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Keywords:

  • cancer;
  • survivors;
  • rural health;
  • health status;
  • mental health;
  • unemployment;
  • comorbidity;
  • health status disparities

Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. FUNDING SOURCES
  8. REFERENCES

BACKGROUND:

Although rural residents are more likely to be diagnosed with more advanced cancers and to die of cancer, little is known about rural-urban disparities in self-reported health among survivors.

METHODS:

The authors identified adults who had a self-reported history of cancer from the National Health Interview Survey (2006-2010). Rural-urban residence was defined using US Census definitions. Logistic regression with weighting to account for complex sampling was used to assess rural-urban differences in health status after accounting for differences in demographic characteristics.

RESULTS:

Of the 7804 identified cancer survivors, 20.8% were rural residents. This translated to a population of 2.8 million rural cancer survivors in the United States. Rural survivors were more likely than urban survivors to be non-Hispanic white (P < .001), to have less education (P < .001), and to lack health insurance (P < .001). Rural survivors reported worse health in all domains. After adjustment for sex, race/ethnicity, age, marital status, education, insurance, time since diagnosis, and number of cancers, rural survivors were more likely to report fair/poor health (odds ratio, 1.39; 95% confidence interval, 1.20-1.62), psychological distress (odds ratio, 1.23; 95% confidence interval, 1.00-1.50), ≥2 noncancer comorbidities (odds ratio, 1.15; 95% confidence interval, 1.01-1.32), and health-related unemployment (odds ratio, 1.66; 95% confidence interval, 1.35-2.03).

CONCLUSIONS:

The current results provide the first estimates of the proportion and number of US adult cancer survivors who reside in rural areas. Rural cancer survivors are at greater risk for a variety of poor health outcomes, even many years after their cancer diagnosis, and should be a target for interventions to improve their health and well being. Cancer 2013. © 2012 American Cancer Society.


INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. FUNDING SOURCES
  8. REFERENCES

Rural residents have higher cancer mortality than urban residents, and the largest disparities are observed for lung, colorectal, prostate, and cervical cancers.1 Disparities associated with rural residence also have been documented in cancer diagnosis and treatment,2-5 but little is known about disparities that may persist into the post-treatment survivorship period. A majority of survivors are now expected to live for at least 5 years after their cancer diagnosis,6 increasing the importance of monitoring long-term health and well being years after treatment is completed. Although estimates of the number of rural cancer survivors have not been published, 21% of the general population resides in rural areas,7 defined by the United States Census as residence outside of areas with an urban core of at least 50,000 individuals and densely settled, contiguous areas.8

Rural residents may face challenges in accessing medical care and necessary support services because of extended and sometimes difficult travel and a limited number of health care facilities.9, 10 Furthermore, rural residents in general tend to be older, poorer, less educated, less likely to have insurance, and more likely to encounter transportation challenges,11-13 exacerbating health disparities. The few studies that have examined quality of life, symptoms, or mental health among rural survivors9, 14, 15 have been limited by patient samples that were recruited from a single state or region. Thus, we know little about the population characteristics and health status of rural cancer survivors in the United States. The lack of information about rural cancer survivors hampers public health planning, allocation of medical resources, and the development of interventions to target this potentially vulnerable population of survivors.

To address these limitations, the objective of the current study was to estimate the number of adult cancer survivors who reside in rural areas of the United States and to describe their self-reported health status relative to urban survivors. Compared with nonrural survivors, we expected that rural survivors would report more medical comorbidities and greater psychological distress and would be more likely to report being in fair/poor health and being unable to work because of a health condition.

MATERIALS AND METHODS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. FUNDING SOURCES
  8. REFERENCES

Data Source

We analyzed data from the National Health Interview Survey (NHIS),16 an annual in-person survey of 30,000 to 40,000 households that provides a representative sample of the US civilian, noninstitutionalized population. The NHIS is administered by trained census workers and uses a complex sampling framework that involves clustering, stratification, and multistage sampling; Black, Hispanic, and Asian individuals are over sampled. Basic demographic information is collected on all members of the household. Information about cancer history is asked on the adult questionnaire, which is administered to 1 randomly chosen adult per family. Data were combined across the years from 2006 to 2010 to increase power for rural-urban subgroup analyses of cancer survivors. During these years, the final response rate for the adult survey ranged from 60.8% to 70.8%. Data collection for the NHIS was approved by the National Center for Health Statistics Research Ethics Review Board, which also approves protocols for use of restricted data that are not publicly available. Analysis of deidentified data from the survey is exempt from the federal regulations for the protection of human research participants, and local approval is not required.

Population Characteristics

Adults with a self-reported history of cancer other than nonmelanoma skin or “skin-type unknown” cancers comprised the survivor sample. We excluded these skin cancers to be consistent with the National Cancer Institute's Surveillance, Epidemiology, and End Results Program cancer survivor estimates, which do not include basal or squamous cell skin cancers, and because the treatment, surveillance, and survivorship of this type of cancer is likely very different from other cancer sites. Cancer site and date of diagnosis for up to 3 cancers are available for each individual. We calculated the time since cancer diagnosis by subtracting age at first cancer diagnosis from age at interview. Self-reported age, education, race/ethnicity, marital status, sex, income, and employment status are contained in the “Person file.”

Rural-Urban Residence

The NHIS rural-urban residence code is based on the US Census metropolitan area definitions that became effective in June 2003. Rural residences were defined as those located outside of urbanized areas and urbanized clusters (defined as core census block groups or blocks that have a population density of at least 1000 individuals per square mile and surrounding census blocks that have an overall density of at least 500 individuals per square mile).8 Rural-urban residence is a restricted variable; therefore, these data were accessed through the National Center for Health Statistics Research Data Center.

Health Status

Self-reported health was assessed with a single global health question that was derived from the Medical Outcomes 36-item Short-Form Survey instrument17 (SF-36): “Would you say your health in general is excellent, very good, good, fair, or poor?” Psychological distress was assessed with the Kessler K-6 scale,18 a brief screening scale that was designed for epidemiologic studies with possible scores that range from 0 to 24. Consistent with prior population research,19, 20 we used a 3-level categorization of psychological distress as follows: no probable distress (scores from 0 to 7), mild-moderate distress (scores from 8 to 12), and serious distress (scores from 13 to 24). These categories correspond to 87.5%, 8.5%, and 3.9% of the general adult population20 and have demonstrated good correspondence with the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), anxiety and mood diagnoses.21 For logistic regression models, we modeled the likelihood of reporting mild/moderate/serious distress (scores from 8 to 24) compared with no distress (scores from 0 to 7). We chose this approach rather than focusing on the clinical cutoff point of >12, in that we were interested in identifying survivors who were at risk for poor outcomes because of subclinical or moderate distress in addition to those with a likely serious anxiety or mood disorder. Consistent with prior approaches,22-24 a noncancer comorbidity score was calculated by summing 5 conditions which are ascertained in the NHIS (hypertension, heart disease, stroke, diabetes, and lung disease). Heart disease included coronary heart disease, angina, myocardial infarction, or any other heart condition; and lung disease included chronic bronchitis, emphysema, and current asthma. Adults who reported that they were not working or looking for a job and were temporarily unable to work for health reasons or disabled were considered unemployed because of health. Data were not available on the specific medical condition leading to unemployment.

Analytic Plan

Chi-square tests were used to assess rural-urban differences in sociodemographic characteristics and to assess unadjusted rural-urban differences in each health status outcome. Then, we defined binary versions of all outcome variables (fair or poor health, a K-6 score >7, ≥2 noncancer comorbidities, and unemployment because of health) and used multivariable logistic regression models to assess rural-urban differences in each dichotomized health status outcome after adjustment for demographic factors (age, sex, race/ethnicity, and marital status), cancer variables (type and number of cancers and time since diagnosis), and socioeconomic resources (education and health insurance coverage). We used education rather than income in models because of significant collinearity between the variables (P < .0001; chi-square test) and the large amount of missing income data. We assessed the impact of the covariates in a hierarchical fashion, adjusting first for the demographic factors; then for the demographic and cancer factors; and finally for the demographic, cancer, and socioeconomic factors. All statistical analyses were conducted using the SURVEYFREQ, SURVEYMEANS, and SURVEYLOGISTIC procedures in the SAS statistical software package (version 9.2; SAS Institute, Inc., Cary, NC), which incorporated strata and cluster information as well as sampling weights to account for the complex survey design of the NHIS. Cancer history was included as a domain to obtain estimates of the effects for cancer survivors. For the sensitivity analysis, we also examined health-related unemployment models that excluded retired individuals. There was very little change in the parameter estimates, so we report models that include all survivors.

RESULTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. FUNDING SOURCES
  8. REFERENCES

For the years 2006 to 2010, in total, 9958 adults reported a history of cancer. We excluded 2154 individuals who reported a history of exclusively nonmelanoma skin or “unknown” skin cancers, resulting in a total survivor sample of 7804.

Population Estimates for Rural Survivors

Of the identified cancer survivors, 20.8% (n = 1642) resided in areas defined as rural. By using population-based weights for the adult sample, we calculate that approximately 2,779,000 US cancer survivors reside in rural areas. Table 1 indicates the distribution of cancer survivors and population estimates by each category of rural-urban status. Survivors were distributed across all categories; it is estimated that approximately 304,000 survivors reside in completely rural areas (Table 1, categories 8 and 9).

Table 1. Distribution of Cancer Survivors by Category of County Rural-Urban Designation: National Health Interview Survey, 2006-2010
RUCA Codes and DescriptionaWeighted Percentage of Survivor SamplePopulation EstimateSD
  • Abbreviations: Metro, metropolitan; RUCA, Rural/Urban Commuting Area; SD, standard deviation.

  • a

    County codes are based 2003 RUCA codes from the Economic Research Service, Department of Agriculture. Metro counties are defined by the population size of their Metropolitan Statistical Area, and nonmetro counties are defined according to the size of their urban population.

1. Metro areas of ≥1 million45.16,024,000167,000
2. Metro areas of 250,000-1,000,00022.42,984,000189,000
3. Metro areas of 50,000-250,00011.71,562,000156,000
Total urban (1-3)79.210,570,000256,000
4. Urban population of 20,000-49,999, adjacent to a metro area7.1951,000124,000
5. Urban population of 20,000-49,999, not adjacent to a metro area1.6208,00065,000
6. Urban population of 2500-19,999, adjacent to a metro area5.8769,000126,000
7. Urban population of 2500-19,999, not adjacent to a metro area4.1548,000101,000
8. Completely rural or <2500 urban population, adjacent to a metro area1.1153,00042,000
9. Completely rural or <2500 urban population, not adjacent to a metro area1.1151,00047,000
Total rural (4-9)20.82,779,000161,000

Descriptive Characteristics of Rural and Urban Survivors

Almost half of patients were aged ≥65 years, and 60% were women as expected in a sample of cancer survivors. Breast and gynecologic cancers were most common in women, and prostate was most common in men; melanoma and colorectal cancer were common in both sexes. Sixty percent of survivors had survived for >5 years since their first cancer diagnosis, and 10% reported more than 1 cancer diagnosis.

Statistically significant differences in sociodemographic characteristics between rural and urban survivors were observed for race/ethnicity, education, poverty status, and health insurance coverage (see Table 2). Rural cancer survivors were significantly more likely than urban cancer survivors to be non-Hispanic white, to report lower levels of education, to report lower incomes, and to lack health insurance coverage. Cancer types generally were similar between urban and rural survivors, with the exception of a significantly higher percentage of gynecologic cancers among rural survivors. There was a slightly higher percentage of long-term survivors (≥10 years after diagnosis) among the rural survivors.

Table 2. Demographic Characteristics of Rural and Urban Cancer Survivors in the National Health Interview Survey, 2006-2010
 Rural Cancer Survivors, n = 1642Urban Cancer Survivors, n = 6162
CharacteristicWeighted PercentageSEWeighted PercentageSE
  • Abbreviations: FPL, Federal Poverty Level; GED, General Educational Development; SE, standard error.

  • a

    In 2009/2010, the FPL was $22,050 for a family of 4.

  • b

    Cancer types do not sum to 7804 because some survivors reported multiple cancers. Gynecologic cancers include cervical, uterine, and ovarian cancer.

Age, y    
 <5020.81.121.20.6
 50-6431.71.430.40.6
 65-7934.21.332.40.7
 ≥8013.21.015.90.6
Sex    
 Men38.91.439.60.7
 Women61.11.460.40.7
Marital status    
 Married or living with partner63.51.462.80.8
 Not married36.51.437.20.8
Race/ethnicity    
 Non-Hispanic white90.60.981.90.6
 Hispanic2.70.66.50.4
 Non-Hispanic black4.50.68.40.5
 Asian/Pacific Islander0.40.22.40.2
 Other1.80.40.80.1
Education    
 <High school23.41.314.50.6
 High school or GED diploma34.51.528.50.7
 Some college42.21.757.00.8
Poverty status, % of FPLa    
 <10011.01.06.70.4
 100-19917.11.011.50.5
 200-39923.51.520.20.7
 ≥40017.91.330.60.8
 Unknown30.51.631.01.0
Health insurance    
 None10.11.05.70.4
 Public only33.31.527.40.7
 Private56.61.866.90.8
Cancer type(s)b    
 Breast, n = 187920.51.122.50.6
 Gynecologic, n = 152021.91.217.60.6
 Prostate, n = 118214.81.016.40.6
 Colorectal, n = 7288.50.89.00.5
 Lung, n = 3263.90.54.00.3
 Melanoma, n = 6699.30.910.40.5
 Hematologic, n = 4616.40.76.30.4
 Other, n = 172023.61.422.70.7
No. of cancers    
 189.90.990.70.5
 >110.10.99.30.5
Time since first cancer diagnosis, y    
 <214.21.014.80.6
 2-525.31.427.50.7
 6-916.51.116.00.6
 ≥1044.11.441.70.8

Health Status in Rural and Urban Cancer Survivors

Rural cancer survivors reported significantly poorer health status for all indicators, as indicated in Table 3. Fair/poor health was reported by 36.7% of rural survivors compared with only 26.6% of urban survivors. Noncancer comorbidities also were more common in rural survivors than in urban survivors (36.5% vs 31.6% with ≥2 comorbidities). Rural survivors also reported greater psychological distress, with 18.8% in the 2 highest categories compared with only 12.8% of urban survivors. Rates of unemployment because of health reasons also were higher among rural survivors (18.5% compared with 10.6% of urban survivors).

Table 3. Self-Reported Health Status for Urban and Rural Cancer Survivors in the National Health Interview Survey, 2006-2010
 Rural Cancer Survivors, N = 1642Urban Cancer Survivors, N = 6162 
OutcomeWeighted PercentageSEWeighted PercentageSEP
  • Abbreviations: SE, standard error.

  • a

    Overall health was measured by a single item from the Medical Outcome Study 36-item short-form health survey.17

  • b

    Noncancer comorbidities included hypertension, heart disease, stroke, diabetes, and lung disease.

  • c

    Psychological distress was measured with the Kessler K-6 scale.25 Scores are indicated in parentheses.

Overall healtha     
 Excellent9.20.713.90.6< .0001
 Very good21.81.026.00.6 
 Good32.31.333.50.7 
 Fair23.41.218.50.6 
 Poor13.31.08.10.4 
Noncancer comorbidiesb     
 None28.81.335.80.7< .0001
 134.71.332.60.8 
 221.01.020.10.6 
 ≥315.51.111.50.4 
Psychological distressc     
 No probable distress (0-7)81.21.287.20.6< .0001
 Mild-moderate distress (8-12)11.61.08.20.5 
 Serious psychological distress (13-24)7.30.74.60.3 
Not employed because of health     
 Retired38.91.842.80.9< .0001
 Employed31.11.738.60.8 
 Unemployed because of health18.51.210.60.5 
 Unemployed for another reason11.51.07.90.4 

Adjustment for sociodemographic characteristics and cancer variables had little impact on the rural residence odds ratios [OR] for all 4 indicators of poor health, as detailed in Table 4. After further adjusting for health insurance coverage and education, rural survivors remained significantly more likely to report fair/poor health (OR, 1.39; 95% confidence interval [CI], 1.20-1.62), mild/moderate/severe psychological distress (OR, 1.23; 95% CI, 1.003-1.504), ≥2 noncancer comorbidities (OR, 1.15; 95% CI, 1.01-1.32), and health-related unemployment (OR, 1.66; 95% CI, 1.35-2.03).

Table 4. Factors Associated With Poorer Self-Reported Health in a Multivariable Linear Model Among US Cancer Survivors in the National Health Interview Survey, 2006-2010
 OR (95% CI)a
VariableRural ResidenceRural Residence Adjusted for DemographicsbRural Residence Adjusted for Demographics and Cancer VariablescRural Residence Adjusted for Demographics, Cancer Variables, and SESd
  • Abbreviations: CI, confidence interval; OR, odds ratio; SES, socioeconomic status.

  • a

    The effect of rural residence was statistically significant (P < .05) for all models.

  • b

    Demographic factors included age, sex, race/ethnicity (non-Hispanic whites vs others), and marital status (married or living with a partner vs others).

  • bCancer variables included the number of cancers (1 vs >1) and the time since diagnosis (<2 year, 2-5 years, 6-9 years, and ≥10 years).

  • c

    SES included education (<high school, high school or General Educational Development diploma, at least some college education) and health insurance (none, private, public only).

Fair or poor self-reported health1.60 (1.39-1.84)1.74 (1.50-2.02)1.76 (1.51-2.05)1.39 (1.20-1.62)
Two or more noncancer comorbidities1.24 (1.10-1.41)1.32 (1.26-1.51)1.32 (1.16-1.51)1.15 (1.01-1.32)
Elevated psychological distress1.61 (1.32-1.96)1.62 (1.33-1.98)1.60 (1.31-1.96)1.23 (1.003-1.50)
Unemployed because of health1.91 (1.58-2.31)2.08 (1.71-2.52)2.12 (1.73-2.59)1.66 (1.35-2.03)

DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. FUNDING SOURCES
  8. REFERENCES

We observed that 21% of US cancer survivors reside in rural areas, representing a population of 2.8 million US survivors. This proportion is almost the same as the general adult population, which is somewhat surprising, because rural residents tend to be older, and cancer incidence increases with age. Rural survivors are significantly more likely than their urban counterparts to report fair or poor health, 2 or more noncancer comorbidities, elevated levels of psychological distress, and unemployment because of health. The notable rural-urban health disparities observed in this study are accounted for partially, but not fully, by differences in socioeconomic resources (education and health insurance coverage).

Few studies have made direct comparisons between rural and urban cancer survivors for health status or quality-of-life outcomes. Our results illustrating poorer heath among rural cancer survivors are consistent with prior work that reported poorer mental health among rural cancer survivors compared with nonrural cancer survivors in Kentucky.14 Another study of rural cancer survivors also reported lower physical functioning health-related quality of life among rural survivors.26 In contrast to our findings, 1 recent Australian study reported similar health-related quality of life 12 months after treatment among urban and nonurban breast cancer survivors.27 A very large majority of our survivors (94%) were more than 1 year after diagnosis, raising the possibility that rural-urban disparities increase during the period after treatment. Alternatively, rural-urban differences may vary across countries because of variation in health care policy, including universal insurance coverage, and/or specific characteristics of rural areas (eg, distance to urban areas, access to health care, and transportation accessibility).

Approximately 19% of the rural survivors in our sample reported mild, moderate, or severe psychological distress compared with only 12.8% of the general rural adult population from prior studies using the Behavioral Risk Factor Surveillance System.19, 24 Our finding of greater distress among rural survivors (18.8% vs 12.8% among urban survivors) is the opposite of the pattern observed in the general adult population, in which urban adults were 22% more likely than rural adults to report mild, moderate, or severe psychological distress.19 There appears to be something about cancer or perhaps aging more generally that interacts with rural residence to alter the observed relations.

Pratt24 established that individuals with the greatest level of psychological distress (a Kessler score ≥11 in their study) had a 2.6 times greater hazard of mortality compared with those in the lowest category, and an increasing hazard of death was demonstrated for all escalating categories of distress. Prior studies also have established the importance of comorbidity burden for cancer survivors; survivors who have multiple comorbidities are much more likely to be in poor health, to report functional limitations, and to be unable to work for health reasons.28 Given the linkage between poor health outcomes and comorbidities, it is concerning that >15% of rural cancer survivors report ≥3 noncancer conditions compared with 11.5% of urban survivors.

Management of these comorbidities and cancer follow-up care in general requires access to the health care system. We expected the slightly higher prevalence of health insurance among urban versus rural survivors.29 Consistent with prior research on cancer survivors,30 we observed that the overall prevalence of health insurance in both groups was higher than in rural communities in general29 and in the US population.31 This likely is because of the older age and accompanying Medicare coverage of cancer survivors.

Although insurance coverage is important, rural residents in general report higher perceived barriers to care32 and appear to rely more heavily on primary care than urban residents.33 Rural cancer patients reportedly travel 6 to 10 times farther for chemotherapy and 2 to 4 times farther for radiation therapy than urban survivors.33 Whereas ongoing care from specialists may be feasible in urban contexts, survivors in rural areas may benefit from survivorship care managed by a primary care provider and coordinated with specialists.

Unemployment among cancer survivors is a well recognized issue, and the overall rate in our population mirrors that reported in other groups of cancer survivors.34, 35 Prior reports have not parsed the reason for unemployment, so a unique contribution of our current analysis is the attribution of more than half of the unemployment among cancer survivors to health issues. These health issues presumably include cancer-related problems and also may arise from other conditions. Another novel finding is the rural-urban disparity in both overall and health-related unemployment, which, to our knowledge, has not been previously reported. This finding is particularly striking, because no such disparity has existed in national unemployment data for the past 2 decades.36 Cancer survivors may find it more difficult to maintain employment in rural settings, in which production, transportation, and service occupations are more common than the professional, management, and business occupations that predominate urban environments.37 Overall, these results reinforce the need to address occupational issues among cancer survivors and suggest that this may be particularly important to survivors who reside in rural areas.

The primary limitation of this study was the use of self-reported rather than registry-confirmed cancer history. Some studies have suggested that individuals may under report a diagnosis of cancer relative to medical record or registry review, with greater under reporting among men.38 Female genital cancers may be particularly problematic; some studies indicate that endometrial and cervical cancers are under reported,39 whereas others indicate over reporting.38 The population estimate for the total number of US survivors suggested by these data (13.3 million), thought of best as a population estimate of the midpoint of the time interval (2008), is slightly higher than National Cancer Institute population estimates using Surveillance, Epidemiology, and End Results registry data.40 However, the most common cancer sites identified in our sample are the most prevalent cancers in the survivor population as estimated by the Surveillance, Epidemiology, and End Results Program.41 In addition, our study may have excluded very ill cancer survivors who resided in institutional settings or were too ill to respond to the study.

The primary strength of this study was the use of a population-based data set that was designed to be representative of the US population. In addition, we used a robust definition of rural residence, based on US Department of Agriculture Rural Urban Commuting Area codes, rather than relying on perceived rural residence or hospital/clinic location as a proxy. This will facilitate comparison with other research using the same definitions.

These data suggest that rural cancer survivors are a vulnerable population at risk for poor health outcomes after a cancer diagnosis. Future studies should examine other factors that may underlie rural-urban differences in health status, including the prevalence of health-compromising behaviors and additional access to care variables. Efforts should be undertaken to identify the needs of rural cancer survivors and to develop comprehensive survivorship care planning programs to address these needs.

FUNDING SOURCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. FUNDING SOURCES
  8. REFERENCES

This work was supported by the National Cancer Institute at the National Institutes of Health (grant R03 CA156641-01).

CONFLICT OF INTEREST DISCLOSURES

The authors made no disclosures.

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. FUNDING SOURCES
  8. REFERENCES
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