Risk Factors for First Fractures Among Males With Duchenne or Becker Muscular Dystrophy.

BACKGROUND: Fractures are a significant concern for individuals with Duchenne/Becker muscular dystrophy with 21% to 44% of males experiencing a fracture. Factors that increase or decrease the risk for fracture have been suggested in past research, although statistical risk has not been determined. METHODS: In this retrospective cohort study, we used the Muscular Dystrophy Surveillance, Tracking and Research Network cohort, a large, population-based sample to identify risk factors associated with first fractures in patients with Duchenne or Becker muscular dystrophy. Our study cohort included males with Duchenne or Becker muscular dystrophy born between 1982 and 2006 who resided in Arizona, Colorado, Georgia, Iowa, and Western New York, retrospectively identified and followed through 2010. We utilized a multivariate Cox proportional hazard model to determine hazard ratios for relevant factors associated with first fracture risk including race/ethnicity, surveillance site, ambulation status, calcium/vitamin D use and duration, bisphosphonate use and duration, and corticosteroid use and duration. RESULTS: Of 747 cases, 249 had at least 1 fracture (33.3%). Full-time wheelchair use increased the risk of first fracture by 75% for every 3 months of use (hazard ratio=1.75, 95% confidence interval, 1.14, 2.68), but corticosteroid use, bisphosphonate use, and calcium/vitamin D use did not significantly affect risk in the final adjusted model. CONCLUSIONS: In this cohort, first fractures were common and full-time wheelchair use, but not corticosteroid use, was identified as a risk factor. The impact of prevention measures should be more thoroughly assessed. CLINICAL RELEVANCE: Fractures are a significant concern for individuals with dystrophinopathies, but the contribution of various risk factors has not been consistently demonstrated.

Identifying patients with opioid use disorder using International Classification of Diseases (ICD) codes: Challenges and opportunities.

BACKGROUND AND AIMS: International Classification of Diseases (ICD) diagnosis codes are often used in research to identify patients with opioid use disorder (OUD), but their accuracy for this purpose is not fully evaluated. This study describes application of ICD-10 diagnosis codes for opioid use, dependence and abuse from an electronic health record (EHR) data extraction using data from the clinics' OUD patient registries and clinician/staff EHR entries. DESIGN: Cross-sectional observational study. SETTING: Four rural primary care clinics in Washington and Idaho, USA. PARTICIPANTS: 307 patients. MEASUREMENTS: This study used three data sources from each clinic: (1) a limited dataset extracted from the EHR, (2) a clinic-based registry of patients with OUD and (3) the clinician/staff interface of the EHR (e.g. progress notes, problem list). Data source one included records with six commonly applied ICD-10 codes for opioid use, dependence and abuse: F11.10 (opioid abuse, uncomplicated), F11.20 (opioid dependence, uncomplicated), F11.21 (opioid dependence, in remission), F11.23 (opioid dependence with withdrawal), F11.90 (opioid use, unspecified, uncomplicated) and F11.99 (opioid use, unspecified with unspecified opioid-induced disorder). Care coordinators used data sources two and three to categorize each patient identified in data source one: (1) confirmed OUD diagnosis, (2) may have OUD but no confirmed OUD diagnosis, (3) chronic pain with no evidence of OUD and (4) no evidence for OUD or chronic pain. FINDINGS: F11.10, F11.21 and F11.99 were applied most frequently to patients who had clinical diagnoses of OUD (64%, 89% and 79%, respectively). F11.20, F11.23 and F11.90 were applied to patients who had a diagnostic mix of OUD and chronic pain without OUD. The four clinics applied codes inconsistently. CONCLUSIONS: Lack of uniform application of ICD diagnosis codes make it challenging to use diagnosis code data from EHR to identify a research population of persons with opioid use disorder.

Parental perspectives on the diagnostic process for Duchenne and Becker muscular dystrophy.

Duchenne and Becker muscular dystrophy (DBMD) are allelic, X-linked recessive, neuromuscular disorders characterized by progressive loss of muscle function. Despite technological advances in diagnostic genetic testing, the mean age at diagnosis (4.7 years) has remained unchanged for decades. The purpose of the study was to characterize parental perceptions of the diagnostic process and identify factors that influence the timeline. Data collection for this qualitative study consisted of six individual and five group interviews. Participants (N = 30) included Hispanic, non-Hispanic black, and non-Hispanic white parents whose son was diagnosed with DBMD. The "help-seeking behavior model" provided an analytical framework to analyze the data. Parents did not move through help-seeking stages unidirectionally as described in other studies. Delays existed at each stage. We identified personal, familial, social, cultural, and provider factors that impeded earlier diagnosis. These barriers prolonged movement through a stage or led families to repeat previous stages. Results should initiate debate among system administrators, patient advocates, and healthcare providers regarding which barriers may be most modifiable and which interventions may reduce the time to diagnosis and limit parental emotional distress.

Care coordination between rural primary care and telemedicine to expand medication treatment for opioid use disorder: Results from a single-arm, multisite feasibility study.

PURPOSE: The use of telemedicine (TM) has accelerated in recent years, yet research on the implementation and effectiveness of TM-delivered medication treatment for opioid use disorder (MOUD) has been limited. This study investigated the feasibility of implementing a care coordination model involving MOUD delivered via an external TM provider for the purpose of expanding access to MOUD for patients in rural settings. METHODS: The study tested a care coordination model in 6 rural primary care sites by establishing referral and coordination between the clinic and a TM company for MOUD. The intervention spanned approximately 6 months from July/August 2020 to January 2021, coinciding with the peak of the COVID-19 pandemic. Each clinic tracked patients with OUD in a registry during the intervention period. A pre-/post-intervention design (N = 6) was used to assess the clinic-level outcome as patient-days on MOUD based on patient electronic health records. FINDINGS: All clinics implemented critical components of the intervention, with an overall TM referral rate of 11.7% among patients in the registry. Five of the 6 sites showed an increase in patient-days on MOUD during the intervention period compared to the 6-month period before the intervention (mean increase per 1,000 patients: 132 days, P = .08, Cohen's d = 0.55). The largest increases occurred in clinics that lacked MOUD capacity or had a greater number of patients initiating MOUD during the intervention period. CONCLUSIONS: To expand access to MOUD in rural settings, the care coordination model is most effective when implemented in clinics that have negligible or limited MOUD capacity.

Disparities in the diagnostic process of Duchenne and Becker muscular dystrophy.

PURPOSE: To determine whether sociodemographic factors are associated with delays at specific steps in the diagnostic process of Duchenne and Becker muscular dystrophy. METHODS: We examined abstracted medical records for 540 males from population-based surveillance sites in Arizona, Colorado, Georgia, Iowa, and western New York. We used linear regressions to model the association of three sociodemographic characteristics with age at initial medical evaluation, first creatine kinase measurement, and earliest DNA analysis while controlling for changes in the diagnostic process over time. The analytical dataset included 375 males with information on family history of Duchenne and Becker muscular dystrophy, neighborhood poverty levels, and race/ethnicity. RESULTS: Black and Hispanic race/ethnicity predicted older ages at initial evaluation, creatine kinase measurement, and DNA testing (P < 0.05). A positive family history of Duchenne and Becker muscular dystrophy predicted younger ages at initial evaluation, creatine kinase measurement and DNA testing (P < 0.001). Higher neighborhood poverty was associated with earlier ages of evaluation (P < 0.05). CONCLUSIONS: Racial and ethnic disparities in the diagnostic process for Duchenne and Becker muscular dystrophy are evident even after adjustment for family history of Duchenne and Becker muscular dystrophy and changes in the diagnostic process over time. Black and Hispanic children are initially evaluated at older ages than white children, and the gap widens at later steps in the diagnostic process.

Rapid mapping of zebrafish mutations with SNPs and oligonucleotide microarrays.

Large-scale genetic screens in zebrafish have identified thousands of mutations in hundreds of essential genes. The genetic mapping of these mutations is necessary to link DNA sequences to the gene functions defined by mutant phenotypes. Here, we report two advances that will accelerate the mapping of zebrafish mutations: (1) The construction of a first generation single nucleotide polymorphism (SNP) map of the zebrafish genome comprising 2035 SNPs and 178 small insertions/deletions, and (2) the development of a method for mapping mutations in which hundreds of SNPs can be scored in parallel with an oligonucleotide microarray. We have demonstrated the utility of the microarray technique in crosses with haploid and diploid embryos by mapping two known mutations to their previously identified locations. We have also used this approach to localize four previously unmapped mutations. We expect that mapping with SNPs and oligonucleotide microarrays will accelerate the molecular analysis of zebrafish mutations.