- Research article
- Open Access
- Open Peer Review
A theoretical decision model to help inform advance directive discussions for patients with COPD
© Hajizadeh et al; licensee BioMed Central Ltd. 2010
- Received: 28 June 2010
- Accepted: 20 December 2010
- Published: 20 December 2010
Advance directives (AD) may promote preference-concordant care yet are absent in many patients with Chronic Obstructive Pulmonary Disease (COPD). In order to begin to inform AD discussions between clinicians and COPD patients, we constructed a decision tree to estimate the impact of alternative AD decisions on both quality and quantity of life (quality adjusted life years, QALYs).
Two aspects of the AD were considered, Do Not Intubate (DNI; i.e., no invasive mechanical ventilation) and Full Code (i.e., may use invasive mechanical ventilation). Model parameters were based on published estimates. Our model follows hypothetical patients with COPD to evaluate the effect of underlying COPD severity and of hypothetical patient-specific preferences (about long-term institutionalization and complications from invasive mechanical ventilation) on the recommended AD.
Our theoretical model recommends endorsing the Full Code advance directive for patients who do not have strong preferences against having a potential complication from intubation (ETT complications) or being discharged to a long-term ECF. However, our model recommends endorsing the DNI advance directive for patients who do have strong preferences against having potential complications of intubation and are were willing to tradeoff substantial amounts of time alive to avoid ETT complications or permanent institutionalization. Our theoretical model also recommends endorsing the DNI advance directive for patients who have a higher probability of having complications from invasive ventilation (ETT).
Our model suggests that AD decisions are sensitive to patient preferences about long-term institutionalization and potential complications of therapy, particularly in patients with severe COPD. Future work will elicit actual patient preferences about complications of invasive mechanical ventilation, and incorporate our model into a clinical decision support to be used for actual COPD patients facing AD decisions.
- Chronic Obstructive Pulmonary Disease
- Chronic Obstructive Pulmonary Disease Patient
- Advance Directive
- Severe Chronic Obstructive Pulmonary Disease
- Chronic Obstructive Pulmonary Disease Exacerbation
Advance directives (AD) allow patients to specify preferences about the care they would receive in the event of acute illness, and are recommended for comprehensive medical care [1–3]. However, compliance with AD specification is < 15% in the general population . While federal policy supports AD , it focuses primarily on the inpatient setting. Lack of AD discussions in the outpatient setting may postpone the discussion inappropriately to the setting of acute illness, when patients may be too sick to consider their options carefully [6, 7]. Indeed, only 25% of patients have AD at the time end of life decisions must be made  which could lead to patient dissatisfaction and misguided use of limited healthcare resources [8–10].
Barriers to discussing AD in the outpatient setting include both patient and physician discomfort; fear that the discussion will cause anxiety or take away hope; and lack of patient-tailored information [11–13]. Lack of tailored information is a particularly important barrier, as most AD use vague and unintuitive hypothetical scenarios [14, 15], rather than the patient-specific information relevant to individual decision making . Prognostic estimates are more accurate when based on disease-specific outcomes, and patients prefer disease-specific AD information .
Chronic Obstructive Pulmonary disease (COPD) is a progressive illness that exemplifies the need for AD discussions, as many patients will experience exacerbations requiring hospital admission. A decision about mechanical ventilation is an important component of AD and can prepare patients for possible treatment scenarios. While intubation and other life-saving interventions can be offered, the outcomes may not always be consistent with a patient's preferences. Decision analytic modeling can synthesize evidence based knowledge to estimate the outcomes of decisions and provide a recommended decision but has not been used before to inform the content of AD. Therefore, we constructed a theoretical decision analytic model using disease-specific information for COPD, to begin to assist COPD patients and their health care providers in the discussion of AD.
To inform the AD discussion for COPD patients, we developed a decision model for advance directives that could accommodate a wide array of patient preferences. Decision analytic modeling is used for complex decision making in which there are competing treatments and prognoses. Treatment pathways and outcomes are represented explicitly, often using computer simulation, with probabilities based on published clinical studies. The 'preferred' or 'recommended' decision is that which maximizes the expected value of the outcome of interest, such as survival, quality of life or cost-effectiveness. Modeling is used to supplement clinical data in situations when the influential variables of the decision need to be discovered and when there is uncertainty about clinical inputs. A well-designed decision model can function as a virtual clinical trial, with the benefit of being able to change all the parameters individually or simultaneously to test the effect on outcomes and to discover the most influential variables.
We constructed our decision analytic model with two alternative decisions for the AD, Do Not Intubate ([DNI] i.e., no invasive mechanical ventilation) and Full Code (i.e., may use invasive mechanical ventilation if necessary) in the event of respiratory failure from a COPD exacerbation. Our outcome of interest was a combination of survival and quality of life (QALYs). We focused on COPD exacerbation as the most common cause of respiratory failure requiring hospitalization in patients with COPD. We performed analyses for three scenarios of COPD severity (mild, moderate and severe), using GOLD criteria . We then used hypothetical patient preferences about discharge location and complications of intubation to evaluate the effect on the recommended AD.
We constructed a decision tree using TreeAge software (Version 1.0.2, 2009, Williamstown MA) to model the impact of yearly AD decisions on quality-adjusted life-years (QALYs). QALYs are a measure of disease burden that integrates quality with quantity of life.
Data used in the model
Three types of data are used in the model: transition probabilities (the probabilities of moving from one branch of the decision tree to the next branch), utilities (values placed on being in a given state of health), and life expectancies (Additional file 1). All data was extracted from published clinical trials when available.
Probabilities used in the model specify treatment pathways (ETT vs. NIMV vs. no mechanical ventilation vs. CMO), their short term outcomes, and their long-term outcomes. Data for the probability of ETT was stratified by severity of respiratory exacerbation (severely ill vs. moderately ill) and by code status. Severe respiratory exacerbation (severely ill) was defined as a pH < 7.29, which was chosen because it was the prevalent threshold in the literature. We used expert opinion for the probability of mechanical ventilation for DNI patients as this data was not available.
"Short term outcomes" were outcomes that occurred in the hospital, and included successful weaning from mechanical ventilation, complications of ventilator support, and death. The literature defines complications heterogeneously, including the inability to discontinue mechanical ventilation [19–21] and end organ damage (e.g., sepsis from ventilator associated pneumonia, renal failure, septic shock and cardiovascular collapse) [22–24]. To reduce heterogeneity we defined ETT complications as end organ damage, infection, or the inability to discontinue mechanical ventilation. NIMV complication was defined as the inability to wean from mechanical ventilation, based on the available literature[22, 23, 25–33].
Long-term outcomes of treatment include permanent institutionalization in an extended care facility (long-term ECF), temporary institutionalization for rehabilitation followed by return to home (short-term ECF), or discharge to home, and were dependent on the baseline severity of COPD exacerbation and preceding short-term outcomes .
A utility is a preference-weighted, generic, quality of life measure on a scale of 0-1. We estimated COPD utilities based on reported estimates for chronic lung diseases . We calculated the utility of discharge to long-term ECF and the utility of ETT complications using time tradeoff scenarios in which hypothetical patients were asked how much time in their current state of health they would tradeoff to avoid 1 month of complications from intubation . These utilities had negative values (corresponding to states worse than death) if the patient was willing to tradeoff large amounts of time alive to avoid 1 month of intubation and associated complications.
We estimated life expectancy (LE) in COPD based on the BODE index data on COPD survival . The mean age for the cohort used to determine COPD survival probabilities was 66, which was similar to the mean age of 70 for hospitalization for COPD exacerbation [37, 38]. We estimated LE in a long-term ECF from a study of one year mortality in nursing homes,  and used the DEALE (Declining Exponential Approximation of Life Expectancy) , to convert survival probabilities to LE.
Rather than arbitrarily choosing single studies to inform parameter estimation, we used decision rules to pool relevant data: when the data were sufficiently homogeneous we pooled results using the random effects method of Der Simonian and Laird. Homogeneity was defined as having a Q-statistic of > 0.10, an I-statistic of < 25% and a p-value of < 0.05 with no significant outliers on Forest plot. If data were insufficiently homogeneous we used the median value as our point estimate and specified plausible ranges based on the lowest and highest reported confidence intervals. If insufficient data was available we used expert opinion and employed a wide plausible range for sensitivity analyses. Finally, back calculation was used for some variables using other parameter estimates in the decision tree.
One-way sensitivity analysis varies each variable independently across a plausible range of values (usually the 95% CI) while keeping all other variables constant to assess the influence of data uncertainty on the robustness of the model. Model robustness was determined by whether the recommended AD changed as the parameter estimates were varied across their plausible ranges, and whether the difference in QALYs between Full Code and DNI changed (eg., whether the difference in QALYs for DNI vs. Full Code changed when the lower bound of the 95% CI was used for probability of ETT complication). For the utility of long-term ECF and of complications from intubation (ETT complications) we used the utilities generated from the hypothetical time tradeoff scenarios.
The recommended AD decision varied substantially with hypothetical patient preferences. When hypothetical patients were not willing to tradeoff any time alive to avoid complications of intubation or long-term institutionalization, a Full Code AD resulted in greater QALYs than DNI. As patients were willing to tradeoff more time alive to avoid complications of intubation or long-term institutionalization, DNI became the recommended choice, particularly for patients with severe COPD.
Hypothetical patients not willing to tradeoff time alive to avoid intubation
For hypothetical patients who did not have a strong preference against complications of intubation (i.e., were not willing to give up life expectancy to avoid complications of intubation), Full Code was recommended when compared to DNI regardless of COPD severity. However, the strength of the recommendation to be Full Code decreased as the severity of baseline COPD increased: for patients with mild COPD the increase in QALYs for choosing Full Code instead of DNI was 0.74 QALYs, whereas for patients with severe COPD the increase in QALYs for choosing Full Code instead of DNI was 0.13 QALYs.
Hypothetical patients willing to tradeoff time alive to avoid intubation
In this study, we constructed a theoretical decision analytic model of advance directive choices for COPD patients in the event of a COPD exacerbation. We looked at the effect of disease severity and hypothetical patient preferences on quality adjusted life years and thus the model's recommended advance directive. The variables with greatest influence on quality adjusted life years were patient preferences regarding permanent institutionalization and ETT complications as well as patients' severity of COPD. Patient preferences were most influential in patients with severe COPD: when the utility of long-term ECF was ≤ 0 (i.e., "I think living in a nursing home permanently is the same as or worse than being dead"), the recommended directive became DNI. Other influential variables were the probabilities of ETT complication and NIMV complication. The recommended directive also changed to DNI when the probability of ETT complications increased, and when the probability of NIMV failure decreased (i.e., higher likelihood of survival with just NIMV treatment).
We chose COPD-related respiratory failure in order to focus on a specific and common scenario requiring decision making. Using our results a clinician can compare and contrast prognoses with different AD choices. It is our hope that this will facilitate clinicians to initiate AD discussion with their COPD patients, incorporating their individual preferences (e.g., about long-term institutionalization). Other patient-specific factors, such as physical and psychiatric comorbidities, prior mechanical ventilation outcomes, prior admissions, baseline functional status (ADLs) and home support, may influence the probability of complications and change the recommended AD decision for individual patients, and future clinical research should explore their relative importance and their feasibility for incorporation into decision supports. Future research may also explore further developing tools to elicit the patient preferences identified by our model.
Although there was insufficient data to inform estimates for some variables requiring us to rely on a single study or on expert opinion, the influential variables on sensitivity analysis were not derived by expert opinion. The probability of ETT complications, however, was an influential variable for which only one study was available , because most studies do not distinguish between mortality from ETT and complications from ETT that lead to mortality . We have thus identified an important variable to focus future clinical research in the intensive care unit. Increased data on the probability of ETT complications will improve advance directive decision making by allowing quality of life to be discussed in the event of survival after intubation. In addition, the preference-specific variables (e.g., willingness to trade off time alive to avoid intubation), were not derived from the literature. We argue that these variables are more informative if patient-specific rather than based on cohort studies from the literature. Actual patient-specific preferences will be obtained in the future by coupling the model to a decision aid that elicits patient-preferences (e.g., preferences about health states) and will allow for individually tailored advance directive recommendations.
Another important limitation of our model is that it does not use state transitions, and therefore is not able to assess the influence of multiple respiratory exacerbations within one year. Patients who have multiple exacerbations have increasing severity exacerbations and poorer outcomes than is reflected in the model [42, 43]. Additionally, we assumed that the utility of discharge home after a COPD exacerbation, and LE, was the same as the utility and LE before COPD exacerbation. The literature suggests that some patients who are discharged home do not return to normal quality of life immediately, and that health related quality of life suffers for some time after the acute symptoms have resolved [43, 44]. Future work includes evolving the decision tree into a Markov state transition model that can represent the clinical course of severe COPD with greater fidelity; and incorporating the model into a decision aid using patient preference to support shared decision making. Future work may also include gathering more knowledge about a wide variety of important domains, such as the effect of clinician's specialty on the AD decisions, the influence of patient-specific factors such as gender, religion, cultural background, surrogate involvement and living situation (i.e., what resources the patient has to assist with home care); and the patient's reactions to the model.
Although we believe that informing all COPD patients about alternate treatment options in the event of severe respiratory exacerbations, the ideal timing of this discussion needs to be established (e.g., after deterioration in PFTs are noted in a patient with severe COPD). Appropriate psychiatric counseling may also need to be made available in the event of any distress caused by the discussion of end of life scenarios, and future work on a decision aid will assess patient's reactions to this discussion.
In summary, our model estimates both the survival from alternate advance directives as well as the resulting quality of life based on hypothetical individual patient preferences. We believe that making our model available to clinicians in the form of a decision aid, coupled with actual patient preference elicitation, will better inform AD shared decision making and is one step towards increasing preference-congruent care at the end of life.
- Lanken PN, Terry PB, Delisser HM, Fahy BF, Hansen-Flaschen J, Heffner JE, Levy M, Mularski RA, Osborne ML, Prendergast TJ, Rocker G, Sibbald WJ, Wilfond B, Yankaskas JR, ATS End-of-Life Care Task Force: An official American Thoracic Society clinical policy statement: palliative care for patients with respiratory diseases and critical illnesses. Am J Respir Crit Care Med. 2008, 177 (8): 912-927. 10.1164/rccm.200605-587ST.View ArticlePubMedGoogle Scholar
- Orentlicher D: From the Office of the General Counsel. Advance medical directives. JAMA. 1990, 263 (17): 2365-2367. 10.1001/jama.263.17.2365.View ArticlePubMedGoogle Scholar
- Anonymous American Health Information Management Association: Position statement. Issue: advance directives. J AHIMA. 1992, 63 (2): 1-2. supplGoogle Scholar
- Kirschner KL: When written advance directives are not enough. Clin Geriatr Med. 2005, 21 (1): 193-209. 10.1016/j.cger.2004.08.006. xView ArticlePubMedGoogle Scholar
- Omnibus reconciliation act 1990, title IV, section 4206. Congressional Record. 1990, 12638-Google Scholar
- Markson L, Clark J, Glantz L, Lamberton V, Kern D, Stollerman G: The doctor's role in discussing advance preferences for end-of-life care: perceptions of physicians practicing in the VA. J Am Geriatr Soc. 1997, 45 (4): 399-406.View ArticlePubMedGoogle Scholar
- Fidler H, Thompson C, Freeman A, Hogan D, Walker G, Weinman J: Barriers to implementing a policy not to attempt resuscitation in acute medical admissions: prospective, cross sectional study of a successive cohort. BMJ. 2006, 332 (7539): 461-462. 10.1136/bmj.38740.855914.BE.View ArticlePubMedPubMed CentralGoogle Scholar
- Upadya A, Muralidharan V, Thorevska N, Amoateng-Adjepong Y, Manthous CA: Patient, physician, and family member understanding of living wills. Am J Respir Crit Care Med. 2002, 166 (11): 1430-1435. 10.1164/rccm.200206-503OC.View ArticlePubMedGoogle Scholar
- Emanuel EJ, Emanuel LL: The economics of dying. The illusion of cost savings at the end of life. N Engl J Med. 1994, 330 (8): 540-544. 10.1056/NEJM199402243300806.View ArticlePubMedGoogle Scholar
- Fagerlin A, Schneider CE: Enough. The failure of the living will. Hastings Cent Rep. 2004, 34 (2): 30-42. 10.2307/3527683.View ArticlePubMedGoogle Scholar
- Beck A, Brown J, Boles M, Barrett P: Completion of advance directives by older health maintenance organization members: the role of attitudes and beliefs regarding life-sustaining treatment. J Am Geriatr Soc. 2002, 50 (2): 300-306. 10.1046/j.1532-5415.2002.50062.x.View ArticlePubMedGoogle Scholar
- Curtis JR, Patrick DL, Caldwell ES, Collier AC: Why don't patients and physicians talk about end-of-life care? Barriers to communication for patients with acquired immunodeficiency syndrome and their primary care clinicians. Arch Intern Med. 2000, 160 (11): 1690-1696. 10.1001/archinte.160.11.1690.View ArticlePubMedGoogle Scholar
- Lynn J: Why I don't have a living will. Law Med Health Care. 1991, 19 (1-2): 101-104.PubMedGoogle Scholar
- Wolf SM, Boyle P, Callahan D, Fins JJ, Jennings B, Nelson JL, Barondess JA, Brock DW, Dresser R, Emanuel L: Sources of concern about the Patient Self-Determination Act. N Engl J Med. 1991, 325 (23): 1666-1671. 10.1056/NEJM199112053252334.View ArticlePubMedGoogle Scholar
- Singer PA: Disease-specific advance directives. Lancet. 1994, 344 (8922): 594-596. 10.1016/S0140-6736(94)91971-2.View ArticlePubMedGoogle Scholar
- Murphy DJ, Burrows D, Santilli S, Kemp AW, Tenner S, Kreling B, Teno J: The influence of the probability of survival on patients' preferences regarding cardiopulmonary resuscitation. N Engl J Med. 1994, 330 (8): 545-549. 10.1056/NEJM199402243300807.View ArticlePubMedGoogle Scholar
- Singer PA, Thiel EC, Salit I, Flanagan W, Naylor CD: The HIV-specific advance directive. J Gen Intern Med. 1997, 12 (12): 729-735. 10.1046/j.1525-1497.1997.07157.x.View ArticlePubMedPubMed CentralGoogle Scholar
- Rabe KF, Hurd S, Anzueto A, Barnes PJ, Buist SA, Calverley P, Fukuchi Y, Jenkins C, Rodriguez-Roisin R, van Weel C, Zielinski J: Global Initiative for Chronic Obstructive Lung Disease: Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2007, 176 (6): 532-555. 10.1164/rccm.200703-456SO.View ArticlePubMedGoogle Scholar
- Esteban A, Frutos F, Tobin MJ, Alia I, Solsona JF, Valverdu I, Fernandez R, de la Cal MA, Benito S, Tomas R: A comparison of four methods of weaning patients from mechanical ventilation. Spanish Lung Failure Collaborative Group. N Engl J Med. 1995, 332 (6): 345-350. 10.1056/NEJM199502093320601.View ArticlePubMedGoogle Scholar
- Cuvelier A, Viacroze C, Benichou J, Molano LC, Hellot MF, Benhamou D, Muir JF: Dependency on mask ventilation after acute respiratory failure in the intermediate care unit. European Respiratory Journal. 2005, 26 (2): 289-297. 10.1183/09031936.05.00117104.View ArticlePubMedGoogle Scholar
- Nevins ML, Epstein SK: Predictors of outcome for patients with COPD requiring invasive mechanical ventilation. Chest. 2001, 119 (6): 1840-1849. 10.1378/chest.119.6.1840.View ArticlePubMedGoogle Scholar
- Conti G, Antonelli M, Navalesi P, Rocco M, Bufi M, Spadetta G, Meduri GU: Noninvasive vs. conventional mechanical ventilation in patients with chronic obstructive pulmonary disease after failure of medical treatment in the ward: a randomized trial. Intensive Care Med. 2002, 28 (12): 1701-1707. 10.1007/s00134-002-1478-0.View ArticlePubMedGoogle Scholar
- Squadrone E, Frigerio P, Fogliati C, Gregoretti C, Conti G, Antonelli M, Costa R, Baiardi P, Navalesi P: Noninvasive vs invasive ventilation in COPD patients with severe acute respiratory failure deemed to require ventilatory assistance. Intensive Care Med. 2004, 30 (7): 1303-1310. 10.1007/s00134-004-2320-7.View ArticlePubMedGoogle Scholar
- Ely EW, Baker AM, Evans GW, Haponik EF: The distribution of costs of care in mechanically ventilated patients with chronic obstructive pulmonary disease. Crit Care Med. 2000, 28 (2): 408-413. 10.1097/00003246-200002000-00020.View ArticlePubMedGoogle Scholar
- Carratu P, Bonfitto P, Dragonieri S, Schettini F, Clemente R, Di Gioia G, Loponte L, Foschino Barbaro MP, Resta O: Early and late failure of noninvasive ventilation in chronic obstructive pulmonary disease with acute exacerbation. Eur J Clin Invest. 2005, 35 (6): 404-409. 10.1111/j.1365-2362.2005.01509.x.View ArticlePubMedGoogle Scholar
- Plant PK, Owen JL, Elliott MW: Non-invasive ventilation in acute exacerbations of chronic obstructive pulmonary disease: long term survival and predictors of in-hospital outcome. Thorax. 2001, 56 (9): 708-712. 10.1136/thorax.56.9.708.View ArticlePubMedPubMed CentralGoogle Scholar
- Confalonieri M, Garuti G, Cattaruzza MS, Osborn JF, Antonelli M, Conti G, Kodric M, Resta O, Marchese S, Gregoretti C, Rossi A, Italian noninvasive positive pressure ventilation (NPPV) study group: A chart of failure risk for noninvasive ventilation in patients with COPD exacerbation. European Respiratory Journal. 2005, 25 (2): 348-355. 10.1183/09031936.05.00085304.View ArticlePubMedGoogle Scholar
- Celikel T, Sungur M, Ceyhan B, Karakurt S: Comparison of noninvasive positive pressure ventilation with standard medical therapy in hypercapnic acute respiratory failure. Chest. 1998, 114 (6): 1636-1642. 10.1378/chest.114.6.1636.View ArticlePubMedGoogle Scholar
- Brochard L, Mancebo J, Wysocki M, Lofaso F, Conti G, Rauss A, Simonneau G, Benito S, Gasparetto A, Lemaire F: Noninvasive ventilation for acute exacerbations of chronic obstructive pulmonary disease. N Engl J Med. 1995, 333 (13): 817-822. 10.1056/NEJM199509283331301.View ArticlePubMedGoogle Scholar
- Carrera M, Marin JM, Anton A, Chiner E, Alonso ML, Masa JF, Marrades R, Sala E, Carrizo S, Giner J, Gomez-Merino E, Teran J, Disdier C, Agusti AG, Barbe F: A controlled trial of noninvasive ventilation for chronic obstructive pulmonary disease exacerbations. J Crit Care. 2009, 24 (3): 473.e7-473.e14. 10.1016/j.jcrc.2008.08.007.View ArticleGoogle Scholar
- Scala R, Nava S, Conti G, Antonelli M, Naldi M, Archinucci I, Coniglio G, Hill NS: Noninvasive versus conventional ventilation to treat hypercapnic encephalopathy in chronic obstructive pulmonary disease. Intensive Care Med. 2007, 33 (12): 2101-2108. 10.1007/s00134-007-0837-2.View ArticlePubMedGoogle Scholar
- Scala R, Naldi M, Archinucci I, Coniglio G, Nava S: Noninvasive positive pressure ventilation in patients with acute exacerbations of COPD and varying levels of consciousness. Chest. 2005, 128 (3): 1657-1666. 10.1378/chest.128.3.1657.View ArticlePubMedGoogle Scholar
- Vitacca M, Clini E, Porta R, Foglio K, Ambrosino N: Acute exacerbations in patients with COPD: predictors of need for mechanical ventilation. European Respiratory Journal. 1996, 9 (7): 1487-1493. 10.1183/09031936.96.09071487.View ArticlePubMedGoogle Scholar
- Tengs TO, Wallace A: One thousand health-related quality-of-life estimates. Med Care. 2000, 38 (6): 583-637. 10.1097/00005650-200006000-00004.View ArticlePubMedGoogle Scholar
- Torrance GW, Boyle MH, Horwood SP: Application of multi-attribute utility theory to measure social preferences for health states. Oper Res. 1982, 30 (6): 1043-1069. 10.1287/opre.30.6.1043.View ArticlePubMedGoogle Scholar
- Celli BR, Cote CG, Marin JM, Casanova C, Montes de Oca M, Mendez RA, Pinto Plata V, Cabral HJ: The body-mass index, airflow obstruction, dyspnea, and exercise capacity index in chronic obstructive pulmonary disease. N Engl J Med. 2004, 350 (10): 1005-1012. 10.1056/NEJMoa021322.View ArticlePubMedGoogle Scholar
- Soler-Cataluna JJ, Martinez-Garcia MA, Roman Sanchez P, Salcedo E, Navarro M, Ochando R: Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease. Thorax. 2005, 60 (11): 925-931. 10.1136/thx.2005.040527.View ArticlePubMedPubMed CentralGoogle Scholar
- Gadoury MA, Schwartzman K, Rouleau M, Maltais F, Julien M, Beaupre A, Renzi P, Begin R, Nault D, Bourbeau J, Chronic Obstructive Pulmonary Disease axis of the Respiratory Health Network, Fonds de la recherche en sante du Quebec (FRSQ): Self-management reduces both short- and long-term hospitalisation in COPD. Eur Respir J. 2005, 26 (5): 853-857. 10.1183/09031936.05.00093204.View ArticlePubMedGoogle Scholar
- van Dijk PT, Mehr DR, Ooms ME, Madsen R, Petroski G, Frijters DH, Pot AM, Ribbe MW: Comorbidity and 1-year mortality risks in nursing home residents. J Am Geriatr Soc. 2005, 53 (4): 660-665. 10.1111/j.1532-5415.2005.53216.x.View ArticlePubMedGoogle Scholar
- Beck JR, Kassirer JP, Pauker SG: A convenient approximation of life expectancy (the "DEALE"). I. Validation of the method. Am J Med. 1982, 73 (6): 883-888. 10.1016/0002-9343(82)90786-0.View ArticlePubMedGoogle Scholar
- Gursel G: Determinants of the length of mechanical ventilation in patients with COPD in the intensive care unit. Respiration. 2005, 72 (1): 61-67. 10.1159/000083402.View ArticlePubMedGoogle Scholar
- Donaldson GC, Seemungal TA, Bhowmik A, Wedzicha JA: Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease. Thorax. 2002, 57 (10): 847-852. 10.1136/thorax.57.10.847.View ArticlePubMedPubMed CentralGoogle Scholar
- Seemungal TA, Donaldson GC, Paul EA, Bestall JC, Jeffries DJ, Wedzicha JA: Effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1998, 157 (5 Pt 1): 1418-1422.View ArticlePubMedGoogle Scholar
- Cote CG, Dordelly LJ, Celli BR: Impact of COPD exacerbations on patient-centered outcomes. Chest. 2007, 131 (3): 696-704. 10.1378/chest.06-1610.View ArticlePubMedGoogle Scholar
- The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6947/10/75/prepub
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