Current approach to genetic testing and genetic evaluation referrals for adults with congenital heart disease.

Background: Congenital heart disease (CHD) is the most common congenital anomaly. Up to 33% have an identifiable genetic etiology. Improved medical and surgical management of CHD has translated into longer life expectancy and a rapidly growing population of adults living with CHD. The adult CHD (ACHD) population did not have access during childhood to the genetic technologies available today and therefore have not had a robust genetic evaluation that is currently recommended for infants with CHD. Given this potential benefit; the aims of this study were to determine how ACHD cardiologists offer genetics services to patients and identify the indications that influence decision-making for genetics care. Methods: We performed a descriptive cross-sectional study of ACHD cardiologists. A study-developed questionnaire was distributed via emailed REDCap link. The recruitment email was sent to 104 potential respondents. The survey was open from 06/2022 to 01/2023. Results: Thirty-five cardiologists participated in the study (response rate of 34%). Most cardiologists identified as white (77%) and male (66%). Cardiologists were more likely to refer patients to genetics (91%) than to order testing themselves (57%). Of the testing ordered, chromosomal testing (55%) was ordered more than gene sequencing (14%). Most cardiologists would refer a patient with a conotruncal lesion (interrupted aortic arch) over other indications for a genetics evaluation. There were more reported barriers to ordering genetic testing (66%) compared to referring to genetics for a genetics evaluation (23%). Cardiologists were more confident recognizing features suggestive of a genetic syndrome than ordering the correct test (p = 0.001). Regarding associations between clinical factors and current practices, more years in practice trended towards less referrals and testing. Evaluating a greater number of patients (p = 0.11) and greater confidence recognizing syndromic features (p = 0.12) and ordering the correct test (p = 0.09) were all associated with ordering more testing. Conclusion: Testing for microdeletion syndromes is being offered and completed in the ACHD population, however testing for single-gene disorders associated with CHD is being under-utilized. Developing guidelines for genetic testing in adults with CHD could increase access to genetic services, impact medical management, reduce uncertainty regarding prognosis, and inform recurrence risk estimates.

The Convergent Validity of the SWAY Balance Application to Assess Postural Stability in Military Cadets Recovering from Concussion.

Background: Concussions are often accompanied by balance disturbances. Clinically accurate evaluation systems are often expensive, large, and inaccessible to most clinicians. The Sway Balance Mobile Application (SWAY) is an accessible method to quantify balance changes. Purpose: To determine the known groups and convergent validity of the SWAY to assess balance after a concussion. Study Design: Case-Control Study. Methods: Twenty participants with acute concussion and twenty controls were recruited. At initial, one-week, and final return to activity (RTA) evaluations, all participants completed the Sports Concussion Assessment Tool (SCAT-5), and balance control measured by SWAY mBESS and NeuroCom Balance Master Sensory Organization Test (SOT). Mixed model ANOVAs were used to detect differences in SWAY mBESS and NeuroCom SOT scores with time (initial, one-week, final RTA) as the within-subjects factor and group (concussed, healthy) as the between-subjects factor. Spearman's Rho correlations explored the associations between NeuroCom SOT scores, SWAY scores, SCAT-5 symptom scores, and time in days to final RTA. Results: The sampled population was predominantly male and age (20 ± 1), and BMI differences were insignificant between groups. The SWAY did not detect differences between healthy and concussed participants and did not detect change over time [F(2,40) = .114, p = 0.89; F(2,40)= .276, p =0.60]. When assessing the relationship between the SWAY and the SOT, no correlation was found at any time point (r = -0.317 to -0.062, p > 0.05). Time to RTA demonstrated a moderate correlation with both SCAT-5 symptom severity score (r = .693, p < 0.01) and SCAT-5 total symptom score (r = .611, p < 0.01) at the one-week follow-up. Conclusion: The SWAY mBESS does not appear to be a valid balance assessment for the concussed patient. The SWAY mBESS in patients with concussion failed to demonstrate convergent validity and did not demonstrate an ability to validate known groups. When assessing the time to final RTA, the one-week post-initial assessment SCAT-5 symptom severity and total scores may help determine the length of recovery in this population. Level of Evidence: Level 3.

Prospective, multi-site study of healthcare utilization after actionable monogenic findings from clinical sequencing.

As large-scale genomic screening becomes increasingly prevalent, understanding the influence of actionable results on healthcare utilization is key to estimating the potential long-term clinical impact. The eMERGE network sequenced individuals for actionable genes in multiple genetic conditions and returned results to individuals, providers, and the electronic health record. Differences in recommended health services (laboratory, imaging, and procedural testing) delivered within 12 months of return were compared among individuals with pathogenic or likely pathogenic (P/LP) findings to matched individuals with negative findings before and after return of results. Of 16,218 adults, 477 unselected individuals were found to have a monogenic risk for arrhythmia (n = 95), breast cancer (n = 96), cardiomyopathy (n = 95), colorectal cancer (n = 105), or familial hypercholesterolemia (n = 86). Individuals with P/LP results more frequently received services after return (43.8%) compared to before return (25.6%) of results and compared to individuals with negative findings (24.9%; p < 0.0001). The annual cost of qualifying healthcare services increased from an average of $162 before return to $343 after return of results among the P/LP group (p < 0.0001); differences in the negative group were non-significant. The mean difference-in-differences was $149 (p < 0.0001), which describes the increased cost within the P/LP group corrected for cost changes in the negative group. When stratified by individual conditions, significant cost differences were observed for arrhythmia, breast cancer, and cardiomyopathy. In conclusion, less than half of individuals received billed health services after monogenic return, which modestly increased healthcare costs for payors in the year following return.

The effectiveness of telehealth gait retraining in addition to standard physical therapy treatment for overuse knee injuries in soldiers: a protocol for a randomized clinical trial.

INTRODUCTION: Running is the most common cardiovascular exercise in the military. However, there is a high incidence of running-related overuse injuries that reduces military readiness. Gait retraining is a common intervention to treat running-related injuries, but the high cost of equipment and lack of clinician expertise and availability reduces utilization. Gait retraining intervention in a telehealth format might improve feasibility. The purpose of this randomized clinical trial is to determine the effectiveness of a telehealth gait retraining intervention on pain, self-reported function, and biomechanical risk factors for injury in service members who present to a Military Health System physical therapy clinic with an overuse knee injury. METHODS: This is a parallel, two-arm, single-blind randomized clinical trial. The two independent variables are intervention (2 levels: telehealth gait retraining intervention with standard of care or only standard of care) and time (3 levels: baseline, 10 weeks or post-intervention, 14 weeks). Participants between the ages of 18 to 60 years will be included if they report knee pain during and/or after running to be anywhere from a 3 to a 7 on the numerical pain rating scale and demonstrate a rearfoot strike pattern. The primary dependent variables are as follows: (1) pain (worst pain during and/or after running) and (2) foot strike pattern (conversion rate from rearfoot to non-rearfoot foot strike pattern during running). Secondary outcomes include patient self-reported function and running biomechanics. DISCUSSION: The effectiveness of a telehealth gait retraining intervention to reduce pain and modify foot strike pattern is not known. The results of this study may help determine the effectiveness and feasibility of a telehealth gait retraining intervention to reduce pain, change foot strike, improve function, and improve running gait biomechanics. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04269473 . Registered 05 February 2020.

Preparedness and training of genetic counselors practicing in inpatient settings.

As rapid genomic testing technology increasingly allows for real-time answers that could alter management for acutely ill patients, opportunities for genetic counselors to work in inpatient settings will increase. However, genetic counselors' preparedness and the training provided by graduate programs to work in inpatient settings are unknown. We conducted semi-structured interviews with 13 genetic counselors who provided services in varied inpatient settings to assess genetic counselors' readiness for inpatient positions. We also surveyed members of the Association of Genetic Counseling Program Directors (AGCPD) about inpatient training practices of genetic counseling graduate programs. Genetic counselors were recruited through the National Society of Genetic Counselors (NSGC) Inpatient Special Interest Group listserv and graduate program faculty were recruited through the AGCPD listserv. Some challenges reported by genetic counselors in inpatient settings included working in a fast-paced hospital environment which necessitated focused interactions with patients; collaborating with diverse providers who may not understand the role of genetic counselors; and navigating grief experiences of families and of themselves as a provider. Although genetic counselors felt that many of their skills developed in graduate school were transferrable to the inpatient setting, those who had minimal or no inpatient exposure in graduate school often described feeling unprepared for working in the inpatient setting. The majority of AGCPD respondents (23/28) indicated their program provided some type of exposure to the inpatient setting for students, the most common (22/23) being an inpatient clinical rotation, which suggests many graduate programs are already recognizing the importance of providing inpatient training. Our findings indicate that while many skills are transferrable to inpatient positions, genetic counselors face unique challenges in inpatient settings. Our results suggest that graduate exposure to the inpatient setting and professional support of inpatient genetic counselors are beneficial to support genetic counselors' preparedness to take on inpatient positions.

Wearable technology assessing running biomechanics and prospective running-related injuries in Active Duty Soldiers.

The purpose of this study was to determine if running biomechanical variables measured by wearable technology were prospectively associated with running injuries in Active Duty Soldiers. A total of 171 Soldiers wore a shoe pod that collected data on running foot strike pattern, step rate, step length and contact time for 6 weeks. Running-related injuries were determined by medical record review 12 months post-study enrollment. Differences in running biomechanics between injured and non-injured runners were compared using independent t-tests or ANCOVA for continuous variables and chi-square analyses for the association of categorical variables. Kaplan-Meier survival curves were used to estimate the time to a running-related injury. Risk factors were carried forward to estimate hazard ratios using Cox proportional hazard regression models. Forty-one participants (24%) sustained a running-related injury. Injured participants had a lower step rate than non-injured participants, but step rate did not have a significant effect on time to injury. Participants with the longest contact time were at a 2.25 times greater risk for a running-related injury; they were also relatively slower, heavier, and older. Concomitant with known demographic risk factors for injury, contact time may be an additional indicator of a running-related injury risk in Active Duty Soldiers.

Outcomes of Returning Medically Actionable Genomic Results in Pediatric Research.

PURPOSE: The electronic Medical Records and Genomics (eMERGE) Phase III study was undertaken to assess clinical utility of returning medically actionable genomic screening results. We assessed pediatric clinical outcomes following return of pathogenic/likely pathogenic (P/LP) variants in autosomal dominant conditions with available effective interventions. METHODS: The two eMERGE III pediatric sites collected outcome data and assessed changes in medical management at 6 and 12 months. RESULTS: We returned P/LP results to 29 participants with outcome data. For 23 of the 29 participants, the P/LP results were previously unknown. Five of the 23 participants were already followed for conditions related to the P/LP variant. Of those receiving novel results and not being followed for the condition related to the P/LP result (n = 18), 14 (77.8%) had a change in healthcare after return of results (RoR). Following RoR, cascade testing of family members occurred for 10 of 23 (43.5%). CONCLUSIONS: The most common outcomes post-RoR included imaging/laboratory testing and health behavior recommendations. A change in healthcare was documented in 77.8% of those receiving results by 6 months. Our findings demonstrate how return of genomic screening results impacts healthcare in pediatric populations.

A clinical scoring system for early onset (neonatal) Marfan syndrome.

PURPOSE: This study aimed to develop objective diagnostic criteria for early onset Marfan syndrome (eoMFS) to facilitate early diagnosis and timely interventions. METHODS: On the basis of an extensive literature review and the responses from a survey distributed among providers with expertise in the diagnosis and management of eoMFS, we developed an age-based, diagnostic scoring system encompassing 10 features common to eoMFS (9 clinical + 1 laboratory) and divided them into cardiac, systemic, and FBN1 (on the basis of the location of the pathogenic FBN1 variant) scores. RESULTS: In total, 77 individuals with eoMFS (13 newly reported) and 49 individuals diagnosed with classical Marfan syndrome during early childhood were used to validate the criteria. Median cardiac (8 vs 0, P < .001), systemic (11 vs 3, P < .001), FBN1 (5 vs 0, P < .001), and total (23 vs 4, P < .001) scores were significantly higher in individuals with eoMFS than in those without. A proposed clinical score (cardiac + systemic) cutoff of ≥14 points showed excellent sensitivity (100%), specificity (92%), and reliability (correctly classified = 94%). CONCLUSION: Distinct from classical Marfan syndrome in phenotype and morbidity, eoMFS can be diagnosed clinically using an objective scoring system encompassing the typical physical features and cardiac disease manifestations. Although genetic testing can be suggestive of eoMFS, genetic testing alone is insufficient for diagnosis.

Normative Data for the NeuroCom Sensory Organization Test in United States Military Academy Boxers.

Background: Balance function is a key indicator in the identification of and recovery from concussion. The NeuroCom Sensory Organization Test (SOT) is used to objectively quantify balance using input from the visual, vestibular, and somatosensory systems. Baseline tests are necessary for comparison post-concussion. Purpose: The primary purpose of this study was to establish baseline SOT measures for the population that will be useful in the concussion assessment, diagnosis, and return to duty decisions following a concussion. Secondary aims were to compare females and males as well as concussed versus non-concussed. To the knowledge of the authors these are the only published normative data for a highly-active military population ages 17-23. Study Design: Cross-sectional study. Methods: Two hundred fifty-three (70 female and 183 male) cadets in a boxing course at a service academy were enrolled. The participants were evaluated on the SOT using the NeuroCom Balance Manager (Natus Medical Inc., Seattle, WA) and each condition, composite (COMP) score, and ratio score were recorded. Results: No significant differences were observed in SOT COMP scores between females (COMP = 76.67 ± 7.25) and males (COMP = 76.57 ± 7.77), nor between participants with history of concussion (COMP = 75.83 ± 7.90) versus those never concussed (COMP = 76.75 ± 7.57). Conclusion: This study provides SOT reference values for young, healthy, active individuals, which will assist in the interpretation of individual scores for concussion diagnosis and recovery, as well as serve as baseline data for future studies. These data on 17-23-year-olds will add to the currently available normative values of 14-15-year-olds and 20-59-year-olds. Level of Evidence: 4.

Retrospective comparison of parent-reported genetics knowledge, empowerment, and familial uptake of cardiac screening between parents who received genetic counseling by a certified genetic counselor and those who did not: A single US academic medical center study.

Bicuspid aortic valve (BAV) is the most common congenital heart defect, which can cause severe cardiac complications. BAVs cluster in families and demonstrate high heritability. Cardiac screening for first-degree relatives of individuals with a BAV is recommended. This retrospective two-group study evaluated the impact of cardiovascular genetic counseling provided by a board-certified genetic counselor on parent-reported outcomes by comparing parental responses of those who received genetic counseling by a genetic counselor (GC group) for family history of BAV to those who did not (non-GC group). A retrospective chart review from May 2016 to June 2019 identified 133 pediatric patients with an isolated BAV. Parents of eligible probands were invited to complete an online survey assessing genetics knowledge, empowerment (Genomics Outcome Scale), and familial uptake of cardiac screening. Surveys were completed by 38/97 (39%) parents in the non-GC group and 20/36 (56%) parents in the GC group. The median genetics knowledge score was not significantly different between the two groups (GC group: 8, range 3-11 out of a maximum possible of 12; non-GC group: 7, range 2-11; p = .08). The mean empowerment score was not significantly different between the two groups (GC group: mean 24.6, SD 2.2; non-GC group: mean 23.2, SD 3.5; p = .06). The uptake of cardiac screening was significantly higher in the GC group with 39/59 (66%) total first-degree relatives reported as having been screened compared with 36/91 (40%) in the non-GC group (p = .002). Parent-reported outcomes in our study suggest that receiving genetic counseling by a board-certified genetic counselor significantly increased familial uptake of cardiac screening for first-degree relatives of pediatric patients with a BAV. Studies with larger sample sizes are needed to confirm the findings of this study; however, a referral to a genetic counselor should be considered for patients with a BAV.

The genetic architecture of pediatric cardiomyopathy.

To understand the genetic contribution to primary pediatric cardiomyopathy, we performed exome sequencing in a large cohort of 528 children with cardiomyopathy. Using clinical interpretation guidelines and targeting genes implicated in cardiomyopathy, we identified a genetic cause in 32% of affected individuals. Cardiomyopathy sub-phenotypes differed by ancestry, age at diagnosis, and family history. Infants < 1 year were less likely to have a molecular diagnosis (p < 0.001). Using a discovery set of 1,703 candidate genes and informatic tools, we identified rare and damaging variants in 56% of affected individuals. We see an excess burden of damaging variants in affected individuals as compared to two independent control sets, 1000 Genomes Project (p < 0.001) and SPARK parental controls (p < 1 × 10-16). Cardiomyopathy variant burden remained enriched when stratified by ancestry, variant type, and sub-phenotype, emphasizing the importance of understanding the contribution of these factors to genetic architecture. Enrichment in this discovery candidate gene set suggests multigenic mechanisms underlie sub-phenotype-specific causes and presentations of cardiomyopathy. These results identify important information about the genetic architecture of pediatric cardiomyopathy and support recommendations for clinical genetic testing in children while illustrating differences in genetic architecture by age, ancestry, and sub-phenotype and providing rationale for larger studies to investigate multigenic contributions.

The Effect of Blood Flow Restriction Therapy on Shoulder Function Following Shoulder Stabilization Surgery: A Case Series.

Background: Traumatic shoulder instability is a common injury in athletes and military personnel. Surgical stabilization reduces recurrence, but athletes often return to sport before recovering upper extremity rotational strength and sport-specific abilities. Blood flow restriction (BFR) may stimulate muscle growth without the need for heavy resistance training post-surgically. Hypothesis/Purpose: To observe changes in shoulder strength, self-reported function, upper extremity performance, and range of motion (ROM) in military cadets recovering from shoulder stabilization surgery who completed a standard rehabilitation program with six weeks of BFR training. Study Design: Prospective case series. Methods: Military cadets who underwent shoulder stabilization surgery completed six weeks of upper extremity BFR training, beginning post-op week six. Primary outcomes were shoulder isometric strength and patient-reported function assessed at 6-weeks, 12-weeks, and 6-months postoperatively. Secondary outcomes included shoulder ROM assessed at each timepoint and the Closed Kinetic Chain Upper Extremity Stability Test (CKCUEST), the Upper Extremity Y-Balance Test (UQYBT), and the Unilateral Seated Shotput Test (USPT) assessed at the six-month follow-up. Results: Twenty cadets performed an average 10.9 BFR training sessions over six weeks. Statistically significant and clinically meaningful increases in surgical extremity external rotation strength (p < 0.001; mean difference, .049; 95% CI: .021, .077), abduction strength (p < 0.001; mean difference, .079; 95% CI: .050, .108), and internal rotation strength (p < 0.001; mean difference, .060; CI: .028, .093) occurred from six to 12 weeks postoperatively. Statistically significant and clinically meaningful improvements were reported on the Single Assessment Numeric Evaluation (p < 0.001; mean difference, 17.7; CI: 9.4, 25.9) and Shoulder Pain and Disability Index (p < 0.001; mean difference, -31.1; CI: -44.2, -18.0) from six to 12 weeks postoperatively. Additionally, over 70 percent of participants met reference values on two to three performance tests at 6-months. Conclusion: While the degree of improvement attributable to the addition of BFR is unknown, the clinically meaningful improvements in shoulder strength, self-reported function, and upper extremity performance warrant further exploration of BFR during upper extremity rehabilitation. Level of Evidence: 4, Case Series.

The Effect of Blood Flow Restriction Training on Muscle Atrophy Following Meniscal Repair or Chondral Restoration Surgery in Active Duty Military: A Randomized Controlled Trial.

CONTEXT: Recently, blood flow restriction (BFR) training has gained popularity as an alternative to high-load resistance training for improving muscle strength and hypertrophy. Previous BFR studies have reported positive treatment effects; however, clinical benefits to using BFR following meniscal repair or chondral surgery are unknown. The purpose of this study was to determine the effect of resistance exercises with BFR training versus exercises alone on self-reported knee function, thigh circumference, and knee flexor/extensor strength postmeniscal or cartilage surgery. DESIGN: Single-blinded randomized controlled trial in an outpatient military hospital setting. Twenty participants were randomized into 2 groups: BFR group (n = 11) and control group (n = 9). METHODS: Participants completed 12 weeks of postoperative thigh strengthening. The BFR group performed each exercise with the addition of BFR. Both groups continued with the prescribed exercises without BFR from 12 weeks until discharged from therapy. Thigh circumference and self-reported knee function were measured at 1, 6, 12, and 24 weeks postoperatively along with knee extensor and flexor strength at 12 and 24 weeks. Change scores between time points were calculated for knee function. Limb symmetry indices (LSI) were computed for thigh circumference and knee strength variables. RESULTS: Seventeen participants were included in the final analyses (BFR = 8 and control = 9) due to COVID-19 restrictions. There were no interactions or main effects for group. Time main effects were established for change in knee function scores, thigh circumference LSI, and knee extensor strength LSI. However, knee flexor strength LSI had no main effect for time. CONCLUSION: The outcomes of this trial suggest that resistance exercises with and without BFR training may result in similar changes to function, thigh atrophy, and knee extensor strength postmeniscus repair/chondral restoration, though further study with larger sample sizes is needed.

Impact of Genetic Testing for Cardiomyopathy on Emotional Well-Being and Family Dynamics: A Study of Parents and Adolescents.

BACKGROUND: Genetic testing is indicated for children with a personal or family history of hereditary cardiomyopathy to determine appropriate management and inform risk stratification for family members. The implications of a positive genetic result for children can potentially impact emotional well-being. Given the nuances of cardiomyopathy genetic testing for minors, this study aimed to understand how parents involve their children in the testing process and investigate the impact of genetic results on family dynamics. METHODS: A survey was distributed to participants recruited from the Children's Cardiomyopathy Foundation and 7 North American sites in the Pediatric Cardiomyopathy Registry. The survey explored adolescent and parent participants' emotions upon receiving their/their child's genetic results, parent-child result communication and its impact on family functionality, using the McMaster Family Assessment Device. RESULTS: One hundred sixty-two parents of minors and 48 adolescents who were offered genetic testing for a personal or family history of cardiomyopathy completed the survey. Parents whose child had cardiomyopathy were more likely to disclose positive diagnostic genetic results to their child (P=0.014). Parents with unaffected children and positive predictive testing results were more likely to experience negative emotions about the result (P≤0.001) but also had better family functioning scores than those with negative predictive results (P=0.019). Most adolescents preferred results communicated directly to the child, but parents were divided about whether their child's result should first be released to them or their child. CONCLUSIONS: These findings have important considerations for how providers structure genetic services for adolescents and facilitate discussion between parents and their children about results.

A human importin-ß-related disorder: Syndromic thoracic aortic aneurysm caused by bi-allelic loss-of-function variants in IPO8.

Importin 8, encoded by IPO8, is a ubiquitously expressed member of the importin-ß protein family that translocates cargo molecules such as proteins, RNAs, and ribonucleoprotein complexes into the nucleus in a RanGTP-dependent manner. Current knowledge of the cargoes of importin 8 is limited, but TGF-ß signaling components such as SMAD1-4 have been suggested to be among them. Here, we report that bi-allelic loss-of-function variants in IPO8 cause a syndromic form of thoracic aortic aneurysm (TAA) with clinical overlap with Loeys-Dietz and Shprintzen-Goldberg syndromes. Seven individuals from six unrelated families showed a consistent phenotype with early-onset TAA, motor developmental delay, connective tissue findings, and craniofacial dysmorphic features. A C57BL/6N Ipo8 knockout mouse model recapitulates TAA development from 8-12 weeks onward in both sexes but most prominently shows ascending aorta dilatation with a propensity for dissection in males. Compliance assays suggest augmented passive stiffness of the ascending aorta in male Ipo8-/- mice throughout life. Immunohistological investigation of mutant aortic walls reveals elastic fiber disorganization and fragmentation along with a signature of increased TGF-ß signaling, as evidenced by nuclear pSmad2 accumulation. RT-qPCR assays of the aortic wall in male Ipo8-/- mice demonstrate decreased Smad6/7 and increased Mmp2 and Ccn2 (Ctgf) expression, reinforcing a role for dysregulation of the TGF-ß signaling pathway in TAA development. Because importin 8 is the most downstream TGF-ß-related effector implicated in TAA pathogenesis so far, it offers opportunities for future mechanistic studies and represents a candidate drug target for TAA.

Genetic Causes of Cardiomyopathy in Children: First Results From the Pediatric Cardiomyopathy Genes Study.

Background Pediatric cardiomyopathy is a genetically heterogeneous disease with substantial morbidity and mortality. Current guidelines recommend genetic testing in children with hypertrophic, dilated, or restrictive cardiomyopathy, but practice variations exist. Robust data on clinical testing practices and diagnostic yield in children are lacking. This study aimed to identify the genetic causes of cardiomyopathy in children and to investigate clinical genetic testing practices. Methods and Results Children with familial or idiopathic cardiomyopathy were enrolled from 14 institutions in North America. Probands underwent exome sequencing. Rare sequence variants in 37 known cardiomyopathy genes were assessed for pathogenicity using consensus clinical interpretation guidelines. Of the 152 enrolled probands, 41% had a family history of cardiomyopathy. Of 81 (53%) who had undergone clinical genetic testing for cardiomyopathy before enrollment, 39 (48%) had a positive result. Genetic testing rates varied from 0% to 97% between sites. A positive family history and hypertrophic cardiomyopathy subtype were associated with increased likelihood of genetic testing (P=0.005 and P=0.03, respectively). A molecular cause was identified in an additional 21% of the 63 children who did not undergo clinical testing, with positive results identified in both familial and idiopathic cases and across all phenotypic subtypes. Conclusions A definitive molecular genetic diagnosis can be made in a substantial proportion of children for whom the cause and heritable nature of their cardiomyopathy was previously unknown. Practice variations in genetic testing are great and should be reduced. Improvements can be made in comprehensive cardiac screening and predictive genetic testing in first-degree relatives. Overall, our results support use of routine genetic testing in cases of both familial and idiopathic cardiomyopathy. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01873963.

Wearable Technology May Assist in Retraining Foot Strike Patterns in Previously Injured Military Service Members: A Prospective Case Series.

A rearfoot strike (RFS) pattern with increased average vertical loading rates (AVLR) while running has been associated with injury. This study evaluated the ability of an instrumented sock, which provides real-time foot strike and cadence audio biofeedback, to transition previously injured military service members from a RFS to a non-rearfoot strike (NRFS) running pattern. Nineteen RFS runners (10 males, 9 females) were instructed to wear the instrumented socks to facilitate a change in foot strike while completing an independent walk-to-run progression and lower extremity exercise program. Kinetic data were collected during treadmill running while foot strike was determined using video analysis at initial (T1), post-intervention (T2), and follow-up (T3) data collections. Nearly all runners (18/19) transitioned to a NRFS pattern following intervention (8 ± 2.4 weeks after the initial visit). Most participants (16/18) maintained the transition at follow-up (5 ± 0.8 weeks after the post-intervention visit). AVLR of the involved and uninvolved limb decreased 29% from initial [54.7 ± 13.2 bodyweights per sec (BW/s) and 55.1 ± 12.7 BW/s] to post-intervention (38.7 ± 10.1 BW/s and 38.9 ± 10.0 BW/s), respectively. This effect persisted 5-weeks later at follow-up, representing an overall 30% reduction on the involved limb and 24% reduction on the uninvolved limb. Cadence increased from the initial to the post-intervention time-point (p = 0.045); however, this effect did not persist at follow-up (p = 0.08). With technology provided feedback from instrumented socks, approximately 90% of participants transitioned to a NRFS pattern, decreased AVLR, reduced stance time and maintained these running adaptations 5-weeks later.

Gait Retraining Improves Running Impact Loading and Function in Previously Injured U.S. Military Cadets: A Pilot Study.

INTRODUCTION: Running-related musculoskeletal injury (RRI) among U.S. military service members continues to negatively impact force readiness. There is a paucity of evidence supporting the use of RRI interventions, such as gait retraining, in military populations. Gait retraining has demonstrated effectiveness in altering running biomechanics and reducing running load. The purpose of this pilot study was to investigate the clinical effect of a gait retraining intervention on a military cadet population recovering from a lower-extremity RRI. MATERIALS AND METHODS: The study design is a pilot study. Before study initiation, institutional approval was granted by the Keller Army Community Hospital Office of Human Research Protections. Nine rearfoot strike (RFS) runners recovering from a lower-extremity RRI at the U.S. Military Academy were prospectively enrolled and completed a gait retraining intervention. Participants followed-up with their assigned medical provider 6 times over 10 weeks for a clinical evaluation and running gait retraining. Gait retraining was provided utilizing verbal, visual, and audio feedback to facilitate a change in running foot strike pattern from RFS to non-rearfoot strike (NRFS) and increase preferred running step rate. At pre-intervention and post-intervention running ground reaction forces (GRF) [average vertical loading rate (AVLR), peak vertical GRF], kinematic (foot strike pattern) and temporospatial (step rate, contact time) data were collected. Participants self-reported their level of function via the Single Assessment Numeric Evaluation, Patient-Specific Functional Scale, and total weekly running minutes. Paired samples t-tests and Wilcoxon signed rank tests were used to compare pre- and post-intervention measures of interest. Values of P < .05 were considered statistically significant. RESULTS: Nine patients completed the 10-week intervention (age, 20.3 ± 2.2 years; height, 170.7 ± 13.8 cm; mass, 71.7 ± 14.9 kg; duration of injury symptoms, 192.4 ± 345.5 days; running speed, 2.8 ± 0.38 m/s). All nine runners (100%) transitioned from RFS to NRFS. Left AVLR significantly decreased from 60.3 ± 17.0 bodyweight per second (BW/s) before intervention to 25.9 ± 9.1 BW/s after intervention (P = 0.008; effect size (d) = 2.5). Right AVLR significantly decreased from 60.5 ± 15.7 BW/s to 32.3 ± 12.5 BW/s (P < .001; d = 2.0). Similarly, step rate increased from 169.9 ± 10.0 steps per minute (steps/min) before intervention to 180.5 ± 6.5 steps/min following intervention (P = .005; d = 1.3). Single Assessment Numeric Evaluation scores improved significantly from 75 ± 23 to 100 ± 8 (P = .008; d = 1.5) and Patient-Specific Functional Scale values significantly improved from 6 ± 2.3 to 9.5 ± 1.6 (P = .007; d = 1.8) after intervention. Peak vertical GRF (left, P = .127, d = 0.42; right, P = .052, d = 0.53), contact time (left, P = 0.127, d = 0.42; right, P = 0.052, d = 0.53), and total weekly continuous running minutes (P = 0.095, d = 0.80) remained unchanged at post-intervention. All 9 patients remained injury free upon a 6-month medical record review. CONCLUSIONS: In 9 military service members with a RRI, a 10-week NRFS gait retraining intervention was effective in improving running mechanics and measures of function. Patients remained injury-free 6 months following enrollment. The outcomes of this pilot study suggest that individuals recovering from certain lower-extremity RRIs may benefit from transitioning to an NRFS running pattern.

Agreement Between the OptoGait and Instrumented Treadmill System for the Quantification of Spatiotemporal Treadmill Running Parameters.

The measurement of spatiotemporal gait parameters is commonly utilized to assess gait in healthy and injured individuals. The OptoGait system is a portable system and can be mounted to a treadmill to collect data in a clinical, training, or research setting. The purpose of this method comparison study was to examine the agreement of spatiotemporal gait parameters calculated by the OptoGait compared to an instrumented treadmill system during running. Thirty healthy runners ran on an instrumented treadmill with the OptoGait 1-m system mounted along the treadmill platform. Spatiotemporal running variables of step rate, step length, and contact time were calculated during the final minute of treadmill running. The level of agreement between the OptoGait and treadmill was analyzed using intraclass correlation coefficients [ICC (2,3)] for step rate, step length, and contact time. Step rate and step length demonstrated excellent agreement. Contact time demonstrated good agreement. Intraclass correlation coefficients for spatiotemporal parameters ranged from 0.83 to 0.99. The OptoGait demonstrated good to excellent agreement in the evaluation of running step rate, step length, and contact time and should be considered for use in clinical, training, or research settings.

The effectiveness of battlefield acupuncture in addition to standard physical therapy treatment after shoulder surgery: a protocol for a randomized clinical trial.

INTRODUCTION: There is a large incidence of shoulder instability among active young athletes and military personnel. Shoulder stabilization surgery is the commonly employed intervention for treating individuals with instability. Following surgery, a substantial proportion of individuals experience acute post-operative pain, which is usually managed with opioid pain medications. Unfortunately, the extended use of opioid medications can have adverse effects that impair function and reduce military operational readiness, but there are currently few alternatives. However, battlefield acupuncture (BFA) is a minimally invasive therapy demonstrating promise as a non-pharmaceutical intervention for managing acute post-operative pain. METHODS: This is a parallel, two-arm, single-blind randomized clinical trial. The two independent variables are intervention (2 levels, standard physical therapy and standard physical therapy plus battlefield acupuncture) and time (5 levels, 24 h, 48 h, 72 h, 1 week, and 4 weeks post shoulder stabilization surgery). The primary dependent variables are worst and average pain as measured on the visual analog scale. Secondary outcomes include medication usage, Profile of Mood States, and Global Rating of Change. DISCUSSION: The magnitude of the effect of BFA is uncertain; current studies report confidence intervals of between-group differences that include minimal clinically important differences between intervention and control groups. The results of this study may help determine if BFA is an effective adjunct to physical therapy in reducing pain and opioid usage in acute pain conditions. TRIAL REGISTRATION: ClinicalTrials.gov NCT04094246 . Registered on 16 September 2019.