteroids was the strongest predictor in spring and summer. The multivariate models had the best predictive power for fall exacerbations (30.5% variance attributed). Conclusions Among a large cohort of inner city children with asthma, patient risk factors for exacerbations vary by season. Thus, individual patient information may be beneficial in strategies to prevent these seasonal events. Clinical Implications Inner city children remain at risk for asthma exacerbations despite appropriate therapy. Because their risk factors vary by season, strategies to prevent them may need to differ as

  12. Modeling the acute health effects of astronauts from exposure to large solar particle events.

    PubMed

    Hu, Shaowen; Kim, Myung-Hee Y; McClellan, Gene E; Cucinotta, Francis A

    2009-04-01

    Radiation exposure from Solar Particle Events (SPE) presents a significant health concern for astronauts for exploration missions outside the protection of the Earth's magnetic field, which could impair their performance and result in the possibility of failure of the mission. Assessing the potential for early radiation effects under such adverse conditions is of prime importance. Here we apply a biologically based mathematical model that describes the dose- and time-dependent early human responses that constitute the prodromal syndromes to consider acute risks from SPEs. We examine the possible early effects on crews from exposure to some historically large solar events on lunar and/or Mars missions. The doses and dose rates of specific organs were calculated using the Baryon radiation transport (BRYNTRN) code and a computerized anatomical man model, while the hazard of the early radiation effects and performance reduction were calculated using the Radiation-Induced Performance Decrement (RIPD) code. Based on model assumptions we show that exposure to these historical events would cause moderate early health effects to crew members inside a typical spacecraft or during extra-vehicular activities, if effective shielding and medical countermeasure tactics were not provided. We also calculate possible even worse cases (double intensity, multiple occurrences in a short period of time, etc.) to estimate the severity, onset and duration of various types of early illness. Uncertainties in the calculation due to limited data on relative biological effectiveness and dose-rate modifying factors for protons and secondary radiation, and the identification of sensitive sites in critical organs are discussed.

  13. Modeling the acute health effects of astronauts from exposure to large solar particle events.

    PubMed

    Hu, Shaowen; Kim, Myung-Hee Y; McClellan, Gene E; Cucinotta, Francis A

    2009-04-01

    Radiation exposure from Solar Particle Events (SPE) presents a significant health concern for astronauts for exploration missions outside the protection of the Earth's magnetic field, which could impair their performance and result in the possibility of failure of the mission. Assessing the potential for early radiation effects under such adverse conditions is of prime importance. Here we apply a biologically based mathematical model that describes the dose- and time-dependent early human responses that constitute the prodromal syndromes to consider acute risks from SPEs. We examine the possible early effects on crews from exposure to some historically large solar events on lunar and/or Mars missions. The doses and dose rates of specific organs were calculated using the Baryon radiation transport (BRYNTRN) code and a computerized anatomical man model, while the hazard of the early radiation effects and performance reduction were calculated using the Radiation-Induced Performance Decrement (RIPD) code. Based on model assumptions we show that exposure to these historical events would cause moderate early health effects to crew members inside a typical spacecraft or during extra-vehicular activities, if effective shielding and medical countermeasure tactics were not provided. We also calculate possible even worse cases (double intensity, multiple occurrences in a short period of time, etc.) to estimate the severity, onset and duration of various types of early illness. Uncertainties in the calculation due to limited data on relative biological effectiveness and dose-rate modifying factors for protons and secondary radiation, and the identification of sensitive sites in critical organs are discussed. PMID:19276707

  14. An Enduring Somatic Threat Model of Posttraumatic Stress Disorder Due to Acute Life-Threatening Medical Events

    PubMed Central

    Edmondson, Donald

    2014-01-01

    Posttraumatic stress disorder (PTSD) occurs in 12-25% of survivors of acute life-threatening medical events such as heart attack, stroke, and cancer, and is associated with recurrence of cardiac events and mortality in heart attack survivors. This article reviews the current state of knowledge about PTSD after such events, and proposes an Enduring Somatic Threat (EST) model of PTSD due to acute life-threatening medical events to address underappreciated differences between PTSD due to past, discrete/external traumatic events (such as combat) and PTSD due to acute manifestations of chronic disease that are enduring/internal in nature (such as heart attack and stroke). The differences include the external versus internal/somatic source of the threat, the past versus present/future temporal focus of threatening cognitions, the different types and consequences of avoidance behavior, and the different character and consequences of hyperarousal. Although important differences between the two types of PTSD exist, the EST model proposes that the underlying fear of mortality maintains PTSD symptoms due to both discrete/external and ongoing/somatic events. Finally, this article offers a research agenda for testing the EST model, with a particular focus on areas that may improve cardiovascular prognosis and health behaviors in survivors of heart attack and stroke. PMID:24920956

  15. Patient characteristics associated with risk of first hospital admission and readmission for acute exacerbation of chronic obstructive pulmonary disease (COPD) following primary care COPD diagnosis: a cohort study using linked electronic patient records

    PubMed Central

    Hunter, L C; Lee, R J; Butcher, I; Weir, C J; Fischbacher, C M; McAllister, D; Wild, S H; Hewitt, N; Hardie, R M

    2016-01-01

    Objectives To investigate patient characteristics of an unselected primary care population associated with risk of first hospital admission and readmission for acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Design Retrospective open cohort using pseudonymised electronic primary care data linked to secondary care data. Setting Primary care; Lothian (population approximately 800 000), Scotland. Participants Data from 7002 patients from 72 general practices with a COPD diagnosis date between 2000 and 2008 recorded in their primary care record. Patients were followed up until 2010, death or they left a participating practice. Main outcome measures First and subsequent admissions for AECOPD (International Classification of Diseases (ICD) 10 codes J44.0, J44.1 in any diagnostic position) after COPD diagnosis in primary care. Results 1756 (25%) patients had at least 1 AECOPD admission; 794 (11%) had at least 1 readmission and the risk of readmission increased with each admission. Older age at diagnosis, more severe COPD, low body mass index (BMI), current smoking, increasing deprivation, COPD admissions and interventions for COPD prior to diagnosis in primary care, and comorbidities were associated with higher risk of first AECOPD admission in an adjusted Cox proportional hazards regression model. More severe COPD and COPD admission prior to primary care diagnosis were associated with increased risk of AECOPD readmission in an adjusted Prentice-Williams-Peterson model. High BMI was associated with a lower risk of first AECOPD admission and readmission. Conclusions Several patient characteristics were associated with first AECOPD admission in a primary care cohort of people with COPD but fewer were associated with readmission. Prompt diagnosis in primary care may reduce the risk of AECOPD admission and readmission. The study highlights the important role of primary care in preventing or delaying a first AECOPD admission. PMID:26801463

  16. Design and Rationale of Gulf locals with Acute Coronary Syndrome Events (Gulf Coast) Registry

    PubMed Central

    Zubaid, Mohammad; Thani, Khalid Bin; Rashed, Wafa; Alsheikh-Ali, Alawi; Alrawahi, Najib; Ridha, Mustafa; Akbar, Mousa; Alenezi, Fahad; Alhamdan, Rashed; Almahmeed, Wael; Ouda, Hussam; Al-Mulla, Arif; Baslaib, Fahad; Shehab, Abdulla; Alnuaimi, Abdulla; Amin, Haitham; Krumholz, Harlan M

    2014-01-01

    Objectives: To describe the risk profile, management and one-year outcomes of patients hospitalized with acute coronary syndrome (ACS) in the Gulf region of the Middle East. Subjects and Methods: The Gulf locals with acute coronary syndrome events (Gulf COAST) registry is a prospective, multinational, longitudinal, observational, cohort-based registry of consecutive citizens, from the Gulf region of the Middle East, admitted from January 2012 to January 2013 to 29 hospitals with a diagnosis of ACS. Data entered online included patient demographics, cardiovascular risk profiles, past medical history, physical findings on admission, in-hospital diagnostic tests and therapeutic management, as well as one year outcomes. Results: 3188 patients were recruited. The mean age was 60.4 ± 12.6years (range: 22-112), 2104 (66%) were males and 1084 (34%) females. The discharge diagnosis was ST-segment elevation myocardial infarction (STEMI) in 741 (23.2%), new-onset left bundle branch block myocardial infarction (LBBBMI) in 30 (0.9%), non-ST-segment elevation myocardial infarction (NSTEMI) in 1486 (46.6%) and unstable angina in 931 (29.2%). At hospital presentation, 2105 (66%), 1779 (55.8%), 1703 (53.4%) and 740 (23.2%) had history of hypertension, dyslipidemia, diabetes mellitus and active smoking, respectively. Conclusion: Patients with ACS in our region are young with very high risk profile. The Gulf COAST registry is an example of successful regional collaboration and will provide information on contemporary management of ACS in the region. PMID:25328551

  17. Acute hematological effects of solar particle event proton radiation in the porcine model.

    PubMed

    Sanzari, J K; Wan, X S; Wroe, A J; Rightnar, S; Cengel, K A; Diffenderfer, E S; Krigsfeld, G S; Gridley, D S; Kennedy, A R

    2013-07-01

    Acute radiation sickness (ARS) is expected to occur in astronauts during large solar particle events (SPEs). One parameter associated with ARS is the hematopoietic syndrome, which can result from decreased numbers of circulating blood cells in those exposed to radiation. The peripheral blood cells are critical for an adequate immune response, and low blood cell counts can result in an increased susceptibility to infection. In this study, Yucatan minipigs were exposed to proton radiation within a range of skin dose levels expected for an SPE (estimated from previous SPEs). The proton-radiation exposure resulted in significant decreases in total white blood cell count (WBC) within 1 day of exposure, 60% below baseline control value or preirradiation values. At the lowest level of the blood cell counts, lymphocytes, neutrophils, monocytes and eosinophils were decreased up to 89.5%, 60.4%, 73.2% and 75.5%, respectively, from the preirradiation values. Monocytes and lymphocytes were decreased by an average of 70% (compared to preirradiation values) as early as 4 h after radiation exposure. Skin doses greater than 5 Gy resulted in decreased blood cell counts up to 90 days after exposure. The results reported here are similar to studies of ARS using the nonhuman primate model, supporting the use of the Yucatan minipig as an alternative. In addition, the high prevalence of hematologic abnormalities resulting from exposure to acute, whole-body SPE-like proton radiation warrants the development of appropriate countermeasures to prevent or treat ARS occurring in astronauts during space travel.

  18. Pathogenesis of Viral Infection in Exacerbations of Airway Disease.

    PubMed

    Ritchie, Andrew I; Farne, Hugo A; Singanayagam, Aran; Jackson, David J; Mallia, Patrick; Johnston, Sebastian L

    2015-11-01

    Chronic airway diseases are a significant cause of morbidity and mortality worldwide, and their prevalence is predicted to increase in the future. Respiratory viruses are the most common cause of acute pulmonary infection, and there is clear evidence of their role in acute exacerbations of inflammatory airway diseases such as asthma and chronic obstructive pulmonary disease. Studies have reported impaired host responses to virus infection in these diseases, and a better understanding of the mechanisms of these abnormal immune responses has the potential to lead to the development of novel therapeutic targets for virus-induced exacerbations. The aim of this article is to review the current knowledge regarding the role of viruses and immune modulation in acute exacerbations of chronic pulmonary diseases and to discuss exciting areas for future research and novel treatments.

  19. Urgent carotid endarterectomy in patients with acute neurological ischemic events within six hours after symptoms onset.

    PubMed

    Gajin, P; Radak, Dj; Tanaskovic, S; Babic, S; Nenezic, D

    2014-06-01

    To analyze the outcome of urgent carotid endarterectomy (CEA) performed within less than six hours in patients with crescendo transient ischemic attack (TIA) and stroke in progression. From January 1998 to December 2008, 58 urgent CEAs were done for acute neurological ischemic events--46 patients with crescendo TIA and 12 patients with stroke in progression. Brain computed tomography (CT) was done prior and after the surgery. Disability level was assessed prior to and after urgent CEA using modified Rankin scale. Median follow-up was 42.1 ± 16.6 months. In the early postoperative period stroke rate was 0% for the patients in crescendo TIA group while in patients with stroke in progression group 3 patients (25%) had positive postoperative brain CT, yet neurological status significantly improved. Mid-term stroke rate was 2.2% in crescendo TIA group and 8.3% in stroke in progression group. In the early postoperative period there were no lethal outcomes, mid-term mortality was 8.3% in stroke in progression while in crescendo TIA group lethal outcomes were not observed. In conclusion, based on our results urgent CEA is a safe and effective treatment option for patients with crescendo TIA and stroke in progression with acceptable rate of postoperative complications.

  20. Acute myocardial infarction versus other cardiovascular events in community-acquired pneumonia

    PubMed Central

    Ramirez, Julio; Cosentini, Roberto; Valenti, Vincenzo; Voza, Antonio; Rossi, Paolo; Stolz, Daiana; Legnani, Delfino; Pesci, Alberto; Richeldi, Luca; Peyrani, Paula; Massari, Fernando Maria; Blasi, Francesco

    2015-01-01

    The aim of the present study was to define the prevalence, characteristics, risk factors and impact on clinical outcomes of acute myocardial infarction (AMI) versus other cardiovascular events (CVEs) in patients with community-acquired pneumonia (CAP). This was an international, multicentre, observational, prospective study of CAP patients hospitalised in eight hospitals in Italy and Switzerland. Three groups were identified: those without CVEs, those with AMI and those with other CVEs. Among 905 patients, 21 (2.3%) patients experienced at least one AMI, while 107 (11.7%) patients experienced at least one other CVE. Patients with CAP and either AMI or other CVEs showed a higher severity of the disease than patients with CAP alone. Female sex, liver disease and the presence of severe sepsis were independent predictors for the occurrence of AMI, while female sex, age >65 years, neurological disease and the presence of pleural effusion predicted other CVEs. In-hospital mortality was significantly higher among those who experienced AMI in comparison to those experiencing other CVEs (43% versus 21%, p=0.039). The presence of AMI showed an adjusted odds ratio for in-hospital mortality of 3.57 (p=0.012) and for other CVEs of 2.63 (p=0.002). These findings on AMI versus other CVEs as complications of CAP may be important when planning interventional studies on cardioprotective medications.

  1. Antenatal Magnesium Sulfate Exposure and Acute Cardiorespiratory Events in Preterm Infants

    PubMed Central

    DE JESUS, Lilia C.; SOOD, Beena G.; SHANKARAN, Seetha; KENDRICK, Mr. Douglas; DAS, Abhik; BELL, Edward F.; STOLL, Barbara J.; LAPTOOK, Abbot R.; WALSH, Michele C.; CARLO, Waldemar A.; SANCHEZ, Pablo J.; VAN MEURS, Krisa P.; BARA, Ms. Rebecca; HALE, Ellen C.; NEWMAN, Ms. Nancy S.; BALL, Ms. M. Bethany; HIGGINS, Rosemary D.

    2014-01-01

    Objective Antenatal magnesium (anteMg) is used for tocolysis, pregnancy-induced hypertension (PIH) and neuroprotection for preterm birth. Infants exposed to anteMg are at risk for respiratory depression and resuscitation in the delivery room (DR). The study objective was to compare the risk of acute cardio-respiratory (CR) events among preterm infants exposed to anteMg and those unexposed (noMg). Study Design This was a retrospective analysis of prospective data collected in the NICHD Neonatal Research Network's Generic Database from 4/1/11 to 3/31/12. The primary outcome was DR intubation or mechanical ventilation (MV) at birth or on day 1 of life. Secondary outcomes were endotracheal MV (eMV), hypotension and other neonatal morbidities and mortality. Logistic regression analysis evaluated the risk of primary outcomes after adjustment for gestational age (GA), center, antenatal steroids (ANS) and PIH/eclampsia. Results We evaluated 1,544 infants <29 weeks GA (1,091 in anteMg group and 453 in noMg group). Mothers in the anteMg group were more likely to have higher education, PIH/eclampsia and ANS; while their infants were younger in gestation and weighed less (P<0.05). The primary outcome, mortality and neonatal morbidities were similar between groups; while eMV and hypotension were significantly less among the anteMg group compared to the noMg group. AnteMg exposure was significantly associated with decreased risk of hypotension on day 1 of life and eMV on day 3 of life in the regression analysis. Conclusion Preterm infants <29 weeks GA who were exposed to anteMg did not suffer worse CR outcomes compared to those without exposure. PMID:25046806

  2. Acute Coronary Syndrome in Indian Subcontinent Patients Residing in the Middle East: Results From Gulf Registry of Acute Coronary Events II.

    PubMed

    Panduranga, Prashanth; Sulaiman, Kadhim J; Al-Zakwani, Ibrahim; Alhabib, Khalid F; Hersi, Ahmad; Suwaidi, Jassim Al; Alsheikh-Ali, Alawi A; Almahmeed, Wael; Saif, Shukri Al; Al-Faleh, Hussam; Al-Lawati, Jawad; Asaad, Nidal; Al-Motarreb, Ahmed; Amin, Haitham

    2015-10-01

    We compared baseline characteristics, clinical presentation, and in-hospital outcomes between Middle Eastern Arabs and Indian subcontinent patients presenting with acute coronary syndrome (ACS). Of the 7930 patients enrolled in Gulf Registry of Acute Coronary Events II (RACE II), 23% (n = 1669) were from the Indian subcontinent. The Indian subcontinent patients, in comparison with the Middle Eastern Arabs, were younger (49 vs 60 years; P < .001), more were males (96% vs 80%; P < .001), had lower proportion of higher Global Registry of Acute Coronary Events risk score (8% vs 27%; P < .001), and less likely to be associated with diabetes (34% vs 42%; P < .001), hypertension (36% vs 51%; P < .001), and hyperlipidemia (29% vs 39%; P < .001) but more likely to be smokers (55% vs 29%; P < .001). After multivariable adjustment, the Middle Eastern Arabs were less likely to be associated with in-hospital congestive heart failure (odds ratio [OR], 0.65; 95% confidence interval [CI]: 0.50-0.86; P = .003) but more likely to be associated with recurrent ischemia (OR 1.33; 95% CI: 1.03-1.71; P = .026) when compared to the Indian subcontinent patients. Despite the baseline differences, there were largely no significant differences in in-hospital outcomes between the Indians and the Middle Eastern Arabs. PMID:25381144

  3. The effect of acute microgravity on mechanically-induced membrane damage and membrane-membrane fusion events

    NASA Technical Reports Server (NTRS)

    Clarke, M. S.; Vanderburg, C. R.; Feeback, D. L.; McIntire, L. V. (Principal Investigator)

    2001-01-01

    Although it is unclear how a living cell senses gravitational forces there is no doubt that perturbation of the gravitational environment results in profound alterations in cellular function. In the present study, we have focused our attention on how acute microgravity exposure during parabolic flight affects the skeletal muscle cell plasma membrane (i.e. sarcolemma), with specific reference to a mechanically-reactive signaling mechanism known as mechanically-induced membrane disruption or "wounding". Both membrane rupture and membrane resealing events mediated by membrane-membrane fusion characterize this response. We here present experimental evidence that acute microgravity exposure can inhibit membrane-membrane fusion events essential for the resealing of sarcolemmal wounds in individual human myoblasts. Additional evidence to support this contention comes from experimental studies that demonstrate acute microgravity exposure also inhibits secretagogue-stimulated intracellular vesicle fusion with the plasma membrane in HL-60 cells. Based on our own observations and those of other investigators in a variety of ground-based models of membrane wounding and membrane-membrane fusion, we suggest that the disruption in the membrane resealing process observed during acute microgravity is consistent with a microgravity-induced decrease in membrane order.

  4. The Effect of Acute Microgravity on Mechanically-Induced Membrane Damage and Membrane-Membrane Fusion Events

    NASA Technical Reports Server (NTRS)

    Clarke, Mark, S. F.; Vanderburg, Charles R.; Feedback, Daniel L.

    2001-01-01

    Although it is unclear how a living cell senses gravitational forces there is no doubt that perturbation of the gravitational environment results in profound alterations in cellular function. In the present study, we have focused our attention on how acute microgravity exposure during parabolic flight affects the skeletal muscle cell plasma membrane (i.e. sarcolemma), with specific reference to a mechanically-reactive signaling mechanism known as mechanically-induced membrane disruption or "wounding". This response is characterized by both membrane rupture and membrane resealing events mediated by membrane-membrane fusion. We here present experimental evidence that acute microgravity exposure can inhibit membrane-membrane fusion events essential for the resealing of sarcolemmal wounds in individual human myoblasts. Additional evidence to support this contention comes from experimental studies that demonstrate acute microgravity exposure also inhibits secretagogue-stimulated intracellular vesicle fusion with the plasma membrane in HL-60 cells. Based on our own observations and those of other investigators in a variety of ground-based models of membrane wounding and membrane-membrane fusion, we suggest that the disruption in the membrane resealing process observed during acute microgravity is consistent with a microgravity-induced decrease in membrane order.

  5. Airway microbiome dynamics in exacerbations of chronic obstructive pulmonary disease.

    PubMed

    Huang, Yvonne J; Sethi, Sanjay; Murphy, Timothy; Nariya, Snehal; Boushey, Homer A; Lynch, Susan V

    2014-08-01

    Specific bacterial species are implicated in the pathogenesis of exacerbations of chronic obstructive pulmonary disease (COPD). However, recent studies of clinically stable COPD patients have demonstrated a greater diversity of airway microbiota, whose role in acute exacerbations is unclear. In this study, temporal changes in the airway microbiome before, at the onset of, and after an acute exacerbation were examined in 60 sputum samples collected from subjects enrolled in a longitudinal study of bacterial infection in COPD. Microbiome composition and predicted functions were examined using 16S rRNA-based culture-independent profiling methods. Shifts in the abundance (≥ 2-fold, P < 0.05) of many taxa at exacerbation and after treatment were observed. Microbiota members that were increased at exacerbation were primarily of the Proteobacteria phylum, including nontypical COPD pathogens. Changes in the bacterial composition after treatment for an exacerbation differed significantly among the therapy regimens clinically prescribed (antibiotics only, oral corticosteroids only, or both). Treatment with antibiotics alone primarily decreased the abundance of Proteobacteria, with the prolonged suppression of some microbiota members being observed. In contrast, treatment with corticosteroids alone led to enrichment for Proteobacteria and members of other phyla. Predicted metagenomes of particular microbiota members involved in these compositional shifts indicated exacerbation-associated loss of functions involved in the synthesis of antimicrobial and anti-inflammatory products, alongside enrichment in functions related to pathogen-elicited inflammation. These trends reversed upon clinical recovery. Further larger studies will be necessary to determine whether specific compositional or functional changes detected in the airway microbiome could be useful indicators of exacerbation development or outcome.

  6. Aspirin Exacerbated Respiratory Disease.

    PubMed

    Fruth, Kai; Gosepath, Jan

    2016-01-01

    Aspirin exacerbated respiratory disease (AERD) has been defined as a non-steroidal anti-inflammatory drug (NSAID)-triggered hypersensitivity, non-allergic bronchial asthma and chronic rhinosinusitis (CRS) with nasal polyps. The underlying pathophysiology of AERD is not completely understood so far. An altered arachidonic acid metabolism and dysregulated enzyme activity are regarded to be causal. AERD is characterized by recalcitrant CRS with recurrent nasal polyps after sinus surgery, accompanied by difficult to treat bronchial asthma and adverse reaction after NSAID ingestion such as nasal blockage, itching, laryngospasm and severe asthma attacks. Affected individuals suffer from poor quality of life. Besides functional endoscopic sinus surgery, the application of topical and systemic steroids and symptomatic therapy, aspirin desensitization is the only causative treatment option. The diagnostic approach to AERD, the ideal desensitization protocol and especially the following daily maintenance dose is part of an ongoing debate. This article summarizes the current knowledge about the pathophysiology, focuses on modern diagnostic approaches of AERD and discusses various aspirin desensitization protocols with respect to efficacy as well as to undesirable side effects. PMID:27466843

  7. Home-Based Telehealth Hospitalization for Exacerbation of Chronic Obstructive Pulmonary Disease: Findings from “The Virtual Hospital” Trial

    PubMed Central

    Laursen, Lars C.; Rydahl-Hansen, Susan; Østergaard, Birte; Gerds, Thomas Alexander; Emme, Christina; Schou, Lone; Phanareth, Klaus

    2015-01-01

    Abstract Background: Telehealth interventions for patients with chronic obstructive pulmonary disease (COPD) have focused primarily on stable outpatients. Telehealth designed to handle the acute exacerbation that normally requires hospitalization could also be of interest. The aim of this study was to compare the effect of home-based telehealth hospitalization with conventional hospitalization for exacerbation in severe COPD. Materials and Methods: A two-center, noninferiority, randomized, controlled effectiveness trial was conducted between June 2010 and December 2011. Patients with severe COPD admitted because of exacerbation were randomized 1:1 either to home-based telehealth hospitalization or to continue standard treatment and care at the hospital. The primary outcome was treatment failure defined as re-admission due to exacerbation in COPD within 30 days after initial discharge. The noninferiority margin was set at 20% of the control group's risk of re-admission. Secondary outcomes were mortality, need for manual or mechanical ventilation or noninvasive ventilation, length of hospitalization, physiological parameters, health-related quality of life, user satisfaction, healthcare costs, and adverse events. Results: In total, 57 patients were randomized: 29 participants in the telehealth group and 28 participants in the control group. Testing the incidence of re-admission within 30 days after discharge could not confirm noninferiority (lower 95% confidence limit [CL], −24.8%; p=0.35). Results were also nonsignificant at 90 days (lower 95% CL, −16.2%; p=0.33) and 180 days (lower 95% CL, −16.6%; p =0.33) after discharge. Superiority testing on secondary outcomes showed nonsignificant differences between groups. Healthcare costs have not yet been evaluated. Conclusions: Whether home-based telehealth hospitalization is noninferior to conventional hospitalization requires further investigation. The results indicate that a subgroup of patients with severe COPD

  8. Clinical Insights into Pulmonary Exacerbations in Cystic Fibrosis from the Microbiome. What Are We Missing?

    PubMed

    Whelan, Fiona J; Surette, Michael G

    2015-11-01

    Pulmonary exacerbations account for much of the decrease in lung function and consequently most of the morbidity and mortality in patients with cystic fibrosis. These events are driven by an acute inflammatory response to infection. Recent technological advancements in molecular profiling techniques have allowed for a proliferation of microbiome studies of the lower airways of patients with cystic fibrosis. But these methods may not provide a comprehensive and unbiased measure of the lung microbiota in these patients and molecular profiles do not always translate to quantitative microbiology. Furthermore, these studies have not yet been able to provide much in the way of mechanistic insights into exacerbations or to guide patient therapy. We propose a model in which pulmonary exacerbations may be driven by an active subpopulation of the lung microbiota, which may represent only a small portion of the microbiota measured in a clinical sample. Methodology should be focused on the ultimate goal, which is to use the best available approaches to provide accurate quantitative measures of the microbiome to inform clinical decisions and provide rapid assessment of treatment efficacy. These strategies would be relevant to other chronic lung diseases such as chronic obstructive pulmonary disease and neutrophilic asthma.

  9. The intersection between asthma and acute chest syndrome in children with sickle-cell anaemia.

    PubMed

    DeBaun, Michael R; Strunk, Robert C

    2016-06-18

    Acute chest syndrome is a frequent cause of acute lung disease in children with sickle-cell disease. Asthma is common in children with sickle-cell disease and is associated with increased incidence of vaso-occlusive pain events, acute chest syndrome episodes, and earlier death. Risk factors for asthma exacerbation and an acute chest syndrome episode are similar, and both can present with shortness of breath, chest pain, cough, and wheezing. Despite overlapping risk factors and symptoms, an acute exacerbation of asthma or an episode of acute chest syndrome are two distinct entities that need disease-specific management strategies. Although understanding has increased about asthma as a comorbidity in sickle-cell disease and its effects on morbidity, substantial gaps remain in knowledge about best management. PMID:27353685

  10. The intersection between asthma and acute chest syndrome in children with sickle-cell anaemia.

    PubMed

    DeBaun, Michael R; Strunk, Robert C

    2016-06-18

    Acute chest syndrome is a frequent cause of acute lung disease in children with sickle-cell disease. Asthma is common in children with sickle-cell disease and is associated with increased incidence of vaso-occlusive pain events, acute chest syndrome episodes, and earlier death. Risk factors for asthma exacerbation and an acute chest syndrome episode are similar, and both can present with shortness of breath, chest pain, cough, and wheezing. Despite overlapping risk factors and symptoms, an acute exacerbation of asthma or an episode of acute chest syndrome are two distinct entities that need disease-specific management strategies. Although understanding has increased about asthma as a comorbidity in sickle-cell disease and its effects on morbidity, substantial gaps remain in knowledge about best management.

  11. Asthma exacerbations · 1: Epidemiology

    PubMed Central

    Johnston, N W; Sears, M R

    2006-01-01

    Asthma exacerbations may be triggered by a number of atmospheric and domiciliary environmental factors as well as by those encountered in schools and workplaces. The majority of exacerbations, particularly in children, coincide with respiratory viral infections, most commonly rhinovirus. As most respiratory viruses and many aeroallergens appear in seasonal patterns, asthma exacerbations, particularly those requiring emergency treatment, show analogous seasonal cycles which differ in form in children and adults. While similar in form between the sexes, they differ in amplitude, with boys having higher risks of exacerbation in childhood and women in adult life. Simultaneous exposure of asthmatics with respiratory viral infections to allergens or air pollutants may significantly increase the risks of exacerbation. Access to and compliance with inhaled corticosteroid treatment is an important predictor of the likelihood of asthma exacerbations occurring, including those that occur during respiratory viral infections. Epidemiologically, the degree of asthma control achieved by asthmatics is an important predictor of the likelihood of disease exacerbation including respiratory failure, death, and health service consumption. PMID:16877691

  12. Stressful life events preceding the acute onset of schizophrenia: a cross-national study from the World Health Organization.

    PubMed

    Day, R; Nielsen, J A; Korten, A; Ernberg, G; Dube, K C; Gebhart, J; Jablensky, A; Leon, C; Marsella, A; Olatawura, M

    1987-06-01

    This study reports on the findings from a WHO sponsored cross-national investigation of life events and schizophrenia. Data are presented from a series of 386 acutely ill schizophrenic patients selected from nine field research centers located in developing and developed countries (Aarhus, Denmark; Agra, India; Cali, Colombia; Chandigarh, India; Honolulu, USA; Ibadan, Nigeria; Nagasaki, Japan; Prague, Czechoslovakia; Rochester, USA). On a methodological level, the study demonstrates that life event methodologies originating in the developed countries can be adapted for international studies and may be used to collect reasonably reliable and comparable cross-cultural data on psychosocial factors affecting the course of schizophrenic disorders. Substantive findings replicate the results of prior studies which conclude that socioenvironmental stressors may precipitate schizophrenic attacks and such events tend to cluster in the two to three week period immediately preceding illness onset.

  13. Differential Effects of Acute Alcohol on Prepulse Inhibition and Event-Related Potentials in Adolescent and Adult Wistar Rats

    PubMed Central

    Pian, Jerry P.; Criado, Jose R.; Ehlers, Cindy L.

    2009-01-01

    Background Previous studies have demonstrated that adolescent and adult rats show differential sensitivity to many of the acute effects of alcohol. We recently reported evidence of developmental differences in the effects of acute alcohol on the cortical electroencephalogram (EEG). However, it is unclear whether developmental differences are also observed in other neurophysiological and neurobehavioral measurements known to be sensitive to alcohol exposure. The present study determined the age-related effects of acute alcohol on behavioral and event-related potential (ERP) responses to acoustic startle (AS) and prepulse inhibition (PPI). Methods Male adolescent and adult Wistar rats were implanted with cortical recording electrodes. The effects of acute alcohol (0.0, 0.75, and 1.5 g/kg) on behavioral and ERP responses to AS and PPI were assessed. Results Acute alcohol (0.75 and 1.5 g/kg) significantly reduced the behavioral and electrophysiological response to AS in adolescent and adult rats. Both 0.75 and 1.5 g/kg alcohol significantly enhanced the behavioral response to PPI in adolescent, but not in adult rats. During prepulse+pulse trials, 1.5 g/kg alcohol significantly increased the N10 pulse response in the adolescent frontal cortex. Acute alcohol (0.75 and 1.5 g/kg) also increased the N1 ERP pulse response to prepulse stimuli in frontal and parietal cortices in adult rats, but not in adolescent rats. Conclusions These data suggest that alcohol’s effect on behavioral and electrophysiological indices of AS do not differ between adults and adolescents whereas developmental stage does appear to significantly modify alcohol influenced response to PPI. PMID:18828807

  14. Do pollution time-series studies contain uncontrolled or residual confounding by risk factors for acute health events?

    PubMed

    Bukowski, John

    2008-07-01

    Acute health effects from air pollution are based largely on weak associations identified in time-series studies comparing daily air pollution levels to daily mortality. Much of this mortality is due to cardiovascular disease. Time-series studies have many potential limitations, but are not thought to be confounded by traditional cardiovascular risk factors (e.g., smoking status or hypertension) because these chronic risk factors are not obviously associated with daily pollution levels. However, acute psychobehavioral variants of these risk factors (e.g., smoking patterns and episodes of stress on any given day) are plausible confounders for the associations observed in time-series studies, given that time-series studies attempt to predict acute rather than chronic health outcomes. There is a fairly compelling literature on the strong link between cardiovascular events and daily "triggers" such as stress. Stress-related triggers are plausibly associated with daily pollution levels through surrogate stressors such as ambient temperature, daily workload, local traffic congestion, or other correlates of air pollution. For example, variables such as traffic congestion and industrial activity increase both stress-related health events and air pollution, suggesting the potential for classical confounding. Support for this argument is illustrated through examples of the well-demonstrated relationship between emotional stress and heart attack/stroke.

  15. Lung VITAL: Rationale, design, and baseline characteristics of an ancillary study evaluating the effects of vitamin D and/or marine omega-3 fatty acid supplements on acute exacerbations of chronic respiratory disease, asthma control, pneumonia and lung function in adults.

    PubMed

    Gold, Diane R; Litonjua, Augusto A; Carey, Vincent J; Manson, JoAnn E; Buring, Julie E; Lee, I-Min; Gordon, David; Walter, Joseph; Friedenberg, Georgina; Hankinson, John L; Copeland, Trisha; Luttmann-Gibson, Heike

    2016-03-01

    Laboratory and observational research studies suggest that vitamin D and marine omega-3 fatty acids may reduce risk for pneumonia, acute exacerbations of respiratory diseases including chronic obstructive lung disease (COPD) or asthma, and decline of lung function, but prevention trials with adequate dosing, adequate power, and adequate time to follow-up are lacking. The ongoing Lung VITAL study is taking advantage of a large clinical trial-the VITamin D and OmegA-3 TriaL (VITAL)--to conduct the first major evaluation of the influences of vitamin D and marine omega-3 fatty acid supplementation on pneumonia risk, respiratory exacerbation episodes, asthma control and lung function in adults. VITAL is a 5-year U.S.-wide randomized, double-blind, placebo-controlled, 2 × 2 factorial trial of supplementation with vitamin D3 ([cholecalciferol], 2000 IU/day) and marine omega-3 FA (Omacor® fish oil, eicosapentaenoic acid [EPA]+docosahexaenoic acid [DHA], 1g/day) for primary prevention of CVD and cancer among men and women, at baseline aged ≥50 and ≥55, respectively, with 5107 African Americans. In a subset of 1973 participants from 11 urban U.S. centers, lung function is measured before and two years after randomization. Yearly follow-up questionnaires assess incident pneumonia in the entire randomized population, and exacerbations of respiratory disease, asthma control and dyspnea in a subpopulation of 4314 randomized participants enriched, as shown in presentation of baseline characteristics, for respiratory disease, respiratory symptoms, and history of cigarette smoking. Self-reported pneumonia hospitalization will be confirmed by medical record review, and exacerbations will be confirmed by Center for Medicare and Medicaid Services data review.

  16. Catechol-O-Methyltransferase Gene Polymorphism Modifies the Effect of Coffee Intake on Incidence of Acute Coronary Events

    PubMed Central

    Happonen, Pertti; Voutilainen, Sari; Tuomainen, Tomi-Pekka; Salonen, Jukka T.

    2006-01-01

    Background The role of coffee intake as a risk factor for coronary heart disease (CHD) has been debated for decades. We examined whether the relationship between coffee intake and incidence of CHD events is dependent on the metabolism of circulating catecholamines, as determined by functional polymorphism of the catechol-O-methyltransferase (COMT) gene. Methodology/Principal Findings In a cohort of 773 men who were 42 to 60 years old and free of symptomatic CHD at baseline in 1984–89, 78 participants experienced an acute coronary event during an average follow-up of 13 years. In logistic regression adjusting for age, smoking, family history of CHD, vitamin C deficiency, blood pressure, plasma cholesterol concentration, and diabetes, the odds ratio (90% confidence interval) comparing heavy coffee drinkers with the low activity COMT genotype with those with the high activity or heterozygotic genotypes was 3.2 (1.2–8.4). Urinary adrenaline excretion increased with increasing coffee intake, being over two-fold in heavy drinkers compared with nondrinkers (p = 0.008 for trend). Conclusions/Significance Heavy coffee consumption increases the incidence of acute coronary events in men with low but not high COMT activity. Further studies are required to determine to which extent circulating catecholamines mediate the relationship between coffee intake and CHD. PMID:17205121

  17. Event-free survival and cost-effectiveness in adult acute lymphoblastic leukaemia in first remission treated with allogeneic transplantation.

    PubMed

    Orsi, C; Bartolozzi, B; Messori, A; Bosi, A

    2007-10-01

    Allogeneic transplantation in patients with acute lymphoblastic leukaemia in first remission (ALL-CR1) has been studied in several clinical trials. However, no pooled survival analysis has yet been done. We conducted a survival meta-analysis to compare allogeneic transplantation vs chemotherapy or autologous transplantation using an intention-to-treat approach. Our study included the controlled clinical trials, wherein allocation to allogeneic transplant was based on donor availability. The event-free individual survival data were reconstructed on the basis of published information and Kaplan-Meier graphs. We then generated the meta-analytic event-free survival curves for the two treatments. The mean survival gain per patient was estimated and a simplified cost-effectiveness assessment was carried out. In the allogeneic transplantation group, 293 patients were examined and 479 as controls (four trials). The event-free survival difference was statistically significant (P=0.011). The relative risk for event occurrence was 0.79 for the experimental group vs the controls (95% CI: 0.66-0.96; P=0.017). The mean survival gain was 1 year per patient. The cost per life-year gained was less than the conventional threshold of 50,000 euros. Allogeneic transplantation in ALL-CR1 improves event-free survival as compared to chemotherapy or autologous transplantation. Its cost-effectiveness profile is acceptable. PMID:17660839

  18. Relationship between Inflammatory Markers and New Cardiovascular Events in Patients with Acute Myocardial Infarction Who Underwent Primary Angioplasty

    PubMed Central

    Franca, Eluisa La; Caruso, Marco; Sansone, Angela; Iacona, Rosanna; Ajello, Laura; Mancuso, Dario; Castellano, Fabiana; Novo, Salvatore; Assennato, Pasquale

    2013-01-01

    Introduction: The determination of inflammation markers in circulation has enabled an important improvement in the study of cardiovascular diseases. It was tested the hypothesis that non-specific markers such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and fibrinogen may provide prognostic information in patients with acute myocardial infarction with persistent ST-segment elevation (STEMI) undergoing primary angioplasty (PCI). Methods: Patients: A cohort of 197 consecutive patients with STEMI undergoing primary PCI was enrolled, evaluating during hospitalization, the peak values of the following markers of inflammation: ESR, CRP and fibrinogen. A telephone follow-up has been made in order to investigate any possible new cardiovascular events after hospital discharge and the procedure performed. Results: Higher values of CRP were statistically associated with adverse future events as composite endpoint and with the single endpoint of death. Furthermore, higher age, presence of hypertension, history of previous cardiovascular events, were statistically significantly associated with cardiac events at follow up. In this group were also overrepresented subjects with anterior myocardial infarction in the anterior localization and with an EF ≤ 35% at discharge. Conclusions: CRP appears to be a predictor of future cardiovascular events, confirming that a pro-inflammatory state promotes the progression of atherosclerotic disease and its complications. PMID:23777720

  19. Post-Acute Care Services Received by Older Adults Following a Cardiac Event: A Population-Based Analysis

    PubMed Central

    Xu, Fang; Zullo, Melissa; Shishehbor, Mehdi; Moore, Shirley M.; Rimm, Alfred A.

    2010-01-01

    Background Post-acute care (PAC) is available for older adults who need additional services after hospitalization for acute cardiac events. With the aging population and an increase in the prevalence of cardiac disease, it is important to determine current PAC use for cardiac patients to assist health care workers to meet the needs of older cardiac patients. The purpose of this study was to determine the current PAC use and factors associated with PAC use for older adults following hospitalization for a cardiac event that includes coronary artery bypass graph (CABG) and valve surgeries, myocardial infarction (MI), percutaneous coronary intervention (PCI), and heart failure (HF). Methods and Results A cross-sectional design and the 2003 Medicare Part A database were used for this study. The sample (n=1,493,521) consisted of patients aged 65 years and older discharged after their first cardiac event. Multinomial logistic regression was used to examine factors associated with PAC use. Overall, PAC use was 55% for cardiac valve surgery, 50% for MI, 45% for HF, 44% for CABG, and 5% for PCI. Medical patients use more skilled nursing facility care and surgical patients use more home health care. Only 0.1–3.4% of the cardiac patients use intermediate rehabilitation facilities. Compared to those who do not use PAC, those who use home health care and skilled nursing facility care are older, female, have a longer hospital length of stay, and more comorbidity. Asians, Hispanics and Native Americans were less likely to use PAC after hospitalization for an MI or HF. Conclusions The current rate of PAC use indicates that almost half of non-disabled Medicare patients discharged from the hospital following a cardiac event use one of these services. Healthcare professionals can increase PAC use for Asians, Hispanics and Native Americans by including culturally targeted communication. Optimizing recovery for cardiac patients who use PAC may require focused cardiac rehabilitation

  20. Factor XIa and Thrombin Generation Are Elevated in Patients with Acute Coronary Syndrome and Predict Recurrent Cardiovascular Events

    PubMed Central

    Loeffen, Rinske; van Oerle, René; Leers, Mathie P. G.; Kragten, Johannes A.; Crijns, Harry; Spronk, Henri M. H.; ten Cate, Hugo

    2016-01-01

    Objective In acute coronary syndrome (ACS) cardiac cell damage is preceded by thrombosis. Therefore, plasma coagulation markers may have additional diagnostic relevance in ACS. By using novel coagulation assays this study aims to gain more insight into the relationship between the coagulation system and ACS. Methods We measured plasma thrombin generation, factor XIa and D-dimer levels in plasma from ACS (n = 104) and non-ACS patients (n = 42). Follow-up measurements (n = 73) were performed at 1 and 6 months. Associations between coagulation markers and recurrent cardiovascular events were calculated by logistic regression analysis. Results Thrombin generation was significantly enhanced in ACS compared to non-ACS patients: peak height 148±53 vs. 122±42 nM. There was a significantly diminished ETP reduction (32 vs. 41%) and increased intrinsic coagulation activation (25 vs. 7%) in ACS compared to non-ACS patients. Furthermore, compared to non-ACS patients factor XIa and D-dimer levels were significantly elevated in ACS patients: 1.9±1.1 vs. 1.4±0.7 pM and 495(310–885) vs. 380(235–540) μg/L. Within the ACS spectrum, ST-elevated myocardial infarction patients had the highest prothrombotic profile. During the acute event, thrombin generation was significantly increased compared to 1 and 6 months afterwards: peak height 145±52 vs. 100±44 vs. 98±33 nM. Both peak height and factor XIa levels on admission predicted recurrent cardiovascular events (OR: 4.9 [95%CI 1.2–20.9] and 4.5 [1.1–18.9]). Conclusion ACS patients had an enhanced prothrombotic profile, demonstrated by an increased thrombin generation potential, factor XIa and D-dimer levels. This study is the first to demonstrate the positive association between factor XIa, thrombin generation and recurrent cardiovascular events. PMID:27419389

  1. Metabolic disease in 10 patients with sudden unexpected death in infancy or acute life-threatening events.

    PubMed

    Takahashi, Tomoo; Yamada, Kenji; Kobayashi, Hironori; Hasegawa, Yuki; Taketani, Takeshi; Fukuda, Seiji; Yamaguchi, Seiji

    2015-06-01

    In order to determine the associations between sudden unexpected death in infancy (SUDI) or acute life-threatening events (ALTE) and inborn errors of metabolism, particularly organic acidemia and fatty acid oxidation disorders, we evaluated clinical features in patients with SUDI or ALTE. The subjects were infants between the ages of 7 days and 3 years who developed SUDI or ALTE between January 2004 and December 2013. They were then diagnosed as having inborn errors of metabolism on gas chromatography-mass spectrometry (GC/MS) and/or tandem mass spectrometry (MS/MS). The age distribution, onset forms, and clinical findings were evaluated during the acute phase. Inborn errors of metabolism were detected in three of 196 patients with SUDI, and in seven of 167 patients with ALTE. Of these 10 patients, nine had a history of poor feeding and somnolence during the neonatal period, and symptoms of infection such as cough, fever or vomiting during infancy. Routine laboratory tests during an acute phase indicated hyperammonemia, liver dysfunction, increased blood creatine kinase, acidosis, positive ketone bodies in urine or blood, or hypoglycemia. When SUDI or ALTE are encountered in the emergency unit, it is essential that a detailed medical history is taken, particularly with regard to the neonatal period, and that specific abnormalities are investigated on routine laboratory tests. Moreover, samples such as urine, serum, and filter paper blood specimens should be collected for GC/MS and/or MS/MS of organic acids and acylcarnitines, to identify inborn metabolic disorders.

  2. Acute deep brain stimulation in the thalamic reticular nucleus protects against acute stress and modulates initial events of adult hippocampal neurogenesis.

    PubMed

    Magdaleno-Madrigal, Víctor Manuel; Pantoja-Jiménez, Christopher Rodrigo; Bazaldúa, Adrián; Fernández-Mas, Rodrigo; Almazán-Alvarado, Salvador; Bolaños-Alejos, Fernanda; Ortíz-López, Leonardo; Ramírez-Rodriguez, Gerardo Bernabé

    2016-11-01

    Deep brain stimulation (DBS) is used as an alternative therapeutic procedure for pharmacoresistant psychiatric disorders. Recently the thalamic reticular nucleus (TRN) gained attention due to the description of a novel pathway from the amygdala to this nucleus suggesting that may be differentially disrupted in mood disorders. The limbic system is implicated in the regulation of these disorders that are accompanied by neuroplastic changes. The hippocampus is highly plastic and shows the generation of new neurons, process affected by stress but positively regulated by antidepressant drugs. We explored the impact of applying acute DBS to the TRN (DBS-TRN) in male Wistar rats exposed to acute stress caused by the forced-swim Porsolt's test (FST) and on initial events of hippocampal neurogenesis. After the first session of forced-swim, rats were randomly subdivided in a DBS-TRN and a Sham group. Stimulated rats received 10min of DBS, thus the depressant-like behavior reflected as immobility was evaluated in the second session of forced-swim. Locomotricity was evaluated in the open field test. Cell proliferation and doublecortin-associated cells were quantified in the hippocampus of other cohorts of rats. No effects of electrode implantation were found in locomotricity. Acute DBS-TRN reduced immobility in comparison to the Sham group (p<0.001). DBS-TRN increased cell proliferation (Ki67 or BrdU-positive cells; p=0.02, p=0.02) and the number of doublecortin-cells compared to the Sham group (p<0.02). Similar effects were found in rats previously exposed to the first session of forced-swim. Our data could suggest that TRN brain region may be a promising target for DBS to treat intractable depression.

  3. Acute deep brain stimulation in the thalamic reticular nucleus protects against acute stress and modulates initial events of adult hippocampal neurogenesis.

    PubMed

    Magdaleno-Madrigal, Víctor Manuel; Pantoja-Jiménez, Christopher Rodrigo; Bazaldúa, Adrián; Fernández-Mas, Rodrigo; Almazán-Alvarado, Salvador; Bolaños-Alejos, Fernanda; Ortíz-López, Leonardo; Ramírez-Rodriguez, Gerardo Bernabé

    2016-11-01

    Deep brain stimulation (DBS) is used as an alternative therapeutic procedure for pharmacoresistant psychiatric disorders. Recently the thalamic reticular nucleus (TRN) gained attention due to the description of a novel pathway from the amygdala to this nucleus suggesting that may be differentially disrupted in mood disorders. The limbic system is implicated in the regulation of these disorders that are accompanied by neuroplastic changes. The hippocampus is highly plastic and shows the generation of new neurons, process affected by stress but positively regulated by antidepressant drugs. We explored the impact of applying acute DBS to the TRN (DBS-TRN) in male Wistar rats exposed to acute stress caused by the forced-swim Porsolt's test (FST) and on initial events of hippocampal neurogenesis. After the first session of forced-swim, rats were randomly subdivided in a DBS-TRN and a Sham group. Stimulated rats received 10min of DBS, thus the depressant-like behavior reflected as immobility was evaluated in the second session of forced-swim. Locomotricity was evaluated in the open field test. Cell proliferation and doublecortin-associated cells were quantified in the hippocampus of other cohorts of rats. No effects of electrode implantation were found in locomotricity. Acute DBS-TRN reduced immobility in comparison to the Sham group (p<0.001). DBS-TRN increased cell proliferation (Ki67 or BrdU-positive cells; p=0.02, p=0.02) and the number of doublecortin-cells compared to the Sham group (p<0.02). Similar effects were found in rats previously exposed to the first session of forced-swim. Our data could suggest that TRN brain region may be a promising target for DBS to treat intractable depression. PMID:27435420

  4. Validity of the GRACE (Global Registry of Acute Coronary Events) acute coronary syndrome prediction model for six month post‐discharge death in an independent data set

    PubMed Central

    Bradshaw, P J; Ko, D T; Newman, A M; Donovan, L R

    2006-01-01

    Objective To determine the validity of the GRACE (Global Registry of Acute Coronary Events) prediction model for death six months after discharge in all forms of acute coronary syndrome in an independent dataset of a community based cohort of patients with acute myocardial infarction (AMI). Design Independent validation study based on clinical data collected retrospectively for a clinical trial in a community based population and record linkage to administrative databases. Setting Study conducted among patients from the EFFECT (enhanced feedback for effective cardiac treatment) study from Ontario, Canada. Patients Randomly selected men and women hospitalised for AMI between 1999 and 2001. Main outcome measure Discriminatory capacity and calibration of the GRACE prediction model for death within six months of hospital discharge in the contemporaneous EFFECT AMI study population. Results Post‐discharge crude mortality at six months for the EFFECT study patients with AMI was 7.0%. The discriminatory capacity of the GRACE model was good overall (C statistic 0.80) and for patients with ST segment elevation AMI (STEMI) (0.81) and non‐STEMI (0.78). Observed and predicted deaths corresponded well in each stratum of risk at six months, although the risk was underestimated by up to 30% in the higher range of scores among patients with non‐STEMI. Conclusions In an independent validation the GRACE risk model had good discriminatory capacity for predicting post‐discharge death at six months and was generally well calibrated, suggesting that it is suitable for clinical use in general populations. PMID:16387810

  5. Cancer Events After Acute or Chronic Exposure to Sulfur Mustard: A Review of the Literature

    PubMed Central

    Razavi, Seyed Mansour; Abdollahi, Mohammad; Salamati, Payman

    2016-01-01

    Background: Sulfur mustard (SM) has been considered as a carcinogen in the laboratory studies. However, its carcinogenic effects on human beings were not well discussed. The main purpose of our study is to assess carcinogenesis of SM following acute and/or chronic exposures in human beings. Methods: The valid scientific English and Persian databases including PubMed, Web of Science, Scopus, IranMedex, and Irandoc were searched and the collected papers reviewed. The used keywords were in two languages: English and Persian. The inclusion criteria were the published original articles indexed in above-mentioned databases. Eleven full-texts out of 296 articles were found relevant and then assessed. Results: Studies on the workers of the SM factories during the World Wars showed that the long-term chronic exposure to mustards can cause a variety of cancers in the organs such as oral cavity, larynx, lung, and skin. Respiratory system was the most important affected system. Acute single exposure to SM was assumed as the carcinogenic inducer in the lung and blood and for few cancers including basal cell carcinoma and squamous cell carcinoma. Conclusions: SM is a proven carcinogen in chronic situations although data are not enough to strongly conclude in acute exposure. PMID:27280012

  6. Acute clinical events in 299 homozygous sickle cell patients living in France. French Study Group on Sickle Cell Disease.

    PubMed

    Neonato, M G; Guilloud-Bataille, M; Beauvais, P; Bégué, P; Belloy, M; Benkerrou, M; Ducrocq, R; Maier-Redelsperger, M; de Montalembert, M; Quinet, B; Elion, J; Feingold, J; Girot, R

    2000-09-01

    A subset of 299 patients with homozygous sickle cell anaemia, enrolled in the cohort of the French Study Group on sickle cell disease (SCD), was investigated in this study. The majority of patients were children (mean age 10.1 +/- 5.8 yr) of first generation immigrants from Western and Central Africa, the others originated from the French West Indies (20.2%). We report the frequency of the main clinical events (mean follow-up 4.2 +/- 2.2 yr). The prevalence of meningitis-septicaemia and osteomyelitis was, respectively, 11.4% and 12% acute chest syndrome was observed in 134 patients (44.8%). Twenty patients (6.7%) developed stroke with peak prevalence at 10-15 yr of age. One hundred and seventy-two patients (58%) suffered from one or more painful sickle cell crises, while the others (42.5%) never suffered from pain. The overall frequency of acute anaemic episodes was 50.5%, (acute aplastic anaemia 46%; acute splenic sequestration 26%). A group of 27 patients were asymptomatic (follow-up > 3 yr). Epistatic mechanisms influencing SCD were studied. Coinherited alpha-thalassemia strongly reduced the risk of stroke (p <0.001) and increased that of painful crises (p < 0.02). There was a low prevalence of Senegal and Bantu (CAR) betas-chromosomes in patients with meningitis (p <0.04) and osteomyelitis (p < 0.03). Prevalence of Senegal betas-chromosomes was lower in the asymptomatic group of 27 patients (p < 0.02). The patients come from a population of unmixed immigrants in whom the beta-globin gene haplotype strongly reflects the geographic origin and identifies subgroups with a homogenous genetic background. Thus the observed effects might result more from differences in as yet unidentified determinants in the genetic background than from the direct linkage with differences in the beta-globin gene locus.

  7. China Patient-centered Evaluative Assessment of Cardiac Events Prospective Study of Acute Myocardial Infarction: Study Design

    PubMed Central

    Li, Jing; Dreyer, Rachel P; Li, Xi; Du, Xue; Downing, Nicholas S; Li, Li; Zhang, Hai-Bo; Feng, Fang; Guan, Wen-Chi; Xu, Xiao; Li, Shu-Xia; Lin, Zhen-Qiu; Masoudi, Frederick A; Spertus, John A; Krumholz, Harlan M; Jiang, Li-Xin

    2016-01-01

    Background: Despite the rapid growth in the incidence of acute myocardial infarction (AMI) in China, there is limited information about patients’ experiences after AMI hospitalization, especially on long-term adverse events and patient-reported outcomes (PROs). Methods: The China Patient-centered Evaluative Assessment of Cardiac Events (PEACE)-Prospective AMI Study will enroll 4000 consecutive AMI patients from 53 diverse hospitals across China and follow them longitudinally for 12 months to document their treatment, recovery, and outcomes. Details of patients’ medical history, treatment, and in-hospital outcomes are abstracted from medical charts. Comprehensive baseline interviews are being conducted to characterize patient demographics, risk factors, presentation, and healthcare utilization. As part of these interviews, validated instruments are administered to measure PROs, including quality of life, symptoms, mood, cognition, and sexual activity. Follow-up interviews, measuring PROs, medication adherence, risk factor control, and collecting hospitalization events are conducted at 1, 6, and 12 months after discharge. Supporting documents for potential outcomes are collected for adjudication by clinicians at the National Coordinating Center. Blood and urine samples are also obtained at baseline, 1- and 12-month follow-up. In addition, we are conducting a survey of participating hospitals to characterize their organizational characteristics. Conclusion: The China PEACE-Prospective AMI study will be uniquely positioned to generate new information regarding patient's experiences and outcomes after AMI in China and serve as a foundation for quality improvement activities. PMID:26712436

  8. Acute Effects of Asian Dust Events on Respiratory Symptoms and Peak Expiratory Flow in Children with Mild Asthma

    PubMed Central

    Yoo, Young; Choung, Ji Tae; Yu, Jinho; Kim, Do Kyun

    2008-01-01

    The aim of this study was to investigate the possible adverse effects of Asian dust events on respiratory health in asthmatic children. Fifty-two children with mild asthma were studied for eight consecutive weeks in the spring of 2004 (March 8 to May 2). During the study period, five Asian dust days were identified; we included a lag period of two days following each of the events. Subjects recorded their respiratory symptom diaries and peak expiratory flow (PEF) twice daily during the study period; and they underwent methacholine bronchial challenge tests. The subjects reported a significantly higher frequency of respiratory symptoms during the Asian dust days than during the control days. They showed significantly more reduced morning and evening PEF values, and more increased PEF variability (10.1%±3.5% vs. 5.5%±2.2%) during the Asian dust days than during the control days. Methacholine PC20 was not significantly different between before and after the study period (geometric mean: 2.82 mg/mL vs. 3.16 mg/mL). These results suggest that the short-term Asian dust events might be associated with increased acute respiratory symptoms and changes in PEF outcomes. However, there might be little long-term influence on airway hyperresponsiveness in children with mild asthma. PMID:18303201

  9. Effects of acute low-temperature events on development of Erysiphe necator and susceptibility of Vitis vinifera.

    PubMed

    Moyer, Michelle M; Gadoury, David M; Cadle-Davidson, Lance; Dry, Ian B; Magarey, Peter A; Wilcox, Wayne F; Seem, Robert C

    2010-11-01

    Growth and development of Erysiphe necator (syn. Uncinula necator) has been extensively studied under controlled conditions, primarily with a focus on development of grapevine powdery mildew within the optimal temperature range and the lethal effects of high temperatures. However, little is known of the effect of cold temperatures (above freezing but <8 degrees C) on pathogen development or host resistance. Pretreatment of susceptible Vitis vinifera leaf tissue by exposure to cold temperatures (2 to 8 degrees C for 2 to 8 h) reduced infection efficiency and colony expansion when tissues were subsequently inoculated. Furthermore, nascent colonies exposed to similar cold events exhibited hyphal mortality, reduced expansion, and increased latent periods. Historical weather data and an analysis of the radiational cooling of leaf tissues in the field indicated that early-season cold events capable of inducing the foregoing responses occur commonly and frequently across many if not most viticultural regions worldwide. These phenomena may partially explain (i) the unexpectedly slow development of powdery mildew during the first month after budbreak in some regions and (ii) the sudden increase in epidemic development once seasonal temperatures increase above the threshold for acute cold events. PMID:20649419

  10. Predictors of Hospitalized Exacerbations and Mortality in Chronic Obstructive Pulmonary Disease

    PubMed Central

    Santibáñez, Miguel; Garrastazu, Roberto; Ruiz-Nuñez, Mario; Helguera, Jose Manuel; Arenal, Sandra; Bonnardeux, Cristina; León, Carlos; García-Rivero, Juan Luis

    2016-01-01

    Background and Aim Exacerbations of chronic obstructive pulmonary disease (COPD) carry significant consequences for patients and are responsible for considerable health-care costs—particularly if hospitalization is required. Despite the importance of hospitalized exacerbations, relatively little is known about their determinants. This study aimed to analyze predictors of hospitalized exacerbations and mortality in COPD patients. Methods This was a retrospective population-based cohort study. We selected 900 patients with confirmed COPD aged ≥35 years by simple random sampling among all COPD patients in Cantabria (northern Spain) on December 31, 2011. We defined moderate exacerbations as events that led a care provider to prescribe antibiotics or corticosteroids and severe exacerbations as exacerbations requiring hospital admission. We observed exacerbation frequency over the previous year (2011) and following year (2012). We categorized patients according to COPD severity based on forced expiratory volume in 1 second (Global Initiative for Chronic Obstructive Lung Disease [GOLD] grades 1–4). We estimated the odds ratios (ORs) by logistic regression, adjusting for age, sex, smoking status, COPD severity, and frequent exacerbator phenotype the previous year. Results Of the patients, 16.4% had ≥1 severe exacerbations, varying from 9.3% in mild GOLD grade 1 to 44% in very severe COPD patients. A history of at least two prior severe exacerbations was positively associated with new severe exacerbations (adjusted OR, 6.73; 95% confidence interval [CI], 3.53–12.83) and mortality (adjusted OR, 7.63; 95%CI, 3.41–17.05). Older age and several comorbidities, such as heart failure and diabetes, were similarly associated. Conclusions Hospitalized exacerbations occurred with all grades of airflow limitation. A history of severe exacerbations was associated with new hospitalized exacerbations and mortality. PMID:27362765

  11. Incidence and outcomes of patients hospitalized with COPD exacerbation with and without pneumonia

    PubMed Central

    Søgaard, Mette; Madsen, Morten; Løkke, Anders; Hilberg, Ole; Sørensen, Henrik Toft; Thomsen, Reimar W

    2016-01-01

    Background Pneumonia may be a major contributor to hospitalizations for chronic obstructive pulmonary disease (COPD) exacerbation and influence their outcomes. Methods We examined hospitalization rates, health resource utilization, 30-day mortality, and risk of subsequent hospitalizations for COPD exacerbations with and without pneumonia in Denmark during 2006–2012. Results We identified 179,759 hospitalizations for COPD exacerbations, including 52,520 first-time hospitalizations (29.2%). Pneumonia was frequent in first-time exacerbations (36.1%), but declined in successive exacerbations to 25.6% by the seventh or greater exacerbation. Pneumonic COPD exacerbations increased 20% from 0.92 per 1,000 population in 2006 to 1.10 per 1,000 population in 2012. Nonpneumonic exacerbations decreased by 6% from 1.74 per 1,000 population to 1.63 per 1,000 population during the same period. A number of markers of health resource utilization were more prevalent in pneumonic exacerbations than in nonpneumonic exacerbations: length of stay (median 7 vs 4 days), intensive care unit admission (7.7% vs 12.5%), and several acute procedures. Thirty-day mortality was 12.1% in first-time pneumonic COPD exacerbations versus 8.3% in first-time nonpneumonic cases (adjusted HR [aHR] 1.20, 95% confidence interval [CI] 1.17–1.24). Pneumonia also predicted increased mortality associated with a second exacerbation (aHR 1.14, 95% CI 1.11–1.18), and up to a seventh or greater exacerbation (aHR 1.10, 95% CI 1.07–1.13). In contrast, the aHR of a subsequent exacerbation was 8%–13% lower for patients with pneumonic exacerbations. Conclusions Pneumonia is frequent among patients hospitalized for COPD exacerbations and is associated with increased health care utilization and higher mortality. Nonpneumonic COPD exacerbations predict increased risk of subsequent exacerbations. PMID:27042038

  12. Implementing emergency manuals: can cognitive aids help translate best practices for patient care during acute events?

    PubMed

    Goldhaber-Fiebert, Sara N; Howard, Steven K

    2013-11-01

    In this article, we address whether emergency manuals are an effective means of helping anesthesiologists and perioperative teams apply known best practices for critical events. We review the relevant history of such cognitive aids in health care, as well as examples from other high stakes industries, and describe why emergency manuals have a role in improving patient care during certain events. We propose 4 vital elements: create, familiarize, use, and integrate, necessary for the widespread, successful development, and implementation of medical emergency manuals, using the specific example of the perioperative setting. The details of each element are presented, drawing from the medical literature as well as from our combined experience of more than 30 years of observing teams of anesthesiologists managing simulated and real critical events. We emphasize the importance of training clinicians in the use of emergency manuals for education on content, format, and location. Finally, we discuss cultural readiness for change, present a system example of successful integration, and highlight the importance of further research on the implementation of emergency manuals.

  13. Effects of Ocean Acidification on the Brown Alga Padina pavonica: Decalcification Due to Acute and Chronic Events

    PubMed Central

    Gil-Díaz, Teba; Haroun, Ricardo; Tuya, Fernando; Betancor, Séfora; Viera-Rodríguez, María A.

    2014-01-01

    Since the industrial revolution, anthropogenic CO2 emissions have caused ocean acidification, which particularly affects calcified organisms. Given the fan-like calcified fronds of the brown alga Padina pavonica, we evaluated the acute (short-term) effects of a sudden pH drop due to a submarine volcanic eruption (October 2011–early March 2012) affecting offshore waters around El Hierro Island (Canary Islands, Spain). We further studied the chronic (long-term) effects of the continuous decrease in pH in the last decades around the Canarian waters. In both the observational and retrospective studies (using herbarium collections of P. pavonica thalli from the overall Canarian Archipelago), the percent of surface calcium carbonate coverage of P. pavonica thalli were contrasted with oceanographic data collected either in situ (volcanic eruption event) or from the ESTOC marine observatory data series (herbarium study). Results showed that this calcified alga is sensitive to acute and chronic environmental pH changes. In both cases, pH changes predicted surface thallus calcification, including a progressive decalcification over the last three decades. This result concurs with previous studies where calcareous organisms decalcify under more acidic conditions. Hence, Padina pavonica can be implemented as a bio-indicator of ocean acidification (at short and long time scales) for monitoring purposes over wide geographic ranges, as this macroalga is affected and thrives (unlike strict calcifiers) under more acidic conditions. PMID:25268231

  14. Effects of ocean acidification on the brown alga Padina pavonica: decalcification due to acute and chronic events.

    PubMed

    Gil-Díaz, Teba; Haroun, Ricardo; Tuya, Fernando; Betancor, Séfora; Viera-Rodríguez, María A

    2014-01-01

    Since the industrial revolution, anthropogenic CO₂ emissions have caused ocean acidification, which particularly affects calcified organisms. Given the fan-like calcified fronds of the brown alga Padina pavonica, we evaluated the acute (short-term) effects of a sudden pH drop due to a submarine volcanic eruption (October 2011-early March 2012) affecting offshore waters around El Hierro Island (Canary Islands, Spain). We further studied the chronic (long-term) effects of the continuous decrease in pH in the last decades around the Canarian waters. In both the observational and retrospective studies (using herbarium collections of P. pavonica thalli from the overall Canarian Archipelago), the percent of surface calcium carbonate coverage of P. pavonica thalli were contrasted with oceanographic data collected either in situ (volcanic eruption event) or from the ESTOC marine observatory data series (herbarium study). Results showed that this calcified alga is sensitive to acute and chronic environmental pH changes. In both cases, pH changes predicted surface thallus calcification, including a progressive decalcification over the last three decades. This result concurs with previous studies where calcareous organisms decalcify under more acidic conditions. Hence, Padina pavonica can be implemented as a bio-indicator of ocean acidification (at short and long time scales) for monitoring purposes over wide geographic ranges, as this macroalga is affected and thrives (unlike strict calcifiers) under more acidic conditions.

  15. Evaluation of the Methods and Management of Acute Coronary Events (EMMACE)-3: protocol for a longitudinal study

    PubMed Central

    Alabas, O A; West, R M; Gillott, R G; Khatib, R; Hall, A S; Gale, C P

    2015-01-01

    Introduction Patients with cardiovascular disease are living longer and are more frequently accessing healthcare resources. The Evaluation of the Methods and Management of Acute Coronary Events (EMMACE)-3 national study is designed to improve understanding of the effect of quality of care on health-related outcomes for patients hospitalised with acute coronary syndrome (ACS). Methods and analysis EMMACE-3 is a longitudinal study of 5556 patients hospitalised with an ACS in England. The study collects repeated measures of health-related quality of life, information about medications and patient adherence profiles, a survey of hospital facilities, and morbidity and mortality data from linkages to multiple electronic health records. Together with EMMACE-3X and EMMACE-4, EMMACE-3 will assimilate detailed information for about 13 000 patients across more than 60 hospitals in England. Ethics and dissemination EMMACE-3 was given a favourable ethical opinion by Leeds (West) Research Ethics committee (REC reference: 10/H131374). On successful application, study data will be shared with academic collaborators. The findings from EMMACE-3 will be disseminated through peer-reviewed publications, at scientific conferences, the media, and through patient and public involvement. Study registration number ClinicalTrials.gov Identifier: NCT01808027. Information about the study is also available at EMMACE.org. PMID:26105029

  16. Predictive value of CHADS2 score for cardiovascular events in patients with acute coronary syndrome and documented coronary artery disease

    PubMed Central

    Kang, In Sook; Pyun, Wook Bum; Shin, Gil Ja

    2016-01-01

    Background/Aims: The CHADS2 score, used to predict the risk of ischemic stroke in atrial fibrillation (AF) patients, has been reported recently to predict ischemic stroke in patients with coronary heart disease, regardless of the presence of AF. However, little data are available regarding the relationship between the CHADS2 score and cardiovascular outcomes. Methods: This was a retrospective study on 104 patients admitted for acute coronary syndrome (ACS) who underwent coronary angiography, carotid ultrasound, and transthoracic echocardiography. Results: The mean age of the subjects was 60.1 ± 12.6 years. The CHADS2 score was as follows: 0 in 46 patients (44.2%), 1 in 31 (29.8%), 2 in 18 (17.3%), and ≥ 3 in 9 patients (8.7%). The left atrial volume index (LAVi) showed a positive correlation with the CHADS2 score (20.8 ± 5.9 for 0; 23.2 ± 6.7 for 1; 26.6 ± 10.8 for 2; and 30.3 ± 8.3 mL/m2 for ≥3; p = 0.001). The average carotid total plaque area was significantly increased with CHADS2 scores ≥ 2 (4.97 ± 7.17 mm2 vs. 15.52 ± 14.61 mm2; p = 0.002). Eight patients experienced cardiovascular or cerebrovascular (CCV) events during a mean evaluation period of 662 days. A CHADS2 score ≥ 3 was related to an increase in the risk of CCV events (hazard ratio, 14.31; 95% confidence interval, 3.53 to 58.06). Furthermore, LAVi and the severity of coronary artery obstructive disease were also associated with an increased risk of CCV events. Conclusions: The CHADS2 score may be a useful prognostic tool for predicting CCV events in ACS patients with documented coronary artery disease. PMID:26767860

  17. One-year Mortality after an Acute Coronary Event and its Clinical Predictors: The ERICO Study

    PubMed Central

    Santos, Itamar Souza; Goulart, Alessandra Carvalho; Brandão, Rodrigo Martins; Santos, Rafael Caire de Oliveira; Bittencourt, Márcio Sommer; Sitnik, Débora; Pereira, Alexandre Costa; Pastore, Carlos Alberto; Samesima, Nelson; Lotufo, Paulo Andrade; Bensenor, Isabela Martins

    2015-01-01

    Background Information about post-acute coronary syndrome (ACS) survival have been mostly short-term findings or based on specialized, cardiology referral centers. Objectives To describe one-year case-fatality rates in the Strategy of Registry of Acute Coronary Syndrome (ERICO) cohort, and to study baseline characteristics as predictors. Methods We analyzed data from 964 ERICO participants enrolled from February 2009 to December 2012. We assessed vital status by telephone contact and official death certificate searches. The cause of death was determined according to the official death certificates. We used log-rank tests to compare the probabilities of survival across subgroups. We built crude and adjusted (for age, sex and ACS subtype) Cox regression models to study if the ACS subtype or baseline characteristics were independent predictors of all-cause or cardiovascular mortality. Results We identified 110 deaths in the cohort (case-fatality rate, 12.0%). Age [Hazard ratio (HR) = 2.04 per 10 year increase; 95% confidence interval (95%CI) = 1.75–2.38], non-ST elevation myocardial infarction (HR = 3.82 ; 95%CI = 2.21–6.60) or ST elevation myocardial infarction (HR = 2.59; 95%CI = 1.38–4.89) diagnoses, and diabetes (HR = 1.78; 95%CI = 1.20‑2.63) were significant risk factors for all-cause mortality in the adjusted models. We found similar results for cardiovascular mortality. A previous coronary artery disease diagnosis was also an independent predictor of all-cause mortality (HR = 1.61; 95%CI = 1.04–2.50), but not for cardiovascular mortality. Conclusion We found an overall one-year mortality rate of 12.0% in a sample of post-ACS patients in a community, non-specialized hospital in São Paulo, Brazil. Age, ACS subtype, and diabetes were independent predictors of poor one‑year survival for overall and cardiovascular-related causes. PMID:25993485

  18. Use of emergency medical services in the second gulf registry of acute coronary events.

    PubMed

    AlHabib, Khalid F; Alfaleh, Hussam; Hersi, Ahmad; Kashour, Tarek; Alsheikh-Ali, Alawi A; Suwaidi, Jassim Al; Sulaiman, Kadhim; Saif, Shukri Al; Almahmeed, Wael; Asaad, Nidal; Amin, Haitham; Al-Motarreb, Ahmed; Thalib, Lukman

    2014-09-01

    Data are scarce regarding emergency medical service (EMS) usage by patients with acute coronary syndrome (ACS) in the Arabian Gulf region. This 9-month in-hospital prospective ACS registry was conducted in Arabian Gulf countries, with 30-day and 1-year follow-up mortality rates. Of 5184 patients with ACS, 1293 (25%) arrived at the hospital by EMS. The EMS group (vs non-EMS) was more likely to be male, have cardiac arrest on presentation, be current or exsmokers, and have moderate or severe left ventricular dysfunction and ST-segment elevation myocardial infarction (STEMI). The EMS group had higher crude mortality rates during hospitalization and after hospital discharge but not after adjustment for clinical factors and treatments. The EMSs are underused in the Arabian Gulf region. Short- and long-term mortality rates in patients with ACS are similar between those who used and did not use EMS. Quality improvement in the EMS infrastructure and establishment of integrated STEMI networks are urgently needed. PMID:24019088

  19. Early coagulation events induce acute lung injury in a rat model of blunt traumatic brain injury.

    PubMed

    Yasui, Hideki; Donahue, Deborah L; Walsh, Mark; Castellino, Francis J; Ploplis, Victoria A

    2016-07-01

    Acute lung injury (ALI) and systemic coagulopathy are serious complications of traumatic brain injury (TBI) that frequently lead to poor clinical outcomes. Although the release of tissue factor (TF), a potent initiator of the extrinsic pathway of coagulation, from the injured brain is thought to play a key role in coagulopathy after TBI, its function in ALI following TBI remains unclear. In this study, we investigated whether the systemic appearance of TF correlated with the ensuing coagulopathy that follows TBI in ALI using an anesthetized rat blunt trauma TBI model. Blood and lung samples were obtained after TBI. Compared with controls, pulmonary edema and increased pulmonary permeability were observed as early as 5 min after TBI without evidence of norepinephrine involvement. Systemic TF increased at 5 min and then diminished 60 min after TBI. Lung injury and alveolar hemorrhaging were also observed as early as 5 min after TBI. A biphasic elevation of TF was observed in the lungs after TBI, and TF-positive microparticles (MPs) were detected in the alveolar spaces. Fibrin(ogen) deposition was also observed in the lungs within 60 min after TBI. Additionally, preadministration of a direct thrombin inhibitor, Refludan, attenuated lung injuries, thus implicating thrombin as a direct participant in ALI after TBI. The results from this study demonstrated that enhanced systemic TF may be an initiator of coagulation activation that contributes to ALI after TBI. PMID:27190065

  20. Predicting frequent COPD exacerbations using primary care data

    PubMed Central

    Kerkhof, Marjan; Freeman, Daryl; Jones, Rupert; Chisholm, Alison; Price, David B

    2015-01-01

    Purpose Acute COPD exacerbations account for much of the rising disability and costs associated with COPD, but data on predictive risk factors are limited. The goal of the current study was to develop a robust, clinically based model to predict frequent exacerbation risk. Patients and methods Patients identified from the Optimum Patient Care Research Database (OPCRD) with a diagnostic code for COPD and a forced expiratory volume in 1 second/forced vital capacity ratio <0.7 were included in this historical follow-up study if they were ≥40 years old and had data encompassing the year before (predictor year) and year after (outcome year) study index date. The data set contained potential risk factors including demographic, clinical, and comorbid variables. Following univariable analysis, predictors of two or more exacerbations were fed into a stepwise multivariable logistic regression. Sensitivity analyses were conducted for subpopulations of patients without any asthma diagnosis ever and those with questionnaire data on symptoms and smoking pack-years. The full predictive model was validated against 1 year of prospective OPCRD data. Results The full data set contained 16,565 patients (53% male, median age 70 years), including 9,393 patients without any recorded asthma and 3,713 patients with questionnaire data. The full model retained eleven variables that significantly predicted two or more exacerbations, of which the number of exacerbations in the preceding year had the strongest association; others included height, age, forced expiratory volume in 1 second, and several comorbid conditions. Significant predictors not previously identified included eosinophilia and COPD Assessment Test score. The predictive ability of the full model (C statistic 0.751) changed little when applied to the validation data set (n=2,713; C statistic 0.735). Results of the sensitivity analyses supported the main findings. Conclusion Patients at risk of exacerbation can be identified

  1. Magnesium sulfate versus ipratropium bromide in chronic obstructive pulmonary disease exacerbation: a randomized trial.

    PubMed

    Nouira, Semir; Bouida, Wahid; Grissa, Mohamed H; Beltaief, Kaouther; Trimech, Mohamed N; Boubaker, Hamdi; Marghli, Soudani; Letaief, Mondher; Boukef, Riadh

    2014-01-01

    Treatment with short-acting β2-agonists for exacerbations of chronic obstructive pulmonary disease (COPD) results in clinical improvement. It has not been established whether combining short-acting β2-agonists to other bronchodilators is more effective than β2-agonists alone. We conducted a study in patients presenting to the emergency department with exacerbation of COPD. They were randomized to receive nebulized ipratropium bromide (IB group; n = 62) or combined nebulized and intravenous bolus of magnesium sulfate (MgSO4 group; n = 62). All nebulized drugs were administered at 30-minute intervals for 2 hours. Primary outcome included hospital admission, endotracheal intubation, and hospital death rates. Secondary outcome measures were improvement in peak expiratory flow, dyspnea score, and arterial blood gas changes within the first 3 hours. There were no significant differences in primary outcome between MgSO4 and IB groups. Patients given IB average 32 L greater improvement in peak expiratory flow rate compared with magnesium sulfate (95% confidence interval, 19-43 L) at 180 minutes. Simultaneously, there was a significant reduction in PaCO2 compared with baseline values in IB group but not in MgSO4 group. There was a statistically nonsignificant trend toward a decrease in dyspnea score in both groups although adverse events were similar. Although the improvement in peak expiratory flow rate and arterial blood gas favored nebulized IB over magnesium sulfate, there was a nonsignificant difference between both drugs with regard to hospital admission, intubation, and hospital death rates in patients with COPD treated in the emergency department for acute exacerbation.

  2. A longitudinal assessment of sleep variables during exacerbations of chronic obstructive pulmonary disease.

    PubMed

    Vanaparthy, R; Mota, P; Khan, R; Ehsan, M; Qureshi, A; ZuWallack, R; Leidy, N

    2015-11-01

    Although sleep disturbance is common in chronic obstructive pulmonary disease (COPD), relatively little is known on the effect of the exacerbation on sleep quality. Accordingly, we longitudinally assessed sleep variables during exacerbations and clinical stability. This is a sub-study of a larger observational analysis. Inclusion criteria were clinically stable COPD and two or more clinical exacerbations in the preceding 12 months. Patients were followed for approximately 6 months and during this time the following were recorded daily: (1) COPD exacerbations, which were determined in two ways, clinically and symptom defined using the exacerbations of chronic pulmonary disease tool (EXACT); (2) daytime sleepiness, which was measured using the Stanford Sleepiness Scale; (3) subjective awakenings, which was measured from a sleep diary; and (4) sleep duration, efficiency, and objective awakenings, which was measured from actigraphy. These variables for exacerbation and non-exacerbation days were compared. Seventeen patients (9 male, age 63 ± 12 years, forced expiratory volume in 1 second 52 ± 20%) entered data over 135 ± 18 days. During this time, 15 patients had 27 symptom-defined exacerbations and 8 had 9 clinically reported exacerbations. Symptom-defined exacerbation days were 26% of the total study days. More daytime sleepiness, decreased total sleep time (TST), and decreased sleep efficiency (SE) were present during exacerbations compared with clinical stability (p < 0.001). These disturbances tended to be greater during clinically reported exacerbations than during unreported events (p < 0.05). Increased daytime sleepiness, less TST, and poorer SE are present during COPD exacerbations.

  3. Usefulness of Coronary Atheroma Burden to Predict Cardiovascular Events in Patients Presenting With Acute Coronary Syndromes (from the PROSPECT Study).

    PubMed

    Shan, Peiren; Mintz, Gary S; McPherson, John A; De Bruyne, Bernard; Farhat, Naim Z; Marso, Steven P; Serruys, Patrick W; Stone, Gregg W; Maehara, Akiko

    2015-12-01

    We investigated the relation between overall atheroma burden and clinical events in the Providing Regional Observations to Study Predictors of Events in the Coronary Tree (PROSPECT) study. In PROSPECT, 660 patients (3,229 nonculprit lesions with a plaque burden ≥ 40% and complete intravascular ultrasound data) were divided into tertiles according to baseline percent atheroma volume (PAV: total plaque/vessel volume). Patients were followed for 3.4 years (median); major adverse cardiac events (MACE: death from cardiac causes, cardiac arrest, myocardial infarction, or rehospitalization because of unstable or progressive angina) were adjudicated to either culprit or nonculprit lesions. Compared with patients in low or intermediate PAV tertiles, patients in the high PAV tertile had the greatest prevalence of plaque rupture and radiofrequency thin-cap fibroatheroma (VH-TCFA) and the highest percentage of necrotic core volume; they were also more likely to have high-risk lesion characteristics: ≥ 1 lesion with minimal luminal area ≤ 4 mm(2), plaque burden >70%, and/or VH-TCFA. Three-year cumulative nonculprit lesion-related MACE was greater in the intermediate and high tertiles than in the low tertile (6.3% vs 14.7% vs 15.1%, low vs intermediate vs high tertiles, p = 0.009). On Cox multivariable analysis, insulin-dependent diabetes (hazard ratio [HR] 3.98, p = 0.002), PAV (HR 1.06, p = 0.03), and the presence of ≥1 VH-TCFA (HR 1.80, p = 0.02) were independent predictors of nonculprit MACE. In conclusion, increasing baseline overall atheroma burden was associated with more advanced, complex, and vulnerable intravascular ultrasound lesion morphology and independently predicted nonculprit lesion-related MACE in patients with acute coronary syndromes after successful culprit lesion intervention.

  4. The role of the complement system in acute kidney injury.

    PubMed

    McCullough, James W; Renner, Brandon; Thurman, Joshua M

    2013-11-01

    Acute kidney injury is a common and severe clinical problem. Patients who develop acute kidney injury are at increased risk of death despite supportive measures such as hemodialysis. Research in recent years has shown that tissue inflammation is central to the pathogenesis of renal injury, even after nonimmune insults such as ischemia/reperfusion and toxins. Examination of clinical samples and preclinical models has shown that activation of the complement system is a critical cause of acute kidney injury. Furthermore, complement activation within the injured kidney is a proximal trigger of many downstream inflammatory events within the renal parenchyma that exacerbate injury to the kidney. Complement activation also may account for the systemic inflammatory events that contribute to remote organ injury and patient mortality. Complement inhibitory drugs have now entered clinical use and may provide an important new therapeutic approach for patients suffering from, or at high risk of developing, acute kidney injury.

  5. Referrals in Acute Coronary Events for CARdiac Catheterization: The RACE CAR trial

    PubMed Central

    Kreatsoulas, Catherine; Sloane, Debi; Pogue, Janice; Velianou, James L; Anand, Sonia S

    2010-01-01

    BACKGROUND: Women with acute coronary syndromes have lower rates of cardiac catheterization (CC) than men. OBJECTIVE: To determine whether sex/gender, age, risk level and patient preference influence physician decision making to refer patients for CC. METHODS: Twelve clinical scenarios controlling for sex/gender, age (55 or 75 years of age), Thrombolysis in Myocardial Infarction risk score (low, moderate or high) and patient preference for CC (agreeable or refused/no preference expressed) were designed. Scenarios were administered to specialists across Canada using a web-based computerized survey instrument. Questions were standardized using a five-point Likert scale ranging from 1 (very unlikely to benefit from CC) to 5 (very likely to benefit from CC). Outcomes were assessed using a two-tailed mixed linear regression model. RESULTS: Of 237 scenarios, physicians rated men as more likely to benefit from CC than women (mean [± SE] 4.44±0.07 versus 4.25±0.07, P=0.03), adjusted for age, risk and patient preference. Low-risk men were perceived to benefit more than low-risk women (4.20±0.13 versus 3.54±0.14, P<0.01), and low-risk younger patients were perceived to benefit more than low-risk older patients (4.52±0.17 versus 3.22±0.16, P<0.01). Regardless of risk, patients who agreed to CC were perceived as more likely to benefit from CC than patients who were disagreeable or made no comment at all (5.0±0.23, 3.67±0.21, 2.95±0.14, respectively, P<0.01). CONCLUSION: Canadian specialists’ decisions to refer patients for CC appear to be influenced by sex/gender, age and patient preference in clinical scenarios in which cardiac risk is held constant. Future investigation of possible age and sex/gender biases as proxies for risk is warranted. PMID:20931097

  6. Occurrence of virus-induced COPD exacerbations during four seasons.

    PubMed

    Djamin, Remco S; Uzun, Sevim; Snelders, Eveline; Kluytmans, Jan J W; Hoogsteden, Henk C; Aerts, Joachim G J V; Van Der Eerden, Menno M

    2015-02-01

    In this study, we investigated the occurrence of viral infections in acute exacerbations of chronic obstructive pulmonary disease (COPD) during four seasons. Viral infections were detected by the use of real-time reverse transcriptase polymerase chain reaction on pharyngeal swabs. During a 12-month period pharyngeal swabs were obtained in 136 exacerbations of 63 patients. In 35 exacerbations (25.7%) a viral infection was detected. Most viral infections occurred in the winter (n = 14, 40.0%), followed by summer (n = 9, 25.7%), autumn (n = 6, 17.1%), and spring (n = 6, 17.1%). Rhinovirus was the most frequently isolated virus (n = 19, 51.4%), followed by respiratory syncytial virus (n = 6, 16.2%), human metapneumovirus (n = 5, 13.5%), influenza A (n = 4, 10.8%), parainfluenza 4 (n = 2, 5.4%), and parainfluenza 3 (n = 1, 2.7%). This study showed that virus-induced COPD exacerbations occur in all four seasons with a peak in the winter months. However, the distribution of rhinovirus infections showed a different pattern, with most infections occurring in July.

  7. Viruses in Idiopathic Pulmonary Fibrosis. Etiology and Exacerbation.

    PubMed

    Moore, Bethany B; Moore, Thomas A

    2015-11-01

    Viral infections are important contributors to exacerbation of asthma and chronic obstructive pulmonary disease; however, the role of viruses in the pathogenesis of idiopathic pulmonary fibrosis (IPF) is less clear. This likely reflects that fact that IPF acute exacerbations are defined clinically as "noninfectious," and little attention has been paid to the outcomes of patients with IPF with diagnosed infections. However, accumulating evidence suggests that infections (both bacterial and viral) may influence disease outcomes either as exacerbating agents or initiators of disease. Support for a viral role in disease initiation comes from studies demonstrating the presence of herpesviral DNA and epithelial cell stress in the lungs of asymptomatic relatives at risk for developing familial IPF. In addition, the number of studies that can associate viral (especially herpesviral) signatures in the lung with the development of IPF is steadily growing, and activated leukocyte signatures in patients with IPF provide further support for infectious processes driving IPF progression. Animal modeling has been used to better understand how a gamma herpesvirus infection can modulate the pathogenesis of lung fibrosis and has demonstrated that preceding infections appear to reprogram lung epithelial cells during latency to produce profibrotic factors, making the lung more susceptible to subsequent fibrotic insult, whereas exacerbations of existing fibrosis, or infections in susceptible hosts, involve active viral replication and are influenced by antiviral therapy. In addition, there is new evidence that bacterial burden in the lungs of patients with IPF may predict a poor prognosis. PMID:26595738

  8. Aminophylline Dosage In Asthma Exacerbations in Children: A Systematic Review

    PubMed Central

    2016-01-01

    Background Adequate asthma treatment of childhood exacerbations with IV aminophylline depends on appropriate dosage. Recommendations to aim for a target therapeutic range may be inappropriate as serum concentrations correlate poorly with clinical improvement. This review aims to evaluate the evidence for the optimum dosage strategy of intravenous aminophylline in children suffering an exacerbation of asthma. Methods A systematic review comparing dosage regimens of intravenous aminophylline in children suffering an exacerbation of asthma. Primary outcomes were time until resolution of symptoms, mortality and need for mechanical ventilation. Secondary outcomes were date until discharge criteria are met, actual discharge and adverse effects. Data sources CENTRAL, CINAHL, MEDLINE and Web of Science. Search performed in March 2016 Eligibility criteria Studies using intravenous aminophylline in children with an acute exacerbation of asthma which reported the dosage and clinical outcomes. Findings 14 RCTs were included. There is a poor relationship between the dosage administered to children and symptom resolution, length of stay or need for mechanical ventilation. This study is limited due to its use of indirect evidence. Conclusion The currently recommended dosage regimens may not represent the optimum safety and efficacy of intravenous aminophylline. There is a need to develop the evidence base correlating dosage with patient centered clinical outcomes, to improve prescribing practices. PMID:27483163

  9. Bleeding Risk during Treatment of Acute Thrombotic Events with Subcutaneous LMWH Compared to Intravenous Unfractionated Heparin; A Systematic Review

    PubMed Central

    Costantino, Giorgio; Ceriani, Elisa; Rusconi, Anna Maria; Podda, Gian Marco; Montano, Nicola; Duca, Piergiorgio; Cattaneo, Marco; Casazza, Giovanni

    2012-01-01

    Background Low Molecular Weight Heparins (LMWH) are at least as effective antithrombotic drugs as Unfractionated Heparin (UFH). However, it is still unclear whether the safety profiles of LMWH and UFH differ. We performed a systematic review to compare the bleeding risk of fixed dose subcutaneous LMWH and adjusted dose UFH for treatment of venous thromboembolism (VTE) or acute coronary syndromes (ACS). Major bleeding was the primary end point. Methods Electronic databases (MEDLINE, EMBASE, and the Cochrane Library) were searched up to May 2010 with no language restrictions. Randomized controlled trials in which subcutaneous LMWH were compared to intravenous UFH for the treatment of acute thrombotic events were selected. Two reviewers independently screened studies and extracted data on study design, study quality, incidence of major bleeding, patients’ characteristics, type, dose and number of daily administrations of LMWH, co-treatments, study end points and efficacy outcome. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated using the random effects model. Results Twenty-seven studies were included. A total of 14,002 patients received UFH and 14,635 patients LMWH. Overall, no difference in major bleeding was observed between LMWH patients and UFH (OR = 0.79, 95% CI 0.60–1.04). In patients with VTE LMWH appeared safer than UFH, (OR = 0.68, 95% CI 0.47–1.00). Conclusion The results of our systematic review suggest that the use of LMWH in the treatment of VTE might be associated with a reduction in major bleeding compared with UFH. The choice of which heparin to use to minimize bleeding risk must be based on the single patient, taking into account the bleeding profile of different heparins in different settings. PMID:22984525

  10. Acute aerobic exercise enhances attentional modulation of somatosensory event-related potentials during a tactile discrimination task.

    PubMed

    Popovich, Christina; Staines, W Richard

    2015-03-15

    Neuroimaging research has shown that acute bouts of moderate intensity aerobic exercise can enhance attention-based neuronal activity in frontal brain regions, namely in the prefrontal cortex (PFC), as well as improve cognitive performance. The circuitry of the PFC is complex with extensive reciprocal corticocortical and thalamocortical connections, yet it remains unclear if aerobic exercise can also assist attentional control over modality-specific sensory cortices. To test this, we used a tactile discrimination task to compare tactile event-related potentials (ERPs) prior to and following an acute bout of moderate intensity aerobic exercise. We hypothesized that exercise preceding performance of the task would result in more efficient sensory gating of irrelevant/non-attended and enhancement of relevant/attended sensory information, respectively. Participants received vibrotactile stimulation to the second and fifth digit on the left hand and reported target stimuli on one digit only. ERP amplitudes for the P50, P100, N140 and long latency positivity (LLP) were quantified for attended and non-attended trials at FC4, C4, CP4 and P4 while P300 amplitudes were quantified in response to attended target stimuli at electrodes FCZ, CZ and CPZ. Results showed no effect of attention on the P50, however, both P100 and LLP amplitudes were significantly greater during attended, task-relevant trials, while the N140 was enhanced for non-attended, task-irrelevant stimuli. Moreover, unattended N140 amplitudes over parietal sites contralateral to stimulation were significantly greater post-exercise versus pre-exercise, while LLP modulation varied with greater unattended amplitudes post-exercise over frontal sites and greater attended amplitudes post-exercise over parietal sites. These results suggest that a single session of moderate intensity aerobic exercise facilitated the sensory gating of task-irrelevant tactile stimuli so that relevant sensory signals could be enhanced at

  11. Statistical Prediction of Solar Particle Event Frequency Based on the Measurements of Recent Solar Cycles for Acute Radiation Risk Analysis

    NASA Technical Reports Server (NTRS)

    Myung-Hee, Y. Kim; Shaowen, Hu; Cucinotta, Francis A.

    2009-01-01

    Large solar particle events (SPEs) present significant acute radiation risks to the crew members during extra-vehicular activities (EVAs) or in lightly shielded space vehicles for space missions beyond the protection of the Earth's magnetic field. Acute radiation sickness (ARS) can impair performance and result in failure of the mission. Improved forecasting capability and/or early-warning systems and proper shielding solutions are required to stay within NASA's short-term dose limits. Exactly how to make use of observations of SPEs for predicting occurrence and size is a great challenge, because SPE occurrences themselves are random in nature even though the expected frequency of SPEs is strongly influenced by the time position within the solar activity cycle. Therefore, we developed a probabilistic model approach, where a cumulative expected occurrence curve of SPEs for a typical solar cycle was formed from a non-homogeneous Poisson process model fitted to a database of proton fluence measurements of SPEs that occurred during the past 5 solar cycles (19 - 23) and those of large SPEs identified from impulsive nitrate enhancements in polar ice. From the fitted model, the expected frequency of SPEs was estimated at any given proton fluence threshold (Phi(sub E)) with energy (E) >30 MeV during a defined space mission period. Corresponding Phi(sub E) (E=30, 60, and 100 MeV) fluence distributions were simulated with a random draw from a gamma distribution, and applied for SPE ARS risk analysis for a specific mission period. It has been found that the accurate prediction of deep-seated organ doses was more precisely predicted at high energies, Phi(sub 100), than at lower energies such as Phi(sub 30) or Phi(sub 60), because of the high penetration depth of high energy protons. Estimates of ARS are then described for 90th and 95th percentile events for several mission lengths and for several likely organ dose-rates. The ability to accurately measure high energy protons

  12. Overexpression of SET is a recurrent event associated with poor outcome and contributes to protein phosphatase 2A inhibition in acute myeloid leukemia

    PubMed Central

    Cristóbal, Ion; Garcia-Orti, Laura; Cirauqui, Cristina; Cortes-Lavaud, Xabier; García-Sánchez, María A.; Calasanz, María J.; Odero, María D.

    2012-01-01

    Background Protein phosphatase 2A is a novel potential therapeutic target in several types of chronic and acute leukemia, and its inhibition is a common event in acute myeloid leukemia. Upregulation of SET is essential to inhibit protein phosphatase 2A in chronic myeloid leukemia, but its importance in acute myeloid leukemia has not yet been explored. Design and Methods We quantified SET expression by real time reverse transcriptase polymerase chain reaction in 214 acute myeloid leukemia patients at diagnosis. Western blot was performed in acute myeloid leukemia cell lines and in 16 patients’ samples. We studied the effect of SET using cell viability assays. Bioinformatics analysis of the SET promoter, chromatin immunoprecipitation, and luciferase assays were performed to evaluate the transcriptional regulation of SET. Results SET overexpression was found in 60/214 patients, for a prevalence of 28%. Patients with SET overexpression had worse overall survival (P<0.01) and event-free survival (P<0.01). Deregulation of SET was confirmed by western blot in both cell lines and patients’ samples. Functional analysis showed that SET promotes proliferation, and restores cell viability after protein phosphatase 2A overexpression. We identified EVI1 overexpression as a mechanism involved in SET deregulation in acute myeloid leukemia cells. Conclusions These findings suggest that SET overexpression is a key mechanism in the inhibition of PP2A in acute myeloid leukemia, and that EVI1 overexpression contributes to the deregulation of SET. Furthermore, SET overexpression is associated with a poor outcome in acute myeloid leukemia, and it can be used to identify a subgroup of patients who could benefit from future treatments based on PP2A activators. PMID:22133779

  13. Effect of Diabetes Mellitus on Frequency of Adverse Events in Patients With Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention.

    PubMed

    Piccolo, Raffaele; Franzone, Anna; Koskinas, Konstantinos C; Räber, Lorenz; Pilgrim, Thomas; Valgimigli, Marco; Stortecky, Stefan; Rat-Wirtzler, Julie; Silber, Sigmund; Serruys, Patrick W; Jüni, Peter; Heg, Dik; Windecker, Stephan

    2016-08-01

    Few data are available on the timing of adverse events in relation to the status of diabetes mellitus and the type of acute coronary syndrome (ACS). We investigated this issue in diabetic and nondiabetic patients admitted with a diagnosis of non-ST-segment elevation ACS (NSTE-ACS) or ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention. Patient-level data from 6 studies (n = 16,601) were pooled and only patients with ACS are included (n = 9,492). Early (0 to 30 days), late (31 to 365 days), and overall (0 to 365 days) events were analyzed. Diabetes mellitus was present in 1,927 patients (20.3%). At 1 year, all-cause mortality was highest for diabetic patients with STEMI (13.4%), followed by diabetic patients with NSTE-ACS (10.3%), nondiabetic patients with STEMI (6.4%) and nondiabetic patients with NSTE-ACS (4.4%; p <0.001). Among patients with diabetes, there was a significant interaction (p <0.001) for STEMI versus NSTE-ACS in early compared with late mortality, due to an excess of early mortality associated with STEMI (9.3% vs 3.7%; hazard ratio 2.31, 95% CI 1.52 to 3.54, p <0.001). Compared with diabetic NSTE-ACS patients, diabetic patients with STEMI had an increased risk of early stent thrombosis (hazard ratio 2.26, 95% CI 1.48 to 3.44, p <0.001), as well as a significant interaction (p = 0.009) in the risk of target lesion revascularization between the early and late follow-up. The distribution of fatal and nonfatal events according to the type of ACS was not influenced by diabetic status. In conclusion, diabetes in ACS setting confers a worse prognosis with 1-year mortality >10% in both STEMI and NSTE-ACS. Notwithstanding the high absolute rates, the temporal distribution of adverse events related to the type of ACS is similar between diabetic and nondiabetic patients.

  14. Gender differences in pre-event health status of young patients with acute myocardial infarction: A VIRGO study analysis

    PubMed Central

    Dreyer, Rachel P; Smolderen, Kim G; Strait, Kelly M; Beltrame, John F; Lichtman, Judith H; Lorenze, Nancy P; D’Onofrio, Gail; Bueno, Héctor; Krumholz, Harlan M; Spertus, John A

    2015-01-01

    Aims We assessed gender differences in pre-event health status (symptoms, functioning, quality of life) in young patients with acute myocardial infarction (AMI), and whether or not this association persists following sequential adjustment for important covariates. We also evaluated the interaction between gender and prior coronary artery disease (CAD), given that aggressive symptom control is a cornerstone of care in those with known coronary disease. Methods and Results A total of 3,501 AMI patients (2,349 women) aged 18–55 years were enrolled from 103 United States/24 Spanish hospitals (2008–2012). Clinical/health status information was obtained by medical record abstraction and patient interviews. Pre-event health status was measured by generic [Short Form-12 (SF-12), EuroQoL [EQ-5D)] and disease-specific [Seattle angina questionnaire (SAQ)] measures. T-test/chi-square and multivariable linear/logistic regression analysis was utilized, sequentially adjusting for covariates. Women had more co-morbidities and significantly lower generic mean health scores than men [SF-12 physical health =43±12 vs. 46±11 and mental health= 44±13 vs. 48±11]; EQ-5D utility index=0.7±0.2 vs. 0.8±0.2, and visual analog scale=63±22 vs. 67±20, P<0.0001 for all. Their disease-specific health status was also worse, with more angina [SAQ angina frequency=83±22 vs. 87±18], worse physical function [physical limitation=78±27 vs. 87±21] and poorer quality of life [55±25 vs. 60±22, P<0.0001 for all]. In multivariable analysis, the association between female gender and worse generic physical/mental health persisted, as well as worse disease-specific physical limitation and quality of life. The interaction between gender and prior CAD was not significant in any of the health status outcomes. Conclusion Young women have worse pre-event health status as compared with men, regardless of their CAD history. While future studies of gender differences should adjust for baseline health

  15. Effect of Diabetes Mellitus on Frequency of Adverse Events in Patients With Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention.

    PubMed

    Piccolo, Raffaele; Franzone, Anna; Koskinas, Konstantinos C; Räber, Lorenz; Pilgrim, Thomas; Valgimigli, Marco; Stortecky, Stefan; Rat-Wirtzler, Julie; Silber, Sigmund; Serruys, Patrick W; Jüni, Peter; Heg, Dik; Windecker, Stephan

    2016-08-01

    Few data are available on the timing of adverse events in relation to the status of diabetes mellitus and the type of acute coronary syndrome (ACS). We investigated this issue in diabetic and nondiabetic patients admitted with a diagnosis of non-ST-segment elevation ACS (NSTE-ACS) or ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention. Patient-level data from 6 studies (n = 16,601) were pooled and only patients with ACS are included (n = 9,492). Early (0 to 30 days), late (31 to 365 days), and overall (0 to 365 days) events were analyzed. Diabetes mellitus was present in 1,927 patients (20.3%). At 1 year, all-cause mortality was highest for diabetic patients with STEMI (13.4%), followed by diabetic patients with NSTE-ACS (10.3%), nondiabetic patients with STEMI (6.4%) and nondiabetic patients with NSTE-ACS (4.4%; p <0.001). Among patients with diabetes, there was a significant interaction (p <0.001) for STEMI versus NSTE-ACS in early compared with late mortality, due to an excess of early mortality associated with STEMI (9.3% vs 3.7%; hazard ratio 2.31, 95% CI 1.52 to 3.54, p <0.001). Compared with diabetic NSTE-ACS patients, diabetic patients with STEMI had an increased risk of early stent thrombosis (hazard ratio 2.26, 95% CI 1.48 to 3.44, p <0.001), as well as a significant interaction (p = 0.009) in the risk of target lesion revascularization between the early and late follow-up. The distribution of fatal and nonfatal events according to the type of ACS was not influenced by diabetic status. In conclusion, diabetes in ACS setting confers a worse prognosis with 1-year mortality >10% in both STEMI and NSTE-ACS. Notwithstanding the high absolute rates, the temporal distribution of adverse events related to the type of ACS is similar between diabetic and nondiabetic patients. PMID:27289296

  16. An international observational prospective study to determine the cost of asthma exacerbations (COAX).

    PubMed

    Lane, Stephen; Molina, Jesus; Plusa, Tadeusz

    2006-03-01

    Asthma is a common chronic condition that places substantial burden on patients and healthcare services. Despite the standards of asthma control that international guidelines recommend should be achieved, many patients continue to suffer sub-optimal control of symptoms and experience exacerbations (acute asthma attacks). In addition to being associated with reduced quality of life, asthma exacerbations are a key cost driver in asthma management. Routine clinical practice for the management of asthma exacerbations varies in different healthcare systems, so healthcare providers require local costs to be able to assess the value of therapies that reduce the frequency and severity of exacerbations. This prospective study, conducted in a total of 15 countries, assessed the local cost of asthma exacerbations managed in either primary or secondary care. Healthcare resources used were costed using actual values appropriate to each country in local currency and in Euros. Results are presented for exacerbations managed in primary care in Brazil, Bulgaria, Croatia, Czech Republic, Hungary, Poland, Russia, Slovakia, Slovenia, Spain and Ukraine, and in secondary care in Croatia, Denmark, Ireland, Latvia, Norway, Poland, Russia, Slovakia, Slovenia and Spain. Multiple regression analysis of the 2052 exacerbations included in the economic analysis showed that the cost of exacerbations was significantly affected by country (P<0.0001). Mean costs were significantly higher in secondary care (euro 1349) than primary care (euro 445, P=0.0003). Age was a significant variable (P=0.0002), though the effect showed an interaction with care type (P<0.0001). As severity of exacerbation increased, so did secondary care costs, though primary care costs remained essentially constant. In conclusion, the study showed that asthma exacerbations are costly to manage, suggesting that therapies able to increase asthma control and reduce the frequency or severity of exacerbations may bring economic

  17. A Rare Occurrence of Simultaneous Venous and Arterial Thromboembolic Events – Lower Limb Deep Venous Thrombosis and Pulmonary Thromboembolism as Initial Presentation in Acute Promyelocytic Leukemia

    PubMed Central

    Kutiyal, Aditya S.; Dharmshaktu, Pramila; Kataria, Babita; Garg, Abhilasha

    2016-01-01

    The development of acute myeloid leukemia has been attributed to various factors, including hereditary, radiation, drugs, and certain occupational exposures. The association between malignancy and venous thromboembolism events is well established. Here, we present a case of a 70-year-old Indian man who had presented with arterial and venous thrombosis, and the patient was later diagnosed with acute promyelocytic leukemia (APL). In our case, the patient presented with right lower limb deep venous thrombosis and pulmonary thromboembolism four months prior to the diagnosis of APL. Although thromboembolic event subsequent to the diagnosis of malignancy, and especially during the chemotherapy has been widely reported, this prior presentation with simultaneous occurrence of both venous and arterial thromboembolism has rarely been reported. We take this opportunity to state the significance of a complete medical evaluation in cases of recurrent or unusual thrombotic events. PMID:26949347

  18. To investigate the prevention of OM-85 on bronchiectasis exacerbations (iPROBE) in Chinese patients: study protocol for a randomized controlled trial

    PubMed Central

    2014-01-01

    Background Non-cystic fibrosis bronchiectasis is characterized by the irreversible dilatation of the medium-sized bronchi as a result of airway injury from recurrent or chronic inflammation and lower respiratory tract infections. Bronchiectasis airways are commonly colonized with bacterial species. Infections of the airways play important role in bronchiectasis exacerbations. The non-specific prevention of recurrent airway infections by immunostimulating agents has gained growing interest. OM-85, consisting of extracts of eight kinds of bacteria important in respiratory infections, could support the respiratory tract resistance to the pathogens. OM-85 has been shown to be a benefit by decreasing the risk of acute exacerbation of chronic obstructive pulmonary disease (COPD) in several perspective clinical trials. Exacerbation of bronchiectasis substantially contributes to a more rapid decline in lung function, reduced quality of life, and healthcare costs. In this context, we plan to conduct a clinical trial to investigate the PReventive effect of OM-85 on Bronchiectasis Exacerbation in Chinese patients (iPROBE). Methods/Design This study is designed as a prospective, randomized, double blind, placebo-controlled multicenter trial. A total of 244 patients with bronchiectasis, who have had at least one exacerbation of bronchiectasis in the previous year, will be included. The subjects will randomly receive two courses of 7 mg of OM-85 or a matching placebo. The treatment dose of OM-85 will be one daily capsule taken orally for 10 days each month for 3 consecutive months at the beginning of the study, followed by 3 months of no drug. This schedule will repeat until the patient has been seen for one year. Discussion We will investigate whether long-term treatment with an oral immunostimulant (OM-85) could decrease exacerbations of bronchiectasis over a one-year period. We will also assess other relevant outcomes, including the rate of event-based exacerbation, lung

  19. Acute stroke after intravitreal bevacizumab to treat choroidal neovascularization due to angioid streaks in pseudoxanthoma elasticum : a severe systemic adverse event after an off-label procedure.

    PubMed

    Besozzi, Gianluca; Ferrara, Andrea; Epifani, Enrico; Intini, Daniela; Apruzzese, Margherita; Provenzano, Antonio; Vetrugno, Michele

    2013-04-01

    To report the occurrence of acute stroke after intravitreal bevacizumab administration to treat choroidal neovascularization due to angioid streaks in a patient affected by pseudoxanthoma elasticum. A 54-year-old man with pseudoxanthoma elasticum had vision loss because of choroidal neovascularization due to angioid streaks. He underwent two intravitreal bevacizumab injections. Three days after the second procedure the patient was afflicted by acute stroke. Intravitreal injection of bevacizumab to treat choroidal neovascularization due to angioid streaks in pseudoxanthoma elasticum could lead to severe systemic adverse events. PMID:23065017

  20. Statin adherence and risk of acute cardiovascular events among women: a cohort study accounting for time-dependent confounding affected by previous adherence

    PubMed Central

    Lavikainen, Piia; Helin-Salmivaara, Arja; Eerola, Mervi; Fang, Gang; Hartikainen, Juha; Huupponen, Risto; Korhonen, Maarit Jaana

    2016-01-01

    Objectives Previous studies on the effect of statin adherence on cardiovascular events in the primary prevention of cardiovascular disease have adjusted for time-dependent confounding, but potentially introduced bias into their estimates as adherence and confounders were measured simultaneously. We aimed to evaluate the effect when accounting for time-dependent confounding affected by previous adherence as well as time sequence between factors. Design Retrospective cohort study. Setting Finnish healthcare registers. Participants Women aged 45–64 years initiating statin use for primary prevention of cardiovascular disease in 2001–2004 (n=42 807). Outcomes Acute cardiovascular event defined as a composite of acute coronary syndrome and acute ischaemic stroke was our primary outcome. Low-energy fractures were used as a negative control outcome to evaluate the healthy-adherer effect. Results During the 3-year follow-up, 474 women experienced the primary outcome event and 557 suffered a low-energy fracture. The causal HR estimated with marginal structural model for acute cardiovascular events for all the women who remained adherent (proportion of days covered ≥80%) to statin therapy during the previous adherence assessment year was 0.78 (95% CI: 0.65 to 0.94) when compared with everybody remaining non-adherent (proportion of days covered <80%). The result was robust against alternative model specifications. Statin adherers had a potentially reduced risk of experiencing low-energy fractures compared with non-adherers (HR 0.90, 95% CI 0.76 to 1.07). Conclusions Our study, which took into account the time dependence of adherence and confounders, as well as temporal order between these factors, is support for the concept that adherence to statins in women in primary prevention decreases the risk of acute cardiovascular events by about one-fifth in comparison to non-adherence. However, part of the observed effect of statin adherence on acute cardiovascular events

  1. Cervical spinal cord injury exacerbates ventilator-induced diaphragm dysfunction.

    PubMed

    Smuder, Ashley J; Gonzalez-Rothi, Elisa J; Kwon, Oh Sung; Morton, Aaron B; Sollanek, Kurt J; Powers, Scott K; Fuller, David D

    2016-01-15

    Cervical spinal cord injury (SCI) can dramatically impair diaphragm muscle function and often necessitates mechanical ventilation (MV) to maintain adequate pulmonary gas exchange. MV is a life-saving intervention. However, prolonged MV results in atrophy and impaired function of the diaphragm. Since cervical SCI can also trigger diaphragm atrophy, it may create preconditions that exacerbate ventilator-induced diaphragm dysfunction (VIDD). Currently, no drug therapy or clinical standard of care exists to prevent or minimize diaphragm dysfunction following SCI. Therefore, we first tested the hypothesis that initiating MV acutely after cervical SCI will exacerbate VIDD and enhance proteolytic activation in the diaphragm to a greater extent than either condition alone. Rats underwent controlled MV for 12 h following acute (∼24 h) cervical spinal hemisection injury at C2 (SCI). Diaphragm tissue was then harvested for comprehensive functional and molecular analyses. Second, we determined if antioxidant therapy could mitigate MV-induced diaphragm dysfunction after cervical SCI. In these experiments, SCI rats received antioxidant (Trolox, a vitamin E analog) or saline treatment prior to initiating MV. Our results demonstrate that compared with either condition alone, the combination of SCI and MV resulted in increased diaphragm atrophy, contractile dysfunction, and expression of atrophy-related genes, including MuRF1. Importantly, administration of the antioxidant Trolox attenuated proteolytic activation, fiber atrophy, and contractile dysfunction in the diaphragms of SCI + MV animals. These findings provide evidence that cervical SCI greatly exacerbates VIDD, but antioxidant therapy with Trolox can preserve diaphragm contractile function following acute SCI. PMID:26472866

  2. A Persistent and Diverse Airway Microbiota Present during Chronic Obstructive Pulmonary Disease Exacerbations

    PubMed Central

    Huang, Yvonne J.; Kim, Eugenia; Cox, Michael J.; Brodie, Eoin L.; Brown, Ron; Wiener-Kronish, Jeanine P.

    2010-01-01

    Abstract Acute exacerbations of chronic obstructive pulmonary disease (COPD) are a major source of morbidity and contribute significantly to healthcare costs. Although bacterial infections are implicated in nearly 50% of exacerbations, only a handful of pathogens have been consistently identified in COPD airways, primarily by culture-based methods, and the bacterial microbiota in acute exacerbations remains largely uncharacterized. The aim of this study was to comprehensively profile airway bacterial communities using a culture-independent microarray, the 16S rRNA PhyloChip, of a cohort of COPD patients requiring ventilatory support and antibiotic therapy for exacerbation-related respiratory failure. PhyloChip analysis revealed the presence of over 1,200 bacterial taxa representing 140 distinct families, many previously undetected in airway diseases; bacterial community composition was strongly influenced by the duration of intubation. A core community of 75 taxa was detected in all patients, many of which are known pathogens. Bacterial community diversity in COPD airways is substantially greater than previously recognized and includes a number of potential pathogens detected in the setting of antibiotic exposure. Comprehensive assessment of the COPD airway microbiota using high-throughput, culture-independent methods may prove key to understanding the relationships between airway bacterial colonization, acute exacerbation, and clinical outcomes in this and other chronic inflammatory airway diseases. PMID:20141328

  3. Do frequent moderate exacerbations contribute to progression of chronic obstructive pulmonary disease in patients who are ex-smokers?

    PubMed Central

    Dreyse, Jorge; Díaz, Orlando; Repetto, Paula B; Morales, Arturo; Saldías, Fernando; Lisboa, Carmen

    2015-01-01

    Background In addition to smoking, acute exacerbations are considered to be a contributing factor to progression of chronic obstructive pulmonary disease (COPD). However, these findings come from studies including active smokers, while results in ex-smokers are scarce and contradictory. The purpose of this study was to evaluate if frequent acute moderate exacerbations are associated with an accelerated decline in forced expiratory volume in one second (FEV1) and impairment of functional and clinical outcomes in ex-smoking COPD patients. Methods A cohort of 100 ex-smoking patients recruited for a 2-year follow-up study was evaluated at inclusion and at 6-monthly scheduled visits while in a stable condition. Evaluation included anthropometry, spirometry, inspiratory capacity, peripheral capillary oxygen saturation, severity of dyspnea, a 6-minute walking test, BODE (Body mass index, airflow Obstruction, Dyspnea, Exercise performance) index, and quality of life (St George’s Respiratory Questionnaire and Chronic Respiratory Disease Questionnaire). Severity of exacerbation was graded as moderate or severe according to health care utilization. Patients were classified as infrequent exacerbators if they had no or one acute exacerbation/year and frequent exacerbators if they had two or more acute exacerbations/year. Random effects modeling, within hierarchical linear modeling, was used for analysis. Results During follow-up, 419 (96% moderate) acute exacerbations were registered. At baseline, frequent exacerbators had more severe disease than infrequent exacerbators according to their FEV1 and BODE index, and also showed greater impairment in inspiratory capacity, forced vital capacity, peripheral capillary oxygen saturation, 6-minute walking test, and quality of life. However, no significant difference in FEV1 decline over time was found between the two groups (54.7±13 mL/year versus 85.4±15.9 mL/year in frequent exacerbators and infrequent exacerbators, respectively

  4. Biochemical pathogenesis of aspirin exacerbated respiratory disease (AERD).

    PubMed

    Narayanankutty, Arun; Reséndiz-Hernández, Juan Manuel; Falfán-Valencia, Ramcés; Teran, Luis M

    2013-05-01

    Aspirin exacerbated respiratory disease (AERD) is a distinct clinical entity characterized by eosinophilic rhinosinusitis, asthma and often nasal polyposis. Exposure to aspirin or other nonsteroid anti-inflammatory drugs (NSAIDs) exacerbates bronchospasms with asthma and rhinitis. Disease progression suggests a skewing towards TH2 type cellular response along with moderate to severe eosinophil and mast cell infiltration. Alterations in upper and lower airway cellular milieu with abnormalities in eicosanoid metabolism and altered eicosanoid receptor expression are the key features underlying AERD pathogenesis. Dysregulation of arachidonic acid (AA) metabolism, notably reduced prostaglandin E2 (PGE2) synthesis compared to their aspirin tolerant counterpart and relatively increased PGD2 production, a TH2/eosinophil chemoattractant are reported in AERD. Underproduced PGE2 is metabolized by overexpression of 15 prostaglandin dehydrogenase (15-PGDH) to inactive products further reducing PGE2 at real time. This relives the inhibitory effect of PGE2 on 5-lipoxygenase (5-LOX) resulting in overproduction of cysteinyl leukotrienes (CysLTs). Diminished formation of CysLT antagonists called lipoxins (LXs) also augments CysLTs responsiveness. Occasional intake of NSAIDs favors even more 5-LOX product formation, further narrowing the bronchoconstrictive bottle neck, resulting in acute asthmatic exacerbations along with increased mucus production. This review focuses on abnormalities in biochemical and molecular mechanisms in eicosanoid biosynthesis, eicosanoid receptor dysregulation and associated polymorphisms with special reference to arachidonic acid metabolism in AERD. PMID:23246457

  5. Medroxyprogesterone acetate exacerbates glutamate excitotoxicity.

    PubMed

    Nilsen, Jon; Morales, Alison; Brinton, Roberta Diaz

    2006-07-01

    We previously demonstrated that progesterone functions as a neuroprotective agent whereas medroxyprogesterone acetate (MPA; Provera) does not. Moreover, MPA antagonized the neuroprotective and neurotrophic outcomes induced by 17beta-estradiol (E2). Towards developing effective hormone therapies for protection against neurodegeneration, we sought to determine whether formulation, chemical features or prevention versus treatment mode of exposure affected the outcome of MPA treatment in survival of primary hippocampal neurons. Results of these analyses indicated that both crystalline MPA and a pharmaceutical formulation (Depo-Provera) lacked neuroprotective efficacy, indicating that the effects were not dependent upon MPA formulation. Likewise, MPA in the prevention and treatment paradigms were equally ineffective at promoting neuronal survival, indicating that timing of MPA administration was not a factor. Further, the detrimental effects of MPA were not due to the presence of the acetate group, as medroxyprogesterone was as ineffective as MPA in promoting neuronal survival. Moreover, MPA pretreatment exacerbated neuron death induced by glutamate excitotoxicity as indicated by a 40% increase in neuron death determined by direct live/dead cell count and a commensurate increase in the number of positive cells by terminal deoxynucleotidyl transferase-mediated nick end-labeling. Collectively these results predict that the progestin formulation of hormone therapy will affect the vulnerability of the central nervous system to degenerative insults.

  6. Utility of a Genetic Risk Score to Predict Recurrent Cardiovascular Events 1 Year After an Acute Coronary Syndrome: A Pooled Analysis of the RISCA, PRAXY, and TRIUMPH Cohorts

    PubMed Central

    Labos, Christopher; Martinez, Sara C.; Leo Wang, Rui Hao; Lenzini, Petra A.; Pilote, Louise; Bogaty, Peter; Brophy, James M.; Engert, James C.; Cresci, Sharon; Thanassoulis, George

    2015-01-01

    Background Limited evidence exists regarding the utility of genetic risk scores (GRS) in predicting recurrent cardiovascular events after acute coronary syndrome (ACS). We sought to determine whether a GRS would predict early recurrent cardiovascular events within 1 year of ACS. Methods & Results Participants admitted with acute coronary syndromes from the RISCA, PRAXY, and TRIUMPH cohorts, were genotyped for 30 single nucleotide polymorphisms (SNPs) associated with coronary artery disease (CAD) or myocardial infarction (MI) in prior genome wide association studies. A 30 SNP CAD/MI GRS was constructed. The primary endpoint was defined as all-cause mortality, recurrent ACS or cardiac re-hospitalization within 1 year of ACS admission. Results across all cohorts for the 30 SNP CAD/MI GRS were pooled using a random-effects model. There were 1040 patients from the RISCA cohort, 691 patients from the PRAXY cohort, and 1772 patients from the TRIUMPH cohort included in the analysis and 389 occurrences of the primary endpoint of recurrent events at 1-year post-ACS. In unadjusted and fully adjusted analyses, a 30 SNP GRS was not significantly associated with recurrent events (HR per allele 0.97 (95%CI 0.91–1.03) for RISCA, HR 0.99 (95%CI 0.93–1.05) for PRAXY, 0.98 (95%CI 0.94–1.02) for TRIUMPH, and 0.98 (95%CI 0.95–1.01) for the pooled analysis). Addition of this GRS to the GRACE risk model did not significantly improve risk prediction. Conclusion The 30 MI SNP GRS was not associated with recurrent events 1-year post ACS in pooled analyses across cohorts and did not improve risk discrimination or reclassification indices. Our results suggest that the genetic etiology of early events post-ACS may differ from later events. PMID:26232166

  7. Impact of acute water and feed deprivation events on growth performance, intestinal characteristics, and serum stress markers in weaned pigs.

    PubMed

    Horn, N; Ruch, F; Miller, G; Ajuwon, K M; Adeola, O

    2014-10-01

    The impact of acute stressors (24-h feed or water deprivation) on growth performance, intestinal characteristics, and serum stress markers in weaned pigs was evaluated. Pigs (6.21 ± 0.29 kg) were allotted in a randomized complete block design to 4 treatments on the basis of BW at the time of weaning. There were 8 mixed-sex pigs in each of 12 pens per treatment. Treatments were arranged as a 2 × 2 factorial and consisted of a feed or water stressor that included a 0- or 24-h deprivation period postweaning, and pigs were subsequently allowed access to feed and water. Growth performance was measured 1, 7, 14, and 28 d postweaning. Serum and intestinal samples were taken 1 and 7 d postweaning. Serum was analyzed for cortisol and corticotrophin-releasing factor, and villus height, crypt depth, and mast cell density were measured in the jejunum and the ileum. Expression of mucin (MUC2), tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), claudin 1 (CL-1), occludin (OC), and zonula occludens 1 (ZO-1) genes were measured on d 1 and 7 postweaning in the jejunum and ileum by real-time PCR. There was a decrease (P < 0.05) in ADG with the water stressor 1 d postweaning, although subsequently, there were improvements (P < 0.05) in ADG and feed efficiency. Furthermore, the water stressor reduced ADFI during the last 14 d of the trial and cumulatively (P < 0.05). Seven days postweaning there was an increase (P < 0.05) in jejunal villous height to depth ratio due to the feed stressor and a decrease (P < 0.05) in the ileal villous height to depth ratio due to the water stressor. There was an increase (P < 0.05) in serum cortisol levels due to the water stressor both 1 and 7 d postweaning. Furthermore, there was an increase in serum corticotrophin-releasing factor 1 d but not 7 d postweaning due to the water stressor (P < 0.05). The feed stressor reduced (P < 0.05) TNF-α gene expression, and the water stressor reduced (P < 0.05) OC gene expression in the jejunum 1 d

  8. Resource Use Study In COPD (RUSIC): A prospective study to quantify the effects of COPD exacerbations on health care resource use among COPD patients

    PubMed Central

    FitzGerald, J Mark; Haddon, Jennifer M; Bradley-Kennedy, Carole; Kuramoto, Lisa; Ford, Gordon T

    2007-01-01

    BACKGROUND: There is increasing interest in health care resource use (HRU) in Canada, particularly in resources associated with acute exacerbations of chronic obstructive pulmonary disease (COPD). OBJECTIVE: To identify HRU due to exacerbations of COPD. METHODS: A 52-week, multicentre, prospective, observational study of HRU due to exacerbations in patients with moderate to severe COPD was performed. Patients were recruited from primary care physicians and respirologists in urban and rural centres in Canada. RESULTS: In total, 524 subjects (59% men) completed the study. Their mean age was 68.2±9.4 years, with a forced expiratory volume in 1 s of 1.01±0.4 L. Patients had significant comorbidities. There were 691 acute exacerbations of COPD, which occurred in 53% of patients: 119 patients (23%) experienced one acute exacerbation, 70 patients (13%) had two acute exacerbations and 89 patients (17%) had three or more acute exacerbations. Seventy-five patients were admitted to hospital, with an average length of stay of 13.2 days. Fourteen of the patients spent time in an intensive care unit (average length of stay 5.6 days). Factors associated with acute exacerbations of COPD included lower forced expiratory volume in 1 s (P<0.001), high number of respiratory medications prescribed (P=0.037), regular use of oral corticosteroids (OCSs) (P=0.008) and presence of depression (P<0.001). Of the 75 patients hospitalized, only 53 received OCSs, four received referral for rehabilitation and 15 were referred for home care. CONCLUSIONS: The present study showed a high prevalence of COPD exacerbations, which likely impacted on HRU. There was evidence of a lack of appropriate management of exacerbations, especially with respect to use of OCSs, and referral for pulmonary rehabilitation and home care. PMID:17464378

  9. Inhalation of concentrated ambient air particles exacerbates myocardial ischemia in conscious dogs.

    PubMed Central

    Wellenius, Gregory A; Coull, Brent A; Godleski, John J; Koutrakis, Petros; Okabe, Kazunori; Savage, Sara T; Lawrence, Joy E; Murthy, G G Krishna; Verrier, Richard L

    2003-01-01

    Short-term increases in ambient air pollution have been associated with an increased incidence of acute cardiac events. We assessed the effect of inhalation exposure to concentrated ambient particles (CAPs) on myocardial ischemia in a canine model of coronary artery occlusion. Six mongrel dogs underwent thoracotomy for implantation of a vascular occluder around the left anterior descending coronary artery and tracheostomy to facilitate particulate exposure. After recovery (5-13 weeks), pairs of subjects were exposed for 6 hr/day on 3 or 4 consecutive days. Within each pair, one subject was randomly assigned to breathe CAPs on the second exposure day and filtered air at other times. The second subject breathed CAPs on the third exposure day and filtered air at other times. Immediately after each exposure, subjects underwent 5-min coronary artery occlusion. We determined ST-segment elevation, a measure of myocardial ischemia heart rate, and arrhythmia incidence during occlusion from continuous electrocardiograms. Exposure to CAPs (median, 285.7; range, 161.3-957.3 microg/m3) significantly (p = 0.007) enhanced occlusion-induced peak ST-segment elevation in precordial leads V4 (9.4 +/- 1.7 vs. 6.2 +/- 0.9 mm, CAPs vs. filtered air, respectively) and V5 (9.2 +/- 1.3 vs. 7.5 +/- 0.9 mm). ST-segment elevation was significantly correlated with the silicon concentration of the particles and other crustal elements possibly associated with urban street dust (p = 0.003 for Si). No associations were found with CAPs mass or number concentrations. Heart rate was not affected by CAPs exposure. These results suggest that exacerbation of myocardial ischemia during coronary artery occlusion may be an important mechanism of environmentally related acute cardiac events. PMID:12676590

  10. Acute Cardiovascular Events after Herpes Zoster: A Self-Controlled Case Series Analysis in Vaccinated and Unvaccinated Older Residents of the United States

    PubMed Central

    Minassian, Caroline; Thomas, Sara L.; Smeeth, Liam; Douglas, Ian; Brauer, Ruth; Langan, Sinéad M.

    2015-01-01

    Background Herpes zoster is common and can have serious consequences. Additionally, emerging data suggest an increased risk of acute cardiovascular events following herpes zoster. However, to our knowledge, existing association studies compare outcomes between individuals and are therefore vulnerable to between-person confounding. In this study, we used a within-person study design to quantify any short-term increased risk of acute cardiovascular events (stroke and myocardial infarction [MI]) after zoster and to assess whether zoster vaccination modifies this association. Methods and Findings The self-controlled case series method was used to estimate rates of stroke and acute MI in defined periods after herpes zoster compared to other time periods, within individuals. Participants were fully eligible Medicare beneficiaries aged ≥65 y with a herpes zoster diagnosis and either an ischemic stroke (n = 42,954) or MI (n = 24,237) between 1 January 2006 and 31 December 2011. Age-adjusted incidence ratios (IRs) for stroke and MI during predefined periods up to 12 mo after zoster relative to unexposed time periods were calculated using conditional Poisson regression. We observed a marked increase in the rate of acute cardiovascular events in the first week after zoster diagnosis: a 2.4-fold increased ischemic stroke rate (IR 2.37, 95% CI 2.17–2.59) and a 1.7-fold increased MI rate (IR 1.68, 95% CI 1.47–1.92), followed by a gradual resolution over 6 mo. Zoster vaccination did not appear to modify the association with MI (interaction p-value = 0.44). We also found no evidence for a difference in the IR for ischemic stroke between vaccinated (IR 1.14, 95% CI 0.75–1.74) and unvaccinated (IR 1.78, 95% CI 1.68–1.88) individuals during the first 4 wk after zoster diagnosis (interaction p-value = 0.28). The relatively few vaccinated individuals limited the study’s power to assess the role of vaccination. Conclusions Stroke and MI rates are transiently increased after

  11. Change in Growth Differentiation Factor 15, but Not C-Reactive Protein, Independently Predicts Major Cardiac Events in Patients with Non-ST Elevation Acute Coronary Syndrome

    PubMed Central

    Hernandez-Baldomero, Idaira F.; Bosa-Ojeda, Francisco

    2014-01-01

    Among the numerous emerging biomarkers, high-sensitivity C-reactive protein (hsCRP) and growth-differentiation factor-15 (GDF-15) have received widespread interest, with their potential role as predictors of cardiovascular risk. The concentrations of inflammatory biomarkers, however, are influenced, among others, by physiological variations, which are the natural, within-individual variation occurring over time. The aims of our study are: (a) to describe the changes in hsCRP and GDF-15 levels over a period of time and after an episode of non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and (b) to examine whether the rate of change in hsCRP and GDF-15 after the acute event is associated with long-term major cardiovascular adverse events (MACE). Two hundred and Fifty five NSTE-ACS patients were included in the study. We measured hsCRP and GDF-15 concentrations, at admission and again 36 months after admission (end of the follow-up period). The present study shows that the change of hsCRP levels, measured after 36 months, does not predict MACE in NSTEACS-patients. However, the level of GDF-15 measured, after 36 months, was a stronger predictor of MACE, in comparison to the acute unstable phase. PMID:24839357

  12. Prevention of Medical Events During Air Travel: A Narrative Review.

    PubMed

    Naouri, Diane; Lapostolle, Frederic; Rondet, Claire; Ganansia, Olivier; Pateron, Dominique; Yordanov, Youri

    2016-09-01

    Prior to traveling, and when seeking medical pretravel advice, patients consult their personal physicians. Inflight medical issues are estimated to occur up to 350 times per day worldwide (1/14,000-40,000 passengers). Specific characteristics of the air cabin environment are associated with hypoxia and the expansion of trapped gases into body cavities, which can lead to harm. The most frequent medical events during air travel include abdominal pain; ear, nose, and throat pathologies; psychiatric disorders; and life-threatening events such as acute respiratory failure or cardiac arrest. Physicians need to be aware of the management of these conditions in this unusual setting. Chronic respiratory and cardiovascular diseases are common and are at increased risk of acute exacerbation. Physicians must be trained in these conditions and inform their patients about their prevention. PMID:27267286

  13. Geospatial relationships of air pollution and acute asthma events across the Detroit-Windsor international border: study design and preliminary results.

    PubMed

    Lemke, Lawrence D; Lamerato, Lois E; Xu, Xiaohong; Booza, Jason C; Reiners, John J; Raymond Iii, Delbert M; Villeneuve, Paul J; Lavigne, Eric; Larkin, Dana; Krouse, Helene J

    2014-07-01

    The Geospatial Determinants of Health Outcomes Consortium (GeoDHOC) study investigated ambient air quality across the international border between Detroit, Michigan, USA and Windsor, Ontario, Canada and its association with acute asthma events in 5- to 89-year-old residents of these cities. NO2, SO2, and volatile organic compounds (VOCs) were measured at 100 sites, and particulate matter (PM) and polycyclic aromatic hydrocarbons (PAHs) at 50 sites during two 2-week sampling periods in 2008 and 2009. Acute asthma event rates across neighborhoods in each city were calculated using emergency room visits and hospitalizations and standardized to the overall age and gender distribution of the population in the two cities combined. Results demonstrate that intra-urban air quality variations are related to adverse respiratory events in both cities. Annual 2008 asthma rates exhibited statistically significant positive correlations with total VOCs and total benzene, toluene, ethylbenzene and xylene (BTEX) at 5-digit zip code scale spatial resolution in Detroit. In Windsor, NO2, VOCs, and PM10 concentrations correlated positively with 2008 asthma rates at a similar 3-digit postal forward sortation area scale. The study is limited by its coarse temporal resolution (comparing relatively short term air quality measurements to annual asthma health data) and interpretation of findings is complicated by contrasts in population demographics and health-care delivery systems in Detroit and Windsor.

  14. Geospatial relationships of air pollution and acute asthma events across the Detroit–Windsor international border: Study design and preliminary results

    PubMed Central

    Lemke, Lawrence D; Lamerato, Lois E; Xu, Xiaohong; Booza, Jason C; Reiners, John J; Raymond III, Delbert M; Villeneuve, Paul J; Lavigne, Eric; Larkin, Dana; Krouse, Helene J

    2014-01-01

    The Geospatial Determinants of Health Outcomes Consortium (GeoDHOC) study investigated ambient air quality across the international border between Detroit, Michigan, USA and Windsor, Ontario, Canada and its association with acute asthma events in 5- to 89-year-old residents of these cities. NO2, SO2, and volatile organic compounds (VOCs) were measured at 100 sites, and particulate matter (PM) and polycyclic aromatic hydrocarbons (PAHs) at 50 sites during two 2-week sampling periods in 2008 and 2009. Acute asthma event rates across neighborhoods in each city were calculated using emergency room visits and hospitalizations and standardized to the overall age and gender distribution of the population in the two cities combined. Results demonstrate that intra-urban air quality variations are related to adverse respiratory events in both cities. Annual 2008 asthma rates exhibited statistically significant positive correlations with total VOCs and total benzene, toluene, ethylbenzene and xylene (BTEX) at 5-digit zip code scale spatial resolution in Detroit. In Windsor, NO2, VOCs, and PM10 concentrations correlated positively with 2008 asthma rates at a similar 3-digit postal forward sortation area scale. The study is limited by its coarse temporal resolution (comparing relatively short term air quality measurements to annual asthma health data) and interpretation of findings is complicated by contrasts in population demographics and health-care delivery systems in Detroit and Windsor. PMID:24220215

  15. Functional COMT Val158Met Polymorphism, Risk of Acute Coronary Events and Serum Homocysteine: The Kuopio Ischaemic Heart Disease Risk Factor Study

    PubMed Central

    Voutilainen, Sari; Tuomainen, Tomi-Pekka; Korhonen, Maarit; Mursu, Jaakko; Virtanen, Jyrki K.; Happonen, Pertti; Alfthan, Georg; Erlund, Iris; North, Kari E.; Mosher, M.J.; Kauhanen, Jussi; Tiihonen, Jari; Kaplan, George A.; Salonen, Jukka T.

    2007-01-01

    Background The role of circulating levels of total homocysteine tHcy in the development of coronary heart disease (CHD) is still under debate. One reason for conflicting results between previous studies on homocysteine and heart diseases could be consequence of different interactions between homocysteine and genes in different study populations. Many genetic factors play a role in folate-homocysteine metabolism, like functional polymorphism (Val108Met) in the Catechol-O-methyltransferase (COMT) gene. Methodology and Findings Our aim was to examine the role of COMT Val158Met polymorphism and interaction of this polymorphism with serum tHcy and folate concentration on the risk of acute coronary and events in middle-aged men from eastern Finland. A population-based prospective cohort of 792 men aged 46–64 years was examined as part of the Kuopio Ischaemic Heart Disease Risk Factor Study. During an average follow-up of 9.3 years, there were 69 acute coronary events in men with no previous history of CHD. When comparing the COMT low activity genotype with the others, we found an age and examination year adjusted hazard rate ratio (HRR) of 1.73 (95% confidence interval (CI), 1.07–2.79), and an age, examination year, serum LDL and HDL cholesterol, and triglyceride concentration, systolic blood pressure and smoking adjusted HRR of 1.77 (95% CI, 1.05–2.77). Although serum tHcy concentration was not statistically significantly associated with acute coronary events (HRR for the highest third versus others 1.52, 95% CI, 0.93–2.49), subjects with both high serum tHcy and the COMT low activity genotype had an additionally increased adjusted risk of HRR 2.94 (95% CI 1.50–5.76) as compared with other men. Conclusions This prospective cohort study suggests that the functional COMT Val158Met polymorphism is associated with increased risk of acute coronary events and it may interact with high serum tHcy levels. PMID:17264883

  16. The role of invasive ventilation in exacerbations of chronic obstructive pulmonary disease causing respiratory failure.

    PubMed

    Kosky, Christopher; Turton, Charles

    2006-01-01

    Acute hypercapnic respiratory failure in chronic obstructive pulmonary disease can usually be managed initially with medical treatment and non- invasive ventilation. In circumstances where non- invasive ventilation cannot be used or has failed, intubation and invasive ventilation may be lifesaving. The outcome of patients with an exacerbation of COPD requiring invasive ventilation is better than often thought, with a hospital survival of 70-89%. Decisions regarding invasive ventilation made by physicians and patients with COPD are unpredictable and vary with the individual. This article reviews the role of invasive ventilation in exacerbations of COPD to assist decision making.

  17. High levels of the adhesion molecule CD44 on leukemic cells generate acute myeloid leukemia relapse after withdrawal of the initial transforming event.

    PubMed

    Quéré, R; Andradottir, S; Brun, A C M; Zubarev, R A; Karlsson, G; Olsson, K; Magnusson, M; Cammenga, J; Karlsson, S

    2011-03-01

    Multiple genetic hits are detected in patients with acute myeloid leukemia (AML). To investigate this further, we developed a tetracycline-inducible mouse model of AML, in which the initial transforming event, overexpression of HOXA10, can be eliminated. Continuous overexpression of HOXA10 is required to generate AML in primary recipient mice, but is not essential for maintenance of the leukemia. Transplantation of AML to secondary recipients showed that in established leukemias, ∼80% of the leukemia-initiating cells (LICs) in bone marrow stopped proliferating upon withdrawal of HOXA10 overexpression. However, the population of LICs in primary recipients is heterogeneous, as ∼20% of the LICs induce leukemia in secondary recipients despite elimination of HOXA10-induced overexpression. Intrinsic genetic activation of several proto-oncogenes was observed in leukemic cells resistant to inactivation of the initial transformation event. Interestingly, high levels of the adhesion molecule CD44 on leukemic cells are essential to generate leukemia after removal of the primary event. This suggests that extrinsic niche-dependent factors are also involved in the host-dependent outgrowth of leukemias after withdrawal of HOXA10 overexpression event that initiates the leukemia.

  18. Acute incident rapid response at a mass-gathering event through comprehensive planning systems: a case report from the 2013 Shamrock Shuffle.

    PubMed

    Başdere, Mehmet; Ross, Colleen; Chan, Jennifer L; Mehrotra, Sanjay; Smilowitz, Karen; Chiampas, George

    2014-06-01

    Planning and execution of mass-gathering events involves various challenges. In this case report, the Chicago Model (CM), which was designed to organize and operate such events and to maintain the health and wellbeing of both runners and the public in a more effective way, is described. The Chicago Model also was designed to prepare for unexpected incidents, including disasters, during the marathon event. The model has been used successfully in the planning and execution stages of the Bank of America Shamrock Shuffle and the Bank of America Chicago Marathon since 2008. The key components of the CM are organizational structure, information systems, and communication. This case report describes how the organizers at the 2013 Shamrock Shuffle used the key components of the CM approach in order to respond to an acute incident caused by a man who was threatening to jump off the State Street Bridge. The course route was changed to accommodate this unexpected event, while maintaining access to key health care facilities. The lessons learned from the incident are presented and further improvements to the existing model are proposed. PMID:24820906

  19. [Etiological and exacerbation factors for COPD. Air pollution].

    PubMed

    Ogawa, Kazumasa; Kishi, Kazuma

    2016-05-01

    Recently, it has been found that the number of patients with chronic obstructive pulmonary disease (COPD) who do not have a history of smoking is higher than expected, and a number of factors affect the development of COPD. Although adequate evidence for the relation of ambient air pollution, including the presence of particulate matter (PM2.5), with the development of COPD is lacking, higher mortality from respiratory and cardiovascular diseases has been reported among patients exposed to air pollution for a long time. In addition, several reports have pointed out the possibility that acute exacerbation of COPD can be caused by short-term exposure to air pollution. Tobacco smoke is the main cause of highly concentrated PM2.5 indoors, and second hand smoke is related with the development of COPD and the high mortality from COPD. In developing countries, biomass fuel combustion contributes to COPD, especially among housewives who do not smoke.

  20. [Etiological and exacerbation factors for COPD. Air pollution].

    PubMed

    Ogawa, Kazumasa; Kishi, Kazuma

    2016-05-01

    Recently, it has been found that the number of patients with chronic obstructive pulmonary disease (COPD) who do not have a history of smoking is higher than expected, and a number of factors affect the development of COPD. Although adequate evidence for the relation of ambient air pollution, including the presence of particulate matter (PM2.5), with the development of COPD is lacking, higher mortality from respiratory and cardiovascular diseases has been reported among patients exposed to air pollution for a long time. In addition, several reports have pointed out the possibility that acute exacerbation of COPD can be caused by short-term exposure to air pollution. Tobacco smoke is the main cause of highly concentrated PM2.5 indoors, and second hand smoke is related with the development of COPD and the high mortality from COPD. In developing countries, biomass fuel combustion contributes to COPD, especially among housewives who do not smoke. PMID:27254939

  1. A model for emergency department end-of-life communications after acute devastating events--part I: decision-making capacity, surrogates, and advance directives.

    PubMed

    Limehouse, Walter E; Feeser, V Ramana; Bookman, Kelly J; Derse, Arthur

    2012-09-01

    Making decisions for a patient affected by sudden devastating illness or injury traumatizes a patient's family and loved ones. Even in the absence of an emergency, surrogates making end-of-life treatment decisions may experience negative emotional effects. Helping surrogates with these end-of-life decisions under emergent conditions requires the emergency physician (EP) to be clear, making medical recommendations with sensitivity. This model for emergency department (ED) end-of-life communications after acute devastating events comprises the following steps: 1) determine the patient's decision-making capacity; 2) identify the legal surrogate; 3) elicit patient values as expressed in completed advance directives; 4) determine patient/surrogate understanding of the life-limiting event and expectant treatment goals; 5) convey physician understanding of the event, including prognosis, treatment options, and recommendation; 6) share decisions regarding withdrawing or withholding of resuscitative efforts, using available resources and considering options for organ donation; and 7) revise treatment goals as needed. Emergency physicians should break bad news compassionately, yet sufficiently, so that surrogate and family understand both the gravity of the situation and the lack of long-term benefit of continued life-sustaining interventions. EPs should also help the surrogate and family understand that palliative care addresses comfort needs of the patient including adequate treatment for pain, dyspnea, or anxiety. Part I of this communications model reviews determination of decision-making capacity, surrogacy laws, and advance directives, including legal definitions and application of these steps; Part II (which will appear in a future issue of AEM) covers communication moving from resuscitative to end-of-life and palliative treatment. EPs should recognize acute devastating illness or injuries, when appropriate, as opportunities to initiate end-of-life discussions and to

  2. A model for emergency department end-of-life communications after acute devastating events--part I: decision-making capacity, surrogates, and advance directives.

    PubMed

    Limehouse, Walter E; Feeser, V Ramana; Bookman, Kelly J; Derse, Arthur

    2012-09-01

    Making decisions for a patient affected by sudden devastating illness or injury traumatizes a patient's family and loved ones. Even in the absence of an emergency, surrogates making end-of-life treatment decisions may experience negative emotional effects. Helping surrogates with these end-of-life decisions under emergent conditions requires the emergency physician (EP) to be clear, making medical recommendations with sensitivity. This model for emergency department (ED) end-of-life communications after acute devastating events comprises the following steps: 1) determine the patient's decision-making capacity; 2) identify the legal surrogate; 3) elicit patient values as expressed in completed advance directives; 4) determine patient/surrogate understanding of the life-limiting event and expectant treatment goals; 5) convey physician understanding of the event, including prognosis, treatment options, and recommendation; 6) share decisions regarding withdrawing or withholding of resuscitative efforts, using available resources and considering options for organ donation; and 7) revise treatment goals as needed. Emergency physicians should break bad news compassionately, yet sufficiently, so that surrogate and family understand both the gravity of the situation and the lack of long-term benefit of continued life-sustaining interventions. EPs should also help the surrogate and family understand that palliative care addresses comfort needs of the patient including adequate treatment for pain, dyspnea, or anxiety. Part I of this communications model reviews determination of decision-making capacity, surrogacy laws, and advance directives, including legal definitions and application of these steps; Part II (which will appear in a future issue of AEM) covers communication moving from resuscitative to end-of-life and palliative treatment. EPs should recognize acute devastating illness or injuries, when appropriate, as opportunities to initiate end-of-life discussions and to

  3. Impacts of coexisting bronchial asthma on severe exacerbations in mild-to-moderate COPD: results from a national database

    PubMed Central

    Lee, Hyun; Rhee, Chin Kook; Lee, Byung-Jae; Choi, Dong-Chull; Kim, Jee-Ae; Kim, Sang Hyun; Jeong, Yoolwon; Kim, Tae-Hyung; Chon, Gyu Rak; Jung, Ki-Suck; Lee, Sang Haak; Price, David; Yoo, Kwang Ha; Park, Hye Yun

    2016-01-01

    Background Acute exacerbations are major drivers of COPD deterioration. However, limited data are available for the prevalence of severe exacerbations and impact of asthma on severe exacerbations, especially in patients with mild-to-moderate COPD. Methods Patients with mild-to-moderate COPD (≥40 years) were extracted from Korean National Health and Nutrition Examination Survey data (2007–2012) and were linked to the national health insurance reimbursement database to obtain medical service utilization records. Results Of the 2,397 patients with mild-to-moderate COPD, 111 (4.6%) had severe exacerbations over the 6 years (0.012/person-year). Severe exacerbations were more frequent in the COPD patients with concomitant self-reported physician-diagnosed asthma compared with only COPD patients (P<0.001). A multiple logistic regression presented that asthma was an independent risk factor of severe exacerbations in patients with mild-to-moderate COPD regardless of adjustment for all possible confounding factors (adjusted odds ratio, 1.67; 95% confidence interval, 1.002–2.77, P=0.049). In addition, age, female, poor lung function, use of inhalers, and low EuroQoL five dimensions questionnaire index values were independently associated with severe exacerbation in patients with mild-to-moderate COPD. Conclusion In this population-based study, the prevalence of severe exacerbations in patients with mild-to-moderate COPD was relatively low, compared with previous clinical interventional studies. Coexisting asthma significantly impacted the frequency of severe exacerbations in patients with mild-to-moderate COPD, suggesting application of an exacerbation preventive strategy in these patients. PMID:27143869

  4. Using bacterial biomarkers to identify early indicators of cystic fibrosis pulmonary exacerbation onset.

    PubMed

    Rogers, Geraint B; Hoffman, Lucas R; Johnson, Matt W; Mayer-Hamblett, Nicole; Schwarze, Jürgen; Carroll, Mary P; Bruce, Kenneth D

    2011-03-01

    Acute periods of pulmonary exacerbation are the single most important cause of morbidity in cystic fibrosis patients, and may be associated with a loss of lung function. Intervening prior to the onset of a substantially increased inflammatory response may limit the associated damage to the airways. While a number of biomarker assays based on inflammatory markers have been developed, providing useful and important measures of disease during these periods, such factors are typically only elevated once the process of exacerbation has been initiated. Identifying biomarkers that can predict the onset of pulmonary exacerbation at an early stage would provide an opportunity to intervene before the establishment of a substantial immune response, with major implications for the advancement of cystic fibrosis care. The precise triggers of pulmonary exacerbation remain to be determined; however, the majority of models relate to the activity of microbes present in the patient's lower airways of cystic fibrosis. Advances in diagnostic microbiology now allow for the examination of these complex systems at a level likely to identify factors on which biomarker assays can be based. In this article, we discuss key considerations in the design and testing of assays that could predict pulmonary exacerbations. PMID:21405970

  5. Pulmonary rehabilitation and severe exacerbations of COPD: solution or white elephant?

    PubMed Central

    Puhan, Milo A.; Harrison, Samantha L.; Jordan, Rachel E.; Quint, Jennifer K.; Singh, Sally J.

    2015-01-01

    Hospitalisations for severe exacerbations of chronic obstructive pulmonary disease are associated with significant physical and psychological consequences including an increase in symptom severity, severe reductions in physical activity, a deleterious effect on skeletal muscle, impaired exercise tolerance/ability to self-care, decline in quality of life, and increased anxiety and depression. As these consequences are potentially amenable to exercise training, there is a clear rationale for pulmonary rehabilitation in the peri/post-exacerbation setting. Although a 2011 Cochrane review was overwhelmingly positive, subsequent trials have shown less benefit and real-life observational studies have revealed poor acceptability. Qualitative studies have demonstrated that the patient experience is a determining factor while the presence of comorbidities may influence referral, adherence and response to pulmonary rehabilitation. Systematic reviews of less supervised interventions, such as self-management, have shown limited benefits in the post-exacerbation setting. The recent update of the Cochrane review of peri-exacerbation pulmonary rehabilitation showed that benefits were associated with the “comprehensive” nature of the intervention (the number of sessions received, the intensity of exercise training and education delivered, and the degree of supervision) but implementation is demanding. The challenge is to develop interventions that are deliverable and acceptable around the time of an acute exacerbation but also deliver the desired clinical impact. PMID:27730157

  6. Spatial Hotspot Analysis of Acute Myocardial Infarction Events in an Urban Population: A Correlation Study of Health Problems and Industrial Installation

    PubMed Central

    NAMAYANDE, Motahareh Sadat; NEJADKOORKI, Farhad; NAMAYANDE, Seyedeh Mahdieh; DEHGHAN, Hamidreza

    2016-01-01

    Background: The current study’s objectives were to find any possible spatial patterns and hotspot of cardiovascular events and to perform a correlation study to find any possible relevance between cardiovascular disease (CVE) and location of industrial installation said above. Methods: We used the Acute Myocardial Infarction (AMI) hospital admission record in three main hospitals in Yazd, Yazd Province, Iran during 2013, because of CVDs and searched for possible correlation between industries as point-source pollutants and non-random distribution of AMI events. Results: MI incidence rate in Yazd was obtained 531 per 100,000 person-year among men, 458 per 100,000 person-year among women and 783/100,000 person-yr totally. We applied a GIS Hotspot analysis to determine feasible clusters and two sets of clusters were observed. Mean age of 56 AMI events occurred in the cluster cells was calculated as 62.21±14.75 yr. Age and sex as main confounders of AMI were evaluated in the cluster areas in comparison to other areas. We observed no significant difference regarding sex (59% in cluster cells versus 55% in total for men) and age (62.21±14.7 in cluster cells versus 63.28±13.98 in total for men). Conclusion: We found proximity of AMI events cluster to industries installations, and a steel industry, specifically. There could be an association between road-related pollutants and the observed sets of cluster due to the proximity exist between rather crowded highways nearby the events cluster. PMID:27057527

  7. Antibiotics for treatment and prevention of exacerbations of chronic obstructive pulmonary disease.

    PubMed

    Wilson, Robert; Sethi, Sanjay; Anzueto, Antonio; Miravitlles, Marc

    2013-12-01

    Acute exacerbations (AE) can be recurrent problems for patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) increasing morbidity and mortality. Evidence suggests that ≥50% of acute exacerbations involve bacteria requiring treatment with an antibiotic which should have high activity against the causative pathogens. However, sputum analysis is not a pre-requisite for antibiotic prescription in outpatients as results are delayed and patients are likely to be colonised with bacteria in the stable state. Clinicians rely on the clinical symptoms, sputum appearance and the patient's medical history to decide if an AE-COPD should be treated with antibiotics. This article reviews the available data of antibiotic trials in AE-COPD. Management of frequent exacerbators is particularly challenging for physicians. This may include antibiotic prophylaxis, especially macrolides because of anti-inflammatory properties; though successful in reducing exacerbations, concerns about resistance development remain. Inhalation of antibiotics achieves high local concentrations and minimal systemic exposure; therefore, it may represent an attractive alternative for antibiotic prophylaxis in certain COPD patients. Inhaled antibiotic prophylaxis has been successfully used in other respiratory conditions such as non-cystic fibrosis bronchiectasis which itself might be present in COPD patients who have chronic bacterial infection, particularly with Pseudomonas aeruginosa.

  8. Acute adverse events from over-the-counter Chinese herbal medicines: a population-based survey of Hong Kong Chinese

    PubMed Central

    2013-01-01

    Background Although over-the-counter traditional Chinese herbal medicine (COTC) is commonly used to treat everyday illness in many parts of the world, no population-based study has been done to examine the prevalence and factors associated with COTC-related adverse events. Methods A cross-sectional telephone survey was conducted among Hong Kong Chinese adults in 2011 (n = 1100) with informed verbal consent. Stepwise logistic regression of demographic, attitudinal and behavioral variables was used to determine factors associated with past-year adverse events. Results Of study respondents, 71.7% (789/1100) reported past-year COTC use and 2.3% (25/1100) reported at least one COTC-related adverse event in the past year. Of the 27 adverse events cases reported among COTC users, the most common were allergic reactions (n = 11) dizziness (n = 5), and gastro-intestinal problems (n = 4). Pills/capsules were the dosage form that caused the highest proportion of adverse events (n = 10), followed by plasters (n = 7), creams/ointments (n = 5), and ingestible powders (n = 2). Although COTC users reporting adverse events were more likely to report greater practices to avoid adverse events (OR = 6.47; 95% CI: 1.38-30.3); they were also more likely to possess lower education levels (OR = 9.64, 95% CI: 2.20-42.3) and to have received COTC information from non-reliable, mass-media information sources such as magazines (OR = 3.32; 95% CI: 1.01-8.50) or television (OR = 2.93; 95% CI: 1.03-10.7). Package labels were also felt to be unclear by 42.9% of COTC users. A large proportion of COTC users demonstrated low levels of COTC-related knowledge, while the main impediment to greater information-seeking was the belief that reliable COTC information is not obtainable from Western health professionals. Conclusions Despite global movements toward more stringent complementary medicine regulation, the limited accessibility of reliable information

  9. COPD exacerbations by disease severity in England

    PubMed Central

    Merinopoulou, Evie; Raluy-Callado, Mireia; Ramagopalan, Sreeram; MacLachlan, Sharon; Khalid, Javaria Mona

    2016-01-01

    Objectives Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with accelerated disease progression and are important drivers of health care resource utilization. The study aimed to quantify the rates of COPD exacerbations in England and assess health care resource utilization by severity categories according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2013. Methods Data from the Clinical Practice Research Datalink linked to Hospital Episode Statistics were used to identify patients with a COPD diagnosis aged ≥40 years. Those with complete spirometric, modified Medical Research Council Dyspnea Scale information, and exacerbation history 12 months prior to January 1, 2011 (index date) were classified into GOLD severity groups. Study outcomes over follow-up (up to December 31, 2013) were exacerbation rates and resource utilization (general practitioner visits, hospital admissions). Results From the 44,201 patients in the study cohort, 83.5% were classified into severity levels GOLD A: 33.8%, GOLD B: 21.0%, GOLD C: 18.1%, and GOLD D: 27.0%. Mean age at diagnosis was 66 years and 52.0% were male. Annual exacerbation rates per person-year increased with severity, from 0.83 (95% confidence interval [CI]: 0.81–0.85) for GOLD A to 2.51 (95% CI: 2.47–2.55) for GOLD D. General practitioner visit rates per person-year also increased with severity, from 4.82 (95% CI: 4.74–4.93) for GOLD A to 7.44 (95% CI: 7.31–7.61) for GOLD D. COPD-related hospitalization rates per person-year increased from less symptoms (GOLD A: 0.28, GOLD C: 0.39) to more symptoms (GOLD B: 0.52, GOLD D: 0.84). Conclusion Patients in the most severe category (GOLD D) experienced nearly three times the number of exacerbations and COPD-related hospitalizations as those in the least severe category (GOLD A), in addition to increased general practitioner visits. Better patient management to stabilize the disease progression could allow for an

  10. Acute telogen effluvium onset event is associated with the presence of female androgenetic alopecia: potential therapeutic implications.

    PubMed

    Perez-Mora, Nicolas; Goren, Andy; Velasco, Carlos; Bermudez, Fernando

    2014-01-01

    Acute telogen effluvium (ATE) is often associated with female androgenetic alopecia (FAA), but predictive factors of ATE-FAA association and clinical factors or therapies that may influence the progression of ATE to chronic telogen effluvium (CTE) have not been reported. We have identified predictive factors of ATE-FAA association and retrospectively evaluated the impact of therapies on the progression to CTE. Conclusions are as follows: (i) Triggering cause is a significant independent factor that predicts association of ATE with FAA. (ii) Triggering causes with higher risk of concurrent FAA are severe diet, iron deficiency, and thyroid dysfunction. (iii) Patients suffering ATE may benefit from different therapeutic approaches (depending on which is the triggering cause) to prevent or treat the association with FAA. (iv) Minoxidil use shows a trend to lower the percentage of progression to CTE. (v) Apart from treating the precipitating cause, the different additional oral treatments used have not shown any correlation with progression to CTE. PMID:24850277

  11. The similarities and differences of epidemic cycles of chronic obstructive pulmonary disease and asthma exacerbations.

    PubMed

    Johnston, Neil W

    2007-12-01

    The majority of chronic obstructive pulmonary disease (COPD) and asthma exacerbations in both children and adults are associated with respiratory viral infections and are cyclic in nature. Some variation in these cycles is associated with the timing of the appearance of respiratory viruses, particularly influenza and respiratory syncytial virus. Much more, however, is associated with signal events that are of either fixed or predictable timing. In children, asthma exacerbations reach epidemic levels following school return after the summer vacation and these are predominantly associated with rhinovirus infections. Although younger adults experience a rise in asthma exacerbations at this time, these are secondary to the epidemic in children. Older adults with either COPD or asthma experience only a slightly elevated risk of exacerbations after school return, and hospital presentations for pneumonia in any age group show only marginal increases at that time. Exacerbations of both COPD and adult asthma, with increasing risk with age, are at their highest average annual levels during the Christmas period. This effect appears to be independent of the timing of above average levels of influenza, RSV, parainfluenza, or adenovirus detections; however, hospitalization for respiratory tract infections in all age groups reaches high levels at the same time. Both the post-summer vacation asthma epidemic and the Christmas epidemic of COPD, asthma, and pneumonia are synchronous with the timing of signal events, the day of school return for the former and Christmas Day for the latter, and have been for several years. The agents responsible for the Christmas epidemic of respiratory diseases have not yet been identified. The differences between age and disease exacerbation patterns after school return and at Christmas suggest that either different agents are involved or that the response to a common agent is different between the two signal events.

  12. Exploring disparities in acute myocardial infarction events between Aboriginal and non-Aboriginal Australians: roles of age, gender, geography and area-level disadvantage.

    PubMed

    Randall, D A; Jorm, L R; Lujic, S; Eades, S J; Churches, T R; O'Loughlin, A J; Leyland, A H

    2014-07-01

    We investigated disparities in rates of acute myocardial infarction (AMI) between Aboriginal and non-Aboriginal people in the 199 Statistical Local Areas (SLAs) in New South Wales, Australia. Using routinely collected and linked hospital and mortality data from 2002 to 2007, we developed multilevel Poisson regression models to estimate the relative rates of first AMI events in the study period accounting for area of residence. Rates of AMI in Aboriginal people were more than two times that in non-Aboriginal people, with the disparity greatest in more disadvantaged and remote areas. AMI rates in Aboriginal people varied significantly by SLA, as did the Aboriginal to non-Aboriginal rate ratio. We identified almost 30 priority areas for universal and targeted preventive interventions that had both high rates of AMI for Aboriginal people and large disparities in rates.

  13. Acute Hematological Effects in Mice Exposed to the Expected Doses, Dose-rates, and Energies of Solar Particle Event-like Proton Radiation

    PubMed Central

    Sanzari, Jenine K.; Cengel, Keith A.; Wan, X. Steven; Rusek, Adam; Kennedy, Ann R.

    2014-01-01

    NASA has funded several projects that have provided evidence for the radiation risk in space. One radiation concern arises from solar particle event (SPE) radiation, which is composed of energetic electrons, protons, alpha particles and heavier particles. SPEs are unpredictable and the accompanying SPE radiation can place astronauts at risk of blood cell death, contributing to a weakened immune system and increased susceptibility to infection. The doses, dose rates, and energies of the proton radiation expected to occur during a SPE have been simulated at the NASA Space Radiation Laboratory, Brookhaven National Laboratory, delivering total body doses to mice. Hematological values were evaluated at acute time points, up to 24 hrs. post-radiation exposure. PMID:25202654

  14. [Therapeutical approach in severe exacerbation of COPD associating obstructive sleep apnoea and obesity].

    PubMed

    Dumitrache-Rujinski, Stefan; Croitoru, Alina; Bogdan, Miron Alexandru

    2012-01-01

    COPD exacerbations with respiratory acidosis are difficult to manage, especially when OSA and obesity are associated. The solution is the use of noninvasive ventilation associated with oxygenotherapy in order to correct the hypercapnia, hypoxemia and respiratory acidosis and to prevent the invasive mechanical ventilation. Early respiratory rehabilitation and the use of a domiciliary ventilatory support after the acute episode could be a part of the management for these patients. We present a modality of therapeutical approach through a clinical case.

  15. Effect on short- and long-term major adverse cardiac events of statin treatment in patients with acute myocardial infarction and renal dysfunction.

    PubMed

    Lim, Sang Yup; Bae, Eun Hui; Choi, Joon Seok; Kim, Chang Seong; Park, Jeong Woo; Ma, Seong Kwon; Jeong, Myung Ho; Kim, Soo Wan

    2012-05-15

    The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) reduce major adverse cardiac events (MACE) and mortality in patients with acute coronary syndrome. We investigated the effectiveness of statin therapy in reducing MACE in patients with acute myocardial infarction (AMI) and renal dysfunction (RD). In the present retrospective study of 12,853 patients with AMI, the patients were categorized into 4 groups: group I, statin therapy and no RD (estimated glomerular filtration rate ≥60 ml/min/1.73 m(2)); group II, neither statin therapy nor RD; group III, statin therapy and RD; group IV, no statin therapy but RD. The primary end points were death and complications during the hospital course. The secondary end points were MACE during 1 year of follow-up after AMI. Significant differences in the composite MACE during 12 months of follow-up were observed among the 4 groups (group I, 11.7%; group II, 19.0%; group III, 26.7%; and group IV, 45.5%; p <0.001). In a Cox proportional hazards model, mortality at 12 months increased stepwise from group II to IV compared to group I. Moreover, MACE-free survival in the severe RD group (estimated glomerular filtration rate <30 mL/min/1.73 m(2)) was also greater in the statin-treated group. In conclusion, statin therapy reduced MACE at 1 year of follow-up in patients with AMI regardless of RD.

  16. Identifying Drug (Cocaine) Intake Events from Acute Physiological Response in the Presence of Free-living Physical Activity

    PubMed Central

    Hossain, Syed Monowar; Ali, Amin Ahsan; Rahman, Mahbubur; Ertin, Emre; Epstein, David; Kennedy, Ashley; Preston, Kenzie; Umbricht, Annie; Chen, Yixin; Kumar, Santosh

    2014-01-01

    A variety of health and behavioral states can potentially be inferred from physiological measurements that can now be collected in the natural free-living environment. The major challenge, however, is to develop computational models for automated detection of health events that can work reliably in the natural field environment. In this paper, we develop a physiologically-informed model to automatically detect drug (cocaine) use events in the free-living environment of participants from their electrocardiogram (ECG) measurements. The key to reliably detecting drug use events in the field is to incorporate the knowledge of autonomic nervous system (ANS) behavior in the model development so as to decompose the activation effect of cocaine from the natural recovery behavior of the parasympathetic nervous system (after an episode of physical activity). We collect 89 days of data from 9 active drug users in two residential lab environments and 922 days of data from 42 active drug users in the field environment, for a total of 11,283 hours. We develop a model that tracks the natural recovery by the parasympathetic nervous system and then estimates the dampening caused to the recovery by the activation of the sympathetic nervous system due to cocaine. We develop efficient methods to screen and clean the ECG time series data and extract candidate windows to assess for potential drug use. We then apply our model on the recovery segments from these windows. Our model achieves 100% true positive rate while keeping the false positive rate to 0.87/day over (9+ hours/day of) lab data and to 1.13/day over (11+ hours/day of) field data. PMID:25531010

  17. Relationship of Buckling and Knee Injury to Pain Exacerbation in Knee Osteoarthritis: A Web-Based Case-Crossover Study

    PubMed Central

    Zobel, Isabelle; Erfani, Tahereh; Bennell, Kim L; Makovey, Joanna; Metcalf, Ben; March, Lyn; Zhang, Yuqing; Eckstein, Felix

    2016-01-01

    buckling was associated with experiencing a pain exacerbation (OR 4.0, 95% CI 2.6, 6.2) compared with no buckling and the association increased with a greater number of buckling events (for ≥ 6 buckling events, OR 20.1, 95% CI 3.7, 110). Conclusions Knee injury and buckling are associated with knee pain exacerbation. Reducing the likelihood of these mechanical events through avoidance of particular activities and/or appropriate rehabilitation programs may decrease the risk of pain exacerbation. PMID:27342008

  18. Prediction of fatal or near-fatal cardiac arrhythmia events in patients with depressed left ventricular function after an acute myocardial infarction†

    PubMed Central

    Huikuri, Heikki V.; Raatikainen, M.J. Pekka; Moerch-Joergensen, Rikke; Hartikainen, Juha; Virtanen, Vesa; Boland, Jean; Anttonen, Olli; Hoest, Nis; Boersma, Lucas V.A.; Platou, Eivind S.; Messier, Marc D.; Bloch-Thomsen, Poul-Erik

    2009-01-01

    Aims To determine whether risk stratification tests can predict serious arrhythmic events after acute myocardial infarction (AMI) in patients with reduced left ventricular ejection fraction (LVEF ≤ 0.40). Methods and results A total of 5869 consecutive patients were screened in 10 European centres, and 312 patients (age 65 ± 11 years) with a mean LVEF of 31 ± 6% were included in the study. Heart rate variability/turbulence, ambient arrhythmias, signal-averaged electrocardiogram (SAECG), T-wave alternans, and programmed electrical stimulation (PES) were performed 6 weeks after AMI. The primary endpoint was ECG-documented ventricular fibrillation or symptomatic sustained ventricular tachycardia (VT). To document these arrhythmic events, the patients received an implantable ECG loop-recorder. There were 25 primary endpoints (8.0%) during the follow-up of 2 years. The strongest predictors of primary endpoint were measures of heart rate variability, e.g. hazard ratio (HR) for reduced very-low frequency component (<5.7 ln ms2) adjusted for clinical variables was 7.0 (95% CI: 2.4–20.3, P < 0.001). Induction of sustained monomorphic VT during PES (adjusted HR = 4.8, 95% CI, 1.7–13.4, P = 0.003) also predicted the primary endpoint. Conclusion Fatal or near-fatal arrhythmias can be predicted by many risk stratification methods, especially by heart rate variability, in patients with reduced LVEF after AMI. PMID:19155249

  19. The effect of solar-geomagnetic activity during hospital admission on coronary events within 1 year in patients with acute coronary syndromes

    NASA Astrophysics Data System (ADS)

    Vencloviene, J.; Babarskiene, R.; Milvidaite, I.; Kubilius, R.; Stasionyte, J.

    2013-12-01

    Some evidence indicates the deterioration of the cardiovascular system during space storms. It is plausible that the space weather conditions during and after hospital admission may affect the risk of coronary events in patients with acute coronary syndromes (ACS). We analyzed the data of 1400 ACS patients who were admitted to the Hospital Lithuanian University of Health Sciences, and who survived for more than 4 days. We evaluated the associations between geomagnetic storms (GS), solar proton events (SPE), and solar flares (SF) that occurred 0-3 days before and after hospital admission and the risk of cardiovascular death (CAD), non-fatal ACS, and coronary artery bypass grafting (CABG) during a period of 1 year; the evaluation was based on the multivariate logistic model, controlling for clinical data. After adjustment for clinical variables, GS occurring in conjunction with SF 1 day before admission increased the risk of CAD by over 2.5 times. GS 2 days after SPE occurred 1 day after admission increased the risk of CAD and CABG by over 2.8 times. The risk of CABG increased by over 2 times in patients admitted during the day of GS and 1 day after SPE. The risk of ACS was by over 1.63 times higher for patients admitted 1 day before or after solar flares.

  20. Virus Infection-Induced Bronchial Asthma Exacerbation

    PubMed Central

    Yamaya, Mutsuo

    2012-01-01

    Infection with respiratory viruses, including rhinoviruses, influenza virus, and respiratory syncytial virus, exacerbates asthma, which is associated with processes such as airway inflammation, airway hyperresponsiveness, and mucus hypersecretion. In patients with viral infections and with infection-induced asthma exacerbation, inflammatory mediators and substances, including interleukins (ILs), leukotrienes and histamine, have been identified in the airway secretions, serum, plasma, and urine. Viral infections induce an accumulation of inflammatory cells in the airway mucosa and submucosa, including neutrophils, lymphocytes and eosinophils. Viral infections also enhance the production of inflammatory mediators and substances in airway epithelial cells, mast cells, and other inflammatory cells, such as IL-1, IL-6, IL-8, GM-CSF, RANTES, histamine, and intercellular adhesion molecule-1. Viral infections affect the barrier function of the airway epithelial cells and vascular endothelial cells. Recent reports have demonstrated augmented viral production mediated by an impaired interferon response in the airway epithelial cells of asthma patients. Several drugs used for the treatment of bronchial asthma reduce viral and pro-inflammatory cytokine release from airway epithelial cells infected with viruses. Here, I review the literature on the pathogenesis of the viral infection-induced exacerbation of asthma and on the modulation of viral infection-induced airway inflammation. PMID:22966430

  1. Do bacteria cause exacerbations of COPD?

    PubMed

    Hirschmann, J V

    2000-07-01

    Exacerbations of COPD, which include combinations of dyspnea, cough, wheezing, increased sputum production (and a change in its color to green or yellow), are common. The role of bacterial infection in causing these episodes and the value of antibiotic therapy for them are debated. An assessment of the microbiological studies indicates that conventional bacterial respiratory pathogens, such as Streptococcus pneumoniae and Haemophilus influenzae, are absent in about 50% of attacks. The frequency of isolating these organisms, which often colonize the bronchi of patients in stable condition, does not seem to increase during exacerbations, and their density typically remains unchanged. Serologic studies generally fail to show rises in antibody titers to H influenzae; the only report available demonstrates none to Haemophilus parainfluenzae; and the sole investigation of S pneumoniae is inconclusive. Trials with vaccines against S pneumoniae and H influenzae show no clear benefit in reducing exacerbations. The histologic findings of bronchial biopsies and cytologic studies of sputum show predominantly increased eosinophils, rather than neutrophils, contrary to what is expected with bacterial infections. The randomized, placebo-controlled trials generally show no benefit for antibiotics, but most have studied few patients. A meta-analysis of these demonstrated no clinically significant advantage to antimicrobial therapy. The largest trials suggest that antibiotics confer no advantage for mild episodes; with more severe attacks, in which patients should receive systemic corticosteroids, the addition of antimicrobial therapy is probably not helpful. PMID:10893379

  2. Phylogenetic evidence for intratypic recombinant events in a novel human adenovirus C that causes severe acute respiratory infection in children

    PubMed Central

    Wang, Yanqun; Li, Yamin; Lu, Roujian; Zhao, Yanjie; Xie, Zhengde; Shen, Jun; Tan, Wenjie

    2016-01-01

    Human adenoviruses (HAdVs) are prevalent in hospitalized children with severe acute respiratory infection (SARI). Here, we report a unique recombinant HAdV strain (CBJ113) isolated from a HAdV-positive child with SARI. The whole-genome sequence was determined using Sanger sequencing and high-throughput sequencing. A phylogenetic analysis of the complete genome indicated that the CBJ113 strain shares a common origin with HAdV-C2, HAdV-C6, HAdV-C1, HAdV-C5, and HAdV-C57 and formed a novel subclade on the same branch as other HAdV-C subtypes. BootScan and single nucleotide polymorphism analyses showed that the CBJ113 genome has an intra-subtype recombinant structure and comprises gene regions mainly originating from two circulating viral strains: HAdV-1 and HAdV-2. The parental penton base, pVI, and DBP genes of the recombinant strain clustered with the HAdV-1 prototype strain, and the E1B, hexon, fiber, and 100 K genes of the recombinant clustered within the HAdV-2 subtype, meanwhile the E4orf1 and DNA polymerase genes of the recombinant shared the greatest similarity with those of HAdV-5 and HAdV-6, respectively. All of these findings provide insight into our understanding of the dynamics of the complexity of the HAdV-C epidemic. More extensive studies should address the pathogenicity and clinical characteristics of the novel recombinant. PMID:26960434

  3. Expiratory flow limitation relates to symptoms during COPD exacerbations requiring hospital admission

    PubMed Central

    Jetmalani, Kanika; Timmins, Sophie; Brown, Nathan J; Diba, Chantale; Berend, Norbert; Salome, Cheryl M; Wen, Fu-Qiang; Chen, Peng; King, Gregory G; Farah, Claude S

    2015-01-01

    Background Expiratory flow limitation (EFL) is seen in some patients presenting with a COPD exacerbation; however, it is unclear how EFL relates to the clinical features of the exacerbation. We hypothesized that EFL when present contributes to symptoms and duration of recovery during a COPD exacerbation. Our aim was to compare changes in EFL with symptoms in subjects with and without flow-limited breathing admitted for a COPD exacerbation. Subjects and methods A total of 29 subjects with COPD were recruited within 48 hours of admission to West China Hospital for an acute exacerbation. Daily measurements of post-bronchodilator spirometry, resistance, and reactance using the forced oscillation technique and symptom (Borg) scores until discharge were made. Flow-limited breathing was defined as the difference between inspiratory and expiratory respiratory system reactance (EFL index) greater than 2.8 cmH2O·s·L−1. The physiological predictors of symptoms during recovery were determined by mixed-effect analysis. Results Nine subjects (31%) had flow-limited breathing on admission despite similar spirometry compared to subjects without flow-limited breathing. Spirometry and resistance measures did not change between enrolment and discharge. EFL index values improved in subjects with flow-limited breathing on admission, with resolution in four patients. In subjects with flow-limited breathing on admission, symptoms were related to inspiratory resistance and EFL index values. In subjects without flow-limited breathing, symptoms related to forced expiratory volume in 1 second/forced vital capacity. In the whole cohort, EFL index values at admission was related to duration of stay (Rs=0.4, P=0.03). Conclusion The presence of flow-limited breathing as well as abnormal respiratory system mechanics contribute independently to symptoms during COPD exacerbations. PMID:25999709

  4. Is respiratory viral infection really an important trigger of asthma exacerbations in children?

    PubMed

    Lee, So-lun; Chiu, Shui-seng Susan; Malik, Peiris Joseph S; Chan, Kwok-hung; Wong, Hing-sang Wilfred; Lau, Yu-lung

    2011-10-01

    We performed a prospective cohort study from September 2003 to December 2004 to delineate attributing the effect of different respiratory viral infections including newly discovered ones to asthma exacerbations in children in Hong Kong. One hundred and fourteen children aged 6-14 years with chronic stable asthma and on regular inhaled steroid were monitored for respiratory symptoms over a full calendar year from recruitment. They would attend the study clinic if peak expiratory flow rate decreased to below 80% of their baselines, if they met a predefined symptom score, or if parents subjectively felt them developing a cold. Virological diagnosis using virus culture, antigen detection, and polymerase chain reaction methods on nasal swab specimens would be attempted for all these visits irrespective of triggers. Physician diagnosed outcome of each episode was documented. Three hundred and five episodes of respiratory illnesses were captured in the cohort. Nasal specimens were available in 166 episodes, 92 of which were diagnosed as asthma exacerbations, and 74 non-asthma related episodes. Respiratory viruses were detected in 61 of 166 episodes (36.7%). There was no significant difference in virus detection rate between asthma exacerbations (32 out of 97 episodes, 34.8%) and non-asthma respiratory illnesses (29 out of 79 episodes, 39.2%). Although newly discovered respiratory viruses were identified in these episodes, rhinovirus was the commonest organism associated with both asthma exacerbations and non-asthma related episodes. Plausible explanations for much lower virus detection rate than previously reported include improved personal hygiene and precautionary measures taken during respiratory tract infections in the immediate post-severe acute respiratory syndrome period together with a significant contribution of other adverse factors like environmental air pollution. We conclude that not all viral infections in children with asthma lead to an asthma exacerbation

  5. Lung clearance index in cystic fibrosis subjects treated for pulmonary exacerbations.

    PubMed

    Sonneveld, Nicole; Stanojevic, Sanja; Amin, Reshma; Aurora, Paul; Davies, Jane; Elborn, J Stuart; Horsley, Alex; Latzin, Philipp; O'Neill, Katherine; Robinson, Paul; Scrase, Emma; Selvadurai, Hiran; Subbarao, Padmaja; Welsh, Liam; Yammine, Sophie; Ratjen, Felix

    2015-10-01

    Pulmonary exacerbations are important clinical events for cystic fibrosis (CF) patients. Studies assessing the ability of the lung clearance index (LCI) to detect treatment response for pulmonary exacerbations have yielded heterogeneous results. Here, we conduct a retrospective analysis of pooled LCI data to assess treatment with intravenous antibiotics for pulmonary exacerbations and to understand factors explaining the heterogeneous response.A systematic literature search was performed to identify prospective observational studies. Factors predicting the relative change in LCI and spirometry were evaluated while adjusting for within-study clustering.Six previously reported studies and one unpublished study, which included 176 pulmonary exacerbations in both paediatric and adult patients, were included. Overall, LCI significantly decreased by 0.40 units (95% CI -0.60- -0.19, p=0.004) or 2.5% following treatment. The relative change in LCI was significantly correlated with the relative change in forced expiratory volume in 1 s (FEV1), but results were discordant in 42.5% of subjects (80 out of 188). Higher (worse) baseline LCI was associated with a greater improvement in LCI (slope: -0.9%, 95% CI -1.0- -0.4%).LCI response to therapy for pulmonary exacerbations is heterogeneous in CF patients; the overall effect size is small and results are often discordant with FEV1.

  6. Altered gene expression in T-cell receptor signalling in peripheral blood leucocytes in acute coronary syndrome predicts secondary coronary events

    PubMed Central

    Takashima, Shin-ichiro; Usui, Soichiro; Kurokawa, Keisuke; Kitano, Teppei; Kato, Takeshi; Murai, Hisayoshi; Furusho, Hiroshi; Oda, Hiroyuki; Maruyama, Michiro; Nagata, Yoshiki; Usuda, Kazuo; Kubota, Koji; Takeshita, Yumie; Sakai, Yoshio; Honda, Masao; Kaneko, Shuichi; Takamura, Masayuki

    2016-01-01

    Objective Comprehensive profiling of gene expression in peripheral blood leucocytes (PBLs) in patients with acute coronary syndrome (ACS) as a prognosticator is needed. We explored the specific profile of gene expression in PBLs in ACS for long-term risk stratification. Methods 30 patients with ACS who underwent primary percutaneous coronary intervention (PCI) and 15 age-matched adults who participated in medical check-ups were enrolled from three centres. Peripheral blood samples were collected to extract RNA for microarray analyses. Results During the 5-year follow-up, 36% of this cohort developed the expected non-fatal coronary events (NFEs) of target lesion revascularisation (TLR) and PCI for a de novo lesion. Class comparison analysis (p<0.005) demonstrated that 83 genes among 7785 prefiltered genes (41 upregulated vs 42 downregulated genes) were extracted to classify the patients according to the occurrence of NFE. Pathway analysis based on gene ontology revealed that the NFEs were associated with altered gene expression regarding the T-cell receptor signalling pathway in ACS. Univariate t test showed that the expression level of death-associated protein kinase1 (DAPK1), known to regulate inflammation, was the most significantly negatively regulated gene in the event group (0.61-fold, p<0.0005). Kaplan-Meier curve analysis and multivariate analysis adjusted for baseline characteristics or clinical biomarkers demonstrated that lower DAPK1 expression in PBL emerged as an independent risk factor for the NFEs (HR: 8.73; CI 1.05 to 72.8, p=0.045). Conclusions Altered gene expression in T-cell receptor signalling in PBL in ACS could be a prognosticator for secondary coronary events. Trial registration number UMIN000001932; Results. PMID:27403330

  7. Association of Lower Fractional Flow Reserve Values With Higher Risk of Adverse Cardiac Events for Lesions Deferred Revascularization Among Patients With Acute Coronary Syndrome

    PubMed Central

    Masrani Mehta, Shriti; Depta, Jeremiah P; Novak, Eric; Patel, Jayendrakumar S; Patel, Yogesh; Raymer, David; Facey, Gabrielle; Zajarias, Alan; Lasala, John M; Singh, Jasvindar; Bach, Richard G; Kurz, Howard I

    2015-01-01

    Background The safety of deferring revascularization based on fractional flow reserve (FFR) during acute coronary syndrome (ACS) is unclear. We evaluated the association of FFR and adverse cardiac events among patients with coronary lesions deferred revascularization based on FFR in the setting of ACS versus non-ACS. Methods and Results The study population (674 patients; 816 lesions) was divided into ACS (n=334) and non-ACS (n=340) groups based on the diagnosis when revascularization was deferred based on FFR values >0.80 between October 2002 and July 2010. The association and interaction between FFR and clinical outcomes was evaluated using Cox proportional hazards models within each group (mean follow-up of 4.5±2.1 years). Subsequent revascularization of a deferred lesion was classified as a deferred lesion intervention (DLI), whereas the composite of DLI or myocardial infarction (MI) attributed to a deferred lesion was designated as deferred lesion failure (DLF). In the non-ACS group, lower FFR values were not associated with any increase in adverse cardiac events. In the ACS group, every 0.01 decrease in FFR was associated with a significantly higher rate of cardiovascular death, MI, or DLI (hazard ratio [HR], 1.08; 95% confidence interval [CI], 1.03 to 1.12), MI or DLI (HR, 1.09; 95% CI: 1.04 to 1.14), DLF (HR, 1.12; 95% CI, 1.06 to 1.18), MI (HR, 1.07; 95% CI, 1.00 to 1.14), and DLI (HR, 1.12; 95% CI, 1.06 to 1.18). Conclusion Lower FFR values among ACS patients with coronary lesions deferred revascularization based on FFR are associated with a significantly higher rate of adverse cardiac events. This association was not observed in non-ACS patients. PMID:26289346

  8. PTEN permits acute increases in D3-phosphoinositide levels following TCR stimulation but inhibits distal signaling events by reducing the basal activity of Akt.

    PubMed

    Seminario, Maria-Cristina; Precht, Patricia; Bunnell, Stephen C; Warren, Sarah E; Morris, Christa M; Taub, Dennis; Wange, Ronald L

    2004-11-01

    Phosphoinositide 3-kinase (PI3K) is important in TCR signaling. PI3K generates phosphatidylinositol 3, 4, 5-trisphosphate (PI-3,4,5-P3), which regulates membrane localization and/or activity of multiple signaling proteins. PTEN (phosphatase and tensin homologue deleted on chromosome 10) opposes PI3K, reversing this reaction. Maintaining the balance between these two enzymes is important for normal T cell function. Here we use the PTEN-null Jurkat T cell line to address the role of PTEN in modulating proximal and distal TCR-signaling events. PTEN expression at levels that restored low basal Akt phosphorylation (an indicator of PI-3,4,5-P3 levels), but which were not themselves cytotoxic, had minimal effect on TCR-stimulated activation of phospholipase Cgamma1 and Ca2+ flux, but reduced the duration of extracellular signal-regulated kinase (Erk) activation. Distal signaling events, including nuclear factor of activated T cells (NFAT) activation, CD69 expression and IL-2 production, were all inhibited by PTEN expression. Notably, PTEN did not block TCR-stimulated PI-3,4,5-P3 accumulation. The effect of PTEN on distal TCR signaling events was strongly correlated with the loss of the constitutive Akt activation and glycogen synthase kinase-3 (GSK3) inhibition that is typical of Jurkat cells, and could be reversed by expression of activated Akt or pharmacologic inhibition of GSK3. These results suggest that PTEN acts in T cells primarily to control basal PI-3,4,5-P3 levels, rather than opposing PI3K acutely during TCR stimulation.

  9. Immunological profiling in chronic rhinosinusitis with nasal polyps reveals distinct VEGF and GMCSF signatures during symptomatic exacerbations

    PubMed Central

    Divekar, Rohit D.; Samant, Shefali; Rank, Matthew A.; Hagan, John; Lal, Devyani; O’Brien, Erin K.; Kita, Hirohito

    2015-01-01

    Background The mechanisms and immune pathways associated with chronic rhinosinusitis (CRS) are not fully understood. Immunological changes during acute exacerbation of CRS may provide valuable clues to the pathogenesis and perpetuation of the disease. Objective To characterize local and systemic immune responses associated with acute worsening of sinonasal symptoms during exacerbation in CRS with nasal polyps (CRSwNP) compared to controls. Methods This was a noninterventional prospective study of individuals with CRSwNP and normal controls. Subjects underwent a baseline visit with collection of nasal secretions, nasal washes, and serum specimens. Within 3 days of acute worsening of sinonasal symptoms, subjects underwent a study visit, followed by a post-visit 2 weeks later. The Sinonasal Outcome Test-22 (SNOT-22) scores and immunological parameters in the specimens were analyzed using a novel, unsupervised learning method and by conventional univariate analysis. Results Both CRSwNP patients and control subjects showed a significant increase in SNOT-22 scores during acute exacerbation. Increased nasal levels of IL-6, IL-5, and eosinophil major basic protein were observed in CRSwNP patients. A network analysis of serum specimens revealed changes in a set of immunological parameters, which are distinctly associated with CRSwNP but not with controls. In particular, systemic increases in VEGF and GM-CSF levels were notable and were validated by a conventional analysis. Conclusions CRSwNP patients demonstrate distinct immunological changes locally and systemically during acute exacerbation. Growth factors VEGF and GM-CSF may be involved in the immunopathogenesis of subjects with CRS and nasal polyps experiencing exacerbation. PMID:25429844

  10. The Effects of Acute Dopamine Precursor Depletion on the Cognitive Control Functions of Performance Monitoring and Conflict Processing: An Event-Related Potential (ERP) Study

    PubMed Central

    Primosch, Mark; Leyton, Marco; Steffensen, Scott C.

    2015-01-01

    Studies using medications and psychiatric populations implicate dopamine in cognitive control and performance monitoring processes. However, side effects associated with medication or studying psychiatric groups may confound the relationship between dopamine and cognitive control. To circumvent such possibilities, we utilized a randomized, double-blind, placebo-controlled, within-subjects design wherein participants were administered a nutritionally-balanced amino acid mixture (BAL) and an amino acid mixture deficient in the dopamine precursors tyrosine (TYR) and phenylalanine (PHE) on two separate occasions. Order of sessions was randomly assigned. Cognitive control and performance monitoring were assessed using response times (RT), error rates, the N450, an event-related potential (ERP) index of conflict monitoring, the conflict slow potential (conflict SP), an ERP index of conflict resolution, and the error-related negativity (ERN) and error positivity (Pe), ERPs associated with performance monitoring. Participants were twelve males who completed a Stroop color-word task while ERPs were collected four hours following acute PHE and TYR depletion (APTD) or balanced (BAL) mixture ingestion in two separate sessions. N450 and conflict SP ERP amplitudes significantly differentiated congruent from incongruent trials, but did not differ as a function of APTD or BAL mixture ingestion. Similarly, ERN and Pe amplitudes showed significant differences between error and correct trials that were not different between APTD and BAL conditions. Findings indicate that acute dopamine precursor depletion does not significantly alter cognitive control and performance monitoring ERPs. Current results do not preclude the role of dopamine in these processes, but suggest that multiple methods for dopamine-related hypothesis testing are needed. PMID:26492082

  11. Promoting engagement by patients and families to reduce adverse events in acute care settings: a systematic review

    PubMed Central

    Berger, Zackary; Flickinger, Tabor E; Pfoh, Elizabeth; Martinez, Kathryn A; Dy, Sydney M

    2014-01-01

    Introduction Patient-centeredness is central to healthcare. Hospitals should address patients’ unique needs to improve safety and quality. Patient engagement in healthcare, which may help prevent adverse events, can be approached as an independent patient safety practice (PSP) or as part of a multifactorial PSP. Objectives This review examines how interventions encouraging this engagement have been implemented in controlled trials. Methods We searched Medline, CINAHL, Embase and Cochrane from 2000 to 2012 for English language studies in hospital settings with prospective controlled designs, addressing the effectiveness or implementation of patient/family engagement in PSPs. We separately reviewed interventions implemented as part of selected broader PSPs by way of example: hand hygiene, ventilator-associated pneumonia, rapid response systems and care transitions. Results Six articles met the inclusion criteria for effectiveness with a primary focus on patient engagement. We identified 12 studies implementing patient engagement as an aspect of selected broader PSPs. A number of studies relied on patients’ possible function as a reporter of error to healthcare workers and patients as a source of reminders regarding safety behaviours, while others relied on direct activation of patients or families. Definitions of patient and family engagement were lacking, as well as evidence regarding the types of patients who might feel comfortable engaging with providers, and in what contexts. Conclusions While patient engagement in safety is appealing, there is insufficient high-quality evidence informing real-world implementation. Further work should evaluate the effectiveness of interventions on patient and family engagement and clarify the added benefit of incorporating engagement in multifaceted approaches to improve patient safety endpoints. In addition, strategies to assess and overcome barriers to patients’ willingness to actively engage in their care should be

  12. Immune activation and viral burden in acute disease induced by simian immunodeficiency virus SIVsmmPBj14: correlation between in vitro and in vivo events.

    PubMed Central

    Schwiebert, R; Fultz, P N

    1994-01-01

    The simian immunodeficiency virus SIVsmmPBj14 (SIV-PBj14) is an atypical lentivirus that causes acute disease and death in pig-tailed macaques and in vitro replicates efficiently in resting macaque lymphocytes and activates and induces proliferation of lymphocytes. The present study was conducted to test the hypothesis that production of large quantities of SIV-PBj14 induces widespread immune activation and elaboration of cytokines which lead directly to the death of infected pig-tailed macaques. Following intravenous inoculation of pig-tailed macaques with SIV-PBj14, acute disease developed and was characterized by high levels of plasma viremia, p27gag antigenemia, tumor necrosis factor alpha, and interleukin-6 (IL-6). All animals died within 10 days of infection, at which time some animals had as many as 100% CD4+ cells in the periphery and lymphoid tissues infected. During the last few days before death, titers of infectious virus in blood increased as much as 10(5)-fold. By using dual-label immunofluorescence assays for detection of cell surface activation markers, both CD4+ and CD8+ lymphocytes were shown to express the IL-2 and transferrin receptors following either in vivo or in vitro infection with SIV-PBj14. Furthermore, in vitro infection of quiescent macaque lymphocytes by SIV-PBj14 was accompanied by proliferation of both CD4+ and CD8+ lymphocyte subsets, as measured by incorporation of [3H]thymidine. Increases in numbers of activated lymphocytes and levels of proinflammatory cytokines in plasma coincided with increased amounts of detectable virus in vivo. Clinical signs of disease and pathologic findings were most consistent with death from a shock-like syndrome, in which acute-phase inflammatory cytokines are known to play a major role. Tumor necrosis factor alpha, IL-2, and IL-6 were detected in some cultures infected with SIV-PBj14, but this finding was not consistent. When cytokines were detected, their concentrations were essentially no different

  13. Exacerbation rate, health status and mortality in COPD – a review of potential interventions

    PubMed Central

    Seemungal, Terence AR; Hurst, John R; Wedzicha, Jadwiga A

    2009-01-01

    COPD is prevalent in Western society and its incidence is rising in the developing world. Acute exacerbations of COPD, about 50% of which are unreported, lead to deterioration in quality of life and contribute significantly to disease burden. Quality of life deteriorates with time; thus, most of the health burden occurs in more severe disease. COPD severity and frequent and more severe exacerbations are all related to an increased risk of mortality. Inhaled corticosteroids (ICS) have similar effects on quality of life but ICS/long-acting bronchodilator combinations and the long-acting antimuscarinic tiotropium all improve health status and exacerbation rates and are likely to have an effect on mortality but perhaps only with prolonged use. Erythromycin has been shown to decrease the rate of COPD exacerbations. Pulmonary rehabilitation and regular physical activity are indicated in all severities of COPD and improve quality of life. Noninvasive ventilation is associated with improved quality of life. Long-term oxygen therapy improves mortality but only in hypoxic COPD patients. The choice of an inhaler device is a key component of COPD therapy and this requires more attention from physicians than perhaps we are aware of. Disease management programs, characterized as they are by patient centeredness, improve quality of life and decrease hospitalization rates. Most outcomes in COPD can be modified by interventions and these are well tolerated and have acceptable safety profiles. PMID:19554195

  14. Treatment of patients with COPD and recurrent exacerbations: the role of infection and inflammation.

    PubMed

    Santos, Salud; Marin, Alicia; Serra-Batlles, Joan; de la Rosa, David; Solanes, Ingrid; Pomares, Xavier; López-Sánchez, Marta; Muñoz-Esquerre, Mariana; Miravitlles, Marc

    2016-01-01

    Exacerbations of COPD represent an important medical and health care problem. Certain susceptible patients suffer recurrent exacerbations and as a consequence have a poorer prognosis. The effects of bronchial infection, either acute or chronic, and of the inflammation characteristic of the disease itself raise the question of the possible role of antibiotics and anti-inflammatory agents in modulating the course of the disease. However, clinical guidelines base their recommendations on clinical trials that usually exclude more severe patients and patients with more comorbidities, and thus often fail to reflect the reality of clinicians attending more severe patients. In order to discuss aspects of clinical practice of relevance to pulmonologists in the treatment and prevention of recurrent exacerbations in patients with severe COPD, a panel discussion was organized involving expert pulmonologists who devote most of their professional activity to day hospital care. This article summarizes the scientific evidence currently available and the debate generated in relation to the following aspects: bacterial and viral infections, chronic bronchial infection and its treatment with cyclic oral or inhaled antibiotics, inflammatory mechanisms and their treatment, and the role of computerized tomography as a diagnostic tool in patients with severe COPD and frequent exacerbations.

  15. Treatment of patients with COPD and recurrent exacerbations: the role of infection and inflammation

    PubMed Central

    Santos, Salud; Marin, Alicia; Serra-Batlles, Joan; de la Rosa, David; Solanes, Ingrid; Pomares, Xavier; López-Sánchez, Marta; Muñoz-Esquerre, Mariana; Miravitlles, Marc

    2016-01-01

    Exacerbations of COPD represent an important medical and health care problem. Certain susceptible patients suffer recurrent exacerbations and as a consequence have a poorer prognosis. The effects of bronchial infection, either acute or chronic, and of the inflammation characteristic of the disease itself raise the question of the possible role of antibiotics and anti-inflammatory agents in modulating the course of the disease. However, clinical guidelines base their recommendations on clinical trials that usually exclude more severe patients and patients with more comorbidities, and thus often fail to reflect the reality of clinicians attending more severe patients. In order to discuss aspects of clinical practice of relevance to pulmonologists in the treatment and prevention of recurrent exacerbations in patients with severe COPD, a panel discussion was organized involving expert pulmonologists who devote most of their professional activity to day hospital care. This article summarizes the scientific evidence currently available and the debate generated in relation to the following aspects: bacterial and viral infections, chronic bronchial infection and its treatment with cyclic oral or inhaled antibiotics, inflammatory mechanisms and their treatment, and the role of computerized tomography as a diagnostic tool in patients with severe COPD and frequent exacerbations. PMID:27042040

  16. Influence of gender on the risk of death and adverse events in patients with acute myocardial infarction undergoing pharmacoinvasive strategy.

    PubMed

    Lanaro, Eduardo; Caixeta, Adriano; Soares, Juliana A; Alves, Cláudia Maria Rodrigues; Barbosa, Adriano Henrique Pereira; Souza, José Augusto Marcondes; Sousa, José Marconi Almeida; Amaral, Amaury; Ferreira, Guilherme M; Moreno, Antônio Célio; Júnior, Iran Gonçalves; Stefanini, Edson; Carvalho, Antônio Carlos

    2014-11-01

    Pharmacoinvasive treatment is an acceptable alternative for patients with ST-segment elevation myocardial infarction (STEMI) in developing countries. The present study evaluated the influence of gender on the risks of death and major adverse cardiovascular events (MACE) in this population. Seven municipal emergency rooms and the Emergency Mobile Healthcare Service in São Paulo treated STEMI patients with tenecteplase. The patients were subsequently transferred to a tertiary teaching hospital for early (<24 h) coronary angiography. A total of 469 patients were evaluated [329 men (70.1%)]. Compared to men, women had more advanced age (60.2 ± 12.3 vs. 56.5 ± 11 years; p = 0.002); lower body mass index (BMI; 25.85 ± 5.07 vs. 27.04 ± 4.26 kg/m2; p = 0.009); higher rates of hypertension (70.7 vs. 59.3%, p = 0.02); higher incidence of hypothyroidism (20.0 vs. 5.5%; p < 0.001), chronic renal failure (10.0 vs. 8.8%; p = 0.68), peripheral vascular disease (PVD; 19.3 vs. 4.3%; p = 0.03), and previous history of stroke (6.4 vs. 1.3%; p = 0.13); and higher thrombolysis in myocardial infarction risk scores (40.0 vs. 23.7%; p < 0.001). The overall in-hospital mortality and MACE rates for women versus men were 9.3 versus 4.9% (p = 0.07) and 12.9 versus 7.9% (p = 0.09), respectively. By multivariate analysis, diabetes (OR 4.15; 95% CI 1.86-9.25; p = 0.001), previous stroke (OR 4.81; 95% CI 1.49-15.52; p = 0.009), and hypothyroidism (OR 3.75; 95% CI 1.44-9.81; p = 0.007), were independent predictors of mortality, whereas diabetes (OR 2.05; 95% CI 1.03-4.06; p = 0.04), PVD (OR 2.38; 95% CI 0.88-6.43; p = 0.08), were predictors of MACE. In STEMI patients undergoing pharmacoinvasive strategy, mortality and MACE rates were twice as high in women; however, this was due to a higher prevalence of risk factors and not gender itself. PMID:24671733

  17. Exacerbation of pulmonary sarcoidosis after liver transplantation.

    PubMed

    Shibolet, Oren; Kalish, Yossi; Wolf, Dana; Pappo, Orit; Laxer, Uri; Berkman, Neville; Shaham, Dorit; Ashur, Yaffa; Ilan, Yaron

    2002-10-01

    Patients with hepatic sarcoidosis rarely require orthotopic liver transplantation (OLT). Progression of granulomatous activity involving other organs after OLT has rarely been described. We describe a 32-year-old woman who underwent liver transplantation for sarcoidosis-associated end-stage liver disease. She presented 4 years later with shortness of breath, hilar lymphadenopathy, and interstitial lung abnormalities. Liver functions were normal. Open lung biopsy results revealed granulomata compatible with sarcoidosis. The patient made a complete recovery after corticosteroid treatment. To the best of our knowledge, this is a first description of severe exacerbation of pulmonary sarcoidosis in an immunosuppressed patient who underwent liver transplantation for sarcoidosis-associated liver disease.

  18. A platelet P-selectin test predicts adverse cardiovascular events in patients with acute coronary syndromes treated with aspirin and clopidogrel.

    PubMed

    Thomas, Mark R; Wijeyeratne, Yanushi D; May, Jane A; Johnson, Andrew; Heptinstall, Stan; Fox, Susan C

    2014-01-01

    There is wide variation in response to antiplatelet therapy and high on-treatment platelet reactivity is associated with adverse cardiovascular events. The objective here was to determine whether the results of a novel strategy for assessing platelet reactivity (based on P-selectin measurement) are associated with clinical outcomes in patients with acute coronary syndromes (ACS). This was a prospective cohort study of 100 ACS patients taking aspirin and clopidogrel. P-selectin tests designed to assess response to P2Y12 antagonists or aspirin were performed alongside light transmission aggregometry. For the P2Y12 P-selectin test, an optimal cutoff for high platelet reactivity was determined by receiver operating characteristic (ROC) curve analysis. Patients were divided into two cohorts based on this value: patients with (n = 42) or without (n = 58) high platelet reactivity. The primary endpoint was defined as the composite of cardiovascular death, myocardial infarction and stent thrombosis. After 12 months, the primary endpoint occurred in 12 patients. ROC curve analysis determined that the P2Y12 P-selectin test results were predictive of the primary endpoint (area under curve = 0.69, p = 0.046). The primary endpoint occurred more frequently in patients with high on-treatment platelet reactivity compared to those without (21.4% vs. 5.2%; hazard ratio (HR) 4.14; p = 0.026). The P2Y12 P-selectin test results correlated with light transmission aggregometry (Spearman p < 0.0001). Using the Aspirin P-selectin test, only two patients demonstrated high on-treatment platelet reactivity. This study suggests that a P2Y12 P-selectin test is capable of detecting high on-treatment platelet reactivity, which is associated with subsequent cardiovascular events.

  19. Inflammatory cytokines imbalance in the very early phase of acute coronary syndrome: correlations with angiographic findings and in-hospital events.

    PubMed

    Brunetti, Natale Daniele; Munno, Irene; Pellegrino, Pier Luigi; Ruggero, Vincenzo; Correale, Michele; De Gennaro, Luisa; Cuculo, Andrea; Campanale, Erasmo Giulio; Di Biase, Matteo

    2011-02-01

    The aim of this study is to investigate the release of some inflammatory cytokines (Cks) during the very early phase (first 24 h) of acute coronary syndrome (ACS). Twenty-six consecutive subjects admitted to coronary care unit with ACS underwent serial blood sampling in order to evaluate concentrations of interleukin (IL)-2, IL-10, IL-18, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ. Blood samples were taken within 6 h after onset of chest pain (T₀), at 12 h (T₁), and at 24 h (T₂). Patients were thus divided into four groups comparing pro-inflammatory Ck release (IL-2, TNF-α, and IFN-γ) and anti-inflammatory activity (IL-10). Clinical features, risk factors, incidence of adverse events, and coronary angiography findings were compared with Ck activation. Ck levels were significantly increased if compared with baseline. Subjects with marked inflammatory response showed a higher incidence of left anterior descending coronary disease (IL-2, p < 0.001; TNF-α and IFN-γ, p < 0.05) and more often incurred early complications (IL-2, p < 0.05; IFN-γ, p < 0.001). A correlation was detectable between IL-18 levels and myocardial enzyme release (creatine kinase, r = 0.47; lactate dehydrogenase, r = 0.54; troponin I, r = 0.58; p < 0.05). TNF-α levels were associated with a worse prognosis at follow-up (Log rank, p < 0.05). A Ck activation characterizes the early phase of ACS. Early inflammatory reaction seems to correlate with coronary disease and adverse events.

  20. A pilot study of prognostic value of non-invasive cardiac parameters for major adverse cardiac events in patients with acute coronary syndrome treated with percutaneous coronary intervention

    PubMed Central

    Yuan, Min-Jie; Pan, Ye-Sheng; Hu, Wei-Guo; Lu, Zhi-Gang; Zhang, Qing-Yong; Huang, Dong; Huang, Xiao-Li; Wei, Meng; Li, Jing-Bo

    2015-01-01

    The objective of this study was to determine the combination of left ventricular ejection fraction (LVEF) and individual electrocardiographic parameters related to abnormal depolarization/repolarization or baroreceptor sensitivity that had the best predictive value for major adverse cardiac events (MACE) in patients with acute coronary syndrome (ACS). Patients with ACS who underwent coronary angiography and percutaneous coronary intervention (PCI) were included in this prospective study. Ventricular late potential (VLP), heart rate turbulence (HRT), heart rate variability (HRV), and T wave alternans (TWA) parameters were measured using 24 h Holter monitoring 2-4 weeks after onset of ACS. Initial and follow-up LVEF was measured by ultrasound. Patients were followed for at least 6 months to record the occurrence of MACE. Models using combinations of the individual independent prognostic factors found by multivariate analysis were then constructed to use for estimation of risk of MACE. In multivariate analysis, VLP measured as QRS duration, HRV measured as standard deviation of normal RR intervals, and followup LVEF, but none of the other parameters studied, were independent risk factors for MACE. Areas under ROC curve (AUCs) for combinations of 2 or all 3 factors ranged from 0.73 to 0.76. Combinations of any of the three independent risk factors for MACE in ACS patients with PCI improved prediction and, because these risk factors were obtained non-invasively, may have future clinical usefulness. PMID:26885226

  1. The Modification Effect of Influenza Vaccine on Prognostic Indicators for Cardiovascular Events after Acute Coronary Syndrome: Observations from an Influenza Vaccination Trial.

    PubMed

    Sribhutorn, Apirak; Phrommintikul, Arintaya; Wongcharoen, Wanwarang; Chaikledkaew, Usa; Eakanunkul, Suntara; Sukonthasarn, Apichard

    2016-01-01

    Introduction. The prognosis of acute coronary syndrome (ACS) patients has been improved with several treatments such as antithrombotics, beta-blockers, and angiotensin-converting enzyme inhibitors (ACEI) as well as coronary revascularization. Influenza vaccination has been shown to reduce adverse outcomes in ACS, but no information exists regarding the interaction of other treatments. Methods. This study included 439 ACS patients from Phrommintikul et al. A single dose of inactivated influenza vaccine was given by intramuscular injection in the vaccination group. The cardiovascular outcomes were described as major cardiovascular events (MACEs) which included mortality, hospitalization due to ACS, and hospitalization due to heart failure (HF). The stratified and multivariable Cox's regression analysis was performed. Results. The stratified Cox's analysis by influenza vaccination for each cardiovascular outcome and discrimination of hazard ratios showed that beta-blockers had an interaction with influenza vaccination. Moreover, the multivariable hazard ratios disclosed that influenza vaccine is associated with a significant reduction of hospitalization due to HF in patients who received beta-blockers (HR = 0.05, 95% CI = 0.004-0.71, P = 0.027), after being adjusted for prognostic indicators (sex, dyslipidemia, serum creatinine, and left ventricular ejection fraction). Conclusions. The influenza vaccine was shown to significantly modify the effect of beta-blockers in ACS patients and to reduce the hospitalization due to HF. However, further study of a larger population and benefits to HF patients should be investigated. PMID:27200206

  2. Usefulness of Beta2-Microglobulin as a Predictor of All-Cause and Nonculprit Lesion-Related Cardiovascular Events in Acute Coronary Syndromes (from the PROSPECT Study).

    PubMed

    Möckel, Martin; Muller, Reinhold; Searle, Julia; Slagman, Anna; De Bruyne, Bernard; Serruys, Patrick; Weisz, Giora; Xu, Ke; Holert, Fabian; Müller, Christian; Maehara, Akiko; Stone, Gregg W

    2015-10-01

    In the Providing Regional Observations to Study Predictors of Events in the Coronary Tree (PROSPECT) study, plaque burden, plaque composition, and minimal luminal area were associated with an increased risk of adverse cardiovascular events arising from untreated atherosclerotic lesions (vulnerable plaques) in patients with acute coronary syndromes (ACS). We sought to evaluate the utility of biomarker profiling and clinical risk factors to predict 3-year all-cause and nonculprit lesion-related major adverse cardiac events (MACEs). Of 697 patients who underwent successful percutaneous coronary intervention (PCI) for ACS, an array of 28 baseline biomarkers was analyzed. Median follow-up was 3.4 years. Beta2-microglobulin displayed the strongest predictive power of all variables assessed for all-cause and nonculprit lesion-related MACE. In a classification and regression tree analysis, patients with beta2-microglobulin >1.92 mg/L had an estimated 28.7% 3-year incidence of all-cause MACE; C-peptide <1.32 ng/ml was associated with a further increase in MACE to 51.2%. In a classification and regression tree analysis for untreated nonculprit lesion-related MACE, beta2-microglobulin >1.92 mg/L identified a cohort with a 3-year rate of 18.5%, and C-peptide <2.22 ng/ml was associated with a further increase to 25.5%. By multivariable analysis, beta2-microglobulin was the strongest predictor of all-cause and nonculprit MACE during follow-up. High-density lipoprotein (HDL), transferrin, and history of angina pectoris were also independent predictors of all-cause MACE, and HDL was an independent predictor of nonculprit MACE. In conclusion, in the PROSPECT study, beta2-microglobulin strongly predicted all-cause and nonculprit lesion-related MACE within 3 years after PCI in ACS. C-peptide and HDL provided further risk stratification to identify angiographically mild nonculprit lesions prone to future MACE.

  3. Usefulness of Beta2-Microglobulin as a Predictor of All-Cause and Nonculprit Lesion-Related Cardiovascular Events in Acute Coronary Syndromes (from the PROSPECT Study).

    PubMed

    Möckel, Martin; Muller, Reinhold; Searle, Julia; Slagman, Anna; De Bruyne, Bernard; Serruys, Patrick; Weisz, Giora; Xu, Ke; Holert, Fabian; Müller, Christian; Maehara, Akiko; Stone, Gregg W

    2015-10-01

    In the Providing Regional Observations to Study Predictors of Events in the Coronary Tree (PROSPECT) study, plaque burden, plaque composition, and minimal luminal area were associated with an increased risk of adverse cardiovascular events arising from untreated atherosclerotic lesions (vulnerable plaques) in patients with acute coronary syndromes (ACS). We sought to evaluate the utility of biomarker profiling and clinical risk factors to predict 3-year all-cause and nonculprit lesion-related major adverse cardiac events (MACEs). Of 697 patients who underwent successful percutaneous coronary intervention (PCI) for ACS, an array of 28 baseline biomarkers was analyzed. Median follow-up was 3.4 years. Beta2-microglobulin displayed the strongest predictive power of all variables assessed for all-cause and nonculprit lesion-related MACE. In a classification and regression tree analysis, patients with beta2-microglobulin >1.92 mg/L had an estimated 28.7% 3-year incidence of all-cause MACE; C-peptide <1.32 ng/ml was associated with a further increase in MACE to 51.2%. In a classification and regression tree analysis for untreated nonculprit lesion-related MACE, beta2-microglobulin >1.92 mg/L identified a cohort with a 3-year rate of 18.5%, and C-peptide <2.22 ng/ml was associated with a further increase to 25.5%. By multivariable analysis, beta2-microglobulin was the strongest predictor of all-cause and nonculprit MACE during follow-up. High-density lipoprotein (HDL), transferrin, and history of angina pectoris were also independent predictors of all-cause MACE, and HDL was an independent predictor of nonculprit MACE. In conclusion, in the PROSPECT study, beta2-microglobulin strongly predicted all-cause and nonculprit lesion-related MACE within 3 years after PCI in ACS. C-peptide and HDL provided further risk stratification to identify angiographically mild nonculprit lesions prone to future MACE. PMID:26254706

  4. Action plans for COPD: strategies to manage exacerbations and improve outcomes

    PubMed Central

    Jalota, Leena; Jain, Vipul V

    2016-01-01

    COPD is the third-largest killer in the world, and certainly takes a toll on the health care system. Recurrent COPD exacerbations accelerate lung-function decline, worsen mortality, and consume over US$50 billion in health care spending annually. This has led to a tide of payment reforms eliciting interest in strategies reducing preventable COPD exacerbations. In this review, we analyze and discuss the evidence for COPD action plan-based self-management strategies. Although action plans may provide stabilization of acute symptomatology, there are several limitations. These include patient-centered attributes, such as comprehension and adherence, and nonadherence of health care providers to established guidelines. While no single intervention can be expected independently to translate into improved outcomes, structured together within a comprehensive integrated disease-management program, they may provide a robust paradigm. PMID:27330286

  5. Action plans for COPD: strategies to manage exacerbations and improve outcomes.

    PubMed

    Jalota, Leena; Jain, Vipul V

    2016-01-01

    COPD is the third-largest killer in the world, and certainly takes a toll on the health care system. Recurrent COPD exacerbations accelerate lung-function decline, worsen mortality, and consume over US$50 billion in health care spending annually. This has led to a tide of payment reforms eliciting interest in strategies reducing preventable COPD exacerbations. In this review, we analyze and discuss the evidence for COPD action plan-based self-management strategies. Although action plans may provide stabilization of acute symptomatology, there are several limitations. These include patient-centered attributes, such as comprehension and adherence, and nonadherence of health care providers to established guidelines. While no single intervention can be expected independently to translate into improved outcomes, structured together within a comprehensive integrated disease-management program, they may provide a robust paradigm. PMID:27330286

  6. COPD exacerbation care bundle improves standard of care, length of stay, and readmission rates

    PubMed Central

    Parikh, Raj; Shah, Trushil G; Tandon, Rajive

    2016-01-01

    Introduction COPD is the third leading cause of death in the world. Utilizing care bundles during acute COPD exacerbations results in fewer complications and lower costs. Our aim was to construct a COPD exacerbation care bundle and evaluate the effects on patient care. Methods We conducted a prospective analysis of 44 patients admitted with a COPD exacerbation to a single tertiary care facility. Primary outcomes included length of stay, readmission rates, and hospital costs. Secondary outcomes included patient education, pulmonologist follow-up, and timeliness of medication administration. Two cohorts were analyzed: those treated with an electronic COPD care bundle (cases; N=22) versus those treated without the care bundle (controls; N=22). Results Mean length of stay (51.2 vs 101.1 hours in controls; P-value =0.001), 30-day readmission rates (9.1% vs 54.4% in controls; P-value =0.001), and 60-day readmission rates (22.7% vs 77% in controls; P-value =0.0003) decreased in the care bundle group. Ninety-day hospital costs had a significant difference in the care bundle group (US$7,652 vs US$19,954 in controls; P-value =0.044). Secondary outcomes included a 100% rate of COPD inhaler teaching (vs 27.3% in controls; P-value <0.001), 59.1% rate of pulmonologist follow-up after discharge (vs 18.2% in controls; P-value =0.005), and a mean reduction in time to steroid administration (7.0 hours; P-value =0.015) seen in the care bundle cases. Conclusion Our significant findings coupled with the recent success of standardized algorithms in managing COPD exacerbations stress the importance of enforcing clinical guidelines that can enhance patient care. We demonstrated improved care for COPD exacerbation patients during hospitalizations, thereby decreasing morbidity and the financial burden hospitals face in regard to this increasingly prevalent disease. PMID:27042046

  7. COPD Exacerbation Biomarkers Validated Using Multiple Reaction Monitoring Mass Spectrometry

    PubMed Central

    Leung, Janice M.; Chen, Virginia; Hollander, Zsuzsanna; Dai, Darlene; Tebbutt, Scott J.; Aaron, Shawn D.; Vandemheen, Kathy L.; Rennard, Stephen I.; FitzGerald, J. Mark; Woodruff, Prescott G.; Lazarus, Stephen C.; Connett, John E.; Coxson, Harvey O.; Miller, Bruce; Borchers, Christoph; McManus, Bruce M.; Ng, Raymond T.; Sin, Don D.

    2016-01-01

    Background Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) result in considerable morbidity and mortality. However, there are no objective biomarkers to diagnose AECOPD. Methods We used multiple reaction monitoring mass spectrometry to quantify 129 distinct proteins in plasma samples from patients with COPD. This analytical approach was first performed in a biomarker cohort of patients hospitalized with AECOPD (Cohort A, n = 72). Proteins differentially expressed between AECOPD and convalescent states were chosen using a false discovery rate <0.01 and fold change >1.2. Protein selection and classifier building were performed using an elastic net logistic regression model. The performance of the biomarker panel was then tested in two independent AECOPD cohorts (Cohort B, n = 37, and Cohort C, n = 109) using leave-pair-out cross-validation methods. Results Five proteins were identified distinguishing AECOPD and convalescent states in Cohort A. Biomarker scores derived from this model were significantly higher during AECOPD than in the convalescent state in the discovery cohort (p<0.001). The receiver operating characteristic cross-validation area under the curve (CV-AUC) statistic was 0.73 in Cohort A, while in the replication cohorts the CV-AUC was 0.77 for Cohort B and 0.79 for Cohort C. Conclusions A panel of five biomarkers shows promise in distinguishing AECOPD from convalescence and may provide the basis for a clinical blood test to diagnose AECOPD. Further validation in larger cohorts is necessary for future clinical translation. PMID:27525416

  8. Impact of anemia on short-term survival in severe COPD exacerbations: a cohort study

    PubMed Central

    Ergan, Begum; Ergün, Recai

    2016-01-01

    Purpose Anemia is reported to be an independent predictor of hospitalizations and survival in COPD. However, little is known of its impact on short-term survival during severe COPD exacerbations. The primary objective of this study was to determine whether the presence of anemia increases the risk of death in acute respiratory failure due to severe COPD exacerbations. Patients and methods Consecutive patients with COPD exacerbation who were admitted to the intensive care unit with the diagnosis of acute respiratory failure and required either invasive or noninvasive ventilation (NIV) were analyzed. Results A total of 106 patients (78.3% male; median age 71 years) were included in the study; of them 22 (20.8%) needed invasive ventilation immediately and 84 (79.2%) were treated with NIV. NIV failure was observed in 38 patients. Anemia was present in 50% of patients, and 39 patients (36.8%) died during hospital stay. When compared to nonanemic patients, hospital mortality was significantly higher in the anemic group (20.8% vs 52.8%, respectively; P=0.001). Stepwise multivariate logistic regression analysis showed that presence of anemia and NIV failure were independent predictors of hospital mortality with odds ratios (95% confidence interval) of 3.99 ([1.39–11.40]; P=0.010) and 2.56 ([1.60–4.09]; P<0.001), respectively. Anemia was not associated with long-term survival in this cohort. Conclusion Anemia may be a risk factor for hospital death in severe COPD exacerbations requiring mechanical ventilatory support. PMID:27536089

  9. Acute asthma during pregnancy.

    PubMed Central

    Stenius-Aarniala, B. S.; Hedman, J.; Teramo, K. A.

    1996-01-01

    BACKGROUND: Acute asthma during pregnancy is potentially dangerous to the fetus. The aim of this study was to investigate the effect of an acute attack of asthma during pregnancy on the course of pregnancy or delivery, or the health of the newborn infant, and to identify undertreatment as a possible cause of the exacerbations. METHODS: Five hundred and four pregnant asthmatic subjects were prospectively followed and treated. The data on 47 patients with an attack of asthma during pregnancy were compared with those of 457 asthmatics with no recorded acute exacerbation and with 237 healthy parturients. RESULTS: Of 504 asthmatics, 177 patients were not initially treated with inhaled corticosteroids. Of these, 17% had an acute attack compared with only 4% of the 257 patients who had been on inhaled anti-inflammatory treatment from the start of pregnancy. There were no differences between the groups as to length of gestation, length of the third stage of labour, or amount of haemorrhage after delivery. No differences were observed between pregnancies with and without an exacerbation with regard to relative birth weight, incidence of malformations, hypoglycaemia, or need for phototherapy for jaundice during the neonatal period. CONCLUSIONS: Patients with inadequate inhaled anti-inflammatory treatment during pregnancy run a higher risk of suffering an acute attack of asthma than those treated with an anti-inflammatory agent. However, if the acute attack of asthma is relatively mild and promptly treated, it does not have a serious effect on the pregnancy, delivery, or the health of the newborn infant. PMID:8733495

  10. [Treatment of multiple sclerosis symptoms and exacerbations].

    PubMed

    Prieto González, José María

    2014-12-01

    In the last few years, there has been an explosion of new drugs acting on the clinical course of multiple sclerosis (MS) but less attention has been paid to better knowledge of the symptoms of this disease and their pathogenesis and treatment, which is essential to improve patients' quality of life. Because many patients have numerous concurrent symptoms during their clinical course, their management is complex and consequently it is important to know which symptoms are a direct result of the degenerative lesions of MS. The present article describes all the therapeutic options available for spasticity and its associated pain, paroxystic symptoms, fatigue, genitourinary disorders and sexual dysfunction, tremor, ataxia, gait disorder and cognitive impairment, with special emphasis on novel treatments. The article also defines exacerbations, how to recognize them and the available treatments, mainly oral administration of high-dose methylprednisolone and plasmapheresis. PMID:25732949

  11. Immunomodulatory treatments for aspirin exacerbated respiratory disease

    PubMed Central

    Moebus, Rachel G.

    2012-01-01

    Background: Aspirin triad is a subclass of chronic sinusitis characterized by nasal polyposis, nonallergic induced asthma, and aspirin sensitivity. Also known as Samter's triad or aspirin-exacerbated respiratory disease, aspirin triad commonly affects the adult population and is seldom found in pediatric patients. Methods: This rhinosinusitis has multiple layers of pathological process, but the ultimate predicament is caused by cysteinyl leukotrienes (cysLTs). Results: Pharmacotherapies include oral steroid, lipoxygenase inhibitor, and cysLT receptor inhibitor drugs, which can provide some relief for these patients. Conclusion: Immunomodulation via aspirin desensitization is considered when pharmacotherapy has failed. When aspirin triad is unmanageable with medical treatment alone, endoscopic sinus surgery with polypectomy can alleviate the patient's symptoms, allowing for a better response to postoperative medical management such as topical medication as well as delivery of topical medications. PMID:22487291

  12. How do patients with exacerbated chronic obstructive pulmonary disease experience care in the intensive care unit?

    PubMed Central

    Torheim, Henny; Kvangarsnes, Marit

    2014-01-01

    The aim was to gain insight into how patients with advanced chronic obstructive pulmonary disease (COPD) experience care in the acute phase. The study has a qualitative design with a phenomenological approach. The empirics consist of qualitative in-depth interviews with ten patients admitted to the intensive care units in two Norwegian hospitals. The interviews were carried out from November 2009 to June 2011. The data have been analysed through meaning condensation, in accordance with Amadeo Giorgi's four-step method. Kari Martinsen's phenomenological philosophy of nursing has inspired the study. An essential structure of the patients' experiences of care in the intensive care unit by acute COPD-exacerbation may be described as: Feelings of being trapped in a life-threatening situation in which the care system assumes control over their lives. This experience is conditioned not only by the medical treatment, but also by the entire interaction with the caregivers. The essence of the phenomenon is presented through three themes which describe the patient's lived experience: preserving the breath of life, vulnerable interactions and opportunities for better health. Acute COPD-exacerbation is a traumatic experience and the patients become particularly vulnerable when they depend on others for breathing support. The phenomenological analysis shows that the patients experience good care during breath of life preservation when the care is performed in a way that gives patients more insight into their illness and gives new opportunities for the future. PMID:24313779

  13. (n-3) Fatty acid content of red blood cells does not predict risk of future cardiovascular events following an acute coronary syndrome.

    PubMed

    Aarsetoey, Hildegunn; Pönitz, Volker; Grundt, Heidi; Staines, Harry; Harris, William S; Nilsen, Dennis W T

    2009-03-01

    A reduced risk of fatal coronary artery disease has been associated with a high intake of (n-3) fatty acids (FA) and a direct cardioprotective effect by their incorporation into myocardial cells has been suggested. Based on these observations, the omega-3 index (eicosapentaenoic acid + docosahexaenoic acid in cell membranes of RBC expressed as percent of total FA) has been suggested as a new risk marker for cardiac death. In this study, our aim was to evaluate the omega-3 index as a prognostic risk marker following hospitalization with an acute coronary syndrome (ACS). The omega-3 index was measured at admission in 460 patients with an ACS as defined by Troponin-T (TnT) > or = 0.02 microg/L. During a 2-y follow-up, recurrent myocardial infarctions (MI) (defined as TnT > 0.05 microg/L with a typical MI presentation) and cardiac and all-cause mortality were registered. Cox regression analyses were used to relate the risk of new events to the quartiles of the omega-3 index at inclusion. After correction for age, sex, previous heart disease, hypertension, diabetes, smoking, high-sensitivity C-reactive protein, brain natriuretic peptide, creatinine, total cholesterol, HDL-cholesterol, triacylglycerol, homocysteine, BMI, and medication, there was no significant reduction in risk for all-cause mortality, cardiac death, or MI with increasing values of the index. In conclusion, we could not confirm the omega-3 index as a useful prognostic risk marker following an ACS. PMID:19158216

  14. Improved Early Event-Free Survival With Imatinib in Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia: A Children's Oncology Group Study

    PubMed Central

    Schultz, Kirk R.; Bowman, W. Paul; Aledo, Alexander; Slayton, William B.; Sather, Harland; Devidas, Meenakshi; Wang, Chenguang; Davies, Stella M.; Gaynon, Paul S.; Trigg, Michael; Rutledge, Robert; Burden, Laura; Jorstad, Dean; Carroll, Andrew; Heerema, Nyla A.; Winick, Naomi; Borowitz, Michael J.; Hunger, Stephen P.; Carroll, William L.; Camitta, Bruce

    2009-01-01

    Purpose Imatinib mesylate is a targeted agent that may be used against Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL), one of the highest risk pediatric ALL groups. Patients and Methods We evaluated whether imatinib (340 mg/m2/d) with an intensive chemotherapy regimen improved outcome in children ages 1 to 21 years with Ph+ ALL (N = 92) and compared toxicities to Ph− ALL patients (N = 65) given the same chemotherapy without imatinib. Exposure to imatinib was increased progressively in five patient cohorts that received imatinib from 42 (cohort 1; n = 7) to 280 continuous days (cohort 5; n = 50) before maintenance therapy. Patients with human leukocyte antigen (HLA) –identical sibling donors underwent blood and marrow transplantation (BMT) with imatinib given for 6 months following BMT. Results Continuous imatinib exposure improved outcome in cohort 5 patients with a 3-year event-free survival (EFS) of 80% ± 11% (95% CI, 64% to 90%), more than twice historical controls (35% ± 4%; P < .0001). Three-year EFS was similar for patients in cohort 5 treated with chemotherapy plus imatinib (88% ± 11%; 95% CI, 66% to 96%) or sibling donor BMT (57% ± 22%; 95% CI, 30.4% to 76.1%). There were no significant toxicities associated with adding imatinib to intensive chemotherapy. The higher imatinib dosing in cohort 5 appears to improve survival by having an impact on the outcome of children with a higher burden of minimal residual disease after induction. Conclusion Imatinib plus intensive chemotherapy improved 3-year EFS in children and adolescents with Ph+ ALL, with no appreciable increase in toxicity. BMT plus imatinib offered no advantage over BMT alone. Additional follow-up is required to determine the impact of this treatment on long-term EFS and determine whether chemotherapy plus imatinib can replace BMT. PMID:19805687

  15. Resting heart rate associates with one-year risk of major adverse cardiovascular events in patients with acute coronary syndrome after percutaneous coronary intervention

    PubMed Central

    Wang, Shao-Li; Wang, Cheng-Long; Wang, Pei-Li; Xu, Hao; Du, Jian-Peng; Zhang, Da-Wu; Gao, Zhu-Ye; Zhang, Lei; Fu, Chang-Geng; Chen, Ke-Ji

    2015-01-01

    The study was to access the association between resting heart rate (RHR) and one-year risk of major adverse cardiovascular events (MACE) in acute coronary syndrome (ACS) patients after percutaneous coronary intervention (PCI). Patients with ACS after PCI (n = 808) were prospectively followed-up for MACE. RHR was obtained from electrocardiogram. MACE was defined as a composite of cardiac death, nonfatal recurrent myocardial infarction, ischemic-driven revascularization, and ischemic stroke. The association between RHR and one-year risk of MACE was assessed using Cox proportional hazards regression model. Compared with patients with RHR >76 bpm, the adjusted hazard ratio (AHR) was 0.51 (95% confidence intervals [CI]: 0.23–1.14; P = 0.100) for patients with RHR < 61 bpm, and 0.44 (95%CI: 0.23–0.85; P = 0.014) for those with RHR 61–76 bpm. For patients with RHR ≥ 61 bpm, an increase of 10 bpm in RHR was associated with an increase by 38.0% in the risk of MACE (AHR: 1.38; 95% CI: 1.04–1.83; P = 0.026). ACS patients after PCI with RHR >76 bpm were at higher risk of MACE during one-year follow-up compared with patients with RHR 61–76 bpm. An elevated RHR ≥ 61 bpm was associated with increased risk of one-year MACE in ACS patients. PMID:26585407

  16. Viral Profile of COPD Exacerbations According to Patients§

    PubMed Central

    Dimopoulos, G; Tsiodras, S; Lerikou, M; Chranioti, Aik; Perros, E; Anagnostopoulou, U; Karakitsos, P; Armaganidis, A

    2015-01-01

    Background : To compare the differences between elderly and non-elderly patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) due to viral infections. Methods : Patients with chronic obstructive pulmonary disease (COPD) exacerbation were recruited and classified as elderly (>65 years) and non-elderly (≤ 65 years). Sputum and oropharyngeal samples were assessed, PCR for respiratory viruses and cultures for common pathogens were performed. Results : 247 patients (median age: 69.3±9.5 years) were recruited and categorized into group A: non-elderly patients [n=81 (32.8%), median age 58±5.99] and group B: elderly patients [n=166 (67.2%), median age 74.8±4.8] years. In 133 (53.8%) patients a viral infection was identified and in 34 (13.8%) a bacterial pathogen was isolated from cultures. In 18 (7.3%) patients a double infection (bacterial+viral) was identified. In group B, the presence of cardiac failure (46.6% vs 28.3%, p<0.001), renal failure (10.5% vs 4%, p=0.03), bacterial co-infection (13.8% vs 7.4%, p=0.04), influenza vaccination rates (45.5% vs 215, p<0.001), and longer hospital stay (8.4±4.4 vs 7.5±3.2 days, p=0.02) were higher than group A. The overall rate of viral infections did not differ according to age. A trend to higher rates of infection with parainfluenza 3 [19 (20%) patients in group B vs3 (7.5%) patients in group A, p=0.04] was observed in older patients. Conclusion : No differences on the rate and type of viral infections were noted for elderly vs non elderly patients. However, they tended to have more bacterial co-infections that led to AECOPD and longer hospitalization stays compared to non-elderly patients. PMID:25741393

  17. Acute interstitial pneumonia.

    PubMed

    Bouros, D; Nicholson, A C; Polychronopoulos, V; du Bois, R M

    2000-02-01

    The term "acute interstitial pneumonia" (AIP) describes an idiopathic clinicopathological condition, characterized clinically by an interstitial lung disease causing rapid onset of respiratory failure, which is distinguishable from the other more chronic forms of interstitial pneumonia. It is synonymous with Hamman-Rich syndrome, occurring in patients without pre-existing lung disease. The histopathological findings are those of diffuse alveolar damage. AIP radiologically and physiologically resembles acute respiratory distress syndrome (ARDS) and is considered to represent the small subset of patients with idiopathic ARDS. It is frequently confused with other clinical entities characterized by rapidly progressive interstitial pneumonia, especially secondary acute interstitial pneumonia, acute exacerbations and accelerated forms of cryptogenic fibrosing alveolitis . Furthermore, many authors use the above terms, both erroneously and interchangeably. It has a grave prognosis with >70% mortality in 3 months, despite mechanical ventilation. This review aims to clarify the relative clinical and pathological issues and terminology.

  18. Metabolomics of pulmonary exacerbations reveals the personalized nature of cystic fibrosis disease

    PubMed Central

    Lim, Yan Wei; Mak, Tytus D.; Whiteson, Katrine; Conrad, Douglas; Rohwer, Forest; Dorrestein, Pieter

    2016-01-01

    Background. Cystic fibrosis (CF) is a genetic disease that results in chronic infections of the lungs. CF patients experience intermittent pulmonary exacerbations (CFPE) that are associated with poor clinical outcomes. CFPE involves an increase in disease symptoms requiring more aggressive therapy. Methods. Longitudinal sputum samples were collected from 11 patients (n = 44 samples) to assess the effect of exacerbations on the sputum metabolome using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The data was analyzed with MS/MS molecular networking and multivariate statistics. Results. The individual patient source had a larger influence on the metabolome of sputum than the clinical state (exacerbation, treatment, post-treatment, or stable). Of the 4,369 metabolites detected, 12% were unique to CFPE samples; however, the only known metabolites significantly elevated at exacerbation across the dataset were platelet activating factor (PAF) and a related monacylglycerophosphocholine lipid. Due to the personalized nature of the sputum metabolome, a single patient was followed for 4.2 years (capturing four separate exacerbation events) as a case study for the detection of personalized biomarkers with metabolomics. PAF and related lipids were significantly elevated during CFPEs of this patient and ceramide was elevated during CFPE treatment. Correlating the abundance of bacterial 16S rRNA gene amplicons to metabolomics data from the same samples during a CFPE demonstrated that antibiotics were positively correlated to Stenotrophomonas and Pseudomonas, while ceramides and other lipids were correlated with Streptococcus, Rothia, and anaerobes. Conclusions. This study identified PAF and other inflammatory lipids as potential biomarkers of CFPE, but overall, the metabolome of CF sputum was patient specific, supporting a personalized approach to molecular detection of CFPE onset. PMID:27602256

  19. Metabolomics of pulmonary exacerbations reveals the personalized nature of cystic fibrosis disease.

    PubMed

    Quinn, Robert A; Lim, Yan Wei; Mak, Tytus D; Whiteson, Katrine; Furlan, Mike; Conrad, Douglas; Rohwer, Forest; Dorrestein, Pieter

    2016-01-01

    Background. Cystic fibrosis (CF) is a genetic disease that results in chronic infections of the lungs. CF patients experience intermittent pulmonary exacerbations (CFPE) that are associated with poor clinical outcomes. CFPE involves an increase in disease symptoms requiring more aggressive therapy. Methods. Longitudinal sputum samples were collected from 11 patients (n = 44 samples) to assess the effect of exacerbations on the sputum metabolome using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The data was analyzed with MS/MS molecular networking and multivariate statistics. Results. The individual patient source had a larger influence on the metabolome of sputum than the clinical state (exacerbation, treatment, post-treatment, or stable). Of the 4,369 metabolites detected, 12% were unique to CFPE samples; however, the only known metabolites significantly elevated at exacerbation across the dataset were platelet activating factor (PAF) and a related monacylglycerophosphocholine lipid. Due to the personalized nature of the sputum metabolome, a single patient was followed for 4.2 years (capturing four separate exacerbation events) as a case study for the detection of personalized biomarkers with metabolomics. PAF and related lipids were significantly elevated during CFPEs of this patient and ceramide was elevated during CFPE treatment. Correlating the abundance of bacterial 16S rRNA gene amplicons to metabolomics data from the same samples during a CFPE demonstrated that antibiotics were positively correlated to Stenotrophomonas and Pseudomonas, while ceramides and other lipids were correlated with Streptococcus, Rothia, and anaerobes. Conclusions. This study identified PAF and other inflammatory lipids as potential biomarkers of CFPE, but overall, the metabolome of CF sputum was patient specific, supporting a personalized approach to molecular detection of CFPE onset. PMID:27602256

  20. Metabolomics of pulmonary exacerbations reveals the personalized nature of cystic fibrosis disease

    PubMed Central

    Lim, Yan Wei; Mak, Tytus D.; Whiteson, Katrine; Conrad, Douglas; Rohwer, Forest; Dorrestein, Pieter

    2016-01-01

    Background. Cystic fibrosis (CF) is a genetic disease that results in chronic infections of the lungs. CF patients experience intermittent pulmonary exacerbations (CFPE) that are associated with poor clinical outcomes. CFPE involves an increase in disease symptoms requiring more aggressive therapy. Methods. Longitudinal sputum samples were collected from 11 patients (n = 44 samples) to assess the effect of exacerbations on the sputum metabolome using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The data was analyzed with MS/MS molecular networking and multivariate statistics. Results. The individual patient source had a larger influence on the metabolome of sputum than the clinical state (exacerbation, treatment, post-treatment, or stable). Of the 4,369 metabolites detected, 12% were unique to CFPE samples; however, the only known metabolites significantly elevated at exacerbation across the dataset were platelet activating factor (PAF) and a related monacylglycerophosphocholine lipid. Due to the personalized nature of the sputum metabolome, a single patient was followed for 4.2 years (capturing four separate exacerbation events) as a case study for the detection of personalized biomarkers with metabolomics. PAF and related lipids were significantly elevated during CFPEs of this patient and ceramide was elevated during CFPE treatment. Correlating the abundance of bacterial 16S rRNA gene amplicons to metabolomics data from the same samples during a CFPE demonstrated that antibiotics were positively correlated to Stenotrophomonas and Pseudomonas, while ceramides and other lipids were correlated with Streptococcus, Rothia, and anaerobes. Conclusions. This study identified PAF and other inflammatory lipids as potential biomarkers of CFPE, but overall, the metabolome of CF sputum was patient specific, supporting a personalized approach to molecular detection of CFPE onset.

  1. Prevention of COPD exacerbations: medications and other controversies

    PubMed Central

    Lange, Peter

    2015-01-01

    Exacerbations have significant impact on the morbidity and mortality of patients with chronic obstructive pulmonary disease. Most guidelines emphasise prevention of exacerbations by treatment with long-acting bronchodilators and/or anti-inflammatory drugs. Whereas most of this treatment is evidence-based, it is clear that patients differ regarding the nature of exacerbations and are likely to benefit differently from different types of treatment. In this short review, we wish to highlight this, suggest a first step in differentiating pharmacological exacerbation prevention and call for more studies in this area. Finally, we wish to highlight that there are perhaps easier ways of achieving similar success in exacerbation prevention using nonpharmacological tools.

  2. A systematic review of acute pancreatitis as an adverse event of type 2 diabetes drugs: from hard facts to a balanced position.

    PubMed

    Giorda, C B; Nada, E; Tartaglino, B; Marafetti, L; Gnavi, R

    2014-11-01

    The question whether antidiabetes drugs can cause acute pancreatitis dates back to the 1970s. Recently, old concerns have re-emerged following claims that use of incretins, a new class of drugs for type 2 diabetes, might increase the relative risk of acute pancreatitis up to 30-fold. Given that diabetes is per se a potent risk factor for acute pancreatitis and that drug-related acute pancreatitis is rare and difficult to diagnose, we searched the medical databases for information linking acute pancreatitis and type 2 diabetes drugs. Among the biguanides, both phenformin and metformin (the latter in patients with renal insufficiency) have been cited in case reports as a potential cause of acute pancreatitis. Sulphonylureas, as both entire class and single compound (glibenclamide), have also been found in cohort studies to increase its risk. No direct link was found between pancreatic damage and therapy with metaglinide, acarbose, pramlintide or SGLT-2 inhibitors. In animal models, thiazolinediones have demonstrated proprieties to attenuate pancreatic damage, opening perspectives for their use in treating acute pancreatitis in humans. Several case reports and the US Food and Drug Administration pharmacovigilance database indicate an association between acute pancreatitis and incretins, dipeptidyl peptidase-4 (DPP-4) inhibitors, and GLP-1 receptor agonists. To date, however, a clear-cut odds ratio for this association has been reported in only one of eight pharmacoepidemiological studies. Finally, none of the intervention trials investigating these compounds, including two large randomized controlled trials with cardiovascular endpoints, confirmed the purportedly increased risk of acute pancreatitis with incretin use.

  3. Dexrazoxane exacerbates doxorubicin-induced testicular toxicity.

    PubMed

    Levi, Mattan; Tzabari, Moran; Savion, Naphtali; Stemmer, Salomon M; Shalgi, Ruth; Ben-Aharon, Irit

    2015-10-01

    Infertility induced by anti-cancer treatments pose a major concern for cancer survivors. Doxorubicin (DXR) has been previously shown to exert toxic effects on the testicular germinal epithelium. Based upon the cardioprotective traits of dexrazoxane (DEX), we studied its potential effect in reducing DXR-induced testicular toxicity. Male mice were injected with 5  mg/kg DXR, 100  mg/kg DEX, combination of both or saline (control) and sacrificed either 1, 3 or 6 months later. Testes were excised and further processed. Glutathione and apoptosis assays were performed to determine oxidative stress. Immunohistochemistry and confocal microscopy were used to study the effects of the drugs on testicular histology and on spermatogonial reserve. DXR and the combined treatment induced a striking decline in testicular weight. DEX prevented DXR-induced oxidative stress, but enhanced DXR-induced apoptosis within the testes. Furthermore, the combined treatment depleted the spermatogonial reserve after 1 month, with impaired recovery at 3 and 6 months post-treatment. This resulted in compromised sperm parameters, testicular and epididymal weights as well as significantly reduced sperm motility, all of which were more severe than those observed in DXR-treated mice. The activity of DEX in the testis may differ from its activity in cardiomyocytes. Adding DEX to DXR exacerbates DXR-induced testicular toxicity. PMID:26329125

  4. Predicting asthma exacerbations using artificial intelligence.

    PubMed

    Finkelstein, Joseph; Wood, Jeffrey

    2013-01-01

    Modern telemonitoring systems identify a serious patient deterioration when it already occurred. It would be much more beneficial if the upcoming clinical deterioration were identified ahead of time even before a patient actually experiences it. The goal of this study was to assess artificial intelligence approaches which potentially can be used in telemonitoring systems for advance prediction of changes in disease severity before they actually occur. The study dataset was based on daily self-reports submitted by 26 adult asthma patients during home telemonitoring consisting of 7001 records. Two classification algorithms were employed for building predictive models: naïve Bayesian classifier and support vector machines. Using a 7-day window, a support vector machine was able to predict asthma exacerbation to occur on the day 8 with the accuracy of 0.80, sensitivity of 0.84 and specificity of 0.80. Our study showed that methods of artificial intelligence have significant potential in developing individualized decision support for chronic disease telemonitoring systems.

  5. [Exacerbations of asthma--precipitating factors: drugs].

    PubMed

    Sanfiorenzo, C; Pipet, A

    2011-10-01

    Asthmatic exacerbations are sometimes triggered by medications, primarily the non-steroidal anti-inflammatory agents (NSAIDS) and beta-blockers. Asthma attacks induced by NSAIDS occur rapidly and can be severe. Widal syndrome is a specific disease entity whose physiopathology remains incompletely explained. Asthma is characteristically severe and steroid dependent; desensitisation with aspirin has been proposed, but this remains controversial. Beta-blockers are contra-indicated in asthma; the β1 "cardioselectivity" of some agents is not absolute, disappearing at high doses and the "partial agonists" are not better tolerated. However, certain authors have called into question the harmful effect of beta-blockade in moderate and stable asthma. More studies are needed, but the current data suggest that in some cases beta-blockers may be safe but their use requires close supervision. Other molecules can pose problems in asthmatics (dipyridamole, synthetic sex hormones and certain excipients). On the whole, there has been little innovation concerning the hazard that drugs can pose for some asthmatics. The task for the future will be to specify the physiopathology of Widal syndrome, and to clarify the categories of patients in whom beta-blockers can be safely employed as the public health consequences of cardiovascular pathologies make this an important issue for lung specialists.

  6. u-MCHC: a predictive framework for ubiquitous management of exacerbations in chronic diseases.

    PubMed

    Andriopoulou, Foteini Gr; Birkos, Konstantinos D; Lymberopoulos, Dimitrios K

    2013-01-01

    Exacerbations are crucial events in chronic diseases that require continuous management. Knowledge of the exacerbation risk enhances patient's quality of life and enables self-management and self-organizing of unscheduled doctor visits and/or hospitalization. This paper proposes a new framework for ubiquitous management of chronic diseases named u-MCHC. The proposed framework incorporates monitoring, decision-making, notification and management processes in order to deliver personalized therapeutical options and services. The delivery of services is realized by means of Next Generation Service Delivery Platform (NG-SDP). A prototype implementation of u-MCHC and its performance is demonstrated in a real world case for Chronic Obstructive Pulmonary Disease (COPD).

  7. Clinical characteristics, management and 1-year outcomes of patients with acute coronary syndrome in Iran: the Iranian Project for Assessment of Coronary Events 2 (IPACE2)

    PubMed Central

    Kassaian, Seyed Ebrahim; Masoudkabir, Farzad; Sezavar, Hashem; Mohammadi, Mohammad; Pourmoghaddas, Ali; Kojouri, Javad; Ghaffari, Samad; Sanaati, Hamidreza; Alaeddini, Farshid; Pourmirza, Bahin; Mir, Elham

    2015-01-01

    Objectives To assess contemporary data on characteristics, management and 1-year postdischarge outcomes in Iranian patients hospitalised with acute coronary syndrome (ACS). Setting 11 tertiary care hospitals in 5 major cities in the Islamic Republic of Iran. Participants Patients aged ≥20 and ≤80 years discharged alive with confirmed diagnosis of ACS including ST-segment elevation myocardial infarction (STEMI), non-STEMI (NSTEMI) and high-risk unstable angina (HR-UA). Primary and secondary outcome measures Patients were followed up regarding the use of medications and the end points of the study at 1 month and 1 year after discharge. The primary end point of the study was 1-year postdischarge major adverse cardiac and cerebrovascular events (MACCEs), defined as mortality (cardiac and non-cardiac), ACS and cerebrovascular attack (stroke and/or transient ischaemic attack). The secondary end points were hospital admission because of congestive heart failure, revascularisation by coronary artery bypass grafting surgery or percutaneous coronary intervention (PCI), and major and minor bleeds. Results A total of 1799 patients (25.7% STEMI and 74.3% HR-UA/NSTEMI) discharged alive with confirmed diagnosis of ACS were included in the final analysis. During hospitalisation, the majority of the patients received aspirin (98.6%), clopidogrel (91.8%), anticoagulants (93.4%), statins (94.3%) and β-blockers (89.3%). Reperfusion therapy was performed in 62.6% of patients with STEMI (46.3% thrombolytic therapy and 17.3% primary PCI). The mean door-to-balloon and door-to-needle times were 82.9 and 45.6 min, respectively. In our study, 64.7% and 79.5% of the patients in HR-UA/NSTEMI and STEMI groups, respectively, underwent coronary angiography. During the 12 months after discharge, MACCEs occurred in 15.0% of all patients. Conclusions Our study showed that the composition of Iranian patients with ACS regarding the type of ACS is similar to that in developed European

  8. Red blood cell distribution width independently predicts medium-term mortality and major adverse cardiac events after an acute coronary syndrome

    PubMed Central

    Turcato, Gianni; Serafini, Valentina; Dilda, Alice; Bovo, Chiara; Caruso, Beatrice; Ricci, Giorgio

    2016-01-01

    Background The value of red blood cell distribution width (RDW), a simple and inexpensive measure of anisocytosis, has been associated with the outcome of many human chronic disorders. Therefore, this retrospective study was aimed to investigate whether RDW may be associated with medium-term mortality and major adverse cardiac events (MACE) after an acute coronary syndrome (ACS). Methods A total number of 979 patients diagnosed with ACS were enrolled from June 2014 to November 2014, and followed-up until June 2015. Results The RDW value in patients with 3-month MACE and in those who died was significantly higher than that of patients without 3-month MACE (13.3% vs. 14.0%; P<0.001) and those who were still alive at the end of follow-up (13.4% vs. 14.4%; P<0.001). In univariate analysis, RDW was found to be associated with 3-month MACE [odds ratio (OR), 1.70; 95% CI, 1.44–2.00, P<0.001]. In multivariate analysis, RDW remained independently associated with 3-month MACE (adjusted OR, 1.36; 95% CI, 1.19–1.55; P<0.001) and death (adjusted OR, 1.34; 95% CI, 1.05–1.71; P=0.020). The accuracy of RDW for predicting 3-month MACE was 0.67 (95% CI, 0.66–0.72; P<0.001). The most efficient discriminatory RDW value was 14.8%, which was associated with 3.8 (95% CI, 2.6–5.7; P<0.001) higher risk of 3-month MACE. Patients with RDW >14.8% exhibited a significantly short survival than those with RDW ≤14.8% (331 vs. 465 days; P<0.001). Conclusions The results of this study confirm that RDW may be a valuable, easy and inexpensive parameter for stratifying the medium-term risk in patients with ACS. PMID:27500155

  9. Characteristics of Lumbar Disc Herniation With Exacerbation of Presentation Due to Spinal Manipulative Therapy

    PubMed Central

    Huang, Sheng-Li; Liu, Yan-Xi; Yuan, Guo-Lian; Zhang, Ji; Yan, Hong-Wei

    2015-01-01

    Abstract The aim of this article was to delineate the characteristics of lumbar disc herniation (LDH) in patients with exacerbation of symptoms caused by spinal manipulative therapy (SMT). The main emphasis should be on the prevention of this condition by identifying relevant risk factors. Detailed clinico-radiological profiles of a total number of 10 LDH patients with exacerbation of presentation after SMT were reviewed. All the patients underwent neurological and magnetic resonance imaging examinations. Laminectomy and discectomy were performed, and follow-up was carried out in all patients. The duration of symptoms in the patients before SMT was 4–15 years. After the therapy, an acute exacerbation of back and radicular pain was observed within 24 h. Magnetic resonance imaging showed that L4–L5 was the most frequently affected level observed (7 patients), and each patient had a large disc fragment in the spinal canal. The disc fragments were classified into 3 types according to their localizations. The time internal between the exacerbation of presentation and surgery was 23.1 days. No perioperative complications were noted. All the patients were relieved of radicular pain a few days after surgery. During postoperative follow-up, all patients regained the ability to walk; one patient received catheterization for 1 month and another for 6 months. Eight patients reported a complete resolution of presentation and the rest 2 patients were significantly improved. SMT should be prohibited in some LDH patients to prevent neurological damages, in whom there are 5 possible risk factors. Surgical results for these patients are encouraging. PMID:25816037

  10. Characteristics of lumbar disc herniation with exacerbation of presentation due to spinal manipulative therapy.

    PubMed

    Huang, Sheng-Li; Liu, Yan-Xi; Yuan, Guo-Lian; Zhang, Ji; Yan, Hong-Wei

    2015-03-01

    The aim of this article was to delineate the characteristics of lumbar disc herniation (LDH) in patients with exacerbation of symptoms caused by spinal manipulative therapy (SMT). The main emphasis should be on the prevention of this condition by identifying relevant risk factors. Detailed clinico-radiological profiles of a total number of 10 LDH patients with exacerbation of presentation after SMT were reviewed. All the patients underwent neurological and magnetic resonance imaging examinations. Laminectomy and discectomy were performed, and follow-up was carried out in all patients. The duration of symptoms in the patients before SMT was 4-15 years. After the therapy, an acute exacerbation of back and radicular pain was observed within 24 h. Magnetic resonance imaging showed that L4-L5 was the most frequently affected level observed (7 patients), and each patient had a large disc fragment in the spinal canal. The disc fragments were classified into 3 types according to their localizations. The time internal between the exacerbation of presentation and surgery was 23.1 days. No perioperative complications were noted. All the patients were relieved of radicular pain a few days after surgery. During postoperative follow-up, all patients regained the ability to walk; one patient received catheterization for 1 month and another for 6 months. Eight patients reported a complete resolution of presentation and the rest 2 patients were significantly improved. SMT should be prohibited in some LDH patients to prevent neurological damages, in whom there are 5 possible risk factors. Surgical results for these patients are encouraging. PMID:25816037

  11. Long-Term Fluticasone Propionate/Formoterol Fumarate Combination Therapy Is Associated with a Low Incidence of Severe Asthma Exacerbations

    PubMed Central

    Mansur, Adel H.; Pertseva, Tetyana; Kaiser, Kirsten; McIver, Tammy; Grothe, Birgit; Dissanayake, Sanjeeva

    2016-01-01

    Abstract Background: A primary goal of asthma management is the reduction of exacerbation risk. We assessed the occurrence of oral corticosteroid-requiring exacerbations (OCS exacerbations) with long-term fluticasone/formoterol therapy, and compared it with the occurrence of similar events reported with other inhaled corticosteroid/long acting β2-agonist (ICS/LABA) combinations. Methods: The occurrence of OCS exacerbations was assessed in two open-label trials of fixed-dose fluticasone/formoterol administered for between 26 to 60 weeks in adults and adolescents with asthma. The incidence of OCS exacerbations with fluticasone/formoterol was compared with those reported in three recent Cochrane meta-analyses of other ICS/LABAs. Results: The pooled incidence of OCS exacerbations with long-term fluticasone/formoterol was 2.1% (95% CI: 1.1, 3.2%, n/N = 16/752). In only two of the nineteen treatment arms summarized by Cochrane did OCS exacerbation incidence approximate that seen in the two fluticasone/formoterol trials (single-inhaler fluticasone/salmeterol [2.9%]; separate inhaler budesonide, beclometasone, or flunisolide plus formoterol [3.4%]). In Lasserson's review the pooled incidence of OCS exacerbations for single-inhaler combinations was 9.5% (95% CI: 8.4, 10.6%; n/N = 239/2516) for fluticasone/salmeterol, and 10.6% (95% CI: 9.3, 11.8%; n/N = 257/2433) for budesonide/formoterol. In Ducharme's and Chauhan's meta-analyses (primarily incorporating separate inhaler combinations [fluticasone, budesonide, beclometasone, or flunisolide plus salmeterol or formoterol]), the pooled incidences of OCS exacerbations were 16.0% (95% CI: 14.2, 17.8%, n/N = 258/1615) and 16.7% (95% CI: 14.9, 18.5, n/N = 275/1643), respectively. Conclusions: The incidence of exacerbations in two fixed-dose fluticasone/formoterol studies was low and less than in the majority of comparable published studies involving other ICS/LABA combinations. This difference could not be

  12. The complexity of managing COPD exacerbations: a grounded theory study of European general practice

    PubMed Central

    Risør, Mette Bech; Spigt, Mark; Iversen, R; Godycki-Cwirko, M; Francis, N; Altiner, A; Andreeva, E; Kung, K; Melbye, H

    2013-01-01

    Objectives To understand the concerns and challenges faced by general practitioners (GPs) and respiratory physicians about primary care management of acute exacerbations in patients with chronic obstructive pulmonary disease (COPD). Design 21 focus group discussions (FGDs) were performed in seven countries with a Grounded Theory approach. Each country performed three rounds of FGDs. Setting Primary and secondary care in Norway, Germany, Wales, Poland, Russia, The Netherlands, China (Hong Kong). Participants 142 GPs and respiratory physicians were chosen to include urban and rural GPs as well as hospital-based and out patient-clinic respiratory physicians. Results Management of acute COPD exacerbations is dealt with within a scope of concerns. These concerns range from ‘dealing with comorbidity’ through ‘having difficult patients’ to ‘confronting a hopeless disease’. The first concern displays medical uncertainty regarding diagnosis, medication and hospitalisation. These clinical processes become blurred by comorbidity and the social context of the patient. The second concern shows how patients receive the label ‘difficult’ exactly because they need complex attention, but even more because they are time consuming, do not take responsibility and are non-compliant. The third concern relates to the emotional reactions by the physicians when confronted with ‘a hopeless disease’ due to the fact that most of the patients do not improve and the treatment slows down the process at best. GPs and respiratory physicians balance these concerns with medical knowledge and practical, situational knowledge, trying to encompass the complexity of a medical condition. Conclusions Knowing the patient is essential when dealing with comorbidities as well as with difficult relations in the consultations on exacerbations. This study suggests that it is crucial to improve the collaboration between primary and secondary care, in terms of, for example, shared consultations

  13. Lights and shadows of non-invasive mechanical ventilation for chronic obstructive pulmonary disease (COPD) exacerbations

    PubMed Central

    Lopez-Campos, Jose Luis; Jara-Palomares, Luis; Muñoz, Xavier; Bustamante, Víctor; Barreiro, Esther

    2015-01-01

    Despite the overwhelming evidence justifying the use of non-invasive ventilation (NIV) for providing ventilatory support in chronic obstructive pulmonary disease (COPD) exacerbations, recent studies demonstrated that its application in real-life settings remains suboptimal. European clinical audits have shown that 1) NIV is not invariably available, 2) its availability depends on countries and hospital sizes, and 3) numerous centers declare their inability to provide NIV to all of the eligible patients presenting throughout the year. Even with an established indication, the use of NIV in acute respiratory failure due to COPD exacerbations faces important challenges. First, the location and personnel using NIV should be carefully selected. Second, the use of NIV is not straightforward despite the availability of technologically advanced ventilators. Third, NIV therapy of critically ill patients requires a thorough knowledge of both respiratory physiology and existing ventilatory devices. Accordingly, an optimal team-training experience, the careful selection of patients, and special attention to the selection of devices are critical for optimizing NIV outcomes. Additionally, when applied, NIV should be closely monitored, and endotracheal intubation should be promptly available in the case of failure. Another topic that merits careful consideration is the use of NIV in the elderly. This patient population is particularly fragile, with several physiological and social characteristics requiring specific attention in relation to NIV. Several other novel indications should also be critically examined, including the use of NIV during fiberoptic bronchoscopy or transesophageal echocardiography, as well as in interventional cardiology and pulmonology. The present narrative review aims to provide updated information on the use of NIV in acute settings to improve the clinical outcomes of patients hospitalized for COPD exacerbations. PMID:25829958

  14. Does eosinophilic COPD exacerbation have a better patient outcome than non-eosinophilic in the intensive care unit?

    PubMed Central

    Saltürk, Cüneyt; Karakurt, Zuhal; Adiguzel, Nalan; Kargin, Feyza; Sari, Rabia; Celik, M Emin; Takir, Huriye Berk; Tuncay, Eylem; Sogukpinar, Ozlem; Ciftaslan, Nezihe; Mocin, Ozlem; Gungor, Gokay; Oztas, Selahattin

    2015-01-01

    Background COPD exacerbations requiring intensive care unit (ICU) admission have a major impact on morbidity and mortality. Only 10%–25% of COPD exacerbations are eosinophilic. Aim To assess whether eosinophilic COPD exacerbations have better outcomes than non-eosinophilic COPD exacerbations in the ICU. Methods This retrospective observational cohort study was conducted in a thoracic, surgery-level III respiratory ICU of a tertiary teaching hospital for chest diseases from 2013 to 2014. Subjects previously diagnosed with COPD and who were admitted to the ICU with acute respiratory failure were included. Data were collected electronically from the hospital database. Subjects’ characteristics, complete blood count parameters, neutrophil to lymphocyte ratio (NLR), delta NLR (admission minus discharge), C-reactive protein (CRP) on admission to and discharge from ICU, length of ICU stay, and mortality were recorded. COPD subjects were grouped according to eosinophil levels (>2% or ≤2%) (group 1, eosinophilic; group 2, non-eosinophilic). These groups were compared with the recorded data. Results Over the study period, 647 eligible COPD subjects were enrolled (62 [40.3% female] in group 1 and 585 [33.5% female] in group 2). Group 2 had significantly higher C-reactive protein, neutrophils, NLR, delta NLR, and hemoglobin, but a lower lymphocyte, monocyte, and platelet count than group 1, on admission to and discharge from the ICU. Median (interquartile range) length of ICU stay and mortality in the ICU in groups 1 and 2 were 4 days (2–7 days) vs 6 days (3–9 days) (P<0.002), and 12.9% vs 24.9% (P<0.034), respectively. Conclusion COPD exacerbations with acute respiratory failure requiring ICU admission had a better outcome with a peripheral eosinophil level >2%. NLR and peripheral eosinophilia may be helpful indicators for steroid and antibiotic management. PMID:26392758

  15. Chronic obstructive pulmonary disease exacerbations: latest evidence and clinical implications

    PubMed Central

    Qureshi, Hammad; Sharafkhaneh, Amir

    2014-01-01

    Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide and results in an economic and social burden that is both substantial and increasing. The natural history of COPD is punctuated by exacerbations which have major short- and long-term implications on the patient and healthcare system. Evidence-based guidelines stipulate that early detection and prompt treatment of exacerbations are essential to ensure optimal outcomes and to reduce the burden of COPD. Several factors can identify populations at risk of exacerbations. Implementing prevention measures in patients at risk is a major goal in the management of COPD. PMID:25177479

  16. Comorbidity and Inflammatory Markers May Contribute to Predict Mortality of High-Risk Patients With Chronic Obstructive Pulmonary Disease Exacerbation

    PubMed Central

    Kim, Yu Jin; Lim, Byeongwoo; Kyung, Sun Young; Park, Jeong-woong; Jeong, Sung Hwan

    2016-01-01

    Background Acute exacerbation of chronic obstructive pulmonary disease (COPD) causes not only an accelerated disease progression, but also an increased mortality rate. The purpose of this study was to analyze the factors associated with clinical features, comorbidities and mortality in patients at high risk for acute COPD exacerbation who had been hospitalized at least once in a year. Methods The study enrolled 606 patients who had been diagnosed with and were being treated for COPD at university affiliated hospital. Among them, there were 61 patients at high risk for acute exacerbation of COPD who had been hospitalized at least once in a year. A retrospective analysis was conducted to examine the factors affecting mortality. The analysis divided the patients into non-survivor and survivor groups, and reviewed their medical records for clinical aspects, comorbidities, pulmonary function tests and blood tests. Results In the high-risk group, the number of comorbidities at diagnosis (P = 0.020) and the Charlson comorbidity index value (P = 0.018) were higher in the non-survivor group than in the survivor group. During hospitalization, the non-survivor group had a significantly higher neutrophil (%) and a significantly lower lymphocyte (%) in complete blood count. Under stable conditions, the high-sensitivity C-reactive protein (hsCRP) concentration in blood plasma and neutrophil (%) were significantly higher (P = 0.025 and P = 0.036), while the lymphocyte (%) was significantly lower (P = 0.005) in the non-survivor group. A pulmonary function test revealed no statistically significant differences between the two groups. Conclusion The number of comorbidities, neutrophil (%), lymphocyte (%) in complete blood cell (CBC) and hsCRP in blood plasma concentration among the groups at high risk for COPD exacerbation are associated with increased mortality. PMID:27298662

  17. Management of Chronic Obstructive Pulmonary Disease in Patients Admitted to a Tertiary Care Centre for Exacerbation of Their Disease

    PubMed Central

    Dault, Roxanne; Dubé, Anne-Isabelle; Blais, Lucie; Boileau, Robert; Larrivée, Pierre; Dumas, Mario-Eddy; Beauchesne, Marie-France

    2012-01-01

    Background: Acute exacerbation of chronic obstructive pulmonary disease (COPD) is associated with an accelerated decline in lung function and a significant decrease in health status. Maintenance therapy with respiratory medications can reduce the risk of such exacerbations. Objective: To determine whether respiratory maintenance medications were being prescribed in accordance with the 2007 COPD guidelines of the Canadian Thoracic Society for patients admitted to hospital for acute exacerbation of COPD. Methods: A chart review was conducted for admissions to the Centre hospitalier universitaire de Sherbrooke, in Sherbrooke, Quebec, for acute exacerbation of COPD (according to diagnostic codes in the International Statistical Classification of Diseases and Related Health Problems, 10th revision) between January 1, 2008, and January 31, 2011. Data were extracted from patients’ medical charts concerning respiratory medications prescribed before the admission, during the hospital stay, and at discharge. Results: A total of 846 hospital admissions involving 561 patients were reviewed. In almost 70% of admissions for which data were available on respiratory medications prescribed before the admission, during the hospital stay, and at discharge (238/341 [69.8%]), a combination of 3 medications was prescribed at discharge: tiotropium, a long-acting ß2 agonist, and an inhaled corticosteroid. For more than 80% of the admissions, a prescription for at least one inhaled long-acting bronchodilator was documented both on admission and at discharge. Few patients had a prescription for inhaled corticosteroid without long-acting ß2 agonist, but the number of admissions with a prescription for regular use of systemic corticosteroids increased at discharge. Conclusions: Respiratory medications were generally prescribed in accordance with Canadian COPD guidelines, but improvements could be made regarding use of the combination of tiotropium, long-acting ß2agonist, and inhaled

  18. Can resistive breathing injure the lung? Implications for COPD exacerbations

    PubMed Central

    Vassilakopoulos, Theodoros; Toumpanakis, Dimitrios

    2016-01-01

    In obstructive lung diseases, airway inflammation leads to bronchospasm and thus resistive breathing, especially during exacerbations. This commentary discusses experimental evidence that resistive breathing per se (the mechanical stimulus) in the absence of underlying airway inflammation leads to lung injury and inflammation (mechanotransduction). The potential implications of resistive breathing-induced mechanotrasduction in COPD exacerbations are presented along with the available clinical evidence. PMID:27713628

  19. Occupational exposures associated with severe exacerbation of asthma

    PubMed Central

    Henneberger, P. K.; Liang, X.; Lillienberg, L.; Dahlman-Höglund, A.; Torén, K.; Andersson, E.

    2015-01-01

    SUMMARY BACKGROUND The exacerbation of asthma by workplace conditions is common, but little is known about which agents pose a risk. OBJECTIVE We used data from an existing survey of adults with asthma to identify occupational exposures associated with severe exacerbation of asthma. DESIGN Questionnaires were completed by 557 working adults with asthma. Severe exacerbation of asthma in the past 12 months was defined as asthma-related hospitalization, or reports of both unplanned asthma care and treatment with a short course of oral corticosteroids. Occupational exposures for the same time period were assessed using an asthma-specific job exposure matrix. We modeled severe exacerbation to yield prevalence ratios (PRs) for exposures while controlling for potential confounders. RESULTS A total of 164 participants (29%) were positive for severe exacerbation, and 227 (40.8%) were assessed as being exposed to asthma agents at work. Elevated PRs were observed for several specific agents, notably the irritant subcategories of environmental tobacco smoke (PR 1.84, 95%CI 1.34–2.51) among all participants, inorganic dusts (PR 2.53, 95%CI 1.37– 4.67) among men, and the low molecular weight subcategory of other highly reactive agents (PR 1.97, 95%CI 1.08–3.60) among women. CONCLUSION Among working adults with asthma, severe exacerbation was associated with several occupational agents. PMID:25574926

  20. Comparison of the clinical characteristics and treatment outcomes of patients requiring hospital admission to treat eosinophilic and neutrophilic exacerbations of COPD

    PubMed Central

    Kang, Hye Seon; Rhee, Chin Kook; Kim, Sung Kyoung; Kim, Jin Woo; Lee, Sang Haak; Yoon, Hyung Kyu; Ahn, Joong Hyun; Kim, Yong Hyun

    2016-01-01

    Purpose We compared the clinical characteristics and treatment outcomes of patients with eosinophilic and neutrophilic COPD exacerbations requiring hospital admission. Patients and methods This was a retrospective multicenter study performed between January 2010 and December 2014. In all, 1,688 COPD patients admitted via the outpatient clinics or emergency departments of six university hospitals were enrolled. The patients were grouped by complete blood counts: eosinophilic group, >2% peripheral blood eosinophils, and neutrophilic group, >65% peripheral blood neutrophils or >11,000 leukocytes/mL. The patients with radiographic evidence of pneumonia at the time of admission, those with lung cancer, those admitted for treatment of other medical problems, and those who chronically used steroids were excluded. Results A total of 605 patients hospitalized with COPD exacerbations (177 eosinophilic and 380 neutrophilic) were included. Pulmonary functions, including the forced expiratory volume in 1 second and forced vital capacity, were better in patients with eosinophilic exacerbations. Treatment outcomes, including the rate of admission to the intensive care unit and mortality, were poorer in patients with neutrophilic exacerbations (4.5% vs 12.4%, P=0.004; 1.1% vs 4.5%, P=0.043, respectively). Congestive heart failure (odds ratio [OR] =3.40, 95% confidence interval [CI]: 1.28–9.01) and neutrophilic exacerbation (OR = 2.81, 95% CI: 1.21–6.52) were independent risk factors for intensive care unit admission. Conclusion COPD patients with neutrophilic exacerbations experienced worse clinical outcomes than did those with eosinophilic exacerbations. The peripheral blood eosinophil count may be a useful predictor of clinical progress during hospitalization of COPD patients with acute exacerbations. PMID:27757029

  1. Co-morbidities and 90-day outcomes in hospitalized COPD exacerbations.

    PubMed

    Roberts, Christopher M; Stone, Robert A; Lowe, Derek; Pursey, Nancy A; Buckingham, Rhona J

    2011-10-01

    COPD exacerbations resulting in hospitalization are accompanied by high mortality and morbidity. The contribution of specific co-morbidities to acute outcomes is not known in detail: existing studies have used either administrative data or small clinical cohorts and have provided conflicting results. Identification of co-existent diseases that affect outcomes provides opportunities to address these conditions proactively and improve overall COPD care. Cases were identified prospectively on admission then underwent retrospective case note audit to collect data including co-morbidities on up to 60 unselected consecutive acute COPD admissions between March and May in each hospital participating in the 2008 UK National COPD audit. Outcomes recorded were death in hospital, length of stay, and death and readmission at 90 days after index admission. 232 hospitals collected data on 9716 patients, mean age 73, 50% male, mean FEV1 42% predicted. Prevalence of co-morbidities were associated with increased age but better FEV1 and ex-smoker status and with worse outcomes for all four measures. Hospital mortality risk was increased with cor pulmonale, left ventricular failure, neurological conditions and non-respiratory malignancies whilst 90 day death was also increased by lung cancer and arrhythmias. Ischaemic and other heart diseases were important factors in readmission. This study demonstrates that co-morbidities adversely affect a range of short-term patient outcomes related to acute admission to hospital with exacerbations of COPD. Recognition of relevant accompanying diseases at admission provides an opportunity for specific interventions that may improve short-term prognosis. PMID:21864116

  2. Risk factors for acute chemical releases with public health consequences: Hazardous Substances Emergency Events Surveillance in the U.S., 1996–2001

    PubMed Central

    Ruckart, Perri Z; Wattigney, Wendy A; Kaye, Wendy E

    2004-01-01

    Background Releases of hazardous materials can cause substantial morbidity and mortality. To reduce and prevent the public health consequences (victims or evacuations) from uncontrolled or illegally released hazardous substances, a more comprehensive analysis is needed to determine risk factors for hazardous materials incidents. Methods Hazardous Substances Emergency Events Surveillance (HSEES) data from 1996 through 2001 were analyzed using bivariate and multiple logistic regression. Fixed-facility and transportation-related events were analyzed separately. Results For fixed-facility events, 2,327 (8%) resulted in at least one victim and 2,844 (10%) involved ordered evacuations. For transportation-related events, 759 (8%) resulted in at least one victim, and 405 (4%) caused evacuation orders. Fire and/or explosion were the strongest risk factors for events involving either victims or evacuations. Stratified analysis of fixed-facility events involving victims showed a strong association for acid releases in the agriculture, forestry, and fisheries industry. Chlorine releases in fixed-facility events resulted in victims and evacuations in more industry categories than any other substance. Conclusions Outreach efforts should focus on preventing and preparing for fires and explosions, acid releases in the agricultural industry, and chlorine releases in fixed facilities. PMID:15496226

  3. Acute Pancreatitis and Pregnancy

    MedlinePlus

    ... sudden inflammation of the pancreas manifested clinically by abdominal pain, nausea and dehydration that is usually self-limiting ... room for evaluation should they develop any abnormal abdominal pain symptoms. Conclusions While a rare event, acute pancreatitis ...

  4. Acute heart failure with low cardiac output: can we develop a short-term inotropic agent that does not increase adverse events?

    PubMed

    Campia, Umberto; Nodari, Savina; Gheorghiade, Mihai

    2010-09-01

    Acute heart failure represents an increasingly common cause of hospitalization, and may require the use of inotropic drugs in patients with low cardiac output and evidence of organ hypoperfusion. However, currently available therapies may have deleterious effects and increase mortality. An ideal inotropic drug should restore effective tissue perfusion by enhancing myocardial contractility without causing adverse effects. Such a drug is not available yet. New agents with different biological targets are under clinical development. In particular, istaroxime seems to dissociate the inotropic effect exerted by digitalis (inhibition of the membrane sodium/potassium adenosine triphosphatase) from the arrhythmic effect and to ameliorate diastolic dysfunction (via sarcoendoplasmic reticulum calcium adenosine triphosphatase activation). Additionally, the myosin activator omecamtiv mecarbil appears to have promising characteristics, while genetic therapy has been explored in animal studies only. Further investigations are needed to confirm and expand the effectiveness and safety of these agents in patients with acute heart failure and low cardiac output.

  5. Acute Pancreatitis

    PubMed Central

    Geokas, Michael C.

    1972-01-01

    For many decades two types of acute pancreatitis have been recognized: the edematous or interstitial and the hemorrhagic or necrotic. In most cases acute pancreatitis is associated with alcoholism or biliary tract disease. Elevated serum or urinary α-amylase is the most important finding in diagnosis. The presence of methemalbumin in serum and in peritoneal or pleural fluid supports the diagnosis of the hemorrhagic form of the disease in patients with a history and enzyme studies suggestive of pancreatitis. There is no characteristic clinical picture in acute pancreatitis, and its complications are legion. Pancreatic pseudocyst is probably the most common and pancreatic abscess is the most serious complication. The pathogenetic principle is autodigestion, but the precise sequence of biochemical events is unclear, especially the mode of trypsinogen activation and the role of lysosomal hydrolases. A host of metabolic derangements have been identified in acute pancreatitis, involving lipid, glucose, calcium and magnesium metabolism and changes of the blood clotting mechanism, to name but a few. Medical treatment includes intestinal decompression, analgesics, correction of hypovolemia and other supportive and protective measures. Surgical exploration is advisable in selected cases, when the diagnosis is in doubt, and is considered imperative in the presence of certain complications, especially pancreatic abscess. PMID:4559467

  6. Sea level anomalies exacerbate beach erosion

    NASA Astrophysics Data System (ADS)

    Theuerkauf, Ethan J.; Rodriguez, Antonio B.; Fegley, Stephen R.; Luettich, Richard A.

    2014-07-01

    Sea level anomalies are intra-seasonal increases in water level forced by meteorological and oceanographic processes unrelated to storms. The effects of sea level anomalies on beach morphology are unknown but important to constrain because these events have been recognized over large stretches of continental margins. Here, we present beach erosion measurements along Onslow Beach, a barrier island on the U.S. East Coast, in response to a year with frequent sea level anomalies and no major storms. The anomalies enabled extensive erosion, which was similar and in most places greater than the erosion that occurred during a year with a hurricane. These results highlight the importance of sea level anomalies in facilitating coastal erosion and advocate for their inclusion in beach-erosion models and management plans. Sea level anomalies amplify the erosive effects of accelerated sea level rise and changes in storminess associated with global climate change.

  7. Management of Patients Admitted with Acute Decompensated Heart Failure

    PubMed Central

    Krim, Selim R.; Campbell, Patrick T.; Desai, Sapna; Mandras, Stacy; Patel, Hamang; Eiswirth, Clement; Ventura, Hector O.

    2015-01-01

    Background Hospital admission for the treatment of acute decompensated heart failure is an unfortunate certainty in the vast majority of patients with heart failure. Regardless of the etiology, inpatient treatment for acute decompensated heart failure portends a worsening prognosis. Methods This review identifies patients with heart failure who need inpatient therapy and provides an overview of recommended therapies and management of these patients in the hospital setting. Results Inpatient therapy for patients with acute decompensated heart failure should be directed at decongestion and symptom improvement. Clinicians should also treat possible precipitating events, identify comorbid conditions that may exacerbate heart failure, evaluate and update current guideline-directed medical therapy, and perform risk stratification for all patients. Finally, efforts should be made to educate patients about the importance of restricting salt and fluid, monitoring daily weights, and adhering to a graded exercise program. Conclusion Early discharge follow-up and continued optimization of guideline-directed medical therapy are key to preventing future heart failure readmissions. PMID:26413005

  8. Prulifloxacin vs Levofloxacin for Exacerbation of COPD after Failure of Other Antibiotics.

    PubMed

    Giusti, Massimo; Blasi, Francesco; Iori, Ido; Mazzone, Antonino; Sgambato, Francesco; Politi, Cecilia; Colagrande, Paola; Casali, Annamaria; Valerio, Antonella; Gussoni, Gualberto; Bonizzoni, Erminio; Campanini, Mauro

    2016-10-01

    The chronic course and evolution of chronic obstructive pulmonary disease (COPD) is often characterized by periods of exacerbation of symptoms, which have a negative impact on the quality of life of patients, as well as on the evolution of COPD, and represent a significant cause of medical intervention and hospitalization. Very few data are available on the efficacy of rescue antibiotics in patients with acute exacerbation of COPD (AECOPD) unresponsive to previous treatment. The aim of this study was to evaluate the efficacy of two fluoroquinolones in AECOPD previously treated without success. The FADOI-FLOR study is a randomized, single-blind, non-inferiority comparison between levofloxacin and prulifloxacin. Primary end-point was "therapeutic success" at Day 10 of treatment, defined as disappearance of signs/symptoms or decrease of at least three points of a global score of symptomatology (maximum score = 15). 258 patients were enrolled (128 levofloxacin and 130 prulifloxacin), in 25 centers. A very high proportion of patients in the two groups had therapeutic success at Day-10 (levofloxacin 93.0% vs prulifloxacin 96.7%, population intention-to-treat; 94.6% vs 99.1%, population per-protocol). Earlier therapeutic success (within 7 days) was achieved in 32.0% and 36.2% of patients receiving levofloxacin or prulifloxacin, respectively. At 3-month follow-up, re-exacerbations occurred in 17.8% of patients treated with levofloxacin and 14.2% of those receiving prulifloxacin (p = 0.44). In conclusion, fluoroquinolones are very effective in the treatment of AECOPD resistant to other antibiotics. PMID:27027547

  9. Nutrition support in acute pancreatitis.

    PubMed

    McClave, Stephen A

    2007-03-01

    The benefit of early enteral nutrition (EN) for the disease process and for patient outcome in severe acute pancreatitis is dramatic. A narrow window of opportunity exists during which there is potential for EN to decrease disease severity and reduce overall complications. Most patients with severe pancreatitis tolerate enteral feeds. Any signs of symptom exacerbation or increasing inflammation in response to EN may be ameliorated by subtle adjustments in the feeding strategy. In this manner, provision of EN represents primary therapy in the management of the patient with acute pancreatitis and is emerging as the gold standard of therapy in nutrition support for this disease process.

  10. Acute and subacute idiopathic interstitial pneumonias.

    PubMed

    Taniguchi, Hiroyuki; Kondoh, Yasuhiro

    2016-07-01

    Idiopathic interstitial pneumonias (IIPs) may have an acute or subacute presentation, or acute exacerbation may occur in a previously subclinical or unrecognized chronic IIP. Acute or subacute IIPs include acute interstitial pneumonia (AIP), cryptogenic organizing pneumonia (COP), nonspecific interstitial pneumonia (NSIP), acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) and AE-NSIP. Interstitial lung diseases (ILDs) including connective tissue disease (CTD) associated ILD, hypersensitivity pneumonitis, acute eosinophilic pneumonia, drug-induced lung disease and diffuse alveolar haemorrhage need to be differentiated from acute and subacute IIPs. Despite the severe lack of randomized controlled trials for the treatment of acute and subacute IIPs, the mainstream treatment remains corticosteroid therapy. Other potential therapies reported in the literature include corticosteroids and immunosuppression, antibiotics, anticoagulants, neutrophil elastase inhibitor, autoantibody-targeted treatment, antifibrotics and hemoperfusion therapy. With regard to mechanical ventilation, patients in recent studies with acute and subacute IIPs have shown better survival than those in previous studies. Therefore, a careful value-laden decision about the indications for endotracheal intubation should be made for each patient. Noninvasive ventilation may be beneficial to reduce ventilator associated pneumonia. PMID:27123874

  11. Acute and subacute idiopathic interstitial pneumonias.

    PubMed

    Taniguchi, Hiroyuki; Kondoh, Yasuhiro

    2016-07-01

    Idiopathic interstitial pneumonias (IIPs) may have an acute or subacute presentation, or acute exacerbation may occur in a previously subclinical or unrecognized chronic IIP. Acute or subacute IIPs include acute interstitial pneumonia (AIP), cryptogenic organizing pneumonia (COP), nonspecific interstitial pneumonia (NSIP), acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) and AE-NSIP. Interstitial lung diseases (ILDs) including connective tissue disease (CTD) associated ILD, hypersensitivity pneumonitis, acute eosinophilic pneumonia, drug-induced lung disease and diffuse alveolar haemorrhage need to be differentiated from acute and subacute IIPs. Despite the severe lack of randomized controlled trials for the treatment of acute and subacute IIPs, the mainstream treatment remains corticosteroid therapy. Other potential therapies reported in the literature include corticosteroids and immunosuppression, antibiotics, anticoagulants, neutrophil elastase inhibitor, autoantibody-targeted treatment, antifibrotics and hemoperfusion therapy. With regard to mechanical ventilation, patients in recent studies with acute and subacute IIPs have shown better survival than those in previous studies. Therefore, a careful value-laden decision about the indications for endotracheal intubation should be made for each patient. Noninvasive ventilation may be beneficial to reduce ventilator associated pneumonia.

  12. Respiratory microbiota resistance and resilience to pulmonary exacerbation and subsequent antimicrobial intervention

    PubMed Central

    Cuthbertson, Leah; Rogers, Geraint B; Walker, Alan W; Oliver, Anna; Green, Laura E; Daniels, Thomas W V; Carroll, Mary P; Parkhill, Julian; Bruce, Kenneth D; van der Gast, Christopher J

    2016-01-01

    Pulmonary symptoms in cystic fibrosis (CF) begin in early life with chronic lung infections and concomitant airway inflammation leading to progressive loss of lung function. Gradual pulmonary function decline is interspersed with periods of acute worsening of respiratory symptoms known as CF pulmonary exacerbations (CFPEs). Cumulatively, CFPEs are associated with more rapid disease progression. In this study multiple sputum samples were collected from adult CF patients over the course of CFPEs to better understand how changes in microbiota are associated with CFPE onset and management. Data were divided into five clinical periods: pre-CFPE baseline, CFPE, antibiotic treatment, recovery, and post-CFPE baseline. Samples were treated with propidium monoazide prior to DNA extraction, to remove the impact of bacterial cell death artefacts following antibiotic treatment, and then characterised by 16S rRNA gene-targeted high-throughput sequencing. Partitioning CF microbiota into core and rare groups revealed compositional resistance to CFPE and resilience to antibiotics interventions. Mixed effects modelling of core microbiota members revealed no significant negative impact on the relative abundance of Pseudomonas aeruginosa across the exacerbation cycle. Our findings have implications for current CFPE management strategies, supporting reassessment of existing antimicrobial treatment regimens, as antimicrobial resistance by pathogens and other members of the microbiota may be significant contributing factors. PMID:26555248

  13. Patient and System-Related Delays of Emergency Medical Services Use in Acute ST-Elevation Myocardial Infarction: Results from the Third Gulf Registry of Acute Coronary Events (Gulf RACE-3Ps)

    PubMed Central

    AlHabib, Khalid F.; Sulaiman, Kadhim; Al Suwaidi, Jassim; Almahmeed, Wael; Alsheikh-Ali, Alawi A.; Amin, Haitham; Al Jarallah, Mohammed; Alfaleh, Hussam F.; Panduranga, Prashanth; Hersi, Ahmad; Kashour, Tarek; Al Aseri, Zohair; Ullah, Anhar; Altaradi, Hani B.; Nur Asfina, Kazi; Welsh, Robert C.; Yusuf, Salim

    2016-01-01

    Background Little is known about Emergency Medical Services (EMS) use and pre-hospital triage of patients with acute ST-elevation myocardial infarction (STEMI) in Arabian Gulf countries. Methods Clinical arrival and acute care within 24 h of STEMI symptom onset were compared between patients transferred by EMS (Red Crescent and Inter-Hospital) and those transferred by non-EMS means. Data were retrieved from a prospective registry of 36 hospitals in 6 Arabian Gulf countries, from January 2014 to January 2015. Results We enrolled 2,928 patients; mean age, 52.7 (SD ±11.8) years; 90% men; and 61.7% non-Arabian Gulf citizens. Only 753 patients (25.7%) used EMS; which was mostly via Inter-Hospital EMS (22%) rather than direct transfer from the scene to the hospital by the Red Crescent (3.7%). Compared to the non-EMS group, the EMS group was more likely to arrive initially at a primary or secondary health care facility; thus, they had longer median symptom-onset-to-emergency department arrival times (218 vs. 158 min; p˂.001); they were more likely to receive primary percutaneous coronary interventions (62% vs. 40.5%, p = 0.02); they had shorter door-to-needle times (38 vs. 42 min; p = .04); and shorter door-to-balloon times (47 vs. 83 min; p˂.001). High EMS use was independently predicted mostly by primary/secondary school educational levels and low or moderate socioeconomic status. Low EMS use was predicted by a history of angina and history of percutaneous coronary intervention. The groups had similar in-hospital deaths and outcomes. Conclusion Most acute STEMI patients in the Arabian Gulf region did not use EMS services. Improving Red Crescent infrastructure, establishing integrated STEMI networks, and launching educational public campaigns are top health care system priorities. PMID:26807577

  14. Scoring systems predict the prognosis of acute-on-chronic hepatitis B liver failure: an evidence-based review.

    PubMed

    Wu, Fa-Ling; Shi, Ke-Qing; Chen, Yong-Ping; Braddock, Martin; Zou, Hai; Zheng, Ming-Hua

    2014-08-01

    Acute-on-chronic hepatitis B liver failure is a devastating condition that is associated with mortality rates of over 50% and is consequent to acute exacerbation of chronic hepatitis B in patients with previously diagnosed or undiagnosed chronic liver disease. Liver transplantation is the definitive treatment to lower mortality rate, but there is a great imbalance between donation and potential recipients. An early and accurate prognostic system based on the integration of laboratory indicators, clinical events and some mathematic logistic equations is needed to optimize treatment for patients. As parts of the scoring systems, the MELD was the most common and the donor-MELD was the most innovative for patients on the waiting list for liver transplantation. This review aims to highlight the various features and prognostic capabilities of these scoring systems. PMID:24762209

  15. Chair’s Summary: Mechanisms of Exacerbation of Lung Diseases

    PubMed Central

    Nicod, Laurent P.

    2015-01-01

    This year’s conference focused on the origins of exacerbations in chronic lung diseases, such as asthma, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, and cystic fibrosis. Common themes emerged, with the role of viral infections being key. In addition, there were data presented supporting the role of the microbiota and microbial dysbiosis either in the gut or in the lung contributing to disease progression and the susceptibility to disease exacerbation. These effects can be amplified by the triggering of biologic cascades that include alterations in oxidative stress and inflammatory mediator release, which can be driven by epithelial cell injury or activation. PMID:26595726

  16. A case of Reiter's disease exacerbated by lithium

    PubMed Central

    Monteiro, Rochelle C.; Bhat, Ramesh M.; Sukumar, D.; Srinath, M. K.

    2011-01-01

    Reiter's disease is characterized by the triad of peripheral arthritis, urethritis, and conjunctivitis. A 38-year-old male, who was on treatment with lithium for mania, presented to us with all features of this triad. He was previously diagnosed and treated as seronegative arthritis. However, his symptoms persisted despite therapy. His skin lesions regressed only once lithium was stopped. Lithium is known to exacerbate or precipitate a multitude of dermatological conditions. However, there is no previous reported association of lithium exacerbating preexisting Reiter's disease. We report this case as it is the first known association of its kind. PMID:22021977

  17. Hyperpolarized helium-3 magnetic resonance imaging of chronic obstructive pulmonary disease exacerbation.

    PubMed

    Kirby, Miranda; Kanhere, Nikhil; Etemad-Rezai, Roya; McCormack, David G; Parraga, Grace

    2013-05-01

    A chronic obstructive pulmonary disease (COPD) exsmoker underwent pulmonary function tests and hyperpolarized helium-3 ((3) He) magnetic resonance imaging (MRI) serially over 4 years, twice prior to and twice following an acute exacerbation (AE). About 2.5 years pre-AE, (3) He ventilation defect percent (VDP) was 16%, the apparent diffusion coefficient (ADC) was 0.34 cm(2) /s, and forced expiratory volume in 1 sec (FEV1 ) was 41%pred . Six months pre-AE, VDP and ADC were worse (29% and 0.38 cm(2) /s, respectively) without worsening FEV1 (47%pred ). After hospitalization and AE treatment, VDP was 20%, whereas FEV1 did not improve (45%pred ); 16 months post-AE, both VDP and ADC remained improved and similar to 4 years prior.

  18. Nicotinamide Exacerbates Hypoxemia in Ventilator-Induced Lung Injury Independent of Neutrophil Infiltration

    PubMed Central

    Jones, Heather D.; Yoo, Jeena; Crother, Timothy R.; Kyme, Pierre; Ben-Shlomo, Anat; Khalafi, Ramtin; Tseng, Ching W.; Parks, William C.; Arditi, Moshe

    2015-01-01

    Background Ventilator-induced lung injury is a form of acute lung injury that develops in critically ill patients on mechanical ventilation and has a high degree of mortality. Nicotinamide phosphoribosyltransferase is an enzyme that is highly upregulated in ventilator-induced lung injury and exacerbates the injury when given exogenously. Nicotinamide (vitamin B3) directly inhibits downstream pathways activated by Nicotinamide phosphoribosyltransferase and is protective in other models of acute lung injury. Methods We administered nicotinamide i.p. to mice undergoing mechanical ventilation with high tidal volumes to study the effects of nicotinamide on ventilator-induced lung injury. Measures of injury included oxygen saturations and bronchoalveolar lavage neutrophil counts, protein, and cytokine levels. We also measured expression of nicotinamide phosophoribosyltransferase, and its downstream effectors Sirt1 and Cebpa, Cebpb, Cebpe. We assessed the effect of nicotinamide on the production of nitric oxide during ventilator-induced lung injury. We also studied the effects of ventilator-induced lung injury in mice deficient in C/EBPε. Results Nicotinamide treatment significantly inhibited neutrophil infiltration into the lungs during ventilator-induced lung injury, but did not affect protein leakage or cytokine production. Surprisingly, mice treated with nicotinamide developed significantly worse hypoxemia during mechanical ventilation. This effect was not linked to increases in nitric oxide production or alterations in expression of Nicotinamide phosphoribosyl transferase, Sirt1, or Cebpa and Cebpb. Cebpe mRNA levels were decreased with either nicotinamide treatment or mechanical ventilation, but mice lacking C/EBPε developed the same degree of hypoxemia and ventilator-induced lung injury as wild-type mice. Conclusions Nicotinamide treatment during VILI inhibits neutrophil infiltration of the lungs consistent with a strong anti-inflammatory effect, but

  19. Role of interleukin 1 in antigen-induced exacerbations of murine arthritis.

    PubMed Central

    van de Loo, A. A.; Arntz, O. J.; Bakker, A. C.; van Lent, P. L.; Jacobs, M. J.; van den Berg, W. B.

    1995-01-01

    The mechanism underlying the chronic and intermittent course of rheumatoid arthritis is not elucidated. In the present study, the role of interleukin 1 (IL-1) was investigated in exacerbations of antigen-induced arthritis in mice. A flare-up of smoldering inflammation (weeks 3 to 4 of antigen-induced arthritis) was inducible by injection of a small amount of methylated bovine serum albumin into the hypersensitive knee joint. Immunohistochemistry showed IL-1 expression in the synovial lining layer and in focal areas of the inflamed synovium during the flare-up. IL-1 was also measured in 1-hour culture supernatant of synovial tissue taken during the flare-up by a bioassay. The expression of both immunoreactive and bioactive IL-1 in the hypersensitive joint peaked around 6 hours after antigen (2 micrograms of methylated bovine serum albumin) injection and declined thereafter. Antigen rechallenge induced an acute joint swelling of the arthritic joint but not in the naive joint of the sensitized mouse, yet synovia of both joints produced IL-1 after antigen injection. Remarkably, a single intravenous injection of rabbit anti-IL-1 alpha and -beta antibodies 1 hour before antigen rechallenge neutralized IL-1 in the joint. Anti-IL-1 treatment significantly reduced the antigen-induced joint swelling (30 to 40%) but did not affect the profound influx of polymorphonuclear cells in the onset of the exacerbation. However, a profound relief of the inflammation (synovitis) was obtained by IL-1 blockade on day 4 of the exacerbation. Chondrocyte proteoglycan synthesis was markedly suppressed in the antigen-challenged naive knee joints suggesting that this was a direct IL-1 effect as the inflammation was insignificant. Anti-IL-1 treatment was able to maintain chondrocyte proteoglycan synthesis in the antigen-rechallenged joint, which was highly suppressed in the control group. Furthermore, the enhanced proteoglycan breakdown in the antigen-rechallenged joints was significantly

  20. Cystitis - acute

    MedlinePlus

    Uncomplicated urinary tract infection; UTI - acute; Acute bladder infection; Acute bacterial cystitis ... International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 ...

  1. Bacterial infection in exacerbated COPD with changes in sputum characteristics.

    PubMed Central

    Monsó, E.; Garcia-Aymerich, J.; Soler, N.; Farrero, E.; Felez, M. A.; Antó, J. M.; Torres, A.

    2003-01-01

    We examined the risk factors for bacterial exacerbation, defined as the presence of pathogenic bacteria in sputum, in 90 chronic obstructive pulmonary disease (COPD) patients with an exacerbation and changes in sputum characteristics. Smoking, alcohol, lung function, body mass index, medical visits and treatments were the independent variables assessed using multivariable logistic regression modelling (OR, 95% CI). A bacterial exacerbation was diagnosed in 39 (43.3%) of 90 patients. Bacterial exacerbations were more prevalent among current smokers (OR 3.77, 95% CI 1.17-12.12), in patients with poor compliance with inhalation therapy (OR 3.25, 95% CI 1.18-8.93) and with severe lung function impairment (FEV1 OR 0.96, 95% CI 0.93-1.00). Prior use of antibiotics was a risk factor for Pseudomonas aeruginosa infection (OR 6.06, 95% CI 1.29-28.44) and influenza vaccination appeared to have a protective effect against this infection (OR 0.15, 95% CI 0.03-0.67). We conclude that severe impairment of lung function, smoking and poor compliance with therapy are risk factors for bacterial infection in COPD, and P. aeruginosa should be suspected in patients who have been treated with antibiotics and in those not vaccinated against influenza. PMID:12948381

  2. Effects of N-acetylcysteine on asthma exacerbation.

    PubMed

    Aliyali, Masoud; Poorhasan Amiri, Ali; Sharifpoor, Ali; Zalli, Fatemeh

    2010-06-01

    Airway mucus hypersecretion and increased oxidative stress are clinical and pathophysiological features of asthma exacerbation. We studied effects of N-acetylcysteine (NAC) as a mucolytic and antioxidant agent in asthma exacerbation. In this randomized, single-blinded, placebo-controlled study 50 patients ( 17 male, 33 female, mean age 48.94+/-13.68) with asthma exacerbation were randomized to receive either oral 600 mg b.d. N-acetylcysteine or placebo in addition to standard treatment during 5 days hospitalization. Daily measurements of wheezing, dyspnea, cough, sputum, expectoration, night sleep scores and morning PEFR were performed. There was no significant difference in wheezing score between patients assigned NAC and those assigned placebo in day 5(0.84[SD 0.94] VS 0.87[SD 0.79]) and also in cough score (0.72[SD 0.84] VS 0.79[SD 0.97]), dyspnea score (0.84[SD 1.06] VS 0.91[SD 1.01]), sputum score(0.79[SD 0.83] VS 0.62[SD 0.71]), expectoration score(0.79[SD 0.97] VS 0.83[SD 1.09]), night sleep score(1[SD 1.17] VS 0.67[SD 0.98] and morning PEFR (256[SD 96.36] VS 282[SD 98.86]). We concluded that addition of N-acetylcysteine to usual asthma medication has no significant effect in treatment of asthma exacerbation.

  3. How Clinical Diagnosis Might Exacerbate the Stigma of Mental Illness

    ERIC Educational Resources Information Center

    Corrigan, Patrick W.

    2007-01-01

    Stigma can greatly exacerbate the experience of mental illness. Diagnostic classification frequently used by clinical social workers may intensify this stigma by enhancing the public's sense of "groupness" and "differentness" when perceiving people with mental illness. The homogeneity assumed by stereotypes may lead mental health professionals and…

  4. Frequent epigenetic inactivation of KIBRA, an upstream member of the Salvador/Warts/Hippo (SWH) tumor suppressor network, is associated with specific genetic event in B-cell acute lymphocytic leukemia.

    PubMed

    Hill, Victoria K; Dunwell, Thomas L; Catchpoole, Daniel; Krex, Dietmar; Brini, Anna T; Griffiths, Mike; Craddock, Charles; Maher, Eamonn R; Latif, Farida

    2011-03-01

    The WW-domain containing protein KIBRA has recently been identified as a new member of the Salvador/Warts/Hippo (SWH) pathway in Drosophila and is shown to act as a tumor suppressor gene in Drosophila. This pathway is conserved in humans and members of the pathway have been shown to act as tumor suppressor genes in mammalian systems. We determined the methylation status of the 5' CpG island associated with the KIBRA gene in human cancers. In a large panel of cancer cell lines representing common epithelial cancers KIBRA was unmethylated. But in pediatric acute lymphocytic leukemia (ALL) cell lines KIBRA showed frequent hypermethylation and silencing of gene expression, which could be reversed by treatment with 5-aza-2'-deoxycytidine. In ALL patient samples KIBRA was methylated in 70% B-ALL but was methylated in < 20% T-ALL leukemia (p = 0.0019). In B-ALL KIBRA methylation was associated with ETV6/RUNX1 [t(12;21) (p13;q22)] chromosomal translocation (p = 0.0082) phenotype, suggesting that KIBRA may play an important role in t(12;21) leukemogenesis. In ALL paired samples at diagnosis and remission KIBRA methylation was seen in diagnostic but not in any of the remission samples accompanied by loss of KIBRA expression in disease state compared to patients in remission. Hence KIBRA methylation occurs frequently in B-cell acute lymphocytic leukemia but not in epithelial cancers and is linked to specific genetic event in B-ALL.

  5. Acute health effects of ambient air pollution: the ultrafine particle hypothesis.

    PubMed

    Utell, M J; Frampton, M W

    2000-01-01

    A strong and consistent association has been observed between adjusted mortality rates and ambient particle concentration. The strongest associations are seen for respiratory and cardiac deaths, particularly among the elderly. Particulate air pollution is also associated with asthma exacerbations, increased respiratory symptoms, decreased lung function, increased medication use, and increased hospital admissions. The U.S. Environmental Protection Agency (EPA) has recently promulgated a new national ambient air quality standard for fine particles, and yet the mechanisms for health effects at such low particle mass concentrations remain unclear. Hypotheses to identify the responsible particles have focused on particle acidity, particle content of transition metals, bioaerosols, and ultrafine particles. Because ultrafine particles are efficiently deposited in the respiratory tract and may be important in initiating airway inflammation, we have initiated clinical studies with ultrafine carbon particles in healthy subjects. These studies examine the role of ultrafines in: (1) the induction of airway inflammation; (2) expression of leukocyte and endothelial adhesion molecules in blood; (3) the alteration of blood coagulability; and (4) alteration in cardiac electrical activity. These events could lead to exacerbation of underlying cardiorespiratory disease. For example, airway inflammation may activate endothelium and circulating leukocytes, and induce a systemic acute phase response with transient hypercoagulability; this could explain the epidemiologic linkages between pollutant exposures and cardiovascular events. These approaches should be useful in identifying mechanisms for pollutant-induced respiratory and systemic effects, and in providing data for determining appropriate air quality standards.

  6. Effect of budesonide/formoterol maintenance and reliever therapy on asthma exacerbations

    PubMed Central

    Kuna, P; Peters, M J; Manjra, A I; Jorup, C; Naya, I P; Martínez-Jimenez, N E; Buhl, R

    2007-01-01

    This randomised, double-blind, 6-month study compared budesonide/formoterol for maintenance and relief with salmeterol/fluticasone and a fixed maintenance dose of budesonide/formoterol, both with terbutaline for relief. Following a 2-week run-in, 3335 symptomatic adults and adolescents (mean FEV1 73% predicted, mean inhaled corticosteroid dose 745 μg/day) received budesonide/formoterol 160/4.5 μg one inhalation bid plus additional inhalations as needed, salmeterol/fluticasone 25/125 μg two inhalations bid plus as-needed terbutaline or budesonide/formoterol 320/9 μg one inhalation bid plus as-needed terbutaline. Budesonide/formoterol for maintenance and relief prolonged the time to first severe exacerbation requiring hospitalisation, emergency room treatment or oral steroids (primary variable) vs. fixed-dose salmeterol/fluticasone and budesonide/formoterol (p = 0.0034 and p = 0.023 respectively; log-rank test). Exacerbation rates were 19, 16 and 12 events/100 patients/6 months for salmeterol/fluticasone, fixed-dose budesonide/formoterol and budesonide/formoterol for maintenance and relief, respectively, [rate reduction vs. fixed-dose salmeterol/fluticasone (0.61; 95% CI 0.49–0.76, p < 0.001) and vs. fixed-dose budesonide/formoterol (0.72; 95% CI 0.57–0.90, p = 0.0048)]. Budesonide/formoterol maintenance and relief patients used less inhaled corticosteroid vs. salmeterol/fluticasone and fixed-dose budesonide/formoterol patients. All treatments provided similar marked improvements in lung function, asthma control days and asthma-related quality of life. Budesonide/formoterol for maintenance and relief reduces asthma exacerbations and maintains similar daily asthma control at a lower overall drug load compared with fixed-dose salmeterol/fluticasone and budesonide/formoterol. PMID:17362472

  7. The Clinical and Economic Impact of Exacerbations of Chronic Obstructive Pulmonary Disease: A Cohort of Hospitalized Patients

    PubMed Central

    Blasi, Francesco; Cesana, Giancarlo; Conti, Sara; Chiodini, Virginio; Aliberti, Stefano; Fornari, Carla; Mantovani, Lorenzo Giovanni

    2014-01-01

    Background Chronic Obstructive Pulmonary Disease (COPD) is a common disease with significant health and economic consequences. This study assesses the burden of COPD in the general population, and the influence of exacerbations (E-COPD) on disease progression and costs. Methods This is a secondary data analysis of healthcare administrative databases of the region of Lombardy, in northern Italy. The study included ≥ 40 year-old patients hospitalized for a severe E-COPD (index event) during 2006. Patients were classified in relation to the number and type of E-COPD experienced in a three-year pre-index period. Subjects were followed up until December 31st, 2009, collecting data on healthcare resource use and vital status. Results 15857 patients were enrolled –9911 males, mean age: 76 years (SD 10). Over a mean follow-up time of 2.4 years (1.36), 81% of patients had at least one E-COPD with an annual rate of 3.2 exacerbations per person-year and an all-cause mortality of 47%. A history of exacerbation influenced the occurrence of new E-COPD and mortality after discharge for an E-COPD. On average, the healthcare system spent 6725€ per year per person (95%CI 6590–6863). Occurrence and type of exacerbations drove the direct healthcare cost. Less than one quarter of patients presented claims for pulmonary function tests. Conclusions COPD imposes a substantial burden on healthcare systems, mainly attributable to the type and occurrence of E-COPD, or in other words, to the exacerbator phenotypes. A more tailored approach to the management of COPD patients is required. PMID:24971791

  8. Concomitant therapy with Cineole (Eucalyptole) reduces exacerbations in COPD: A placebo-controlled double-blind trial

    PubMed Central

    Worth, Heinrich; Schacher, Christian; Dethlefsen, Uwe

    2009-01-01

    Background The clinical effects of mucolytics in patients with chronic obstructive pulmonary disease (COPD) are discussed controversially. Cineole is the main constituent of eucalyptus oil and mainly used in inflammatory airway diseases as a mucolytic agent. We hypothesised that its known mucolytic, bronchodilating and anti-inflammatory effects as concomitant therapy would reduce the exacerbation rate and show benefits on pulmonary function tests as well as quality of life in patients with COPD. Methods In this double-blind, placebo-controlled multi-center-study we randomly assigned 242 patients with stable COPD to receive 200 mg of cineole or placebo 3 times daily as concomitant therapy for 6 months during winter-time. The frequency, duration and severity of exacerbations were combined as primary outcome measures for testing as multiple criteria. Secondary outcome measures included changes of lung function, respiratory symptoms and quality of life as well as the single parameters of the exacerbations. Results Baseline demographics, lung function and standard medication of both groups were comparable. During the treatment period of 6 months the multiple criteria frequency, severity and duration of exacerbations were significantly lower in the group treated with cineole in comparison to placebo. Secondary outcome measures validated these findings. Improvement of lung function, dyspnea and quality of life as multiple criteria were statistically significant relative to placebo. Adverse events were comparable in both groups. Conclusion Concomitant therapy with cineole reduces exacerbations as well as dyspnea and improves lung function and health status. This study further suggests cineole as an active controller of airway inflammation in COPD by intervening in the pathophysiology of airway inflammation of the mucus membrane. Trial registration ISRCTN07600011 PMID:19624838

  9. Acute pancreatitis: clinical vs. CT findings

    SciTech Connect

    Hill, M.C.; Barkin, J.; Isikoff, M.B.; Silver stein, W.; Kalser, M.

    1982-08-01

    In a prospective study of 91 patients with acute pancreatitis, computed tomographic (CT) findings were correlated with the clinical type of acute pancreatitis. In acute edematous pancreatitis (63 patients; 16 with repeat CT), CT was normal (28%) or showed inflammation limited to the pancreas (61%). Phlegmonous changes were present in 11%, including one patient with focal pancreatic hemorrhage, indicating that clinically unsuspected hemorrhagic pancreatitis can occur. In acute necrotizing (hemorrhagic, suppurative) pancreatitis (nine patients; eight with repeat CT), no patient had a normal CT scan and 89% had phlegmonous changes. One patient had hemorrhagic pancreatitis and three had abscesses. In acute exacerbation of chronic pancreatitis (10 patients; three with repeat CT), there were pancreatic calcifications (70%), a focal mass (40%), and pancreatic ductal dilation (30%). On follow-up CT, the findings of acute pancreatitis did not always disappear with resolution of the clinical symptons. This was especialy true of phlegmonous pancreatitis, where the CT findings could persist for months.

  10. [Good practice in occupational health services--Certification of stroke as an accident at work. Need for secondary prevention in people returning to work after acute cerebrovascular events].

    PubMed

    Marcinkiewicz, Andrzej; Walusiak-Skorupa, Jolanta

    2015-01-01

    The classification of an acute vascular episode, both heart infarct and stroke, as an accident at work poses difficulties not only for post accidental teams, but also to occupational health professionals, experts and judges at labor and social insurance courts. This article presents the case of a 41-year-old office worker, whose job involved client services. While attending a very aggressive customer she developed solid stress that resulted in symptoms of the central nervous system (headache, speech disturbances). During her hospitalisation at the neurological unit ischemic stroke with transient mixed type aphasia was diagnosed. Magnetic resonance imaging (MRI) scan of the head revealed subacute ischemia. After an analysis of the accident circumstances, the employer's post accidental team decided that ischemic stroke had been an accident at work, because it was a sudden incident due to an external cause inducing work-related traumatic stroke. As a primary cause tough stress and emotional strain due to the situation developed while attending the customer were acknowledged. During control medical check up after 5 months the patient was found to be fit for work, so she could return to work. However, it should be noted that such a check up examination of subjects returning to work after stroke must be holistic, including the evaluation of job predispositions and health education aimed at secondary prevention of heart and vascular diseases with special reference to their risk factors. PMID:26536976

  11. [Good practice in occupational health services--Certification of stroke as an accident at work. Need for secondary prevention in people returning to work after acute cerebrovascular events].

    PubMed

    Marcinkiewicz, Andrzej; Walusiak-Skorupa, Jolanta

    2015-01-01

    The classification of an acute vascular episode, both heart infarct and stroke, as an accident at work poses difficulties not only for post accidental teams, but also to occupational health professionals, experts and judges at labor and social insurance courts. This article presents the case of a 41-year-old office worker, whose job involved client services. While attending a very aggressive customer she developed solid stress that resulted in symptoms of the central nervous system (headache, speech disturbances). During her hospitalisation at the neurological unit ischemic stroke with transient mixed type aphasia was diagnosed. Magnetic resonance imaging (MRI) scan of the head revealed subacute ischemia. After an analysis of the accident circumstances, the employer's post accidental team decided that ischemic stroke had been an accident at work, because it was a sudden incident due to an external cause inducing work-related traumatic stroke. As a primary cause tough stress and emotional strain due to the situation developed while attending the customer were acknowledged. During control medical check up after 5 months the patient was found to be fit for work, so she could return to work. However, it should be noted that such a check up examination of subjects returning to work after stroke must be holistic, including the evaluation of job predispositions and health education aimed at secondary prevention of heart and vascular diseases with special reference to their risk factors.

  12. NOTCH2 and FLT3 gene mis-splicings are common events in patients with acute myeloid leukemia (AML): new potential targets in AML

    PubMed Central

    Bar-Natan, Michal; Haibe-Kains, Benjamin; Pilarski, Patrick M.; Bach, Christian; Pevzner, Samuel; Calimeri, Teresa; Avet-Loiseau, Herve; Lode, Laurence; Verselis, Sigitas; Fox, Edward A.; Galinsky, Ilene; Mathews, Steven; Dagogo-Jack, Ibiayi; Wadleigh, Martha; Steensma, David P.; Motyckova, Gabriela; Deangelo, Daniel J.; Quackenbush, John; Tenen, Daniel G.; Stone, Richard M.; Griffin, James D.

    2014-01-01

    Our previous studies revealed an increase in alternative splicing of multiple RNAs in cells from patients with acute myeloid leukemia (AML) compared with CD34+ bone marrow cells from normal donors. Aberrantly spliced genes included a number of oncogenes, tumor suppressor genes, and genes involved in regulation of apoptosis, cell cycle, and cell differentiation. Among the most commonly mis-spliced genes (>70% of AML patients) were 2, NOTCH2 and FLT3, that encode myeloid cell surface proteins. The splice variants of NOTCH2 and FLT3 resulted from complete or partial exon skipping and utilization of cryptic splice sites. Longitudinal analyses suggested that NOTCH2 and FLT3 aberrant splicing correlated with disease status. Correlation analyses between splice variants of these genes and clinical features of patients showed an association between NOTCH2-Va splice variant and overall survival of patients. Our results suggest that NOTCH2 and FLT3 mis-splicing is a common characteristic of AML and has the potential to generate transcripts encoding proteins with altered function. Thus, splice variants of these genes might provide disease markers and targets for novel therapeutics. PMID:24574459

  13. Rationale and design of a secondary prevention trial of lowering normal plasma cholesterol levels after acute myocardial infarction: the Cholesterol and Recurrent Events trial (CARE)

    PubMed

    Sacks, F M; Pfeffer, M A; Moye', L; Brown, L E; Hamm, P; Cole, T G; Hawkins, C M; Braunwald, E

    1991-12-01

    Recent clinical trials of primary and secondary prevention of cardiovascular disease have demonstrated that lowering plasma cholesterol decreases the incidence of coronary heart disease in patients with elevated plasma cholesterol. However, it is not known whether patients with established coronary artery disease and normal plasma cholesterol can be benefited. Several previous prevention trials reviewed in this report found that patients who had plasma cholesterol levels at baseline in the upper portion of the eligibility range (e.g., greater than 240 mg/dl) received greater benefit from hypolipidemic diet or drug therapy than patients who had lower plasma cholesterol levels at baseline. The recent availability of drugs that are more potent and less prone to cause adverse reactions than previous regimens permits this important question to be addressed. The Cholesterol and Recurrent Events trial is testing whether pravastatin, a hydroxymethylglutaryl coenzyme A reductase inhibitor, will decrease the sum of fatal coronary heart disease and nonfatal myocardial infarction (MI) in patients who have recovered from a MI and who have normal total cholesterol levels. Fatal cardiovascular disease and total mortality are important secondary end points. The trial is enrolling 4,000 men and women from 80 centers throughout North America, age 21 to 75 years, who have survived MI for 3 to 20 months, who have plasma total cholesterol less than 240 mg/dl (6.2 mmol/liter) and low-density cholesterol of 115 to 174 mg/dl (3.0 to 4.5 mmol/liter), and who are representative of the general population of patients with MI. Patients are randomized to either active or inactive drug therapy. Active therapy consists of pravastatin, 40 mg/day, designed to achieve an average decrease in low-density lipoprotein cholesterol of approximately 30%, and an increase in high-density lipoprotein of 5%. The average duration of follow-up will be greater than or equal to 5 years. To protect against a lower

  14. High event-free survival rate with minimum-dose-anthracycline treatment in childhood acute promyelocytic leukaemia: a nationwide prospective study by the Japanese Paediatric Leukaemia/Lymphoma Study Group.

    PubMed

    Takahashi, Hiroyuki; Watanabe, Tomoyuki; Kinoshita, Akitoshi; Yuza, Yuki; Moritake, Hiroshi; Terui, Kiminori; Iwamoto, Shotaro; Nakayama, Hideki; Shimada, Akira; Kudo, Kazuko; Taki, Tomohiko; Yabe, Miharu; Matsushita, Hiromichi; Yamashita, Yuka; Koike, Kazutoshi; Ogawa, Atsushi; Kosaka, Yoshiyuki; Tomizawa, Daisuke; Taga, Takashi; Saito, Akiko M; Horibe, Keizo; Nakahata, Tatsutoshi; Miyachi, Hayato; Tawa, Akio; Adachi, Souichi

    2016-08-01

    We evaluated the efficacy of treatment using reduced cumulative doses of anthracyclines in children with acute promyelocytic leukaemia (APL) in the Japanese Paediatric Leukaemia/Lymphoma Study Group AML-P05 study. All patients received two and three subsequent courses of induction and consolidation chemotherapy respectively, consisting of all-trans retinoic acid (ATRA), cytarabine and anthracyclines, followed by maintenance therapy with ATRA. Notably, a single administration of anthracyclines was introduced in the second induction and all consolidation therapies to minimize total doses of anthracycline. The 3-year event-free (EFS) and overall survival rates for 43 eligible children were 83·6% [95% confidence interval (CI): 68·6-91·8%] and 90·7% (95% CI: 77·1-96·4%), respectively. Although two patients died of intracranial haemorrhage or infection during induction phases, no cardiac adverse events or treatment-related deaths were observed during subsequent phases. Patients not displaying M1 marrow after the first induction therapy, or those under 5 years of age at diagnosis, showed inferior outcomes (3-year EFS rate; 33·3% (95% CI: 19·3-67·6%) and 54·6% (95% CI: 22·9-78·0%), respectively). In conclusion, a single administration of anthracycline during each consolidation phase was sufficient for treating childhood APL. In younger children, however, conventional ATRA and chemotherapy may be insufficient so that alternative therapies should be considered.

  15. Exercise training exacerbates tourniquet ischemia-induced decreases in GLUT4 expression and muscle atrophy in rats.

    PubMed

    Tsai, Ying-Lan; Hou, Chien-Wen; Liao, Yi-Hung; Chen, Chung-Yu; Lin, Fang-Ching; Lee, Wen-Chih; Chou, Shih-Wei; Kuo, Chia-Hua

    2006-05-15

    The current study determined the interactive effects of ischemia and exercise training on glycogen storage and GLUT4 expression in skeletal muscle. For the first experiment, an acute 1-h tourniquet ischemia was applied to one hindlimb of both the 1-week exercise-trained and untrained rats. The contralateral hindlimb served as control. For the second experiment, 1-h ischemia was applied daily for 1 week to both trained (5 h post-exercise) and untrained rats. GLUT4 mRNA was not affected by acute ischemia, but exercise training lowered GLUT4 mRNA in the acute ischemic muscle. GLUT4 protein levels were elevated by exercise training, but not in the acute ischemic muscle. Exercise training elevated muscle glycogen above untrained levels, but this increase was reversed by chronic ischemia. GLUT4 mRNA and protein levels were dramatically reduced by chronic ischemia, regardless of whether the animals were exercise-trained or not. Chronic ischemia significantly reduced plantaris muscle mass, with a greater decrease found in the exercise-trained rats. In conclusion, the exercise training effect on muscle GLUT4 protein expression was prevented by acute ischemia. Furthermore, chronic ischemia-induced muscle atrophy was exacerbated by exercise training. This result implicates that exercise training could be detrimental to skeletal muscle with severely impaired microcirculation.

  16. Naproxen 500 mg bid versus acetaminophen 1000 mg qid: effect on swelling and other acute postoperative events after bilateral third molar surgery.

    PubMed

    Bjørnsson, G A; Haanaes, H R; Skoglund, L A

    2003-08-01

    A controlled, randomized, double-blind crossover study, in which the patients acted as their own controls, was carried out to test the efficacy of naproxen 500 mg x 2 versus acetaminophen 1000 mg x 4 for 3 days on the postoperative course following third molar surgery. Acetaminophen reduced the mean swelling on the 3rd postoperative day by 22.4% (p = 0.023) compared to that after naproxen. On the 6th postoperative day, there was 20.9% less mean swelling with naproxen (p = 0.44), although the total swelling measurements were much less than those measured on the 3rd postoperative day. Summed pain intensity (SUMPI3.5-11) on the day of surgery revealed no statistically significant difference between the acetaminophen or naproxen regimen with the exception of 0.5 hours (p = 0.002) and 1 hour (p = 0.009) after first medication when acetaminophen gave less pain than naproxen. Since the drug regimens were different, summed PI for the first acetaminophen dose interval (SUMPI3.5-6) and the first naproxen dose interval (SUMPI3.5-9) was calculated. There was a tendency toward a statistically significant difference in favor of acetaminophen for SUMPI3.5-6 (p = 0.055) but no statistically significant difference (p = 0.41) between the treatments with respect to SUMPI3.5-9. Naproxen was statistically superior (p < or = 0.002) to acetaminophen at 08:00, 12:00, and 16:00 hours on the 1st postoperative day and at 08:00 hours on the 2nd postoperative day, when the pain intensity level was lower than that on the day of surgery. A 3-day acetaminophen regimen reduces acute postoperative swelling better than naproxen on the 3rd postoperative day after third molar surgery but not on the 6th postoperative day when the total swelling is less. PMID:12953342

  17. Usefulness of Combining Galectin-3 and BIVA Assessments in Predicting Short- and Long-Term Events in Patients Admitted for Acute Heart Failure

    PubMed Central

    De Berardinis, Benedetta; Magrini, Laura; Zampini, Giorgio; Zancla, Benedetta; Salerno, Gerardo; Cardelli, Patrizia; Di Stasio, Enrico; Gaggin, Hanna K.; Belcher, Arianna; Parry, Blair A.; Nagurney, John T.; Januzzi, James L.; Di Somma, Salvatore

    2014-01-01

    Introduction. Acute heart failure (AHF) is associated with a higher risk for the occurrence of rehospitalization and death. Galectin-3 (GAL3) is elevated in AHF patients and is an indicator in predicting short-term mortality. The total body water using bioimpedance vector analysis (BIVA) is able to identify mortality within AHF patients. The aim of this study was to evaluate the short- and long-term predictive value of GAL3, BIVA, and the combination of both in AHF patients in Emergency Department (ED). Methods. 205 ED patients with AHF were evaluated by testing for B type natriuretic peptide (BNP) and GAL3. The primary endpoint was death and rehospitalization at 30, 60, 90, and 180 days and 12 and 18 months. AHF patients were evaluated at the moment of ED arrival with clinical judgment and GAL3 and BIVA measurement. Results. GAL3 level was significantly higher in patients >71 years old, and with eGFR < 30 cc/min. The area under the curve (AUC) of GAL3 + BIVA, GAL3 and BIVA for death and rehospitalization both when considered in total and when considered serially for the follow-up period showed that the combination has a better prognostic value. Kaplan-Meier survival curve for GAL3 values >17.8 ng/mL shows significant survival difference. At multivariate Cox regression analysis GAL3 is an independent variable to predict death + rehospitalization with a value of 32.24 ng/mL at 30 days (P < 0.005). Conclusion. In patients admitted for AHF an early assessment of GAL3 and BIVA seems to be useful in identifying patients at high risk for death and rehospitalization at short and long term. Combining the biomarker and the device could be of great utility since they monitor the severity of two pathophysiological different mechanisms: heart fibrosis and fluid overload. PMID:25101304

  18. Serum Reactive Oxygen Metabolite Levels Predict Severe Exacerbations of Asthma

    PubMed Central

    Nakamoto, Keitaro; Watanabe, Masato; Sada, Mitsuru; Inui, Toshiya; Nakamura, Masuo; Honda, Kojiro; Wada, Hiroo; Mikami, Yu; Matsuzaki, Hirotaka; Horie, Masafumi; Noguchi, Satoshi; Yamauchi, Yasuhiro; Koyama, Hikari; Kogane, Toshiyuki; Kohyama, Tadashi; Takizawa, Hajime

    2016-01-01

    Background and Purpose Bronchial asthma (BA) is a chronic airway disease characterized by airway hyperresponsiveness and remodeling, which are intimately linked to chronic airway inflammation. Reactive oxygen species (ROS) such as hydrogen peroxide are generated by inflammatory cells that are involved in the pathogenesis of BA. However, the role of ROS in the management of BA patients is not yet clear. We attempted to determine the role of ROS as a biomarker in the clinical setting of BA. Subjects and Methods We enrolled patients with BA from 2013 through 2015 and studied the degrees of asthma control, anti-asthma treatment, pulmonary function test results, fractional exhaled nitric oxide (FeNO), serum reactive oxygen metabolite (ROM) levels, and serum levels of interleukin (IL)-6 and IL-8. Results We recruited 110 patients with BA. Serum ROM levels correlated with white blood cell (WBC) count (rs = 0.273, p = 0.004), neutrophil count (rs = 0.235, p = 0.014), CRP (rs = 0.403, p < 0.001), and IL-6 (rs = 0.339, p < 0.001). Serum ROM levels and IL-8 and CRP levels negatively correlated with %FEV1 (rs = -0.240, p = 0.012, rs = -0.362, p < 0.001, rs = -0.197, p = 0.039, respectively). Serum ROM levels were significantly higher in patients who experienced severe exacerbation within 3 months than in patients who did not (339 [302–381] vs. 376 [352–414] CARR U, p < 0.025). Receiver-operating characteristics analysis showed that ROM levels correlated significantly with the occurrence of severe exacerbation (area under the curve: 0.699, 95% CI: 0.597–0.801, p = 0.025). Conclusions Serum levels of ROM were significantly associated with the degrees of airway obstruction, WBC counts, neutrophil counts, IL-6, and severe exacerbations. This biomarker may be useful in predicting severe exacerbations of BA. PMID:27776186

  19. Effects of N-acetylcysteine on asthma exacerbation.

    PubMed

    Aliyali, Masoud; Poorhasan Amiri, Ali; Sharifpoor, Ali; Zalli, Fatemeh

    2010-06-01

    Airway mucus hypersecretion and increased oxidative stress are clinical and pathophysiological features of asthma exacerbation. We studied effects of N-acetylcysteine (NAC) as a mucolytic and antioxidant agent in asthma exacerbation. In this randomized, single-blinded, placebo-controlled study 50 patients ( 17 male, 33 female, mean age 48.94+/-13.68) with asthma exacerbation were randomized to receive either oral 600 mg b.d. N-acetylcysteine or placebo in addition to standard treatment during 5 days hospitalization. Daily measurements of wheezing, dyspnea, cough, sputum, expectoration, night sleep scores and morning PEFR were performed. There was no significant difference in wheezing score between patients assigned NAC and those assigned placebo in day 5(0.84[SD 0.94] VS 0.87[SD 0.79]) and also in cough score (0.72[SD 0.84] VS 0.79[SD 0.97]), dyspnea score (0.84[SD 1.06] VS 0.91[SD 1.01]), sputum score(0.79[SD 0.83] VS 0.62[SD 0.71]), expectoration score(0.79[SD 0.97] VS 0.83[SD 1.09]), night sleep score(1[SD 1.17] VS 0.67[SD 0.98] and morning PEFR (256[SD 96.36] VS 282[SD 98.86]). We concluded that addition of N-acetylcysteine to usual asthma medication has no significant effect in treatment of asthma exacerbation. PMID:20683104

  20. Application of appropriateness criteria for hospitalization in COPD exacerbation.

    PubMed

    Garcia-Gutierrez, Susana; Quintana, José M; Barrio, Irantzu; Bare, Marisa; Fernandez, Nerea; Vidal, Silvia; Gonzalez, Nerea; Lafuente, Iratxe; Arteta, Edurne; Esteban, Cristóbal; Pulido, Esther

    2013-06-01

    The IRYSS-COPD appropriateness study was developed in 16 hospitals belonging to the Spanish National Health Service from June 2008 to September 2010 (n = 2,877). The objectives were to apply a set of explicit criteria for the appropriateness of hospital admission created by the RAND/UCLA methodology to patients evaluated in the emergency department (ED) for exacerbations of COPD. This is a prospective cohort study. We explored the relationship between appropriateness of admission as defined by the explicit criteria and the final decision to admit or discharge. A total of 2,877 patients were included for analysis; of these, 1,747 (60.7 %) were admitted and 1,130 (39.3 %) were discharged from the ED to home. Among patients classified by the explicit criteria as appropriate for hospital admission, 81.3 % were admitted, compared with 64.81 % of those classified as uncertain and 48.65 % of those classified as inappropriate for admission. Severity of exacerbation was the most influencing variable in the decision. Application of our explicit criteria for appropriate hospital admission among a large sample of patients experiencing an exacerbation of COPD in the ED setting suggests that these criteria could be used as the basis for clinical decision-making and health-care assessment.

  1. Infection as an Environmental Trigger of Multiple Sclerosis Disease Exacerbation

    PubMed Central

    Steelman, Andrew J.

    2015-01-01

    Over the past several decades, significant advances have been made in identifying factors that contribute to the pathogenesis of multiple sclerosis (MS) and have culminated in the approval of some effective therapeutic strategies for disease intervention. However, the mechanisms by which environmental factors, such as infection, contribute to the pathogenesis and/or symptom exacerbation remain to be fully elucidated. Relapse frequency in MS patients contributes to neurological impairment and, in the initial phases of disease, serves as a predictor of poor disease prognosis. The purpose of this review is to examine the evidence that supports a role for peripheral infection in modulating the natural history of this disease. Evidence supporting a role for infection in promoting exacerbation in animal models of MS is also reviewed. Finally, a few mechanisms by which infection may exacerbate symptoms of MS and other neurological diseases are discussed. Those who comprise the majority of MS patients acquire approximately two upper-respiratory infections per year; furthermore, this type of infection doubles the risk for MS relapse, underscoring the contribution of this relationship as being potentially important and particularly detrimental. PMID:26539193

  2. Integrated care prevents hospitalisations for exacerbations in COPD patients.

    PubMed

    Casas, A; Troosters, T; Garcia-Aymerich, J; Roca, J; Hernández, C; Alonso, A; del Pozo, F; de Toledo, P; Antó, J M; Rodríguez-Roisín, R; Decramer, M

    2006-07-01

    Hospital admissions due to chronic obstructive pulmonary disease (COPD) exacerbations have a major impact on the disease evolution and costs. The current authors postulated that a simple and well-standardised, low-intensity integrated care intervention can be effective to prevent such hospitalisations. Therefore, 155 exacerbated COPD patients (17% females) were recruited after hospital discharge from centres in Barcelona (Spain) and Leuven (Belgium). They were randomly assigned to either integrated care (IC; n = 65; age mean+/-sd 70+/-9 yrs; forced expiratory volume in one second (FEV(1)) 1.1+/-0.5 L, 43% predicted) or usual care (UC; n = 90; age 72+/-9 yrs; FEV(1) 1.1+/-0.05 L, 41% pred). The IC intervention consisted of an individually tailored care plan upon discharge shared with the primary care team, as well as accessibility to a specialised nurse case manager through a web-based call centre. After 12 months' follow-up, IC showed a lower hospitalisation rate (1.5+/-2.6 versus 2.1+/-3.1) and a higher percentage of patients without re-admissions (49 versus 31%) than UC without differences in mortality (19 versus 16%, respectively). In conclusion, this trial demonstrates that a standardised integrated care intervention, based on shared care arrangements among different levels of the system with support of information technologies, effectively prevents hospitalisations for exacerbations in chronic obstructive pulmonary disease patients.

  3. The role of particulate matter in exacerbation of atopic asthma.

    PubMed

    Gavett, S H; Koren, H S

    2001-01-01

    Increasing evidence shows that elevated levels of particulate matter (PM) can exacerbate existing asthma, while evidence that PM can promote the induction of asthma is limited. PM in ambient air has been associated with increased emergency room visits and medication use by asthmatics. Controlled human exposure studies of acid aerosols suggest increased responses among adolescent asthmatics. Increased ambient and indoor levels of bioaerosols (e.g., house dust mite, fungal spores, endotoxin) have been associated with exacerbation of asthma. Environmental Protection Agency (EPA) studies focus on the effects of exposing humans and animal models to a combination of various PM samples (e.g., diesel exhaust particles, oil fly ash) and allergens (e.g., house dust mite, ovalbumin). These research efforts to understand the mechanisms by which PM exposure can promote allergic sensitization and exacerbate existing asthma concentrate on the role of transition metals. Exposure of animal models to combined PM and allergen promotes allergic sensitization and increases allergic inflammation and airway hyperresponsiveness. Exposure of healthy human volunteers to emission source PM samples promotes inflammation and increased indices of oxidant formation correlating with the quantity of transition metals in the samples. Results of these studies suggest that transition metals in ambient PM promote the formation of reactive oxygen species and subsequent lung injury, inflammation, and airway hyperresponsiveness leading to airflow limitation and symptoms of asthma.

  4. Lung ultrasound-guided management of acute breathlessness during pregnancy.

    PubMed

    Zieleskiewicz, L; Lagier, D; Contargyris, C; Bourgoin, A; Gavage, L; Martin, C; Leone, M

    2013-01-01

    Lung ultrasonography is a standard tool in the intensive care unit and in emergency medicine, but has not been described in the particular setting of the labour ward. During pregnancy, acute respiratory failure and pulmonary oedema are not uncommon life-threatening events. We present two case reports outlining the potential of lung ultrasonography in parturients. In case 1, lung ultrasonography allowed early diagnosis and treatment of acute dyspnoea in a parturient admitted for suspected asthma exacerbation. Lung ultrasonography revealed a 'B-pattern' of vertical lines radiating into the lung tissue, indicating severe pulmonary oedema complicating previously undiagnosed pre-eclampsia. In case 2, a pre-eclamptic patient was managed with combined transthoracic echocardiography and lung ultrasonography. The accuracy of lung ultrasonography in detecting interstitial oedema at a pre-clinical stage allowed adequate fluid resuscitation in this patient who had a high risk of alveolar pulmonary oedema. We believe that these cases strongly support the prospective validation of lung ultrasound for management of lung disorders in pregnant women. PMID:23088788

  5. Endothelial dysfunction exacerbates renal interstitial fibrosis through enhancing fibroblast Smad3 linker phosphorylation in the mouse obstructed kidney.

    PubMed

    Sun, Yu Bo Yang; Qu, Xinli; Li, Xueling; Nikolic-Paterson, David J; Li, Jinhua

    2013-01-01

    Endothelial dysfunction and enhanced transforming growth factor-β (TGF-β)/Smad3 signalling are common features of progressive renal fibrosis. This study investigated a potential link between these mechanisms. In unilateral ureteric obstruction (UUO) we observed an acute (6 hr) down-regulation of nitric oxide synthase 3 (NOS3/eNOS) levels and increased phosphorylation of the linker region of Smad3 at T179 and S208 in Smad3/JNK complexes. These events preceded Smad3 C-terminal domain phosphorylation and the induction of myofibroblast proliferation at 48 hrs. Mice deficient in NOS3 showed enhanced myofibroblast proliferation and collagen accumulation compared to wild type mice in a 7 day UUO model. This was associated with enhanced phosphorylation of Smad3 T179 and S208 by 92% and 88%, respectively, whereas Smad3-C-terminal phosphorylation was not affected. Resolvin D1 (RvD1) can suppress renal fibrosis in the UUO model, and further analysis herein showed that RvD1 protected against endothelial dysfunction and suppressed Smad3/JNK complex formation with a consequent reduction in phosphorylation of Smad3 T179 and S208 by 78% and 65%, respectively, while Smad3 C-terminal phosphorylation was unaltered. In vitro, conditioned media from mouse microvascular endothelial cells (MMEC) treated with a general inhibitor of nitric oxide synthase (L-NAME) augmented the proliferation and collagen production of renal fibroblasts (NRK49F cells) compared to control MMEC media and this was associated with increased phosphorylation of JNK and Smad3 T179 and S208, whereas Smad3-C-terminal domain phosphorylation was unaffected. The addition of RvD1 to L-NAME treated MMEC abrogated these effects of the conditioned media on renal fibroblasts. Finally, Smad3 T179/V and S208/A mutations significantly inhibit TGF-β1 induced up-regulation collagen I promoter. In conclusion, these data suggest that endothelial dysfunction can exacerbate renal interstitial fibrosis through increased fibroblast

  6. Independent effect of prior exacerbation frequency and disease severity on the risk of future exacerbations of COPD: a retrospective cohort study.

    PubMed

    Margüello, Miguel Santibañez; Garrastazu, Roberto; Ruiz-Nuñez, Mario; Helguera, Jose Manuel; Arenal, Sandra; Bonnardeux, Cristina; León, Carlos; Miravitlles, Marc; García-Rivero, Juan Luis

    2016-01-01

    Few studies have researched the independent effect of COPD severity on the risk of future exacerbations adjusted by previous exacerbation frequency. We aimed to analyse the independent effect of COPD severity on the risk of exacerbations in the following year, and whether this effect was stronger or not than the effect of a previous history of exacerbations. We conducted a retrospective population-based cohort study including 900 patients with confirmed COPD. Exacerbation frequency was observed for the previous year and for the following year. Patients were defined as 'Frequent Exacerbator' (FE) phenotype if they suffered ⩾2 exacerbations in a year, and were categorised according to the severity of COPD (GOLD Grades 1-4). Odds ratios (ORs) were estimated by logistic regression adjusting for age, gender, smoking status, severity of COPD and being FE in the previous year. The main predictor of being FE among all grades of COPD severity was a history of frequent exacerbations in the previous year: adjusted OR 4.97; 95% confidence interval (CI) (3.54-6.97). COPD severity was associated with a higher risk of being FE: Crude OR GOLD Grade 4 3.86; 95% CI (1.50-9.93). However, this association diminished after adjusting for being FE in the previous year: adjusted OR 2.08; 95% CI (0.75-5.82). Our results support that a history of frequent exacerbations in the previous year is the most important independent predictor of exacerbations in the following year, also among the most severe COPD patients. Severity of COPD would be associated with a higher risk of exacerbations, but this effect would be partly determined by the exacerbations suffered in the previous year. PMID:27604472

  7. First case report of exacerbated ulcerative colitis after anti-interleukin-6R salvage therapy

    PubMed Central

    Atreya, Raja; Billmeier, Ulrike; Rath, Timo; Mudter, Jonas; Vieth, Michael; Neumann, Helmut; Neurath, Markus F

    2015-01-01

    We present the case of a 53-year-old woman with long-standing ulcerative colitis and severe, steroid-dependent disease course unresponsive to treatment with azathioprine, methotrexate, anti-TNF antibodies (infliximab, adalimumab) and tacrolimus, who refused colectomy as a therapeutic option. As the pro-inflammatory cytokine interleukin-6 (IL-6) had been identified as a crucial regulator in the immunopathogenesis of inflammatory bowel diseases, we treated the patient with biweekly intravenous infusions of an anti-IL-6R antibody (tocilizumab) for 12 wk. However, no clinical improvement of disease activity was noted. In fact, endoscopic, histological and endomicroscopic assessment demonstrated exacerbation of mucosal inflammation and ulcer formation upon anti-IL-6R therapy. Mechanistic studies revealed that tocilizumab treatment failed to suppress intestinal IL-6 production, impaired epithelial barrier function and induced production of pro-inflammatory cytokines such as TNF, IL-21 and IFN-γ. Inhibition of IL-6 by tocilizumab had no clinical benefit in this patient with intractable ulcerative colitis and even led to exacerbation of mucosal inflammation. Our findings suggest that anti-IL-6R antibody therapy may lead to aggravation of anti-TNF resistant ulcerative colitis. When targeting IL-6, the differential responsiveness of target cells has to be taken into account, as IL-6 on the one side promotes acute and chronic mucosal inflammation via soluble IL-6R signaling but on the other side also strongly contributes to epithelial cell survival via membrane bound IL-6R signaling. PMID:26668517

  8. Cigarette Smoke Exposure Exacerbates Lung Inflammation and Compromises Immunity to Bacterial Infection

    PubMed Central

    Lugade, Amit A.; Bogner, Paul N.; Thatcher, Thomas H.; Sime, Patricia J.; Phipps, Richard P.; Thanavala, Yasmin

    2014-01-01

    The detrimental impact of tobacco on human health is clearly recognized and despite aggressive efforts to prevent smoking, close to one billion individuals worldwide continue to smoke. People with chronic obstructive pulmonary disease (COPD) are susceptible to recurrent respiratory infections with pathogens, including non-typeable Haemophilus influenzae (NTHI), yet the reasons for this increased susceptibility are poorly understood. As mortality rapidly increases with multiple exacerbations, development of protective immunity is critical to improving patient survival. Acute NTHI infection has been studied in the context of cigarette smoke exposure, but this is the first study to investigate chronic infection and the generation of adaptive immune responses to NTHI following chronic smoke exposure. After chronic NTHI infection, mice that had previously been exposed to cigarette smoke developed increased lung inflammation and compromised adaptive immunity relative to air-exposed controls. Importantly, NTHI-specific T cells from mice exposed to cigarette smoke produced lower levels of IFN-γ and IL-4, and B cells produced reduced levels of antibodies against outer membrane lipoprotein P6, with impaired IgG1, IgG2a and IgA class-switching. However, production of IL-17, which is associated with neutrophilic inflammation, was enhanced. Interestingly, cigarette smoke exposed mice exhibited a similar defect in the generation of adaptive immunity following immunization with P6. Our study has conclusively demonstrated that cigarette smoke exposure has a profound suppressive effect on the generation of adaptive immune responses to NTHI and suggests the mechanism by which prior cigarette smoke exposure predisposes COPD patients to recurrent infections, leading to exacerbations and contributing to mortality. PMID:24752444

  9. Acute Bronchitis

    MedlinePlus

    ... tightness. There are two main types of bronchitis: acute and chronic. Most cases of acute bronchitis get better within several days. But your ... that cause colds and the flu often cause acute bronchitis. These viruses spread through the air when ...

  10. Periodontal Treatment Reduces Risk of Adverse Respiratory Events in Patients With Chronic Obstructive Pulmonary Disease

    PubMed Central

    Shen, Te-Chun; Chang, Pei-Ying; Lin, Cheng-Li; Chen, Chia-Hung; Tu, Chih-Yen; Hsia, Te-Chun; Shih, Chuen-Ming; Hsu, Wu-Huei; Sung, Fung-Chang; Kao, Chia-Hung

    2016-01-01

    Abstract Treatment of periodontal diseases has been associated with benefit outcomes for patients with chronic obstructive pulmonary disease (COPD). However, no population-based cohort study has been conducted. We evaluated this relationship by retrospective cohort study using a large population data. Using the National Health Insurance claims data of Taiwan, we identified 5562 COPD patients with periodontal diseases who had received periodontal treatment as the treatment group. The comparison group was selected at a 1:1 ratio matched by the propensity score estimated with age, sex, date of COPD diagnosis and periodontal treatment, and comorbidities. Both groups were followed up for 5 years to compare risks of acute exacerbation, pneumonia, and acute respiratory failure. The incidence rates of adverse respiratory events were significantly lower in the treatment group than in the comparison group: 3.79 versus 4.21 per 100 person-years for emergency room visits, 2.75 versus 3.65 per 100 person-years for hospitalizations, and 0.66 versus 0.75 per 100 person-years for intensive care unit admissions. The treatment group also had a 37% reduced risk of deaths (1.81 vs 2.87 per 100 person-years), with an adjusted hazard ratio of 0.57 (95% confidence interval 0.52–0.62). Periodontal treatment for COPD patients could reduce the risk of adverse respiratory events and mortality. The adequate periodontal health care is important for COPD patients with periodontal diseases. PMID:27196497

  11. Incidence of utilization- and symptom-defined COPD exacerbations in hospital- and population-recruited patients

    PubMed Central

    Erdal, Marta; Johannessen, Ane; Eagan, Tomas Mikal; Bakke, Per; Gulsvik, Amund; Grønseth, Rune

    2016-01-01

    Objectives The objectives of this study were to estimate the impact of recruitment source and outcome definition on the incidence of acute exacerbations of COPD (AECOPD) and explore possible predictors of AECOPD. Patients and methods During a 1-year follow-up, we performed a baseline visit and four telephone interviews of 81 COPD patients and 132 controls recruited from a population-based survey and 205 hospital-recruited COPD patients. Both a definition based on health care utilization and a symptom-based definition of AECOPD were applied. For multivariate analyses, we chose a negative binomial regression model. Results COPD patients from the population- and hospital-based samples experienced on average 0.4 utilization-defined and 2.9 symptom-defined versus 1.0 and 5.9 annual exacerbations, respectively. The incidence rate ratios for utilization-defined AECOPD were 2.45 (95% CI 1.22–4.95), 3.43 (95% CI 1.59–7.38), and 5.67 (95% CI 2.58–12.48) with Global Initiative on Obstructive Lung Disease spirometric stages II, III, and IV, respectively. The corresponding incidence rate ratios for the symptom-based definition were 3.08 (95% CI 1.96–4.84), 3.45 (95% CI 1.92–6.18), and 4.00 (95% CI 2.09–7.66). Maintenance therapy (regular long-acting muscarinic antagonists, long-acting beta-2 agonists, inhaled corticosteroids, or theophylline) also increased the risk of AECOPD with both exacerbation definitions (incidence rate ratios 1.65 and 1.73, respectively). The risk of AECOPD was 59%–78% higher in the hospital sample than in the population sample. Conclusion If externally valid conclusions are to be made regarding incidence and predictors of AECOPD, studies should be based on general population samples or adjustments should be made on account of a likely higher incidence in other samples. Likewise, the effect of different AECOPD definitions should be taken into consideration.

  12. Incidence of utilization- and symptom-defined COPD exacerbations in hospital- and population-recruited patients

    PubMed Central

    Erdal, Marta; Johannessen, Ane; Eagan, Tomas Mikal; Bakke, Per; Gulsvik, Amund; Grønseth, Rune

    2016-01-01

    Objectives The objectives of this study were to estimate the impact of recruitment source and outcome definition on the incidence of acute exacerbations of COPD (AECOPD) and explore possible predictors of AECOPD. Patients and methods During a 1-year follow-up, we performed a baseline visit and four telephone interviews of 81 COPD patients and 132 controls recruited from a population-based survey and 205 hospital-recruited COPD patients. Both a definition based on health care utilization and a symptom-based definition of AECOPD were applied. For multivariate analyses, we chose a negative binomial regression model. Results COPD patients from the population- and hospital-based samples experienced on average 0.4 utilization-defined and 2.9 symptom-defined versus 1.0 and 5.9 annual exacerbations, respectively. The incidence rate ratios for utilization-defined AECOPD were 2.45 (95% CI 1.22–4.95), 3.43 (95% CI 1.59–7.38), and 5.67 (95% CI 2.58–12.48) with Global Initiative on Obstructive Lung Disease spirometric stages II, III, and IV, respectively. The corresponding incidence rate ratios for the symptom-based definition were 3.08 (95% CI 1.96–4.84), 3.45 (95% CI 1.92–6.18), and 4.00 (95% CI 2.09–7.66). Maintenance therapy (regular long-acting muscarinic antagonists, long-acting beta-2 agonists, inhaled corticosteroids, or theophylline) also increased the risk of AECOPD with both exacerbation definitions (incidence rate ratios 1.65 and 1.73, respectively). The risk of AECOPD was 59%–78% higher in the hospital sample than in the population sample. Conclusion If externally valid conclusions are to be made regarding incidence and predictors of AECOPD, studies should be based on general population samples or adjustments should be made on account of a likely higher incidence in other samples. Likewise, the effect of different AECOPD definitions should be taken into consideration. PMID:27621614

  13. Neural respiratory drive predicts clinical deterioration and safe discharge in exacerbations of COPD

    PubMed Central

    Suh, Eui-Sik; Mandal, Swapna; Harding, Rachel; Ramsay, Michelle; Kamalanathan, Meera; Henderson, Katherine; O'Kane, Kevin; Douiri, Abdel; Hopkinson, Nicholas S; Polkey, Michael I; Rafferty, Gerrard; Murphy, Patrick B; Moxham, John; Hart, Nicholas

    2015-01-01

    Rationale Hospitalised patients with acute exacerbation of COPD may deteriorate despite treatment, with early readmission being common. Objectives To investigate whether neural respiratory drive, measured using second intercostal space parasternal muscle electromyography (EMGpara), would identify worsening dyspnoea and physician-defined inpatient clinical deterioration, and predict early readmission. Methods Patients admitted to a single-site university hospital with exacerbation of COPD were enrolled. Spirometry, inspiratory capacity (IC), EMGpara, routine physiological parameters, modified early warning score (MEWS), modified Borg scale for dyspnoea and physician-defined episodes of deterioration were recorded daily until discharge. Readmissions at 14 and 28 days post discharge were recorded. Measurements and main results 120 patients were recruited (age 70±9 years, forced expiratory volume in 1 s (FEV1) of 30.5±11.2%). Worsening dyspnoea, defined as at least one-point increase in Borg scale, was associated with increases in EMGpara%max and MEWS, whereas an increase in EMGpara%max alone was associated with physician-defined inpatient clinical deterioration. Admission-to-discharge change (Δ) in the normalised value of EMGpara (ΔEMGpara%max) was inversely correlated with ΔFEV1 (r=−0.38, p<0.001) and ΔIC (r=−0.44, p<0.001). ΔEMGpara%max predicted 14-day readmission (OR 1.13, 95% 1.03 to 1.23) in the whole cohort and 28-day readmission in patients under 85 years (OR 1.09, 95% CI 1.01 to 1.18). Age (OR 1.08, 95% CI 1.03 to 1.14) and 12-month admission frequency (OR 1.29, 1.01 to 1.66), also predicted 28-day readmission in the whole cohort. Conclusions Measurement of neural respiratory drive by EMGpara represents a novel physiological biomarker that may be helpful in detecting inpatient clinical deterioration and identifying the risk of early readmission among patients with exacerbations of COPD. Trial registration NCT01361451. PMID:26194996

  14. Antibiotics against Pseudomonas aeruginosa for COPD exacerbation in ICU: a 10-year retrospective study

    PubMed Central

    Planquette, Benjamin; Péron, Julien; Dubuisson, Etienne; Roujansky, Ariane; Laurent, Virginie; Le Monnier, Alban; Legriel, Stephane; Ferre, Alexis; Bruneel, Fabrice; Chiles, Peter G; Bedos, Jean P

    2015-01-01

    Summary Chronic obstructive pulmonary disease (COPD) is a frequent source of hospitalization. Antibiotics are largely prescribed during COPD exacerbation. Our hypothesis is that large broad-spectrum antibiotics are more and more frequently prescribed. Our results confirm this trend and highlight that the increase in large broad-spectrum use in COPD exacerbation is largely unexplained. Background Acute COPD exacerbation (AECOPD) is frequently due to respiratory tract infection, and the benefit of antipseudomonal antibiotics (APA) is still debated. Health care–associated pneumonia (HCAP) was defined in 2005 and requires broad-spectrum antibiotherapy. The main objectives are to describe the antibiotic use for AECOPD in intensive care unit and to identify factors associated with APA use and AECOPD prognosis. Methods We conducted a monocentric, retrospective study on all AECOPDs in the intensive care unit treated by antibiotics for respiratory tract infection. Treatment failure (TF) was defined by death, secondary need for mechanical ventilation, or secondary systemic steroid treatment. A multivariate analysis was used to assess factors associated with APA prescription and TF. Results From January 2000 to December 2011, 111 patients were included. Mean age was 69 years (±12), mean forced expiratory volume 38% of theoretic value (±13). Thirty-five (31%) patients were intubated, and 52 (47%) were treated with noninvasive ventilation. From 107 patients, 8 (7%) cases of Pseudomonas aeruginosa were documented. APAs were prescribed in 21% of patients before 2006 versus 57% after (P=0.001). TF prevalence was 31%. Risk factors for P. aeruginosa in COPD and HCAP diagnosis did not influence APA, whereas the post-2006 period was independently associated with APA prescription (odds ratio 6.2; 95% confidence interval 1.9–20.3; P=0.0013). APA did not improve TF (odds ratio 1.09; 95% confidence interval 0.37–3.2). Conclusion HCAP guidelines were followed by an increase in APA

  15. Interaction with host factors exacerbates Trypanosoma cruzi cell invasion capacity upon oral infection.

    PubMed

    Covarrubias, Charles; Cortez, Mauro; Ferreira, Daniele; Yoshida, Nobuko

    2007-12-01

    Outbreaks of severe acute Chagas' disease acquired by oral infection, leading to death in some cases, have occurred in recent years. Using the mouse model, we investigated the basis of such virulence by analyzing a Trypanosoma cruzi isolate, SC, from a patient with severe acute clinical symptoms, who was infected by oral route. It has previously been shown that, upon oral inoculation into mice, T. cruzi metacyclic trypomastigotes invade the gastric mucosal epithelium by engaging the stage-specific surface glycoprotein gp82, whereas the surface molecule gp90 functions as a down-modulator of cell invasion. We found that, when orally inoculated into mice, metacyclic forms of the SC isolate, which express high levels of gp90, produced high parasitemias and high mortality, in sharp contrast with the reduced infectivity in vitro. Upon recovery from the mouse stomach 1h after oral inoculation, the gp90 molecule of the parasites was completely degraded, and their entry into HeLa cells, as well as into Caco-2 cells, was increased. The gp82 molecule was more resistant to digestive action of the gastric juice. Host cell invasion of SC isolate metacyclic trypomastigotes was augmented in the presence of gastric mucin. No alteration in infectivity was observed in T. cruzi strains CL and G which were used as references and which express gp90 molecules resistant to degradation by gastric juice. Taken together, our findings suggest that the exacerbation of T. cruzi infectivity, such as observed upon interaction of the SC isolate with the mouse stomach components, may be responsible for the severity of acute Chagas' disease that has been reported in outbreaks of oral T. cruzi infection.

  16. Independent effect of prior exacerbation frequency and disease severity on the risk of future exacerbations of COPD: a retrospective cohort study

    PubMed Central

    Margüello, Miguel Santibañez; Garrastazu, Roberto; Ruiz-Nuñez, Mario; Helguera, Jose Manuel; Arenal, Sandra; Bonnardeux, Cristina; León, Carlos; Miravitlles, Marc; García-Rivero, Juan Luis

    2016-01-01

    Few studies have researched the independent effect of COPD severity on the risk of future exacerbations adjusted by previous exacerbation frequency. We aimed to analyse the independent effect of COPD severity on the risk of exacerbations in the following year, and whether this effect was stronger or not than the effect of a previous history of exacerbations. We conducted a retrospective population-based cohort study including 900 patients with confirmed COPD. Exacerbation frequency was observed for the previous year and for the following year. Patients were defined as ‘Frequent Exacerbator’ (FE) phenotype if they suffered ⩾2 exacerbations in a year, and were categorised according to the severity of COPD (GOLD Grades 1–4). Odds ratios (ORs) were estimated by logistic regression adjusting for age, gender, smoking status, severity of COPD and being FE in the previous year. The main predictor of being FE among all grades of COPD severity was a history of frequent exacerbations in the previous year: adjusted OR 4.97; 95% confidence interval (CI) (3.54–6.97). COPD severity was associated with a higher risk of being FE: Crude OR GOLD Grade 4 3.86; 95% CI (1.50–9.93). However, this association diminished after adjusting for being FE in the previous year: adjusted OR 2.08; 95% CI (0.75–5.82). Our results support that a history of frequent exacerbations in the previous year is the most important independent predictor of exacerbations in the following year, also among the most severe COPD patients. Severity of COPD would be associated with a higher risk of exacerbations, but this effect would be partly determined by the exacerbations suffered in the previous year. PMID:27604472

  17. Respiratory virus transmission dynamics determine timing of asthma exacerbation peaks: Evidence from a population-level model.

    PubMed

    Eggo, Rosalind M; Scott, James G; Galvani, Alison P; Meyers, Lauren Ancel

    2016-02-23

    Asthma exacerbations exhibit a consistent annual pattern, closely mirroring the school calendar. Although respiratory viruses--the "common cold" viruses--are implicated as a principal cause, there is little evidence to link viral prevalence to seasonal differences in risk. We jointly fit a common cold transmission model and a model of biological and environmental exacerbation triggers to estimate effects on hospitalization risk. Asthma hospitalization rate, influenza prevalence, and air quality measures are available, but common cold circulation is not; therefore, we generate estimates of viral prevalence using a transmission model. Our deterministic multivirus transmission model includes transmission rates that vary when school is closed. We jointly fit the two models to 7 y of daily asthma hospitalizations in adults and children (66,000 events) in eight metropolitan areas. For children, we find that daily viral prevalence is the strongest predictor of asthma hospitalizations, with transmission reduced by 45% (95% credible interval =41-49%) during school closures. We detect a transient period of nonspecific immunity between infections lasting 19 (17-21) d. For adults, hospitalizations are more variable, with influenza driving wintertime peaks. Neither particulate matter nor ozone was an important predictor, perhaps because of the large geographic area of the populations. The school calendar clearly and predictably drives seasonal variation in common cold prevalence, which results in the "back-to-school" asthma exacerbation pattern seen in children and indirectly contributes to exacerbation risk in adults. This study provides a framework for anticipating the seasonal dynamics of common colds and the associated risks for asthmatics. PMID:26858436

  18. Respiratory virus transmission dynamics determine timing of asthma exacerbation peaks: Evidence from a population-level model

    PubMed Central

    Scott, James G.; Galvani, Alison P.; Meyers, Lauren Ancel

    2016-01-01

    Asthma exacerbations exhibit a consistent annual pattern, closely mirroring the school calendar. Although respiratory viruses—the “common cold” viruses—are implicated as a principal cause, there is little evidence to link viral prevalence to seasonal differences in risk. We jointly fit a common cold transmission model and a model of biological and environmental exacerbation triggers to estimate effects on hospitalization risk. Asthma hospitalization rate, influenza prevalence, and air quality measures are available, but common cold circulation is not; therefore, we generate estimates of viral prevalence using a transmission model. Our deterministic multivirus transmission model includes transmission rates that vary when school is closed. We jointly fit the two models to 7 y of daily asthma hospitalizations in adults and children (66,000 events) in eight metropolitan areas. For children, we find that daily viral prevalence is the strongest predictor of asthma hospitalizations, with transmission reduced by 45% (95% credible interval =41–49%) during school closures. We detect a transient period of nonspecific immunity between infections lasting 19 (17–21) d. For adults, hospitalizations are more variable, with influenza driving wintertime peaks. Neither particulate matter nor ozone was an important predictor, perhaps because of the large geographic area of the populations. The school calendar clearly and predictably drives seasonal variation in common cold prevalence, which results in the “back-to-school” asthma exacerbation pattern seen in children and indirectly contributes to exacerbation risk in adults. This study provides a framework for anticipating the seasonal dynamics of common colds and the associated risks for asthmatics. PMID:26858436

  19. Daily activity during stability and exacerbation of chronic obstructive pulmonary disease

    PubMed Central

    2014-01-01

    Background During most COPD exacerbations, patients continue to live in the community but there is little information on changes in activity during exacerbations due to the difficulties of obtaining recent, prospective baseline data. Methods Patients recorded on daily diary cards any worsening in respiratory symptoms, peak expiratory flow (PEF) and the number of steps taken per day measured with a Yamax Digi-walker pedometer. Exacerbations were defined by increased respiratory symptoms and the number of exacerbations experienced in the 12 months preceding the recording of daily step count used to divide patients into frequent (> = 2/year) or infrequent exacerbators. Results The 73 COPD patients (88% male) had a mean (±SD) age 71(±8) years and FEV1 53(±16)% predicted. They recorded pedometer data on a median 198 days (IQR 134–353). At exacerbation onset, symptom count rose by 1.9(±1.3) and PEF fell by 7(±13) l/min. Mean daily step count fell from 4154(±2586) steps/day during a preceding baseline week to 3673(±2258) step/day during the initial 7 days of exacerbation (p = 0.045). Patients with larger falls in activity at exacerbation took longer to recover to stable level (rho = −0.56; p < 0.001). Recovery in daily step count was faster (median 3.5 days) than for exacerbation symptoms (median 11 days; p < 0.001). Recovery in step count was also faster in untreated compared to treated exacerbation (p = 0.030). Daily step count fell faster over time in the 40 frequent exacerbators, by 708 steps/year, compared to 338 steps/year in 33 infrequent exacerbators (p = 0.002). Conclusions COPD exacerbations reduced physical activity and frequent exacerbations accelerate decline in activity over time. PMID:24885188

  20. Aspirin-exacerbated respiratory disease: pathophysiological insights and clinical advances

    PubMed Central

    Steinke, John W; Wilson, Jeff M

    2016-01-01

    Asthma and chronic rhinosinusitis are heterogeneous airway diseases of the lower and upper airways, respectively. Molecular and cellular studies indicate that these diseases can be categorized into unique endotypes, which have therapeutic implications. One such endotype is aspirin-exacerbated respiratory disease (AERD), which encompasses the triad of asthma, aspirin (or nonsteroidal anti-inflammatory drug) hypersensitivity, and nasal polyposis. AERD has unique pathophysiological features that distinguish it from aspirin-tolerant asthma and other forms of chronic rhinosinusitis. This review details molecular and cellular features of AERD and highlights current and future therapies that are based on these insights. PMID:27022293

  1. Exacerbation of posttraumatic stress disorder symptoms with medical illness.

    PubMed

    Hamner, M B

    1994-03-01

    Chronic posttraumatic stress disorder (PTSD) may increase the risk for associated psychiatric and medical illnesses. In turn, the onset of medical illness may result in an exacerbation of PTSD symptoms leading to excessive or maladaptive psychological and physiological reactions. Five combat veterans with PTSD and medical disease are presented to illustrate this potential for worsening of PTSD with concurrent medical illness. Health care workers in general hospital settings should be aware of unique psychological vulnerabilities in PTSD patients. Prospective studies are needed to assess the impact of medical comorbidity on the course of PTSD.

  2. [How I prevent...exacerbation of atopic dermatitis].

    PubMed

    Xhauflaire-Uhoda, E; Piérard-Franchimont, C; Nikkels, A F; Piérard, G E

    2006-01-01

    Atopic dermatitis is under the influence of series of environmental factors. The contact with unsuited cleaning agents and rough textiles can exacerbate pruritus and inflammation. Preventive and adjuvant measures can thus help the care procedures of the disease. Appropriate hygiene measures and the use of emollients are particularly helpful. Clothing measures are also in place. Undergarments and pyjamas made of knitted natural silk are available. Other measures, sometimes corresponding to anecdotal claims--antihistamines, thermal cures, unconventional medicine, probiotics, chinese herbals, essential fatty acids--have not proven their preventive efficacy in atopic dermatitis. PMID:17020235

  3. The heart-liver metabolic axis: defective communication exacerbates disease.

    PubMed

    Baskin, Kedryn K; Bookout, Angie L; Olson, Eric N

    2014-04-01

    The heart has been recognized as an endocrine organ for over 30 years (de Bold, 2011); however, little is known about how the heart communicates with other organs in the body, and even less is known about this process in the diseased heart. In this issue of EMBO Molecular Medicine, Magida and Leinwand (2014) introduce the concept that a primary genetic defect in the heart results in aberrant hepatic lipid metabolism, which consequently exacerbates hypertrophic cardiomyopathy (HCM). This study provides evidence in support of the hypothesis that crosstalk occurs between the heart and liver, and that this becomes disrupted in the diseased state.

  4. Acute exacerbation of psychiatric symptoms during influenza treatment with oseltamivir in chronic schizophrenia.

    PubMed

    Lan, Chen-Chia; Liu, Chia-Chien; Chen, Ying-Sheue

    2015-06-01

    Influenza treatment and prophylaxis with oseltamivir are critically important in reducing the morbidity and mortality of patients in chronic psychiatric facilities. Abnormal behavior, delusions, perceptual disturbances, mania, and depression have all been reported as oseltamivir-related psychiatric side effects. We hereby report two chronic schizophrenia patients in Taiwan manifesting psychiatric instability who were being treated with oseltamivir for suspected influenza infection, and further discuss other potential contributing factors. The possibility that oseltamivir can cause psychotic or affective symptoms suggests that additional caution is necessary for its use in patients with an established psychiatric diagnosis. PMID:25823677

  5. 77 FR 59929 - Guidance for Industry on Acute Bacterial Exacerbations of Chronic Bronchitis in Patients With...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-01

    ... regarding the overall development program and clinical trial designs for drugs to support an indication for... Innovation Act of 2012 that FDA review guidances for the conduct of clinical trials with respect to... for clinical trial sponsors entitled ``Establishment and Operation of Clinical Trial Data...

  6. Ambient air pollution particles and the acute exacerbation of chronic obstructive pulmonary disease

    EPA Science Inventory

    Investigation has repeatedly demonstrated an association between exposure to ambient air pollution particles and numerous indices of human morbidity and mortality. Individuals with chronic obstructive pulmonary disease (COPD) are among those with an increased sensitivity to air p...

  7. Effects of the tulobuterol patch on the treatment of acute asthma exacerbations in young children.

    PubMed

    Katsunuma, Toshio; Ohya, Yukihiro; Fujisawa, Takao; Akashi, Kenichi; Imamura, Naoto; Ebisawa, Motohiro; Daikoku, Kazunari; Kondo, Naomi; Terada, Akihiko; Doi, Satoru; Nishimuta, Toshiyuki; Noma, Takeshi; Hamasaki, Yuhei; Kurihara, Kazuyuki; Masuda, Kei; Yamada, Takashi; Yamada, Masanori; Yoshihara, Shigemi; Watanabe, Kazuhiko; Watanabe, Tohru; Kitabayashi, Taeru; Morikawa, Akihiro; Nishima, Sankei

    2012-01-01

    The tulobuterol patch (TP) is a beta(2)-adrenergic agonist with a favorable pharmacokinetic profile used for asthma management in Japan. Because it contains tulobuterol in a molecular, crystallized form that is gradually absorbed percutaneously, TP exerts a prolonged bronchodilator effect exceeding 24 hours. Although it is a well-established treatment for asthma and wheezing, few studies have investigated whether it can reduce or prevent the symptoms associated with upper respiratory tract infections (URTIs) in young children. This study evaluated the effect of TP on the long-term management of asthma in young children. In this 1-year, randomized, multicenter, double-blind, placebo-controlled study, children aged 0.5-3 years old with mild-to-moderate persistent asthma were treated with either TP or placebo patch. The parents/guardians applied the TP or placebo patch to their children after URTI symptoms appeared. Respiratory symptoms were recorded daily during the 1-year observation period. Overall, 86 patients were enrolled and 80 were treated and analyzed in this study. All patients had been treated with anti-inflammatory drugs before enrollment. The time to symptom resolution was significantly shorter (p = 0.001) and the total respiratory symptom score (p = 0.0457) was significantly lower in the TP group than in the placebo group. In young children with mild-to-moderate asthma who had been treated with anti-inflammatory drugs, using the TP soon after the appearance of URTI symptoms led to quicker resolution of respiratory symptoms and lower respiratory symptom scores.

  8. Ambient air pollution particles and the acute exacerbation of chronic obstructive pulmonary disease.

    PubMed

    Sint, Thaw; Donohue, James F; Ghio, Andrew J

    2008-01-01

    Investigation has repeatedly demonstrated an association between exposure to ambient air pollution particles and numerous indices of human morbidity and mortality. Individuals with chronic obstructive pulmonary disease (COPD) are among those with an increased sensitivity to air pollution particles. Current and ex-smokers account for 80 to 85% of all those with COPD. The human breathing in an urban site with a significant level of particulate matter (PM) may be exposed to 720 microg daily. A single cigarette introduces 15,000 to 40,000 microg particle into the respiratory tract of the smoker. It is subsequently confounding why such a relatively small mass of airborne PM should have any biological effect in the patient with COPD, as these individuals are repeatedly exposed to particles (with a similar size and composition) at perhaps a thousandfold the mass of ambient PM. Regarding this increased sensitivity of COPD patients to air pollution particles, there are several possible explanations for this seeming contradiction, including correlations of PM levels with other components of air pollution, an accumulation of multiple independent risk factors in a patient, changes in individual activity patterns, disparities in dosimetry between healthy subjects and COPD patients, and some unique characteristic of an ambient air pollution PM. Regardless of the underlying mechanism for the increased sensitivity of COPD patients, exposures of these individuals to elevated levels of PM should be discouraged. To provide a greater awareness of PM levels, the U.S. Environmental Protection Agency now includes levels of air pollution particles in an air quality index.

  9. CCR7 Deficiency Exacerbates Injury in Acute Nephritis Due to Aberrant Localization of Regulatory T Cells

    PubMed Central

    Eller, Kathrin; Weber, Tobias; Pruenster, Monika; Wolf, Anna M.; Mayer, Gert

    2010-01-01

    The homing of dendritic cells and T cells to secondary lymphoid organs requires chemokine receptor 7 (CCR7) expression on these cells. T cells mediate the pathogenesis of experimental accelerated nephrotoxic serum nephritis (NTS), including its suppression by regulatory T cells (Tregs), but the contribution of CCR7 to this disease is unknown. Here, we compared the development of NTS in CCR7-knockout (KO) and wild-type (WT) mice. Compared with WT mice, CCR7KO mice developed more severe disease with significantly more inflammatory cells infiltrating the kidney. These cells included FoxP3+ Tregs, which were virtually absent from WT kidneys. The adoptive transfer of WT Tregs into CCR7KO mice at the time of immunization protected the recipients from disease; these cells homed to secondary lymphoid organs but not to kidneys. Conversely, adoptive transfer of CCR7KO Tregs into WT mice did not inhibit development of NTS. These data suggest that NTS can develop without CCR7 expression, but Treg-mediated disease suppression, which seems to occur in secondary lymphoid organs, requires CCR7. PMID:19917782

  10. [Clinico-psychopathologic varieties of the acute Kandinsky-Clerambault syndrome in schizophrenia].

    PubMed

    Dikaia, V I

    1985-01-01

    Acute cases of the Kandinsky-Clerambault syndrome first manifested in adulthood were studied in schizophrenic patients. On the basis of the clinical mechanisms of the development of psychosis and the specific features of acute delirious disturbances in the structure of psychosis 3 clinical variants of the acute syndrome of psychic automatism were identified: developing according to the type of reaction in the structure of acute paranoid (the first variant), according to the regularities of endogenic paroxysm in the picture of acute sensory delirium (the second variant) and according to the mechanism of exacerbation of chronic delirium entering the structure of acute interpretative delirium (the third variant).

  11. Osteoarthritis accelerates and exacerbates Alzheimer's disease pathology in mice

    PubMed Central

    2011-01-01

    Background The purpose of this study was to investigate whether localized peripheral inflammation, such as osteoarthritis, contributes to neuroinflammation and neurodegenerative disease in vivo. Methods We employed the inducible Col1-IL1βXAT mouse model of osteoarthritis, in which induction of osteoarthritis in the knees and temporomandibular joints resulted in astrocyte and microglial activation in the brain, accompanied by upregulation of inflammation-related gene expression. The biological significance of the link between peripheral and brain inflammation was explored in the APP/PS1 mouse model of Alzheimer's disease (AD) whereby osteoarthritis resulted in neuroinflammation as well as exacerbation and acceleration of AD pathology. Results Induction of osteoarthritis exacerbated and accelerated the development of neuroinflammation, as assessed by glial cell activation and quantification of inflammation-related mRNAs, as well as Aβ pathology, assessed by the number and size of amyloid plaques, in the APP/PS1; Col1-IL1βXAT compound transgenic mouse. Conclusion This work supports a model by which peripheral inflammation triggers the development of neuroinflammation and subsequently the induction of AD pathology. Better understanding of the link between peripheral localized inflammation, whether in the form of osteoarthritis, atherosclerosis or other conditions, and brain inflammation, may prove critical to our understanding of the pathophysiology of disorders such as Alzheimer's, Parkinson's and other neurodegenerative diseases. PMID:21899735

  12. Do visual field deficits exacerbate visuo-spatial neglect?

    PubMed Central

    Halligan, P W; Marshall, J C; Wade, D T

    1990-01-01

    A significant association between visual field deficits (VFD) and visuo-spatial neglect is well established, although cases of double-dissociation between the two conditions are not uncommon. It has been argued that VFD typically exacerbates the behavioural manifestations of neglect. We examined a series of 51 patients with unilateral right-hemisphere stroke for the presence of visual field deficit and visuo-spatial neglect. Patients were assigned to the neglect group (N+) or the non-neglect group (N-) on the basis of their aggregate scores on the recently standardised Behavioural Inattention Test (BIT). The association between neglect and VFD was confirmed. Four groups of eight patients (N+, VFD+; N+, VFD-; N-, VFD+; N-, VFD-) were then selected from the initial sample so that they were matched for age, IQ, and days post onset of stroke. Within the neglect groups, the severity of neglect did not differ significantly between those patients with and without VFD; within the non-neglect groups, scores on subtests of the BIT likewise did not differ (with the sole exception of Letter Cancellation) between the VFD+ and the VFD- subgroups. It was concluded that visual field deficits do not exacerbate neglect, and that poor functional recovery in many patients with VFDs is due to the association of sensory loss with the underlying causal factor of neglect. PMID:2380729

  13. Prolonged sleep fragmentation of mice exacerbates febrile responses to lipopolysaccharide

    PubMed Central

    Ringgold, Kristyn M.; Barf, R. Paulien; George, Amrita; Sutton, Blair C.; Opp, Mark R.

    2013-01-01

    Background Sleep disruption is a frequent occurrence in modern society. Whereas many studies have focused on the consequences of total sleep deprivation, few have investigated the condition of sleep disruption. New Method We disrupted sleep of mice during the light period for 9 consecutive days using an intermittently-rotating disc. Results Electroencephalogram (EEG) data demonstrated that non-rapid eye movement (NREM) sleep was severely fragmented and REM sleep was essentially abolished during the 12 h light period. During the dark period, when sleep was not disrupted, neither NREM sleep nor REM sleep times differed from control values. Analysis of the EEG revealed a trend for increased power in the peak frequency of the NREM EEG spectra during the dark period. The fragmentation protocol was not overly stressful as body weights and water consumption remained unchanged, and plasma corticosterone did not differ between mice subjected to 3 or 9 days of sleep disruption and home cage controls. However, mice subjected to 9 days of sleep disruption by this method responded to lipopolysaccharide with an exacerbated febrile response. Comparison with existing methods Existing methods to disrupt sleep of laboratory rodents often subject the animal to excessive locomotion, vibration, or sudden movements. This method does not suffer from any of these confounds. Conclusions This study demonstrates that prolonged sleep disruption of mice exacerbates febrile responses to lipopolysaccharide. This device provides a method to determine mechanisms by which chronic insufficient sleep contributes to the etiology of many pathologies, particularly those with an inflammatory component. PMID:23872243

  14. The Importance of Bacterial and Viral Infections Associated with Adult Asthma Exacerbations in Clinical Practice

    PubMed Central

    Iikura, Motoyasu; Hojo, Masayuki; Koketsu, Rikiya; Watanabe, Sho; Sato, Ayano; Chino, Haruka; Ro, Shoki; Masaki, Haruna; Hirashima, Junko; Ishii, Satoru; Naka, Go; Takasaki, Jin; Izumi, Shinyu; Kobayashi, Nobuyuki; Yamaguchi, Sachiko; Nakae, Susumu; Sugiyama, Haruhito

    2015-01-01

    Background Viral infection is one of the risk factors for asthma exacerbation. However, which pathogens are related to asthma exacerbation in adults remains unclear. Objective The relation between various infections and adult asthma exacerbations was investigated in clinical practice. Methods The study subjects included 50 adult inpatients due to asthma exacerbations and 20 stable outpatients for comparison. The pathogens from a nasopharyngeal swab were measured by multiplex PCR analysis. Results Asthma exacerbations occurred after a common cold in 48 inpatients. The numbers of patients with viral, bacterial, or both infections were 16, 9, and 9, respectively. The dominant viruses were rhinoviruses, respiratory syncytial virus, influenza virus, and metapneumovirus. The major bacteria were S. pneumoniae and H. influenzae. Compared to pathogen-free patients, the patients with pathogens were older and non-atopic and had later onset of disease, lower FeNO levels, lower IgE titers, and a higher incidence of comorbid sinusitis, COPD, or pneumonia. Compared to stable outpatients, asthma exacerbation inpatients had a higher incidence of smoking and comorbid sinusitis, COPD, or pneumonia. Viruses were detected in 50% of stable outpatients, but a higher incidence of rhinovirus, respiratory syncytial virus, and metapneumovirus infections was observed in asthma exacerbation inpatients. H. influenzae was observed in stable asthmatic patients. Other bacteria, especially S. pneumoniae, were important in asthma exacerbation inpatients. Conclusion Viral or bacterial infections were observed in 70% of inpatients with an asthma exacerbation in clinical practice. Infection with S. pneumoniae was related to adult asthma exacerbation. PMID:25901797

  15. Pharmacological strategies to reduce exacerbation risk in COPD: a narrative review.

    PubMed

    Miravitlles, Marc; D'Urzo, Anthony; Singh, Dave; Koblizek, Vladimir

    2016-01-01

    Identifying patients at risk of exacerbations and managing them appropriately to reduce this risk represents an important clinical challenge. Numerous treatments have been assessed for the prevention of exacerbations and their efficacy may differ by patient phenotype. Given their centrality in the treatment of COPD, there is strong rationale for maximizing bronchodilation as an initial strategy to reduce exacerbation risk irrespective of patient phenotype. Therefore, in patients assessed as frequent exacerbators (>1 exacerbation/year) we propose initial bronchodilator treatment with a long-acting muscarinic antagonist (LAMA)/ long-acting β2-agonist (LABA). For those patients who continue to experience >1 exacerbation/year despite maximal bronchodilation, we advocate treating according to patient phenotype. Based on currently available data on adding inhaled corticosteroids (ICS) to a LABA, ICS might be added to a LABA/LAMA combination in exacerbating patients who have an asthma-COPD overlap syndrome or high blood eosinophil counts, while in exacerbators with chronic bronchitis, consideration should be given to treating with a phosphodiesterase (PDE)-4 inhibitor (roflumilast) or high-dose mucolytic agents. For those patients who experience frequent bacterial exacerbations and/or bronchiectasis, addition of mucolytic agents or a macrolide antibiotic (e.g. azithromycin) should be considered. In all patients at risk of exacerbations, pulmonary rehabilitation should be included as part of a comprehensive management plan. PMID:27613392

  16. The successful management of a patient with exacerbation of non-cystic fibrosis bronchiectasis and bilateral fibrothorax using a venovenous extracorporeal carbon dioxide removal system.

    PubMed

    Arcaro, Giovanna; Vianello, Andrea

    2014-12-01

    Following unsuccessful treatment with noninvasive ventilation (NIV), patients requiring subsequent placement on invasive mechanical ventilation have a high mortality rate. Invasive mechanical ventilation is particularly problematic in patients with acute respiratory failure due to bronchiectasis exacerbation, as it is associated with a mortality rate of 19-35% and prolonged ICU stay. Here, we describe the successful management of a patient with exacerbated non-cystic fibrosis bronchiectasis using a pump-assisted venovenous system for extracorporeal CO2 removal (ProLUNG system) as an alternative to endotracheal intubation following NIV failure. The extracorporeal CO2 removal system proved to be safe and efficacious in this case study, and further studies focusing on its use in these types of cases seem warranted.

  17. Sputum colour and bacteria in chronic bronchitis exacerbations: a pooled analysis.

    PubMed

    Miravitlles, Marc; Kruesmann, Frank; Haverstock, Daniel; Perroncel, Renee; Choudhri, Shurjeel H; Arvis, Pierre

    2012-06-01

    We examined the correlation between sputum colour and the presence of potentially pathogenic bacteria in acute exacerbations of chronic bronchitis (AECBs). Data were pooled from six multicentre studies comparing moxifloxacin with other antimicrobials in patients with an AECB. Sputum was collected before antimicrobial therapy, and bacteria were identified by culture and Gram staining. Association between sputum colour and bacteria was determined using logistic regression. Of 4,089 sputum samples, a colour was reported in 4,003; 1,898 (46.4%) were culture-positive. Green or yellow sputum samples were most likely to yield bacteria (58.9% and 45.5% of samples, respectively), compared with 18% of clear and 39% of rust-coloured samples positive for potentially pathogenic microorganisms. Factors predicting a positive culture were sputum colour (the strongest predictor), sputum purulence, increased dyspnoea, male sex and absence of fever. Green or yellow versus white sputum colour was associated with a sensitivity of 94.7% and a specificity of 15% for the presence of bacteria. Sputum colour, particularly green and yellow, was a stronger predictor of potentially pathogenic bacteria than sputum purulence and increased dyspnoea in AECB patients. However, it does not necessarily predict the need for antibiotic treatment in all patients with AECB.

  18. Rehydration with soft drink-like beverages exacerbates dehydration and worsens dehydration-associated renal injury.

    PubMed

    García-Arroyo, Fernando E; Cristóbal, Magdalena; Arellano-Buendía, Abraham S; Osorio, Horacio; Tapia, Edilia; Soto, Virgilia; Madero, Magdalena; Lanaspa, Miguel A; Roncal-Jiménez, Carlos; Bankir, Lise; Johnson, Richard J; Sánchez-Lozada, Laura-Gabriela

    2016-07-01

    Recurrent dehydration, such as commonly occurs with manual labor in tropical environments, has been recently shown to result in chronic kidney injury, likely through the effects of hyperosmolarity to activate both vasopressin and aldose reductase-fructokinase pathways. The observation that the latter pathway can be directly engaged by simple sugars (glucose and fructose) leads to the hypothesis that soft drinks (which contain these sugars) might worsen rather than benefit dehydration associated kidney disease. Recurrent dehydration was induced in rats by exposure to heat (36°C) for 1 h/24 h followed by access for 2 h to plain water (W), a 11% fructose-glucose solution (FG, same composition as typical soft drinks), or water sweetened with noncaloric stevia (ST). After 4 wk plasma and urine samples were collected, and kidneys were examined for oxidative stress, inflammation, and injury. Recurrent heat-induced dehydration with ad libitum water repletion resulted in plasma and urinary hyperosmolarity with stimulation of the vasopressin (copeptin) levels and resulted in mild tubular injury and renal oxidative stress. Rehydration with 11% FG solution, despite larger total fluid intake, resulted in greater dehydration (higher osmolarity and copeptin levels) and worse renal injury, with activation of aldose reductase and fructokinase, whereas rehydration with stevia water had opposite effects. In animals that are dehydrated, rehydration acutely with soft drinks worsens dehydration and exacerbates dehydration associated renal damage. These studies emphasize the danger of drinking soft drink-like beverages as an attempt to rehydrate following dehydration. PMID:27053647

  19. [Endoscopic gallbladder stenting for acute cholecystitis].

    PubMed

    Maekawa, Satoshi; Nomura, Ryosuke; Murase, Takayuki; Ann, Yasuyoshi; Oeholm, Masayuki; Harada, Masaru

    2014-12-01

    Acute cholecystitis is an inflammatory disease of the gallbladder. Inflammation often remains in the gallbladder, but some patients may take a fatal course with exacerbation of inflammation. Although laparoscopic cholecystectomy is recommended for moderate and severe acute cystitis, sometimes cholecystectomy is impossible in elder patients. Because many elder patients have bad general conditions, cholecystectomy should not be performed. Such patients are generally treated by percutaneous transhepatic gallbladder drainage (PTGBD), but PTGBD has the risk of intra-abdominal bleeding. In previous reports, endoscopic gallbladder stenting (EGBS) has been shown to be an effective strategy in cirrhosis patients with symptomatic cholelithiasis as a bridge to transplantation. Recent studies on EGBS have demonstrated an effective long-term management of acute cholecystitis in elderly patients who are poor surgical candidates. Here, we reviewed EGBS for the management of acute cholecystitis.

  20. Does aspirin-induced oxidative stress cause asthma exacerbation?

    PubMed

    Kacprzak, Dorota; Pawliczak, Rafał

    2015-06-19

    Aspirin-induced asthma (AIA) is a distinct clinical syndrome characterized by severe asthma exacerbations after ingestion of aspirin or other non-steroidal anti-inflammatory drugs. The exact pathomechanism of AIA remains unknown, though ongoing research has shed some light. Recently, more and more attention has been focused on the role of aspirin in the induction of oxidative stress, especially in cancer cell systems. However, it has not excluded the similar action of aspirin in other inflammatory disorders such as asthma. Moreover, increased levels of 8-isoprostanes, reliable biomarkers of oxidative stress in expired breath condensate in steroid-naïve patients with AIA compared to AIA patients treated with steroids and healthy volunteers, has been observed. This review is an attempt to cover aspirin-induced oxidative stress action in AIA and to suggest a possible related pathomechanism.

  1. Thrombin exacerbates brain edema in focal cerebral ischemia.

    PubMed

    Hua, Y; Wu, J; Keep, R F; Hoff, J T; Xi, G

    2003-01-01

    Thrombin contributes to edema formation after intracerebral hemorrhage. Recent studies suggest that thrombin may also play a role in ischemic brain damage. In the present study, adult male Sprague-Dawley rats were anesthetized with pentobarbital. Middle cerebral artery (MCA) was occluded using the suture method. We found that brain thrombin activity was elevated after permanent MCA occlusion as was prothrombin messenger RNA expression. Intracerebral injection of a thrombin inhibitor, hirudin, reduced neurological deficits following cerebral ischemia. In contrast, intracerebral administration of exogenous thrombin (at a dose that is non-toxic to normal brain), markedly exacerbated brain edema after transient focal cerebral ischemia. These results indicate that extravascular thrombin inhibition may be a new therapeutic target for cerebral ischemia.

  2. [Etiological and exacerbation factors for COPD. Body weight loss].

    PubMed

    Yokoyama, Akihito

    2016-05-01

    Hunger or malnutrition is not only a historical issue but also a current problem worldwide. Biological responses to hunger are evolutionary prepared in our body, including energy generation by degradation of body proteins. Extreme weight loss (malnutrition) can cause air space enlargement in human and rodents. However, the changes in rodents could be reversible, since refeeding could repair the pathology. On the other hand, weight loss is a common feature in patients with more severe COPD. Complex factors, such as increased energy consumption, decreased food uptake by low grade inflammation, socio-economic factors and so on, are involved in weight loss. Weight loss in patients with COPD also increases the risk of exacerbation, hospitalization, and death. PMID:27254941

  3. RIP3-dependent necrosis induced inflammation exacerbates atherosclerosis.

    PubMed

    Meng, Lingjun; Jin, Wei; Wang, Yuhui; Huang, Huanwei; Li, Jia; Zhang, Cai

    2016-04-29

    Atherothrombotic vascular disease is already the leading cause of mortality worldwide. Atherosclerosis shares features with diseases caused by chronic inflammation. More attention should concentrates on the innate immunity effect atherosclerosis progress. RIP3 (receptor-interacting protein kinase 3) act through the transcription factor named Nr4a3 (Nuclear orphan receptors) to regulate cytokine production. Deletion RIP3 decreases IL-1α production. Injection of anti-IL-1α antibody protects against the progress of atherosclerosis in ApoE -/- mice. RIP3 as a molecular switch in necrosis, controls macrophage necrotic death caused inflammation. Inhibiting necrosis will certainly reduce atherosclerosis through limit inflammation. Necrotic cell death caused systemic inflammation exacerbated cardiovascular disease. Inhibition of necrosis may yield novel therapeutic targets for treatment in years to come.

  4. Suppression of autophagy exacerbates Mefloquine-mediated cell death.

    PubMed

    Shin, Ji Hyun; Park, So Jung; Jo, Yoon Kyung; Kim, Eun Sung; Kang, Hee; Park, Ji-Ho; Lee, Eunjoo H; Cho, Dong-Hyung

    2012-05-01

    Mefloquine is an effective treatment drug for malaria. However, it can cause several adverse side effects, and the precise mechanism associated with the adverse neurological effects of Mefloquine is not clearly understood. In this study, we investigated the effect of Mefloquine on autophagy in neuroblastoma cells. Mefloquine treatment highly induced the formation of autophagosomes and the conversion of LC3I into LC3II. Moreover, Mefloquine-induced autophagy was efficiently suppressed by an autophagy inhibitor and by down regulation of ATG6. The autophagy was also completely blocked in ATG5 deficient mouse embryonic fibroblast cells. Moreover, suppression of autophagy significantly intensified Mefloquine-mediated cytotoxicity in SH-SY5Y cells. Our findings suggest that suppression of autophagy may exacerbate Mefloquine toxicity in neuroblastoma cells.

  5. Monitoring asthma in childhood: symptoms, exacerbations and quality of life.

    PubMed

    Brand, Paul L P; Mäkelä, Mika J; Szefler, Stanley J; Frischer, Thomas; Price, David

    2015-06-01

    Monitoring asthma in children in clinical practice is primarily performed by reviewing disease activity (daytime and night-time symptoms, use of reliever medication, exacerbations requiring frequent use of reliever medication and urgent visits to the healthcare professional) and the impact of the disease on children's daily activities, including sports and play, in a clinical interview. In such an interview, most task force members also discuss adherence to maintenance therapy and the patients' (and parents') views and beliefs on the goals of treatment and the amount of treatment required to achieve those goals. Composite asthma control and quality of life measures, although potentially useful in research, have limited value in clinical practice because they have a short recall window and do not cover the entire spectrum of asthma control. Telemonitoring of children with asthma cannot replace face-to-face follow-up and monitoring because there is no evidence that it is associated with improved health outcomes.

  6. Food allergen-mediated exacerbations of oral lichen planus.

    PubMed

    Chen, H X; Yount, W J; Culton, D A

    2016-10-01

    Erosive oral lichen planus (OLP) is a chronic autoimmune condition of unknown aetiology, characterized by periods of exacerbation and quiescence. Many patients with OLP report triggers of flares that overlap with triggers of other oral diseases, including oral allergy syndrome (OAS), an IgE-mediated food allergy. We report a case that, to our knowledge, is the first reported case of concurrent OLP and OAS diagnoses, which provides insight into the triggers of OLP and the role of trigger avoidance. A woman in her 60s presented with erosive OLP refractory to prednisone and azathioprine. She reported that certain food exposures triggered flares of her OLP. She was subsequently diagnosed with concurrent OAS, and avoidance of food allergens resulted in a clinically significant improvement in her OLP, eventually allowing her to taper off systemic treatment altogether. Further studies are needed to pinpoint common triggers and examine the role of trigger avoidance as a management strategy for OLP. PMID:27663157

  7. A rare case of ulcerative colitis exacerbated by VZV infection.

    PubMed

    Nishimura, Satoshi; Yoshino, Takuya; Fujikawa, Yoshiki; Watanabe, Masaki; Yazumi, Shujiro

    2015-12-01

    A 16-years old man with severe ulcerative colitis (UC) was admitted to our hospital. After initiating treatment with corticosteroid for UC, chicken pox appeared. At the same time of appearance of chicken pox, the disease activity of UC was exacerbated. After initiating the treatment with acyclovir, both chicken pox and UC improved. Because colonoscopic findings revealed the remaining of moderately active UC, initiating the treatment with infliximab could induce clinical remission of UC without relapse of varicella-zoster virus (VZV) infection. This is a very rare case of UC with concomitant VZV infection. According to our report, the vaccination for VZV prior to immunosuppressive treatments would be necessary for VZV naïve patients with UC. PMID:26552918

  8. Glycation exacerbates the neuronal toxicity of β-amyloid

    PubMed Central

    Li, X-H; Du, L-L; Cheng, X-S; Jiang, X; Zhang, Y; Lv, B-L; Liu, R; Wang, J-Z; Zhou, X-W

    2013-01-01

    Accumulation evidence shows that β-amyloid (Aβ) is a neurotoxic and accumulation of Aβ is responsible for the pathology of Alzheimer's disease (AD). However, it is currently not fully understood what makes Aβ toxic and accumulated. Previous studies demonstrate that Aβ is a suitable substrate for glycation, producing one form of the advanced glycation endproducts (AGEs). We speculated that Aβ-AGE formation may exacerbate the neurotoxicity. To explore whether the Aβ-AGE is more toxic than the authentic Aβ and to understand the molecular mechanisms, we synthesized glycated Aβ by incubating Aβ with methylglyoxal (MG) in vitro and identified the formation of glycated Aβ by fluorescence spectrophotometer. Then, we treated the primary hippocampal neurons cultured 8 days in vitro with Aβ-AGE or Aβ for 24 h. We observed that glycation exacerbated neurotoxicity of Aβ with upregulation of receptor for AGE (RAGE) and activation of glycogen synthase kinase-3 (GSK-3), whereas simultaneous application of RAGE antibody or GSK-3 inhibitor reversed the neuronal damages aggravated by glycated Aβ. Thereafter, we found that Aβ is also glycated with an age-dependent elevation of AGEs in Tg2576 mice, whereas inhibition of Aβ-AGE formation by subcutaneously infusion of aminoguanidine for 3 months significantly rescued the early cognitive deficit in mice. Our data reveal for the first time that the glycated Aβ is more toxic. We propose that the glycated Aβ with the altered secondary structure may be a more suitable ligand than Aβ for RAGE and subsequent activation of GSK-3 that can lead to cascade pathologies of AD, therefore glycated Aβ may be a new therapeutic target for AD. PMID:23764854

  9. Exposure to particulate hexavalent chromium exacerbates allergic asthma pathology

    SciTech Connect

    Schneider, Brent C.; Constant, Stephanie L.; Patierno, Steven R.; Jurjus, Rosalyn A.; Ceryak, Susan M.

    2012-02-15

    Airborne hexavalent chromate, Cr(VI), has been identified by the Environmental Protection Agency as a possible health threat in urban areas, due to the carcinogenic potential of some of its forms. Particulate chromates are produced in many different industrial settings, with high levels of aerosolized forms historically documented. Along with an increased risk of lung cancer, a high incidence of allergic asthma has been reported in workers exposed to certain inhaled particulate Cr(VI) compounds. However, a direct causal association between Cr(VI) and allergic asthma has not been established. We recently showed that inhaled particulate Cr(VI) induces an innate neutrophilic inflammatory response in BALB/c mice. In the current studies we investigated how the inflammation induced by inhaled particulate Cr(VI) might alter the pathology of an allergic asthmatic response. We used a well-established mouse model of allergic asthma. Groups of ovalbumin protein (OVA)-primed mice were challenged either with OVA alone, or with a combination of OVA and particulate zinc chromate, and various parameters associated with asthmatic responses were measured. Co-exposure to particulate Cr(VI) and OVA mediated a mixed form of asthma in which both eosinophils and neutrophils are present in airways, tissue pathology is markedly exacerbated, and airway hyperresponsiveness is significantly increased. Taken together these findings suggest that inhalation of particulate forms of Cr(VI) may augment the severity of ongoing allergic asthma, as well as alter its phenotype. Such findings may have implications for asthmatics in settings in which airborne particulate Cr(VI) compounds are present at high levels. -- Highlights: ► Allergic asthma correlated with exposure to certain inhaled particulate chromates. ► Direct causal association between Cr(VI) and allergic asthma not established. ► Cr exacerbated pathology and airway hyperresponsiveness in an OVA-challenged mouse. ► Particulate Cr

  10. Pathogens in COPD exacerbations identified by comprehensive real-time PCR plus older methods

    PubMed Central

    Shimizu, Kenichiro; Yoshii, Yutaka; Morozumi, Miyuki; Chiba, Naoko; Ubukata, Kimiko; Uruga, Hironori; Hanada, Shigeo; Saito, Nayuta; Kadota, Tsukasa; Ito, Saburo; Wakui, Hiroshi; Takasaka, Naoki; Minagawa, Shunsuke; Kojima, Jun; Hara, Hiromichi; Numata, Takanori; Kawaishi, Makoto; Saito, Keisuke; Araya, Jun; Kaneko, Yumi; Nakayama, Katsutoshi; Kishi, Kazuma; Kuwano, Kazuyoshi

    2015-01-01

    Respiratory infection is a major cause of exacerbation in chronic obstructive pulmonary disease (COPD). Infectious contributions to exacerbations remain incompletely described. We therefore analyzed respiratory tract samples by comprehensive real-time polymerase chain reaction (PCR) in combination with conventional methods. We evaluated multiple risk factors for prolonged hospitalization to manage COPD exacerbations, including infectious agents. Over 19 months, we prospectively studied 46 patients with 50 COPD exacerbations, collecting nasopharyngeal swab and sputum samples from each. We carried out real-time PCR designed to detect six bacterial species and eleven viruses, together with conventional procedures, including sputum culture. Infectious etiologies of COPD exacerbations were identified in 44 of 50 exacerbations (88%). Infections were viral in 17 of 50 exacerbations (34%). COPD exacerbations caused by Gram-negative bacilli, including enteric and nonfermenting organisms, were significantly associated with prolonged hospitalization for COPD exacerbations. Our results support the use of a combination of real-time PCR and conventional methods for determining both infectious etiologies and risk of extended hospitalization. PMID:26451098

  11. Acute Intraoperative Pulmonary Aspiration

    PubMed Central

    Nason, Katie S.

    2015-01-01

    Synopsis Acute intraoperative aspiration is a potentially fatal complication with significant associated morbidity. Patients undergoing thoracic surgery are at increased risk for anesthesia-related aspiration, largely due to the predisposing conditions associated with this complication. Awareness of the risk factors, predisposing conditions, maneuvers to decrease risk and immediate management options by both the thoracic surgeon and the anesthesia team is imperative to reducing risk and optimizing patient outcomes associated with acute intraoperative pulmonary aspiration. Based on the root-cause analyses that many of the aspiration events can be traced back to provider factors, having an experienced anesthesiologist present for high-risk cases is also critical. PMID:26210926

  12. Time course of inflammation resolution in patients with frequent exacerbations of chronic obstructive pulmonary disease

    PubMed Central

    Chang, Chun; Yao, Wanzhen

    2014-01-01

    Background When exacerbation of chronic obstructive pulmonary disease (AECOPD) occurs frequently, patients have high levels of airway and systemic inflammation and a poor quality of life. This study compared the nature and course of systemic and airway inflammation during AECOPD between patients who experienced frequent exacerbations and those with non-frequent exacerbations. Material/Methods Consecutive hospitalized patients with AECOPD were recruited and divided into 2 groups according to the frequency of AECOPD they had experienced in the previous year. Frequent exacerbators (defined as 2 or more AECOPD in the previous year) and non-frequent exacerbators (defined as zero or 1 AECOPD in the previous year). Inflammatory (interleukin 6, interleukin 8, myeloperoxidase, and C-reactive protein) and clinical (dyspnea, COPD assessment test (CAT), and peak expiratory flow) indices were assessed on the day of admission before starting therapy, day 7 of treatment, the day of planned discharge (day 10–14), and 8 weeks after discharge. Results We analyzed data from 135 patients; 78 (57.8%) were non-frequent exacerbators and 57 (42.2%) were frequent exacerbators. In both groups, the inflammatory and clinical indices at day 7, the day of planned discharge (day 10–14), and 8 weeks were significantly improved compared to those at admission. Frequent exacerbators had a smaller reduction in their inflammatory indices and CAT scores between exacerbation onset and all the other time points compared with infrequent exacerbators. Conclusions Frequent exacerbators have a reduced response to treatment of AECOPD in terms of inflammatory indices and quality of life. PMID:24569299

  13. Multiphasic acute disseminated encephalomyelitis associated with atypical rubella virus infection.

    PubMed

    Shinoda, Koji; Asahara, Hideaki; Uehara, Taira; Miyoshi, Katsue; Suzuki, Satoshi O; Iwaki, Toru; Kira, Jun-ichi

    2015-02-01

    We report the first case of an occurrence of multiphasic acute disseminated encephalomyelitis (ADEM) associated with atypical rubella virus infection with no rash and long-term increased titers of serum anti-rubella IgM in a 17-year-old male who had no history of rubella vaccination. He suffered from at least six clinical exacerbations with disseminated hyperintense lesions on FLAIR MR images during the course of 18 months. Repeated methylprednisolone pulse therapy and intravenous immunoglobulin therapy resolved the exacerbations. In patients with multiphasic ADEM of unknown etiology, clinicians should also consider the possibility of preceding infection with rubella virus.

  14. Augmentation of arginase 1 expression by exposure to air pollution exacerbates the airways hyperresponsiveness in murine models of asthma

    PubMed Central

    2011-01-01

    Background Arginase overexpression contributes to airways hyperresponsiveness (AHR) in asthma. Arginase expression is further augmented in cigarette smoking asthmatics, suggesting that it may be upregulated by environmental pollution. Thus, we hypothesize that arginase contributes to the exacerbation of respiratory symptoms following exposure to air pollution, and that pharmacologic inhibition of arginase would abrogate the pollution-induced AHR. Methods To investigate the role of arginase in the air pollution-induced exacerbation of airways responsiveness, we employed two murine models of allergic airways inflammation. Mice were sensitized to ovalbumin (OVA) and challenged with nebulized PBS (OVA/PBS) or OVA (OVA/OVA) for three consecutive days (sub-acute model) or 12 weeks (chronic model), which exhibit inflammatory cell influx and remodeling/AHR, respectively. Twenty-four hours after the final challenge, mice were exposed to concentrated ambient fine particles plus ozone (CAP+O3), or HEPA-filtered air (FA), for 4 hours. After the CAP+O3 exposures, mice underwent tracheal cannulation and were treated with an aerosolized arginase inhibitor (S-boronoethyl-L-cysteine; BEC) or vehicle, immediately before determination of respiratory function and methacholine-responsiveness using the flexiVent®. Lungs were then collected for comparison of arginase activity, protein expression, and immunohistochemical localization. Results Compared to FA, arginase activity was significantly augmented in the lungs of CAP+O3-exposed OVA/OVA mice in both the sub-acute and chronic models. Western blotting and immunohistochemical staining revealed that the increased activity was due to arginase 1 expression in the area surrounding the airways in both models. Arginase inhibition significantly reduced the CAP+O3-induced increase in AHR in both models. Conclusions This study demonstrates that arginase is upregulated following environmental exposures in murine models of asthma, and contributes

  15. [Exacerbation of hypertension and disturbances of the geomagnetic field].

    PubMed

    Vershinina, N I; Petrochenko, N A; Shumilov, I S

    1997-01-01

    The authors consider relationships between emergence of acute episodes of essential hypertension (hospital admittances) and disturbance of the geomagnetic field. The authors report male- and female-specific ranges of the geomagnetic field variations which are threatening for hypertensive subjects. PMID:9229606

  16. Acute intermittent porphyria with SIADH and fluctuating dysautonomia.

    PubMed

    Nabin, A; Thapa, L J; Paudel, R; Rana, P V S

    2012-01-01

    Three cases of acute intermittent porphyria are reported. While in first case severe pain in abdomen with intermittent exacerbation was the only presentation, the second patient presented as accelerated hypertension and acute abdominal crises in whom the clinical course was characterized by development of deep coma due to inappropriate secretion of antidiuretic hormone before she made complete recovery. The third patient, initially manifested as acute encephalitic syndrome. After initial improvement, she developed features of acute intermittent porphyria i.e. acute abdomen, neuropsychiatric symptoms, and rapidly progressing acute motor neuropathy leading to respiratory and bulbar paralysis. In addition, she developed severe and fluctuating dysautonomia leading to cardiac arrest and fatal termination. The importance of early diagnosis, recognition of autonomic disturbances, prompt treatment and counseling for avoidance of precipitating factors is stressed.

  17. Acute interstitial pneumonia (AIP): relationship to Hamman-Rich syndrome, diffuse alveolar damage (DAD), and acute respiratory distress syndrome (ARDS).

    PubMed

    Mukhopadhyay, Sanjay; Parambil, Joseph G

    2012-10-01

    Acute interstitial pneumonia (AIP) is a term used for an idiopathic form of acute lung injury characterized clinically by acute respiratory failure with bilateral lung infiltrates and histologically by diffuse alveolar damage (DAD), a combination of findings previously known as the Hamman-Rich syndrome. This review aims to clarify the diagnostic criteria of AIP, its relationship with DAD and acute respiratory distress syndrome (ARDS), key etiologies that need to be excluded before making the diagnosis, and the salient clinical features. Cases that meet clinical and pathologic criteria for AIP overlap substantially with those that fulfill clinical criteria for ARDS. The main differences between AIP and ARDS are that AIP requires a histologic diagnosis of DAD and exclusion of known etiologies. AIP should also be distinguished from "acute exacerbation of IPF," a condition in which acute lung injury (usually DAD) supervenes on underlying usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF).

  18. Exacerbations of asthma during pregnancy: Impact on pregnancy complications and outcome.

    PubMed

    Ali, Z; Hansen, A V; Ulrik, C S

    2016-05-01

    Asthma is common among pregnant women, and the incidence of asthma exacerbations during pregnancy is high. This literature review provides an overview of the impact of exacerbations of asthma during pregnancy on pregnancy-related complications. The majority of published retrospective studies reveal that asthma exacerbations during pregnancy increase the risk of pre-eclampsia, gestational diabetes, placental abruption and placenta praevia. Furthermore, these women also have higher risk for breech presentation, haemorrhage, pulmonary embolism, caesarean delivery, maternal admission to the intensive care unit and longer postpartum hospital stay. Asthma has been associated with increased risk of intrauterine growth retardation, small-for-gestational age, low birth weight, infant hypoglycaemia and preterm birth, but more recent prospective studies have not revealed significant associations with regard to these outcomes. In conclusion, asthma exacerbations during pregnancy are associated with complications of pregnancy, labour and delivery. Prevention of exacerbations is essential to reduce the risk of complications and poor outcome.

  19. Biomarkers in Exhaled Breath Condensate Are Not Predictive for Pulmonary Exacerbations in Children with Cystic Fibrosis: Results of a One-Year Observational Study

    PubMed Central

    van Horck, Marieke; Alonso, Ariel; Wesseling, Geertjan; de Winter—de Groot, Karin; van Aalderen, Wim; Hendriks, Han; Winkens, Bjorn; Rijkers, Ger; Jöbsis, Quirijn; Dompeling, Edward

    2016-01-01

    Background Cystic Fibrosis (CF) is characterized by chronically inflamed airways, and inflammation even increases during pulmonary exacerbations. These adverse events have an important influence on the well-being, quality of life, and lung function of patients with CF. Prediction of exacerbations by inflammatory markers in exhaled breath condensate (EBC) combined with early treatment may prevent these pulmonary exacerbations and may improve the prognosis. Aim To investigate the diagnostic accuracy of a set of inflammatory markers in EBC to predict pulmonary exacerbations in children with CF. Methods In this one-year prospective observational study, 49 children with CF were included. During study visits with an interval of 2 months, a symptom questionnaire was completed, EBC was collected, and lung function measurements were performed. The acidity of EBC was measured directly after collection. Inflammatory markers interleukin (IL)-6, IL-8, tumor necrosis factor α (TNF-α), and macrophage migration inhibitory factor (MIF) were measured using high sensitivity bead based flow immunoassays. Pulmonary exacerbations were recorded during the study and were defined in two ways. The predictive power of inflammatory markers and the other covariates was assessed using conditionally specified models and a receiver operating characteristic curve (SAS version 9.2). In addition, k-nearest neighbors (KNN) algorithm was applied (SAS version 9.2). Results Sixty-five percent of the children had one or more exacerbations during the study. The conditionally specified models showed an overall correct prediction rate of 55%. The area under the curve (AUC) was equal to 0.62. The results obtained with the KNN algorithm were very similar. Conclusion Although there is some evidence indicating that the predictors outperform random guessing, the general diagnostic accuracy of EBC acidity and the EBC inflammatory markers IL-6, IL-8, TNF-α and MIF is low. At present it is not possible to

  20. Acute Decompensated Heart Failure

    PubMed Central

    Joseph, Susan M.; Cedars, Ari M.; Ewald, Gregory A.; Geltman, Edward M.; Mann, Douglas L.

    2009-01-01

    Hospitalizations for acute decompensated heart failure are increasing in the United States. Moreover, the prevalence of heart failure is increasing consequent to an increased number of older individuals, as well as to improvement in therapies for coronary artery disease and sudden cardiac death that have enabled patients to live longer with cardiovascular disease. The main treatment goals in the hospitalized patient with heart failure are to restore euvolemia and to minimize adverse events. Common in-hospital treatments include intravenous diuretics, vasodilators, and inotropic agents. Novel pharmaceutical agents have shown promise in the treatment of acute decompensated heart failure and may simplify the treatment and reduce the morbidity associated with the disease. This review summarizes the contemporary management of patients with acute decompensated heart failure. PMID:20069075

  1. Age exacerbates HIV-associated white matter abnormalities.

    PubMed

    Seider, Talia R; Gongvatana, Assawin; Woods, Adam J; Chen, Huaihou; Porges, Eric C; Cummings, Tiffany; Correia, Stephen; Tashima, Karen; Cohen, Ronald A

    2016-04-01

    Both HIV disease and advanced age have been associated with alterations to cerebral white matter, as measured with white matter hyperintensities (WMH) on fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI), and more recently with diffusion tensor imaging (DTI). This study investigates the combined effects of age and HIV serostatus on WMH and DTI measures, as well as the relationships between these white matter measures, in 88 HIV seropositive (HIV+) and 49 seronegative (HIV-) individuals aged 23-79 years. A whole-brain volumetric measure of WMH was quantified from FLAIR images using a semi-automated process, while fractional anisotropy (FA) was calculated for 15 regions of a whole-brain white matter skeleton generated using tract-based spatial statistics (TBSS). An age by HIV interaction was found indicating a significant association between WMH and older age in HIV+ participants only. Similarly, significant age by HIV interactions were found indicating stronger associations between older age and decreased FA in the posterior limbs of the internal capsules, cerebral peduncles, and anterior corona radiata in HIV+ vs. HIV- participants. The interactive effects of HIV and age were stronger with respect to whole-brain WMH than for any of the FA measures. Among HIV+ participants, greater WMH and lower anterior corona radiata FA were associated with active hepatitis C virus infection, a history of AIDS, and higher current CD4 cell count. Results indicate that age exacerbates HIV-associated abnormalities of whole-brain WMH and fronto-subcortical white matter integrity.

  2. Exacerbations of childhood asthma and ozone pollution in Atlanta

    SciTech Connect

    White, M.C.; Etzel, R.A.; Lloyd, C. ); Wilcox, W.D. )

    1994-04-01

    Asthma prevalence and mortality due to asthma have been increasing during the last decade, and both the rates and the increases in rates have been higher for blacks than whites and higher for children than adults. Whether environmental factors such as air pollution contribute to these increases is unknown. The purpose of this study was to examine the relationship between emergency visits to a hospital for childhood asthma and exposure to ozone in an indigent, predominantly black population. Data were collected by abstracting clinical records for all children with asthma or reactive airway disease in one public hospital during the summer of 1990. From June 1, 1990, to August 31, 1990, 609 visits were made by children aged 1 to 16 years to an emergency clinic for treatment of asthma or reactive airway disease. Monitoring data indicated that maximum ozone levels equalled or exceeded 0.11 ppm on 6 days during the study period. The average number of visits for asthma or reactive airway disease was 37% higher on the days after those 6 days (from 6:00 PM to 6:00 PM the next day) than on other days (95% Cl, RR = 1.02-1.73). The results of the study suggest that among black children from low-income families, asthma may be exacerbated following periods of high ozone pollution. 45 refs., 1 fig., 4 tabs.