Assessment of the upper limb function, strength, and mobility in treatment-naive children with spinal muscular atrophy Types 2 and 3.

INTRODUCTION/AIMS: Current upper limb assessments in pediatric spinal muscular atrophy (SMA) may not adequately capture change with disease progression. Our aim was to examine the relationship between motor function, strength, and hand/finger mobility of the upper limb in treatment-naïve children with SMA Types 2 and 3 to assess new methods to supplement current outcomes. METHODS: The Revised Upper Limb Module (RULM), grip and pinch strength, and hand/finger mobility data were collected from 19 children with SMA Types 2 and 3 aged 5.2-16.9 years over a year. RESULTS: A median loss between 0.5 and 2.5 points in the RULM was seen across all SMA subgroups with the biggest median loss recorded between 10 and 14 years of age. The grip strength loss was -0.06 kg (-4.69 to 3.49; IQR, 1.21); pinch improvement of 0.05 (-0.65 to 1.27; IQR, 0.48); hand/finger mobility test improvement of 4 points (-24 to 14; IQR, 6.75) for the whole cohort. Significant correlations were found between the RULM and grip strength (p < .001), RULM and pinch strength (p < .001), RULM and revised Brooke (p < .001), grip strength and pinch strength (p < .001). DISCUSSION: The combined use of the RULM, dynamometry, and hand mobility provide insight about correlations between function and strength in children with SMA. The RULM and grip strength assessments captured a significant decline in upper limb function, whereas the pinch and finger/hand mobility showed an improvement over the course of 1 year and these results should be considered for future studies.

Nursing students' perceived knowledge, therapeutic attitudes, and interest in addictions education.

BACKGROUND: Nurses care for people who use substances (SU) and have addictions across healthcare settings; however, education has been lacking about these issues. Experiences working with patients with SU paired with lack of knowledge may negatively affect attitudes. PURPOSE: Prior to designing an addictions curriculum, we aimed to assess nursing students' perceived knowledge, attitudes, and educational interests in SU and addictions, and compare pre-licensure nursing students to registered nurses and advanced practice RNs (RN/APRNs). METHODS: The student body at a large mid-Atlantic school of nursing was surveyed online, Fall 2019. Of 1987 students, 647 (33 %) responded; 567 complete responses were analyzed. Pre-licensure and RN/APRN student responses were compared, and comments were summarized. RESULTS: Virtually all students agreed that it is important to be educated about SU and addictions (96 %). Students were interested in addiction courses (80 %) and a graduate certificate program (61 %), and 70 % of undergraduates were in favor of an addictions focus area as part of their BSN degree program. Perceived knowledge to address addictions was rated moderately overall. As far as learning needs, students felt they knew the least about problem gambling, communicating about SU, considering readiness to change and using community resources. RN/APRNs rated their motivation and job satisfaction in working with people with SU lower than pre-licensure students. CONCLUSIONS: Students' responses supported and informed the development of addictions curricula, with a broad focus on addictions including substances, gambling and other addictions. Elective courses, an undergraduate focus area, and a graduate-level certificate were developed, piloted, and are now offered by the School of Nursing.

Determining minimal clinically important differences in the North Star Ambulatory Assessment (NSAA) for patients with Duchenne muscular dystrophy.

The North Star ambulatory assessment (NSAA) is a functional motor outcome measure in Duchenne muscular dystrophy (DMD), widely used in clinical trials and natural history studies, as well as in clinical practice. However, little has been reported on the minimal clinically important difference (MCID) of the NSAA. The lack of established MCID estimates for NSAA presents challenges in interpreting the significance of the results of this outcome measure in clinical trials, natural history studies and clinical practice. Combining statistical approaches and patient perspectives, this study estimated MCID for NSAA using distribution-based estimates of 1/3 standard deviation (SD) and standard error of measurement (SEM), an anchor-based approach, with six-minute walk distance (6MWD) as the anchor, and evaluation of patient and parent perception using participant-tailored questionnaires. The MCID for NSAA in boys with DMD aged 7 to 10 years based on 1/3 SD ranged from 2.3-2.9 points, and that on SEM ranged from 2.9-3.5 points. Anchored on the 6MWD, the MCID for NSAA was estimated as 3.5 points. When the impact on functional abilities was considered using participant response questionnaires, patients and parent perceived a complete loss of function in a single item or deterioration of function in one to two items of the assessment as an important change. Our study examines MCID estimates for total NSAA scores using multiple approaches, including the impact of patient and parent perspective on within scale changes in items based on complete loss of function and deterioration of function, and provides new insight on evaluation of differences in these widely used outcome measure in DMD.

Wearable full-body motion tracking of activities of daily living predicts disease trajectory in Duchenne muscular dystrophy.

Artificial intelligence has the potential to revolutionize healthcare, yet clinical trials in neurological diseases continue to rely on subjective, semiquantitative and motivation-dependent endpoints for drug development. To overcome this limitation, we collected a digital readout of whole-body movement behavior of patients with Duchenne muscular dystrophy (DMD) (n = 21) and age-matched controls (n = 17). Movement behavior was assessed while the participant engaged in everyday activities using a 17-sensor bodysuit during three clinical visits over the course of 12 months. We first defined new movement behavioral fingerprints capable of distinguishing DMD from controls. Then, we used machine learning algorithms that combined the behavioral fingerprints to make cross-sectional and longitudinal disease course predictions, which outperformed predictions derived from currently used clinical assessments. Finally, using Bayesian optimization, we constructed a behavioral biomarker, termed the KineDMD ethomic biomarker, which is derived from daily-life behavioral data and whose value progresses with age in an S-shaped sigmoid curve form. The biomarker developed in this study, derived from digital readouts of daily-life movement behavior, can predict disease progression in patients with muscular dystrophy and can potentially track the response to therapy.

Workplace Exposures and Prescription Drug Misuse Among Nurses.

OBJECTIVE: This study examined the association between workplace exposure and prescription drug misuse in nurses. BACKGROUND: Studies have found RNs and other health providers have higher rates of prescription misuse than the general population and have suggested that workplace exposures along with excessive job demands create circumstances fostering misuse. METHODS: Survey data from 1170 RNs on workplace exposures (availability, frequency of administration, knowledge of substances, and workplace controls) were described by workplace, position, and specialty. Exposures were then related to prescription drug misuse using logistic regression. RESULTS: Each workplace exposure was associated with past year prescription drug misuse. An index combining all exposures was significantly related to misuse ( P = 0.001), and odds of misuse increased by 38% for each point increase in the exposure index. CONCLUSIONS: Consideration of the health and well-being of nurses at higher odds of exposure to prescription drugs with misuse potential is warranted. Workplace support to help nurses maintain and restore their health should be a priority.

Choice of extended release medication for OUD in young adults (buprenorphine or naltrexone): A pilot enhancement of the Youth Opioid Recovery Support (YORS) intervention.

BACKGROUND: The Youth Opioid Recovery Support (YORS) intervention is a promising approach for the treatment of opioid use disorder (OUD) in young adults that seeks to improve adherence to extended-release medications for OUD (XR-MOUD) and reduce opioid relapse through assertive outreach techniques. YORS was previously tested with individuals seeking extended-release naltrexone (XR-NTX), but has not been tested on individuals pursuing extended-release buprenorphine (XR-BUP). METHODS: This pilot study tested the YORS intervention among a group choosing either XR-MOUD compared to historical treatment as usual (H-TAU) and intervention conditions from a previous study. This study also tested feasibility of a stepped care approach using a protocol for transition to standard care. Twenty-two young adults (ages 18-26) with OUD intending to pursue outpatient treatment with XR-NTX (n = 11) or XR-BUP (n = 11) were recruited from inpatient treatment and received 12-24 weeks of the YORS intervention. RESULTS: Participants in YORS compared to H-TAU received more outpatient doses at 12 weeks (1.91 vs. 0.40, p < .001) and 24 weeks (3.76 vs. 0.70, p < .001), had lower relapse rates at 12 weeks (36.4% vs.75.0%; p = .012) and 24 weeks(52.9% vs. 95.0%; p = .003), and had greater cumulative relapse-free survival over 24 weeks (HR = 2.65, 95% CI: 1.17-6.02, p < .05). Rates of continuing MOUD in a standard care setting after the intervention ended were extremely poor. Outcomes did not differ by medication choice. CONCLUSIONS: These results are consistent with previous findings and demonstrate feasibility and efficacy of YORS with patient choice of medication. The results highlight the need for innovative strategies to sustain positive outcomes and step-down care successfully in these vulnerable young adults.

Novel free-circulating and extracellular vesicle-derived miRNAs dysregulated in Duchenne muscular dystrophy.

Aim: To perform cross-sectional and longitudinal miRNA profiling in plasma from Duchenne muscular dystrophy (DMD) subjects and find non-invasive biomarkers in DMD. Subjects/materials & methods: Plasma was collected from 14 age and sex matched controls and 46 DMD subjects. Free-circulating and extracellular vesicle (EV)-derived miRNA expression was measured by RT-qPCR. Results: Free-circulating and EVs derived miR-29c-3p and miR-133a-3p are dysregulated in DMD subjects. Free-circulating and EV-derived miR-29c-3p are reduced in DMD subjects undergoing daily corticosteroid treatment. Free-circulating miR-1-3p and miR-122-5p are longitudinally upregulated in ambulant DMD subjects. Conclusion: We detected novel free-circulating and EV-derived dysregulated miRNAs in plasma from DMD subjects and characterized the longitudinal profile of free-circulating miRNA on plasma from DMD subjects.

A novel de novo ACTA1 variant in a patient with nemaline myopathy and mitochondrial Complex I deficiency.

We describe the presentation and follow-up of a three-year-old girl with nemaline myopathy due to a de-novo variant in ACTA1 (encoding skeletal alpha actin) and moderately low enzyme level of Complex I of the mitochondrial respiratory chain. She presented in the neonatal period with hypotonia, followed by weakness in the facial, bulbar, respiratory and neck flexors muscles. A biopsy of her quadriceps muscle at the age of one year showed nemaline rods. Based on her clinical presentation of a congenital myopathy and histopathological features on a muscle biopsy, ACTA1 was sequenced, and this revealed a novel sequence variant, c.760 A>C p. (Asn254His). In addition, mitochondrial respiratory chain enzymatic activity of skeletal muscle biopsy showed a moderately low activity of complex I (nicotinamide adenine dinucleotide (NADH): ubiquinone oxidoreductase). Disturbances of Complex I of the respiratory chain have been reported in patients with nemaline myopathy, although the mechanism remains unclear.

Volunteerism and self-selection bias in human positron emission tomography neuroimaging research.

Scientists have known for decades that persons who volunteer for behavioral research may be different from those who decline participation and that characteristics differentiating volunteers from non-volunteers may vary depending on the nature of the research. There is evidence that volunteer self-selection can impact representativeness of samples in studies involving physically or psychologically stressful procedures, such as electric shocks, sensory isolation, or drug effects. However, the degree to which self-selection influences sample characteristics in "stressful" studies involving positron emission tomography (PET) has not been evaluated. Since estimation of population parameters, robustness of findings, and validity of inferred relationships can all be impacted by volunteer bias, it is important to determine if self-selection may act as an unrecognized confound in such studies. In the present investigation, we obtained baseline data on 114 (56M, 58F) subjects who participated in a study involving completion of several self-report questionnaires and behavioral performance tasks. Participants were later given the opportunity to enroll in an [11C]raclopride PET study involving intravenous amphetamine (AMPH) administration. Demographic characteristics, personality traits, and task performance of subjects who consented to the latter study were compared with those who declined participation. Findings showed that the principal personality trait that distinguished the two groups was sensation-seeking; volunteers scored significantly higher on this dimension than non-volunteers. Males were more likely to volunteer than females. However, results of mediation analysis suggested that the relationship between gender and volunteer status was mediated by greater sensation-seeking traits in the males. Implications of these findings are discussed.