Table 4.

Summary of recommendations in published CPGs for the diagnosis and treatment of DMD.

Diagnosis (MINSA COL)
•It is recommended to consider the age at onset, 3.3+1.56 years, to ask about symptoms of lower limb weakness and motor impairment, and to explore the presence of Gowers's sign and gastrocnemius pseudohypertrophy to guide the clinical diagnosis of DMD (Strongly in favor, very low quality of evidence) (⊕○○○). •It is recommended to use the measurement of serum creatine kinase as part of the initial diagnostic approach for patients with a clinical picture compatible with muscular dystrophy (strong support, very low quality of evidence) (⊕○○○). •It is recommended to use electromyography for the diagnosis of primary muscle fiber disease in patients with muscle weakness, high serum creatine kinase values, and no family history of muscular dystrophy (strongly in favor, moderate quality of evidence) (⊕⊕⊕○). •It is recommended to confirm the diagnosis by Western blotting for muscle dystrophin in patients with clinical suspicion of increased creatine phosphokinase (CPK) levels or electrodiagnosis of Duchenne or Becker muscular dystrophy, provided that trained personnel are available at certified institutions (strong support, low quality of evidence) (⊕⊕○○). •In the case of inability to perform Western blotting, confirmation of the diagnosis by immunohistochemical testing for dystrophin in muscle in patients with clinical suspicion, by increased creatine phosphokinase (CPK) levels or by electrodiagnosis of Duchenne or Becker muscular dystrophy is recommended, provided there are trained personnel in qualified institutions (strongly in favor, low quality of evidence) (⊕⊕○○). •In the case of inability to perform Western blotting or immunohistochemistry tests, it is recommended to use multiplex ligation-dependent probe amplification (MLPA) to detect deletions and duplications; if these are negative, gene sequencing tests can be performed (weakly in favor, low quality of evidence) (⊕⊕○○).
Treatment with corticosteroids
MINSA COL	AAN
•Treatment with steroids, 0.75 mg/kg/day of prednisone or 0.9 mg/kg/day of deflazacort, is recommended for patients with DMD to reduce mortality, prolong independent walking ability, and reduce scoliosis progression (strongly in favor, low quality of evidence) (⊕⊕○○). •It is suggested to discuss with patients and parents the continuation of steroid treatment after loss of independent walking; its use may be justified to preserve upper limb strength, reduce scoliosis progression and delay respiratory and cardiac alterations. Medical surveillance is suggested for long-term adverse effects, including periodic ophthalmologic surveillance (weakly in favor, low quality of evidence) (⊕⊕○○). •The use of steroid treatment to reduce mortality in patients with DMD without weakness; to prolong independent walking ability; to reduce the progression of scoliosis, dyspnea, and fatigue; or to improve quality of life is not recommended (strongly against, low quality of evidence) (⊕⊕○○). •The initiation of steroid therapy for patients with a diagnosis of DMD on an individualized basis is suggested, depending on functional abilities, age (no earlier than two years of age), pre-existing factors, and when motor or skill gains stop or falls increase. The initiation of steroids should be timely once motor losses occur and should be discussed with the parents and caregivers (weakly in favor, very low quality of evidence) (⊕○○○). •Intermittent steroid therapy is suggested if there are adverse events such as weight gain more than 10% that of baseline in three months, elevated blood glucose, increased blood pressure, fractures, or another intolerable event for the patient (weakly in favor, low quality of evidence) (⊕⊕○○).	•Prednisone as an intervention for patients with DMD should be used to improve strength (B) and may be used to improve timed motor function (C), should be used to improve pulmonary function (B) and may be used to reduce the need for scoliosis surgery (C), and may be used to delay the onset of cardiomyopathy by 18 years of age (C). •Deflazacort as an intervention for patients with DMD may be used to improve strength and timed motor function and delay the age at loss of ambulation by 1.4 to 2.5 years (C), may be used to improve pulmonary function (C), may be used to reduce the need for scoliosis surgery (C), may be used to delay the onset of cardiomyopathy by 18 years of age (C), and may be used to increase survival at 5 and 15 years of follow-up (C). •Deflazacort and prednisone may be equivalent in improving motor function (C). There is insufficient evidence to establish a difference in effect on cardiac function (U). Prednisone may be associated with increased weight gain in the first years of treatment compared with deflazacort (C). Deflazacort may be associated with increased risk of cataracts compared with prednisone (C). •If patients with DMD are treated with prednisone, 0.75 mg/kg/day of prednisone should be the preferred dosing regimen (B). Ten mg/kg/weekend of prednisone is equally effective over 12 months, but long-term outcomes are not yet established. A prednisone dosage of 0.75 mg/kg/day is probably associated with significant risk of weight gain, hirsutism, and cushingoid appearance (B), with an equal side effect profile seen over 12 months with the 10 mg/kg/weekend dosing. A prednisone dosage of 0.3 mg/kg/day may be used as an alternative dosing regimen with lesser efficacy and fewer AEs (level C). A prednisone dosage of 1.5 mg/kg/day is another alternative regimen; it may be equivalent to 0.75 mg/kg/day but may be associated with more AEs (C).
Treatment with ataluren
MINSA COL	NICE
•Treatment with ataluren is not recommended for patients with DMD to reduce mortality, improve quality of life, prolong independent walking ability, or reduce dyspnea and fatigue (strongly against, very low quality of evidence) (⊕○○○).	•Ataluren, within its marketing authorization, is recommended for treating Duchenne muscular dystrophy resulting from a nonsense mutation in the dystrophin gene in people aged 2 years and older who can walk. •The committee concluded that, because of the uncertainty about the clinical benefits in the relevant population in clinical practice, ataluren would represent acceptable value for money to the NHS only when it was given in the context of a managed access agreement at a price that incorporated the patient access scheme and included other financial components that reduced the total costs to the NHS.
Management strategies-Australian CPG
•We suggest dietary counseling (food or supplements) to increase the intake of calcium to the age-appropriate recommended dietary intake. (⊕○○○) •We suggest serial casting for selected* ambulatory patients to increase ankle dorsiflexion range of motion. (⊕○○○) •We suggest the use of handheld dynamometry to assess strength. If the necessary equipment is not available, we suggest manual muscle testing to assess strength, if the evaluator is highly skilled in this assessment and testing is conducted in a standardized manner by the same evaluator. Reliability: ++; Measurement error: +++ •We suggest exercise be encouraged for boys with DMD. (⊕○○○) •We suggest nutritional supplements be used to assist strength in ambulatory boys. (⊕○○○) •We suggest the 6-minute walk test (6MWT)† be used to assess mobility. Internal Consistency: ?; Reliability: ++; Measurement error: +++; Content validity: +++; Hypothesis testing: +; Responsiveness: ? •We suggest the North Star Ambulatory Assessment (NSAA)† be used to assess function. Internal Consistency: +++; Reliability: ++; Content validity: +++; Responsiveness: +++; Item response theory: +++
•We suggest that ankle-foot orthoses (AFOs) not be used for ambulation due to risk of harm. (⊕○○○) •We suggest that knee-ankle-foot orthoses (KAFOs) should only be implemented with careful consideration of the high resource requirements and individual variation in values and preferences. (⊕○○○) •We suggest the Performance of the Upper Limb (PUL) assessment be used†. Internal consistency: ++; Reliability: ++ •We suggest the Egen Klassifikation Scale (EK scale) † be used to assess activities of daily living in non-ambulant patients. Reliability: +++; Content validity: +++; Criterion validity: ++ •We suggest the adoption of the 2018 DMD Care Standards for the assessment and management of respiratory function. •We suggest skinfold measures not be used to estimate body composition. Criterion validity:? •We suggest that the Schofield weight equation be used to estimate resting energy requirements. (⊕○○○) •We suggest that gastrostomy feeding, when indicated, may be effective in improving nutritional status in patients with DMD. (⊕○○○) •We suggest the adoption of the 2018 DMD Care Standards for the assessment and management of learning difficulties. •We suggest the adoption of the 2018 DMD Care Standards for the assessment and management of behavioral difficulties. •We suggest the adoption of the 2018 DMD Care Standards for the assessment and management of the transition to adult services.