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Long-term Outcomes of IBD // the Manitoba IBD Cohort Study

From 2002 through 2016, our IBD Centre had continuous funding from the Canadian Institutes of Health Research for an ongoing study, where we followed the same group (known as a cohort) of individuals with IBD over several years. Our goal was to understand what factors predicted disease outcomes in this group of persons with IBD, and how their mental health affected their outcomes. 

What did we do?

We recruited adults within 7 years of diagnosis, so they were relatively new to the disease experience. These individuals provided information every 6 months through survey questions, and we met with them once a year for an in-person interview and to draw blood. Everyone was recruited from the University of Manitoba IBD Research Registry, which includes people with IBD from all across the province (not just from a specialty clinic), which means that the findings from this cohort study could represent the experiences of all Manitobans with IBD.

What did we find?

Clinical Understanding of IBD

  • Irritable bowel syndrome in IBD: We found that about 14% of persons with IBD may also have irritable bowel syndrome. This is important to know for treatment planning, as it may be that some of the gut related symptoms do not need anti inflammatory treatments for those who have IBS in addition to IBD.

Burgmann T, Clara I, Graff L, Walker J, Lix L, Rawsthorne P, McPhail C, Rogala L, Miller N, Bernstein CN. The Manitoba IBD Cohort study: Prolonged symptoms before diagnosis-How much is IBS? Clinical Gastroenterology and Hepatology 2006; 4: 614-20.

  • Adherence to taking medicines: We looked at how consistently people take their medication for IBD, and found that about one-third were ‘low adherers’, meaning they did not fully adhere to or follow their medication plan. Men were more likely to take their medication consistently than women, and older women were more likely to take their medication regularly than younger (less than 30 years old) women.  Not surprisingly, those who had more obstacles related to using medication, such as cost of the medication were less consistent in taking them.

Ediger JP, Walker JR, Graff L, Lix L, Clara I, Rawsthorne P, Rogala L, Miller N,  McPhail C, Deering K, Bernstein CN. Predictors of medication adherence in inflammatory bowel disease. American Journal of Gastroenterology 2007;102: 1417-26.

  • Bone health in IBD: Research has found that individuals with IBD are more likely to develop osteoporosis (a disease where the bones becomes less dense and can fracture more easily) or have decreased bone mineral density, so we assessed bone health over time in our Cohort participants. We found that serum levels of vitamin D, a hormone that maintains bone health, were related to bone mineral density (a measure of whether people had osteoporosis) at the start of the study, such that the higher the vitamin D levels, the higher the bone mineral density. We also found that greater weight, height, and body mass were associated with greater bone density. However, we found that only 22% of recently diagnosed persons with IBD participants had optimal circulating levels of vitamin D, a hormone that maintains bone health. This suggests that addressing levels of vitamin D, proper nutrition, and body weight early in the disease course may play an important role in preventing IBD-related bone disease.

  • We tested the bone mineral density and looked at X-rays of the vertebrae (the small individual bones that make up the spine-also called the backbone) a second time 4 years after the first measurement at study entry.We found that those with IBD under 50 years old typically did not have any significant loss of bone mineral density, and that vertebral (spine) fractures were not very common. Age over 50 years, decreasing body mass index (usually meaning lower weight), and corticosteroid use (such as prednisone) were related to bone density loss. Only 5% of individuals in the Cohort over 50 years experienced a definite fracture that could be confirmed on X-ray. Also there were no major fractures experienced in other areas of the body beside the spine. Overall, these findings suggest that persons with IBD do not appear to have significantly accelerated bone mineral density loss, which is good news for bone health.

Leslie WD, Miller N, Rogala L, Bernstein CN. Vitamin D status and bone density in recently diagnosed inflammatory bowel disease: The Manitoba IBD Cohort Study. American Journal of Gastroenterology 2008; 103:1451-9.

Leslie WD, Miller N, Rogala L, Bernstein CN. Body mass and composition affect bone density in recently diagnosed inflammatory bowel disease: the Manitoba IBD Cohort Study. Inflamm Bowel Dis. 2009 Jan;15(1):39-46.

Targownik LE, Leslie WD, Carr R, Clara I, Miller N, Rogala L, Graff LA, Walker JR, Bernstein CN.  Longitudinal change in bone mineral density in a population-based cohort of patients with inflammatory bowel disease. Calcific Tissue International 2012; 91; 356-61.

  • Fatigue and IBD: Fatigue is one of the most common symptoms persons with IBD experience, so we took a closer look at how commonly it occurs and what might help to explain why or when it occurs. We found that almost three-quarters (72%) of those with active disease reached clinical thresholds for significant fatigue, as did 30% of those with inactive disease. We also evaluated sleep quality and found that 77% with active IBD, and almost half (49%) of those with inactive disease experienced poor sleep. The strongest predictors of fatigue were active disease, poor sleep quality, and level of stress.   However, the number of hours of sleep did not predict fatigue, and neither did serum hemoglobin (which reflects iron levels in the blood) or serum C reactive protein (CRP) l (which is a measure in the blood of inflammation).

  • We also looked at fatigue levels 2 years later to understand changes over time. First, levels of fatigue were clearly related to disease activity; for example, participants whose IBD was consistently inactive across the two year period had the lowest levels of fatigue. Fatigue levels were more likely to increase over time for women, those with higher levels of distress, lower levels of psychological well-being, and those with poor sleep quality. These findings suggested that fatigue can worsen even for those whose disease is in remission (inactive), and that psychological factors and sleep may be useful targets for intervention to reduce fatigue. 

 

  • Finally, we studied iron levels in the blood and whether having just iron deficiency (low iron levels) but not anemia (anemia refers to low hemoglobin levels in the blood) was associated with fatigue, since there has been an assumption that just lowering iron stores to a subnormal range can cause fatigue and replenishing the blood iron level to normal could reverse the fatigue. Overall, 18% of Cohort participants had anemia.  Iron deficiency was identified in 20% of those with Crohn's disease and 27% with ulcerative colitis. Looking at those with low iron levels but no anemia, they were no more likely to experience fatigue compared with those whose iron levels were normal.

Graff LA, Vincent N, Walker JR, Clara I, Carr R, Ediger J, Miller N, Rogala L, Rawsthorne P, Lix L, Bernstein CN. A population-based study of fatigue and sleep difficulties in inflammatory bowel disease. Inflammatory Bowel Diseases 2011; 17: 1882-9.

Graff LA, Clara I, Walker JR, Lix L, Carr R, Miller N, Rogala L, Bernstein CN. Fatigue, over 2 years, is associated with disease activity and psychological factors in longitudinal study of inflammatory bowel disease. Clinical Gastroenterology and  Hepatology 2013; 11: 1140-6.

Graff LA, Clara I, Walker JR, Lix L, Carr R, Miller N, Rogala L, Bernstein CN. Fatigue, over 2 years, is associated with disease activity and psychological factors in longitudinal study of inflammatory bowel disease. Clinical Gastroenterology and  Hepatology 2013; 11: 1140-6.

  • Complementary and alternative medicine: IBD patients have told us that they have tried different types of health products and sometimes worked with other types of health professionals besides medical staff for their IBD, so we aimed to determine what people were using and how common was the use of these complementary products and services was over time. We asked about the use of 12 types of complementary and alternative medicine (CAM) service providers and 13 CAM products over a 4.5 year period. Overall, 74% used a CAM service or product, with approximately 40% using some type of CAM at each time point, and 14% using CAM consistently at every time point. Women were just slightly more likely to use CAM more than men; there was no difference in CAM use between individuals with Crohn's disease and those with ulcerative colitis. The most commonly used CAM services (on average) were massage therapy (30%), chiropractic (14%), physiotherapy (4%), acupuncture (3.5%) and naturopathy/homeopathy (3.5%). A wide range of CAM products were tried, with Lactobacillus acidophilus (8%), fish and other oils (5.5%), glucosamine (4%) and chamomile (3.5%) as the most common. On average, only 18% of those using CAM products or services were trying them for their IBD, so the majority chose them for other reasons.

 

  • These findings suggested that CAM products and services are not usually used by patients with IBD for disease management, but clinicians should be aware that many will try out these types of services and products.

Rawsthorne P, Clara I, Graff LA, Bernstein KI, Carr R, Walker JR, Ediger J, Rogala L, Miller N, Bernstein CN. The Manitoba IBD Cohort Study: A prospective longitudinal evaluation of the use of complementary and alternative medicine services and products. Gut 2012; 61:521-7.

  • Nutrition: IBD patients have many questions about diet and how foods interact with their disease.  We looked at eating patterns, comparing the diet, sugar intake and patterns of food avoidance of those in our IBD Cohort compared with non-IBD Canadian cohort using our with people from across Manitoba who were of similar age.  We were able to use nutrition questions from a national Canadian survey (the Canadian Health Measures Survey (CHMS)). We found that the most likely food items to be avoided by individuals with IBD were alcohol, popcorn, legumes, nuts, seeds, deep-fried food, and processed deli meat, and that avoidance of these foods was more common among those with active disease. Individuals with active IBD also consumed significantly larger amounts of sports drinks and sweetened beverages compared to those with inactive disease.

 

  • Compared with other Canadians who do not have IBD, those in our IBD Cohort consumed significantly less iron-rich food, and tended to have more milk. Otherwise diets were fairly similar. 

 

  • We concluded that food avoidance was fairly common among those with IBD, but that it may be in part to managing the disease and in part due to personal preferences. There was some concern that sugar-laden beverages may be displacing other foods which are higher in nutrients. Since malnutrition is a risk in IBD, nutrition education by trained dietitians who are familiar with the disease should be part of the overall care of the IBD patient, in order to address food avoidance and ensure optimal nutrition.

Vagianos K, Clara, I, Carr, R, Graff LA, Walker JR, Targownik LE, Lix LM, Rogala, L, Miller, N, Bernstein CN. What are adults with IBD eating? A closer look at the dietary habits of a population-based Canadian IBD cohort. Journal of Enteral and Parenteral Nutrition 2016; 40: 405-411.

  • Predictors of disease complications: There are wide variations in the course of the disease and it can be very difficult to predict why disease settles for some people, and others experience various IBD complications. In this study we investigated whether blood markers, genes or psychological characteristics were associated with complicated Crohn’s disease, with complicated disease defined as the occurrence of strictures (scarred narrowed areas in the bowel) or fistulas (tracts that develop from the bowel to another organ or to the skin) in the gastrointestinal tract,, and surgery. Of the 182 persons in the Cohort study with Crohn’s disease, 65% had complicated disease and 42% underwent surgery. The presence of an antibody called ASCA early in disease course helped to predict who developed strictures/fistulas 10 years later. In turn, this complicated type of Crohn’ s disease was strongly related to the likelihood of having surgery. Gene profiles and psychological characteristics were not significantly associated with these disease complications, serological profile, or genotype.

Ryan JD, Silverberg MS, Xu W, Graff LA, Targownik LE, Walker JR, Carr R, Clara I, Miller N, Rogala L, Bernstein CN. Predicting complicated Crohn’s disease and surgery: phenotypes, genetics, serology and psychological characteristics of a population based cohort. Alimentary Pharmacology and Therapeutics 2013; 38: 274-83.

  • Disability: Disability is defined by chronic limitations that get in the way of participating in usual daily activities. We examined the level of disability and the factors associated with it, a decade or more after diagnosis, by interviewing  244 persons in the Cohort study at approximately 12 years since their diagnosis.  Some level of disability or interference of the IBD in day to day activities such as household responsibilities, self-care, recreational activities, or work, for example, was reported by 19% of those with Crohn’s disease, and by 11% of those with ulcerative colitis. Disability was associated with a poorer quality of life. Long-term active disease and a history of major depression at some point in the past were associated with disability, whereas history of IBD-related surgeries or hospitalizations was not. 

 

  • Overall, we found that a minority of persons with IBD have significant disability after a decade of disease, and that it is a little more likely that individuals with Crohn’s disease will be impacted by disease interference than those with ulcerative colitis. Depression should be treated as aggressively as the IBD.

Israeli E, Graff LA, Clara I, Walker JR, Lix LM, Targownik LE, Bernstein CN. Low prevalence of disability among patients with inflammatory bowel diseases a decade after diagnosis. Clinical Gastroenterology and Hepatology 2014; 12: 1330-7.

 

Psychological Health and IBD

In our first report assessing psychological functioning in persons with IBD we found that persons with active disease had higher levels of distress, health anxiety, and perceived stress, lower social support, well-being and mastery, and poorer disease-specific QOL, relative to those with inactive disease. There were no differences for persons with Crohn’s disease compared with persons with ulcerative colitis for psychological functioning or quality of life. Given the strong association between disease-specific QOL, psychological functioning, and disease activity, it is important to be aware of related difficulties in patients with active IBD.

We wanted to assess psychological functioning over and quality of life over time. We assessed disease activity in relation to these outcomes over the first two years of follow up within the Cohort Study. Half of the participants had fluctuating disease activity, while almost one-third of participants reported consistent active disease. Participants with the fluctuating activity pattern showed significant improvement in disease-specific quality of life compared to participants with consistent activity. Perceived stress, health anxiety, and pain anxiety decreased while pain catastrophizing and mastery increased over time, although the amount of change was not significantly different among disease activity patterns. We concluded that change in IBD quality of life was influenced by one's longitudinal profile of disease activity, but change in psychological functioning was not. Effects of disease activity on psychological functioning were modest, suggesting that disease has an impact even when patients are not experiencing active symptoms.

For our next report we asked persons with IBD in our Cohort the same questions asked of Canadians in the general population as part the Canadian Community Health Surveys (CCHS) to assess psychosocial variables. We used a sample of respondents to the CCHS as a control group to compare to our IBD Cohort.  Overall, the IBD sample had lower psychological well-being and mastery, as well as higher distress than persons without IBD. Those with IBD used avoidant coping significantly more often, and active coping modestly more often than those without IBD. Persons with Crohn's disease and ulcerative colitis had similarly poor levels of functioning along these dimensions compared to persons without IBD. However, those with inactive IBD were similar to the non-IBD sample. Psychological factors explained a greater amount of variance in perceived health for the IBD than for those without IBD in the community. We concluded that those with IBD have significantly poorer psychological health than do those without IBD and view their general health status more negatively. However, when the disease was inactive there was little change in psychological functioning compared to persons in the general community. Hence, we advocated that at times of active disease clinicians need to consider psychological needs in the care of an IBD patient.

In a second study comparing the IBD Cohort to the community sample, persons with IBD participants received more emotional support in the prior year and were more likely to have experienced a positive social interaction. Those with IBD were as likely to be employed as those in the community sample, although they reported greater rates of reduced activity and days missed. Individuals with IBD were twice as likely to report unmet healthcare needs than the community sample; however, there was agreement across both groups regarding common barriers, including long waits and availability. We concluded that persons with IBD had similar levels of stress as persons in the community but appeared to have enhanced social supports relative to those in the community without IBD.

In another study comparing our IBD Cohort with persons in the general community we found that persons with IBD were twice as likely than persons in the community to have a history of major depression long before their diagnosis of IBD. Comparing persons with IBD with and without lifetime anxiety or mood disorder, those with a disorder reported lower quality of life and earlier onset of IBD symptoms and there was a trend toward earlier IBD diagnosis. We concluded that clinicians should be aware of the increased prevalence of depression and possibly other anxiety disorders in persons with IBD as these disorders may influence response to treatment and quality of life.

Self-efficacy describes a person's confidence in their ability to manage demands, and is predictive of health outcomes in chronic disease such as hospitalization and health status. We undertook a study to validate a scale measuring self-efficacy in persons with IBD- Inflammatory Bowel Disease Self-Efficacy scale (IBD-SE). We validated the scale and found that those with currently inactive disease had higher self-efficacy than those with active disease group. Because self-efficacy is a modifiable psychological characteristic that can contribute to positive health outcomes, the IBD-SE may prove to be a valuable instrument for research and in targeted intervention to improve self-efficacy in persons with IBD.

We also aimed to determine the prevalence of adverse childhood experiences in persons with IBD and whether having adverse childhood experiences was associated with health care utilization post IBD diagnosis. 345 participants from the population-based Manitoba IBD Cohort Study self-reported adverse childhood experiences (i.e., physical abuse, sexual abuse, death of a very close friend or family member, severe illness or injury, upheaval between parents, and any other experience thought to significantly impacts one’s life or personality) at a median of 5.3 years following IBD diagnosis. Cohort Study data were linked to administrative health databases that captured use of hospitals, physician visits, and prescription drugs; use was classified as IBD- and non-IBD-related. The prevalence of at least one adverse childhood experiences was 74.2%. There was no statistically significant association between having experienced an adverse childhood experience and health care use. However, mean annual non-IBD-related general practitioner visits were significantly higher for participants exposed to physical and sexual abuse than those not exposed. Selected rates of IBD-related healthcare use were lower for participants who reported exposure to an upheaval between parents and high perceived trauma from adverse childhood experiences. In summary, the estimated prevalence of at least one self-reported adverse childhood experience in persons with diagnosed IBD was high. Health care use among those who experienced adverse childhood experiences may reflect the impacts of adverse childhood experiences on health care anxiety.

Graff LA, Walker JR, Lix L, Clara I, Rawsthorne P, Rogala L, Miller N, Jakul L, McPhail C, Ediger J, Bernstein CN. The relationship of inflammatory bowel disease type and activity to psychological functioning and quality of life. Clinical Gastroenterology and Hepatology 2006; 4:1491-1501.

 

Rogala L, Miller N, Graff LA, Rawsthorne P, Clara I, Walker JR, Lix L, Ediger JP, McPhail C, Bernstein CN. A population-based controlled study of social support, self perceived stress, activity and work issues and access to health care in IBD. Inflammatory Bowel Diseases 2008; 14: 526-35.

 

Lix LM, Graff LA, Walker JR, Clara I, Rawsthorne P, Rogala L, Miller N, Ediger J, Pretorius T, Bernstein CN. Longitudinal study of quality of life and psychological functioning for active, fluctuating, and inactive disease patterns in inflammatory bowel disease. Inflammatory Bowel Diseases 2008; 14: 1575-84.

 

Graff LA, Walker JR, Clara I, Lix L, Miller N, Rogala L, Rawsthorne P, Bernstein CN. Stress coping, distress, and health perceptions in inflammatory bowel disease and community controls. American Journal of Gastroenterology 2009; 104:2959-69.

 

Graff LA, Sexton KA, Walker JR, Clara I, Targownik LE, Bernstein CN. Validating a measure of patient self-efficacy in disease self-management using a population-based IBD cohort: the IBD Self-Efficacy Scale. Inflammatory Bowel Diseases 2016; 22: 2165-72.

 

Walker JR, Ediger JP, Graff LA, Greenfeld JM, Clara I, Lix L, Rawsthorne P, Miller N, Rogala L, McPhail C, Bernstein CN. The Manitoba IBD Cohort Study: A population-based study of the prevalence of lifetime and twelve-month anxiety and mood disorders. American Journal of Gastroenterology 2008; 103:1989-97.

Witges K, Bernstein CN, Sexton K, Afifi T, Walker JR, Nugent Z, Lix L. The relationship between adverse childhood experiences and healthcare use in the Manitoba IBD cohort study. Inflammatory Bowel Diseases 2019; in press.

 

Informing patients about their disease

Understanding the information needs and preferred ways to deliver information to patients with inflammatory bowel disease (IBD) will enhance their care. We surveyed persons in the IBD Cohort as to their information needs and preferred vehicles of information delivery. Recalling time of diagnosis, at least 80% rated as very important information about common symptoms of IBD, possible complications, long-term prognosis, medication side effects, self management of symptoms and when to involve the doctor, yet only 10% to 36% believed they received the right amount of information about these issues. Dietary guidance was also regarded as important by 80% to 89%, yet only 8% to 16% received the correct amount of information.

Regarding current needs, a large proportion believed it would be very helpful to have more information about long-term prognosis (66%) and diet considerations (60% to 68%). The following information sources were regarded as very acceptable: medical specialist (81%); brochure (79%); family doctor (64%); and website (64%), with 51% ranking the medical specialist as the first choice. In a comparison of the responses of this cohort to those diagnosed within 6 month, there was remarkable consistency in the information needs and most desired sources of information. In our IBD Cohort with longstanding disease, dietary information was regarded as the least adequately addressed. There was clear openness to receiving information through other routes than just the medical specialist, suggesting that optimizing brochures and websites would be an important adjunct source of information. We concluded that approximately 10 years after diagnosis, only a small percentage of persons with IBD believed they received the correct amount of information about the issues they regarded as most important to have discussed at diagnosis.

 

In a substudy of our IBD Cohort Study we undertook in depth open ended interviews with 45 persons of different ages and disease durations. One important finding was the changing need for health-related information over time. Participants identified six contextual factors influencing engagement with information to make health decisions: (1) emotional and attitudinal responses, (2) perceived benefits and risks, (3) trust in the source of the information, (4) knowledge and skills to access and use information, (5) availability of evidence to support decisions, and (6) social and economic environments.

We concluded that practitioners can be responsive to information needs of people with IBD by having high quality information available at the right time in a variety of formats and by supporting the incorporation of information in daily life.

We also assessed how our interviewees adapted to work. Our interviewees reported that IBD symptoms and treatments interacted with other personal and environmental factors to shape the experiences of work. Experiences were shaped by: (1) personal health and well-being, (2) personal values, beliefs, and knowledge, (3) job characteristics, (4) workplace physical environment, (5) workplace culture, and (6) financial factors. Participants identified personal strategies and environmental supports that assisted them to navigate their work roles.

Bernstein KI, Promislow S, Carr R, Walker JR, Rawsthorne P, Bernstein CN. The information needs and preferences of recently diagnosed patients with IBD. Inflammatory Bowel Diseases 2011; 17: 590-98.

Wong S, Walker JR, Graff LA, Carr R, Clara I, Promislow S, Miller N, Rogala L,

Bernstein CN. The information needs and preferences of persons with longstanding IBD. Canadian Journal of Gastroenterology 2012; 26: 525-31.

 

Restall G, Simms A, Walker JR, Graff LA, Sexton KA, Rogala L, Miller N, Haviva C, Targownik LE, Bernstein CN. Understanding work experiences of people with inflammatory bowel disease. Inflammatory Bowel Diseases 2016; 22:1688-97.

 

Restall GJ, Simms AM,  Walker, JR, Haviva C,  Graff LA, Sexton KA, Miller,. Targownik LE, Bernstein CN. Coping with Inflammatory Bowel Disease: Engaging with Information to Inform Health-Related Decision-Making in Daily Life. Inflammatory Bowel Disease 2017 Aug; 23(8): 1247-1256.

 

Methods for Conducting Research Studies in IBD

Another goal of our IBD Cohort Study was to enhance our understanding of conducting cohort studies in IBD. We developed a single question that could be used to determine how persons with IBD have been doing regarding their disease activity over the prior 6 months. When we started our IBD Cohort Study the only available disease activity assessment tools assessed the prior week. We developed the Manitoba IBD Index as a tool to assess disease activity over the prior 6 months. We have repeatedly used it throughout our IBD Cohort Study and in other studies we have undertaken.

We pursued a study to determine how well persons with IBD could recall their health service utilization (ie doctor visits and hospitalizations) by comparing their self report to their actual administrative health data maintained in the Manitoba Health Administrative Health Databases. People generally recalled their hospitalizations with a high degree of accuracy. Physician visits were significantly under-reported and there was a trend to over-report the number of nights in hospital. Administrative health data are the most accurate way to determine health care utilization, however, we concluded that If administrative data are not available, self-report information may be a cost-effective alternative, particularly for hospitalizations.

We also undertook studies to evaluate our analyses of our multiple measures that were frequently repeated over time. We studied the optimal statistical methods to use in analyzing these very large sets of data.

Clara I, Lix LM, Walker JR, Graff LA, Miller N, Rogala L, Rawsthorne P, Bernstein CN. The Manitoba IBD Index: Evidence for a New and Simple Indicator of  IBD Activity. American Journal of Gastroenterology 2009; 104(7):1754-63.

 

Longobardi T, Walker JR, Graff LA, Bernstein, CN. Health service utilization in IBD: Comparison of self-report and administrative data. 2011 May 31;11(1):137.

 

Sajobi TT, Lix LM, Clara I, Walker J, Graff LA, Rawsthorne P, Miller N, Rogala L, Carr R, Bernstein CN. Measures of relative importance for health-related quality of life. Quality of Life Research 2012;21:1-11.

 

Lix LM, Sajobi TT, Sawatzky R, Jiu J, Mayo NE, Huang Y, Graff LA, Walker JR, Ediger J, Clara I, Sexton K, Carr R, Bernstein CN. Relative importance measures for reprioritization response shift. Quality of Life Research 2012; 22: 695-703.

 

Mayo NE, Scott SC, Bernstein CN, Lix LM. How are you? Do people with inflammatory bowel disease experience response shift on this question? Health and Quality of Life Outcomes 2015; May 6: 13: 52.