Impact of Cancer Therapy on Clonal Hematopoiesis Mutations and Subsequent Clinical Outcomes.

Exposure to cancer therapies is associated with an increased risk of clonal hematopoiesis (CH). The objective of our study was to investigate the genesis and evolution of CH following cancer therapy. In this prospective study, we undertook error-corrected duplex DNA sequencing in blood samples collected prior to and at two timepoints following chemoradiation in patients with esophageal or lung cancer recruited from 2013-2018. We applied a customized workflow to identify the earliest changes in CH mutation count and clone size and determine their association with clinical outcomes. Our study included 29 patients (87 samples). Their median age was 67 years, 76% (n = 22) were male; the median follow-up period was 3.9 years. The most mutated genes were DNMT3A, TET2, TP53, and ASXL1. We observed a two-fold increase in the number of mutations from before to after treatment in TP53, which differed from all other genes examined (P < .001). Among mutations detected before and after treatment, we observed an increased clone size in 38% and a decreased clone size in 5% of TP53 mutations (odds ratio = 3.7; 95% CI = 1.75-7.84; P < .001). Changes in mutation count and clone size were not observed in other genes. Individuals with an increase in the number of TP53 mutations following chemoradiation experienced shorter overall survival (hazard ratio = 7.07; 95% CI = 1.50-33.46; P = .014). In summary, we found an increase in the number and size of TP53 CH clones following chemoradiation that were associated with clinical outcomes.

Policy Interventions to Enhance Medical Care for People With Obesity in the United States-Challenges, Opportunities, and Future Directions.

Policy Points Health policymakers have insufficiently addressed care for people with obesity (body mass index ≥ 30 kg/m2) in the United States. Current federal policies targeting obesity medications reflect this unfortunate reality. We argue for a novel policy framework to increase access to effective obesity therapeutics and care, recognizing that, though prevention is critical, the epidemic proportions of obesity in the United States warrant immediate interventions to augment care. Reducing barriers to and improving the quality of existing anti-obesity medications, intensive behavioral therapy, weight management nutrition and dietary counseling, and bariatric surgery are critical. Moreover, to ensure continuity of care and patient-clinician trust, combating physician and broader weight stigma must represent a central component of any viable obesity care agenda.

Physical Therapists' Use and Alteration of Standardized Assessments of Motor Function in Children.

PURPOSE: This study presents survey responses of pediatric physical therapists' use and alteration of standardized assessments of motor function in children aged 2 to 10 years. METHODS: Electronic and paper surveys were distributed to practicing physical therapists through the APTA Academy of Pediatric Physical Therapy electronic newsletter and 2 national conferences. Data were analyzed by response frequencies, qualitative responses, and χ(2) analyses for demographic characteristics. RESULTS: A total of 497 pediatric physical therapists responded. Most (93%) reported using standardized assessments, with the majority (84%) reporting the normative scores. Almost all respondents (94%) also reported that they at least occasionally modify assessments. CONCLUSION: Standardized assessments are used by most therapists, but the high use of modifications during testing is concerning. Survey reports from therapists indicate a disconnect between standardized assessments and the needs of the child, leaving clinicians working to report required scores while maintaining validity of testing procedures.

Effects of Two Football Stud Types on Knee and Ankle Kinetics of Single-Leg Land-Cut and 180° Cut Movements on Infilled Synthetic Turf.

Higher ACL injury rates have been recorded in cleats with higher torsional resistance in American football, which warrants better understanding of shoe/stud-dependent joint kinetics. The purpose of this study was to determine differences in knee and ankle kinetics during single-leg land cuts and 180° cuts on synthetic infilled turf while wearing 3 types of shoes. Fourteen recreational football players performed single-leg land cuts and 180° cuts in nonstudded running shoes (RS) and in football shoes with natural (NTS) and synthetic turf studs (STS). Knee and ankle kinetic variables were analyzed with a 3 × 2 (shoe × movement) repeated-measures ANOVA (P < .05). A significant shoe-by-movement interaction was found in loading response peak knee adduction moments, with NTS producing smaller moments compared with both STS and RS only in 180° cuts. Reduced peak negative plantar flexor powers were also found in NTS compared with STS. The single-leg land cut produced greater loading response and push-off peak knee extensor moments, as well as peak negative and positive extensor and plantar flexor powers, but smaller loading peak knee adduction moments and push-off peak ankle eversion moments than 180° cuts. Overall, the STS and 180° cuts resulted in greater frontal plane knee loading and should be monitored for possible increased ACL injury risks.

Effects of two football stud configurations on biomechanical characteristics of single-leg landing and cutting movements on infilled synthetic turf.

Multiple playing surfaces and footwear used in American football warrant a better understanding of relationship between different combinations of turf and footwear. The purpose of this study was to examine effects of shoe and stud types on ground reaction force (GRF) and ankle and knee kinematics of a 180° cut and a single-leg 90° land-cut on synthetic turf. Fourteen recreational football players performed five trials of the 180° cut and 90° land-cut in three shoe conditions: non-studded running shoe, and football shoe with natural and synthetic turf studs. Variables were analyzed with a 3 × 2 (shoe × movement) repeated measures analysis of variance (p < 0.05). Peak vertical GRF (p < 0.001) and loading rate (p < 0.001) were greater during 90° land-cut than 180° cut. For 180° cut, natural turf studs produced smaller peak medial GRFs compared to synthetic turf studs and non-studded shoe (p = 0.012). For land-cut, peak eversion velocity was reduced in running shoes compared to natural (p = 0.016) and synthetic (p = 0.002) turf studs. The 90° land-cut movement resulted in greater peak vertical GRF and loading rate compared to the 180° cut. Overall, increased GRFs in the 90° land-cut movement may increase the chance of injury.

Gait biomechanics of a second generation unstable shoe.

The recent popularity of unstable shoes has sparked much interest in the efficacy of the shoe design. Anecdotal evidence suggests that earlier designs appear bulky and less aesthetically appealing for everyday use. The purpose of this study was to examine effects of a second generation unstable shoe on center of pressure (COP), ground reaction force (GRF), kinematics, and kinetics of the ankle joint during level walking at normal and fast speeds. In addition, findings were compared with results from the first generation shoe. Fourteen healthy males performed five successful level walking trials in four testing conditions: walking in unstable and control shoes at normal (1.3 m/s) and fast (1.8 m/s) speeds. The unstable shoe resulted in an increase in mediolateral COP displacement, first peak vertical GRF loading rate, braking GRF, ankle eversion range of motion (ROM), and inversion moment; as well as a decrease in anteroposterior COP displacement, second peak vertical GRF, ankle plantarflexion ROM, and dorsiflexion moment. Only minor differences were found between the shoe generations. Results of the generational comparisons suggest that the lower-profile second generation shoe may be as effective at achieving the desired unstable effects while promoting a smoother transition from heel contact through toe off compared with the first generation shoe.

RE-AIM: evidence-based standards and a Web resource to improve translation of research into practice.

BACKGROUND: Health services data indicate that under present conditions evidence-based medical and preventive practices are not consistently implemented in clinical practice and affect the quality of care provided to patients. Operating with similar conditions and resources, it is unlikely that evidence-based behavioral medicine (EBBM) practices will be more successfully implemented. PURPOSE: In this article we propose ways to help improve the implementation of EBBM practice. METHODS: This article describes the RE-AIM (Reach, Efficacy/Effectiveness, Adoption, Implementation, and Maintenance) framework that is available on a free-use Web site (http://www.re-aim.org), which offers practical research translation tools, resources, and support for program planners, community leaders, and researchers. The material located at www.re-aim.org can be used to help anticipate and overcome likely barriers to dissemination and to estimate eventual public health impact. RESULTS: Data on Web site utilization and lessons learned thus far in its implementation are presented. CONCLUSIONS: Scientists and public health leaders should devote greater attention to reporting practice-oriented issues such as generalizability, breadth of application, and pragmatic and setting or contextual issues in addition to the current focus on internal validity issues. We hope that this and similar efforts will assist EBBM interventions to have broader applications, be consistently implemented, and be sustained.