ABSTRACT
BACKGROUND: Although radiologic honeycombing is generally associated with progressive fibrosis and a dismal prognosis, some patients display an unexpectedly indolent clinical course. We aimed to assess for variants of honeycombing associated with a more favorable prognosis. METHODS: A computer-assisted search was conducted to identify patients encountered at Mayo Clinic from 1998 to 2022 who had undergone chest CT that manifested exuberant honeycombing. Medical records and chest imaging studies were reviewed to identify clinical, pulmonary function and radiologic features. RESULTS: Among 136 patients with exuberant honeycombing, 23 patients were identified with CT features of what we termed "bubbly lung" characterized by extensive macrocystic fibrosis; 17 (74%) were female with a median age of 71 years (range, 32-88) at baseline. Underlying diagnoses were ANCA associated vasculitis (22%), overlap CTD (22%), rheumatoid arthritis (17%), IPF (17%), IPAF (9%), systemic sclerosis (4%), undifferentiated CTD (4%), and dermatomyositis (4%). Median FVC was 78% predicted (range 35-112), median DLco was 41% predicted (range 10-92), and median TLC was 73% predicted (range 57-116). Serial FVC measurements were available for 19 (83%) patients with a median interval of 4.7 years (range: 0.4-20); median FVC change per year was 23 ml (range -279 to +232) and median FVC % predicted change per year was 0.00% (range -3.20 to +6.79%). The median survival was 7.1 years, 5-year survival was 76% (95% CI: 58%-100%) and 10-year survival was 48%. CONCLUSIONS: "Bubbly lung" is a variant of exuberant honeycombing that is associated with better-than-expected outcome and FVC decline per year.
ABSTRACT
INTRODUCTION: Limited research has examined how technology and digital literacy may affect patients' use of video visits. This study explored the relationship of demographic factors and patient-reported confidence in digital literacy skills to access to video visits among patients who never used them during the COVID-19 pandemic. METHODS: Using existing survey data, the current study examined data from respondents who did not engage in video appointments but instead attended face-to-face appointments between April and December 2020 for nonemergent health concerns. A multivariable logistic regression model was used to investigate whether demographic and social determinants of health factors, context of care (primary care or psychiatry/psychology), and digital literacy confidence were associated with video visit engagement. Collinearity was assessed using the variance inflation factor. RESULTS: This study found that living in rural areas and having a self-reported lack of confidence in logging video appointments using the Mayo Clinic patient portal were associated with persistent nonuse of video appointments in a cohort of patients who did not use video visits at this institution during the early part of the COVID-19 pandemic. DISCUSSION: The research findings reported herein reveal that individuals living in rural areas and those who lack confidence in logging into patient portals to access video visits tend to persistently avoid using video appointments. More investment is needed at the federal and corporate levels to improve digital connectivity. Digital navigators and community involvement can promote digital adoption. CONCLUSION: To encourage digital competency in rural communities, it is important to implement support strategies through community stakeholders and other resources.
ABSTRACT
BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) is associated with atherosclerotic cardiovascular disease (ASCVD). Friedewald, Sampson, and Martin-Hopkins equations are used to calculate LDL-C. This study compares the impact of switching between these equations in a large geographically defined population. MATERIALS AND METHODS: Data for individuals who had a lipid panel ordered clinically between 2010 and 2019 were included. Comparisons were made across groups using the two-sample t-test or chi-square test as appropriate. Discordances between LDL measures based on clinically actionable thresholds were summarized using contingency tables. RESULTS: The cohort included 198,166 patients (mean age 54 years, 54% female). The equations perform similarly at the lower range of triglycerides but began to diverge at a triglyceride level of 125 mg/dL. However, at triglycerides of 175 mg/dL and higher, the Martin-Hopkins equation estimated higher LDL-C values than the Samson equation. This discordance was further exasperated at triglyceride values of 400 to 800 mg/dL. When comparing the Sampson and Friedewald equations, at triglycerides are below 175 mg/dL, 9% of patients were discordant at the 70 mg/dL cutpoint, whereas 42.4% were discordant when triglycerides are between 175 and 400 mg/dL. Discordance was observed at the clinically actionable LDL-C cutpoint of 190 mg/dL with the Friedewald equation estimating lower LDL-C than the other equations. In a high-risk subgroup (ASCVD risk score > 20%), 16.3% of patients were discordant at the clinical cutpoint of LDL-C < 70 mg/dL between the Sampson and Friedewald equations. CONCLUSIONS: Discordance at clinically significant LDL-C cutpoints in both the general population and high-risk subgroups were observed across the three equations. These results show that using different methods of LDL-C calculation or switching between different methods could have clinical implications for many patients.
Subject(s)
Cholesterol, LDL , Triglycerides , Humans , Cholesterol, LDL/blood , Female , Middle Aged , Male , Triglycerides/blood , Aged , Atherosclerosis/blood , Adult , Risk FactorsABSTRACT
PURPOSE: Antibody-drug conjugates (ADC) are targeted therapies with robust efficacy in solid cancers, and there is intense interest in using EGFR-specific ADCs to target EGFR-amplified glioblastoma (GBM). Given GBM's molecular heterogeneity, the bystander activity of ADCs may be important for determining treatment efficacy. In this study, the activity and toxicity of two EGFR-targeted ADCs with similar auristatin toxins, Losatuxizumab vedotin (ABBV-221) and Depatuxizumab mafodotin (Depatux-M), were compared in GBM patient-derived xenografts (PDX) and normal murine brain following direct infusion by convection-enhanced delivery (CED). EXPERIMENTAL DESIGN: EGFRviii-amplified and non-amplified GBM PDXs were used to determine in vitro cytotoxicity, in vivo efficacy, and bystander activities of ABBV-221 and Depatux-M. Nontumor-bearing mice were used to evaluate the pharmacokinetics (PK) and toxicity of ADCs using LC-MS/MS and immunohistochemistry. RESULTS: CED improved intracranial efficacy of Depatux-M and ABBV-221 in three EGFRviii-amplified GBM PDX models (Median survival: 125 to >300 days vs. 20-49 days with isotype control AB095). Both ADCs had comparable in vitro and in vivo efficacy. However, neuronal toxicity and CD68+ microglia/macrophage infiltration were significantly higher in brains infused with ABBV-221 with the cell-permeable monomethyl auristatin E (MMAE), compared with Depatux-M with the cell-impermeant monomethyl auristatin F. CED infusion of ABBV-221 into the brain or incubation of ABBV-221 with normal brain homogenate resulted in a significant release of MMAE, consistent with linker instability in the brain microenvironment. CONCLUSIONS: EGFR-targeting ADCs are promising therapeutic options for GBM when delivered intratumorally by CED. However, the linker and payload for the ADC must be carefully considered to maximize the therapeutic window.
Subject(s)
Antibodies, Monoclonal, Humanized , Bystander Effect , ErbB Receptors , Glioblastoma , Immunoconjugates , Xenograft Model Antitumor Assays , Animals , Glioblastoma/drug therapy , Glioblastoma/pathology , Glioblastoma/metabolism , Immunoconjugates/pharmacokinetics , Immunoconjugates/pharmacology , Immunoconjugates/administration & dosage , Humans , ErbB Receptors/antagonists & inhibitors , Mice , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/pharmacokinetics , Brain Neoplasms/drug therapy , Brain Neoplasms/pathology , Cell Line, Tumor , FemaleABSTRACT
INTRODUCTION: Alaska Native and American Indian (ANAI) peoples in Alaska currently experience a disproportionate burden of morbidity and mortality from tobacco cigarette use. Financial incentives for smoking cessation are evidence-based, but a family-level incentive structure has not been evaluated. We used a community-based participatory research and qualitative approach to culturally adapt a smoking cessation intervention with ANAI families. METHODS: We conducted individual, semi-structured telephone interviews with 12 ANAI adults who smoke, 12 adult family members, and 13 Alaska Tribal Health System stakeholders statewide between November 2022-March 2023. Through content analysis, we explored intervention receptivity, incentive preferences, culturally aligned recruitment and intervention messaging, and future implementation needs. RESULTS: Participants were receptive to the intervention. Involving a family member was viewed as novel and aligned with ANAI cultural values of commitment to community and familial interdependence. Major themes included choosing a family member who is supportive and understanding, keeping materials positive and encouraging, and offering cash and non-cash incentives for family members to choose (e.g., fuel, groceries, activities). Participants indicated that messaging should emphasize family collaboration and that cessation resources and support tips should be provided. Stakeholders also reinforced that program materials should encourage the use of other existing evidence-based cessation therapies (e.g., nicotine replacement, counseling). CONCLUSIONS: Adaptations, grounded in ANAI cultural strengths were made to the intervention and recruitment materials based on participant feedback. Next steps include a beta-test for feasibility and a randomized controlled trial for efficacy. IMPLICATIONS: This is the first study to design and adapt a financial incentives intervention promoting smoking cessation among Alaska Native or American Indian (ANAI) peoples and the first to involve the family system. Feedback from this formative work was used to develop a meaningful family-level incentive structure with ANAI people who smoke and family members and ensure intervention messaging is supportive and culturally aligned. The results provide qualitative knowledge that can inform future family-based interventions with ANAI communities, including our planned randomized controlled trial of the intervention.
ABSTRACT
BACKGROUND: Clinical risk scores are used to identify those at high risk of atherosclerotic cardiovascular disease (ASCVD). Despite preventative efforts, residual risk remains for many individuals. Very low-density lipoprotein cholesterol (VLDL-C) and lipid discordance could be contributors to the residual risk of ASCVD. METHODS AND RESULTS: Cardiovascular disease-free residents, aged ≥40 years, living in Olmsted County, Minnesota, were identified through the Rochester Epidemiology Project. Low-density lipoprotein cholesterol (LDL-C) and VLDL-C were estimated from clinically ordered lipid panels using the Sampson equation. Participants were categorized into concordant and discordant lipid pairings based on clinical cut points. Rates of incident ASCVD, including percutaneous coronary intervention, coronary artery bypass grafting, stroke, or myocardial infarction, were calculated during follow-up. The association of LDL-C and VLDL-C with ASCVD was assessed using Cox proportional hazards regression. Interaction between LDL-C and VLDL-C was assessed. The study population (n=39 098) was primarily White race (94%) and female sex (57%), with a mean age of 54 years. VLDL-C (per 10-mg/dL increase) was significantly associated with an increased risk of incident ASCVD (hazard ratio, 1.07 [95% CI, 1.05-1.09]; P<0.001]) after adjustment for traditional risk factors. The interaction between LDL-C and VLDL-C was not statistically significant (P=0.11). Discordant individuals with high VLDL-C and low LDL-C experienced the highest rate of incident ASCVD events, 16.9 per 1000 person-years, during follow-up. CONCLUSIONS: VLDL-C and lipid discordance are associated with a greater risk of ASCVD and can be estimated from clinically ordered lipid panels to improve ASCVD risk assessment.
Subject(s)
Atherosclerosis , Cardiovascular Diseases , Humans , Female , Middle Aged , Cholesterol, LDL , Cholesterol, VLDL , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Risk Factors , Risk Assessment , Atherosclerosis/epidemiologyABSTRACT
ATM is a key mediator of radiation response, and pharmacological inhibition of ATM is a rational strategy to radiosensitize tumors. AZD1390 is a brain-penetrant ATM inhibitor and a potent radiosensitizer. This study evaluated the spectrum of radiosensitizing effects and the impact of TP53 mutation status in a panel of IDH1 wild-type (WT) glioblastoma (GBM) patient-derived xenografts (PDXs). AZD1390 suppressed radiation-induced ATM signaling, abrogated G0-G1 arrest, and promoted a proapoptotic response specifically in p53-mutant GBM in vitro. In a preclinical trial using 10 orthotopic GBM models, AZD1390/RT afforded benefit in a cohort of TP53-mutant tumors but not in TP53-WT PDXs. In mechanistic studies, increased endogenous DNA damage and constitutive ATM signaling were observed in TP53-mutant, but not in TP53-WT, PDXs. In plasmid-based reporter assays, GBM43 (TP53-mutant) showed elevated DNA repair capacity compared with that in GBM14 (p53-WT), whereas treatment with AZD1390 specifically suppressed homologous recombination (HR) efficiency, in part, by stalling RAD51 unloading. Furthermore, overexpression of a dominant-negative TP53 (p53DD) construct resulted in enhanced basal ATM signaling, HR activity, and AZD1390-mediated radiosensitization in GBM14. Analyzing RNA-seq data from TCGA showed up-regulation of HR pathway genes in TP53-mutant human GBM. Together, our results imply that increased basal ATM signaling and enhanced dependence on HR represent a unique susceptibility of TP53-mutant cells to ATM inhibitor-mediated radiosensitization.
Subject(s)
Glioblastoma , Pyridines , Quinolones , Tumor Suppressor Protein p53 , Humans , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism , Glioblastoma/drug therapy , Glioblastoma/genetics , Glioblastoma/radiotherapy , Signal Transduction , DNA Repair/genetics , Ataxia Telangiectasia Mutated Proteins/metabolismABSTRACT
BACKGROUND: During the COVID-19 outbreak, video appointments became a popular method for health care delivery, particularly in the early stages of the pandemic. Although Mayo Clinic aimed to reduce face-to-face (F2F) appointments to prevent the spread of the virus, some patients continued seeing their health care providers in person. In the later stages of the pandemic, many patients became comfortable with video appointments, even if they were initially hesitant. However, a subset of patients continued to avoid video appointments. It is not yet clear what sociodemographic factors may be associated with this group of patients. OBJECTIVE: This cross-sectional study aimed to examine demographic and social determinant of health (SDoH) factors associated with persistent nonusers of video appointments among a sample of patients within a multistate health care organization. We also explored patient beliefs about the use of video for health care appointments. METHODS: We conducted a 1-time cross-sectional paper survey, mailed between July and December 2022, of patients matching the eligibility criteria: (1) aged ≥18 years as of April 2020, (2) Mayo Clinic Midwest, Florida, or Arizona patient, (3) did not use video appointment services during April-December 2020 but attended F2F appointments in the departments of primary care and psychiatry/psychology. The survey asked patients, "Have you ever had a video appointment with a healthcare provider?" "Yes" respondents were defined as "users" (adapted to video appointments), and "no" respondents were defined as "persistent nonusers" of video appointments. We analyzed demographics, SDoH, and patient beliefs toward video appointments in 2 groups: persistent nonusers of video appointments and users. We used chi-square and 2-tailed t tests for analysis. RESULTS: Our findings indicate that patients who were older, lived in rural areas, sought care at Mayo Clinic Midwest, and did not have access to the patient portal system were likely to be persistent nonusers of video appointments. Only 1 SDoH factor (not having a disability, handicap, or chronic disease) was associated with persistent nonuse of video appointments. Persistent nonusers of video appointments held personal beliefs such as discomfort with video communication, difficulty interpreting nonverbal cues, and personal preference for F2F appointments over video. CONCLUSIONS: Our study identified demographic (older age and rural residence), sociodemographic factors (not having a disability, handicap, or chronic disease), and personal beliefs associated with patients' decisions to choose between video versus F2F appointments for health care delivery. Health care institutions should assess patients' negative attitudes toward technology prior to introducing them to digital health care services. Failing to do so may result in its restricted usage, negative patient experience, and wasted resources. For patients who hold negative beliefs about technology but are willing to learn, a "digital health coordinator" could be assigned to assist with various digital health solutions.
ABSTRACT
Radioresistance of melanoma brain metastases limits the clinical utility of conventionally fractionated brain radiation in this disease, and strategies to improve radiation response could have significant clinical impact. The catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) is critical for repair of radiation-induced DNA damage, and inhibitors of this kinase can have potent effects on radiation sensitivity. In this study, the radiosensitizing effects of the DNA-PKcs inhibitor peposertib were evaluated in patient-derived xenografts of melanoma brain metastases (M12, M15, M27). In clonogenic survival assays, peposertib augmented radiation-induced killing of M12 cells at concentrations ≥100 nmol/L, and a minimum of 16 hours exposure allowed maximal sensitization. This information was integrated with pharmacokinetic modeling to define an optimal dosing regimen for peposertib of 125 mpk dosed just prior to and 7 hours after irradiation. Using this drug dosing regimen in combination with 2.5 Gy × 5 fractions of radiation, significant prolongation in median survival was observed in M12-eGFP (104%; P = 0.0015) and M15 (50%; P = 0.03), while more limited effects were seen in M27 (16%, P = 0.04). These data support the concept of developing peposertib as a radiosensitizer for brain metastases and provide a paradigm for integrating in vitro and pharmacokinetic data to define an optimal radiosensitizing regimen for potent DNA repair inhibitors.
Subject(s)
Brain Neoplasms , DNA-Activated Protein Kinase , Melanoma , Radiation-Sensitizing Agents , Xenograft Model Antitumor Assays , Animals , Humans , Brain Neoplasms/secondary , Brain Neoplasms/drug therapy , Brain Neoplasms/radiotherapy , Mice , DNA-Activated Protein Kinase/antagonists & inhibitors , Radiation-Sensitizing Agents/pharmacology , Radiation-Sensitizing Agents/pharmacokinetics , Radiation-Sensitizing Agents/therapeutic use , Melanoma/drug therapy , Melanoma/pathology , Cell Line, Tumor , Sulfones/pharmacology , Female , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/pharmacokinetics , Protein Kinase Inhibitors/therapeutic useABSTRACT
OBJECTIVE: To describe demographic, clinical, and radiographic features of tumefactive demyelination (TD) and identify factors associated with severe attacks and poor outcomes. METHODS: Retrospective review of TD cases seen at Mayo Clinic, 1990-2021. RESULTS: Of 257 patients with TD, 183/257 (71%) fulfilled the 2017 multiple sclerosis (MS) McDonald criteria at the last follow-up, 12/257 (5%) had myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), 0 had aquaporin-4-IgG seropositive neuromyelitis optic spectrum disorders (AQP4+ NMOSD), and 62/257 (24%) were cryptogenic. Onset before age 18 was present in 18/257 (7%). Female to male ratio was 1.3:1. Cerebrospinal fluid oligoclonal (CSF) bands were present in 95/153 (62%). TD was the first demyelinating attack in 176/257 (69%). At presentation, 59/126 (47%) fulfilled Barkhof criteria for dissemination in space, 59/100 (59%) had apparent diffusion coefficient (ADC) restriction, and 57/126 (45%) had mass effect. Despite aggressive clinical presentation at onset, 181/257 (70%) of patients remained fully ambulatory (Expanded Disability Status Scale [EDSS] ≤4) after a 3.0-year median follow-up duration. Severe initial attack-related disability (EDSS ≥4) was more common in patients with motor symptoms (81/143 vs. 35/106, p < 0.0001), encephalopathy (20/143 vs. 2/106, p < 0.0001) and ADC restriction on initial MRI (42/63 vs. 15/33, p = 0.04). Poor long-term outcome (EDSS ≥4) was more common in patients with older onset age (41.9 ± 15 vs. 36.8 ± 15.6, p = 0.02) and motor symptoms at onset (49/76 vs. 66/171, p < 0.0001). INTERPRETATION: Most TD patients should be considered part of the MS spectrum after excluding MOGAD and NMOSD. Motor symptoms and older age at presentation portend a poor outcome.
Subject(s)
Brain Diseases , Multiple Sclerosis , Neuromyelitis Optica , Male , Female , Humans , Retrospective Studies , Neuromyelitis Optica/diagnosis , Aquaporin 4 , Multiple Sclerosis/complicationsABSTRACT
BACKGROUND AND OBJECTIVES: Prevention strategies for Alzheimer disease and Alzheimer disease-related dementias (AD/ADRDs) are urgently needed. Lipid variability, or fluctuations in blood lipid levels at different points in time, has not been examined extensively and may contribute to the risk of AD/ADRD. Lipid panels are a part of routine screening in clinical practice and routinely available in electronic health records (EHR). Thus, in a large geographically defined population-based cohort, we investigated the variation of multiple lipid types and their association to the development of AD/ADRD. METHODS: All residents living in Olmsted County, Minnesota on the index date January 1, 2006, aged 60 years or older without an AD/ADRD diagnosis were identified. Persons with ≥3 lipid measurements including total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), or high-density lipoprotein cholesterol (HDL-C) in the 5 years before index date were included. Lipid variation was defined as any change in individual's lipid levels over time regardless of direction and was measured using variability independent of the mean (VIM). Associations between lipid variation quintiles and incident AD/ADRD were assessed using Cox proportional hazards regression. Participants were followed through 2018 for incident AD/ADRD. RESULTS: The final analysis included 11,571 participants (mean age 71 years; 54% female). Median follow-up was 12.9 years with 2,473 incident AD/ADRD cases. After adjustment for confounding variables including sex, race, baseline lipid measurements, education, BMI, and lipid-lowering treatment, participants in the highest quintile of total cholesterol variability had a 19% increased risk of incident AD/ADRD, and those in highest quintile of triglycerides, variability had a 23% increased risk. DISCUSSION: In a large EHR derived cohort, those in the highest quintile of variability for total cholesterol and triglyceride levels had an increased risk of incident AD/ADRD. Further studies to identify the mechanisms behind this association are needed.
Subject(s)
Alzheimer Disease , Humans , Female , Aged , Male , Alzheimer Disease/epidemiology , Triglycerides , Cholesterol, HDL , Cholesterol, LDL , Minnesota/epidemiologyABSTRACT
Background: Although the epidermal growth factor receptor (EGFR) is a frequent oncogenic driver in glioblastoma (GBM), efforts to therapeutically target this protein have been largely unsuccessful. The present preclinical study evaluated the novel EGFR inhibitor WSD-0922. Methods: We employed flank and orthotopic patient-derived xenograft models to characterize WSD-0922 and compare its efficacy to erlotinib, a potent EGFR inhibitor that failed to provide benefit for GBM patients. We performed long-term survival studies and collected short-term tumor, plasma, and whole-brain samples from mice treated with each drug. We utilized mass spectrometry to measure drug concentrations and spatial distribution and to assess the impact of each drug on receptor activity and cellular signaling networks. Results: WSD-0922 inhibited EGFR signaling as effectively as erlotinib in in vitro and in vivo models. While WSD-0922 was more CNS penetrant than erlotinib in terms of total concentration, comparable concentrations of both drugs were measured at the tumor site in orthotopic models, and the concentration of free WSD-0922 in the brain was significantly less than the concentration of free erlotinib. WSD-0922 treatment provided a clear survival advantage compared to erlotinib in the GBM39 model, with marked suppression of tumor growth and most mice surviving until the end of the study. WSD-0922 treatment preferentially inhibited phosphorylation of several proteins, including those associated with EGFR inhibitor resistance and cell metabolism. Conclusions: WSD-0922 is a highly potent inhibitor of EGFR in GBM, and warrants further evaluation in clinical studies.
ABSTRACT
Rural populations are more vulnerable to the impacts of COVID-19 compared to their urban counterparts as they are more likely to be older, uninsured, to have more underlying medical conditions, and live further from medical care facilities. We engaged the Southeastern MN (SEMN) community (N = 7,781, 51% rural) to conduct a survey of motivators and barriers to masking to prevent COVID-19. We also assessed preferences for types of and modalities to receive education/intervention, exploring both individual and environmental factors primarily consistent with Social Cognitive Theory. Our results indicated rural compared to urban residents performed fewer COVID-19 prevention behaviors (e.g. 62% rural vs. 77% urban residents reported wearing a mask all of the time in public, p<0.001), had more negative outcome expectations for wearing a mask (e.g. 50% rural vs. 66% urban residents thought wearing a mask would help businesses stay open, p<0.001), more concerns about wearing a mask (e.g. 23% rural vs. 14% urban were very concerned about being 'too hot', p<0.001) and lower levels of self-efficacy for masking (e.g. 13.9±3.4 vs. 14.9±2.8, p<0.001). It appears that masking has not become a social norm in rural SEMN, with almost 50% (vs. 24% in urban residents) disagreeing with the expectation 'others in my community will wear a mask to stop the spread of Coronavirus'. Except for people (both rural and urban) who reported not being at all willing to wear a mask (7%), all others expressed interest in future education/interventions to help reduce masking barriers that utilized email and social media for delivery. Creative public health messaging consistent with SCT tailored to rural culture and norms is needed, using emails and social media with pictures and videos from role models they trust, and emphasizing education about when masks are necessary.
Subject(s)
Attitude to Health , COVID-19 , Health Behavior , Rural Population , Urban Population , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , COVID-19/epidemiology , COVID-19/prevention & control , Masks/statistics & numerical data , Midwestern United States/epidemiology , Rural Population/statistics & numerical data , Surveys and Questionnaires , Urban Population/statistics & numerical dataABSTRACT
Background: Alaska Native and American Indian (ANAI) communities in Alaska are disproportionately affected by commercial tobacco use. Financial incentive interventions promote cigarette smoking cessation, but family-level incentives have not been evaluated. We describe the study protocol to adapt and evaluate the effectiveness and implementation of a remotely delivered, family-based financial incentive intervention for cigarette smoking among Alaskan ANAI people. Methods: The study has 3 phases: 1) qualitative interviews with ANAI adults who smoke, family members, and stakeholders to inform the intervention, 2) beta-test of the intervention, and 3) randomized controlled trial (RCT) evaluating intervention reach and effectiveness on verified, prolonged smoking abstinence at 6- and 12-months post-treatment. In the RCT, adult dyads (ANAI person who smokes [index participant] and family member) recruited throughout Alaska will be randomized to a no-incentives control condition (n = 328 dyads) or a 6-month incentive intervention (n = 328 dyads). All dyads will receive cessation support and family wellness materials. Smoking status will be assessed weekly for four weeks and at three and six months. Intervention index participants will receive escalating incentives for verified smoking abstinence at each time point (maximum $750 total); the family member will receive rewards of equal value. Results: A community advisory committee contributed input on the study design and methods for relevance to ANAI people, particularly emphasizing the involvement of families. Conclusion: Our study aligns with the strength and value AIAN people place on family. Findings, processes, and resources will inform how Indigenous family members can support smoking cessation within incentive interventions. Clinical Trials Registry: NCT05209451.
ABSTRACT
Background Larger within-patient variability of lipid levels has been associated with increased risk of cardiovascular disease (CVD); however, measures of lipid variability require ≥3 measurements and are not currently used clinically. We investigated the feasibility of calculating lipid variability within a large electronic health record-based population cohort and assessed associations with incident CVD. Methods and Results We identified all individuals ≥40 years of age who resided in Olmsted County, MN, on January 1, 2006 (index date), without prior CVD, defined as myocardial infarction, coronary artery bypass graft surgery, percutaneous coronary intervention, or CVD death. Patients with ≥3 measurements of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or triglycerides during the 5 years before the index date were retained. Lipid variability was calculated using variability independent of the mean. Patients were followed through December 31, 2020 for incident CVD. We identified 19 652 individuals (mean age 61 years; 55% female), who were CVD-free and had variability independent of the mean calculated for at least 1 lipid type. After adjustment, those with highest total cholesterol variability had a 20% increased risk of CVD (Q5 versus Q1 hazard ratio, 1.20 [95% CI, 1.06-1.37]). Results were similar for low-density lipoprotein cholesterol and high-density lipoprotein cholesterol. Conclusions In a large electronic health record-based population cohort, high variability in total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol was associated with an increased risk of CVD, independent of traditional risk factors, suggesting it may be a possible risk marker and target for intervention. Lipid variability can be calculated in the electronic health record environment, but more research is needed to determine its clinical utility.
Subject(s)
Cardiovascular Diseases , Humans , Female , Middle Aged , Male , Cardiovascular Diseases/epidemiology , Cohort Studies , Electronic Health Records , Cholesterol, HDL , Cholesterol, LDLABSTRACT
BACKGROUND: Spinal cord lesions have been associated with progressive disease in individuals with typical relapsing remitting MS (RRMS). OBJECTIVE: In the current study, we aimed to determine if progressive disease is associated with spinal cord lesions in those with tumefactive multiple sclerosis (MS). METHODS: Retrospective chart review of individuals presenting to Mayo Clinic with tumefactive MS with spinal cord MRIs available (n=159). Clinical data were extracted by chart review. Brain and spinal cord MRIs were reviewed to characterize the tumefactive demyelinating lesion(s) and assess the burden of spinal cord disease. RESULTS: A total of 69 (43%) had spinal cord lesions. Progressive demyelinating disease was documented in 13 (8%); the majority (11/13) with secondary progressive disease. The method of progression was myelopathic in 8/13 (62%), cognitive in 3/13 (23%), motor from a supratentorial lesion in 2/13 (16%). EDSS at last follow-up was higher in those with progression than those without (median 6.0 (2.0-10.0) vs. 2.5 (0-10.0), p = < 0.001). Progressive demyelinating disease occurred in a minority. CONCLUSIONS: Patients with progression typically experienced progressive motor impairment, and this occurred exclusively in individuals with lesions in the corticospinal tracts of the brain and/or the spinal cord.
Subject(s)
Multiple Sclerosis , Spinal Cord Diseases , Humans , Multiple Sclerosis/complications , Multiple Sclerosis/diagnostic imaging , Multiple Sclerosis/pathology , Pyramidal Tracts/diagnostic imaging , Retrospective Studies , Disease Progression , Spinal Cord/diagnostic imaging , Spinal Cord/pathology , Brain/diagnostic imaging , Brain/pathology , Magnetic Resonance Imaging/methods , Spinal Cord Diseases/diagnostic imaging , Spinal Cord Diseases/pathologyABSTRACT
D-2-hydroxyglutarate (D-2-HG) is a well-established oncometabolite of isocitrate dehydrogenase (IDH) mutant gliomas. While prior studies have demonstrated that D-2-HG is elevated in the cerebrospinal fluid (CSF) of patients with IDH-mutant gliomas 1,2 , no study has determined if CSF D-2-HG can provide a plausible method to evaluate therapeutic response. We are obtaining CSF samples from consenting patients during their disease course via intra-operative collection and Ommaya reservoirs. D-2-HG and D/L-2-HG consistently decreased following tumor resection and throughout chemoradiation in patients monitored longitudinally. Our early experience with this strategy demonstrates the potential for intracranial CSF D-2-HG as a monitoring biomarker for IDH-mutant gliomas.
ABSTRACT
CONTEXT: Metformin is the first-line drug for treating diabetes but has a high failure rate. OBJECTIVE: To identify demographic and clinical factors available in the electronic health record (EHR) that predict metformin failure. METHODS: A cohort of patients with at least 1 abnormal diabetes screening test that initiated metformin was identified at 3 sites (Arizona, Mississippi, and Minnesota). We identified 22 047 metformin initiators (48% female, mean age of 57 ± 14 years) including 2141 African Americans, 440 Asians, 962 Other/Multiracial, 1539 Hispanics, and 16 764 non-Hispanic White people. We defined metformin failure as either the lack of a target glycated hemoglobin (HbA1c) (<7%) within 18 months of index or the start of dual therapy. We used tree-based extreme gradient boosting (XGBoost) models to assess overall risk prediction performance and relative contribution of individual factors when using EHR data for risk of metformin failure. RESULTS: In this large diverse population, we observed a high rate of metformin failure (43%). The XGBoost model that included baseline HbA1c, age, sex, and race/ethnicity corresponded to high discrimination performance (C-index of 0.731; 95% CI 0.722, 0.740) for risk of metformin failure. Baseline HbA1c corresponded to the largest feature performance with higher levels associated with metformin failure. The addition of other clinical factors improved model performance (0.745; 95% CI 0.737, 0.754, P < .0001). CONCLUSION: Baseline HbA1c was the strongest predictor of metformin failure and additional factors substantially improved performance suggesting that routinely available clinical data could be used to identify patients at high risk of metformin failure who might benefit from closer monitoring and earlier treatment intensification.
Subject(s)
Diabetes Mellitus, Type 2 , Metformin , Humans , Adult , Middle Aged , Aged , Metformin/therapeutic use , Hypoglycemic Agents/therapeutic use , Electronic Health Records , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Glycated Hemoglobin , Drug Repositioning , Retrospective StudiesABSTRACT
INTRODUCTION: There is some evidence that social media interventions can promote smoking cessation. This randomized controlled pilot study is the first to evaluate the feasibility and potential efficacy of a Facebook smoking cessation intervention among Alaska Native (AN) adults. AIMS AND METHODS: Recruitment and data collection occurred from December 2019 to March 2021. Participants were recruited statewide in Alaska using Facebook advertisements with a targeted sample of 60 enrolled. Participants were stratified by gender, age, and rural or urban residence and randomly assigned to receive referral resources on evidence-based cessation treatments (EBCTs) (control, n = 30) or these resources plus a 3-month, closed (private), culturally tailored, Facebook group (intervention, n = 31) that connected participants to EBCT resources and was moderated by two Alaska Native Trained Tobacco Specialists. Assessments were conducted online post-randomization at 1, 3, and 6 months. Outcomes were feasibility (recruitment, retention, and intervention engagement), self-reported use of EBCTs, and biochemically confirmed seven-day point-prevalence smoking abstinence. RESULTS: Of intervention participants, 90% engaged (eg posted, commented) more than once. Study retention was 57% at 6 months (no group differences). The proportion utilizing EBCTs was about double for intervention compared with the control group participants at 3 and 6 months. Smoking abstinence was higher for intervention than control participants at 3 months (6.5% vs. 0%, p = .16) but comparable at 6 months (6.4% vs. 6.7%, p = .97). CONCLUSIONS: While additional research is needed to promote long-term cessation, this pilot trial supports recruitment feasibility during the Coronavirus Disease 2019 (COVID-19) pandemic, consumer uptake, and a signal for intervention efficacy on the uptake of cessation treatment and short-term smoking abstinence. IMPLICATIONS: This study is the first evaluation of a social media intervention for smoking cessation among Indigenous people. We learned that statewide Facebook recruitment of AN adults who smoke was feasible and there was a signal for the efficacy of a Facebook intervention on the uptake of EBCT and short-term (3 months) biochemically verified smoking abstinence. Clinically, social media platforms may complement current care models by connecting AN individuals and others living in hard-to-reach communities to cessation treatment resources.