Comparison Between Courses of Home and Inpatients Mechanical Ventilation in Patients with Muscular Dystrophy in Japan

In Japan, 27 hospitals specialize in treatment of muscular dystrophy patients, including inpatient care, of which 26 belong to the National Hospital Organization, and the other is the National Center of Neurology and Psychiatry. Since 1999, Japanese muscular dystrophy research groups investigating nervous and mental disorder have been developing a database of cases treated at these 27 institutions. In that regard, we conducted a survey of inpatients and home-mechanical ventilation patients (HMV patients) with muscular dystrophy and other neuromuscular disorders based on data collected by the National Hospital Organization and National Center of Neurology and Psychiatry.


Introduction
In Japan, 27 hospitals specialize in treatment of muscular dystrophy patients, including inpatient care, of which 26 belong to the National Hospital Organization, and the other is the National Center of Neurology and Psychiatry.Since 1999, Japanese muscular dystrophy research groups investigating nervous and mental disorder have been developing a database of cases treated at these 27 institutions.In that regard, we conducted a survey of inpatients and home-mechanical ventilation patients (HMV patients) with muscular dystrophy and other neuromuscular disorders based on data collected by the National Hospital Organization and National Center of Neurology and Psychiatry.
Herein, we examined data obtained in order to evaluate efficacy of mechanical ventilation therapy for HMV patients and mechanical ventilation-dependent inpatients (MV inpatients) with those wards.

Subjects and methods
The database includes numbers of inpatients, gender, age, diagnosis, respiratory condition, nutritional state, number of death cases, causes of death, and other relevant findings from data collected annually on October 1 every year since 1999.Additionally we collected the data of HMV patients from 27 institutes for this study.
By using the database and newly collected HMV data, we analyzed the courses of HMV patients group and those of MV inpatients of wards.We compared data of these two groups.Examination points are mechanical ventilation periods, outcome of these two groups, and caregiver for HMV patients.

Objective diseases
Objective diseases of this study were muscular dystrophy and spinal muscular atrophy, in particular Duchenne muscular dystrophy and myotonic dystrophy.Amyotrophic lateral sclerosis was not included.

Patients introduced HMV after 1999
The data which we requested 27 institutes specializing muscular dystrophy care was as follows; the number of patients introduced HMV after 1999, diagnosis of disease, gender, age at being introduced HMV, type of mechanical ventilation, such as non-invasive positive pressure ventilation (NPPV) or tracheostomy intermittent ventilation (TIV), present status, death cause for death case, main caregiver, and so on.

Patients introduced MV in muscular dystrophy wards after 1999
We selected data of newly MV introduced inpatients after 1999 from the database of the muscular dystrophy wards.

Mean age at starting mechanical ventilation and type of ventilation
The range of mechanical ventilation introduction age for HMV patients was 6.3~72.8years old (mean 25.9), and that of MV inpatients was 0.0~78.0years old (mean 33.2).The number of NPPV introduction cases of HMV patients was 420, and that of MV inpatients was 517 (Table 1-2).Fifty of NPPV cases of HMV group were switched to tracheostomy during the course.
Table 1-2.Mean age at starting mechanical ventilation and type of ventilation

Survival analysis of HMV patients group and MV inpatients
We performed survival analysis of those two groups.The endpoint for HMV patients was death or transition to hospitalization, and that for MV inpatient was death.Kaplan-Meier analysis showed that 75% life time of HMV patients was 1,689 days, while that of inpatients was 2,988 days (Log Rank (Mantel-Cox) p<0.01) (Fig. 1).

Analysis data of Duchenne muscular dystrophy and myotonic dystrophy
As the number of patients with Duchenne muscular dystrophy and myotonic dystrophy was great in these two groups, we analyzed the data of Duchenne muscular dystrophy and myotonic dystrophy separately.

Mean age at starting mechanical ventilation and type of ventilation of patients with Duchenne muscular dystrophy
Mean age at starting mechanical ventilation of Duchenne muscular dystrophy was 19.8 years old, ranged from 11.5 to 39.9 years old.While that of inpatient with Duchenne muscular dystrophy was 21.5 years old, ranged from 10.0 to 42.0 years old.There was no significant difference.The number of NPPV introduction cases of HMV patients with Duchenne muscular dystrophy was 220, and that of MV inpatients was 338 (Table 2).
Table 2. Mean age at starting mechanical ventilation and type of mechanical ventilation (Duchenne muscular dystrophy )

Type of nutrition of patients with Duchenne muscular dystrophy
The number of patients who required tube feeding, including a nasal or oral nutrition tube, and undergoing a percutaneous endoscopic gastrostomy (PEG) was apparently greater in MV inpatients group than HMV group (Table 3).

Survival analysis of two Duchenne muscular dystrophy groups
We performed survival analysis of those two Duchenne muscular dystrophy groups.The endpoint for HMV patients was death or transition to hospitalization, and that for MV inpatient was death.Kaplan-Meier analysis showed that 75% life time of HMV patients was 1,562 days, while that of inpatients was 3,739 days (Log Rank (Mantel-Cox) p<0.01) (Fig. 2).

Mean age at starting mechanical ventilation and type of ventilation of patients with myotonic dystrophy
Mean age at starting mechanical ventilation of myotonic dystrophy was 46.8 years old, ranged from 15.8 to 72.8 years old.While that of inpatient with myotonic dystrophy was 50.6 years old, ranged from 12.0 to 76.0 years old.There was no significant difference between two groups.The number of NPPV introduction cases of HMV patients with myotonic dystrophy was 55, and that of TIV was 5.The number of NPPV case was greater than TIV.While the number of NPPV introduction cases of MV patients with myotonic dystrophy was 108, and that of TIV was 114.In MV patients with myotonic dystrophy, the number and proportion of NPPV and TIV were almost equal (Table 4).Table 4. Mean age at starting mechanical ventilation and type of mechanical ventilation (myotonic dystrophy )

Type of nutrition of patients with myotonic dystrophy
The trend of nutrition was similar to Duchenne muscular dystrophy.The number who required tube feeding in MV inpatients group was apparently greater than HMV group (Table 5).

Survival analysis of two myotonic dystrophy groups
Similarly, we performed survival analysis of those two myotonic dystrophy groups.The endpoint for HMV patients was death or transition to hospitalization, and that for MV inpatient was death.Kaplan-Meier analysis showed that 75% life time of HMV patients was 1,557 days, while that of inpatients was 1,972 days.There was no significance (Fig. 3).

Death case
The total number of death cases was 215 (Table 1-1).As the number of death case of Duchenne muscular dystrophy and myotonic dystrophy was the majority, we analyzed the data of Duchenne muscular dystrophy and myotonic dystrophy separately.

Cause of death of Duchenne muscular dystrophy
The number of death cases of HMV patients was 29, and that of MV inpatients was 67.

Comparison Between Courses of Home and Inpatients Mechanical Ventilation in Patients with Muscular Dystrophy in Japan 111
The most frequent cause of death was heart related disorders, such as heart failure and arrhythmia, accounting for 16/29 for HMV group and 33/67 for MV inpatient group.Frequency was not significantly different between two groups.In MV inpatient group, respiratory related disorders, such as respiratory failure and respiratory infection, accounted for 23/67．HMV group included more sudden death cases than MV inpatient, and had an accidental case (Table 6).Table 6.Cause of death (Duchenne muscular dystrophy )

Cause of death of myotonic dystrophy
The majority of death case of myotonic dystrophy was reported from MV inpatient group.The most frequent cause was respiratory related disorders, such as respiratory tract infection and respiratory failure, which accounted for 29/56.Sudden death case was conspicuous in HMV group, accounting for 3/6(Table 7).

Outcome of HMV patients and MV inpatients with Duchenne muscular dystrophy and myotonic dystrophy
One hundred ninty four cases with Duchenne muscular dystrophy among 262 cases continued HMV, while 46 cases with myotonic dystrophy among 60 cases continued HMV (Table 8).Twenty two cases with Duchenne muscular dystrophy were switched to hospitalization.Table 8.Outcome (Duchenne muscular dystrophy and myotonic dystrophy )

Caregivers for HMV patients
Caregivers for most of HMV patients with Duchenne muscular dystrophy were patients' families (Table 9).In particular, patients' mothers were playing important role in continuing HMV.Similarly, caregivers for HMV patients with myotonic dystrophy were patients' families.On reflecting their age, some caregivers were patient' spouse (Table 9).

Summary of results of Duchenne muscular dystrophy and myotonic dystrophy
Proportion of TIV was higher in MV inpatients group than HMV group.And proportion of tube feeding was also higher in MV inpatients group than HMV group.Namely, respiratory condition and nutritional status were more severe in MV inpatients group than HMV group (both Duchenne muscular dystrophy and myotonic dystrophy).
In Survival analysis, outcome of patients with Duchenne muscular dystrophy of MV inpatients group was better than HMV group.Meanwhile in that of myotonic dystrophy, HMV group was better than inpatient group.
In MV inpatient group of Duchenne muscular dystrophy, respiratory related death was remarkable.
In HMV group, some sudden death cases and accidental death case were conspicuous.
Caregivers of HMV group were constructed by patients' families, centrally mother.

Conclusion
Approximate 2500 beds for patients with muscular dystrophy and related disorders are now provided among 27 institutions in Japan.In accordance with progress in therapeutic strategies for respiratory failure (American Thoracic Society Documents, 2004) and heart failure (Ishikawa, 1999;Matsumura, 2010), the life span of patients with muscular dystrophy prolonged (Bushby 2010a, b).Now, most inpatients admitted to muscular dystrophy wards have severe general conditions and many are assisted by mechanical ventilation (Tatara, 2006;2008), which is accordance with our data of MV patients in this study.
In recent two decades, social welfare systems and home medical care systems in Japan have been changing gradually.HMV has been penetrating into home medical care (Joseph, 2007).The number of HMV patients has been increasing (Tatara, 2006).Stable mechanical ventilated patients have been getting back home.
Our study demonstrated that the course of HMV patients was fairly good, although there was difference between Duchenne muscular dystrophy and myotonic dystrophy in long term outcome.However, the support system for patients and caregivers is not perfect.Our study also showed that burden of caregivers was supposed to be severe.The system for patients and caregivers should be adjusted (Dybwik, 2011).And safety net systems also should be adjusted to avoid accidental event leading to patient's death.
The muscular dystrophy wards may be requested to offer the circumstances for those who have difficulties in continuing HMV.There is necessarily needs for hospitalization of HMV patients (Windisch, 2008).
Study limitation: This study has limitation on bias of collecting patients' information.Specifically, information of HMV patients were reported from 14 institutes among 27 institutes, and MV inpatient information is the result of extraction from muscular dystrophy wards database.Extracted data from database has some ambiguous points in connection with obscure time-sequential analysis.
On analysis of institutes-restricted HMV patients group and MV inpatients group, differences in regard to therapeutic conditions among institutions may be problem.

Acknowledgments
This study was supported by a Research Grant for Nervous and Mental Disorders from the Ministry of Health, Labour and Welfare of Japan.
Institutions specializing in muscular dystrophy treatment in Japan (Fig. 4)

Fig. 1 .
Fig. 1.Comparison between HMV Patients and Mechanical Ventilation Inpatients (Total) Endpoint for HMV patient: death or transition to hospitalization Endpoint for MV inpatient: death

Fig. 2 .
Fig. 2. Comparison between HMV Patients and Mechanical Ventilation Inpatients (Duchenne muscular dystrophy ) Endpoint for HMVpatient: death or transition to hospitalization Endpoint for MV inpatient: death

Fig. 3 .
Fig. 3. Comparison between HMV Patients and Mechanical Ventilation Inpatients (myotonic dystrophy ) Endpoint for HMVpatient: death or transition to hospitalization Endpoint for MV inpatient: death

Fig. 4 .
Fig. 4. Institutions specializing in muscular dystrophy treatment in Japan

Table 9 .
HMV-continuing cases main caregiver (Duchenne muscular dystrophy and myotonic dystrophy) Comparison Between Courses of Home and Inpatients Mechanical Ventilation in Patients with Muscular Dystrophy in Japan 113