**2. Current management strategies**

Until there is a definitive cure for DMD, current treatment strategies focus on promoting well-balanced diet and physical activity as tolerated, delaying the onset of complications via pharmaceutical treatments, and optimizing health outcomes through appropriate medical and psychosocial support. Therapeutic interventions include the use of corticosteroids (such as prednisone or deflazacort) for skeletal muscle weakness and afterload reduction (such as angiotensin converting enzyme inhibitor or beta-blocker) for cardiomyopathy. Corticosteroid therapy offers benefit to DMD boys by improving muscle strength and function [Mendell et al, 1989; Griggs et al, 1991], prolonging independent ambulation [Biggar et al, 2001; Schara et al, 2001], plus slowing the progression of cardiomyopathy [Markham et al, 2008] and scoliosis [Kinali et al, 2007]. As well, the introduction of noninvasive positive pressure ventilation has prolonged the survival of individuals with DMD [Bach & Martinez, 2011].

A number of recent publications have provided comprehensive reviews on the diagnosis and multidisciplinary management of DMD, including the use of prednisone or deflazacort to preserve muscle strength [Bushby et al, 2004; Moxley et al, 2005], optimizing growth and development, surveillance for spinal deformities [Muntoni et al, 2006], managing respiratory complications [Finder et al, 2004; Birnkrant et al, 2010], and treating cardiomyopathy [American Academy of Pediatrics, 2005; Baxter, 2006]. As well, bone health, nutrition, learning disability, behaviour problems, access to wheelchair and other adaptive technology should be included as part of the comprehensive treatment plan [Bushby et al, 2010a; Bushby et al, 2010b]. As standard of care guidelines typically focus on medical management and there are no systematic strategies to meet the psychosocial needs of boys with DMD and their families, the remaining of this paper will present some of our results on pediatric HRQOL, parental experience, and family-centered care approach to DMD that may help to identify the needs and incorporate psychosocial support strategies into clinical practice. We propose the use of a modified Family Needs Survey for DMD (DMD-FNS) to help clinicians to address needs and tailor services for each family across the different stages of the disease.

#### **3. DMD and health-related quality of life**

82 Neuromuscular Disorders

cognitive impairment and learning disability [Fitzpatrick et al, 1986; Leibowitz & Dubowitz, 1981]. Serum creatine kinase is usually markedly elevated due to on-going muscle damage and regenerative failure. Progressive muscle weakness leads to loss of independent ambulation by early teens, scoliosis, quadriplegia, respiratory insufficiency,

Detection of *DMD* mutations include multiplex polymerase chain reaction (PCR) that examines the most commonly deleted regions of the gene, or other molecular genetic assays that interrogate all 79 exons, such as multiplex ligation-dependent probe amplification (MLPA) and comparative genomic hybridization (CGH) microarray. If the presence of a disease-causing deletion or duplication is not identified by a state-of-the-art DNA diagnostic technique, complete gene sequencing is needed to define the precise mutational event [Baskin et al, 2009; Takeshima et al, 2010]. A muscle biopsy can also be obtained for confirmation of dystrophin deficiency by immunostaining plus extraction of cDNA and

Recent scientific advances have led to potentially new disease modifying treatments for many neuromuscular diseases including DMD [Wagner, 2008; Fairclough et al, 2011]. The main therapeutic strategies include: a) muscle membrane stabilization and up-regulation of compensatory cytoskeleton proteins such as biglycan and utrophin [Amenta et al, 2011; Tinsley et al, 2011]; b) enhancement of muscle regeneration via up-regulation of insulin growth factor (IGF-1) and modulation of members of transforming growth factor-beta such as myostatin [Schertzer et al, 2008; Morine et al, 2010]; c) reduction of the inflammatory cascade by selective nuclear factor-kappa B (NF-κB) inhibition [Tang et al, 2010]; and d) gene therapy including the use of adeno-associated virus microdystrophin [Trollet et al, 2009], nonsense suppression therapy [Welch et al, 2007; Malik et al, 2010], and exon-skipping to restore partial dystrophin protein production [Muntoni et al, 2005; van Deutekom et al, 2007]. Effective treatment of DMD will likely require multiple interventions targeting different disease processes, and updated information about DMD clinical trials is available at http://www.clinicaltrials.gov. The success of new and emerging therapeutic strategies depends on early diagnosis and precise mutational analysis for boys with DMD, the creation of a national or global disease-specific patient registries, plus on-going advocacy and

Until there is a definitive cure for DMD, current treatment strategies focus on promoting well-balanced diet and physical activity as tolerated, delaying the onset of complications via pharmaceutical treatments, and optimizing health outcomes through appropriate medical and psychosocial support. Therapeutic interventions include the use of corticosteroids (such as prednisone or deflazacort) for skeletal muscle weakness and afterload reduction (such as angiotensin converting enzyme inhibitor or beta-blocker) for cardiomyopathy. Corticosteroid therapy offers benefit to DMD boys by improving muscle strength and function [Mendell et al, 1989; Griggs et al, 1991], prolonging independent ambulation [Biggar et al, 2001; Schara et al, 2001], plus slowing the progression of cardiomyopathy [Markham et al, 2008] and scoliosis [Kinali et al, 2007]. As well, the introduction of noninvasive positive pressure ventilation has prolonged the survival of individuals with DMD

cardiomyopathy, and death around the third decade of life.

RNA for further genetic testing [Mah et al, 2011].

interdisciplinary collaboration.

[Bach & Martinez, 2011].

**2. Current management strategies** 

Chronic neurological disorders such as DMD have a significant impact on pediatric health-related quality of life (HRQOL) and functional ability. Both medical services and community-based programs are often required to address their physical, emotional, social, and educational needs. A large prospective study led by Dr. Craig McDonald and his colleagues will provide valuable longitudinal data on the natural history of DMD, associated HRQOL, and health services utilization; this 5-year study includes more than three hundred boys with a confirmed diagnosis of DMD from 20 participating CINRG centers in the United States and other international sites (personal communication). Given the lack of information on the processes of care and health outcomes of children with chronic neurological disabilities in Canada, a brief 3-month cross-sectional pilot survey was performed at the Alberta Children's Hospital, a tertiary pediatric neurosciences center in Calgary, Alberta to explore the use of health services and HRQOL among DMD and other pediatric neurosciences patients. Specifically, parents of 278 children (165 male, mean age = 11 4.5 years) were asked to describe their child's functional ability, healthrelated quality of life (HRQOL), and use of health services including access to medical professionals, rehabilitation programs, education, and social support in their communities. The children were followed because of chronic neurological diseases including brain tumour (n=33), traumatic brain injury (n=23), hydrocephalus (n=46), myelomeningocele (n=29), refractory epilepsy (n=89), or neuromuscular disease (n=58), including 14 boys with DMD. As part of the study procedure, the parents completed questionnaires regarding their socio-demographic status, their experience with rehabilitative and supportive services, their child's functional ability using the Functional Independence Measure (FIMTM/WeeFIM®)*,* and their child's HRQOL using the PedsQLTM (version 4.0) generic core.

The FIM and WeeFIM are designed to measure functional abilities and limitations in activities of daily living. The FIM is used for persons seven years of age or older, while the WeeFIM is designed for children between six months to seven years in age. Both versions

Psychosocial Support Needs of Families of Boys with Duchenne Muscular Dystrophy 85

52.49 58.92

68.56 85.64

83.09 53.99

68.05 69.61

68.25 72.32

80.96 54.10

Table 1. Comparison of Pediatric Health-Related Quality of Life Scores among children with

Dependent variable Independent variables Odds Ratio Wald's test p value 95% CI

0.911 2.672 0.979 3.407

0.295 0.069 0.025 0.261 0.207 0.851 0.969 0.978 2.419

0.975 0.960 2.521 3.359

0.961 2.294

0.977 2.375

Table 2. Multiple regression analysis of rehabilitation and supportive services utilization by

30.59 26.87

31.13 21.69

20.26 30.81

21.10 18.33

23.89 16.63

17.90 21.36

> 0.004 0.001 0.002 0.000

> 0.037 0.000 0.002 0.039 0.002 0.000 0.000 0.017 0.024

> 0.000 0.000 0.037 0.003

0.000 0.009

0.014 0.018






57 29

45 23

33 88

58 29

45 23

33 89

0.855 – 0.970 1.488 – 4.799 0.965 – 0.992 1.877 – 6.184

0.094 – 0.927 0.018 – 0.263 0.002 – 0.251 0.073 – 0.935 0.077 – 0.555 0.783 – 0.926 0.957 – 0.981 0.961 – 0.996 1.124 – 5.207

0.961 – 0.988 0.939 – 0.980 1.060 – 5.998 1.509 – 7.477

0.950 – 0.972 1.232 – 4.272

0.959 – 0.995 1.160 – 4.864

Mean SD Frequency

Physical functioning (/100) Neuromuscular Disease Myelomeningocele

Psychosocial functioning (/100) Neuromuscular Disease Myelomeningocele

 Hydrocephalus Brain Injury

 Brain Tumour Refractory Epilepsy

 Hydrocephalus Brain Injury

 Brain Tumour Refractory Epilepsy

1. Utilization of Medical specialists

2. Utilization of Allied Health Professionals

3. Utilization of Educational Services

4. Access to Social Support

Funding Support

† Health-related quality of life ‡ Functional Independence Measure

5. Access to

chronic neurological disorders

Child's age Surgery

Diagnosis

FIM score

FIM score Care coordinator

children with chronic neurological disorders

Psychosocial HRQOL† Care coordinator

Myelomeningocoele Hydrocephalus Brain injury Brain tumor Epilepsy Child's age FIM‡ score

Psychosocial HRQOL Care coordinator

Psychosocial HRQOL Parental education Care coordinator

Psychosocial HRQOL Family income

measure independent performance in self-care, sphincter control, transfers, locomotion, communication, and social cognition. Response to each of the items ranges from 1 to 7, with higher scores indicating more independence. A total score is calculated by combining scores from all eighteen items, and ranges from 18 to 126. The psychometric properties of the FIM have been described in previous studies [Chau et al, 1994; Msall et al, 1994; Ottenbacher et al, 1997].

The PedsQL (version 4.0) generic core scale is a self-report multidimensional instrument designed by Varni et al to measure pediatric HRQOL [Varni et al, 1999]. The raw score for each item is transformed to a 0 to 100 scale, with a higher score indicating better quality of life. It has been validated for use in children [Varni et al, 2001]. The study was approved by the University of Calgary Conjoint Health Research and Ethics Board.

Among the 278 children, close to one-half (49%) had some limitations in daily activities, as reflected by their mean total FIM score of 90.6 (SD 34.4, max FIM score = 126). Approximately 25% were severely disabled and totally dependent on caregivers for selfcare, sphincter control, and transfer. Nearly 40% of patients received regular (weekly to monthly) rehabilitation therapy. The majority of health services were financed by government health care program; 73 (27%) families reported additional out-of-pocket expenses. As anticipated, the use of supportive health services such as physiotherapy or occupational therapy was related to the child's diagnosis, degree of functional ability, and his/her HRQOL (**see Table 2**). On the other hand, socio-demographic variables such as parental age, marital status, education, employment, and place of residence were not significantly associated with health services utilization, except that parental income was associated with varying degree of funding support from the government. Only a small proportion (32%) of these families had access to regular respite, and the frequency of respite correlated with the severity of disability. Having a designated care coordinator was consistently associated with increased use of health services (OR 2.3 to 3.4).

Even though many pediatric neurosciences patients experienced significant functional limitations and required rehabilitative services, the majority (83%) of parents in this study felt that there was adequate medical, educational and financial support in their communities. However, almost half (49%) of the families indicated need for more psychosocial support, despite adequate medical, rehabilitative, and educational services. Parents from visible minority groups, those with English as a second language, and those who reported poor mental health were more likely to express need for more social support.

Overall, the physical and psychosocial HRQOL scores for this group of children were lower than published healthy controls; their mean PedsQL physical and psychosocial scores were 63.2 (SD 30.1) and 65.9 (SD 22.4) respectively (maximum PedsQL score = 100). Children with refractory epilepsy had the lowest mean psychosocial scores, while those with DMD and other neuromuscular diseases scored lowest on the physical scale (**see Table 1**). This suggests that despite their physical limitations, children with neuromuscular diseases enjoyed better HRQOL than those with refractory epilepsy. As seen in a subsequent study, children with DMD and other progressive neuromuscular diseases experienced further decline in their HRQOL, especially when they required the use of assisted mechanical ventilation at home [Mah et al, 2008].


measure independent performance in self-care, sphincter control, transfers, locomotion, communication, and social cognition. Response to each of the items ranges from 1 to 7, with higher scores indicating more independence. A total score is calculated by combining scores from all eighteen items, and ranges from 18 to 126. The psychometric properties of the FIM have been described in previous studies [Chau et al, 1994; Msall et al, 1994; Ottenbacher et

The PedsQL (version 4.0) generic core scale is a self-report multidimensional instrument designed by Varni et al to measure pediatric HRQOL [Varni et al, 1999]. The raw score for each item is transformed to a 0 to 100 scale, with a higher score indicating better quality of life. It has been validated for use in children [Varni et al, 2001]. The study was approved by

Among the 278 children, close to one-half (49%) had some limitations in daily activities, as reflected by their mean total FIM score of 90.6 (SD 34.4, max FIM score = 126). Approximately 25% were severely disabled and totally dependent on caregivers for selfcare, sphincter control, and transfer. Nearly 40% of patients received regular (weekly to monthly) rehabilitation therapy. The majority of health services were financed by government health care program; 73 (27%) families reported additional out-of-pocket expenses. As anticipated, the use of supportive health services such as physiotherapy or occupational therapy was related to the child's diagnosis, degree of functional ability, and his/her HRQOL (**see Table 2**). On the other hand, socio-demographic variables such as parental age, marital status, education, employment, and place of residence were not significantly associated with health services utilization, except that parental income was associated with varying degree of funding support from the government. Only a small proportion (32%) of these families had access to regular respite, and the frequency of respite correlated with the severity of disability. Having a designated care coordinator was

Even though many pediatric neurosciences patients experienced significant functional limitations and required rehabilitative services, the majority (83%) of parents in this study felt that there was adequate medical, educational and financial support in their communities. However, almost half (49%) of the families indicated need for more psychosocial support, despite adequate medical, rehabilitative, and educational services. Parents from visible minority groups, those with English as a second language, and those who reported poor mental health were more likely to express need for more social

Overall, the physical and psychosocial HRQOL scores for this group of children were lower than published healthy controls; their mean PedsQL physical and psychosocial scores were 63.2 (SD 30.1) and 65.9 (SD 22.4) respectively (maximum PedsQL score = 100). Children with refractory epilepsy had the lowest mean psychosocial scores, while those with DMD and other neuromuscular diseases scored lowest on the physical scale (**see Table 1**). This suggests that despite their physical limitations, children with neuromuscular diseases enjoyed better HRQOL than those with refractory epilepsy. As seen in a subsequent study, children with DMD and other progressive neuromuscular diseases experienced further decline in their HRQOL, especially when they required the use of assisted mechanical

the University of Calgary Conjoint Health Research and Ethics Board.

consistently associated with increased use of health services (OR 2.3 to 3.4).

al, 1997].

support.

ventilation at home [Mah et al, 2008].


Table 1. Comparison of Pediatric Health-Related Quality of Life Scores among children with chronic neurological disorders


† Health-related quality of life

‡ Functional Independence Measure

Table 2. Multiple regression analysis of rehabilitation and supportive services utilization by children with chronic neurological disorders

Psychosocial Support Needs of Families of Boys with Duchenne Muscular Dystrophy 87

In order to further understand parental stress and psychosocial support needs of families caring for children with DMD and other neuromuscular diseases (NMD), a qualitative research study based on phenomenology was used to describe the experience of parents caring for children affected by NMD requiring HMV [Mah et al, 2008]. Data was collected from interviews in parents' homes. The interviews were subsequently modified based on an iterative approach to identify the core of the parents' caregiving experience (**see Figure 1**).

Fig. 1. Parental experience in caring for a child with neuromuscular disease [Mah et al, 2008b].

Given the emphasis by parents on providing the best possible care and ensuring optimal HRQOL for their child with NMD, the rest of the family unit's needs including those of the siblings, the spouse, and the primary caregiver tended to become secondary priorities. In addition being their child's primary caregivers, parents also took on the various functions of health care professionals (HCP) such as nursing and respiratory therapy. Given sufficient practice, they soon became experts on their child's care and the child's NMD. For most parents, the demand of caring for their child with NMD was disruptive to family life; they found it hard to spend quality time together. Over time, these demands became part of their normal daily routine. One parent summed up major losses such as friendship, income, privacy, and personal identity. The loss was not solely related to the child's NMD and declining health, but also due the impact of the parents' decision to give up their careers, passions, and personal desires to meet their child's needs. Parents lived with uncertainty in anticipation of future losses and limitations that their children might experience, as well as

**5. Understanding the parental experience** 

Reproduced with permission.

anxiety as to how their children would react to those losses.

### **4. Impact of home mechanical ventilation on HRQOL**

The purpose of this study was to explore the impact of the use of life-sustaining assisted technologies such as home mechanical ventilation (HMV) on children and adolescents with NMD. We compared the HRQOL and parental stress among pediatric neuromuscular patients with or without home mechanical ventilation, and again boys with DMD (n = 24) were included as part of the study. Parents completed the Parenting Stress Index or the Stress Index for Parents of Adolescents, depending on their child's age. The Parenting Stress Index is a 120-item questionnaire that has been standardized for use with parents of children aged 1 month to 12 years [Abidin, 1993]. Each item is rated on a 5-point Likert-type scale that ranges from 1 (strongly agree) to 5 (strongly disagree). A Total Stress score, a Child Domain score, and a Parent Domain score are calculated from the responses. The 112-item Stress Index for Parents of Adolescents is an upward extension of the Parenting Stress Index for parents of adolescents aged 12 to 18 years [Sheras et al, 1998]. The Stress Index for Parents of Adolescents examines the relationship of parenting stress to adolescent characteristics, parent characteristics, the quality of adolescent-parent interactions, and stressful life circumstances. A Total Stress score, an Adolescent Domain score, a Parent Domain score, an Adolescent-Parent Relationship Domain score and a Life Stress score are calculated from the responses. Support for the content, convergent and discriminant validity of both versions of the Parental Stress Index is available. The PedsQL (version 4.0) generic core was again used to measure the HRQOL of children with neuromuscular disease.

109 families participated; 19 (17%) of them had a child with neuromuscular disease requiring HMV. Relative to healthy children and other chronically ill children, the pediatric neuromuscular patients in this study displayed poorer physical and psychosocial HRQOL. In addition, children on HMV had significantly lower mean total PedsQL scores than nonventilated children (47.9 vs. 61.5 respectively, p=0.013) (**see Table 3**); the difference was likely the consequence of a more severe disease process in children requiring assisted ventilation. Furthermore, the opportunities that these children have to be involved in social activities outside of home and at school may be limited by the lack of portability of the assisted ventilation devices and/or availability of trained caregivers. However, no significant difference in mean total stress scores was found between parents of pediatric neuromuscular patients with or without HMV. We postulated that these parents had been living with the constant demands of caring for their child with neuromuscular disease requiring home mechanical ventilation and that over time, these caretaking demands had become part of "normal" life and were not identified as creating additional stress.


\* PedsQL refers to Pediatric Quality of Life Inventory; † HMV refers to Home Mechanical Ventilation

Table 3. Comparison of Mean Pediatric Quality of Life Inventory scores between Mechanically Ventilated and Non-Ventilated Pediatric Neuromuscular Subgroups [Mah et al, 2008a]. Reproduced with permission.
