Original Article
Factors Associated With Health-Related Quality of Life in Children With Duchenne Muscular Dystrophy
Journal of Child Neurology 1-8 ª The Author(s) 2016 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0883073815627879 jcn.sagepub.com
Yi Wei, MSc1,2, Kathy Nixon Speechley, PhD1,2,3, Guangyong Zou, PhD3, and Craig Campbell, MD, MSc, FRCP(C)1,2,3,4
Abstract This study investigated clinical and family characteristics associated with health-related quality of life in children with Duchenne muscular dystrophy. Families of 176 boys with Duchenne muscular dystrophy were identified and mailed questionnaires via the Canadian Neuromuscular Disease Registry. Multiple linear regressions analyses were used to examine the relationship between clinical and family characteristics and child-self and parent-proxy reported health-related quality of life. Greater fatigue and use of wheelchairs were consistently associated with worse health-related quality of life independent of other factors. Higher household income and parent having a postsecondary degree were associated with better health-related quality of life in some of the measures. A greater clinical focus on and efforts to reduce fatigue could lead to improvement of health-related quality of life in the Duchenne muscular dystrophy population. This study also sets the ground for longitudinal studies where changes in health-related quality of life can be monitored over time. Keywords neuromuscular, Duchenne muscular dystrophy, health-related quality of life, fatigue, registry Received April 30, 2015. Received revised December 7, 2015. Accepted for publication December 17, 2015.
Duchenne muscular dystrophy is a neuromuscular disorder affecting between 1 in 3 500 and 1 in 5 000 newborn boys. It is characterized by progressive muscle loss resulting in profound physical disability. Most boys succumb to the disease before age 30 years due to respiratory or cardiac failure.1 There is no cure for Duchenne muscular dystrophy, the standard of care involves corticosteroids to prolong ambulation and ventilation to extend life expectancy.2 A number of promising therapies are undergoing various stages of clinical trials, making outcome assessment an important research goal. The Food and Drug Administration has mandated that patient-reported outcomes such as health-related quality of life be part of all clinical trials.3 Health-related quality of life is a subjective and multidimensional construct.4 Health-related quality of life measures can be divided into disease-specific and generic ones, which should be used complementarily whenever possible.5 Similarly, in pediatric health-related quality of life research, child and parent proxy reports used together provide the most comprehensive view of the child’s health-related quality of life.6 Research on health-related quality of life in the pediatric Duchenne muscular dystrophy population has been scarce. Previous studies found health-related quality of life in this population was significantly impaired in all domains compared to
their healthy peers.7-14 In addition, older boys with Duchenne muscular dystrophy had worse physical health-related quality of life but not necessarily psychological health-related quality of life than younger boys.9,11,13-15 A number of limitations exist in these studies, including small sample sizes, use of only parent-reported health-related quality of life, and recruitment from single clinics, which limits the generalizability of the results. Furthermore, no study has examined factors associated with health-related quality of life using multiple regression analyses. Multivariable analyses allow for the identification of variables associated with health-related quality of life, which may contribute toward its improvement in this population.
1
Department of Pediatrics, University of Western Ontario, London, Ontario, Canada 2 University of Western Ontario, Children’s Health Research Institute, Lawson Health Research Institute, London, Ontario, Canada 3 Epidemiology and Biostatistics, London, Ontario, Canada 4 Clinical Neurological Sciences, London, Ontario, Canada Corresponding Author: Craig Campbell, MD, MSc, FRCPC, Victoria Hospital, London Health Sciences Centre, London, Ontario, Canada. Email: [email protected]
Downloaded from jcn.sagepub.com at RMIT University Library on February 23, 2016
2
Journal of Child Neurology
The objectives of the present study were to (1) provide a comprehensive description of health-related quality of life in boys with Duchenne muscular dystrophy and (2) determine factors associated with health-related quality of life as reported by the boys themselves and their parents using multiple regression analyses.
Methods Patient Population Patients were identified via the Canadian Neuromuscular Disease Registry, a national registry that collects demographic and clinical information of patients with neuromuscular diseases across Canada. A detailed review of the design and recruitment approach of the Canadian Neuromuscular Disease Registry can be found elsewhere.16 Seven pediatric clinics across Canada were enrolling patients with Duchenne muscular dystrophy into the registry at the time the study was carried out. Approval was obtained from the Research Ethics Board at the University of Western Ontario and the registry. The eligibility criteria for our study were as follows: (1) enrollment in the Canadian Neuromuscular Disease Registry and patient (or parent) has indicated interest to be contacted for research studies; (2) males between 4 and 18 years of age; (3) a confirmed diagnosis of Duchenne muscular dystrophy in the registry; and (4) availability of primary caregiver to complete the parent questionnaire. Patients were excluded from the study if they had any significant co-morbid medical diagnosis not related to Duchenne muscular dystrophy or if they were unable to comply with study protocol (eg, lack of language skills to complete questionnaire). Questionnaires were compiled in London and forwarded to the registry’s national office for mail-out in June 2013. Contact and follow-up procedures in accordance to the Tailored Design Method were employed to maximize the response rate.17 Data were entered in SPSS Statistics 21; analyses were carried out in the Statistical Analysis Software (SAS) 9.3 (SAS Corporation, Cary, NC).
Measures Health-related quality of life. Health-related quality of life was assessed with the Pediatric Quality of Life (PedsQL) Inventory, a repertoire of generic and disease-specific health-related quality of life measures. The Pediatric Quality of Life 4.0 Generic Core module was used, along with the Neuromuscular and Duchenne muscular dystrophy modules; all have been found to be feasible, reliable, and valid in the Duchenne population.13,14 Each item in the modules asks the extent to which an event had been a problem for the child in the past month and is measured on a Likert scale from 0 to 4. All items are reverse scored and linearly transformed into a scale out of 100 such that higher scores indicate better health-related quality of life.18 Each module yields a total score, with the Generic Core module also yielding a physical and a psychosocial summary score. All modules have parallel child self-report and parent proxy-reports and are divided into young child, child, and teen versions. If the child was unable to read, parents were asked to act as interviewers to their child.19 Clinical and family information. Clinical information on the child was collected from parent proxy reports and the Canadian Neuromuscular Disease Registry database, including ambulation status, wheelchair
status, steroid usage, scoliosis status, presence of cardiomyopathy, ventilation status, whether the child had been diagnosed with a comorbid condition, or a developmental or mental condition. Family information was collected from the parents and included family income, parent’s employment status, parent’s highest level of education, and a measure of the level of stress the family has experienced in the past year, the Family Inventory of Life Events.20 Boys with Duchenne muscular dystrophy and their parents also assessed the child’s level of fatigue with the Pediatric Quality of Life 3.0 Multidimensional Fatigue module. Respondents indicated how much of a problem the child with Duchenne muscular dystrophy had with a fatigue-related event, and the scores were reverse coded so that higher scores indicate less fatigue.21
Statistical Analyses Univariate analyses were used to examine characteristics of the sample (mean and standard deviation for continuous variables, frequencies and percentages for categorical variables). Bivariate analyses (t and w2 tests) were used to determine whether nonrespondents were different from respondents on clinical characteristics obtained from the Canadian Neuromuscular Disease Registry database. A 2-sided P value
Factors Associated With Health-Related Quality of Life in Children With Duchenne Muscular Dystrophy
Journal of Child Neurology 1-8 ª The Author(s) 2016 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0883073815627879 jcn.sagepub.com
Yi Wei, MSc1,2, Kathy Nixon Speechley, PhD1,2,3, Guangyong Zou, PhD3, and Craig Campbell, MD, MSc, FRCP(C)1,2,3,4
Abstract This study investigated clinical and family characteristics associated with health-related quality of life in children with Duchenne muscular dystrophy. Families of 176 boys with Duchenne muscular dystrophy were identified and mailed questionnaires via the Canadian Neuromuscular Disease Registry. Multiple linear regressions analyses were used to examine the relationship between clinical and family characteristics and child-self and parent-proxy reported health-related quality of life. Greater fatigue and use of wheelchairs were consistently associated with worse health-related quality of life independent of other factors. Higher household income and parent having a postsecondary degree were associated with better health-related quality of life in some of the measures. A greater clinical focus on and efforts to reduce fatigue could lead to improvement of health-related quality of life in the Duchenne muscular dystrophy population. This study also sets the ground for longitudinal studies where changes in health-related quality of life can be monitored over time. Keywords neuromuscular, Duchenne muscular dystrophy, health-related quality of life, fatigue, registry Received April 30, 2015. Received revised December 7, 2015. Accepted for publication December 17, 2015.
Duchenne muscular dystrophy is a neuromuscular disorder affecting between 1 in 3 500 and 1 in 5 000 newborn boys. It is characterized by progressive muscle loss resulting in profound physical disability. Most boys succumb to the disease before age 30 years due to respiratory or cardiac failure.1 There is no cure for Duchenne muscular dystrophy, the standard of care involves corticosteroids to prolong ambulation and ventilation to extend life expectancy.2 A number of promising therapies are undergoing various stages of clinical trials, making outcome assessment an important research goal. The Food and Drug Administration has mandated that patient-reported outcomes such as health-related quality of life be part of all clinical trials.3 Health-related quality of life is a subjective and multidimensional construct.4 Health-related quality of life measures can be divided into disease-specific and generic ones, which should be used complementarily whenever possible.5 Similarly, in pediatric health-related quality of life research, child and parent proxy reports used together provide the most comprehensive view of the child’s health-related quality of life.6 Research on health-related quality of life in the pediatric Duchenne muscular dystrophy population has been scarce. Previous studies found health-related quality of life in this population was significantly impaired in all domains compared to
their healthy peers.7-14 In addition, older boys with Duchenne muscular dystrophy had worse physical health-related quality of life but not necessarily psychological health-related quality of life than younger boys.9,11,13-15 A number of limitations exist in these studies, including small sample sizes, use of only parent-reported health-related quality of life, and recruitment from single clinics, which limits the generalizability of the results. Furthermore, no study has examined factors associated with health-related quality of life using multiple regression analyses. Multivariable analyses allow for the identification of variables associated with health-related quality of life, which may contribute toward its improvement in this population.
1
Department of Pediatrics, University of Western Ontario, London, Ontario, Canada 2 University of Western Ontario, Children’s Health Research Institute, Lawson Health Research Institute, London, Ontario, Canada 3 Epidemiology and Biostatistics, London, Ontario, Canada 4 Clinical Neurological Sciences, London, Ontario, Canada Corresponding Author: Craig Campbell, MD, MSc, FRCPC, Victoria Hospital, London Health Sciences Centre, London, Ontario, Canada. Email: [email protected]
Downloaded from jcn.sagepub.com at RMIT University Library on February 23, 2016
2
Journal of Child Neurology
The objectives of the present study were to (1) provide a comprehensive description of health-related quality of life in boys with Duchenne muscular dystrophy and (2) determine factors associated with health-related quality of life as reported by the boys themselves and their parents using multiple regression analyses.
Methods Patient Population Patients were identified via the Canadian Neuromuscular Disease Registry, a national registry that collects demographic and clinical information of patients with neuromuscular diseases across Canada. A detailed review of the design and recruitment approach of the Canadian Neuromuscular Disease Registry can be found elsewhere.16 Seven pediatric clinics across Canada were enrolling patients with Duchenne muscular dystrophy into the registry at the time the study was carried out. Approval was obtained from the Research Ethics Board at the University of Western Ontario and the registry. The eligibility criteria for our study were as follows: (1) enrollment in the Canadian Neuromuscular Disease Registry and patient (or parent) has indicated interest to be contacted for research studies; (2) males between 4 and 18 years of age; (3) a confirmed diagnosis of Duchenne muscular dystrophy in the registry; and (4) availability of primary caregiver to complete the parent questionnaire. Patients were excluded from the study if they had any significant co-morbid medical diagnosis not related to Duchenne muscular dystrophy or if they were unable to comply with study protocol (eg, lack of language skills to complete questionnaire). Questionnaires were compiled in London and forwarded to the registry’s national office for mail-out in June 2013. Contact and follow-up procedures in accordance to the Tailored Design Method were employed to maximize the response rate.17 Data were entered in SPSS Statistics 21; analyses were carried out in the Statistical Analysis Software (SAS) 9.3 (SAS Corporation, Cary, NC).
Measures Health-related quality of life. Health-related quality of life was assessed with the Pediatric Quality of Life (PedsQL) Inventory, a repertoire of generic and disease-specific health-related quality of life measures. The Pediatric Quality of Life 4.0 Generic Core module was used, along with the Neuromuscular and Duchenne muscular dystrophy modules; all have been found to be feasible, reliable, and valid in the Duchenne population.13,14 Each item in the modules asks the extent to which an event had been a problem for the child in the past month and is measured on a Likert scale from 0 to 4. All items are reverse scored and linearly transformed into a scale out of 100 such that higher scores indicate better health-related quality of life.18 Each module yields a total score, with the Generic Core module also yielding a physical and a psychosocial summary score. All modules have parallel child self-report and parent proxy-reports and are divided into young child, child, and teen versions. If the child was unable to read, parents were asked to act as interviewers to their child.19 Clinical and family information. Clinical information on the child was collected from parent proxy reports and the Canadian Neuromuscular Disease Registry database, including ambulation status, wheelchair
status, steroid usage, scoliosis status, presence of cardiomyopathy, ventilation status, whether the child had been diagnosed with a comorbid condition, or a developmental or mental condition. Family information was collected from the parents and included family income, parent’s employment status, parent’s highest level of education, and a measure of the level of stress the family has experienced in the past year, the Family Inventory of Life Events.20 Boys with Duchenne muscular dystrophy and their parents also assessed the child’s level of fatigue with the Pediatric Quality of Life 3.0 Multidimensional Fatigue module. Respondents indicated how much of a problem the child with Duchenne muscular dystrophy had with a fatigue-related event, and the scores were reverse coded so that higher scores indicate less fatigue.21
Statistical Analyses Univariate analyses were used to examine characteristics of the sample (mean and standard deviation for continuous variables, frequencies and percentages for categorical variables). Bivariate analyses (t and w2 tests) were used to determine whether nonrespondents were different from respondents on clinical characteristics obtained from the Canadian Neuromuscular Disease Registry database. A 2-sided P value
