What Huntington's Disease Patients Say About Their Illness: An Online Direct-to-Participant Pilot Study.

Background: Direct-to-participant online reporting facilitates the conduct of clinical research by increasing access and clinically meaningful patient engagement. Objective: We assessed feasibility of online data collection from adults with diagnosed Huntington's disease (HD) who directly reported their problems and impact in their own words. Methods: Data were collected online from consenting United States residents who self-identified as 1) having been diagnosed with Huntington's disease, 2) able to ambulate independently, and 3) self-sufficient for most daily needs. Data for this pilot study were collected using the Huntington Study Group myHDstory online research platform. The Huntington Disease Patient Report of Problems (HD-PROP), an open-ended questionnaire, was used to capture verbatim bothersome problems and functional impact. Natural language processing, human-in-the-loop curation of verbatim reports involving clinical and experience experts, and machine learning classified verbatim-reports into clinically meaningful symptoms. Results: All 8 questionnaires in the online pilot study were completed by 345 participants who were 60.9% men, 34.5±9.9 (mean±SD) years old, and 9.5±8.4 years since HD diagnosis. Racial self-identification was 46.4% Caucasian, 28.7% African American, 15.4% American Indian/Alaska Native, and 9.5% other. Accuracy of verbatim classification was 99%. Non-motor problems were the most frequently reported symptoms; depression and cognitive impairment were the most common. Conclusions: Online research participation was feasible for a diverse cohort of adults who self-reported an HD diagnosis and predominantly non-motor symptoms related to mood and cognition. Online research tools can help inform what bothers HD patients, identify clinically meaningful outcomes, and facilitate participation by diverse and under-represented populations.

Trends in Adolescent Firearm-Related Injury: A Time Series Analysis.

BACKGROUND: Firearm-related injury (FRI) became the leading cause of death among children/adolescents in 2019. PURPOSE: This study sought to determine changes over time in the population of adolescents affected by FRI in Atlanta, Georgia, such that high risk cohorts could be identified. RESEARCH DESIGN: City-wide retrospective cohort review. STUDY SAMPLE: Adolescent victims (age 11-21 years of age) of FRI, defined by ICD9/10 codes, in Atlanta, Georgia. DATA ANALYSIS: Descriptive, multivariate and time series analysis. RESULTS: There were 1,453 adolescent FRI victims in this time period, predominantly Black (86%) and male (86.6%). Unintentional injury was higher among ages 11-14 years (43.1%) compared to 15-17 years (10.2%) and 18-21 years (9.3%) (P < .01). FRI affecting females increased at a rate of 8.1 injuries/year (P < .01), and unintentional injuries increased at by 7.6/year (P < .01). Mortality declined from 16% in 2016 to 7.7% in 2021. CONCLUSION: Our data provides evidence for firearm policy reform. Interventions should target prevention of intentional injury among AQ4 females and seek to reverse the trend in unintentional injuries.

Stress-Induced Mouse Model of the Cardiac Manifestations of Friedreich's Ataxia Corrected by AAV-mediated Gene Therapy.

Friedreich's ataxia (FA), an autosomal recessive disorder caused by a deficiency in the expression of frataxin (FXN), is characterized by progressive ataxia and hypertrophic cardiomyopathy. Although cardiac dysfunction is the most common cause of mortality in FA, the cardiac disease remains subclinical for most of the clinical course because the neurologic disease limits muscle oxygen demands. Previous FXN knockout mouse models exhibit fatal cardiomyopathy similar to human FA, but in contrast to the human condition, untreated mice become moribund by 2 months of age, unlike humans where the cardiac disease often does not manifest until the third decade. The study was designed to create a mouse model for early FA disease relevant to the time for which a gene therapy would likely be most effective. To generate a cardiac-specific mouse model of FA cardiomyopathy similar to the human disease, we used a cardiac promoter (αMyhc) driving CRE recombinase cardiac-specific excision of FXN exon 4 to generate a mild, cardiac-specific FA model that is normal at rest, but exhibits the cardiac phenotype with stress. The hearts of αMyhc mice had decreased levels of FXN and activity of the mitochondrial complex II/complex IV respiratory chain. At rest, αMyhc mice exhibited normal cardiac function as assessed by echocardiographic assessment of ejection fraction and fractional shortening, but when the heart was stressed chemically with dobutamine, αMyhc mice compared with littermate control mice had a 62% reduction in the stress ejection fraction (p < 2 × 10-4) and 71% reduction in stress-related fractional shortening (p < 10-5). When assessing functional cardiac performance using running on an inclined treadmill, αMyhc mice stayed above the midline threefold less than littermate controls (p < 0.02). A one-time intravenous administration of 1011 genome copies of AAVrh.10hFXN, an adeno-associated virus (AAV) serotype rh10 gene transfer vector expressing human FXN, corrected the stress-induced ejection fraction and fractional shortening phenotypes. Treated αMyhc mice exhibited exercise performance on a treadmill indistinguishable from littermate controls (p > 0.07). These αMyhc mice provide an ideal model to study long-term cardiac complications due to FA and AAV-mediated gene therapy correction of stress-induced cardiac phenotypes typical of human FA.

Somatic mitochondrial DNA mutations in early Parkinson and incidental Lewy body disease.

Somatic mutations in mitochondrial DNA (mtDNA) are hypothesized to play a role in Parkinson disease (PD), but large increases in mtDNA mutations have not previously been found in PD, potentially because neurons with high mutation levels degenerate and thus are absent in late stage tissue. To address this issue, we studied early stage PD cases and cases of incidental Lewy body disease (ILBD), which is thought to represent presymptomatic PD. We show for the first time that mtDNA mutation levels in substantia nigra neurons are significantly elevated in this group of early PD and ILBD cases.

Unmet health care needs in children with cerebral palsy: a cross-sectional study.

Children with potentially severe health conditions such as cerebral palsy (CP) are at risk for unmet health care needs. We sought to determine whether children with CP had significantly greater unmet health care needs than children with other special health care needs (SHCN), and whether conditions associated with CP increased the odds of unmet health care needs. We analyzed data from the National Survey of Children with Special Health Care Needs, 2005-2006, using multivariate logistic regression to calculate the adjusted odds of children with CP having one or more unmet health care needs compared to children with other SHCN. We also determined the association of CP-related conditions with unmet health care needs in children with CP. After weighting to national averages, our sample represented 178,536 children with CP (1.9%), and 9,236,794 with children with other SHCN (98.1%). Although having CP increased the odds that children had unmet health care needs (OR = 1.46, 95% CI [1.07-1.99]), the presence of a "severe" health condition weakened the association. Gastrointestinal problems and emotional problems increased the odds that children with CP would have unmet health care needs above that of children without the associated conditions (p ≤ .01). Children with CP are similar to children with other SHCN and may benefit from collaborative programs targeting severe chronic conditions. However, children with CP and associated conditions have increased odds of unmet health care needs in comparison to children without those problems.

The effects of telephone prompting on attendance for starting treatment and retention in treatment at a specialist alcohol clinic.

OBJECTIVE: To examine the effects of telephone prompting on attendance for the start of treatment and retention in treatment in a specialist alcohol clinic. METHOD: The study setting was a specialist alcohol treatment clinic. Participants were 172 clients attending as out-patients. An ABABAB design was used with planned alternating conditions, respectively, with or without a telephone prompt the day before the client was due to attend, over a succession of six consecutive 4-week periods. RESULTS: Clients who were prompted were more likely to start treatment and attend further treatment sessions than clients who were not prompted. CONCLUSIONS: Telephone prompting is a simple and effective way to improve attendance for the start of treatment and retention in alcohol treatment.