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Clinical Investigations: COPD |

Mortality After Hospitalization for COPD* FREE TO VIEW

Pedro Almagro, MD; Esther Calbo, MD; Anna Ochoa de Echagüen, MD; Bienvenido Barreiro, MD; Salvador Quintana, MD; José L. Heredia, MD; Javier Garau, MD
Author and Funding Information

*From the Internal Medicine (Drs. Almagro, Calbo, Ochoa de Echagüen, and Garau), Respiratory (Drs. Heredia and Barreiro), and Intensive Care Unit (Dr. Quintana) Services, Hospital Mútua de Terrassa, University of Barcelona, Barcelona, Spain.

Correspondence to: Pedro Almagro, MD, Department of Medicine, Hospital Mútua de Terrassa, Pl Dr Robert, 5. Terrassa 08221 Barcelona, Spain; e-mail: 19908pam@comb.es



Chest. 2002;121(5):1441-1448. doi:10.1378/chest.121.5.1441
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Objectives: To identify variables associated with mortality in patients admitted to the hospital for acute exacerbation of COPD.

Design: Prospective cohort study.

Setting: Acute-care hospital in Barcelona (Spain).

Patients: One hundred thirty-five consecutive patients hospitalized for acute exacerbation of COPD, between October 1996 and May 1997.

Measurements and results: Clinical, spirometric, and gasometric variables were evaluated at the time of inclusion in the study. Socioeconomic characteristics, comorbidity, dyspnea, functional status, depression, and quality of life were analyzed. Mortality at 180 days, 1 year, and 2 years was 13.4%, 22%, and 35.6%, respectively. Sixty-four patients (47.4%) were dead at the end of the study (median follow-up duration, 838 days). Greater mortality was observed in the bivariate analysis among the oldest patients (p < 0.0001), women (p < 0.01), and unmarried patients (p < 0.002). Hospital admission during the previous year (p < 0.001), functional dependence (Katz index) [p < 0.0004], greater comorbidity (Charlson index) [p < 0.0006], depression (Yesavage Scale) [p < 0.00001]), quality of life (St. George’s Respiratory Questionnaire [SGRQ]) [p < 0.01], and Pco2 at discharge (p < 0.03) were also among the significant predictors of mortality. In the multivariate analysis, the activity SGRQ subscale (p < 0.001; odds ratio [OR], 2.62; confidence interval [CI], 1.43 to 4.78), comorbidity (p < 0.005; OR, 2.2; CI, 1.26 to 3.84), depression (p < 0.004; OR, 3.6; CI, 1.5 to 8.65), hospital readmission (p < 0.03; OR, 1.85; CI, 1.26 to 3.84), and marital status (p < 0.0002; OR, 3.12; CI, 1.73 to 5.63) were independent predictors of mortality.

Conclusions: Quality of life, marital status, depressive symptoms, comorbidity, and prior hospital admission provide relevant information of prognosis in this group of COPD patients.

Figures in this Article

COPD is one of the leading causes of morbidity and mortality worldwide.1Given the slow evolution of COPD, only large cohorts followed up for lengthy periods have provided useful data on trends in mortality, showing that age, smoking status, and poor pulmonary function are important predictors.24

Hospitalization for acute exacerbation of COPD usually occurs in the advanced phase of disease and is thus associated with a greater risk of mortality in subsequent years.57 In recent years, two studies have evaluated prognosis after hospitalization for COPD. Seneff et al8found mortality to be 60% 1 year after hospitalization in patients > 65 years of age requiring admission to an ICU, while Connors et al,9 in a study of patients hospitalized with hypercapnia, found that mortality rates 1 year and 2 years postdischarge were 43% and 49%, respectively. Mortality in the latter study was independently related to age, body mass index (BMI), prior functional status, and cor pulmonale, among other variables. However, both studies were carried out in the subgroup of patients with more advanced disease and both did not perform spirometry, even though such an assessment is considered one of the best predictors of mortality in the population of COPD patients overall.

The present study was designed to evaluate prospectively prognosis after hospital discharge in a group of patients admitted for acute exacerbation of COPD. Variables that might be predictors of mortality were analyzed.

Subjects

Between October 1996 and May 1997, we recruited all consecutive patients admitted with COPD exacerbation to any medical ward of Hospital Mútua de Terrassa, a 520-bed, acute-care teaching referral center, in the province of Barcelona, Spain. Inclusion criteria were a clinical diagnosis of COPD, and forced spirometry at discharge showing FEV1 < 70% of the reference value and FEV1/FVC < 70%. Exacerbation was defined as breathlessness, respiratory failure (Po2 < 60 mm Hg and/or Pco2 > 50 mm Hg), or change in mental status due to COPD as the main reason for admission.

Exclusion criteria included a history of asthma, death during hospital stay, pneumonia or pulmonary edema at hospital admission, hospitalization for causes other than COPD exacerbation, patient inability to perform spirometric tests, or patient refusal to participate in the study. The study protocol was reviewed and approved by the hospital research and ethics committee.

Measurements

Determinations of arterial blood gas level, serum albumin level, and body mass index (BMI) were performed at hospital admission. Cor pulmonale was diagnosed by clinical criteria (signs of right-sided heart failure secondary to COPD or diuretic use for prior documented diagnosis). Information collected from patients included home use of oxygen therapy prior to hospital admission and a history of smoking. At some time during the 24 h before discharge, lung function (forced spirometry and bronchodilator tests) and arterial blood gas determinations were repeated. The following specific questionnaires were completed the last day before discharge.

Questionnaire on Regular Treatment:

The number of drugs and corresponding doses per day taken by the patient at home prior to admission were recorded. For inhaled drugs, one dose was considered to be one or more puffs of the same agent. Other treatment aspects, such as medication compliance and monitoring by the patient or family and knowledge of the nature of the medication being taken, were evaluated. All patients were asked to demonstrate how they administered the inhaled medication at home.

Quality-of-Life Questionnaire:

The validated Spanish version of St. George’s Respiratory Questionnaire (SGRQ),10 a specific questionnaire for COPD patients, was administered. It consists of 50 items with 76 weighted responses and three component scores: symptoms, activities, and impact. A total score is calculated from all three components, with zero indicating no health impairment and 100 representing maximum impairment. Questions 2 and 4, which ask about the frequency of mucus hypersecretion and wheezing, were analyzed separately and regrouped as frequent wheezing and mucus hypersecretion (when these symptoms occurred daily or several days per week), or infrequent (when they occurred only a few days per month, only when the patient had pulmonary infection, or never).

Dyspnea Assessment:

Dyspnea was evaluated on two scales: a visual analog scale of 10 cm and an adapted version of the American Thoracic Society dyspnea scale.11

Comorbidity Assessment:

Comorbidity was documented using the previously validated Charlson index,12 a standard scale with 15 chronic diseases graded for severity of disease. Furthermore, the most frequent chronic illnesses were analyzed separately.

Cognitive Deterioration Questionnaire:

The presence of cognitive impairment was assessed through the Pfeiffer Short Portable Mental Status Questionnaire,13 which consists of 10 items evaluating orientation, memory, concentration, and mental calculation. A correction factor to reflect the patient’s educational and cultural level is incorporated. Scores run from 0, representing no deterioration, to 10, indicating severe deterioration.

Functional Status:

At 2 weeks prior to hospital admission, functional ability was measured with the Katz Activities of Daily Living Scale,14 which reflects dependence in six primary social-biological functions: bathing, dressing, toileting, continence, walking, and eating. Scores range from 0 (independence) to 6 (high dependency).

Social Resources Interview:

Information about family composition, personal relationships, and the availability of care was collected in a structured interview using the social resources scale of the Older Americans Research and Service Center (OARS).15 The scores range from 1 (excellent social resources) to 6 (social disability). Marital status was dichotomized into two groups, married or unmarried. Unmarried patients included those who were divorced, separated, widowed, and never married.

Socioeconomic Level Estimation:

Information about educational level was collected, and three categories were defined: illiterate, without studies (noncompletion of elementary education), and with studies (completed elementary schooling). The patient was asked about the type of work performed throughout his or her lifetime. Answers were given on an item list, and the patient was then placed in one of two occupational categories (manual or other) according to the highest level of work reported.

Depression:

The presence of depression was detected by the Yesavage scale in its shortened version,16 which has 15 yes/no questions. The Yesavage scale is well suited for use in acutely ill persons because it focuses on symptoms of depression that are likely to be directly influenced by somatic illness. Scores from 0 to 5 are considered normal, scores from 6 to 10 are indicative of depression, and scores ≥ 11 are considered consistent with severe depression.

Patients were interviewed once by one of four trained interviewers. The latter filled in the questionnaires except the dyspnea analog scale and the SGRQ, specifically designed to be answered by the patient; interviewers could read the questionnaires to patients with problems of reading.

After discharge, each patient’s history of prior hospital admission was collected. The data available included number of hospital admissions attributed to COPD exacerbation, length of stay, and visits to the emergency department during the previous year. The length of stay of the current hospital admission was also determined. Readmission was defined if one or more hospitalizations had taken place in the previous year. If patients had been in the emergency department for a visit of < 24 h in duration, this was not considered a hospital admission.

After hospital discharge, the patients were monitored by their usual physicians and continued to receive their usual medications, receiving no intervention or follow-up provided by the investigators, who proceeded to collect data on mortality (date and cause of death when possible) in July 1999. The search was carried out by telephoning the patient or family and/or checking hospital records and the Mortality Register. Subjects who could not be located at follow-up and who were not clearly identified as dead (n = 6) were considered as missing data.

Statistical Analysis

Analyses were carried out using software (SPSS 6.2 for Windows; SPSS; Chicago, IL). Qualitative variables were expressed in percentages, quantitative variables as means ± SD, or medians and interquartile ranges (IQR, 25th to 75th percentile) to describe time values. In bivariate analysis, the relationship between survival time and patient characteristics was determined with the Cox proportional hazard model and Kaplan Meier survival curves. Multivariate analyses also were carried out with the Cox model after adjustment for FEV1. The analyzed variables were chosen based on statistical significance in the bivariate analyses and on clinical relevance. Significant variables in this model were then used to dichotomize the study population to statistically verify clinically relevant distinctions. Interactions between all terms included in the model were tested. Confidence intervals (CIs) for the odds ratios (ORs) of significant variables were calculated. Results were considered statistically significant at p < 0.05.

Of the 141 patients originally evaluated during hospital admission, follow-up information was available for 135 patients (96%; 124 men and 11 women). Six patients (4%) were unavailable for follow-up and were excluded from analysis. Mean age of the population studied was 72.2 ± 9.25 years. The women were older than the men: 79.36 ± 8.96 years vs 71.62 ± 9.03 years (p < 0.007). Mean length of stay was 13.47 ± 9.6 days (range, 2 to 76 days). Seventy patients (58.5%) were in respiratory failure (Po2 < 60 mm Hg) at the time of hospital admission; of those, 35 patients (25.8%) were also hypercapnic (Pco2 > 50 mm Hg). Eight patients required mechanical ventilation. All patients were treated with bronchodilators, systemic steroids, and oxygen. The administration of antibiotics was left to the physician’s discretion.

Sixty-four patients (47.4%) were dead at the end of the study; mortality data at 180 days, 1 year, and 2 years are shown in Figure 1 . Median follow-up duration was 378.5 days (IQR, 578.8 days) for deceased patients and 950 days (IQR, 130 days) for living patients. Causes of death are given in Table 1 .

Bivariate analysis indicated that mortality was higher among the oldest patients (p < 0.0001), women (p < 0.01), patients with fewer social resources (p < 0.03), and unmarried patients (p < 0.002). Nonsignificant differences in mortality were detected in relation to socioeconomic level represented by level of education and type of work (Table 2 ).

Sixty-nine patients were hospitalized on more than one occasion for exacerbation of COPD in the year prior to the study and they were classified as readmitted patients. This group had a higher rate of mortality (p < 0.001; odds ratio [OR], 2.28; confidence interval [CI], 1.36 to 3.82) than the rest, and mortality increased with the number of hospital admissions (p < 0.01; OR, 1.2; CI, 1.04 to 1.38).

Patients undergoing long-term oxygen therapy (p < 0.007) and with greater functional dependence (p < 0.0004), worse scores on the Pfeiffer scale (p < 0.01), and greater comorbidity (p < 0.0006) measured by the Charlson index had lower survival rates. The most frequently associated comorbidity was chronic heart failure and the only one that was significant in the bivariate analysis (p < 0.001; OR, 2.3; CI, 1.39 to 2.83; Table 3 ).

Prior to hospitalization, patients were receiving a mean of 5.23 ± 2.6 drugs and a mean of 11.39 ± 6.19 doses per day. Receiving either a greater number of drugs or higher doses was associated with a worse prognosis (p < 0.0006 and p < 0.009, respectively). A total of 99 patients (76.7%) managed their own medication without assistance. Mortality was less among patients who demonstrated greater understanding of their medication (p < 0.003). We found no association between incorrect use of inhalers and mortality (Table 4 ).

The score on the American Thoracic Society scale of dyspnea was also associated with mortality (p < 0.0002) in the bivariate analysis, whereas no differences in mortality were related to visual analog scale assessment of dyspnea. No significant differences related to mortality were found for albumin on hospital admission, BMI, frequency of expectoration or wheezing, presence of cor pulmonale, or current smoking. Similarly, no significant differences were found between the deceased and living patients with respect to prebronchodilator and postbronchodilator FVC, and FEV1 expressed as a percentage of the predicted value. In the analysis of arterial blood gas pressures, we found differences only for Pco2 at discharge (p < 0.03; Table 5 ).

The Yesavage depression scale score was associated with higher mortality (p < 0.00001). It was 3.11 times higher among patients whose score was ≥ 11 than among nondepressed patients (score ≤ 5; p < 0.0003; CI, 1.46 to 6.59; Fig 2 ). Worse scores on the SGRQ overall and on three SGRQ subscales were also associated with greater mortality, although only the activity subscale (10 points; OR, 1.32; CI, 1.14 to 1.53) and the global scale (10 points; OR, 1.21; CI, 1.04 to 1.4) reached statistical significance (Fig 3 ).

The multivariate analysis was adjusted for FEV1. The variables included were age, sex, comorbidity, functional dependence, marital status, hospital admission in the previous year, number of drugs taken at home, depression, dyspnea scale score, SGRQ activity subscale score, and Pco2 at discharge. Comorbidity, hospital readmission, depression, marital status, and the SGRQ activity subscale were independently associated with mortality. These variables were categorized at clinically relevant cut-off points. The Yesavage score was dichotomized at the level suggestive of severe depression (≥ 11 points) and a comorbidity index of ≥ 3 points on the Charlson scale, corresponding to two chronic diseases or one severe disease apart from COPD, was used. We considered patients to have a poor quality of life when the activity subscale score was ≥ 66 (Table 6 ).

The purpose of this study was to evaluate mortality predictors after discharge of patients hospitalized for acute exacerbation of COPD. This population consists of aging patients with associated chronic diseases and a high rate of functional dependence. We can expect that the factors predictive of mortality in such patients would be likely to differ from those reported for COPD patients overall. Our study confirms the importance of other factors, namely comorbidity, hospital readmission, the presence of depression, marital status, and quality of life, as the strongest predictors of mortality.

We found mortality in the first year after hospital admission for acute exacerbation of COPD to be 22%, a rate similar to that reported by other series (Fig 4 ).57 Mortality is lower in studies of outpatients, even when severe functional impairment is present. Thus, Postma et al3reported a 5-year mortality rate of 31% in patients with FEV1 < 1,000 mL, while Anthonisen et al4 reported a 3-year rate of 23% in patients with mean FEV1 of 36%. The better prognosis in those studies were confirmed in pulmonary rehabilitation patients with FEV1, age, and comorbidity similar to those of our series.,1718 Our results and those of other prospective studies59 suggest that hospitalization for acute exacerbation of COPD identifies a subgroup of the COPD population with a worse prognosis, and are consistent with those of Connors et al,9 who observed a higher rate of mortality among readmitted patients. This pattern, although demonstrated for other diseases,1920 is practically unexplored in COPD.

No predictive value was suggested when FEV1 was analyzed. These results are similar to those of other studies carried out in patients with low FEV1 values,5,2122 and are probably explained by the inability to differentiate between survivors and nonsurvivors on the basis of FEV1 when the range of values is low and homogeneous. Our gasometric findings agree with the experience of Costello et al,23 who demonstrated that Pco2 at discharge was a better predictor of survival than Pco2 on hospital admission. The lack of significance of low Po2 at discharge would be explained by the use of long-term oxygen therapy at home after discharge in hypoxic patients. The prognosis for those patients tends to improve to equal that of nonhypoxic patients.24

Functional dependence has been shown to influence prognosis in patients hospitalized for exacerbation of COPD.9,2526 In our study, we also found increased mortality in patients with greater functional dependence, as measured by the Katz index. Similarly, in our population, survival was poor among patients with worse scores on the SGRQ activity scale, which measures activities limited by dyspnea. In our study, the SGRQ activity score was a better predictor of mortality than the Katz index, probably because the former has been specifically developed for the patients with COPD or asthma. Previous studies relating mortality to quality of life in patients with COPD have been carried out using generic questionnaires4,27 or a single question.9 To our knowledge, our study is the first to demonstrate the relationship between mortality and quality of life using a specific questionnaire for COPD.

Married patients lived longer in our study, a finding that is consistent with several previous studies2829 reporting that unmarried patients have a poorer prognosis in other diseases. Better compliance in the utilization of prescribed medication30 has been demonstrated for married COPD patients, and a lower mortality rate was reported for married patients.27 The protective effect of marriage may be related to a shorter delay in seeking medical care, to psychological factors or to better compliance with treatment. In our study, being unmarried was an independent predictor of mortality, whereas no differences were found in patients living alone and in relation to socioeconomic status.

The Charlson index has been validated as a measure of comorbidity in a hospital population, and it is useful as a predictor of mortality in outpatients and in the geriatric population.31Our results showing a higher mortality rate among patients with greater comorbidity confirm those findings. Moreover, our results agree with those of Antonelli Incalz et al,32 even though those authors failed to find significant differences in survival rates in relation to the Charlson index. This discrepancy is probably explained by study design, ours being prospective whereas that of Antonelli Incalz et al32 was based on a retrospective review of associated comorbidity from case histories. This may explain our patients higher Charlson index scores of 2.22 (as compared to 1.38 as reported by Antonelli Incalz et al32), even though both populations were similar in age, FEV1, and hospital admission.

In our study, we observed a strong relationship between the presence of depression, assessed on the Yesavage scale, and medium-term mortality (death between 1 year and 3 years after discharge). Several studies have demonstrated similar associations in other diseases. Covinsk et al,33using the same Yesavage scale with a group of patients > 70 years of age who were hospitalized for a variety of reasons, found mortality to be 56% among depressed patients at 3 years. Although we know that the prevalence of depression in patients with advanced COPD is high,34few studies have explored the relationship in COPD between depression and mortality. In a prospective study of 16 patients with advanced illness, Ashutosh et al35 reported greater mortality at 4 years in depressed patients, even when differences in FEV1 were not present. Our study of a larger series confirms that finding, as well as the utility of the Yesavage scale to detect the population at risk. Since patients hospitalized for COPD are frequently depressed and there is a direct relation between depression and mortality, we believe that psychological status should be carefully assessed and the use of antidepressant medications or psychological interventions considered in patients with severe depression.

One limitation of this study is that only patients who could perform spirometry were enrolled. Although we were thus able to guarantee that all enrolled patients had confirmed diagnoses of COPD, in doing so we thereby possibly excluded the most severely affected patients. A second limitation is that spirometric and gasometric determinations were obtained on the day of discharge, a mean of 2 weeks after hospital admission, and they cannot therefore be considered baseline values. These limitations, however, do not change the main findings of the present study. Our work identifies several causes that are useful predictors of mortality after hospital admission for acute exacerbation of COPD, namely hospital readmission, depression, unmarried status, greater comorbidity, and poor quality of life. Some of these variables, which have until now been little analyzed in the context of COPD, can be at least partially influenced by health-care interventions.

Abbreviations: BMI = body mass index; CI = confidence interval; IQR = interquartile range; OARS = Older Americans Research and Service Center; OR = odds ratio; SGRQ = St. George’s Respiratory Questionnaire

Figure Jump LinkFigure 1. Kaplan-Meier survival curves in 135 patients hospitalized for acute exacerbation of COPD.Grahic Jump Location
Table Graphic Jump Location
Table 1. Causes of Death
Table Graphic Jump Location
Table 2. Patient Characteristics*
* 

Data are presented as mean ± SD or No. (%).

 

Unmarried patients include divorced, separated, widowed, and never-married individuals.

 

Social resources were assessed on the OARS scale; possible scores 0–6.

§ 

Did not complete elementary school.

 

Completed elementary school.

Table Graphic Jump Location
Table 3. Mortality and Chronic Comorbid Diseases*
* 

Data are presented as No. (%).

Table Graphic Jump Location
Table 4. Predictors of Mortality, Bivariate Study*
* 

Data are presented as No. (%) or mean ± SD.

 

Functional dependence valued by Katz index.

 

Comorbidity valued Charlson index.

§ 

Cognitive deterioration.

 

American Thoracic Society scale.

Table Graphic Jump Location
Table 5. Respiratory Function*
* 

Data are presented as mean ± SD.

 

Postbronchodilator (pbd) FEV1, percentage of the predicted value.

Figure Jump LinkFigure 2. FEV1 grouped in tertiles and mortality. *p < 0.001 among patients with FEV1 < 46% and those with FEV1 ≥ 47% of the predicted value.Grahic Jump Location
Figure Jump LinkFigure 3. Kaplan-Meier survival curves according to the Yesavage scale. ≤ 5 = not depressed patients; 6 to 10 = depressed patients; ≥ 11 = severely depressed patients.Grahic Jump Location
Table Graphic Jump Location
Table 6. Multivariate Analysis
* 

Patients with scores ≥ 66 vs ≤ 66 on the SGRQ activity subscale.

 

Patients with scores ≥ 3 vs ≤ 2 on the Charlson index.

 

Patients readmitted in previous year.

§ 

Patients with scores ≥ 11 vs ≤ 10 on the Yesavage scale.

 

Marital status: married vs widowed, separated, or never married.

Figure Jump LinkFigure 4. Quality of life and mortality measured by the SGRQ. *activity subscale p < 0.0002; †total scale p < 0.01.Grahic Jump Location

We thank Dr. Pau Sanchez for critical review of the article, and Ms. Mary Ellen Kerans for assistance in writing the article.

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Figures

Figure Jump LinkFigure 1. Kaplan-Meier survival curves in 135 patients hospitalized for acute exacerbation of COPD.Grahic Jump Location
Figure Jump LinkFigure 2. FEV1 grouped in tertiles and mortality. *p < 0.001 among patients with FEV1 < 46% and those with FEV1 ≥ 47% of the predicted value.Grahic Jump Location
Figure Jump LinkFigure 3. Kaplan-Meier survival curves according to the Yesavage scale. ≤ 5 = not depressed patients; 6 to 10 = depressed patients; ≥ 11 = severely depressed patients.Grahic Jump Location
Figure Jump LinkFigure 4. Quality of life and mortality measured by the SGRQ. *activity subscale p < 0.0002; †total scale p < 0.01.Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1. Causes of Death
Table Graphic Jump Location
Table 2. Patient Characteristics*
* 

Data are presented as mean ± SD or No. (%).

 

Unmarried patients include divorced, separated, widowed, and never-married individuals.

 

Social resources were assessed on the OARS scale; possible scores 0–6.

§ 

Did not complete elementary school.

 

Completed elementary school.

Table Graphic Jump Location
Table 3. Mortality and Chronic Comorbid Diseases*
* 

Data are presented as No. (%).

Table Graphic Jump Location
Table 4. Predictors of Mortality, Bivariate Study*
* 

Data are presented as No. (%) or mean ± SD.

 

Functional dependence valued by Katz index.

 

Comorbidity valued Charlson index.

§ 

Cognitive deterioration.

 

American Thoracic Society scale.

Table Graphic Jump Location
Table 5. Respiratory Function*
* 

Data are presented as mean ± SD.

 

Postbronchodilator (pbd) FEV1, percentage of the predicted value.

Table Graphic Jump Location
Table 6. Multivariate Analysis
* 

Patients with scores ≥ 66 vs ≤ 66 on the SGRQ activity subscale.

 

Patients with scores ≥ 3 vs ≤ 2 on the Charlson index.

 

Patients readmitted in previous year.

§ 

Patients with scores ≥ 11 vs ≤ 10 on the Yesavage scale.

 

Marital status: married vs widowed, separated, or never married.

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