Citations

Abstract INTRODUCTION This ongoing, prospective study examines the effectiveness of methods used to successfully recruit and retain 238 Black older adults in a longitudinal, observational Alzheimer's disease (AD) study. METHODS Recruitment strategies included traditional media, established research registries, speaking engagements, community events, and snowball sampling. Participants were asked to complete an annual office testing session, blood‐based biomarker collection, optional one‐time magnetic resonance imaging (MRI) scan, and community workshop. RESULTS Within the first 22 months of active recruitment, 629 individuals expressed interest in participating, and 238 enrolled in the ongoing study. Of the recruitment methods used, snowball sampling, community events, and speaking engagements were the most effective. DISCUSSION The systemic underrepresentation of Black participants in AD research impacts the ability to generalize research findings and determine the effectiveness and safety of disease‐modifying treatments. Research to slow, stop, or prevent AD remains a top priority but requires diversity in sample representation. Highlights Provide flexible appointments in the evening or weekends, offering transportation assistance, and allowing participants to complete study visits at alternative locations, such as senior centers or community centers. Continuously monitor and analyze recruitment data to identify trends, challenges, and opportunities for improvement. Implement targeted strategies to recruit participants who are underrepresented based on sex, gender, or education to increase representation. Diversify the research team to include members who reflect the racial and cultural backgrounds of the target population, to enhance trust and rapport with prospective participants.

Abstract Introduction/Objective: To assess the clinical utility of the FM/a® chemokine-cytokine assay in diagnosing fibromyalgia at an academic medical center. Methods: We performed a cross-sectional study on 50 patients diagnosed with fibromyalgia at a specialty fibromyalgia clinic between January 1, 2021 through July 31, 2021. Patients completed questionnaires and provided a venous blood sample sent to EpicGenetics, to complete the FM/a® test. Demographic, symptom, and historical data was obtained from chart review. Statistical analysis was performed. Results: Of 50 patients with a clinical diagnosis of fibromyalgia, the FM/a® test was positive in 45 (90%). Performance of the FM/a® test compared to the 2016 ACR criteria yielded an odds ratio of 3.5 with sensitivity of 0.91, specificity of 0.25. Univariate regression demonstrated an area under the curve (AUC) of 0.7337, which improved to 0.89 when adjusted for age, gender, and race. When compared to the 1990 ACR criteria, a positive FM/a® test had an odds ratio of 2.33 with sensitivity 0.92 and specificity 0.17. Univariate regression analysis demonstrated an AUC of 0.571, when adjusted for age, gender and race, AUC was similar at 0.585. Conclusion: The FM/a® test performed well overall, though inferiorly compared to the 1990 and 2016 ACR diagnostic criteria. When adjusted for age, gender, and race the test performed almost equivalently to the 2016 ACR criteria. The FM/a® test may be useful in general clinical practices to differentiate patients who are more likely to have FM.

ABSTRACT Although severe coronavirus disease 2019 (COVID-19) and hospitalization associated with COVID-19 are generally preventable among healthy vaccine recipients, patients with immunosuppression have poor immunogenic responses to COVID-19 vaccines and remain at high risk of infection with SARS-CoV-2 and hospitalization. In addition, monoclonal antibody therapy is limited by the emergence of novel SARS-CoV-2 variants that have serially escaped neutralization. In this context, there is interest in understanding the clinical benefit associated with COVID-19 convalescent plasma collected from persons who have been both naturally infected with SARS-CoV-2 and vaccinated against SARS-CoV-2 (“vax-plasma”). Thus, we report the clinical outcome of 386 immunocompromised outpatients who were diagnosed with COVID-19 and who received contemporary COVID-19-specific therapeutics (standard-of-care group) and a subgroup who also received concomitant treatment with very high titer COVID-19 convalescent plasma (vax-plasma group) with a specific focus on hospitalization rates. The overall hospitalization rate was 2.2% (5 of 225 patients) in the vax-plasma group and 6.2% (10 of 161 patients) in the standard-of-care group, which corresponded to a relative risk reduction of 65% ( P = 0.046). Evidence of efficacy in nonvaccinated patients cannot be inferred from these data because 94% (361 of 386 patients) of patients were vaccinated. In vaccinated patients with immunosuppression and COVID-19, the addition of vax-plasma or very high titer COVID-19 convalescent plasma to COVID-19-specific therapies reduced the risk of disease progression leading to hospitalization. IMPORTANCE As SARS-CoV-2 evolves, new variants of concern (VOCs) have emerged that evade available anti-spike monoclonal antibodies, particularly among immunosuppressed patients. However, high-titer COVID-19 convalescent plasma continues to be effective against VOCs because of its broad-spectrum immunomodulatory properties. Thus, we report clinical outcomes of 386 immunocompromised outpatients who were treated with COVID-19-specific therapeutics and a subgroup also treated with vaccine-boosted convalescent plasma. We found that the administration of vaccine-boosted convalescent plasma was associated with a significantly decreased incidence of hospitalization among immunocompromised COVID-19 outpatients. Our data add to the contemporary data providing evidence to support the clinical utility of high-titer convalescent plasma as antibody replacement therapy in immunocompromised patients.

Background The phase 2 PIONEER‐HCM (Phase 2 Open‐label Pilot Study Evaluating Mavacamten in Subjects With Symptomatic Hypertrophic Cardiomyopathy and Left Ventricular Outflow Tract Obstruction) study showed that mavacamten improved left ventricular outflow tract gradients, exercise capacity, and symptoms in patients with obstructive hypertrophic cardiomyopathy (HCM), but the results of longer‐term treatment are less well described. We report interim results from the PIONEER‐OLE (PIONEER Open‐Label Extension) study, the longest‐term study of mavacamten in patients with symptomatic obstructive HCM. Methods and Results Patients who previously completed PIONEER‐HCM (n=20) were eligible to enroll in PIONEER‐OLE. Patients received oral mavacamten, 5 mg once daily (starting dose), with individualized dose titration at week 6. Evaluations included serial monitoring of safety, echocardiography, Kansas City Cardiomyopathy Questionnaire–Overall Summary Score, and serum NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) levels. Thirteen patients enrolled and received mavacamten (median study duration at data cutoff, 201 weeks). Most patients (92.3%) received β‐blockers concomitantly. Treatment‐emergent adverse events were predominantly mild/moderate. One patient had an isolated reduction in left ventricular ejection fraction to 47%, which recovered and remained normal with continued treatment at a reduced dose. At week 180, mavacamten was associated with New York Heart Association class improvements from baseline (class II to I, n=9; class III to II, n=1; and unchanged, n=2), sustained reductions in left ventricular outflow tract gradients (mean [SD] change from baseline: resting, −50 [55] mm Hg; Valsalva, −70 [41] mm Hg), and serum NT‐proBNP levels (median [interquartile range] change from baseline: −498 [−2184 to −76] ng/L), and improved Kansas City Cardiomyopathy Questionnaire–Overall Summary Score (mean [SD] change from baseline: +17 [16]). Conclusions This long‐term analysis supports the continued safety and effectiveness of mavacamten for >3 years in obstructive HCM. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03496168.

Background: Endovascular thrombectomy (EVT) and intravenous thrombolysis (IVT) outcomes are unclear in patients with pre-stroke dementia or cognitive impairment. Although these individuals make up ~12% of acute stroke patients, they are often excluded from both stroke trials and routine care. This systematic review and meta-analysis explored reperfusion therapy outcomes in this population. Methods: Using the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines, this systematic review investigated studies on acute ischemic stroke patients with dementia or cognitive impairment treated with either IVT or EVT. Primary outcome was defined as favorable 90-day outcome (modified Rankin Scale (mRS) score 0-2). Secondary outcomes included 90-day mortality, radiographic intracranial hemorrhage (ICH) and symptomatic ICH (SICH). Results: 9 articles were included from 825 screened. 5 observational studies of IVT use in patients with (n=1078) and without dementia (n=2805) were selected for a meta-analysis. There were no significant differences in favourable 90-day mRS (adjusted OR 0.61, 95% CI 0.24 to 1.59), 90-day mortality (unadjusted OR of 1.19, 95% CI 0.86 to 1.64), ICH (unadjusted OR 1.32, 95% CI 0.79 to 2.19) and SICH (unadjusted OR of 0.94, 95% CI 0.70 to 1.25). EVT in dementia patients in one study found only increased odds of ICH (adjusted OR 1.57 95%CI 1.03 to 2.40). For patients with cognitive impairment, no significant association was found with assessed outcomes in a pooled analysis of 3 IVT studies and one EVT study found poorer 90-day mRS outcomes. Conclusions: This systematic review and meta-analysis suggests no considerable safety concerns for IVT or EVT use in patients with pre-existing dementia or cognitive impairment, compared to those without. Uncertainty remains in the efficacy of these therapies for these individuals. Rigorous, patient-caregiver informed design, and a more nuanced outcome approach are warranted for future studies. REGISTRATION: URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42021240499.

AbstractBackgroundDermatology grand rounds are popular educational activities among dermatologists and trainees, contributing to improved knowledge and skills. Dermatology hospital conferences at Mayo Clinic Dermatology are separate from dermatology grand rounds in that they focus on inpatient consultations and dermatology admissions.ObjectivesThis study aimed to determine the types of cases presented during dermatology hospital grand rounds and evaluate the educational value of this continuing medical education (CME)‐accredited activity.MethodsThis retrospective study reviewed all inpatient dermatology cases presented during hospital grand rounds at Mayo Clinic Dermatology in Rochester, MN from 2019 to 2022; this study also reviewed the compiled surveys of faculty participants at our institution from 2019 to 2022.ResultsA total of 389 cases met the inclusion criteria for analysis. The most common diagnostic category was inflammatory/autoimmune diseases (157 cases, 40%), followed by infection or infestation (73 cases, 19%), drug‐induced eruptions (49 cases, 13%), neoplastic or metastatic diseases (41 cases, 11%), genetic/congenital disorders (21 cases, 5%), depositional/nutritional/metabolic conditions (15 cases, 4%) and wound/traumatic/iatrogenic dermatoses (12 cases, 3%), which were the least common. Most cases were presented for discussion of diagnosis and management (246 cases, 63%), but others focused on the arrival of diagnosis (119 cases, 31%) or management alone (24 cases, 6%). The compiled surveys of faculty participants (n = 50) indicated high satisfaction with dermatology hospital grand rounds, with the majority expressing that evidence‐based research was incorporated and positively impacted their practice. Most respondents indicated that hospital conference participation improved knowledge (97%), competence (64%), clinician performance (54%), patient outcomes (52%) and team performance (50%).ConclusionsThe cases presented during these conferences spanned from challenging inflammatory diseases to simple dermatoses, with over 800 literature references reviewed. Dermatology hospital grand rounds provide high value as a CME‐accredited activity for dermatology faculty, even for those without a specific interest in hospital/inpatient dermatology.

Objective This study was undertaken to evaluate the frequency of modifiable dementia risk factors and their association with cognitive impairment and rate of decline in diverse participants engaged in studies of memory and aging. Methods Modifiable dementia risk factors and their associations with cognitive impairment and cognitive decline were determined in community‐dwelling African American (AA; n = 261) and non‐Hispanic White (nHW; n = 193) participants who completed ≥2 visits at the Mayo Clinic Alzheimer Disease Research Center in Jacksonville, Florida. Risk factors and their associations with cognitive impairment (global Clinical Dementia Rating [CDR] ≥ 0.5) and rates of decline (CDR Sum of Boxes) in impaired participants were compared in AA and nHW participants, controlling for demographics, APOE ɛ4 status, and Area Deprivation Index. Results Hypertension, hypercholesterolemia, obesity, and diabetes were overrepresented in AA participants, but were not associated with cognitive impairment. Depression was associated with increased odds of cognitive impairment in AA (odds ratio [OR] = 4.30, 95% confidence interval [CI] = 2.13–8.67) and nHW participants (OR = 2.79, 95% CI = 1.21–6.44) but uniquely associated with faster decline in AA participants (β = 1.71, 95% CI = 0.69–2.73, p = 0.001). Fewer AA participants reported antidepressant use (9/49, 18%) than nHW counterparts (57/78, 73%, p < 0.001). Vitamin B12 deficiency was also associated with an increased rate of cognitive decline in AA participants (β = 2.65, 95% CI = 0.38–4.91, p = 0.023). Interpretation Modifiable dementia risk factors are common in AA and nHW participants, representing important risk mitigation targets. Depression was associated with dementia in AA and nHW participants, and with accelerated declines in cognitive function in AA participants. Optimizing depression screening and treatment may improve cognitive trajectories and outcomes in AA participants. ANN NEUROL 2024;95:518–529

Background: Endovascular thrombectomy (EVT) and intravenous thrombolysis (IVT) have an unclear benefit in those with pre-stroke dementia or cognitive impairment, as these patients were often excluded from landmark stroke trials. We performed a systematic review and meta-analysis to assess the outcomes of IVT and EVT in these populations. Aims: Our systematic review, conforming to the Meta-Analysis of Observational Studies in Epidemiology guidelines, investigated studies on acute ischemic stroke patients with pre-stroke dementia or cognitive impairment treated with IVT or EVT. Primary outcome was favorable 90-day outcome (mRS 0–2). Secondary outcomes included 90-day mortality, symptomatic intracranial hemorrhage (SICH), and radiographic intracranial hemorrhage (ICH). Summary of review: Nine articles were identified, with five observational studies of IVT use in patients with (n = 1078) and without dementia (n = 2805) being selected for the meta-analysis. There were no significant differences in favorable outcome (adjusted OR: 0.61, 95% CI 0.24–1.59), mortality (unadjusted OR: 1.19, 95% CI 0.86–1.64), ICH (unadjusted OR: 1.32, 95% CI 0.79–2.19), and symptomatic ICH (unadjusted OR: 0.94, 95% CI 0.70–1.25) for patients undergoing IVT with pre-stroke dementia versus those without. One EVT study (n = 615 with dementia vs n = 9600 without) found no significant differences in outcomes apart from an increased odds of ICH for those with pre-existing dementia (adjusted OR: 1.57, 95% CI 1.03–2.40). A pooled analysis of three IVT studies showed no significant association of cognitive impairment (n = 93 vs n = 211 without) with all assessed outcomes, whereas a study of EVT found that pre-stroke cognitive impairment was associated with poor 90-day outcomes (mRS 3–6). Conclusion: These results suggest no substantial safety issues in the use of IVT or EVT for patients with pre-existing dementia or cognitive impairment compared to those without. However, the efficacy of these therapies in this demographic remains uncertain. Further rigorous studies that include a more nuanced outcome measurement approach are warranted. Registration: URL: https://www.crd.york.ac.uk/PROSPERO/ ; Unique identifier: CRD42021240499.