Citations

OBJECTIVE The Centers for Medicare & Medicaid Services (CMS) requires a low C-peptide level for insulin pump coverage unless the individual is β-cell autoantibody positive, which precludes coverage of automated insulin delivery (AID) systems for many people with type 2 diabetes. RESEARCH DESIGN AND METHODS In the Randomized Trial Evaluating the Efficacy and Safety of Control-IQ+ Technology in Adults With Type 2 Diabetes Using Basal-Bolus Insulin Therapy study evaluating the t:slim X2 insulin pump with Control-IQ+ technology, adults with insulin-treated type 2 diabetes were categorized into high C-peptide (n = 195) and low C-peptide (n = 59) groups based on CMS criteria. RESULTS In the AID group, mean HbA1c decreased from baseline by 0.8%, which was significantly greater than in the control group with both high (P < 0.001) and low (P = 0.02) C-peptide levels. Results were similar in participants ≥65 years old. CONCLUSIONS The benefit of AID is present with high and low C-peptide levels. Thus, requiring a low C-peptide level as a prerequisite for AID therapy is not warranted.

Importance Advances in Alzheimer disease (AD) have shifted research focus to earlier disease stages, necessitating more scalable approaches to identify cognitively unimpaired individuals with amyloid β (Aβ) pathology. Objective To assess the utility of plasma phosphorylated tau 217 (p-tau217) for classifying Aβ status in cognitively unimpaired individuals, both as a stand-alone test and in a 2-step approach where positive plasma results were confirmed using a second modality (Aβ positron emission tomography [PET] or cerebrospinal fluid [CSF]). Design, Setting, and Participants This cross-sectional cohort study used data collected between June 2009 and March 2024. We included 2916 cognitively unimpaired participants from 12 international independent observational cohorts in the US, Europe, Australia, and Canada with available plasma p-tau217 levels and CSF or PET Aβ biomarkers. Performance comparisons between mass spectrometry and immunoassay-based p-tau217 measurements were also performed (n = 964). Exposures Plasma p-tau217 levels measured by immunoassay. Main Outcome and Measures Aβ status, determined by CSF or Aβ PET biomarkers. Results Participants had a mean (SD) age of 66.9 (9.9) years; 971 (33.3%) were Aβ positive by either CSF or PET, 1667 (57.2%) were women, and 1108 (38.1%) carried at least 1 APOE ε4 allele. As a stand-alone test, plasma p-tau217 achieved a positive predictive value (PPV) of 79% (95% CI, 74-84) and an overall accuracy of 81% (95% CI, 80-82). In a 2-step workflow, the PPV and accuracy significantly increased to 91% (95% CI, 86-95). While this approach required screening of 677 individuals with plasma p-tau217 to identify 100 Aβ-positive individuals, compared to 536 participants when using PET alone, it reduced the need for PET testing to 124. Immunoassays demonstrated comparable PPVs to mass spectrometry (80% [95% CI, 74-86] vs 85% [95% CI, 81-90]; P = .12) but significantly lower overall accuracy (82% [95% CI, 79-84]% vs 88 [95% CI, 86-90]; P < .001) and true Aβ-positive detection rate (49% [95% CI, 43-55] vs 69% [95% CI, 64-75]; P < .001). Conclusions and Relevance The findings highlight the potential of plasma p-tau217 as a stand-alone test—or when used in a sequential 2-step approach alongside PET or CSF testing—as a cost-effective, scalable, and minimally burdensome strategy for identifying preclinical AD. Tailored screening workflows that incorporate p-tau217 can improve efficiency in participant selection for preclinical AD trials and, in the future, help guide access to disease-modifying treatments.

IntroductionAlcohol withdrawal syndrome (AWS) is among the most severe components of alcohol dependence (AD). Severe AWS, especially complicated with seizures and delirium, was a common reason for medical complications and death. The introduction of benzodiazepines decreased but did not eliminate those risks. The definition of AWS evolved in different versions of Diagnostic and Statistical Manual for Mental Disorders (DSM) from having hand tremor plus one or more other symptoms in DSM-III-R to any two or more symptoms in DSM-IV, which was retained in the current version of DSM-5.ObjectivesComparing subgroups of individuals with AUD based on AWS symptoms profile to define phenotypes for investigation of biological underpinnings of AWS phenomenology and treatment response.MethodsTreatment-seeking individuals diagnosed with DSM-IV alcohol dependence (AD; n=473; 35.5% females) were assessed with Psychiatric Research Interview for Substance and Mental Disorders (PRISM), Timeline Follow back (past 90 days) alcohol consumption, Penn Alcohol Craving Scale (PACS), Pittsburgh Sleep Quality Index (PSQI), Patient Health Questionnaire-9 (PHQ9), and General Anxiety Disorder-7 (GAD-7). Latent class analysis was used to classify subjects according to lifetime prevalence of AWS symptoms according to DSM-III-R or DSM-IV/5. Demographic and other clinical variables were compared among clusters by linear model ANOVA and chi-squared test.ResultsFour clusters were identified: subjects with (1) no history of meeting any AWS criteria (n=50); (4) with complete number of AWS symptoms, meeting both DSM definitions (n=259); and two clusters of subjects with smaller number of AWS symptoms: (3) those meeting only DSM-IV/5 criteria (n=94) and (2) those also meeting DSM-III-R criteria (n=70). Compared to cluster 2, the Cluster 3 members had higher frequency of anxiety, insomnia, and restlessness during withdrawal. The clusters also differed in the total number of drinks (p=0.021), average drinks per drinking days (p=0.013), history of anxiety disorder (p=0.006), substance-induced depression (p=0.019), and higher scores of PSQI (p<0.001), PHQ9 (p<0.001), and GAD-7 (p<0.001) with a relative increase in frequency between clusters as follows 1<2<3<4. Group 4 also had the highest percentages of subjects with history of seizure, delirium or hallucinations.ConclusionsDifferent definitions of AWS capture clusters of AD patients with different symptomatology, comorbidity and consumption patterns. Understanding of biological underpinnings behind those differences may guide improvement in personalized treatment selection.Disclosure of InterestNone Declared

Objectives To evaluate whether patients with systemic lupus erythematosus (SLE) have different nailfold videocapillaroscopy (NVC) findings compared with healthy controls (HCs) and whether there is an association between NVC abnormalities and disease activity, clinical and/or laboratory features in SLE. Methods This is an observational, multicentre, international, matched case–control study. 381 subjects (203 patients with SLE and 178 HCs) were enrolled from 16 centres in 10 countries. Clinical and laboratory data were collected using ad hoc forms. 5861 NVC images were acquired, coded and uploaded for central blinded analysis. Results A normal NVC pattern was observed in most patients with SLE (86.6%) and, a significantly higher frequency of NVC abnormalities such as enlarged and giant capillaries, microhaemorrhages and irregular nail bed architecture (p<0.001) were found in the remaining patients. Multiple correspondence analysis outlined two NVC patterns, one of which, the more severe (cluster 2), present in 12% of patients, was characterised by a higher prevalence of lower capillary density, abnormally shaped and enlarged capillaries and irregular nail bed architecture. NVC cluster 2 had significantly higher disease activity compared with cluster 1 for both Systemic Lupus Erythematosus Disease Activity Index cut-off points ≥3 and ≥4 (p=0.016 and p=0.028, respectively). SLE with ‘more severe’ NVC pattern (cluster 2) have a significantly higher frequency of arthritis, renal involvement and ongoing glucocorticoid therapy, whereas serositis was significantly associated with ‘less severe’ NVC pattern (cluster 1). Conclusions This study has shown that changes in NVC patterns are associated with important aspects of SLE disease activity. Future prospective studies are needed to further support the use of NVC in SLE monitoring. Trial registration number NCT02801812.

OBJECTIVE Open resective surgery (ORS) has become the standard of care for focal drug-resistant epilepsy (DRE). However, minimally invasive surgical alternatives, such as laser interstitial thermal therapy (LITT), have also been shown to be safe and effective. A meta-analysis comparing both treatments is warranted to assess the benefits of each modality for focal DRE. METHODS A literature search was conducted until March 14, 2024, to identify studies comparing LITT and ORS in patients with DRE. The primary outcomes included seizure freedom (SF), length of hospital stay (LHS), and complication rate (CR). Subgroup analyses were performed based on age, epilepsy etiology, and propensity score–matched (PSM) studies. RESULTS Of 558 articles, 15 cohort studies met the authors’ inclusion criteria, encompassing 3873 patients for analysis. The rate of SF in the LITT group was 52.5% (95% CI 0.453–0.597, I 2 = 47.4%) and 67.1% (95% CI 0.602–0.739, I 2 = 57.4%) for the ORS group. LITT showed a significantly lower rate of SF compared to ORS (risk ratio [RR] 0.78, 95% CI 0.70–0.88, p ≤ 0.0001). However, when PSM studies (RR 0.85, 95% CI 0.63–1.15, p = 0.30) and studies on patients with temporal lobe epilepsy (TLE) (RR 0.88, 95% CI 0.67–1.14, p = 0.34) were analyzed, the SF rates were similar. Patients who underwent LITT had a significantly shorter LHS (mean difference 2.95 days, 95% CI 1.12–4.78, p < 0.00001), lower CR (RR 0.54, 95% CI 0.37–0.79, p < 0.002, I 2 = 32%), lower rate of ischemic stroke (RR 0.15, 95% CI 0.04–0.65, p = 0.01), and lower rate of permanent neurological deficits (RR 0.13, 95% CI 0.05–0.36, p < 0.0001). CONCLUSIONS Across unmatched studies evaluating focal DRE, ORS showed a higher rate of SF. However, pooled matched-cohort analyses showed no difference between interventions in achieving SF, a trend also noted in the authors’ PSM TLE sample. LITT, however, offered significantly shorter LHS and lower CRs. Future prospective studies should match patient populations to control for confounding factors and assess key outcomes, such as postoperative neurocognitive follow-up and quality of life measurements, in order to fully evaluate the risks and benefits of each approach.

Abstract Context Patients with endogenous hypercortisolism experience glucocorticoid withdrawal syndrome (GWS) after surgery. Meditation may be an effective intervention to alleviate the severity of GWS. Objective To determine the acceptability of a portable, wearable electroencephalography device for guided meditation (MUSE headband) and the impact of MUSE use on GWS and quality of life 12 weeks postsurgery. Methods We conducted a single-center prospective cohort study of adults with endogenous hypercortisolism undergoing curative surgery from 2019 to 2024. Patients had baseline and postsurgical assessments over 12 weeks. The study comprised patients using MUSE for ≥ 6 weeks (MUSE cohort) and patients matched by age, sex, BMI, hypercortisolism type, and glucocorticoid type at 1:4 ratio. Quality of life and GWS symptoms were assessed with AddiQoL, CushingQoL, and 36-item Short Form Health Survey mental and physical component (SF-36 MCS and PCS) questionnaires. Results MUSE was offered to 52 patients, and 22 (42%) used MUSE for ≥ 6 weeks within 12 weeks after surgery. At baseline, compared to 88 matched subjects, 22 MUSE participants demonstrated similar prevalence of comorbidities and clinical and biochemical hypercortisolism severity, but lower AddiQoL (mean 73 vs 66, P = .031) and SF-36 MCS (mean 39 vs 33, P = .022). At 12 weeks, these differences in quality of life were no longer present. After adjusting for age, sex, BMI, clinical severity score, and baseline quality of life, MUSE use was an independent predictor of improved SF-36 PCS at 12 weeks postsurgery (beta 4.2, 95% CI: 0.5-7.9, P = .026). Conclusion Postsurgical meditation intervention may improve physical symptoms and accelerate recovery.

Background: Ventricular tachycardia (VT) is a life-threatening arrhythmia frequently observed in structural heart diseases, including LMNA-related cardiomyopathy, a genetic disorder associated with high risk of sudden cardiac death and progressive systolic dysfunction. While catheter ablation is an established therapeutic option for VT, its efficacy in cardiac laminopathy remains poorly defined. Objectives: To synthesize available evidence on the role and outcomes of VT ablation in patients with cardiac laminopathy. Methods: A systematic review and single-arm meta-analysis was performed in accordance with PRISMA guidelines. PubMed, Embase, and Cochrane databases were searched for studies reporting VT ablation outcomes in LMNA-related cardiomyopathy. An inverse variance random-effects model was applied for meta-analysis of proportions. Results: Seven studies (six cohorts, one abstract) comprising 62 patients (mean age 53.2 ± 9.7 years; 85% male; 88% with implantable cardioverter-defibrillator) were included. An endocardial/endo-epicardial approach was used in 93% of cases. Acute procedural success was achieved in 37% (95% CI: 14–63%; I 2 = 27.4%), and 28% required multiple procedures. Over a median follow-up of 26 (9–35) months, VT recurrence occurred in 91% (95% CI: 76–100%; I 2 = 37.2%). All-cause mortality was 54% (95% CI: 39–70%; I 2 = 28%), predominantly from cardiac causes (51%, 95% CI: 25–76%; I 2 = 53%), and 14% (95% CI: 1–34%; I 2 = 42%) underwent heart transplantation. Conclusions: In LMNA-related cardiomyopathy, catheter ablation is associated with high VT recurrence, limited long-term success, and substantial cardiovascular mortality and transplantation rates, underscoring the importance of ICD implantation and the need for alternative strategies, including variant-specific and molecularly targeted therapies.

BACKGROUND AND OBJECTIVES: Embolization is part of multidisciplinary brain arteriovenous malformations (AVMs) treatment, yet safety data for novel liquid embolization agents (LEAs) such as Squid and PHIL remain limited. This study reports complications and outcomes from curative embolization using Onyx, Squid, PHIL, and Glue. METHODS: Adult patients with brain AVMs treated with LEAs from July 2015 to December 2022 were reviewed for intraprocedural technical issues, postoperative hemorrhagic, and ischemic complications. Minor (modified Rankin Scale ≤2) and major complication rate (morbidity/modified Rankin Scale >2), mortality, and 6-month angiographic cure rate were evaluated. RESULTS: In total, 135 patients (62.2% male, mean age 41.7 ± 15.1 years) with 206 embolizations (34% Onyx, 18.9% Squid, 17.5% PHIL, 28.2% Glue) were included. Overall, 87.4% procedures were in ruptured AVMs and 84% treated by the transarterial technique (84%). The 6-month angiographic cure rate was 53.3%, higher when nonadhesive LEAs were used than Glue (65.3% vs 17.6%, P < .001). In adjusted analysis, only eloquent location (odds ratio [OR] = 4.4; P = .007) and Glue (OR = 9.1; 95% CI 2.9-28.9, P < .001) were predictors of lower angiographic occlusion rate, whereas size had an inverse correlation (OR = 0.67; P = .019). Technical procedural complications, hemorrhagic, and ischemic rates were 10.2% (2.2% morbidity), 13.1% (3.7% morbidity and 2.2% mortality), and 9.2% (2.2% morbidity, 0% mortality), respectively, regardless of the preferred LEA. Minor, major complications, and mortality rates were 3.7%, 4.4%, and 2.2%, respectively. Hemorrhage was the major contributor to morbidity and mortality, whereas deep venous drainage was an independent predictor of hemorrhage and mortality. CONCLUSION: PHIL and Squid demonstrated complication and angiographic cure rates comparable with Onyx. However, curative embolization of brain AVMs resulted in only moderate angiographic occlusion. Larger multicenter studies with standardized operator protocols, cost-effectiveness assessments, and extended follow-up are warranted to validate these findings.

Background Although telehealth cardiac rehabilitation (CR) may improve access, there are concerns about its long‐term effectiveness and impact on equity as compared with in‐person CR. Our objective was to tailor a patient‐centered telehealth CR program for diverse populations. Methods CR patients and caregivers were recruited between January and September 2023 from 4 US academic medical centers. Participants engaged in human‐centered design sessions to iteratively refine a telehealth CR program. Sessions had planned topics, but there was variation across sites to account for site‐specific needs and participant feedback. Sessions were qualitatively analyzed using rapid template analysis with preselected behavioral science constructs and other emergent codes. Results The study included 21 participants (71% aged ≥60 years, 48% women, 62% non‐Hispanic White individuals; 90% CR patients, 10% CR caregivers). Participants thought that telehealth CR could be helpful for personalized support at home and convenience but recognized that technology is not always easy to use. Some expressed concerns about the safety of telehealth CR, especially at the beginning, and desired monitoring through a mobile device or video observation of exercise. Safety protocols and technology training were developed, which addressed concerns about telehealth CR. Opportunities for social support with telehealth CR were also desired. From these findings, an implementation toolkit was developed, including a graphic program description, safety plan, home exercise plan for during and after CR, and scripts for technology training and individual and group telehealth visits. Conclusions A patient‐centered telehealth CR program and implementation toolkit were systematically tailored to address the needs of diverse populations.

Importance Obesity is associated with a higher risk of recurrence, mortality, comorbidities, treatment-related adverse effects, and poor quality of life in patients with breast cancer. Scalable interventions are needed to promote weight loss in this population. Objective To evaluate the impact of a remotely delivered weight loss intervention (WLI) on weight change at 1 year in patients with breast cancer and obesity and to explore factors associated with weight change. Design, Setting, and Participants The Breast Cancer Weight Loss trial is a phase 3, randomized clinical trial evaluating the impact of a telephone-based WLI on invasive disease–free survival and other outcomes in women with obesity and early breast cancer at 637 sites across the US and Canada. Participants were enrolled to the study between August 2016 and February 2021. Participants included women with stage II to III, ERBB2 -negative breast cancer and a body mass index (BMI) of 27 or higher. Interventions Participants were randomized to a 2-year, telephone-based WLI plus health education or health education alone control group. Main Outcome and Measures The primary end point for this prespecified secondary analysis was weight change at 1 year. Weight was measured at baseline and 1 year, and changes in weight were compared between groups. Weight change was evaluated with a linear mixed-effects model including treatment group, weight over time, a time-by-group interaction, menopausal status, race and ethnicity, and hormone receptor status. Results A total of 3180 women with breast cancer and BMI of 27 and higher were included in the study; 1591 were randomized to the WLI and 1589 to the control group. At baseline, the mean (SD) age of participants was 53.4 (10.6), and the mean (SD) BMI was 34.4 (5.6). The racial and ethnic breakdown included 406 (12.8%) Black, 231 (7.3%) Hispanic or Latino, 2906 (91.4%) non-Hispanic, and 2555 (80.3%) White participants. WLI participants lost a mean of 4.3 kg (95% CI 3.9-4.6 kg), or 4.7% (95% CI, 4.3%-5.0%) of baseline body weight at 1 year vs control participants, who gained 0.9 kg (95% CI, 0.5-1.3 kg), or 1.0% (95% CI 0.1%-1.4%) of baseline body weight ( P &amp;lt; .001). Participants randomized to WLI experienced significant weight loss (vs control group participants) across demographic and tumor factors. WLI effect differed significantly by menopausal status, with postmenopausal participants having greater weight loss than premenopausal participants, and by race and ethnicity, with Black and Hispanic participants having less weight loss compared to other races and ethnicities. Conclusions and Relevance In this secondary analysis of a randomized clinical trial, a telephone-based WLI induced significant weight loss in patients with breast cancer with overweight and obesity across demographic and treatment factors. Further follow-up of the Breast Cancer Weight Loss trial will evaluate whether the WLI improves disease outcomes. Trial Registration ClinicalTrials.gov Identifier: NCT02750826