Methylphenidate for the Treatment of Post-COVID Cognitive Dysfunction (Brain Fog).

A substantial number of patients develop cognitive dysfunction after contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), significantly contributing to long-coronavirus disease (COVID) morbidity. Despite the urgent and overwhelming clinical need, there are currently no proven interventions to treat post-COVID cognitive dysfunction (PCCD). Psychostimulants like methylphenidate may enhance both noradrenergic and dopaminergic pathways in mesolimbic and pre-frontal areas, thus improving memory and cognition. We present a case series of six patients who were treated at the Johns Hopkins Post-Acute COVID-19 Team (PACT) clinic for PCCD with methylphenidate 5 - 20 mg in the context of routine clinical care and followed for 4 to 8 weeks. Baseline and post-treatment outcomes included subjective cognitive dysfunction and objective performance on a battery devised to measure cognitive dysfunction in long-COVID patients. Three out of the six patients reported subjective improvement with methylphenidate, one patient described it as "notable" and another as "marked" improvement in memory and concentration. We also found significant pre-treatment subjective complaints of cognitive dysfunction; however, formal cognitive assessment scores were not severely impaired. A statistically significant difference in pre and post scores, favoring intervention, was found for the following cognitive assessments: Hopkins verbal learning test (HVLT) immediate recall, HVLT delayed recall and category-cued verbal fluency. The current series demonstrates promising neurocognitive effects of methylphenidate for long-COVID cognitive impairment, particularly in recall and verbal fluency domains.

Incidence of post-operative delirium increases as severity of frailty increases.

OBJECTIVE: The surgical population is ageing and often frail. Frailty increases the risk for poor post-operative outcomes such as delirium, which carries significant morbidity, mortality and cost. Frailty is often measured in a binary manner, limiting pre-operative counselling. The goal of this study was to determine the relationship between categorical frailty severity level and post-operative delirium. METHODS: We performed an analysis of a retrospective cohort of older adults from 12 January 2018 to 3 January 2020 admitted to a tertiary medical center for elective surgery. All participants underwent frailty screening prior to inpatient elective surgery with at least two post-operative delirium assessments. Planned ICU admissions were excluded. Procedures were risk-stratified by the Operative Stress Score (OSS). Categorical frailty severity level (Not Frail, Mild, Moderate, and Severe Frailty) was measured using the Edmonton Frail Scale. Delirium was determined using the 4 A's Test and Confusion Assessment Method-Intensive Care Unit. RESULTS: In sum, 324 patients were included. The overall post-operative delirium incidence was 4.6% (15 individuals), which increased significantly as the categorical frailty severity level increased (2% not frail, 6% mild frailty, 23% moderate frailty; P < 0.001) corresponding to increasing odds of delirium (OR 2.57 [0.62, 10.66] mild vs. not frail; OR 12.10 [3.57, 40.99] moderate vs. not frail). CONCLUSIONS: Incidence of post-operative delirium increases as categorical frailty severity level increases. This suggests that frailty severity should be considered when counselling older adults about their risk for post-operative delirium prior to surgery.

The Medicare annual wellness visit: An opportunity to improve health system identification of hearing loss?

BACKGROUND: Hearing loss is prevalent and consequential but under-diagnosed and managed. The Medicare Annual Wellness Visit (AWV) health risk assessment elicits patient-reported hearing concerns but whether such information affects documentation, diagnosis, or referral is unknown. METHODS: We use 5 years of electronic medical record (EMR) data (2017-2022) for a sample of 13,776 older primary care patients. We identify the first (index) AWV indication of hearing concerns and existing and subsequent hearing loss EMR diagnoses (visit diagnoses or problem list diagnoses) and audiology referrals. For a 20% random sample of AWV notes (n = 474) we compared hearing loss EMR diagnoses to documentation of (1) hearing concerns, (2) hearing loss/aid use, and (3) referrals for hearing care. RESULTS: Of 3845 (27.9%) older adults who identified hearing concerns (mean age 79.1 years, 57% female, 75% white) 24% had an existing hearing diagnosis recorded. Among 474 patients with AWV clinical notes reviewed, 90 (19%) had an existing hearing loss diagnosis. Clinicians were more likely to document hearing concerns or hearing loss/aid use for those with (vs. without) an existing EMR diagnosis (50.6% vs. 35.9%, p = 0.01; 68.9% vs. 37.5%, p < 0.001, respectively). EMR diagnoses of hearing loss were recorded for no more than 40% of those with indicated hearing concerns. Among those without prior diagnosis 38 (9.9%) received a hearing care referral within 1 month. Subgroup analysis suggest greater likelihood of documenting hearing concerns for patients age 80+ (OR:1.51, 95% confidence interval [CI]: 1.03, 2.19) and decreased likelihood of documenting known hearing loss among patients with more chronic conditions (OR: 0.49, 95% CI: 0.27, 0.9), with no differences observed by race. CONCLUSION: Documentation of hearing loss in EMR and AWV clinical notes is limited among older adults with subjective hearing concerns. Systematic support and incorporation of hearing into EMR and clinical notes may increase hearing loss visibility by care teams.

A world-wide study on delirium assessments and presence of protocols.

BACKGROUND: Delirium is a common complication of older people in hospitals, rehabilitation and long-term facilities. OBJECTIVE: To assess the worldwide use of validated delirium assessment tools and the presence of delirium management protocols. DESIGN: Secondary analysis of a worldwide one-day point prevalence study on World Delirium Awareness Day, 15 March 2023. SETTING: Cross-sectional online survey including hospitals, rehabilitation and long-term facilities. METHODS: Participating clinicians reported data on delirium, the presence of protocols, delirium assessments, delirium-awareness interventions, non-pharmacological and pharmacological interventions, and ward/unit-specific barriers. RESULTS: Data from 44 countries, 1664 wards/units and 36 048 patients were analysed. Validated delirium assessments were used in 66.7% (n = 1110) of wards/units, 18.6% (n = 310) used personal judgement or no assessment, and 10% (n = 166) used other assessment methods. A delirium management protocol was reported in 66.8% (n = 1094) of wards/units. The presence of protocols for delirium management varied across continents, ranging from 21.6% (on 21/97 wards/units) in Africa to 90.4% (235/260) in Australia, similar to the use of validated delirium assessments with 29.6% (29/98) in Africa to 93.5% (116/124) in North America. Wards/units with a delirium management protocol [n = 1094/1664, 66.8%] were more likely to use a validated delirium test than those without a protocol [odds ratio 6.97 (95% confidence interval 5.289-9.185)]. The presence of a delirium protocol increased the chances for valid delirium assessment and, likely, evidence-based interventions. CONCLUSION: Wards/units that reported the presence of delirium management protocols had a higher probability of using validated delirium assessments tools to assess for delirium.

Delirium in the United States: Results From the 2023 Cross-Sectional World Delirium Awareness Day Prevalence Study.

BACKGROUND: Delirium is an acute brain dysfunction associated with an increased risk of mortality and future dementia. OBJECTIVES: To describe the prevalence of clinically documented delirium in the United States on World Delirium Awareness Day 2023. METHODS: This is a sub-analysis of a prospective, cross-sectional, online, international survey. All health care settings were eligible, with the exception of operating rooms and outpatient clinics. Health care clinicians, administrators, and researchers completed the survey. The primary outcome was the prevalence of clinically documented delirium at 8:00 a.m. and 8:00 p.m. on March 15, 2023. Secondary outcomes were related to health care delivery. Descriptive statistics are reported. Differences between unit types (non-intensive care unit vs intensive care unit) were examined for all outcomes. RESULTS: Ninety-one hospital units reported on 1318/1213 patients. The prevalence of clinically documented delirium was 16.4% (n = 216/1318) at 8:00 a.m. and 17.9% (n = 217/1213) at 8:00 p.m. (P = 0.316) and significantly differed between age groups, reported discipline, unit, and hospital types. Significant differences were identified between non-intensive care unit and intensive care unit settings in the use of delirium-related protocols, nonpharmacologic and pharmacologic management, educational processes, and barriers to evidence-based delirium care. CONCLUSIONS: To our knowledge, this is the first epidemiologic survey of clinically documented delirium across two time points in the United States. Delirium remains a significant burden and challenge for health care systems. The high percentage of units using delirium management protocols suggests administrator and clinician awareness of evidence-based strategies for its detection and mitigation. We provide recommendations for future studies and quality improvement projects to improve clinical recognition and management of delirium.

Managing Delirium in the Emergency Department: An Updated Narrative Review.

Purpose of Review: Emergency departments (EDs) are facing an epidemic of overcrowding and ED boarding, particularly of older adults who often present with, or develop, delirium in the ED. Delirium is associated with increased complications, longer hospital length of stay, mortality, and costs to the healthcare system. However, we only have limited knowledge of how to successfully prevent and treat delirium in the ED in a pragmatic, sustainable, and cost-effective way. We present a narrative review of recent literature of delirium prevention and treatment programs in the ED. We aim to describe the components of successful delirium management strategies to be used by EDs in building delirium management programs. Recent Findings: We reviewed 10 studies (2005-2023) that report delirium interventions in the ED, and describe the different components of these interventions that have been studied. These interventions included: optimizing hemodynamics and oxygenation, treating pain, hydration and nutrition support, avoiding sedative hypnotics, antipsychotics and anticholinergics, promoting sleep, sensory stimulation, limiting the time spent in the ED, educating providers and staff, and developing multidisciplinary delirium protocols integrated into the electronic health record. Summary: Through our narrative review of the recent literature on delirium prevention and treatment programs in the ED, we have identified nine components of successful delirium prevention strategies in the ED. We also discuss three high priority areas for further research including identification of most effective components of delirium prevention strategies, conduct of additional high-quality trials in non-hip.

Hearing loss and cognitive decline: Prioritizing equity in a world in which hearing health matters.

Alzheimer's disease and related dementias (ADRDs) and age-related hearing loss are the intersection of two major public health challenges. With age as the primary risk factor for both disease processes, the burden of ADRDs and age-related hearing loss is growing, and each field maintains significant barriers to broadscale identification and management that is affordable and accessible. With the disproportionate burden of ADRDs among racial and ethnic minority older adults and existing disparities within hearing care, both areas face challenges in achieving equitable access and outcomes across diverse populations. The publication of the Aging and Cognitive Health Evaluation in Elders (ACHIEVE) trial in July 2023 marked a significant moment in the fields of brain and hearing health. The ACHIEVE trial was the first randomized controlled trial to examine whether providing hearing intervention, specifically provision of hearing aids, compared to an education control, would reduce cognitive changes over 3 years. The participants most at risk for cognitive decline, with lower education, lower income, more likely to identify as Black, and have more cardiovascular risk factors, were the participants who benefited most from the hearing intervention and are also the least likely to be represented in research and the least likely to obtain hearing care. With growing evidence of the interconnection between cognitive and sensory health, we have an opportunity to prioritize equity, from purposeful inclusion of diverse participants in trials to influencing the emerging market of over-the-counter hearing aids to supporting expanded models of hearing care that reach those who have traditionally gone unserved. No longer can hearing go unrecognized by clinicians, researchers, and advocates for brain health. At the same time, the fields of brain and hearing health must center equity if we are going to meet the needs of diverse older adults in a world in which hearing health matters.

The Delphi Delirium Management Algorithms. A practical tool for clinicians, the result of a modified Delphi expert consensus approach.

Delirium is common in hospitalised patients, and there is currently no specific treatment. Identifying and treating underlying somatic causes of delirium is the first priority once delirium is diagnosed. Several international guidelines provide clinicians with an evidence-based approach to screening, diagnosis and symptomatic treatment. However, current guidelines do not offer a structured approach to identification of underlying causes. A panel of 37 internationally recognised delirium experts from diverse medical backgrounds worked together in a modified Delphi approach via an online platform. Consensus was reached after five voting rounds. The final product of this project is a set of three delirium management algorithms (the Delirium Delphi Algorithms), one for ward patients, one for patients after cardiac surgery and one for patients in the intensive care unit.

A pragmatic tool to screen for pre-transplant cognitive impairment among potential candidates for liver transplant.

INTRODUCTION: Cognitive impairment (CI) among liver transplant (LT) candidates is associated with increased risk of waitlist mortality and inferior outcomes. While formal neurocognitive evaluation is the gold standard for CI diagnosis, the Montreal Cognitive Assessment (MoCA) is often used for first-line cognitive screening. However, MoCA requires specialized training and may be too lengthy for a busy evaluation appointment. An alternate approach may be the Quick Dementia Rating System (QDRS), which is patient- and informant-based and can be administered quickly. We compared potential LT candidates identified by MoCA and QDRS as potentially benefiting from further formal cognitive evaluation. METHODS: We identified 46 potential LT candidates enrolled at a single center of a prospective, observational cohort study who were administered MoCA and QDRS during transplant evaluation (12/2021-12/2022). Scores were dichotomized as (1) normal versus abnormal and (2) normal/mild impairment versus more-than-mild impairment. We calculated sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of QDRS compared to MoCA. RESULTS: By MoCA, this population had a prevalence of 48% normal cognition, 48% mild, 4% moderate, and 0% severe impairment. This was categorized as 96% normal/mild and 4% more-than-mild impairment. When comparing to MoCA cognitive screening, QDRS had a sensitivity of 61%, specificity of 56%, NPV of 56%, and PPV of 61%. When identifying more-than-mild impairment, QDRS had a sensitivity of 100%, specificity of 73%, NPV of 100%, and PPV of 10%. CONCLUSION: The high sensitivity and NPV of QDRS in identifying more-than-mild impairment suggests it could identify potential LT candidates who would benefit from further formal cognitive evaluation. The ability to administer QDRS quickly and remotely makes it a pragmatic option for pre-transplant screening.

A fluid biomarker reveals loss of TDP-43 splicing repression in presymptomatic ALS-FTD.

Although loss of TAR DNA-binding protein 43 kDa (TDP-43) splicing repression is well documented in postmortem tissues of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), whether this abnormality occurs during early-stage disease remains unresolved. Cryptic exon inclusion reflects loss of function of TDP-43, and thus detection of proteins containing cryptic exon-encoded neoepitopes in cerebrospinal fluid (CSF) or blood could reveal the earliest stages of TDP-43 dysregulation in patients. Here we use a newly characterized monoclonal antibody specific to a TDP-43-dependent cryptic epitope (encoded by the cryptic exon found in HDGFL2) to show that loss of TDP-43 splicing repression occurs in ALS-FTD, including in presymptomatic C9orf72 mutation carriers. Cryptic hepatoma-derived growth factor-like protein 2 (HDGFL2) accumulates in CSF at significantly higher levels in familial ALS-FTD and sporadic ALS compared with controls and is elevated earlier than neurofilament light and phosphorylated neurofilament heavy chain protein levels in familial disease. Cryptic HDGFL2 can also be detected in blood of individuals with ALS-FTD, including in presymptomatic C9orf72 mutation carriers, and accumulates at levels highly correlated with those in CSF. Our findings indicate that loss of TDP-43 cryptic splicing repression occurs early in disease progression, even presymptomatically, and that detection of the HDGFL2 cryptic neoepitope serves as a potential diagnostic biomarker for ALS, which should facilitate patient recruitment and measurement of target engagement in clinical trials.

Automating the analysis of eye movement for different neurodegenerative disorders.

The clinical observation and assessment of extra-ocular movements is common practice in assessing neurodegenerative disorders but remains observer-dependent. In the present study, we propose an algorithm that can automatically identify saccades, fixation, smooth pursuit, and blinks using a non-invasive eye tracker. Subsequently, response-to-stimuli-derived interpretable features were elicited that objectively and quantitatively assess patient behaviors. The cohort analysis encompasses persons with mild cognitive impairment (MCI), Alzheimer's disease (AD), Parkinson's disease (PD), Parkinson's disease mimics (PDM), and controls (CTRL). Overall, results suggested that the AD/MCI and PD groups had significantly different saccade and pursuit characteristics compared to CTRL when the target moved faster or covered a larger visual angle during smooth pursuit. These two groups also displayed more omitted antisaccades and longer average antisaccade latency than CTRL. When reading a text passage silently, people with AD/MCI had more fixations. During visual exploration, people with PD demonstrated a more variable saccade duration than other groups. In the prosaccade task, the PD group showed a significantly smaller average hypometria gain and accuracy, with the most statistical significance and highest AUC scores of features studied. The minimum saccade gain was a PD-specific feature different from CTRL and PDM. These features, as oculographic biomarkers, can be potentially leveraged in distinguishing different types of NDs, yielding more objective and precise protocols to diagnose and monitor disease progression.

Optimizing delirium care in the era of Age-Friendly Health System.

Delirium is a significant geriatric condition associated with adverse clinical and economic outcomes. The cause of delirium is usually multifactorial, and person-centered multicomponent approaches for proper delirium management are required. In 2017, the John A. Hartford Foundation and the Institute for Healthcare Improvement (IHI) launched a national initiative, Age-Friendly Health System (AFHS), promoting the use of a framework called 4Ms (what matters, medication, mentation, and mobility). The 4Ms framework's primary goal is to provide comprehensive and practical person-centered care for older adults and it aligns with the core concepts of optimal delirium management. In this special article, we demonstrate how a traditional delirium prevention and management model can be assessed from the perspective of AFHS. An example is the crosswalk with the Hospital Elder Life Program (HELP) Core Interventions and the 4MS, which demonstrates alignment in delirium management. We also introduce useful tools to create an AFHS environment in delirium management. Although much has been written about delirium management, there is a need to identify the critical steps in advancing the overall delirium care in the context of the AFHS. In this article, we suggest future directions, including the need for more prospective and comprehensive research to assess the impact of AFHS on delirium care, the need for more innovative and sustainable education platforms, fundamental changes in the healthcare payment system for proper adoption of AFHS in any healthcare setting, and application of AFHS in the community for continuity of care for older adults with delirium.

Hearing Loss, Hearing Aids, and Satisfaction With Health Care in the National Health Interview Survey.

OBJECTIVE: Hearing loss may negatively impact satisfaction with health care via patient-provider communication barriers and may be amenable to hearing care treatment. STUDY DESIGN: Cross-sectional. SETTING: National Health Interview Survey, a nationally representative survey of noninstitutionalized US residents, 2013 to 2018 pooled cycles. METHODS: Participants described satisfaction with health care in the past year, categorized as optimal (very satisfied) versus suboptimal (satisfied, dissatisfied, very dissatisfied) satisfaction. Self-report hearing without hearing aids (excellent, good, a little trouble, moderate trouble, a lot of trouble) and hearing aid use (yes, no) were collected. Weighted Poisson regression models adjusted for sociodemographic and health covariates were used to estimate prevalence rate ratios (PRRs) of satisfaction with care by hearing loss and hearing aid use. RESULTS: Among 137,216 participants (mean age 50.9 years, 56% female, 12% black), representing 77.2 million Americans in the weighted model, 19% reported trouble hearing. Those with good (PRR = 1.20, 95% confidence interval [CI]: 1.18-1.23), a little trouble (PRR = 1.27, 95% CI, 1.23-1.31), moderate trouble (PRR = 1.29, 95% CI, 1.24-1.35), and a lot of trouble hearing (PRR = 1.26, 95% CI, 1.18-1.33) had a higher prevalence rate of suboptimal satisfaction with care relative to those with excellent hearing. Among all participants with trouble hearing, hearing aid users had a 17% decrease in the prevalence rate of suboptimal satisfaction with care (PRR = 0.83, 95% CI, 0.78-0.88) compared to nonusers. CONCLUSION: Hearing loss decreases patient satisfaction with health care, which is tied to Medicare hospital reimbursement models. Hearing aid use may improve patient-provider communication and patient satisfaction, although prospective studies are warranted to truly establish their protective effect.

Advancing specificity in delirium: The delirium subtyping initiative.

BACKGROUND: Delirium, a common syndrome with heterogeneous etiologies and clinical presentations, is associated with poor long-term outcomes. Recording and analyzing all delirium equally could be hindering the field's understanding of pathophysiology and identification of targeted treatments. Current delirium subtyping methods reflect clinically evident features but likely do not account for underlying biology. METHODS: The Delirium Subtyping Initiative (DSI) held three sessions with an international panel of 25 experts. RESULTS: Meeting participants suggest further characterization of delirium features to complement the existing Diagnostic and Statistical Manual of Mental Disorders Fifth Edition Text Revision diagnostic criteria. These should span the range of delirium-spectrum syndromes and be measured consistently across studies. Clinical features should be recorded in conjunction with biospecimen collection, where feasible, in a standardized way, to determine temporal associations of biology coincident with clinical fluctuations. DISCUSSION: The DSI made recommendations spanning the breadth of delirium research including clinical features, study planning, data collection, and data analysis for characterization of candidate delirium subtypes. HIGHLIGHTS: Delirium features must be clearly defined, standardized, and operationalized. Large datasets incorporating both clinical and biomarker variables should be analyzed together. Delirium screening should incorporate communication and reasoning.

ACR Appropriateness Criteria® Tinnitus: 2023 Update.

Tinnitus is abnormal perception of sound and has many subtypes. Clinical evaluation, audiometry, and otoscopy should be performed before ordering any imaging, as the choice of imaging will depend on various factors. Type of tinnitus (pulsatile or nonpulsatile) and otoscopy findings of a vascular retrotympanic lesion are key determinants to guide the choice of imaging studies. High-resolution CT temporal bone is an excellent tool to detect glomus tumors, abnormal course of vessels, and some other abnormalities when a vascular retrotympanic lesion is seen on otoscopy. CTA or a combination of MR and MRA/MRV are used to evaluate arterial or venous abnormalities like dural arteriovenous fistula, arteriovenous malformation, carotid stenosis, dural sinus stenosis, and bony abnormalities like sigmoid sinus wall abnormalities in cases of pulsatile tinnitus without a vascular retrotympanic lesion. MR of the brain is excellent in detecting mass lesions such as vestibular schwannomas in cases of unilateral nonpulsatile tinnitus. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

The association of hearing loss with frailty among community-dwelling older adults: findings from the National Health and Aging Trends Study.

BACKGROUND: The identification of modifiable risk factors is crucial for the prevention and/or reversal of frailty, which is associated with significant morbidity and mortality. Hearing loss affects two-thirds of older adults in the United States (U.S.) and is associated with physical and cognitive decline which may increase frailty risk. We investigated the association of hearing loss and hearing aid use with frailty and pre-frailty in a nationally representative sample of older adults in the U.S. METHODS: Cross-sectional analysis of the National Health and Aging Trends Study (2021 round). The better-hearing ear pure-tone average (BPTA) at speech-frequencies (0.5-4 kHz) was modeled continuously (per 10 dB) and categorically (no ≤ 25 dB, mild 26-40 dB, moderate or greater > 40 dB hearing loss). Hearing aid use was self-reported. The physical frailty phenotype (frail, pre-frail, robust) was determined based on Fried criteria: unintentional weight loss, exhaustion, low physical activity, weakness, slow walking speed. We used multinomial multivariable regression adjusted for sociodemographic and health characteristics (odds ratios [95% Confidence Intervals]). RESULTS: Among 2,361 participants (mean age = 81 years, 56% female, 19% Black), 860 (36%) had mild and 864 (37%) had moderate or greater hearing loss. Worse hearing was associated with greater odds of being frail versus robust (OR = 1.20 [1.05-1.38] per 10 dB difference). Categorically, moderate or greater hearing loss was associated with greater odds of being frail (OR = 1.84 [1.01-3.08]) and pre-frail (OR = 1.46 [1.01-2.10]) versus robust. Among 1,724 participants with hearing loss, compared to hearing aid users (N = 522), nonusers had greater odds of being frail (OR = 2.54 [1.54-4.18]) and pre-frail (OR = 1.51 [1.05-2.17]) versus robust, and frail versus pre-frail (OR = 1.68 [1.04-2.72]). CONCLUSIONS: In a nationally representative sample of older adults in the U.S., using gold-standard hearing measures and a validated frailty phenotype, hearing loss and lack of hearing aid use was cross-sectionally associated with frailty and pre-frailty. Future longitudinal studies are needed to establish if hearing loss is a risk factor for frailty, which may have significant clinical importance.