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1.
Prev Chronic Dis ; 21: E46, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38900693

ABSTRACT

Easy access and display of state-level estimates of the prevalence of chronic diseases and their risk factors can guide evidence-based decision-making, policy development, and tailored efforts to improve population health outcomes; however, these estimates are often presented across multiple websites and reports. The Chronic Disease Indicators (CDI) web tool (www.cdc.gov/cdi) disseminates state-level data compiled from various data sources, including surveys, vital records, and administrative data, and applies standardized definitions to estimate and track a wide range of key indicators of chronic diseases and their risk factors. In 2022-2024, the indicators were refreshed to include 113 measures across 21 topic areas, and the web tool was modernized to enhance its key features and functionalities, including standardized indicator definitions; interactive charts, graphs, and maps that present data in a visually appealing format; an easy-to-use web-based interface for users to query and extract the data they need; and state comparison reports to identify geographic variations in disease and risk factor prevalence. National and state-level estimates are provided for the overall population and, where applicable, by sex, race and ethnicity, and age. We review the history of CDIs, describe the 2022-2024 refresh process, and explore the interactive features of the CDI web tool with the goal of demonstrating how practitioners, policymakers, and other users can easily examine and track a wide range of key indicators of chronic diseases and their risk factors to support state-level public health action.


Subject(s)
Internet , Humans , Chronic Disease/epidemiology , United States/epidemiology , Risk Factors , Prevalence , Health Status Indicators
2.
Arthroplast Today ; 27: 101410, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38840694

ABSTRACT

Background: Successful total hip arthroplasty (THA) relies on the correct implant position. THA accuracy can be improved with the use of intraoperative fluoroscopic-assisted computer navigation. Artificial intelligence (AI) software may enhance fluoroscopic navigation; however, the accuracy of the AI compared to human-controlled software in assessing acetabular component position and leg length discrepancy (LLD) has not been studied. Methods: We analyzed 420 consecutive primary THAs performed by a single surgeon using fluoroscopic-assisted computer navigation software. The first cohort of 211 patients required inputs from a human technician (manual), while the second cohort of 209 patients used an automated version of the software controlled by AI. The intraoperative acetabular component placement (inclination and anteversion) and LLD were recorded and compared to the 2-week postoperative standing anterior-posterior pelvis radiograph. Results: Ninety-four percent (199/211) of cups in the manual cohort and 95% (198/209) of cups in the AI cohort were within the Lewinnek "safe-zone" (P = 1.0). In the manual cohort, 69% (146/211) of THAs had a final LLD within ±2 mm of the intraoperatively navigated LLD (ie, ΔLLD ≤2 mm). In the AI cohort, 66% (137/209) of THAs had a final LLD within ±2 mm of the intraoperatively navigated LLD (P = .47). Ninety-nine percent (209/211) of hips in the manual cohort and 98% (205/209) of hips in the AI cohort had a final LLD within ±5 mm of the intraoperatively navigated LLD (P = .45). Conclusions: Both AI and human-controlled versions of the same navigation platform were similarly accurate for navigating cup position within the Lewinnek "safe zone" and LLD accuracy.

3.
Diabetologia ; 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38910151

ABSTRACT

Given the proven benefits of screening to reduce diabetic ketoacidosis (DKA) likelihood at the time of stage 3 type 1 diabetes diagnosis, and emerging availability of therapy to delay disease progression, type 1 diabetes screening programmes are being increasingly emphasised. Once broadly implemented, screening initiatives will identify significant numbers of islet autoantibody-positive (IAb+) children and adults who are at risk of (confirmed single IAb+) or living with (multiple IAb+) early-stage (stage 1 and stage 2) type 1 diabetes. These individuals will need monitoring for disease progression; much of this care will happen in non-specialised settings. To inform this monitoring, JDRF in conjunction with international experts and societies developed consensus guidance. Broad advice from this guidance includes the following: (1) partnerships should be fostered between endocrinologists and primary-care providers to care for people who are IAb+; (2) when people who are IAb+ are initially identified there is a need for confirmation using a second sample; (3) single IAb+ individuals are at lower risk of progression than multiple IAb+ individuals; (4) individuals with early-stage type 1 diabetes should have periodic medical monitoring, including regular assessments of glucose levels, regular education about symptoms of diabetes and DKA, and psychosocial support; (5) interested people with stage 2 type 1 diabetes should be offered trial participation or approved therapies; and (6) all health professionals involved in monitoring and care of individuals with type 1 diabetes have a responsibility to provide education. The guidance also emphasises significant unmet needs for further research on early-stage type 1 diabetes to increase the rigour of future recommendations and inform clinical care.

4.
Diabetes Care ; 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38912694

ABSTRACT

Given the proven benefits of screening to reduce diabetic ketoacidosis (DKA) likelihood at the time of stage 3 type 1 diabetes diagnosis, and emerging availability of therapy to delay disease progression, type 1 diabetes screening programs are being increasingly emphasized. Once broadly implemented, screening initiatives will identify significant numbers of islet autoantibody-positive (IAb+) children and adults who are at risk for (confirmed single IAb+) or living with (multiple IAb+) early-stage (stage 1 and stage 2) type 1 diabetes. These individuals will need monitoring for disease progression; much of this care will happen in nonspecialized settings. To inform this monitoring, JDRF, in conjunction with international experts and societies, developed consensus guidance. Broad advice from this guidance includes the following: 1) partnerships should be fostered between endocrinologists and primary care providers to care for people who are IAb+; 2) when people who are IAb+ are initially identified, there is a need for confirmation using a second sample; 3) single IAb+ individuals are at lower risk of progression than multiple IAb+ individuals; 4) individuals with early-stage type 1 diabetes should have periodic medical monitoring, including regular assessments of glucose levels, regular education about symptoms of diabetes and DKA, and psychosocial support; 5) interested people with stage 2 type 1 diabetes should be offered trial participation or approved therapies; and 6) all health professionals involved in monitoring and care of individuals with type 1 diabetes have a responsibility to provide education. The guidance also emphasizes significant unmet needs for further research on early-stage type 1 diabetes to increase the rigor of future recommendations and inform clinical care.

5.
Sci Transl Med ; 16(746): eadn2404, 2024 05 08.
Article in English | MEDLINE | ID: mdl-38718135

ABSTRACT

CD4+CD25hiCD127lo/-FOXP3+ regulatory T cells (Tregs) play a key role in preventing autoimmunity. In autoimmune type 1 diabetes (T1D), adoptive transfer of autologous polyclonal Tregs has been shown to be safe in adults in phase 1 clinical trials. We explored factors contributing to efficacy of autologous polyclonal expanded Tregs (expTregs) in a randomized phase 2 multi-center, double-blind, clinical trial (Sanford/Lisata Therapeutics T-Rex phase 2 trial, ClinicalTrials.gov NCT02691247). One hundred ten treated children and adolescents with new-onset T1D were randomized 1:1:1 to high-dose (20 × 106 cells/kilogram) or low-dose (1 × 106 cells/kilogram) treatments or to matching placebo. Cytometry as well as bulk and single-cell RNA sequencing were performed on selected expTregs and peripheral blood samples from participants. The single doses of expTregs were safe but did not prevent decline in residual ß cell function over 1 year compared to placebo (P = 0.94 low dose, P = 0.21 high dose), regardless of age or baseline C-peptide. ExpTregs were highly activated and suppressive in vitro. A transient increase of activated memory Tregs was detectable 1 week after infusion in the high-dose cohort, suggesting effective transfer of expTregs. However, the in vitro fold expansion of expTregs varied across participants, even when accounting for age, and lower fold expansion and its associated gene signature were linked with better C-peptide preservation regardless of Treg dose. These results suggest that a single dose of polyclonal expTregs does not alter progression in T1D; instead, Treg quality may be an important factor.


Subject(s)
Diabetes Mellitus, Type 1 , T-Lymphocytes, Regulatory , Humans , Diabetes Mellitus, Type 1/immunology , Diabetes Mellitus, Type 1/therapy , T-Lymphocytes, Regulatory/immunology , Child , Adolescent , Male , Female , Double-Blind Method , Child, Preschool , Transplantation, Autologous
6.
Prev Chronic Dis ; 21: E31, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38723273

ABSTRACT

We estimated the prevalence of respiratory symptoms, chronic obstructive pulmonary disease (COPD) risk level, and receipt of a breathing test among adults without reported COPD in 26 states and the District of Columbia by using 2017-2018 Behavioral Risk Factor Surveillance System data. Among adults without reported COPD, the 3 respiratory symptoms indicating COPD (chronic cough, phlegm or mucus production, shortness of breath) were common (each >10%). About 15.0% were at higher COPD risk (based on the number of symptoms, age, and smoking status); 41.4% of adults at higher risk reported receipt of a breathing test. Patient-provider recognition and communication of risk symptoms, appropriate screening, and follow-up are important for early diagnosis and treatment.


Subject(s)
Behavioral Risk Factor Surveillance System , Pulmonary Disease, Chronic Obstructive , Humans , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/diagnosis , Male , Middle Aged , Female , United States/epidemiology , Adult , Aged , Prevalence , District of Columbia/epidemiology , Risk Factors , Young Adult , Adolescent , Mass Screening/methods
7.
Lupus Sci Med ; 11(1)2024 May 15.
Article in English | MEDLINE | ID: mdl-38754905

ABSTRACT

OBJECTIVE: Trauma history is associated with SLE onset and worse patient-reported outcomes; perceived stress is associated with greater SLE disease activity. Stress perceptions vary in response to life events and may be influenced by psychosocial factors. In an SLE cohort, we examined whether stressful events associated with perceived stress, whether psychosocial factors affected perceived stress, and whether these relationships varied by prior trauma exposure. METHODS: This is a cross-sectional analysis of data from the California Lupus Epidemiology Study, an adult SLE cohort. Multivariable linear regression analyses controlling for age, gender, educational attainment, income, SLE damage, comorbid conditions, glucocorticoids ≥7.5 mg/day and depression examined associations of recent stressful events (Life Events Inventory) and positive (resilience, self-efficacy, emotional support) and negative (social isolation) psychosocial factors with perceived stress. Analyses were stratified by lifetime trauma history (Brief Trauma Questionnaire (BTQ)) and by adverse childhood experiences (ACEs) in a subset. RESULTS: Among 242 individuals with SLE, a greater number of recent stressful events was associated with greater perceived stress (beta (95% CI)=0.20 (0.07 to 0.33), p=0.003). Positive psychosocial factor score representing resilience, self-efficacy and emotional support was associated with lower perceived stress when accounting for number of stressful events (-0.67 (-0.94 to -0.40), p<0.0001); social isolation was associated with higher stress (0.20 (0.14 to 0.25), p<0.0001). In analyses stratified by BTQ trauma and ACEs, associations of psychosocial factors and perceived stress were similar between groups. However, the number of recent stressful events was significantly associated with perceived stress only for people with BTQ trauma (0.17 (0.05 to 0.29), p=0.0077) and ACEs (0.37 (0.15 to 0.58), p=0.0011). CONCLUSION: Enhancing positive and lessening negative psychosocial factors may mitigate deleterious perceived stress, which may improve outcomes in SLE, even among individuals with a history of prior trauma who may be more vulnerable to recent stressful events.


Subject(s)
Lupus Erythematosus, Systemic , Self Efficacy , Social Support , Stress, Psychological , Humans , Female , Lupus Erythematosus, Systemic/psychology , Lupus Erythematosus, Systemic/complications , Male , Adult , Stress, Psychological/psychology , Stress, Psychological/etiology , Stress, Psychological/complications , Cross-Sectional Studies , Middle Aged , Resilience, Psychological , California/epidemiology , Life Change Events , Adverse Childhood Experiences/psychology , Adverse Childhood Experiences/statistics & numerical data , Surveys and Questionnaires , Social Isolation/psychology , Depression/psychology , Depression/epidemiology , Depression/etiology
8.
Epilepsy Behav ; 157: 109852, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38820685

ABSTRACT

Uncontrolled seizures among people with epilepsy increase risk of adverse health and social outcomes including increased risk of death. Previous population-based studies have reported suboptimal seizure control and disparities in seizure control among U.S. adults with active epilepsy (self-reported doctor-diagnosed epilepsy and taking anti-seizure medicine or with ≥ 1 seizures in the past 12 months) by annual family income. This brief is based upon data from the 2021 and 2022 National Health Interview Survey (NHIS) to provide updated national estimates of the percentages of adults with active epilepsy with and without seizure control (0 seizures in past 12 months) vs. ≥ 1) by anti-seizure medication use and by annual family income. Annual family income was operationalized with NHIS poverty-income ratio (PIR) categories (i.e., total family income divided by the US Census Bureau poverty threshold given the family's size and number of children): PIR < 1.0, 1.0 ≤ PIR < 2.0; PIR ≥ 2.0. Among the 1.1 % of US adults with active epilepsy in 2021/2022 (estimated population about 2.9 million), 49.2 % (∼1.4 million) were taking antiseizure medication and reported no seizures (seizure control), 36.2 % (∼1.1 million) were taking antiseizure medication and reported ≥ 1 seizures (uncontrolled seizures), and 14.7 % (∼400,000) were not taking antiseizure medication and had ≥ 1 seizures (uncontrolled seizures). The prevalence of seizure control among those with active epilepsy varied substantially by annual family income, with a larger percentage of adults with PIR ≥ 2.0 reporting seizure control compared with those with PIR < 1.0. Opportunities for intervention include improving provider awareness of epilepsy treatment guidelines, enhancing access and referral to specialty care, providing epilepsy self-management supports, and addressing unmet social needs of people with epilepsy with uncontrolled seizures, especially those at lowest family income levels.

9.
Proc Natl Acad Sci U S A ; 121(22): e2319094121, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38768341

ABSTRACT

Protein-protein and protein-water hydrogen bonding interactions play essential roles in the way a protein passes through the transition state during folding or unfolding, but the large number of these interactions in molecular dynamics (MD) simulations makes them difficult to analyze. Here, we introduce a state space representation and associated "rarity" measure to identify and quantify transition state passage (transit) events. Applying this representation to a long MD simulation trajectory that captured multiple folding and unfolding events of the GTT WW domain, a small protein often used as a model for the folding process, we identified three transition categories: Highway (faster), Meander (slower), and Ambiguous (intermediate). We developed data sonification and visualization tools to analyze hydrogen bond dynamics before, during, and after these transition events. By means of these tools, we were able to identify characteristic hydrogen bonding patterns associated with "Highway" versus "Meander" versus "Ambiguous" transitions and to design algorithms that can identify these same folding pathways and critical protein-water interactions directly from the data. Highly cooperative hydrogen bonding can either slow down or speed up transit. Furthermore, an analysis of protein-water hydrogen bond dynamics at the surface of WW domain shows an increase in hydrogen bond lifetime from folded to unfolded conformations with Ambiguous transitions as an outlier. In summary, hydrogen bond dynamics provide a direct window into the heterogeneity of transits, which can vary widely in duration (by a factor of 10) due to a complex energy landscape.


Subject(s)
Hydrogen Bonding , Molecular Dynamics Simulation , Protein Folding , Proteins , Proteins/chemistry , Proteins/metabolism , Water/chemistry , WW Domains , Protein Conformation , Algorithms
10.
Orthopedics ; : 1-7, 2024 Apr 04.
Article in English | MEDLINE | ID: mdl-38567996

ABSTRACT

BACKGROUND: Recently, fluoroscopy-assisted computer navigation has been developed to assess intraoperative cup inclination/anteversion and leg-length discrepancy (LLD) in the operating room. However, there is a relative dearth of studies investigating the accuracy of this software compared with postoperative radiographs. MATERIALS AND METHODS: We prospectively enrolled 211 navigated anterior total hip arthroplasties using fluoroscopy-assisted computer navigation software. Intraoperative navigated measurements were compared with postoperative anteroposterior radiographs to assess accuracy of cup inclination/anteversion and LLD. Continuous variables were analyzed using the Student's t test, and categorical variables were analyzed using Fisher's exact test. RESULTS: On postoperative radiographs, 94.3% of cups (199 of 211) were positioned within the Lewinnek "safe zone," compared with 99.1% navigated intraoperatively (P=.01). Eighty-two percent of hips (174 of 211) were navigated intraoperatively to LLDs within ±2 mm; on postoperative radiographs, 65% of hips (138 of 211) had LLDs within ±2 mm (P=.0001). Intraoperatively, 100% of hips (211 of 211) were navigated to LLDs within ±5 mm; similarly, on postoperative radiographs, 98% of hips (207 of 211) had LLDs within ±5 mm (P=.12). CONCLUSION: A novel fluoroscopy-assisted computer navigation platform accurately assessed intraoperative cup position and LLD during anterior total hip arthroplasty. Careful attention to fluoroscopic technique, positioning of radiographic landmarks, and knowledge of the limitations of fluoroscopy, including parallax effect, are important concepts that surgeons should incorporate into their decision algorithm. [Orthopedics. 202x;4x(x):xx-xx.].

11.
Commun Med (Lond) ; 4(1): 66, 2024 Apr 06.
Article in English | MEDLINE | ID: mdl-38582818

ABSTRACT

BACKGROUND: Islet autoantibodies form the foundation for type 1 diabetes (T1D) diagnosis and staging, but heterogeneity exists in T1D development and presentation. We hypothesized that autoantibodies can identify heterogeneity before, at, and after T1D diagnosis, and in response to disease-modifying therapies. METHODS: We systematically reviewed PubMed and EMBASE databases (6/14/2022) assessing 10 years of original research examining relationships between autoantibodies and heterogeneity before, at, after diagnosis, and in response to disease-modifying therapies in individuals at-risk or within 1 year of T1D diagnosis. A critical appraisal checklist tool for cohort studies was modified and used for risk of bias assessment. RESULTS: Here we show that 152 studies that met extraction criteria most commonly characterized heterogeneity before diagnosis (91/152). Autoantibody type/target was most frequently examined, followed by autoantibody number. Recurring themes included correlations of autoantibody number, type, and titers with progression, differing phenotypes based on order of autoantibody seroconversion, and interactions with age and genetics. Only 44% specifically described autoantibody assay standardization program participation. CONCLUSIONS: Current evidence most strongly supports the application of autoantibody features to more precisely define T1D before diagnosis. Our findings support continued use of pre-clinical staging paradigms based on autoantibody number and suggest that additional autoantibody features, particularly in relation to age and genetic risk, could offer more precise stratification. To improve reproducibility and applicability of autoantibody-based precision medicine in T1D, we propose a methods checklist for islet autoantibody-based manuscripts which includes use of precision medicine MeSH terms and participation in autoantibody standardization workshops.


Islet autoantibodies are markers found in the blood when insulin-producing cells in the pancreas become damaged and can be used to predict future development of type 1 diabetes. We evaluated published literature to determine whether characteristics of islet antibodies (type, levels, numbers) could improve prediction and help understand differences in how individuals with type 1 diabetes respond to treatments. We found existing evidence shows that islet autoantibody type and number are most useful to predict disease progression before diagnosis. In addition, the age when islet autoantibodies first appear strongly influences rate of progression. These findings provide important information for patients and care providers on how islet autoantibodies can be used to understand future type 1 diabetes development and to identify individuals who have the potential to benefit from intervention or prevention therapy.

12.
Radiol Case Rep ; 19(7): 2719-2723, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38680736

ABSTRACT

Vertebral osteomyelitis is a well-documented disease entity in literature with various known etiologies. However, vertebral diskitis-osteomyelitis secondary to an infected aortic aneurysm is an uncommon and life-threatening complication. We present the case of a 65-year-old male patient who presented with chronic low back pain that acutely worsened for 1 to 1.5 months and was diagnosed with vertebral diskitis-osteomyelitis secondary to a contiguous infection from an adjacent mycotic aortic aneurysm. To our knowledge, this is one of the few cases reported of vertebral diskitis-osteomyelitis secondary to mycotic aortic aneurysm. We discuss the findings on CT and MRI, as well as the value of imaging in guiding management.

13.
PLoS One ; 19(4): e0299890, 2024.
Article in English | MEDLINE | ID: mdl-38662717

ABSTRACT

BACKGROUND: Preventive care is important for managing inflammatory bowel disease (IBD), yet primary care providers (PCPs) often face challenges in delivering such care due to discomfort and unfamiliarity with IBD-specific guidelines. This study aims to assess PCPs' attitudes towards, and practices in, providing preventive screenings for IBD patients, highlighting areas for improvement in guideline dissemination and education. METHODS: Using a web-based opt-in panel of PCPs (DocStyles survey, spring 2022), we assessed PCPs' comfort level with providing/recommending screenings and the reasons PCPs felt uncomfortable (n = 1,503). Being likely to provide/recommend screenings for depression/anxiety, skin cancer, osteoporosis, and cervical cancer were compared by PCPs' comfort level and frequency of seeing patients with IBD. We estimated adjusted odd ratios (AORs) of being likely to recommend screenings and selecting responses aligned with IBD-specific guidelines by use of clinical practice methods. RESULTS: About 72% of PCPs reported being comfortable recommending screenings to patients with IBD. The top reason identified for not feeling comfortable was unfamiliarity with IBD-specific screening guidelines (55%). Being comfortable was significantly associated with being likely to provide/recommend depression/anxiety (AOR = 3.99) and skin cancer screenings (AOR = 3.19) compared to being uncomfortable or unsure. Percentages of responses aligned with IBD-specific guidelines were lower than those aligned with general population guidelines for osteoporosis (21.7% vs. 27.8%) and cervical cancer screenings (34.9% vs. 43.9%), and responses aligned with IBD-specific guidelines did not differ by comfort level for both screenings. Timely review of guidelines specific to immunosuppressed patients was associated with being likely to provide/recommend screenings and selecting responses aligned with IBD-specific guidelines. CONCLUSIONS: Despite a general comfort among PCPs in recommending preventive screenings for IBD patients, gaps in knowledge regarding IBD-specific screening guidelines persist. Enhancing awareness and understanding of these guidelines through targeted education and resource provision may bridge this gap.


Subject(s)
Attitude of Health Personnel , Inflammatory Bowel Diseases , Physicians, Primary Care , Humans , Inflammatory Bowel Diseases/diagnosis , Inflammatory Bowel Diseases/psychology , Female , Male , Middle Aged , Adult , Physicians, Primary Care/psychology , Mass Screening/methods , Primary Health Care , Surveys and Questionnaires , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/prevention & control , Health Knowledge, Attitudes, Practice , Aged , Practice Patterns, Physicians' , Osteoporosis/diagnosis , Osteoporosis/prevention & control
14.
Horm Res Paediatr ; : 1-12, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38663372

ABSTRACT

Teplizumab (TzieldTM, Provention Bio), a monoclonal antibody directed at T-cell marker CD3, is the first medication approved by the FDA to delay progression from stage 2 to stage 3 type 1 diabetes. To date, the overwhelming majority of pediatric endocrinologists do not have experience using immunotherapeutics and seek guidance on the use of teplizumab in clinical practice. To address this need, the Pediatric Endocrine Society (PES) Diabetes Special Interest Group (Diabetes SIG) and Drug and Therapeutics Committee assembled a task force to review clinical trial data and solicit expert recommendations on the approach to teplizumab infusions. We present considerations on all aspects of teplizumab administration, utilizing evidence where possible and providing a spectrum of expert opinions on unknown aspects. We discuss patient selection and prescreening, highlighting the safety and considerations for monitoring and treatment of side effects. We propose a schedule of events, a protocol for administration, and discuss practice management aspects. We advocate for the need for further long-term systematic surveillance studies to continue evaluating the efficacy and safety of teplizumab.

15.
Epilepsy Behav ; 155: 109770, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38636143

ABSTRACT

Studies on epilepsy mortality in the United States are limited. We used the National Vital Statistics System Multiple Cause of Death data to investigate mortality rates and trends during 2011-2021 for epilepsy (defined by the International Classification of Diseases, 10th Revision, codes G40.0-G40.9) as an underlying, contributing, or any cause of death (i.e., either an underlying or contributing cause) for U.S. residents. We also examined epilepsy as an underlying or contributing cause of death by selected sociodemographic characteristics to assess mortality rate changes and disparities in subpopulations. During 2011-2021, the overall age-standardized mortality rates for epilepsy as an underlying (39 % of all deaths) or contributing (61 % of all deaths) cause of death increased 83.6 % (from 2.9 per million to 6.4 per million population) as underlying cause and 144.1 % (from 3.3 per million to 11.0 per million population) as contributing cause (P < 0.001 for both based on annual percent changes). Compared to 2011-2015, in 2016-2020 mortality rates with epilepsy as an underlying or contributing cause of death were higher overall and in nearly all subgroups. Overall, mortality rates with epilepsy as an underlying or contributing cause of death were higher in older age groups, among males than females, among non-Hispanic Black or non-Hispanic American Indian/Alaska Native persons than non-Hispanic White persons, among those living in the West and Midwest than those living in the Northeast, and in nonmetro counties compared to urban regions. Results identify priority subgroups for intervention to reduce mortality in people with epilepsy and eliminate mortality disparity.


Subject(s)
Epilepsy , Humans , Epilepsy/mortality , Epilepsy/epidemiology , United States/epidemiology , Male , Female , Middle Aged , Adult , Aged , Adolescent , Young Adult , Child , Infant , Child, Preschool , Aged, 80 and over , Cause of Death/trends , Infant, Newborn , Mortality/trends , Health Status Disparities
16.
Toxicol Sci ; 199(2): 246-260, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38310335

ABSTRACT

Particulate matter (PM) containing environmentally persistent free radicals (EPFR) is formed by the incomplete combustion of organic wastes, resulting in the chemisorption of pollutants to the surface of PM containing redox-active transition metals. In prior studies in mice, EPFR inhalation impaired endothelium-dependent vasodilation. These findings were associated with aryl hydrocarbon receptor (AhR) activation in the alveolar type-II (AT-II) cells that form the air-blood interface in the lung. We thus hypothesized that AhR activation in AT-II cells promotes the systemic release of mediators that promote endothelium dysfunction peripheral to the lung. To test our hypothesis, we knocked down AhR in AT-II cells of male and female mice and exposed them to 280 µg/m3 EPFR lo (2.7e + 16 radicals/g) or EPFR (5.5e + 17 radicals/g) compared with filtered air for 4 h/day for 1 day or 5 days. AT-II-AhR activation-induced EPFR-mediated endothelial dysfunction, reducing endothelium-dependent vasorelaxation by 59%, and eNOS expression by 50%. It also increased endothelin-1 mRNA levels in the lungs and peptide levels in the plasma in a paracrine fashion, along with soluble vascular cell adhesion molecule-1 and iNOS mRNA expression, possibly via NF-kB activation. Finally, AhR-dependent increases in antioxidant response signaling, coupled to increased levels of 3-nitrotyrosine in the lungs of EPFR-exposed littermate control but not AT-II AhR KO mice suggested that ATII-specific AhR activation promotes oxidative and nitrative stress. Thus, AhR activation at the air-blood interface mediates endothelial dysfunction observed peripheral to the lung, potentially via release of systemic mediators.


Subject(s)
Mice, Inbred C57BL , Particulate Matter , Receptors, Aryl Hydrocarbon , Animals , Receptors, Aryl Hydrocarbon/metabolism , Receptors, Aryl Hydrocarbon/genetics , Male , Particulate Matter/toxicity , Female , Free Radicals/metabolism , Air Pollutants/toxicity , Mice , Endothelium, Vascular/drug effects , Endothelium, Vascular/metabolism , Endothelium, Vascular/physiopathology , Oxidative Stress/drug effects , Inhalation Exposure , Lung/drug effects , Lung/metabolism , Lung/blood supply , Endothelin-1/metabolism , Vasodilation/drug effects , Nitric Oxide Synthase Type III/metabolism , Basic Helix-Loop-Helix Transcription Factors
17.
Lancet Rheumatol ; 6(2): e105-e114, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38267097

ABSTRACT

BACKGROUND: Social determinants of health are consistently associated with systemic lupus erythematosus (SLE) outcomes. However, social determinants of health are typically measured with conventional socioeconomic status factors such as income or education. We assessed the association of economic insecurities (ie, food, housing, health care, and financial insecurity) with patient-reported outcomes in a cohort of patients with SLE. METHODS: In this cross-sectional analysis, data were derived from the California Lupus Epidemiology Study based in the San Francisco Bay Area, CA, USA. Participants were recruited between Feb 25, 2015, and Jan 10, 2018, from rheumatology clinics. Inclusion criteria were Bay Area residency; oral fluency in English, Spanish, Cantonese, or Mandarin; 18 years or older; ability to provide informed consent; and a physician confirmed SLE diagnosis. Food, housing, health care, and financial economic insecurities were assessed by validated screening tools. Patient-reported outcomes were obtained using PROMIS, Quality of Life in Neurological Disorders (known as Neuro-QoL) Cognitive Function short form, Patient Health Questionnaire (PHQ)-8, and General Anxiety Disorder (GAD)-7 instruments. Poverty was defined as household income of 125% or less of the federal poverty limit. Lower education was defined as less than college-graduate education. The association of economic insecurities with patient-reported outcomes was assessed by multivariable linear regression models adjusting for demographics, SLE disease characteristics, and comorbidities. We tested for interactions of insecurities with poverty and education. FINDINGS: The final cohort included 252 participants. Mean age was 49·7 (SD 13·4) years, 228 (90%) of 252 were women and 24 (10%) were men. 80 (32%) individuals self-identified as Asian, 26 (10%) as Black, 101 (40%) as White, eight (3%) as mixed race, and 37 (15%) as other race; 59 (23%) self-identified as Hispanic. 135 (54%) individuals had at least one insecurity. Insecurities were highly prevalent, and more common in those with poverty and lower education. Adjusted multivariate analyses revealed that participants with any insecurity had significantly worse scores across all measured patient-reported outcomes. For physical function, no insecurity had an adjusted mean score of 48·9 (95% CI 47·5-50·3) and any insecurity had 45·7 (44·3-47·0; p=0·0017). For pain interference, no insecurity was 52·0 (50·5-53·5) and any insecurity was 54·4 (53·0-55·8; p=0·031). For fatigue, no insecurity was 50·5 (48·8-52·3) and any insecurity was 54·9 (53·3-56·5; p=0·0005). For sleep disturbance, no insecurity was 49·9 (48·3-51·6) and any insecurity was 52·9 (51·4-54·5; p=0·012). For cognitive function, no insecurity was 49·3 (47·7-50·9) and any insecurity was 45·6 (44·1-47·0; p=0·0011). For PHQ-8, no insecurity was 4·4 (3·6-5·1) and any insecurity was 6·1 (5·4-6·8; p=0·0013). For GAD-7, no insecurity was 3·3 (2·6-4·1) and any insecurity was 5·2 (4·5-5·9; p=0·0008). Individuals with more insecurities had worse patient-reported outcomes. There were no statistically significant interactions between insecurities and poverty or education. INTERPRETATION: Having any economic insecurity was associated with worse outcomes for people with SLE regardless of poverty or education. The findings of this study provide insight into the relationship between economic insecurities and SLE outcomes and underscore the need to assess whether interventions that directly address these insecurities can reduce health disparities in SLE. FUNDING: US Centers for Disease Control, Rheumatology Research Foundation, and National Institute of Arthritis and Musculoskeletal and Skin Diseases.


Subject(s)
Anxiety Disorders , Lupus Erythematosus, Systemic , Quality of Life , Male , Humans , Female , Middle Aged , Cross-Sectional Studies , Lupus Erythematosus, Systemic/epidemiology , San Francisco/epidemiology
18.
Proc Natl Acad Sci U S A ; 121(2): e2306906120, 2024 Jan 09.
Article in English | MEDLINE | ID: mdl-38165940

ABSTRACT

Cold-water species in temperate lakes face two simultaneous climate-driven ecosystem changes: warming and browning of their waters. Browning refers to reduced transparency arising from increased dissolved organic carbon (DOC), which absorbs solar energy near the surface. It is unclear whether the net effect is mitigation or amplification of climate warming impacts on suitable oxythermal habitat (<20 °C, >5 mgO/L) for cold-loving species because browning expands the vertical distribution of both cool water and oxygen depletion. We analyzed long-term trends and high-frequency sensor data from browning lakes in New York's Adirondack region to assess the contemporary status of summertime habitat for lacustrine brook trout. Across two decades, surface temperatures increased twice as fast and bottom dissolved oxygen declined >180% faster than average trends for temperate lakes. We identify four lake categories based on oxythermal habitat metrics: constrained, squeezed, overheated, and buffered. In most of our study lakes, trout face either seasonal loss (7 of 15) or dramatic restriction (12 to 21% of the water column; 5 of 15) of suitable habitat. These sobering statistics reflect rapid upward expansion of oxygen depletion in lakes with moderate or high DOC relative to compression of heat penetration. Only in very clear lakes has browning potentially mitigated climate warming. Applying our findings to extensive survey data suggests that decades of browning have reduced oxythermal refugia in most Adirondack lakes. We conclude that joint warming and browning may preclude self-sustaining cold-water fisheries in many temperate lakes; hence, oxythermal categorization is essential to guide triage strategies and management interventions.


Subject(s)
Ecosystem , Lakes , Animals , Water , Trout , Oxygen
19.
Med Sci Sports Exerc ; 56(2): 230-237, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-37710393

ABSTRACT

INTRODUCTION: Exercise improves vascular function, but it is unclear whether benefits are mediated by traditional cardiovascular risk factors or whether sex differences in training effects exist in older adults. We hypothesized that exercise would improve cardiovascular risk factors, that males and females would benefit similarly, and that improvements in risk factors would correlate with changes in vascular function. METHODS: Seventy-two healthy middle-aged/older adults (age, 62 ± 7 yr; 26%♂) were randomized to a land-walking ( n = 23), water-walking ( n = 25), or a nonexercise control group (C; n = 23). The exercise groups undertook supervised and monitored training three times a week for 50 min per session, across 24 wk. Blood pressure, body composition (dual x-ray absorptiometry), blood lipids and glucose, and flow-mediated brachial artery dilation were assessed in all participants at weeks 0 and 24. To maximize power for sex differences and correlation analyses, we pooled the training groups (land-walking + water-walking). RESULTS: Training prevented increases in LDL and total cholesterol/HDL ratio observed in the nonexercise control group. No group by time interactions were observed for other risk factors. Sex differences in training effects existed for visceral fat (-187 ± 189 g♂ vs -15 ± 161 g♀; P = 0.006) and lean mass (-352 ± 1045 g♂ vs 601 ± 1178 g♀; P = 0.008). Improvement in flow-mediated brachial artery dilation was correlated with decreased waist girth ( r = -0.450, P = 0.036), but not with other risk factors. CONCLUSIONS: Exercise training prevented deterioration in lipid levels, whereas sex differences existed for body composition changes with training. Improvement in vascular function was not dependent on changes in risk factors in middle-aged/older adults, suggesting that artery health may be dependent on other exercise-related stimuli.


Subject(s)
Exercise , Water , Middle Aged , Humans , Female , Male , Aged , Exercise/physiology , Walking/physiology , Risk Factors , Exercise Therapy
20.
Biomech Model Mechanobiol ; 23(1): 255-269, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37805938

ABSTRACT

Cerebrovascular haemodynamics are sensitive to multiple physiological stimuli that require synergistic response to maintain adequate perfusion. Understanding haemodynamic changes within cerebral arteries is important to inform how the brain regulates perfusion; however, methods for direct measurement of cerebral haemodynamics in these environments are challenging. The aim of this study was to assess velocity waveform metrics obtained using transcranial Doppler (TCD) with flow-conserving subject-specific three-dimensional (3D) simulations using computational fluid dynamics (CFD). Twelve healthy participants underwent head and neck imaging with 3 T magnetic resonance angiography. Velocity waveforms in the middle cerebral artery were measured with TCD ultrasound, while diameter and velocity were measured using duplex ultrasound in the internal carotid and vertebral arteries to calculate incoming cerebral flow at rest, during hypercapnia and exercise. CFD simulations were developed for each condition, with velocity waveform metrics extracted in the same insonation region as TCD. Exposure to stimuli induced significant changes in cardiorespiratory measures across all participants. Measured absolute TCD velocities were significantly higher than those calculated from CFD (P range < 0.001-0.004), and these data were not correlated across conditions (r range 0.030-0.377, P range 0.227-0.925). However, relative changes in systolic and time-averaged velocity from resting levels exhibited significant positive correlations when the distinct techniques were compared (r range 0.577-0.770, P range 0.003-0.049). Our data indicate that while absolute measures of cerebral velocity differ between TCD and 3D CFD simulation, physiological changes from resting levels in systolic and time-averaged velocity are significantly correlated between techniques.


Subject(s)
Cerebral Arteries , Hydrodynamics , Humans , Cerebral Arteries/diagnostic imaging , Ultrasonography, Doppler, Transcranial/methods , Brain/diagnostic imaging , Brain/blood supply , Magnetic Resonance Angiography/methods , Blood Flow Velocity/physiology , Cerebrovascular Circulation/physiology
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