Journal of Child Neurology

Journal http://jcn.sagepub.com/ of Child Neurology

Quality of Life in Duchenne Muscular Dystrophy: Subjective Impact on Children and Parents Ilaria Baiardini, Carlo Minetti, Simona Bonifacino, Anna Porcu, Catherine Klersy, Paolo Petralia, Sara Balestracci, Filippo Tarchino, Stefania Parodi, Giorgio Walter Canonica and Fulvio Braido J Child Neurol published online 11 April 2011 DOI: 10.1177/0883073810389043 The online version of this article can be found at: http://jcn.sagepub.com/content/early/2011/04/06/0883073810389043

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Original Article

Quality of Life in Duchenne Muscular Dystrophy: The Subjective Impact on Children and Parents

Journal of Child Neurology 000(00) 1-7 ª The Author(s) 2011 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0883073810389043 http://jcn.sagepub.com

Ilaria Baiardini, PhD1, Carlo Minetti, MD2, Simona Bonifacino, PhD3, Anna Porcu, MD1, Catherine Klersy, PhD4, Paolo Petralia, MD3, Sara Balestracci, MD1, Filippo Tarchino, MD1, Stefania Parodi, PhD1, Giorgio Walter Canonica, MD1, and Fulvio Braido, MD1

Abstract Duchenne muscular dystrophy results in a broad spectrum of physical and psychosocial consequences, both to patient and caregivers. This study was aimed to explore health-related quality of life and its possible determinants in Duchenne muscular dystrophy children and in their parents. Caregivers (21 mothers and 6 fathers; mean age, 40.04 years) of 27 Duchenne muscular dystrophy patients (mean age, 11.26 years) completed the validated Children Health Questionnaire-Parent Form 50 and the Family Strain Questionnaire. Children reported significantly lower scores than normative group in 10 of 15 Children Health Questionnaire dimensions. Only the use of wheelchairs (P ¼ .02) and ventilators (P < .001) was significantly associated to lower healthrelated quality of life in Physical Functioning. On the contrary, Family Strain Questionnaire scores were not influenced by children’s characteristics. Despite the presence of Duchenne muscular dystrophy deeply impairs health-related quality of life, some areas of well-being are present both in children and caregivers. Keywords quality of life, Duchenne muscular dystrophy, caregivers Received July 31, 2010. Accepted for publication October 9, 2010.

Duchenne muscular dystrophy is the most severe of the many forms of muscular dystrophy, and has incidence of approximately 30 per 100 000 live born males.1 It is an X-linked recessive dystrophic myopathy caused by complete absence of the protein dystrophin in the skeletal muscle, myocardium, and brain. Patients develop progressive weakness, contractures, spinal deformity, restrictive lung functional pattern, cardiomyopathy, and variable degrees of cognitive involvement. The disease course is progressive, leading to a state of severe physical dependence.2 Treatment support has increased life expectancy, and the mean age at death has passed from 14.4 years in the 1960s to 25.3 years in the 1990s.3 Despite the rapid progress in basic research on the etiology and pathophysiology of Duchenne muscular dystrophy, no cure is yet available. The presence of a serious chronic disease such as Duchenne muscular dystrophy, causes a great effect upon both patients and caregivers, which can be assessed by measures of patient reported outcomes, defined as ‘‘any report coming from patients about a health condition and its treatment.’’4 Among patient reported outcomes, health-related quality of life, that

is the impact of a disease and its treatment upon a patient, as perceived by the patient himself,5 has been extensively evaluated in many chronic diseases, providing a better understanding of patient’s subjectivity. The disease impact and its consequences can also be measured on caregivers. This aspect is relevant in chronic diseases,6-8 especially when the patient is a

1

Allergy and Respiratory Disease, Department of Internal Medicine, University of Genoa, Genoa, Italy 2 Muscular and Neurodegenerative Disease Unit, University of Genoa and G. Gaslini Institute, Genoa, Italy 3 Unione Italiana Lotta alla Distrofia Muscolare (UILDM), Sezione di Genova, Italy 4 Servizio di Biometria e Statistica-Direzione Scientifica, IRCCS Fondazione Policlinico San Matteo, Pavia, Italy Corresponding Author: Ilaria Baiardini, PhD, Allergy and Respiratory Diseases, Department of Internal Medicine, University of Genoa, Pad. Maragliano, Largo R. Benzi, 10–16132 Genoa, Italy Email: [email protected]


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child or an adolescent, due to the deep involvement of parents. In addition to managing the disease in daily life, clinical features and the rate of progression of Duchenne muscular dystrophy causes a significant emotional burden for parents: the feeling of loss and the thoughts of death are common and painful experiences. As in other severe chronic diseases, having a child with Duchenne muscular dystrophy is accompanied by emotions such as anger, anguish, anxiety,9 and high levels of stress and depression.10,11 The slow and arduous illness course can lead to parental strains12 and deplete family energy and resources. The result is a poorer health status and a higher presence of mood disorders, pain, and disability than members of the general population.13 Despite the increasing emphasis in clinical research and practice to use patient-reported outcomes and subjective perspectives, only recently some papers that evaluate the Duchenne muscular dystrophy impact on patients and on their parents through validated tools have been published. A study by Grootenhuis et al14 analyzed the health-related quality of life in patients with different kinds of muscular dystrophy. Compared with age-related healthy subjects, dystrophic patients reported a worse health-related quality of life in both physical and emotional dimensions of daily life, independently of the disease severity. A reduction in physical functioning and role limitations due to physical health have been also detected in a sample of 35 adult patients with Duchenne muscular dystrophy. On the contrary, levels of general and mental health, emotions, social functioning, and pain, resulted to be comparable to those observed in subjects without chronic illness, independently of the degree of physical disability and respiratory impairment.15 Two recent papers were specifically addressed to explore the use of the same health-related quality of life questionnaire in Duchenne muscular dystrophy patients and their parents. Comparing the answers with the generic Pediatric Quality of Life Inventory in 35 Duchenne muscular dystrophy boys and their parents, a moderate to poor agreement has been detected.16 The validity of Pediatric Quality of Life Inventory-Neuromuscular Module has been assessed in a sample of 44 Duchenne muscular dystrophy patients and their caregivers, showing that the tool can be used as a valid outcome measure in clinical trials.17 Since nowadays only specific aspects of health-related quality of life in Duchenne muscular dystrophy patients have been explored,14-17 the aim of the present study was:

to evaluate the disease burden in patients suffering from Duchenne muscular dystrophy and in their caregivers by means of validated questionnaires; to compare patients’ health-related quality of life profiles with those of the corresponding normative data; to relate patients’ health-related quality of life with the caregivers’ subjective experience; to identify possible determinants of patients’ health-related quality and caregivers’ subjective experience.

Methods Patients Population and Method We performed a cross-sectional observational study on subjects affected by Duchenne muscular dystrophy diagnosed according to clinical and laboratory results, including muscle biopsy and molecular genetic study. Patients attending the Unione Italiana per la Lotta alla Distrofia Muscolare Center of Genova, were recruited. The study was performed in collaboration with Gaslini Institute Muscolar and Neuro-Degenerative Diseases Unit in Genoa, by the Quality of Life group of Allergy and Respiratory Diseases Department of Genoa University, which has in charge their pulmonary care or follow-up. During a scheduled control visit, the parents were asked to fill in the Children Health Questionnaire - Parent Form 5018 and the Family Strain Questionnaire,19 as a part of the patients’ assessment, after the informed consent had been obtained.

Questionnaires Duchenne muscular dystrophy patients’ health-related quality of life was assessed by Children Health Questionnaire - Parent Form 50, a generic, well-validated instrument designed to measure overall health in the pediatric population with or without disability, above the age of 5 years and consists of domains representing the most essential components of a child’s health-related quality of life.18 It is a paper-andpencil tool completed by parents of children aged 5 to 18 that includes a broad spectrum of child and family focused health areas, divided into 15 concepts (Physical Functioning, Role/Social Limitations – Physical, General Health Perceptions, Bodily Pain/Discomfort, Family Activities, Role/Social Limitations – Emotional, Role/Social Limitations – Behavioral, Parent Impact Time, Parent Impact Emotion, Self-Esteem, Mental Health, Behavior, Family Cohesion, Change in Health). Individual items ask the caregivers to answer on a Likerttype scale with higher scores indicating better or more positive health status. Individual profile scores for each concept can be calculated. It is also possible to derive 2 summary scores (Physical and Psychosocial). The official Children Health Questionnaire - Parent Form 50, cross culturally adapted and validated Italian version,20 was administered to patient’s parents in agreement with standardized methodologies. The Family Strain Questionnaire18 is aimed at evaluating caregiving-related problems. It is composed of 35 self-administered dichotomous items (yes/no) divided into 5 factors: Emotional burden, Problems in social involvement, Need for knowledge about the disease, Satisfaction with family relationships, and Thoughts about death. The higher the score is, the more the caregiver perceives the existence of problems. Family Strain Questionnaire is characterized by a good level of construct validity, internal consistency and test–retest reliability18; it is, therefore, self-sufficient in assessing care-giving-related problems21 and in discriminating caregivers of patients with different diseases.22,23

Statistical Analysis Data were described as mean and standard deviations for continuous variables and as counts and percentages for categorical variables. Patients’ and caregiver’s ages and length of education were dichotomized at their median value. The Spearman correlation coefficient was computed to quantify the association of children’s health-related quality of life and caregivers’ problems. The corresponding 95%


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confidence interval was calculated based on Fisher transformation. Specifically, we assessed the association of the 2 summary measures derived from the Children Health Questionnaire (Physical Summary score and Psychosocial Summary score) with the 5 dimensions of the Family Strain Questionnaire. The 1-sample sign test was used to compare the children health-related quality of life scores with the normative data. The Mann Whitney U test was used to compare health-related quality of life scores across subjects’ characteristics and the Spearman correlation coefficient to measure the association of scores and continuous variables. Differences between groups and their 95% confidence intervals were computed. The Cronbach alpha coefficient was computed to evaluate the internal consistency of the Children Health Questionnaire - Parent Form 50 questionnaire in this population. A Cronbach’s alpha of a multi-item scale of 0.70 or higher was considered to indicate sufficient internal consistency.24 Stata 9 (StataCorp, USA) was used for computations. A 2-sided P value < .05 was considered statistically significant. To correct or multiple comparisons in the primary endpoint, the statistical significance threshold after Bonferroni correction would be .005.

Results Population Characteristics Children and caregivers characteristics are summarized in Table 1. None of the parents, who were asked to take part in the study, refused to fill in the questionnaires. Of 27 patients, 13 were older than 11, with an overall mean age of 11.26 years (standard deviation, 5.08). Fourteen patients were in a wheelchair, and 4 were on home noninvasive ventilatory treatment. The mother was the most prevalent caregiver interviewed (21 versus 6 fathers); 16 caregivers (59.26%) were older than 40; their mean age was 40.0 years (standard deviation, 7.8). The family size was generally small, and in the vast majority (80.8%), both the mother and the father were present. More than half of the caregivers had 10 years education, and 9 had suspended their job for children assistance (3 retired, 2 out of work, and 6 housewives). Among these parents, 5 suspended their job in a definite way, while 4 only temporarily. Table 2 shows Cronbach alpha coefficients of Children Health Questionnaire - Parent Form 50 in our Duchenne muscular dystrophy patients. Sufficient internal consistency was shown for all dimensions of the Children Health Questionnaire Parent Form 50 (Cronbach alpha > 0.70).

Duchenne Muscular Dystrophy Burden on Children and Caregivers Table 3 summarizes the disease burden on children (Children Health Questionnaire - Parent Form 50) and on caregivers (Family Strain Questionnaire). The Children Health Questionnaire - Parent Form 50 scores were compared with the Italian normative data.20 Both the Physical and the Psychological Summary components were significantly lower than the norm (P ¼ < .001; P ¼ .01). Similarly, many single dimensions were all significantly lower than the corresponding norm-based scores (Table 4).

Table 1. Population Characteristics Children

Caregivers

Characteristic Value* Male gender Age (yr) Age 11 yr

Wheelchair Ventilator

Characteristic

27 (100%) Male gender 11.26 (5.08) Age (yr) 13 (48.15%) Age < 40 yr Family size 2 3 4 5 Both parents Marital status (detailed) N¼26 Single Married Separated/divorced 14 (51.85%) Widow(er) 4 (14.81%) Education >10 yr (range 5-13) Working position Retired Out-of-work Housewife Blue collar White collar Other

Value* (%) 6 (22.22) 40.04 (7.8) 16 (52.96) 9 11 6 1 18

(33.33) (40.70) (22.22) (3.70) (78)

2 (7.69) 21 (80.77) 3 (11.54) 13 (54.17)

1 2 15 2 5 2

(3.70) (7.41) (55.56) (7.41) (18.52) (7.41)

*N (%) or mean (standard deviation).

Association of Children’s Health-Related Quality of Life and Caregivers’ Subjective Experience The association of the 5 dimensions of the Family Strain Questionnaire and the Physical Summary score of the Children Health Questionnaire - Parent Form 50 was of moderate strength. The correlation coefficients ranged from –0.287 to 0.157; there was an inverse significant association of Emotional burden and Thoughts about death with Physical Summary score and a direct significant association of Satisfaction with family relationship with Physical Summary score. However, when accounting for multiple tests, no association retained the statistical significance. The correlation coefficients between the 5 dimensions of the Family Strain Questionnaire and the Psychosocial Summary score of the Children Health Questionnaire - Parent Form 50, were even larger and ranged from –0.52 to 0.3. In particular, the lower is the Psychosocial Summary score, the greater is the emotional and social burden of a parent, while the better is the health-related quality of life defined by Physical Summary score, the worse is the familiar cohesion.

Possible Determinants of Children’s Health-Related Quality of Life The association of the possible determiners (wheelchair, ventilator, age) and the health-related quality of life in children


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Table 2. Internal Consistency of the Children Health Questionnaire Parent Form 50 in Duchenne Muscular Dystrophy Patients (N¼27) Cronbach’s a

Dimension Global Health Physical Functioning Role/Social Limitations - Emotional Role/Social Limitations - Physical Bodily Pain and Discomfort Role/Social Limitations -Behavioral Behavior Mental Health Self Esteem General Health Perceptions Change in Health Emotional Impact on Parent Time Impact on Parent Family Activities Family Cohesion

0.7524 0.7998 0.7561 0.7636 0.8188 0.7539 0.7577 0.7531 0.8054 0.7690 0.8009 0.7596 0.7611 0.7624 0.7704

showed that the Children Health Questionnaire - Parent Form 50 scores were not significantly different if we compared the considered categories, with some exceptions: wheelchair patients’ scores were significantly lower concerning the Physical Function domain (effect size –17.59, 95% confidence interval –32.25 to –2.94, P ¼ .02), while patients who used the ventilator had significantly lower scores in Physical Function (effect size –17.80, 95% confidence interval –27.20 to –8.39, P ¼ .05), and Family Cohesion domains (effect size –28.69, 95% confidence interval –54.40 to –2.98, P ¼ .016).

Possible Determinants of Caregivers’ Subjective Experience Need for Knowledge about the disease was higher if the caregiver was older than 40 (P < .001). Fathers reported lower levels of satisfaction with the Family Relationship than mothers (P ¼ .007), and those caregivers who stopped their activity showed a higher Emotional Burden (P ¼ .001). Family Strain Questionnaire scores did not seem to be influenced by children’s characteristics (age, ventilator use, wheelchair).

Conclusion Duchenne muscular dystrophy is a chronic disease in which progression is inevitable, leading to a state of severe physical dependence. Therefore, 1 of the important goals of patient management is to achieve and maintain the highest possible health-related quality of life level. Surprisingly, only few studies evaluated the impact of Duchenne muscular dystrophy on patients and their parents. On the other hand, the importance of patient-reported outcomes in a global assessment of Duchenne patients has been recently highlighted.25 We designed a study to evaluate the disease burden in patients suffering from Duchenne muscular dystrophy and in their caregivers by validated questionnaires. The choice of

health-related quality of life questionnaire for Duchenne muscular dystrophy children and adolescents has been made taking into account both the aim of the study (to document the disease impact on a patient group) and the sample characteristics (clinical status and age range). Usually, when the patient is a child, health-related quality of life can be assessed by patients’ self report or by parental proxy report. Pediatric patient selfreports are considered to be the standard for measuring health-related quality of life; however, proxy reports can be the only available source of data when children are too young, too cognitively impaired, or too sick to complete a questionnaire.26,27 Moreover, considering the age range of the patients involved in the study, it would have been impossible to evaluate their health-related quality of life through the same validated self-reported tool for everyone: the Children Health Questionnaire - Parent Form 50 gave us the possibility of using the same questionnaire for the whole population. As a generic instrument for evaluating health status, the Children Health Questionnaire - Parent Form 50 includes questions aimed at assessing a wide range of domains applicable to a broad spectrum of children. This generic questionnaire highlights subjective perspectives that concentrate on aspects of health important to all children (physical, emotional, social, and family dimensions) independently from health conditions. The questionnaire was confirmed to be a valid instrument in this population, with internal consistency and construct validity. Compared with the normative group, Duchenne muscular dystrophy children have significantly lower scores in many Children Health Questionnaire - Parent Form 50 dimensions and in both Physical and Psychosocial summary scores, indicating an impact that deeply and broadly affects daily life. As expected, Duchenne muscular dystrophy children are significantly limited in performing all physical activities and have problems with school and other daily performances; they experience pain and discomfort, with a consequent impact on the emotional sphere. Despite these aspects, some areas of the personal well-being of the child and his family remain preserved. Parents do not report feelings of nervousness and depression in their children, nor behavioral problems such as aggression, impulsivity, hyperactivity: this can be explained considering the disease’s characteristics. Caregivers are worried and distressed about children’s clinical conditions, and they are aware about the progressive nature of disability. For these reasons, ill children receive more attention and support from their family and friends than healthy subjects. Moreover, the psychological status can represent for children the possibility to build their own health and well-being space inside the family. This can help patients to adapt to live stressful events in other, often new, ways. The impact of illness on family function is severe in terms of emotions, with strong limitations on the organization of activities. However, the sense of cohesion experienced by the family, similar to the 1 reported by the normative sample of reference, can be an adaptive strategy toward the disease. Caregivers’ strain seems neither related to the disease severity nor to children’s health-related quality


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Table 3. Disease Impact in Children and in Their Caregivers (Mean and Standard Deviation) Children Health Questionnaire - Parent Form 50 Dimension Global Health Physical Functioning Role/Social Limitations - Emotional Role/Social Limitations - Physical Bodily Pain and Discomfort Role/Social Limitations -Behavioral Behavior Mental Health Self Esteem General Health Perceptions Change in Health Emotional Impact on Parent Time Impact on Parent Family Activities Family Cohesion Physical Summary score Psychosocial Summary score

Family Strain Questionnaire

Score

Possible range

Dimension

Score

43.33 (20.94) 16.45 (3.88) 52.67 (6.72) 46.79 (7.39) 63.70 (4.80) 68.92 (4.01) 69.44 (4.67) 67.21 (3.94) 63.81 (3.68) 37.75 (3.61) 43.27 (4.29) 42.52 (4.92) 76.81 (5.71) 71.63 (4.07) 69.44 (3.90) 18.25 (1.98) 44.55(2.35)

0-100 0-100 0-100 0-100 0-100 0-100 0-100 0-100 0-100 0-100 0-100 0-100 0-100 0-100 0-100 0-50 0-50

Emotional burden Problem in social involvement Need of knowledge about the disease Satisfaction with family relationships Thoughts about death

7.70 2.70 2.74 3.19 2.52

(3.41) (1.79) (1.10) (1.00) (1.31)

Possible range 0-14 0-7 0-4 0-4 0-6

Table 4. Comparison Between Children Health Questionnaire - Parent Form 50 Scores of Duchenne Muscular Dystrophy Patients and Italian Normative Data CHQ Dimension Global Health Physical Functioning Role/Social Limitations Emotional Role/Social Limitations Physical Bodily Pain and Discomfort Role/Social Limitations Behavioral Behavior Mental Health Self Esteem General Health Perceptions Change in Health Emotional Impact on Parent Time Impact on Parent Family Activities Family Cohesion Physical Summary score Psychosocial Summary core

DMD children mean and Healthy Subjects mean and Difference from nom SD (N¼27) SD (N¼788) (Effect size)

95% Confidence P value versus interval norm

43.33 (20.94) 16.45 (3.88) 52.67 (6.72)

85.4 (16.1) 96.7 (11.9) 95.8 (15)

42.07 80.25 43.13

50.42 to -33.71 88.27 to -72.22 57.03 to -29.22