ABSTRACT
Background: Duchenne muscular dystrophy (DMD) is a disabling and life-threatening, X-linked recessive disorder caused by mutations in dystrophin. Natural history studies can inform the disease characteristics of DMD, and data from these studies can be used to plan and design clinical trials and as external controls for long-term studies. We report 12-month results from the largest natural history study of individuals with DMD in China receiving standard of care treatment. Methods: This ongoing, multicentre, prospective, single-cohort study (ClinicalTrials.gov: NCT03760029) was conducted in Chinese male participants with DMD (ambulatory aged <6 years [Group 1; n = 99]; ambulatory aged ≥6 years [Group 2; n = 177], and non-ambulatory of any age [Group 3; n = 36]. The follow-up period is ≥24 months, with some participants followed for 30 months. The primary endpoint was time to clinical milestones due to DMD disease progression, and motor, pulmonary, and cardiac function. Secondary endpoints were quality of life (QoL) assessments. Findings: Mean (standard deviation [SD]) age at screening was 3.4 (1.2), 8.6 (2.0), 12.3 (2.7) and 7.4 (3.5) years in Groups 1, 2, 3 and total respectively. Mean (SD) North Star Ambulatory Assessment (NSAA) total score at baseline was 21.2 (5.8) in Group 1, 19.5 (8.3) in Group 2 and 20.0 (7.7) in ambulatory total. Overall, the time to clinical milestones due to DMD disease progression was consistent with previous findings, in which loss of ambulation occurred at 13 years. There was a trend towards a decline over 12 months in NSAA and timed motor function from age 6 years, with the greatest reductions observed thereafter. There were no consistent trends in measures of QoL, although participants of any age generally had poorer outcomes at Month 12 versus their domain scores at baseline. Interpretation: This study improves the understanding of DMD progression according to the current standards of care in the Chinese DMD population and may inform selected endpoints and patient populations in clinical trials. Funding: Pfizer Inc.
ABSTRACT
OBJECTIVE: To investigate the treatment given to osteoporotic fracture patients by orthopaedists at major hospitals in China. METHODS: A 25-item quantitative questionnaire survey, categorized into five domains, including primary purpose of osteoporosis treatment, anti-osteoporosis therapy, calcium and vitamin D supplement, monitoring of osteoporosis, and knowledge of osteoporosis treatment, was designed to elicit information on orthopaedists' views on the treatment of osteoporotic fracture. A pre-survey test was conducted with a sample of 40 orthopaedic specialists to confirm the reliability and validity of the questionnaire. Each interview of the survey took approximately 15 min and did not directly involve any patients. The survey was conducted through face-to-face interviews at 119 tier 3 hospitals in 28 cities across Mainland China. RESULTS: A total of 484 valid responses were received. Seven in ten respondents have ≥10 years of professional practice. While two-thirds believed that osteoporosis treatment was to prevent fractures or re-fractures, 95.0% agreed that anti-osteoporosis medication should be administered to patients with a history of fragility fractures. Three in four would prescribe anti-osteoporosis medication perioperatively. Of these, 79.0% regarded bisphosphonates as the first-line drug. Approximately 86.0% of the 21-30 years cohort chose bisphosphonates compared to 71.4% for those with ≤10 years. More of the younger (≤10 years) cohort chose calcitonin compared to their older (21-30 years) colleagues (25.7% vs 11.6%). The most commonly prescribed daily dose is 800 IU for vitamin D supplements and 600 mg/day for calcium. CONCLUSIONS: Our respondents generally adhered to guidelines for the treatment and management of osteoporosis. A significant number had recommended lower dosages of vitamin D and calcium. Some differences exist between the younger cohort and their older colleagues in the prescription of pharmacological therapies. The criteria for initiating therapy should be more holistic and include other factors besides bone mineral density (BMD). Our results demonstrated that more comprehensive guidelines for osteoporosis management and a greater awareness of these guidelines by orthopaedists are needed to enable them to better manage their patients.