Centralized Quality Assurance of Stereotactic Body Radiation Therapy for the Veterans Affairs Cooperative Studies Program Study Number 2005: A Phase 3 Randomized Trial of Lung Cancer Surgery or Stereotactic Radiotherapy for Operable Early-Stage Non-Small Cell Lung Cancer (VALOR).

PURPOSE: The phase 3 Veterans Affairs Lung Cancer Surgery Or Stereotactic Radiotherapy study implemented centralized quality assurance (QA) to mitigate risks of protocol deviations. This report summarizes the quality and compliance of the first 100 participants treated with stereotactic body radiation therapy (SBRT) in this study. METHODS AND MATERIALS: A centralized QA program was developed to credential and monitor study sites to ensure standard-of-care lung SBRT treatments are delivered to participants. Requirements were adapted from protocols established by the National Cancer Institute's Image and Radiation Oncology Core, which provides oversight for clinical trials sponsored by the National Cancer Institute's National Clinical Trials Network. RESULTS: The first 100 lung SBRT treatment plans were reviewed from April 2017 to October 2022. Tumor contours were appropriate in all submissions. Planning target volume (PTV) expansions were less than the minimum 5 mm requirement in 2% of cases. Critical organ-at-risk structures were contoured accurately for the proximal bronchial tree, trachea, esophagus, spinal cord, and brachial plexus in 75%, 92%, 100%, 100%, and 95% of cases, respectively. Prescriptions were appropriate in 98% of cases; 2 central tumors were treated using a peripheral tumor dose prescription while meeting organ-at-risk constraints. PTV V100% (the percentage of target volume that receives 100% or more of the prescription) values were above the protocol-defined minimum of 94% in all but 1 submission. The median dose maximum (Dmax) within the PTV was 125.4% (105.8%-149.0%; SD ± 8.7%), where values reference the percentage of the prescription dose. High-dose conformality (ratio of the volume of the prescription isodose to the volume of the PTV) and intermediate-dose compactness [R50% (ratio of the volume of the half prescription isodose to the volume of the PTV) and D2cm (the maximum dose beyond a 2 cm expansion of the PTV expressed as a percentage of the prescription dose)] were acceptable or deviation acceptable in 100% and 94% of cases, respectively. CONCLUSIONS: The first 100 participants randomized to SBRT in this study were appropriately treated without safety concerns. A response to the incorrect prescriptions led to preventative measures without further recurrences. The program was developed in a health care system without prior experience with a centralized radiation therapy QA program and may serve as a reference for other institutions.

Effect of Pulsed Low-Intensity Ultrasonography on Symptom Relief and Tibiofemoral Articular Cartilage Thickness Among Veterans Affairs Enrollees With Knee Osteoarthritis: A Randomized Clinical Trial.

Importance: Osteoarthritis (OA) is a major cause of disability in the US, with no approved treatments to slow progression, but animal models suggest that pulsed low-intensity ultrasonography (PLIUS) may promote cartilage growth. Objective: To evaluate the efficacy of PLIUS in providing symptom reduction and decreased loss of tibiofemoral cartilage thickness in patients with knee OA. Design, Setting, and Participants: A phase 2A, sham-controlled, parallel, double-blind randomized clinical trial was conducted at 2 Veterans Affairs hospitals in Salt Lake City, Utah, and San Diego, California, from May 22, 2015, to January 31, 2019. Data were analyzed from June 27, 2020, to October 20, 2020. Participants recruited through the US Department of Veterans Affairs (N = 132) with clinical and radiographic evidence of early knee OA were randomly assigned to receive PLIUS or a sham device, self-administered for 20 minutes daily over the medial compartment of the knee. All enrollees participated in a 4-week prerandomization sham run-in period, followed by a 48-week treatment period. Randomization was stratified by study site and Kellgren-Lawrence grades 1 (n = 15), 2 (n = 51), and 3 (n = 66). Intervention: Participants either received 48 weeks of PLIUS or sham ultrasonography. Main Outcomes and Measures: The trial incorporated 2 coprimary outcomes: symptomatic improvement assessed by Outcome Measures in Rheumatology Clinical Trials-Osteoarthritis Research Society International Responder Criteria (ie, met if either >50% improvement in pain and function with at least a 20% absolute improvement of at least 2 of the following 3 factors: improvement by at least 20% [pain, function, and patient global assessment] with at least a 10-mm absolute improvement), and cartilage preservation assessed as change in central medial femoral condyle cartilage thickness by magnetic resonance imaging. Intention-to-treat analysis was used. Results: The mean (SD) participant age was 63.6 (10.7) years and 119 were men (90.2%). The mean (SD) duration of OA symptoms was 13.4 (12.3) years. In the PLIUS group, 70.4% (95% CI, 58.2%-82.6%) of the participants experienced symptomatic improvement, compared with 67.3% (95% CI, 54.9%-79.7%) of participants in the sham group (P = .84); there was no statistically significant difference in response rates between the treatment groups, and the between-group rate difference of 3.1% (95% CI, -14.3% to 20.5%) did not meet the predefined 10% threshold for clinically significant symptomatic improvement from application of PLIUS. At 48 weeks of treatment, central medial femoral condyle cartilage thickness decreased by a mean (SD) of 73.8 (168.1) µm in the PLIUS group and by 42.2 (297.0) µm in the sham group. This 48-week mean change between the 2 groups did not reach statistical significance (P = .44), and the between-group 48-week difference of -31.7 µm (95% CI, -129.0 µm to 65.7 µm) did not meet the predefined threshold. There were 99 nonserious adverse events in the PLIUS group and 89 in the sham group during the trial. No serious adverse events were deemed related to the study device. Conclusions and Relevance: PLIUS, as implemented in this study, demonstrated neither symptomatic benefit nor a decrease in loss of tibiofemoral cartilage thickness in knee OA. Trial Registration: ClinicalTrials.gov Identifier: NCT02034409.

Rivastigmine Transdermal Patch Treatment for Moderate to Severe Cognitive Impairment in Veterans with Traumatic Brain Injury (RiVET Study): A Randomized Clinical Trial.

Cognitive impairment is common in veterans with histories of traumatic brain injury (TBI). Cholinergic deficits have been hypothesized as contributors to this impairment. We report the effects of cholinesterase inhibitor rivastigmine transdermal patch treatment in veterans with TBI and post-traumatic memory impairment. Our objective was to evaluate the efficacy and safety of a 9.5 mg/24 h (10 cm2) rivastigmine patch in veterans of military conflicts with persistent moderate to severe memory impairment at least 12 weeks after TBI. This randomized, outpatient, double-blind, placebo-controlled 12-week trial with an exploratory double-blind phase of an additional 14 weeks was conducted at 5 VA Medical Centers, among veterans with closed, non-penetrating TBI who met or exceeded modified American Congress of Rehabilitation Medicine criteria for mild TBI with verbal memory deficits, as assessed by the Hopkins Verbal Learning Test, Revised (HVLT-R). Patients were randomized 1:1 to rivastigmine or matching placebo patches after a 1-week single-blind, placebo run-in phase. At randomization, patients received 4.6 mg/24 h rivastigmine patches or matching placebo increased to a 9.5 mg/24 h patch after 4 weeks. The primary efficacy outcome measure was the proportion of participants who had at least a five-word improvement on the HVLT-R Total Recall Index (Trials 1-3). A total of 3671 participants were pre-screened, of whom 257 (7.0%) were screened; 96 (37%) randomized, and 94 included in study analyses. Responder rates were 40.8% (20 of 49) and 51.1% (23 of 45) in the rivastigmine and placebo groups, respectively (p = 0.41). A mixed-effect model including treatment, time, and treatment-by-time interaction indicated no significant difference in treatment effect over time between the groups (p = 0.24). Overall, there were no significant differences in changes for all secondary outcomes between the rivastigmine and placebo groups. The most commonly observed adverse events were application site reactions. This trial provides the largest sample to date of veterans with TBI and post-traumatic memory deficits enrolled in a pharmacological trial. Trial Registration: clinicaltrials.gov Identifier: NCT01670526.

Effect of store and forward teledermatology on quality of life: a randomized controlled trial.

IMPORTANCE: Although research on quality of life and dermatologic conditions is well represented in the literature, information on teledermatology's effect on quality of life is virtually absent. OBJECTIVE: To determine the effect of store and forward teledermatology on quality of life. DESIGN: Two-site, parallel-group, superiority randomized controlled trial. SETTING: Dermatology clinics and affiliated sites of primary care at 2 US Department of Veterans Affairs medical facilities. PARTICIPANTS: Patients being referred to a dermatology clinic were randomly assigned, stratified by site, to teledermatology or the conventional consultation process. Among the 392 patients who met the inclusion criteria and were randomized, 326 completed the allocated intervention and were included in the analysis. INTERVENTIONS: Store and forward teledermatology (digital images and a standardized history) or conventional text-based consultation processes were used to manage the dermatology consultations. Patients were followed up for 9 months. MAIN OUTCOME MEASURES: The primary end point was change in Skindex-16 scores, a skin-specific quality-of-life instrument, between baseline and 9 months. A secondary end point was change in Skindex-16 scores between baseline and 3 months. RESULTS: Patients in both randomization groups demonstrated a clinically significant improvement in Skindex-16 scores between baseline and 9 months with no significant difference by randomization group (P = .66, composite score). No significant difference in Skindex-16 scores by randomization group between baseline and 3 months was found (P = .39, composite score). CONCLUSIONS: Compared with the conventional consultation process, store and forward teledermatology did not result in a statistically significant difference in skin-related quality of life at 3 or 9 months after referral. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00488293.