Development of the 2023 ACR/EULAR Antiphospholipid Syndrome Classification Criteria, Phase III-D Report: Multi Criteria Decision Analysis.

BACKGROUND: The 2023 ACR/EULAR Antiphospholipid Syndrome (APS) Classification Criteria development, aiming to identify patients with high likelihood of APS for research, employed a four-phase methodology. Phase I and II resulted in 27 proposed candidate criteria, organized into laboratory and clinical domains. Here, we summarize the last stage of Phase III efforts employing a consensus-based multi-criteria decision analysis (MCDA) to weigh candidate criteria and identify an APS classification threshold score. METHODS: We evaluated 192 unique, international real-world cases referred for "suspected APS" with a wide range of APS manifestations. Using proposed candidate criteria, subcommittee members rank-ordered 20 representative cases from highly unlikely to highly likely APS. During an in-person meeting, the subcommittee refined definitions and participated in an MCDA exercise to identify relative weights of candidate criteria. Using consensus decisions and pairwise criteria comparisons, 1000Minds™ software assigned criteria weights, and we rank ordered 192 cases by their additive scores. A consensus-based threshold score for APS classification was set. RESULTS: Pre-meeting evaluation of 20 representative cases demonstrated variability in APS assessment. MCDA resolved 81 pairwise decisions; relative weights identified domain item hierarchy. After assessing 192 cases by weights and additive scores, the Steering Committee reached consensus that APS classification should require separate clinical and laboratory scores, rather than a single aggregate score, to ensure high specificity. CONCLUSION: Using MCDA, candidate criteria preliminary weights were determined. Unlike other disease classification systems using a single aggregate threshold score, separate clinical and laboratory domain thresholds were incorporated into the new APS classification criteria.

Dietary Acculturation Is Associated With Altered Gut Microbiome, Circulating Metabolites, and Cardiovascular Disease Risk in US Hispanics and Latinos: Results From HCHS/SOL.

BACKGROUND: Dietary acculturation, or adoption of dominant culture diet by migrant groups, influences human health. We aimed to examine dietary acculturation and its relationships with cardiovascular disease (CVD), gut microbiota, and blood metabolites among US Hispanic and Latino adults. METHODS: In the HCHS/SOL (Hispanic Community Health Study/Study of Latinos), US exposure was defined by years in the United States (50 states and Washington, DC) and US nativity. A dietary acculturation pattern was derived from 14 172 participants with two 24-hour dietary recalls at baseline (2008-2011) using least absolute shrinkage and selection operator regression, with food groups as predictors of US exposure. We evaluated associations of dietary acculturation with incident CVD across ≈7 years of follow-up (n=211/14 172 cases/total) and gut microbiota (n=2349; visit 2, 2014 to 2017). Serum metabolites associated with both dietary acculturation-related gut microbiota (n=694) and incident CVD (n=108/5256 cases/total) were used as proxy measures to assess the association of diet-related gut microbiome with incident CVD. RESULTS: We identified an empirical US-oriented dietary acculturation score that increased with US exposure. Higher dietary acculturation score was associated with higher risk of incident CVD (hazard ratio per SD, 1.33 [95% CI, 1.13-1.57]), adjusted for sociodemographic, lifestyle, and clinical factors. Sixty-nine microbial species (17 enriched from diverse species, 52 depleted mainly from fiber-utilizing Clostridia and Prevotella species) were associated with dietary acculturation, driven by lower intakes of whole grains, beans, and fruits and higher intakes of refined grains. Twenty-five metabolites, involved predominantly in fatty acid and glycerophospholipid metabolism (eg, branched-chain 14:0 dicarboxylic acid** and glycerophosphoethanolamine), were associated with both diet acculturation-related gut microbiota and incident CVD. Proxy association analysis based on these metabolites suggested a positive relationship between diet acculturation-related microbiome and risk of CVD (r=0.70, P<0.001). CONCLUSIONS: Among US Hispanic and Latino adults, greater dietary acculturation was associated with elevated CVD risk, possibly through alterations in gut microbiota and related metabolites. Diet and microbiota-targeted interventions may offer opportunities to mitigate CVD burdens of dietary acculturation.

The Impact of Vitamin D and L-Cysteine Co-Supplementation on Upregulating Glutathione and Vitamin D-Metabolizing Genes and in the Treatment of Circulating 25-Hydroxy Vitamin D Deficiency.

Vitamin D receptors are expressed in many organs and tissues, which suggests that vitamin D (VD) affects physiological functions beyond its role in maintaining bone health. Deficiency or inadequacy of 25(OH)VD is widespread globally. Population studies demonstrate that a positive association exists between a high incidence of VD deficiency and a high incidence of chronic diseases, including dementia, diabetes, and heart disease. However, many subjects have difficulty achieving the required circulating levels of 25(OH)VD even after high-dose VD supplementation, and randomized controlled clinical trials have reported limited therapeutic success post-VD supplementation. Thus, there is a discordance between the benefits of VD supplementation and the prevention of chronic diseases in those with VD deficiency. Why this dissociation exists is currently under debate and is of significant public interest. This review discusses the downregulation of VD-metabolizing genes needed to convert consumed VD into 25(OH)VD to enable its metabolic action exhibited by subjects with metabolic syndrome, obesity, and other chronic diseases. Research findings indicate a positive correlation between the levels of 25(OH)VD and glutathione (GSH) in both healthy and diabetic individuals. Cell culture and animal experiments reveal a novel mechanism through which the status of GSH can positively impact the expression of VD metabolism genes. This review highlights that for better success, VD deficiency needs to be corrected at multiple levels: (i) VD supplements and/or VD-rich foods need to be consumed to provide adequate VD, and (ii) the body needs to be able to upregulate VD-metabolizing genes to convert VD into 25(OH)VD and then to 1,25(OH)2VD to enhance its metabolic action. This review outlines the association between 25(OH)VD deficiency/inadequacy and decreased GSH levels, highlighting the positive impact of combined VD+LC supplementation on upregulating GSH, VD-metabolizing genes, and VDR. These effects have the potential to enhance 25(OH)VD levels and its therapeutic efficacy.

Home Blood Pressure Telemonitoring and Nurse Case Management in Black and Hispanic Patients With Stroke: A Randomized Clinical Trial.

Importance: Black and Hispanic patients have high rates of recurrent stroke and uncontrolled hypertension in the US. The effectiveness of home blood pressure telemonitoring (HBPTM) and telephonic nurse case management (NCM) among low-income Black and Hispanic patients with stroke is unknown. Objective: To determine whether NCM plus HBPTM results in greater systolic blood pressure (SBP) reduction at 12 months and lower rate of stroke recurrence at 24 months than HBPTM alone among Black and Hispanic stroke survivors with uncontrolled hypertension. Design, Setting, and Participants: Practice-based, multicenter, randomized clinical trial in 8 stroke centers and ambulatory practices in New York City. Black and Hispanic study participants were enrolled between April 18, 2014, and December 19, 2017, with a final follow-up visit on December 31, 2019. Interventions: Participants were randomly assigned to receive either HBPTM alone (12 home BP measurements/week for 12 months, with results transmitted to a clinician; n = 226) or NCM plus HBPTM (20 counseling calls over 12 months; n = 224). Main Outcomes and Measures: Primary outcomes were change in SBP at 12 months and rate of recurrent stroke at 24 months. Final statistical analyses were completed March 14, 2024. Results: Among 450 participants who were enrolled and randomized (mean [SD] age, 61.7 [11.0] years; 51% were Black [n = 231]; 44% were women [n = 200]; 31% had ≥3 comorbid conditions [n = 137]; 72% had household income <$25 000/y [n = 234/324]), 358 (80%) completed the trial. Those in the NCM plus HBPTM group had a significantly greater SBP reduction than those in the HBPTM alone group at 12 months (-15.1 mm Hg [95% CI, -17.2 to -13.0] vs -5.8 mm Hg [95% CI, -7.9 to -3.7], respectively; P < .001). The between-group difference in SBP reduction at 12 months, adjusted for primary care physician clustering, was -8.1 mm Hg (95% CI, -11.2 to -5.0; P < .001) at 12 months. The rate of recurrent stroke was similar between both groups at 24 months (4.0% in the NCM plus HBPTM group vs 4.0% in the HBPTM alone group, P > .99). Conclusions and Relevance: Among predominantly low-income Black and Hispanic stroke survivors with uncontrolled hypertension, addition of NCM to HBPTM led to greater SBP reduction than HBPTM alone. Additional studies are needed to understand the long-term clinical outcomes, cost-effectiveness, and generalizability of NCM-enhanced telehealth programs among low-income Black and Hispanic stroke survivors with significant comorbidity. Trial Registration: Clinical Trials.gov Identifier: NCT02011685.

Exploring Potential Mechanisms Accounting for Iron Accumulation in the Central Nervous System of Patients with Alzheimer's Disease.

Elevated levels of iron occur in both cortical and subcortical regions of the CNS in patients with Alzheimer's disease. This accumulation is present early in the disease process as well as in more advanced stages. The factors potentially accounting for this increase are numerous, including: (1) Cells increase their uptake of iron and reduce their export of iron, as iron becomes sequestered (trapped within the lysosome, bound to amyloid ß or tau, etc.); (2) metabolic disturbances, such as insulin resistance and mitochondrial dysfunction, disrupt cellular iron homeostasis; (3) inflammation, glutamate excitotoxicity, or other pathological disturbances (loss of neuronal interconnections, soluble amyloid ß, etc.) trigger cells to acquire iron; and (4) following neurodegeneration, iron becomes trapped within microglia. Some of these mechanisms are also present in other neurological disorders and can also begin early in the disease course, indicating that iron accumulation is a relatively common event in neurological conditions. In response to pathogenic processes, the directed cellular efforts that contribute to iron buildup reflect the importance of correcting a functional iron deficiency to support essential biochemical processes. In other words, cells prioritize correcting an insufficiency of available iron while tolerating deposited iron. An analysis of the mechanisms accounting for iron accumulation in Alzheimer's disease, and in other relevant neurological conditions, is put forward.

Microfluidic Isolation of Neuronal-Enriched Extracellular Vesicles Shows Distinct and Common Neurological Proteins in Long COVID, HIV Infection and Alzheimer's Disease.

Long COVID (LongC) is associated with a myriad of symptoms including cognitive impairment. We reported at the beginning of the COVID-19 pandemic that neuronal-enriched or L1CAM+ extracellular vesicles (nEVs) from people with LongC contained proteins associated with Alzheimer's disease (AD). Since that time, a subset of people with prior COVID infection continue to report neurological problems more than three months after infection. Blood markers to better characterize LongC are elusive. To further identify neuronal proteins associated with LongC, we maximized the number of nEVs isolated from plasma by developing a hybrid EV Microfluidic Affinity Purification (EV-MAP) technique. We isolated nEVs from people with LongC and neurological complaints, AD, and HIV infection with mild cognitive impairment. Using the OLINK platform that assesses 384 neurological proteins, we identified 11 significant proteins increased in LongC and 2 decreased (BST1, GGT1). Fourteen proteins were increased in AD and forty proteins associated with HIV cognitive impairment were elevated with one decreased (IVD). One common protein (BST1) was decreased in LongC and increased in HIV. Six proteins (MIF, ENO1, MESD, NUDT5, TNFSF14 and FYB1) were expressed in both LongC and AD and no proteins were common to HIV and AD. This study begins to identify differences and similarities in the neuronal response to LongC versus AD and HIV infection.

Rising Cardiac Troponin: A Prognostic Biomarker for Mortality After Acute Ischemic Stroke.

BACKGROUND: Elevated cardiac troponin (cTn) is detected in 10% to 30% of patients with acute ischemic stroke (AIS) and correlates with poor functional outcomes. Serial cTn measurements differentiate a dynamic cTn pattern (rise/fall >20%), specific for acute myocardial injury, from elevated but stable cTn levels (nondynamic), typically attributed to chronic cardiac/noncardiac conditions. We investigated if the direction of the cTn change (rising versus falling) affects mortality and outcome. METHODS AND RESULTS: We retrospectively screened consecutive patients with AIS admitted to 5 stroke centers for elevated cTn at admission and at least 1 additional cTn measurement within 48 hours. The pattern of cTn was defined as rising if >20% increase from baseline, falling if >20% decrease, or nondynamic if ≤20% change in either direction. Logistic regression analyses were performed to assess the association of cTn patterns and 7-day mortality and unfavorable discharge disposition. Of 3789 patients with AIS screened, 300 were included. Seventy-two had a rising pattern, 66 falling, and 162 nondynamic. In patients with AIS with rising cTn, acute ischemic myocardial infarction was present in 54%, compared with 33% in those with falling cTn (P<0.01). Twenty-two percent of patients with a rising pattern had an isolated dynamic cTn in the absence of any ECG or echocardiogram changes, compared with 53% with falling cTn. A rising pattern was associated with higher risk of 7-day mortality (adjusted odds ratio [OR]=32 [95% CI, 2.5-415.0] rising versus aOR=1.3 [95% CI, 0.1-38.0] falling versus nondynamic as reference) and unfavorable discharge disposition (aOR=2.5 [95% CI, 1.2-5.2] rising versus aOR=0.6 [95% CI, 0.2-1.5] versus falling). CONCLUSIONS: Rising cTn is independently associated with increased mortality and unfavorable discharge disposition in patients with AIS.

Survey of Potential Disparity Issues Among Minority Stroke Survivors in Central Brooklyn.

Medical data and information are ubiquitous due to internet availability. However, most people persist in using and trusting their healthcare professionals for health information. They are increasingly flooded with health information from diverse sources such as the internet, community-based organizations, and family or friends. It is crucial to understand where stroke patients vary in the use and trust of health information to improve their conditions. This pilot study aimed to better understand the nature of the problems confronted by stroke patients, such as the source of reliable health information, trust in the healthcare system, and technology trend awareness. African American and Afro-Caribbean stroke patients (n=64) residing in Central Brooklyn, New York, participated in a survey. The results showed that physicians remained the most highly trusted information sources for stroke patients, particularly among patients with higher education, irrespective of the available communication sources.

Discontinuity of Stroke Care in a Black Urban Cohort: Insight from EHR Data.

This poster describes the findings from a study that attempts to characterize an underserved Black stroke cohort who are at risk for discontinuities of care using electronic health record (EHR). Preliminary analysis revealed that 90.1% of the patients were Black. After being diagnosed with a stroke, 57% of the population did not return for follow-up. The objective is to understand the factors contributing to discontinuity of care in Black stroke patients.

Alzheimer's Disease: A Review of Pathology, Current Treatments, and the Potential Therapeutic Effect of Decreasing Oxidative Stress by Combined Vitamin D and l-Cysteine Supplementation.

Significance: Excess oxidative stress and neuroinflammation are risk factors in the onset and progression of Alzheimer's disease (AD) and its association with amyloid-ß plaque accumulation. Oxidative stress impairs acetylcholine (ACH) and N-methyl-d-aspartate receptor signaling in brain areas that function in memory and learning. Glutathione (GSH) antioxidant depletion positively correlates with the cognitive decline in AD subjects. Treatments that upregulate GSH and ACH levels, which simultaneously decrease oxidative stress and inflammation, may be beneficial for AD. Recent Advances: Some clinical trials have shown a benefit of monotherapy with vitamin D (VD), whose deficiency is linked to AD or with l-cysteine (LC), a precursor of GSH biosynthesis, in reducing mild cognitive impairment. Animal studies have shown a simultaneous decrease in ACH esterase (AChE) and increase in GSH; combined supplementation with VD and LC results in a greater decrease in oxidative stress and inflammation, and increase in GSH levels compared with monotherapy with VD or LC. Therefore, cosupplementation with VD and LC has the potential of increasing GSH, downregulation of oxidative stress, and decreased inflammation and AChE levels. Future Directions: Clinical trials are needed to determine whether safe low-cost dietary supplements, using combined VD+LC, have the potential to alleviate elevated AChE, oxidative stress, and inflammation levels, thereby halting the onset of AD. Goal of Review: The goal of this review is to highlight the pathological hallmarks and current Food and Drug Administration-approved treatments for AD, and discuss the potential therapeutic effect that cosupplementation with VD+LC could manifest by increasing GSH levels in patients. Antioxid. Redox Signal. 40, 663-678.

Do digital health interventions hold promise for stroke prevention and care in Black and Latinx populations in the United States? A scoping review.

BACKGROUND: Black and Latinx populations are disproportionately affected by stroke and are likely to experience gaps in health care. Within fragmented care systems, remote digital solutions hold promise in reversing this pattern. However, there is a digital divide that follows historical disparities in health. Without deliberate attempts to address this digital divide, rapid advances in digital health will only perpetuate systemic biases. This study aimed to characterize the range of digital health interventions for stroke care, summarize their efficacy, and examine the inclusion of Black and Latinx populations in the evidence base. METHODS: We searched PubMed, the Web of Science, and EMBASE for publications between 2015 and 2021. Inclusion criteria include peer-reviewed systematic reviews or meta-analyses of experimental studies focusing on the impact of digital health interventions on stroke risk factors and outcomes in adults. Detailed information was extracted on intervention modality and functionality, clinical/behavioral outcome, study location, sample demographics, and intervention results. RESULTS: Thirty-eight systematic reviews met inclusion criteria and yielded 519 individual studies. We identified six functional categories and eight digital health modalities. Case management (63%) and health monitoring (50%) were the most common intervention functionalities. Mobile apps and web-based interventions were the two most commonly studied modalities. Evidence of efficacy was strongest for web-based, text-messaging, and phone-based approaches. Although mobile applications have been widely studied, the evidence on efficacy is mixed. Blood pressure and medication adherence were the most commonly studied outcomes. However, evidence on the efficacy of the various intervention modalities on these outcomes was variable. Among all individual studies, only 38.0% were conducted in the United States (n = 197). Of these U.S. studies, 54.8% adequately reported racial or ethnic group distribution. On average, samples were 27.0% Black, 17.1% Latinx, and 63.4% White. CONCLUSION: While evidence of the efficacy of selected digital health interventions, particularly those designed to improve blood pressure management and medication adherence, show promise, evidence of how these interventions can be generalized to historically underrepresented groups is insufficient. Including these underrepresented populations in both digital health experimental and feasibility studies is critical to advancing digital health science and achieving health equity.

Examining the Role of a Functional Deficiency of Iron in Lysosomal Storage Disorders with Translational Relevance to Alzheimer's Disease.

The recently presented Azalea Hypothesis for Alzheimer's disease asserts that iron becomes sequestered, leading to a functional iron deficiency that contributes to neurodegeneration. Iron sequestration can occur by iron being bound to protein aggregates, such as amyloid ß and tau, iron-rich structures not undergoing recycling (e.g., due to disrupted ferritinophagy and impaired mitophagy), and diminished delivery of iron from the lysosome to the cytosol. Reduced iron availability for biochemical reactions causes cells to respond to acquire additional iron, resulting in an elevation in the total iron level within affected brain regions. As the amount of unavailable iron increases, the level of available iron decreases until eventually it is unable to meet cellular demands, which leads to a functional iron deficiency. Normally, the lysosome plays an integral role in cellular iron homeostasis by facilitating both the delivery of iron to the cytosol (e.g., after endocytosis of the iron-transferrin-transferrin receptor complex) and the cellular recycling of iron. During a lysosomal storage disorder, an enzyme deficiency causes undigested substrates to accumulate, causing a sequelae of pathogenic events that may include cellular iron dyshomeostasis. Thus, a functional deficiency of iron may be a pathogenic mechanism occurring within several lysosomal storage diseases and Alzheimer's disease.

Stroke-Heart Syndrome: Does Sex Matter?

Background Cardiovascular complications after acute ischemic stroke (AIS) can be related to chronic/comorbid cardiac conditions or acute disruption of the brain-heart autonomic axis (stroke-heart syndrome). Women are known to be more vulnerable to certain stress-induced cardiac complications, such as Takotsubo cardiomyopathy. We investigated sex differences in cardiac troponin (cTn) elevation, cardiac events, and outcomes after AIS. Methods and Results We retrospectively analyzed consecutive patients with AIS from 5 stroke centers. Patients with AIS with elevated baseline cTn and at least 2 cTn measurements were included, while patients with acute comorbid conditions that could impact cTn levels were excluded. Poststroke acute myocardial injury was defined as the presence of a dynamic cTn pattern (rise/fall >20% in serial measurements) in the absence of acute atherosclerotic coronary disease (type 1 myocardial infarction) or cardiac death (type 3 myocardial infarction). From a total cohort of 3789 patients with AIS, 300 patients were included in the study: 160 were women (53%). Women were older, had a lower burden of cardiovascular risk factors, and more frequently had cardioembolic stroke and right insula involvement (P values all <0.05). In multivariate analysis, women were more likely to have a dynamic cTn pattern (adjusted odds ratio, 2.1 [95% CI, 1.2-3.6]) and develop poststroke acute myocardial injury (adjusted odds ratio, 2.1 [95% CI, 1.1-3.8]). Patients with poststroke acute myocardial injury had higher 7-day mortality (adjusted odds ratio, 5.5 [95% CI, 1.2-24.4]). Conclusions In patients with AIS with elevated cTn at baseline, women are twice as likely to develop poststroke acute myocardial injury, and this is associated with higher risk of short-term mortality. Translational studies are needed to clarify mechanisms underlying sex differences in cardiac events and mortality in AIS.

Spectrum of Cerebrovascular disease in Scleroderma: A Case Series and Systematic Review.

Introduction Central nervous system involvement in scleroderma has traditionally been considered uncommon. Recent studies suggest that scleroderma might be associated with an increased risk of cerebrovascular disease (CBVD), independent of conventional cardiovascular risk factors. We present a case series and a systematic review to capture the spectrum of CBVD in scleroderma, through a detailed description of clinical, demographic, laboratory, and radiographical findings. Methods In our case series, we included consecutive patients with scleroderma and CBVD seen over 35 years by our group in different hospitals in the United States. We also performed a systematic review from inception to July 2022. MEDLINE/EMBASE/WoS were searched for "scleroderma", "systemic scleroderma", "systemic sclerosis", "cerebrovascular", "stroke", "cerebrovascular disorders", "cerebrovascular disease". Results Fourteen patients with scleroderma and CBVD were included in our case series (mean age 48-year, 85% female). CBVDs were ischemic stroke (64%), hemorrhagic stroke (7%), venous thrombosis (7%), ischemic optic neuropathy (7%), probable ischemic stroke (14%). Of the 110 studies identified in our systematic review (45,484 patients), 82 reports with patient level data were included for quantitative analysis (93 patients, mean age 48-year, 79% female). Despite 16 different CBVD types identified, ischemic stroke was the most common CBVD (29%), followed by vasculopathy (20%), hemorrhage (12%), vasculitis (11%), and intracranial aneurysm (11%). Discussion/Conclusion Our relatively large case series combined with a systematic review of CBVD in SCL patients shows a heterogeneous spectrum of CBVD etiology, with acute ischemic stroke being the most common in our cases and in our literature review. A complex interaction between chronic inflammation, autoimmune mechanisms, and endothelial dysfunction seems to underlie the CBVD heterogeneity in scleroderma patients. This review informs clinicians about the spectrum of CBVD related to scleroderma and raise awareness about scleroderma being a possible risk factor for early onset CBVD.

The Azalea Hypothesis of Alzheimer Disease: A Functional Iron Deficiency Promotes Neurodegeneration.

Chlorosis in azaleas is characterized by an interveinal yellowing of leaves that is typically caused by a deficiency of iron. This condition is usually due to the inability of cells to properly acquire iron as a consequence of unfavorable conditions, such as an elevated pH, rather than insufficient iron levels. The causes and effects of chlorosis were found to have similarities with those pertaining to a recently presented hypothesis that describes a pathogenic process in Alzheimer disease. This hypothesis states that iron becomes sequestered (e.g., by amyloid ß and tau), causing a functional deficiency of iron that disrupts biochemical processes leading to neurodegeneration. Additional mechanisms that contribute to iron becoming unavailable include iron-containing structures not undergoing proper recycling (e.g., disrupted mitophagy and altered ferritinophagy) and failure to successfully translocate iron from one compartment to another (e.g., due to impaired lysosomal acidification). Other contributors to a functional deficiency of iron in patients with Alzheimer disease include altered metabolism of heme or altered production of iron-containing proteins and their partners (e.g., subunits, upstream proteins). A review of the evidence supporting this hypothesis is presented. Also, parallels between the mechanisms underlying a functional iron-deficient state in Alzheimer disease and those occurring for chlorosis in plants are discussed. Finally, a model describing the generation of a functional iron deficiency in Alzheimer disease is put forward.

User-Centered Mobile Applications for Stroke Survivors (MAPPS): A Mixed-Methods Study of Patient Preferences.

OBJECTIVE: Investigate stroke survivors' (SS) preferences for a hypothetical mHealth app for post-stroke care and to study the influence of demographic variables on these preferences. DESIGN: Mixed-methods, sequential, observational study. SETTING: Focus groups (phase 1) were conducted to identify SS perceptions and knowledge of mHealth applications (apps). Using grounded theory approach, recurring themes were identified. A multiple-choice questionnaire of 5 desired app features was generated using these themes and mailed to SS (national survey, phase 2). SS' demographics and perceived usefulness (yes/no) for each feature were recorded. In-person usability testing (phase 3) was conducted to identify areas of improvement in user interfaces of existing apps. Summative telephone interviews (phase 4) were conducted for final impressions supplementary to national survey. PARTICIPANTS: SS aged >18 years recruited from study hospital, national stroke association database, stroke support and advocacy groups. Non-English speakers and those unable to communicate were excluded. INTERVENTIONS: None. MAIN OUTCOME MEASURES: (1) Percentage of SS (phase 2) identifying proposed app features to be useful. (2) Influence of age, sex, race, education, and time since stroke on perceived usefulness. RESULTS: Ninety-six SS participated in focus groups. High cost, complexity, and lack of technical support were identified as barriers to adoption of mHealth apps. In the national survey (n=1194), ability to track fitness and diet (84%) and communication (70%) were the most and least useful features, respectively. Perceived usefulness was higher among younger SS (P<.001 to .006) and SS of color (African American and Hispanic) (ORs 1.73-4.41). Simple design and accommodation for neurologic deficits were main recommendations from usability testing. CONCLUSIONS: SS are willing to adopt mHealth apps that are free of cost and provide technical support. Apps for SS should perform multiple tasks and be of simple design. Greater interest for the app's features among SS of color may provide opportunities to address health inequities.

The effects of ketamine on symptoms of depression and anxiety in real-world care settings: A retrospective controlled analysis.

INTRODUCTION: Ketamine intravenous therapy (KIT) appears effective for treating depression in controlled trials testing a short series of infusions. A rapidly proliferating number of clinics offer KIT for depression and anxiety, using protocols without a strong evidence basis. Controlled comparison of mood and anxiety from real-world KIT clinics, and the stability of outcomes, is lacking. METHODS: We performed a retrospective controlled analysis on patients treated with KIT in ten community clinics across the US, between 08/2017-03/2020. Depression and anxiety symptoms were evaluated using the Quick Inventory of Depressive Symptomatology-Self Report 16-item (QIDS) and the Generalized Anxiety Disorder 7-item (GAD-7) scales, respectively. Comparison data sets from patients who did not undergo KIT were obtained from previously published real-world studies. RESULTS: Of 2758 patients treated, 714 and 836 met criteria for analysis of KIT induction and maintenance outcomes, respectively. Patients exhibited significant and concordant reduction in both anxiety and depression symptoms after induction (Cohen's d = -1.17 and d = -1.56, respectively). Compared to two external datasets of KIT-naive depressed patients or patients starting standard antidepressant therapy, KIT patients experienced a significantly greater reduction in depression symptoms at eight weeks (Cohen's d = -1.03 and d = -0.62 respectively). Furthermore, we identified a subpopulation of late-responders. During maintenance, up to a year post-induction, increases in symptoms were minimal. LIMITATIONS: Due to the retrospective nature of the analyses, interpreting this dataset is limited by incomplete patient information and sample attrition. CONCLUSIONS: KIT treatment elicited robust symptomatic relief that remained stable up to one year of follow-up.

Neurologic Improvement in Acute Cerebral Ischemia: Frequency, Magnitude, Predictors, and Clinical Outcomes.

BACKGROUND AND OBJECTIVES: Investigations of rapid neurologic improvement (RNI) in patients with acute cerebral ischemia (ACI) have focused on RNI occurring after hospital arrival. However, with stroke routing decisions and interventions increasingly migrating to the prehospital setting, there is a need to delineate the frequency, magnitude, predictors, and clinical outcomes of patients with ACI with ultra-early RNI (U-RNI) in the prehospital and early postarrival period. METHODS: We analyzed prospectively collected data of the prehospital Field Administration of Stroke Therapy-Magnesium (FAST-MAG) randomized clinical trial. Any U-RNI was defined as improvement by 2 or more points on the Los Angeles Motor Scale (LAMS) score between the prehospital and early post-emergency department (ED) arrival examinations and classified as moderate (2-3 point) or dramatic (4-5 point) improvement. Outcome measures included excellent recovery (modified Rankin Scale [mRS] score 0-1) and death by 90 days. RESULTS: Among the 1,245 patients with ACI, the mean age was 70.9 years (SD 13.2); 45% were women; the median prehospital LAMS was 4 (interquartile range [IQR] 3-5); the median last known well to ED-LAMS time was 59 minutes (IQR 46-80 minutes), and the median prehospital LAMS to ED-LAMS time was 33 minutes (IQR 28-39 minutes). Overall, any U-RNI occurred in 31%, moderate U-RNI in 23%, and dramatic U-RNI in 8%. Any U-RNI was associated with improved outcomes, including excellent recovery (mRS score 0-1) at 90 days 65.1% (246/378) vs 35.4% (302/852), p < 0.0001; decreased mortality by 90 days 3.7% (14/378) vs 16.4% (140/852), p < 0.0001; decreased symptomatic intracranial hemorrhage 1.6% (6/384) vs 4.6% (40/861), p = 0.0112; and increased likelihood of being discharged home 56.8% (218/384) vs 30.2% (260/861), p < 0.0001. DISCUSSION: U-RNI occurs in nearly 1 in 3 ambulance-transported patients with ACI and is associated with excellent recovery and decreased mortality at 90 days. Accounting for U-RNI may be useful for routing decisions and future prehospital interventions. TRIAL REGISTRATION INFORMATION: clinicaltrials.gov. Unique identifier: NCT00059332.

Exploring Whether Iron Sequestration within the CNS of Patients with Alzheimer's Disease Causes a Functional Iron Deficiency That Advances Neurodegeneration.

The involvement of iron in the pathogenesis of Alzheimer's disease (AD) may be multifaceted. Besides potentially inducing oxidative damage, the bioavailability of iron may be limited within the central nervous system, creating a functionally iron-deficient state. By comparing staining results from baseline and modified iron histochemical protocols, iron was found to be more tightly bound within cortical sections from patients with high levels of AD pathology compared to subjects with a diagnosis of something other than AD. To begin examining whether the bound iron could cause a functional iron deficiency, a protein-coding gene expression dataset of initial, middle, and advanced stages of AD from olfactory bulb tissue was analyzed for iron-related processes with an emphasis on anemia-related changes in initial AD to capture early pathogenic events. Indeed, anemia-related processes had statistically significant alterations, and the significance of these changes exceeded those for AD-related processes. Other changes in patients with initial AD included the expressions of transcripts with iron-responsive elements and for genes encoding proteins for iron transport and mitochondrial-related processes. In the latter category, there was a decreased expression for the gene encoding pitrilysin metallopeptidase 1 (PITRM1). Other studies have shown that PITRM1 has an altered activity in patients with AD and is associated with pathological changes in this disease. Analysis of a gene expression dataset from PITRM1-deficient or sufficient organoids also revealed statistically significant changes in anemia-like processes. These findings, together with supporting evidence from the literature, raise the possibility that a pathogenic mechanism of AD could be a functional deficiency of iron contributing to neurodegeneration.