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Importance High-quality evidence regarding suppressive valacyclovir treatment in herpes zoster ophthalmicus (HZO) is necessary to guide care. Objective To determine whether suppressive valacyclovir compared with placebo delays the occurrence of new or worsening stromal keratitis (SK), endothelial keratitis (EK), iritis, or dendriform epithelial keratitis (DEK) during 12 months of treatment and if treatment benefit persisted at 18 months (secondary end point). Design, Setting, and Participants The Zoster Eye Disease Study (ZEDS) was a randomized clinical trial conducted in 95 sites from November 2017 to June 2024. Immunocompetent, nonpregnant adults with a history of an HZO rash, documented active keratitis or iritis within 1 year, and an estimated glomerular filtration rate of 45 mL/min/1.73 m 2 or greater were eligible. After determined to be eligible, participants were randomized in 4 strata: age at onset (<60 years vs ≥60 years) and disease duration (<6 months vs ≥6 months). Interventions A total of 12 months of double-masked daily valacyclovir, 1000 mg, or placebo. Main Outcomes and Measures The primary outcome was time to first occurrence within 12 months of new or worsening SK, EK, iritis, or DEK. Results A total of 527 participants (median [IQR] age, 60 [50-68] years; 266 female [50.5%]; 266 in the valacyclovir group; 261 in the placebo group) were randomized in 4 strata; 481 completed 12 months, and 460 completed 18 months. Data were analyzed by intention to treat. At 12 months, primary end points occurred in 86 participants (33%) assigned to placebo and 74 (28%) assigned to valacyclovir, and at 18 months in 104 participants (40%) assigned to placebo and 86 (32%) assigned to valacyclovir. The hazard ratio (HR) of the primary end point at 12 months was 0.77 for participants taking valacyclovir vs placebo (HR, 0.77; adjusted 95% CI, 0.56-1.05; P = .09) and 0.73 at the secondary end point at 18 months (HR, 0.73; adjusted 95% CI, 0.55-0.97; P = .03). There was a reduction of multiple other secondary end points at 12 months (HR, 0.70; 95% CI, 0.52-0.95; P = .02) and 18 months (HR, 0.72; 95% CI, 0.55-0.95; P = .02). Conclusions and Relevance Although the primary outcome did not show a benefit of suppressive valacyclovir treatment, secondary study outcomes showed treatment superiority at the 18-month end point and reduced number of multiple episodes of keratitis or iritis at both 12 and 18 months. These results support consideration of 1 year of suppressive valacyclovir treatment for HZO. Trial Registration ClinicalTrials.gov Identifier: NCT03134196

Importance Evidence regarding suppressive valacyclovir treatment on postherpetic neuralgia is necessary to guide care. Objective To test the hypothesis that suppressive treatment with 1000 mg/d of oral valacyclovir for 12 months reduces the prevalence, severity, and duration of postherpetic neuralgia compared with placebo at 12 and 18 months in participants with herpes zoster ophthalmicus (HZO). Design, Setting, and Participants Multicenter, placebo-controlled randomized clinical trial including 527 immunocompetent, nonpregnant adults with history of HZO rash, documented keratitis, or iritis within 1 year and an estimated glomerular filtration rate of 45 mL/min/1.73 m 2 or greater. The study was conducted at 95 participating sites (in Canada, New Zealand, and the US) from November 2017 to June 2024 and participant visits occurred every 3 months. Intervention Treatment with 1000 mg/d of valacyclovir or placebo for 12 months. Main Outcomes and Measures Prevalence of postherpetic neuralgia, severity as determined by pain score (a score of ≥3 on a scale of 1-10), pain duration (≥3 months after HZO onset), and total daily dose of pain medication. Results Of the 527 participants (490 completed 12 months of treatment and 460 completed 18 months), 73 (14%) had postherpetic neuralgia and were analyzed by age at HZO onset (<60 years or ≥60 years) and disease duration (recent [<6 months] or chronic [≥6 months]). Of the 73 participants with postherpetic neuralgia (34 in the valacyclovir group and 39 in the placebo group), the mean age was 62.4 years (SD, 13.6 years), 59% were female, 5% were Black or African American, and 10% were Hispanic. The prevalence of postherpetic neuralgia at 12 months was not reduced by valacyclovir (12/32 [38%]) compared with placebo (14/35 [40%]) (between-group difference, 2.5% [95% CI, −20.8% to 25.8%]; P >.99). The participants who were younger than 60 years at HZO onset and had a chronic disease duration had lower pain scores in the valacyclovir group (mean score, 0.3 [SD, 0.9]) vs the placebo group (mean score, 0.8 [SD, 1.9]) at 12 months ( P = .045) and at 18 months (mean score, 0.2 [SD, 0.9] vs 1.0 [SD, 2.3], respectively; P = .02). There was a decrease in pain duration in the valacyclovir group at 18 months (mean, 13.6 [SD, 11.4] months) vs the placebo group (mean, 18.7 [SD, 29.5] months) (linear mixed-effects model between-group difference, −3.39 months [95% CI, −6.73 to −0.04 months]; P = .046). The total daily dose of neuropathic pain medication was lower in the valacyclovir group (mean, 271.4 [SD, 593.8] mg/d) vs the placebo group (mean, 363.4 [SD, 592.2] mg/d) at 12 months (linear mixed-effects model P = .006) and at 18 months (mean, 209.0 [SD, 412.8] mg/d vs 286.2 [SD, 577.9] mg/d, respectively; linear mixed-effects model P = .01). Conclusions and Relevance One year of suppressive treatment with valacyclovir was associated with a lower dosage of neuropathic pain medication. Participants in the valacyclovir group, who were younger at HZO onset and had a chronic disease duration, had lower pain scores. These secondary outcomes support consideration of 1 year of suppressive treatment with valacyclovir to reduce dosage of pain medications and pain due to HZO. Trial Registration ClinicalTrials.gov Identifier: NCT03134196

Abstract The substantial carbon footprint imparted by medical services warrants increased attention to their environmental impact. National guideline organizations such as the US Preventive Services Task Force (USPSTF) recommend multiple modalities for average-risk colorectal cancer (CRC) screening with varying resource intensity. The aim of this study was to quantify the environmental burden for 2 of the most used CRC screening modalities, colonoscopy and the multi-target stool DNA (mt-sDNA) test. A validated CRC microsimulation model was used to estimate the number of screening and follow-up tests for a cohort of 1 million average-risk individuals who underwent screening between ages 45 and 75. Component resources used for mt-sDNA, including waste products, energy, and transportation for colonoscopy and mt-sDNA, were collected from January 1, 2023, to January 1, 2024, and converted to carbon-equivalent emissions. Resources used for colonoscopy were captured from the literature. Resources devoted to screening colonoscopy were substantially (59%) higher than those to mt-sDNA, even when including follow-up colonoscopy. Of note, follow-up colonoscopy accounted for the majority (64%) of total emissions for the mt-sDNA screening strategy. Compared with colonoscopy screening, mt-sDNA substantially reduces the carbon emissions attributable to population-level CRC screening. Environmental impact should be included as a factor when choosing among guideline-recommended CRC screening strategies.

Abstract Based on expert consensus, the American Society of Transplantation recommends 7–14 days of preventive antibiotic therapy for solid organ transplant recipients from donors with positive blood cultures. We evaluated management and outcomes of kidney transplant recipients from these donors.

OBJECTIVE The American Association of Neurological Surgeons (AANS) and Congress of Neurological Surgeons (CNS) Section on Pediatric Neurological Surgery domestic traveling fellowship was created to cover the travel and living expenses for a North American neurosurgery resident for 1 month at another institution to gain experience in pediatric neurosurgery. The objective of this work was to guide future direction by surveying past recipients about the fellowship and its impact on their training and career. METHODS Historical data have been maintained by the AANS/CNS Executive Committee and past and current chairs of the Traveling Fellowship Subcommittee. A 10-question REDCap survey was emailed to all previous fellowship recipients. RESULTS There have been 58 recipients of the traveling fellowship since 1998. The most common host program was Boston Children’s Hospital (n = 21), followed by The Hospital for Sick Children (n = 12). Excluding recent recipients after 2017 who may still be working toward certification, 20 of 38 (53%) recipients have been certified by the American Board of Pediatric Neurological Surgery (ABPNS). Twenty-four of 49 (49%) recipients completed the survey. Twenty (83.3%) respondents were either ABPNS certified or planning to seek certification, 17 (70.8%) respondents’ practices consisted of > 50% patients aged ≤ 21 years, and 18 (75%) spent 4–8 weeks at the host program, which was longer than the 1 month funded by the stipend. Twenty-two (91.7%) respondents would recommend the traveling fellowship to a resident interested in pediatric neurosurgery, and 18 (75%) believed the traveling fellowship helped them decide to pursue a career in pediatric neurosurgery, while 17 (70.8%) found that the professional connections they made were the most useful aspect of the fellowship. Fifteen (62.5%) respondents believed that the stipend of $2500 was inadequate to cover the cost of traveling and housing. CONCLUSIONS The majority of respondents are currently practicing pediatric neurosurgeons, would recommend the traveling fellowship to residents interested in neurosurgery, and believed that the experience helped them decide to pursue a career in pediatric neurosurgery. Opportunities for improvement include increasing the stipend to more appropriately fund rotations that have mostly been longer than 1 month.

BACKGROUND: Catheter ablation of ventricular arrhythmias, one of the most rapidly growing procedures in cardiac electrophysiology, is associated with magnetic resonance imaging–detected brain lesions in more than half of cases. Although a retrograde aortic approach is conventional, modern tools enable entry through a transseptal approach that may avoid embolization of debris from the arterial system. We sought to test the hypothesis that a transseptal puncture would mitigate brain injury compared with a retrograde aortic approach. METHODS: The TRAVERSE trial (Transseptal Versus Retrograde Aortic Ventricular Entry to Reduce Systemic Emboli) was a multicenter randomized controlled comparative effectiveness trial. Patients with left ventricular arrhythmias undergoing catheter ablation procedures were randomly assigned to a transseptal puncture approach compared (1:1) with a retrograde aortic approach. The primary outcome was the presence of an acute brain lesion detected by magnetic resonance imaging. Secondary outcomes included clinically manifest complications, procedural efficacy, and 6-month neurocognitive assessments. RESULTS: Among the 62 patients randomly assigned to a retrograde aortic approach with postoperative brain magnetic resonance imaging, 28 (45%) exhibited an acute brain lesion compared with 19 of the 69 (28%) of those randomized to a transseptal puncture ( P =0.036). No differences in clinically manifest complications or procedural efficacy were observed. More patients in the retrograde aortic arm were categorized as having a high likelihood of cognitive impairment at 6 months (33% compared with 19% of those in the transseptal arm), but substantial loss to follow-up was present. CONCLUSIONS: Among patients undergoing left ventricular catheter ablation procedures, a transseptal approach reduced the risk of acute brain lesions by nearly half compared with a retrograde aortic approach without sacrificing safety or efficacy. Given a likely embolic pathogenesis, the brain magnetic resonance imaging findings may reflect a propensity to other organ damage; these findings may extend to other procedures requiring left ventricular entry. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03946072.

Abstract Background Inter‐fractional and intra‐fractional positioning and motion monitoring based on implanted fiducials through kilovoltage (kV) imaging is a cost‐effective approach to enhance intact prostate radiotherapy treatment accuracy. However, comprehensive studies for three‐dimensional (3D) position extraction and the corrective action threshold are lacking. Purpose To develop and verify a fiducial motion monitoring system with 3D position information based on triggered kV images taken during treatment delivery, and to comprehensively evaluate the recommended thresholds for corrective action during treatment. Methods An in‐house fiducial triangulation algorithm was developed to monitor fiducial positions using subsequent kV triggered images. The precision of fiducial triangulation and motion detection was validated on a pelvis phantom with four fiducial inserts. A retrospective study was conducted on prostate cancer patients who received either moderately hypofractionated radiotherapy (MHRT, n = 16) or stereotactic body radiotherapy (SBRT, n = 12), categorized by endo‐rectal balloon (ERB) use. Intra‐fractional positions relative to isocenter were computed, and these positions were analyzed in comparison to the original marker locations of the patient's treatment plan. A linear regression fit was used per fraction to determine correlation coefficients between motions in the left–right (LR), superior–inferior (SI), and anterior–posterior (AP) directions. Average fraction time (AFT) of treatment was reported based on the observed average time spent on steps in the workflow and the percentage of fiducials caught outside of the current two‐dimensional (2D) tolerance threshold of 5 mm. The observed 3D offsets were used to estimate AFT for various 3D tolerance thresholds. Results Overall, our triangulation method proved to be very precise for static cases, where phantom measurements revealed a fiducial position triangulation precision of mm for stationary targets, but had a spread of mm for targets with 1 mm of motion. Employing triangulation, true motion exceeding 5 mm was detected above 4.0 mm in magnitude 90.9% of the time, a noticeable improvement in comparison to the 28%–65% successful detection rate reported by 2D projection methods. Most detection errors were attributed to depth disparity. Similar to other reports, correlation coefficients for intra‐fractional motion generally indicated no LR/SI, no LR/AP, and weak positive SI/AP correlations for MHRT and SBRT patients. Offsets beyond a 3D tolerance threshold of 5 mm were observed at a rate of 4.25%–5.25%, while the 5 mm 2D out‐of‐tolerance catch‐rate was 1.6%. The AFT was 8.1–8.2 min using the 2D tolerance threshold of 5 mm. In comparison, the estimated AFT for the proposed 3D tolerance monitoring of offsets beyond 2–5 mm was slightly higher at 8.2–10.9 min due to the higher amount of out‐of‐tolerance instances for the higher precision intra‐fractional motion management. Conclusions Our study showcases a promising subsequent kV‐based triangulation method for intra‐fractional prostate motion monitoring. Acquiring 3D motion information results in higher out‐of‐tolerance catch‐rates particularly in the depth dimension of the kV images, which is perpendicular to the treatment beam. Failure to properly observe and catch these offsets would result in sub‐optimal conformality and accuracy of the dose delivery.