Citations

Abstract The newly proposed revised criteria for diagnosis and staging of Alzheimer's disease (AD) by the Alzheimer's Association (AA) Workgroup represent a significant milestone in the field. These criteria offer objective measures for diagnosing and staging biological AD, bridging the gap between research and clinical care. Although implementation feasibility may vary across regions and settings, improving the availability and accuracy of biomarkers, especially plasma biomarkers, is expected to enhance the applicability of these criteria in clinical practice. The Fall 2023 Alzheimer's Association Research Roundtable (AARR) meeting served as a forum for gathering industry perspectives and feedback on these revised criteria, ensuring that the new criteria inform research, clinical trial design, and clinical care. In this article, we outline a summary of the newly proposed “Revised Criteria for Diagnosis and Staging of AD: AA Workgroup” and provide highlights from the AARR meeting in fall 2023. Highlights The Alzheimer's Association Research Roundtable (AARR) convened leaders from industry, academia, and government, to review the Revised Criteria for Diagnosis and Staging of AD: AA Workgroup , and gather industry perspectives and feedback on these revised criteria before its publication. The newly proposed revised criteria for diagnosis and staging of Alzheimer's disease (AD) by the AA's Workgroup represent a significant milestone, offering objective measures for the biological and staging of AD and bridging the gap between research and clinical care. Improving the availability and accuracy of biomarkers, especially blood‐based biomarkers (BBMs) is expected to improve clinical research and enhance the applicability of these criteria in clinical practice.

Background: Limited access to the comprehensive assessment of disorders of the upper aerodigestive tract is a barrier to care in rural health facilities. Assessment of the full aerodigestive tract requires a variety of specialists. The inability to access the necessary specialists can result in misdiagnosis, underdiagnosis, and increased associated mortality. Currently, no single differential diagnostic exam comprehensively assesses all functions of the upper aerodigestive tract to bridge this gap. The purpose of this study is to investigate the feasibility and safety of a novel procedure called ADS that can bridge this gap. Methods: Results from 18,464 ADS procedures were retrospectively analyzed for feasibility, safety and comfort. Results: 96.8% of ADS procedures were successfully completed without complication, confirming the efficacy of the procedure. Conclusions: ADS is a single procedure for the assessment of physiological functions of the upper aerodigestive tract, including swallow, voice, respiration, and cough while also screening for impaired gastric retention and obstructive sleep apnea, which may pose additional urgent and emergent airway threats. ADS may improve health outcomes in underserved populations, e.g., those in a rural community, referred to by other health professionals due to complaints of aerodigestive symptoms and signs.

BACKGROUND Previous epidemiologic studies of autoimmune diseases in the US have included a limited number of diseases or used metaanalyses that rely on different data collection methods and analyses for each disease. METHODS To estimate the prevalence of autoimmune diseases in the US, we used electronic health record data from 6 large medical systems in the US. We developed a software program using common methodology to compute the estimated prevalence of autoimmune diseases alone and in aggregate that can be readily used by other investigators to replicate or modify the analysis over time. RESULTS Our findings indicate that over 15 million people, or 4.6% of the US population, have been diagnosed with at least 1 autoimmune disease from January 1, 2011, to June 1, 2022, and 34% of those are diagnosed with more than 1 autoimmune disease. As expected, females (63% of those with autoimmune disease) were almost twice as likely as males to be diagnosed with an autoimmune disease. We identified the top 20 autoimmune diseases based on prevalence and according to sex and age. CONCLUSION Here, we provide, for what we believe to be the first time, a large-scale prevalence estimate of autoimmune disease in the US by sex and age. FUNDING Autoimmune Registry Inc., the National Heart Lung and Blood Institute, the National Center for Advancing Translational Sciences, the Intramural Research Program of the National Institute of Environmental Health Sciences.

AbstractThe aim of this study was to identify hospital‐based workplace violence (WPV) risk factors with the Haddon Matrix Model (HMM) to determine its potential utility to conceptualize multiple risks for WPV events. This descriptive study utilized two independent convenience samples Data from behavioral emergencies (2014–2015) for patient violence (N = 192) and from health care staff (N = 380) 12‐month violence survey responses (2015) in a Midwestern academic hospital were analyzed. Logistic regression examined patient features associated with physical violence. Survey questions pertained to employee, environment, and cultural factors associated with WPV; responses were examined with Chi‐square and two‐sample t‐tests. Violence risk factors populated the 4 Haddon Matrix domains at pre‐event time frames as Host (worker)‐age/demographics, Agent (patient)‐age/gender, Physical Environment‐door/window structure, and Social Environment‐worker safety. Risks at event time frames populated for Agent—behavior/delirium, and Physical Environment—event medication/patient identification. The Haddon Matrix identification of hospital violence risks indicates its utility as a comprehensive approach to workplace violence.

Abstract Introduction Recent literature suggests growing rates of malpractice claims against Urologists, with the incidence of being sued seeming to be unrelated to one’s professional reputation. These cases provide insight into errors that may lead to litigation. Given national trends of rising malpractice cases, estimates that a Urologist can expect to be sued at least twice in their careers are likely underestimates. Malpractice cases can give insight into the common medical errors rising to the level of litigation. Given the elective nature of procedures within sexual medicine, understanding litigation related to these cases is crucial. Objective We aim to analyze malpractice suits related to men’s health and highlight clinical presentations and legal outcomes. Methods Per STROBE guidelines, we searched the publicly available Thomson Reuters Westlaw legal database for “jury verdicts and settlements” from January 1970 to August 2023 to identify medical malpractice cases in Urology. Patient demographics, clinical presentation, alleged error, and legal outcomes were abstracted during full case review by an independent screener. Cases related to men’s sexual health or fertility that named a urologist as the defendant were fully analyzed. Results A total of 553 Urology cases were extracted, with 23 men’s health related cases subsequently analyzed and summarized in Table 1. The most common conditions associated with litigation were erectile dysfunction (penile prosthesis) (39%), epidydimal pathology (13%), and varicocele (13%). The most common allegations were misdiagnosis (26%), surgical complication (22%), lack of informed consent (22%), and violation of standard of care (22%). Of the 23 cases, 57% ruled “no liability” in favor of the urologist, 39% ruled in favor of the plaintiff with a median award of $335,000 (IQR = 100,000-450,000), and one was settled for $316,338. Among cases ruled as negligent, performing the incorrect procedure, surgical complications, and violating the standard of care were prominent allegations. Florida (26%) and Pennsylvania (17%) had the most cases in this sample. Of note, there were no cases for penile plication, plaque excision, microsurgical cord denervation, vasectomy reversal, or sperm retrieval, and only one for vasectomy. Conclusions This study characterizes malpractice cases related to men’s sexual health naming urologists as defendants. Despite fear of litigation, this review of the Westlaw database revealed only 23 cases related to men’s health since 1970. Moreover, the majority of cases ruled in favor of the Urologist. Obtaining comprehensive informed consent, following national guidelines, and responding appropriately to surgical complications may minimize likelihood of litigation and maximize patient outcomes. Disclosure No.

Abstract Purpose: NFE2L2/KEAP1/CUL3 mutations have been validated for radioresistance in cell-based assays and animal models. However, clinical validation of these biomarkers has been challenging because of multimodality treatment regimens. This study aims to investigate the association between NFE2L2/KEAP1/CUL3 mutations and patient outcomes, including local failure, locoregional failure, disease-free survival (DFS), and overall survival, using samples from a phase III trial in which patients were treated with radiation monotherapy at two controlled doses. Patients and Methods: We investigated NFE2L2/KEAP1/CUL3 mutations in 250 randomized patients with T2N0 glottic squamous cell carcinoma receiving definitive radiotherapy in the NRG/RTOG 9512 trial. A total of 119 patients had available biospecimens that were subjected to amplicon-based next-generation sequencing to assess for the presence of NFE2L2/KEAP1/CUL3 mutations without regard to outcomes. Mutations in NFE2L2/KEAP1/CUL3 were assessed blinded to clinical outcomes. Cox models (two-sided α = 0.05) were used to evaluate the association with clinical outcomes, performed by an independent statistical team. Results: Nineteen of 119 patients (16.0%) had NFE2L2/KEAP1/CUL3 mutations. Patient, treatment, and tumor characteristics were similar between those with and without mutations. Patients with mutation compared with those without had significantly more local failure [HR = 3.50; 95% confidence interval (CI), 1.56–7.89; P = 0.0025] and locoregional failure (HR = 3.80; 95% CI, 1.80–8.03; P = 0.0005). DFS was significantly worse for the mutated compared with the nonmutated group in the first 2 years (HR = 2.88; 95% CI, 1.46–5.66; P = 0.0022). The median DFS was shorter in the mutation group (10.3 months) versus those with intact NFE2L2/KEAP1/CUL3 (4.2 years). Conclusions: NFE2L2/KEAP1/CUL3 mutations may predict radiation treatment failure in T2N0 glottic cancer. See related commentary by Rao, p. 1563

The Quantitative Imaging Biomarkers Alliance Profile for dynamic susceptibility contrast (DSC) MRI and its longitudinal claims for the precision of a DSC MRI–derived quantitative imaging biomarker to assess the relative cerebral blood volume changes in gliomas are summarized.

Objectives: Telemedicine is a growing field, with limited data around its utility supporting pediatric emergency care telephone triage. We instituted telemedicine physician support for nurse telephone triage decisions. When the nursing protocols recommended urgent or emergent care, a telemedicine physician reviewed and modified care urgency if appropriate. Our primary study objectives were to evaluate the proportion of patients who were downgraded to less urgent care and assess for potential harm related to the downgrade in care urgency. Methods: We conducted a retrospective observational cohort study of pediatric telephone calls to the Mayo Clinic Health System nurse triage line that were directed to the emergency department telemedicine physician from January 1, 2019, to December 31, 2019. Electronic medical records of patients whose care urgency was downgraded and presented to medical care within 72 hours of the triage call were reviewed. Results: There were 8559 nurse line calls regarding pediatric patients, 882 of which were referred to the telemedicine physician. Among these, 396/882 (44.9%, 95% confidence interval 41.6–48.3) were downgraded. Of downgraded cases, 198 (50.0%) patients sought care within 72 hours of the original call, of which 193 (97.5%) patients were discharged home from that medical visit and 5 (2.5%) patients required admission. No patients were determined to have suffered harm due to the downgrade of visit urgency. Conclusions: Our data suggests that telemedicine physicians can safely downgrade nurse triage care recommendations for pediatric patients. Most downgraded patients sought outpatient care, avoiding unnecessary utilization of the emergency department without evidence of associated harm.

OBJECTIVE To evaluate a regimen of inhaled Technosphere insulin (TI) plus insulin degludec in adults with type 1 diabetes, who prestudy were predominately using either an automated insulin delivery (AID) system or multiple daily insulin injections (MDI) with continuous glucose monitoring. RESEARCH DESIGN AND METHODS At 19 sites, adults with type 1 diabetes were randomly assigned to TI plus insulin degludec (N = 62) or usual care (UC) with continuation of prestudy insulin delivery method (N = 61) for 17 weeks. RESULTS Prestudy, AID was used by 48% and MDI by 45%. Mean ± SD HbA1c was 7.57% ± 0.97% at baseline and 7.62% ± 1.06% at 17 weeks in the TI group and 7.59% ± 0.80% and 7.54% ± 0.77%, respectively, in the UC group (adjusted difference 0.11%, 95% CI −0.10 to 0.33, P value for noninferiority = 0.01). HbA1c improved from baseline to 17 weeks by >0.5% (5.5 mmol/mol) in 12 (21%) in the TI group and in 3 (5%) in the UC group and worsened by >0.5% (5.5 mmol/mol) in 15 (26%) in the TI group and in 2 (3%) in the UC group. The most common TI side effect was a brief cough; eight participants discontinued TI due to side effects. CONCLUSIONS In adults with type 1 diabetes, HbA1c after 17 weeks with a regimen of TI and degludec was noninferior to UC, which consisted predominately of either AID or MDI. TI should be considered an option for people with type 1 diabetes, particularly those who are motivated to further reduce postprandial hyperglycemia.

Introduction Age correlates with survival in patients (pts) with DLBCL, which has a median age at diagnosis of 67 y. Recent therapeutic advances, including bispecifics and cell therapy, have promising efficacy, but safety and accessibility continue to be limited for older pts. The randomized, global, phase 3 ECHELON-3 study (NCT04404283) demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) with brentuximab vedotin (BV) + lenalidomide (Len) + rituximab (R; BV+Len+R) vs placebo+Len+R in pts with R/R DLBCL after ≥ 2 prior systemic therapies who were ineligible for hematopoietic stem cell transplant and/or chimeric antigen receptor (CAR) T-cell therapy. Here, we present safety and efficacy in pts aged ≥65 y. Methods In ECHELON-3, pts were randomized 1:1 to receive BV (1.2 mg/kg) or placebo every 3 weeks (q3w), in combination with R (375 mg/m2) q3w and Len (20 mg) once daily. Granulocyte colony-stimulating factor was required in all cycles. Efficacy was assessed by investigators per Lugano 2014 classification. The primary endpoint was OS, with key secondary endpoints of PFS and ORR. Other secondary endpoints included detailed safety and tolerability. This subgroup analysis comprises pts aged ≥65 y. P values are descriptive. Results A total of 155 pts aged ≥65 y were enrolled from April 2021 to November 2023 and randomized to BV+Len+R (n=79) or placebo+Len+R (n=76). The median age was 75 y (range, 65-89 y); 54% of pts were male, 59% were White, and 19% were Asian. Twenty-three percent and 54% had Ann Arbor stage III and IV disease, respectively, and 64% had high-intermediate or high International Prognostic Index scores (3-5) at enrollment. The most common DLBCL subtype was DLBCL not otherwise specified (58%). Twenty-nine percent of pts had transformed DLBCL. Approximately half (49%) of pts had primary refractory disease, and 81% had disease refractory to their most recent prior line of therapy. Seventy percent of pts had <1% CD30 expression via IHC; 48% of cases had germinal center B-cell origin. Prior CAR-T was reported in 21.9% of pts. At a median follow-up of 16.8 mo (95% CI, 14.3-19.5 mo), median OS was 15.9 mo (95% CI, 11.7 mo-not estimable [NE]) with BV+Len+R vs 8.5 mo (95% CI, 5.5-11.5 mo) with placebo+Len+R (hazard ratio [HR], 0.540; 95% CI, 0.351-0.830; P=.0043). Median PFS was 5.7 mo (95% CI, 4.1-12.7 mo) with BV+Len+R vs 2.8 mo (95% CI, 1.9-4.1 mo) with placebo+Len+R (HR, 0.478; 95% CI, 0.318-0.718; P=.0003). ORR was 70.9% (95% CI, 59.6%-80.6%) with BV+Len+R vs 46.1% (95% CI, 34.5%-57.9%) with placebo+Len+R (P=.0020); complete response (CR) rate was 45.6% vs 19.7%, respectively. Median time to CR was 1.61 mo with both BV+Len+R and placebo+Len+R (range, 1.2-7.3 vs 0.7-4.6 mo, respectively). Median duration of CR was 18.9 mo (95% CI, 12.4 mo-NE) with BV+Len+R vs 5.4 mo (95% CI, 2.8 mo-NE) with placebo+Len+R (HR, 0.416; 95% CI, 0.139-1.250). In total, 154 pts were evaluable for safety analysis (75 pts in placebo+Len+R group). The median number of cycles was 5 (range, 1-34) vs 3 (range, 1-31) in the BV+Len+R and placebo+Len+R groups, respectively. The percentage of pts with any treatment-emergent adverse event (TEAE) was similar between groups (97% with BV+Len+R and 99% with placebo+Len+R); grade ≥3 TEAEs occurred in 89% of pts in the BV+Len+R group and 76% in the placebo+Len+R group. Serious TEAEs and TEAEs leading to death were reported more frequently in the BV+Len+R group (62% and 13%, respectively) than the placebo+Len+R group (47% and 8%, respectively). More pts discontinued study treatment due to TEAEs in the BV+Len+R group than the placebo+Len+R group (20% vs 8%). In total, 39% of pts on BV+Len+R had a peripheral neuropathy event vs 27% of pts on placebo+Len+R; however, the majority of cases were grade 1 (22% and 17%, respectively). Additional information on older pts will be presented. Conclusions BV+Len+R demonstrated a clinically meaningful improvement in all key efficacy outcomes in pts aged ≥65 y, which is consistent with the overall ECHELON-3 population (median age 74 y; 70.5% of pts aged ≥65 y in BV+Len+R group). Differences in some safety endpoints are likely attributable to longer duration of treatment in the BV+Len+R group. No clinically meaningful safety trends in pts aged ≥65 y were identified. These results suggest that BV+Len+R may be an effective treatment option in older pts with R/R DLBCL.