Provider Experience With the Use of Ketamine for Refractory Status Epilepticus.

OBJECTIVE: Refractory status epilepticus (RSE) treated with anesthetic agents can be associated with complications including respiratory depression and hypotension. Ketamine is an emerging RSE treatment, but optimal dosing and timing are unknown. We studied provider attitudes and practices regarding the use of ketamine for RSE. METHODS: A literature review informed the creation of the survey, developed by professionals in epilepsy, pharmacy, and neurocritical care. The survey was distributed to members of the Critical Care EEG Monitoring and Research Consortium, Neurocritical Care Society, American Academy of Neurology Synapse community, American Epilepsy Society, and the Canadian League Against Epilepsy. Descriptive statistics were calculated. RESULTS: There were 109 respondents. First-line agents for RSE were midazolam (53%), propofol (42%), pentobarbital (2%), and ketamine (1%). Reasons for ketamine use included failure of midazolam/propofol to control seizures (81%) or hypotension on another anesthetic (35%). Perceived contraindications included hypertension (37%), elevated intracranial pressure (24%), and heart failure (18%). Perceived benefits included decreased use of vasopressors (53%) and more rapid RSE control when used adjunctively (49%). Routine ketamine users often treated more than 10 RSE cases per year, worked as intensivists or at academic institutions. Of the respondents, 59% found ketamine useful for RSE and 94% were interested in learning more about its use. CONCLUSIONS: Although most participants found ketamine helpful for RSE, it is mainly used as a second-line agent adjunctively with midazolam or propofol. Perceived ketamine benefits included decreased need for hemodynamic support and more rapid seizure control when used in conjunction with other anesthetics. Perceived contraindications centered on cardiac and intracranial pressure concerns.

Understanding the Perspectives and Needs of Latinx Caregivers of Persons with Alzheimer's Disease in the Appalachians: An Interpretive Phenomenological Approach.

Background: Alzheimer's disease and related dementias (ADRD) disproportionately impact Latinx and other communities of color in the United States. The challenges for patients with ADRD and their informal caretakers can be attributed, in part, to the gaps that exist within health care services and systems. Objective: To understand the perspectives of barriers, beliefs, knowledge, and needs for the Latinx informal caregivers that take care of relatives with ADRD in the Upstate of South Carolina, region of Appalachia. Methods: This study was approved by the GHS-Prisma Health and Clemson University IRB, Study #Pro00086707. In-depth phone interviews were conducted with a sample of Latinx informal caregivers. A descriptive and interpretive phenomenological approach was used for analysis. Participants were recruited through community partnerships with local organizations. Results: Salient themes identified in this study included the relevance of caregiver's degree of awareness about the disease and a perspective of Alzheimer's disease as a progressive and degenerative disease. Critical moments identified encompassed challenges related to patient engagement with the outside world, their attitudes, and behaviors, as well as caregiver-related challenges with access to culturally and linguistically relevant resources needed to provide proper care. Caregivers identified several culturally relevant coping strategies used and motivators in providing care for their relatives with ADRD. Conclusions: Linguistically and culturally sensitive programs and resources that account for knowledge, assets, and needs of Latinx informal caregivers of ADRD patients are needed to improve the quality of care and decrease disparities in health outcomes for Latinx older adults.

Measuring older adults' wellbeing when transitioning into assisted living facilities: a confirmatory factor analysis of the Mueller assessment of transition (MAT).

OBJECTIVES: Older adults' wellbeing during the transition into an assisted living facility (ALF) is not well understood and may influence their wellbeing. The Mueller Assessment of Transition (MAT) was created to measure the impact of transition on older adults' wellbeing. Early developmental testing of the MAT revealed a hypothesized model with two constructs (adjustment strategies and constraints to wellbeing). Therefore, the purpose of this study was to confirm the factor structure of the MAT with a representative sample of older adults transitioning into ALFs. METHODS: In a nationwide sample, 108 older adult participants completed the MAT to measure wellbeing when relocating into ALFs. Confirmatory factor analysis (CFA) assessed the structural validity of the MAT. Internal consistency was evaluated, and chi-square tests of association for regional differences in MAT scores were also conducted. RESULTS: The CFA produced strong fit indices to confirm the hypothesized 2-factor (constraints to wellbeing and adjustment strategies) model of the MAT. Cronbach's alpha for the internal consistency was 0.784 and chi-square test indicated no significant regional differences. CONCLUSION: The MAT was established as a valid and reliable standardized assessment. Implications for using the MAT as a tool to measure older adults' wellbeing and future research are discussed.

Weight Loss Is a Strong Predictor of Memory Disorder Independent of Genetic Influences.

BACKGROUND: Past studies identified a link between weight loss and dementia, but lacked consistent conclusions. We sought to establish this link by examining the weight change profiles before and after dementia diagnosis. METHODS: Using data from the Health and Retirement Study (1996-2020), we examined 13,123 participants. We conducted a nested case-control analysis to assess differences in biennial weight change profile while controlling for BMI, longevity polygenic risk scores, and APOE gene variants. RESULTS: Participants with a memory disorder lost weight (-0.63%) biennially, whereas those without a diagnosis did not (+0.013%, p-value < 0.0001). Our case-control study shows a significant difference (p-value < 0.01) in pre-dementia % weight changes between the cases (-0.29%) and controls (0.19%), but not in post-dementia weight changes. The weight loss group have the highest risk (OR = 2.01; p-value < 0.0001) of developing a memory disorder compared to the stable weight and weight gain groups. The observations hold true after adjusting for BMI, longevity polygenic risk scores, and APOE variant in a multivariable model. CONCLUSIONS: We observe that weight loss in dementia is a physiological process independent of genetic factors associated with BMI and longevity. Pre-dementia weight loss may be an important prognostic criterion to assess a person's risk of developing a memory disorder.

Exogenous butyrate inhibits butyrogenic metabolism and alters expression of virulence genes in Clostridioides difficile.

The gut microbiome engenders colonization resistance against the diarrheal pathogen Clostridioides difficile but the molecular basis of this colonization resistance is incompletely understood. A prominent class of gut microbiome-produced metabolites important for colonization resistance against C. difficile is short chain fatty acids (SCFAs). In particular, one SCFA (butyrate) decreases the fitness of C. difficile in vitro and is correlated with C. difficile-inhospitable gut environments, both in mice and in humans. Here, we demonstrate that butyrate-dependent growth inhibition in C. difficile occurs under conditions where C. difficile also produces butyrate as a metabolic end product. Furthermore, we show that exogenous butyrate is internalized into C. difficile cells, is incorporated into intracellular CoA pools where it is metabolized in a reverse (energetically unfavorable) direction to crotonyl-CoA and (S)-3-hydroxybutyryl-CoA and/or 4-hydroxybutyryl-CoA. This internalization of butyrate and reverse metabolic flow of butyrogenic pathway(s) in C. difficile coincides with alterations in toxin production and sporulation. Together, this work highlights butyrate as a signal of a C. difficile inhospitable environment to which C. difficile responds by producing its diarrheagenic toxins and producing environmentally-resistant spores necessary for transmission between hosts. These findings provide foundational data for understanding the molecular and genetic basis of how C. difficile growth is inhibited by butyrate and how butyrate serves as a signal to alter C. difficile virulence in the face of a highly competitive and dynamic gut environment.

Emergency department management of acute intracerebral hemorrhage.

Acute intracerebral hemorrhage accounts for only a small portion of all stroke presentations, but often leads to a high rate of morbidity and mortality. The presentation of patients with ICH is often similar to other stroke patients and requires rapid recognition, imaging, and evaluation. Treatment begins in the emergency department and focuses on correction of abnormal coagulopathies, blood pressure reduction, emergent treatment of intracranial hypertension, and recognition of those in need of urgent surgical decompression. Patients should be admitted to capable critical care units, with expertise in neurocritical care if available. This review presents evidence-based recommendations for the emergency department identification and management of patients with ICH.

Exploring Constraints to Well-Being for Older Adults in Transition Into an Assisted Living Home: A Qualitative Study.

Transitions into an assisted living home (ALH) are difficult and may impact the well-being of older adults. A thematic analysis guided by grounded theory was employed to better understand how a transition into an ALH influenced older adults' overall well-being. Individual, face-to-face interviews were conducted with a convenience sample of 14 participants at an ALH in the rural, southeastern U.S. Two central findings that influenced well-being during the transition process were revealed: loss of independence (sub-themes include loss of physical and mental health and loss of driving) and downsizing in space and possessions. The themes support and broaden the Hierarchical Leisure Constraints Theory, a Modified Constraints to Wellbeing model is proposed, and implications for older adult health care practitioners in ALHs are recommended. Further research is needed on the Modified Constraints to Wellbeing model and how to better describe these constraints to older adults' well-being when relocating into ALHs.

Genetic Factors That Contribute to Antibiotic Resistance through Intrinsic and Acquired Bacterial Genes in Urinary Tract Infections.

The overprescribing and misuse of antibiotics have led to the rapid development of multidrug-resistant bacteria, such as those that cause UTIs. UTIs are the most common outpatient infections and are mainly caused by Escherichia coli and Klebsiella spp., although some Gram-positive bacteria, such as Pseudomonas aeruginosa, have been isolated in many cases. The rise of antimicrobial-resistant bacteria is a major public health concern, as it is predicted to lead to increased healthcare costs and poor patient outcomes and is expected to be the leading cause of global mortality by 2050. Antibiotic resistance among bacterial species can arise from a myriad of factors, including intrinsic and acquired resistance mechanisms, as well as mobile genetic elements, such as transposons, integrons, and plasmids. Plasmid-mediated resistance is of major concern as drug-resistance genes can quickly and efficiently spread across bacterial species via horizontal gene transfer. The emergence of extended-spectrum ß-lactamases (ESBLs) such as NDM-1, OXA, KPC, and CTX-M family members has conferred resistance to many commonly used antibiotics in the treatment of UTIs, including penicillins, carbapenems, cephalosporins, and sulfamethoxazole. This review will focus on plasmid-mediated bacterial genes, especially those that encode ESBLs, and how they contribute to antibiotic resistance. Early clinical detection of these genes in patient samples will provide better treatment options and reduce the threat of antibiotic resistance.

Analyzing Twitter-Based Social Networks of Support Communities for Hispanic and African American Family Caregivers of Persons with Dementia.

We applied social network analysis to compare Hispanic and Black dementia caregiving networks on Twitter that were established as part of a clinical trial from January 12, 2022, to October 31, 2022. We extracted Twitter data from our caregiver support communities (N=1980 followers, 811 enrollees) via the Twitter API and used social network analysis software to compare friend/follower interactions within each Hispanic and Black caregiving network. Analysis of the social networks revealed that enrolled family caregivers without prior social media competency had overall low connectedness compared to both enrolled and non-enrolled caregivers with social media competency, who were more integrated into the communities that developed through the clinical trial, partly due to their ties to external dementia caregiving groups. These observed dynamics will help to guide further social media-based interventions and also support the observation that our recruitment strategies effectively enrolled family caregivers with various levels of social media competency.

Comparing Emotional Valence Scores of Twitter Messages from Human Coding and Machine Learning Algorithms Among Hispanic and African American Family Caregivers of Persons with Dementia.

We compared emotional valence scores as determined via machine learning approaches to human-coded scores of direct messages on Twitter from our 2,301 followers during a Twitter-based clinical trial screening for Hispanic and African American family caregivers of persons with dementia. We manually assigned emotional valence scores to 249 randomly selected direct Twitter messages from our followers (N=2,301), then we applied three machine learning sentiment analysis algorithms to extract emotional valence scores for each message and compared their mean scores to the human coding results. The aggregated mean emotional scores from the natural language processing were slightly positive, while the mean score from human coding as a gold standard was negative. Clusters of strongly negative sentiments were observed in followers' responses to being found non-eligible for the study, indicating a significant need for alternative strategies to provide similar research opportunities to non-eligible family caregivers.

Application of Topic Modeling on Artificial Intelligence Studies as a Foundation to Develop Ethical Guidelines in African American Dementia Caregiving.

We applied natural language processing and topic modeling to publicly available abstracts and titles of 263 papers in the scientific literature mentioning AI and demographics (corpus 1 before Covid-19, corpus 2 after Covid-19) extracted from the MEDLINE database. We found exponential growth of AI studies mentioning demographics since the pandemic (Before Covid-19: N= 40 vs. After Covid-19: N= 223) [forecast model equation: ln(Number of Records) = 250.543*ln(Year) + -1904.38, p = 0.0005229]. Topics related to diagnostic imaging, quality of life, Covid, psychology, and smartphone increased during the pandemic, while cancer-related topics decreased. The application of topic modeling to the scientific literature on AI and demographics provides a foundation for the next steps regarding developing guidelines for the ethical use of AI for African American dementia caregivers.

Clinical features, comparative imaging findings, treatment, and outcome in dogs with discospondylitis: A multi-institutional retrospective study.

BACKGROUND: Limited recent data exists regarding discospondylitis in dogs. HYPOTHESIS/OBJECTIVES: (i) Describe the signalment, clinical and imaging findings, etiologic agents, treatment, and outcome of dogs with discospondylitis, (ii) determine diagnostic agreement between radiographs, CT, and MRI with regard to the presence of discospondylitis and its location, and (iii) determine risk factors for relapse and progressive neurological deterioration. ANIMALS: Three hundred eighty-six dogs. METHODS: Multi-institutional retrospective study. Data extracted from medical records were: signalment, clinical and examination findings, diagnostic results, treatments, complications, and outcome. Potential risk factors were recorded. Breed distribution was compared to a control group. Agreement between imaging modalities was assessed via Cohen's kappa statistic. Other analyses were performed on categorical data, using cross tabulations with chi-squared and Fisher's exact tests. RESULTS: Male dogs were overrepresented (236/386 dogs). L7-S1 (97/386 dogs) was the most common site. Staphylococcus species (23/38 positive blood cultures) were prevalent. There was a fair agreement (κ = 0.22) between radiographs and CT, but a poor agreement (κ = 0.05) between radiographs and MRI with regard to evidence of discospondylitis. There was good agreement between imaging modalities regarding location of disease. Trauma was associated with an increased risk of relapse (P = .01, OR: 9.0, 95% CI: 2.2-37.0). Prior steroid therapy was associated with an increased risk of progressive neurological dysfunction (P = .04, OR: 4.7, 95% CI: 1.2-18.6). CONCLUSIONS AND CLINICAL IMPORTANCE: Radiograph and MRI results could be discrepant in dogs with discospondylitis. Prior trauma and corticosteroids could be associated with relapse and progressive neurological dysfunction, respectively.

Evaluation of Safety Outcomes of Undiluted Levetiracetam Intravenous Push Compared to Intravenous Piggyback.

BACKGROUND: Breakthrough seizures and status epilepticus require urgent management. Administration of intravenous push (IVP) levetiracetam has been demonstrated to be safe as compared to intravenous piggyback (IVPB). This transition can potentially offer faster time to administration and reduced drug and material cost. The objective of this study was to observe safety of administration in patients receiving levetiracetam via IVP compared to IVPB in acute care settings. METHODS: This is a multi-center, observational, retrospective cohort study of 1214 adult patients who received levetiracetam pre- and post-implementation of IVP over a 6 month timespan. Primary outcome was time from order verification to administration of urgent first-time doses. Secondary outcomes included time to administration of loading doses and cost. Safety outcome was infusion site related reactions. RESULTS: Time from order verification to administration of urgent first-time doses pre- and post-implementation of IVP administration was reduced from 61 minutes to 47 minutes (P=0.0002). Infusion site related reactions were observed in 6 out of 5432 doses in the IVPB arm and in 5 out of 4700 doses in the IVP arm (P=1). Total estimated cost was $76,171.96 for the 5449 IVPB total doses and $11,484.33 for the 4721 IVP total doses. CONCLUSIONS: Transition from IVPB to IVP administration reduced time from order verification to administration of urgent first-time doses with both administrations having similar incidence of infusion site related reactions. Cost savings and improved workflow were observed. Levetiracetam administered via IVP may be considered as a safe alternative method of administration in the acute care setting.

Reduction of Eyedrop Volume for Topical Ophthalmic Medications with the Nanodropper Bottle Adaptor.

Purpose: To determine the drop volume and total number of dispensed drops using the Nanodropper eyedrop bottle adaptor (Nanodropper, Inc.) compared to drops dispensed from stock bottles to potentially limit ocular toxicity of these eyedrops and prolong bottle use. Patients and Methods: Six topical ocular hypotensive medications (5 solutions, 1 suspension), one steroid (suspension) and two artificial tears emulsions were selected for this study. An analytical balance was used to determine the mass per 10 drops with and without the volume-reducing adaptor and repeated until the bottles were completely emptied. The density of each product was determined using the calculated density. The average drop volume and number of drops per bottle for the nine medications were compared with and without the adaptor with paired t-testing. Results: When all medications were assessed, the drops delivered with the adaptor were 62.1% smaller than eyedrops administered from standard bottles. Compared to stock bottle eyedrops, which had a mean volume of 39.8 ± 2.1 µL, the adaptor resulted in drops with a mean volume of 15.1 ± 1.0 µL, p<0.0001. The adaptor delivered 2.6x the number of drops dispensed from a standard 2.5 mL bottle (184.1 ± 15.1 drops with adaptor and 69.8 ± 4.9 drops from stock bottle, p<0.0001). Conclusion: The Nanodropper eyedrop bottle adaptor can significantly reduce drop volume and increase the overall number of drops dispensed compared with stock eyedrop bottles. Further studies are needed to elucidate the clinical impact of utilizing decreased drop volume with direct comparison to current standards of care.

Trends and Characteristics of Buprenorphine-Involved Overdose Deaths Prior to and During the COVID-19 Pandemic.

Importance: Buprenorphine remains underused in treating opioid use disorder, despite its effectiveness. During the onset of the COVID-19 pandemic, the US government implemented prescribing flexibilities to support continued access. Objective: To determine whether buprenorphine-involved overdose deaths changed after implementing these policy changes and highlight characteristics and circumstances of these deaths. Design, Setting, and Participants: This cross-sectional study used data from the State Unintentional Drug Overdose Reporting System (SUDORS) to assess overdose deaths in 46 states and the District of Columbia occurring July 2019 to June 2021. Data were analyzed from March 7, 2022, to June 30, 2022. Main Outcomes and Measures: Buprenorphine-involved and other opioid-involved overdose deaths were examined. Monthly opioid-involved overdose deaths and the percentage involving buprenorphine were computed to assess trends. Proportions and exact 95% CIs of drug coinvolvement, demographics, and circumstances were calculated by group. Results: During July 2019 to June 2021, 32 jurisdictions reported 89 111 total overdose deaths and 74 474 opioid-involved overdose deaths, including 1955 buprenorphine-involved overdose deaths, accounting for 2.2% of all drug overdose deaths and 2.6% of opioid-involved overdose deaths. Median (IQR) age was similar for buprenorphine-involved overdose deaths (41 [34-55] years) and other opioid-involved overdose deaths (40 [31-52] years). A higher proportion of buprenorphine-involved overdose decedents, compared with other opioid-involved decedents, were female (36.1% [95% CI, 34.2%-38.2%] vs 29.1% [95% CI, 28.8%-29.4%]), non-Hispanic White (86.1% [95% CI, 84.6%-87.6%] vs 69.4% [95% CI, 69.1%-69.7%]), and residing in rural areas (20.8% [95% CI, 19.1%-22.5%] vs 11.4% [95% CI, 11.2%-11.7%]). Although monthly opioid-involved overdose deaths increased, the proportion involving buprenorphine fluctuated but did not increase during July 2019 to June 2021. Nearly all (92.7% [95% CI, 91.5%-93.7%]) buprenorphine-involved overdose deaths involved at least 1 other drug; higher proportions involved other prescription medications compared with other opioid-involved overdose deaths (eg, anticonvulsants: 18.6% [95% CI, 17.0%-20.3%] vs 5.4% [95% CI, 5.2%-5.5%]) and a lower proportion involved illicitly manufactured fentanyls (50.2% [95% CI, 48.1%-52.3%] vs 85.3% [95% CI, 85.1%-85.5%]). Buprenorphine decedents were more likely to be receiving mental health treatment than other opioid-involved overdose decedents (31.4% [95% CI, 29.3%-33.5%] vs 13.3% [95% CI, 13.1%-13.6%]). Conclusions and Relevance: The findings of this cross-sectional study suggest that actions to facilitate access to buprenorphine-based treatment for opioid use disorder during the COVID-19 pandemic were not associated with an increased proportion of overdose deaths involving buprenorphine. Efforts are needed to expand more equitable and culturally competent access to and provision of buprenorphine-based treatment.

Influence of Hormonal Contraceptive Use and HIV on Cervicovaginal Cytokines and Microbiota in Malawi.

Important questions remain on how hormonal contraceptives alter the local immune environment and the microbiota in the female genital tract and how such effects may impact susceptibility to HIV infection. We leveraged samples from a previously conducted clinical trial of Malawian women with (n = 73) and without (n = 24) HIV infection randomized to depot medroxyprogesterone acetate (DMPA) or the levonogestrel implant in equal numbers within each group and determined the effects of these hormonal contraceptives (HCs) on the vaginal immune milieu and the composition of the vaginal microbiota. Longitudinal data for soluble immune mediators, measured by multiplex bead arrays and enzyme-linked immunosorbent assays (ELISAs), and vaginal microbiota, assessed by 16S rRNA gene amplicon, were collected prior to and over a period of 180 days post-HC initiation. DMPA and levonogestrel had only minimal effects on the vaginal immune milieu and microbiota. In women with HIV, with the caveat of a small sample size, there was an association between the median log10 change in the interleukin-12 (IL-12)/IL-10 ratio in vaginal fluid at day 180 post-HC compared to baseline when these women were classified as having a community state type (CST) IV vaginal microbiota and were randomized to DMPA. Long-lasting alterations in soluble immune markers or shifts in microbiota composition were not observed. Furthermore, women with HIV did not exhibit increased viral shedding in the genital tract after HC initiation. Consistent with the results of the ECHO (Evidence for Contraceptive Options and HIV Outcomes) trial, our data imply that the progestin-based HC DMPA and levonorgestrel are associated with minimal risk for women with HIV. (This study has been registered at ClinicalTrials.gov under registration no. NCT02103660). IMPORTANCE The results of the Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial, the first large randomized controlled clinical trial comparing the HIV acquisition risk of women receiving DMPA, the levonorgestrel (LNG) implant, or the copper intrauterine device (IUD), did not reveal an increased risk of HIV acquisition for women on any of these three contraceptives. Our study results confirm that the two different progestin-based hormonal contraceptives DMPA and levonogestrel will not increase the risk for HIV infection. Furthermore, DMPA and levonogestrel have only minimal effects on the immune milieu and the microbiota in the vaginal tract, attesting to the safety of these hormonal contraceptives.

Drug Overdose Deaths Among Persons Aged 10-19 Years - United States, July 2019-December 2021.

U.S. drug overdose deaths increased 30% from 2019 to 2020 and 15% in 2021, resulting in an estimated 108,000 deaths in 2021.* Among persons aged 14-18 years, overdose deaths increased 94% from 2019 to 2020 and 20% from 2020 to 2021 (1), although illicit drug use declined overall among surveyed middle and high school students during 2019-2020 (2). Widespread availability of illicitly manufactured fentanyls (IMFs),† proliferation of counterfeit pills resembling prescription drugs but containing IMFs or other illicit drugs,§ and ease of purchasing pills through social media¶ have increased fatal overdose risk among adolescents (1,3). Using CDC's State Unintentional Drug Overdose Reporting System (SUDORS), this report describes trends and characteristics of overdose deaths during July 2019-December 2021 among persons aged 10-19 years (hereafter referred to as adolescents). From July-December 2019 to July-December 2021, median monthly overdose deaths increased 109%, and deaths involving IMFs increased 182%. Approximately 90% of overdose deaths involved opioids, and 83.9% involved IMFs; however, only 35% of decedents had documented opioid use history. Counterfeit pill evidence was present in 24.5% of overdose deaths, and 40.9% of decedents had evidence of mental health conditions or treatment. To prevent overdose deaths among adolescents, urgent efforts are needed, including preventing substance use initiation, strengthening partnerships between public health and public safety to reduce availability of illicit drugs, expanding efforts focused on resilience and connectedness of adolescents to prevent substance misuse and related harms, increasing education regarding IMFs and counterfeit pills, expanding naloxone training and access, and ensuring access to treatment for substance use and mental health disorders.

TOMM40 genetic variants associated with healthy aging and longevity: a systematic review.

INTRODUCTION: Healthy aging relies on mitochondrial functioning because this organelle provides energy and diminishes oxidative stress. Single nucleotide polymorphisms (SNPs) in TOMM40, a critical gene that produces the outer membrane protein TOM40 of mitochondria, have been associated with mitochondrial dysfunction and neurodegenerative processes. Yet it is not clear whether or how the mitochondria may impact human longevity. We conducted this review to ascertain which SNPs have been associated with markers of healthy aging. METHODS: Using the PRISMA methodology, we conducted a systematic review on PubMed and Embase databases to identify associations between TOMM40 SNPs and measures of longevity and healthy aging. RESULTS: Twenty-four articles were selected. The TOMM40 SNPs rs2075650 and rs10524523 were the two most commonly identified and studied SNPs associated with longevity. The outcomes associated with the TOMM40 SNPs were changes in BMI, brain integrity, cognitive functions, altered inflammatory network, vulnerability to vascular risk factors, and longevity. DISCUSSIONS: Our systematic review identified multiple TOMM40 SNPs potentially associated with healthy aging. Additional research can help to understand mechanisms in aging, including resilience, prevention of disease, and adaptation to the environment.

Vital Signs: Drug Overdose Deaths, by Selected Sociodemographic and Social Determinants of Health Characteristics - 25 States and the District of Columbia, 2019-2020.

INTRODUCTION: Drug overdose deaths increased approximately 30% from 2019 to 2020 in the United States. Examining rates by demographic and social determinants of health characteristics can identify disproportionately affected populations and inform strategies to reduce drug overdose deaths. METHODS: Data from the State Unintentional Drug Overdose Reporting System (SUDORS) were used to analyze overdose death rates from 2019 to 2020 in 25 states and the District of Columbia. Rates were examined by race and ethnicity and county-level social determinants of health (e.g., income inequality and treatment provider availability). RESULTS: From 2019 to 2020, drug overdose death rates increased by 44% and 39% among non-Hispanic Black (Black) and non-Hispanic American Indian or Alaska Native (AI/AN) persons, respectively. Significant disparities were found across sex, age, and racial and ethnic subgroups. In particular, the rate in 2020 among Black males aged ≥65 years (52.6 per 100,000) was nearly seven times that of non-Hispanic White males aged ≥65 years (7.7). A history of substance use was frequently reported. Evidence of previous substance use treatment was lowest for Black persons (8.3%). Disparities in overdose deaths, particularly among Black persons, were larger in counties with greater income inequality. Opioid overdose rates in 2020 were higher in areas with more opioid treatment program availability compared with areas with lower opioid treatment availability, particularly among Black (34.3 versus 16.6) and AI/AN (33.4 versus 16.2) persons. CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Health disparities in overdose rates continue to worsen, particularly among Black and AI/AN persons; social determinants of health, such as income inequality, exacerbate these inequities. Implementation of available, evidence-based, culturally responsive overdose prevention and response efforts that address health disparities impacting disproportionately affected populations are urgently needed.