Faculty Bibliography

INTRODUCTION/BACKGROUND:A variety of rating scales are currently being used to assess symptom severity and quantify symptoms change in attention-deficit/hyperactivity disorder (ADHD) research and clinical practice. This poses difficulties in interpreting scores from different scales in clinical practice and synthesizing data from studies using different scales. We aimed to develop algorithms for converting scores across the ADHD scales most often used in randomized controlled trials (RCTs) of ADHD medications in children/adolescents and adults, and to develop an online tool for implementing the algorithms. METHODS: RESULTS:We linked six commonly used ADHD scales, such as the ADHD Rating Scale (ADHD-RS-IV; investigator-rated) and the Conners' Parent Rating Scale (CPRS-R:S). Spline models most frequently yielded the lowest prediction error, outperforming alternative conversion algorithms for absolute scores in 6 out of 12 univariable models and 8 out of 12 multivariable models. The tool for scores conversion is available at ADHD_Scale_Conversion_Tool. CONCLUSIONS:Our linkage algorithms enable the comparison and harmonization of findings across studies using different ADHD rating scales. Translating scores across scales improves the interpretability of research findings, facilitates future evidence synthesis across studies, and may support clinical practice. Our online tool supports the practical uptake of our results.

BACKGROUND/UNASSIGNED:The long-term efficacy and safety of vutrisiran in hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) were assessed in the HELIOS-A randomized treatment extension (RTE). METHODS/UNASSIGNED:Patients who completed the 18-month, phase 3, open-label HELIOS-A study could enter an open-label RTE with re-randomization 1:1 to vutrisiran 25 mg every 3 months (Q3M) or 50 mg every 6 months (Q6M; transitioned to 25 mg Q3M following an amendment) for up to 42 months (RTE M18 efficacy assessment; RTE M42 safety and transthyretin (TTR) levels). RESULTS/UNASSIGNED: = 73]). Mean serum TTR reduction from study baseline at RTE M42 for the total vutrisiran group was 84.5%. Efficacy was sustained from RTE baseline through RTE M18 in modified Neuropathy Impairment Score +7, Norfolk Quality of Life-Diabetic Neuropathy score, 10-meter walk test, Rasch-built Overall Disability Scale and modified body mass index (mBMI); most patients (67.8%) had stable polyneuropathy disability scores. Most AEs were mild/moderate in severity with no new safety concerns. CONCLUSIONS/UNASSIGNED:Results from the HELIOS-A RTE demonstrate relative stability with only modest changes in disease activity, sustained serum TTR reductions, and an acceptable safety profile with long-term vutrisiran treatment in patients with ATTRv-PN. UNLABELLED:ClinicalTrials.gov: NCT03759379.

Xenotransplantation has been iteratively improved over the last decade in pre-clinical models, with first-in-human clinical trials underway. The 2025 IXA Congress in Geneva was held in parallel with meetings involving World Health Organization leaders to support the development of new guidance on xenotransplantation in this rapidly evolving field. Key scientific themes of the meeting included the introduction of multiple-gene edited pigs for xenotransplantation research and clinical trials, better characterization of innate and adaptive immune responses and xenograft preservation that optimizes ramifications of ischemia-reperfusion injury during implantation. This comes at a time when gene-edited pig organs are being used for human xenotransplantation, a development that demands safety, reproducibility, durability, and a clear mechanistic understanding of rejection and tolerance.

STUDY OBJECTIVES/OBJECTIVE:Clinical demands in the emergency department (ED) may contribute to decision and attention fatigue as clinician time-on-shift increases, impacting patient care. Emergency department pharmacists review orders and intervene to correct problems related to safety and appropriateness. This study's objective was to evaluate and characterize the rate of pharmacist interventions on ED medication orders. We hypothesized that pharmacist interventions would increase with clinician time-on-shift. METHODS:We performed a retrospective study of 2 EDs within a single health system between January 2022 and November 2023. Medication and pharmacy intervention details were extracted and linked to clinician schedules, pharmacist schedules, and ED crowding scores. Mixed-effects logistic regression modeling identified factors associated with pharmacist interventions. RESULTS:Pharmacists intervened on 9,054 (1.5%) of 622,171 medication orders placed by 308 clinicians. Pharmacy intervention rate increased with clinician time-on-shift (odds ratio 1.04 for each hour; 95% confidence interval 1.03 to 1.05), with meaningful variation in this effect between individual clinicians. Stratified by clinician type (attendings, residents, or physician assistants) and shift timing (overnight versus daytime shifts), the association between time-on-shift and pharmacy intervention rate remained positive. Stratified by site (A versus B), the association was positive at site A but not at site B. CONCLUSION/CONCLUSIONS:The likelihood of orders requiring pharmacist interventions increased as ED clinicians' time-on-shift increased. This association was consistently observed across differing clinician types and shift timing, but variable across the 2 sites of the study. Clinical staffing models and quality of care could be improved by addressing stressors and fatigue accumulation informed by this analytical model.

INTRODUCTION/BACKGROUND:We hypothesized that, in patients at high risk for RE, giving sucralfate prophylactically would reduce the need for opioid pain medication. METHODS AND MATERIALS/METHODS:Patients were enrolled from January 2023 to April 2025 at a single tertiary care center. Patients were randomized to receive 1 gram twice a day within the first five fractions of radiotherapy (RT), with frequency increased during RT at clinician discretion, or standard supportive care. The proportion of patients who took any opioids over the previous 24 hours at the end of the treatment course was compared between groups using logistic regression with the stratification variables and concurrent chemotherapy status as covariates. RESULTS:The trial was closed early due to lack of differences between arms with 117 patients randomized (n=56 in the experimental arm). Rates of opioid use were 30% in both groups (absolute adjusted decrease in the prophylactic sucralfate arm -0.4%; 95% CI -14%, 13%, p>0.9). Rates of grade 2 - 3 RE were non-significantly lower in the prophylactic sucralfate arm (59% vs 69%, absolute adjusted risk decrease 11%; 95% CI -7.2%, 28%; p=0.2). In patients receiving very high esophageal dose (V60 Gy ≥15%), all controls (n=4) experienced grade 2-3 RE compared to only half of those in the experimental arm (6 of 12) (Fisher's exact test p=0.2). CONCLUSIONS:We did not find evidence to support early use of sucralfate in patients at high risk of radiation esophagitis. Limited medical options for the management of RE warrant the continued need to explore further avenues to combat this painful condition.

IMPORTANCE/UNASSIGNED:Currently, there are no standardized outcome domains or measures in clinical trials for facial aging. Heterogeneity in outcome domains and measurement instruments across clinical trials creates difficulty in directly comparing interventions, determining superior therapies, and developing high-quality meta-analyses. OBJECTIVE/UNASSIGNED:To develop a core outcome set (COS) of essential domains to be reported in clinical trials evaluating the efficacy of interventions for facial aging. EVIDENCE REVIEW/UNASSIGNED:PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials, and CINAHL were searched from September 2005 to September 2015. An updated search of the same databases was performed from September 2015 to February 2026. Studies were included if (1) they were randomized clinical trial or controlled clinical trial in design, (2) they assessed the efficacy or safety of an intervention for facial aging, (3) they were published in English, and (4) they involved human participants. Complementary sources, including patient interviews, were used to capture further relevant outcomes. Two rounds of Delphi surveys, followed by consensus meetings, were used to identify outcome domains considered most important by both patient and physician stakeholders. FINDINGS/UNASSIGNED:The final COS consists of 6 outcome domains: (1) overall convenience of treatment; (2) time to return to normal work and social activity; (3) overall assessment of focused area of treatment (at the point in time when treatment is expected to provide peak benefit); (4) duration of treatment effect; (5) severity of persistent local or systemic adverse events, including pigmentary change, skin texture change, delayed healing, scarring, and serious adverse events; and (6) patient satisfaction with treatment. CONCLUSIONS AND RELEVANCE/UNASSIGNED:The 6 outcome domains identified through a Delphi consensus are recommended for reporting in future facial aging trials to ensure that outcomes that matter most to patients and clinicians are measured and that results are comparable across interventions.

BACKGROUND:This study aimed to assess the relationship between coronary CT angiography detected coronary artery disease (CAD) and long-term cardiovascular outcomes among individuals with and without diabetes mellitus (DM). METHODS:A retrospective cohort study of patients undergoing CCTA at two medical centers between 2006 and 2024. Patients with prior CAD, advanced kidney disease, or malignancy were excluded. DM was defined by diagnostic codes or elevated hemoglobin A1c. CCTA findings were categorized as no CAD, nonobstructive CAD (1-49% stenosis), or obstructive CAD (≥ 50% stenosis). The primary outcome was a composite of cardiovascular death (CVD) or myocardial infarction (MI). RESULTS:Among 22,377 patients (median age 56 [IQR 47-65]; 45% women), 3,245 (14.5%) had diabetes. Individuals with diabetes were older and had more cardiovascular risk factors. Obstructive CAD was more frequent in patients with diabetes (33% vs. 19%), whereas no CAD was less common (23% vs. 42%). Over a median follow-up of 6 years (IQR 3.9-9.5), the primary outcome occurred more than twice as often among those with diabetes (7.8% vs. 3.1%; P < 0.001). Event rates increased with CAD severity and remained higher among individuals with diabetes across all categories. After adjustment, obstructive CAD remained significantly associated with the primary outcome in both groups (DM: HR 2.9 [95% CI 1.8-4.6], P < 0.001; non-DM: HR 2.7 [95% CI 2.1-3.4]), p < 0.001). CONCLUSIONS:Among patients undergoing CCTA, CAD was more frequent and severe in those with diabetes, and the risk of CVD or MI increased with CAD severity, approximately doubling in each category when diabetes was present.

BACKGROUND:Apical aneurysms in hypertrophic cardiomyopathy (HCM) have been linked to sudden cardiac death (SCD) and a nidus for thromboembolism. Uncertainty remains regarding the level of risk and significance of aneurysm size. OBJECTIVES/OBJECTIVE:The objective of the study was to determine the rate of SCD events and prevalence of apical thrombus or embolic events by size (maximum transverse dimension). METHODS:Apical aneurysms were identified in 510 patients from 10 centers, followed a median of 4.1 years for SCD events (SCD, appropriate implantable cardioverter defibrillator therapy, and resuscitated SCD) or development of apical thrombus/thromboembolism. Relationship between size and SCD events was analyzed using multivariable Cox proportional hazard models. RESULTS:In 510 HCM patients: 19% had small aneurysms (<10 mm), 39% medium (10-19 mm), 39% large (20-39 mm), and 3% very large (≥40 mm). SCD event rate was 2.1%/year, with risk increasing with increasing aneurysm size: 0.2%/year in small, 2.3%/year in medium, 3.0%/year in large and 8.2%/year in very large (P < 0.001). On multivariable analysis, greater size was associated with SCD events, independent of other risk markers or European Society of Cardiology-SCD score. Either an embolic event (3.6% of patients) or apical thrombus (10% of patients) occurred in 13% of patients and was independently associated with greater aneurysm size, 3% in small to 25% in very large aneurysms (P < 0.001). CONCLUSIONS:In a large cohort of HCM patients with apical aneurysms, rates of SCD events were high, with continuous relationship between size and risk. Small aneurysms (<10 mm) were associated with low risk for SCD events (0.2%/year), whereas aneurysms ≥10 mm with high risk (>2%/year). Although embolic events were uncommon, increasing aneurysm size was associated with the prevalence of apical thrombi.

BACKGROUND:Identifying oral potentially malignant disorders and oral cavity cancer early can lead to better patient outcomes. The guideline panel evaluated the usefulness of light-based adjuncts for screening adults without mucosal abnormalities and for determining the need for biopsy among adults with mucosal abnormalities in the oral cavity or on the lip. TYPES OF STUDIES REVIEWED/METHODS:The authors conducted a living systematic review to evaluate evidence on the benefits and harms of light-based adjuncts and a scoping review to assess people and clinician values and preferences regarding the use of light-based adjuncts and biopsy of mucosal abnormalities. The guideline panel used this evidence to formulate recommendations according to the Grading of Recommendations Assessment, Development and Evaluation Evidence to Decision framework. The framework also guided the panel's consideration of required resources, equity, acceptability, and feasibility in shaping the final recommendations. RESULTS:The guideline panel formulated 2 recommendations and 2 good practice statements. For adults with and without mucosal abnormalities, they formulated conditional recommendations against the use of light-based adjuncts on the basis of very low certainty evidence. The good practice statements urge clinicians to perform a clinical oral examination in all adult patients. CONCLUSIONS AND PRACTICAL IMPLICATIONS/CONCLUSIONS:Biopsy remains the reference standard for establishing a definitive diagnosis of an oral potentially malignant disorder and oral squamous cell carcinoma. All adults should undergo a clinical oral examination in primary care settings. When implementing or adapting these recommendations, local contexts should be considered to promote equitable access to early detection.