Artificial intelligence-guided screening for atrial fibrillation using electrocardiogram during sinus rhythm: a prospective non-randomised interventional trial.

BACKGROUND: Previous atrial fibrillation screening trials have highlighted the need for more targeted approaches. We did a pragmatic study to evaluate the effectiveness of an artificial intelligence (AI) algorithm-guided targeted screening approach for identifying previously unrecognised atrial fibrillation. METHODS: For this non-randomised interventional trial, we prospectively recruited patients with stroke risk factors but with no known atrial fibrillation who had an electrocardiogram (ECG) done in routine practice. Participants wore a continuous ambulatory heart rhythm monitor for up to 30 days, with the data transmitted in near real time through a cellular connection. The AI algorithm was applied to the ECGs to divide patients into high-risk or low-risk groups. The primary outcome was newly diagnosed atrial fibrillation. In a secondary analysis, trial participants were propensity-score matched (1:1) to individuals from the eligible but unenrolled population who served as real-world controls. This study is registered with ClinicalTrials.gov, NCT04208971. FINDINGS: 1003 patients with a mean age of 74 years (SD 8·8) from 40 US states completed the study. Over a mean 22·3 days of continuous monitoring, atrial fibrillation was detected in six (1·6%) of 370 patients with low risk and 48 (7·6%) of 633 with high risk (odds ratio 4·98, 95% CI 2·11-11·75, p=0·0002). Compared with usual care, AI-guided screening was associated with increased detection of atrial fibrillation (high-risk group: 3·6% [95% CI 2·3-5·4] with usual care vs 10·6% [8·3-13·2] with AI-guided screening, p<0·0001; low-risk group: 0·9% vs 2·4%, p=0·12) over a median follow-up of 9·9 months (IQR 7·1-11·0). INTERPRETATION: An AI-guided targeted screening approach that leverages existing clinical data increased the yield for atrial fibrillation detection and could improve the effectiveness of atrial fibrillation screening. FUNDING: Mayo Clinic Robert D and Patricia E Kern Center for the Science of Health Care Delivery.

Smoking Behaviors Among Indigenous Pregnant People Compared to a Matched Regional Cohort.

INTRODUCTION: Smoking commercial tobacco products is highly prevalent in American Indian and Alaska Native (Indigenous) pregnancies. This disparity directly contributes to maternal and fetal mortality. Our objective was to describe cigarette smoking prevalence, cessation intervention uptake, and cessation behaviors of pregnant Indigenous people compared to sex and age-matched regional cohort. AIMS AND METHODS: Pregnancies from an Indigenous cohort in Olmsted County, Minnesota, identified in the Rochester Epidemiology Project, were compared to pregnancies identified in a sex and age-matched non-Indigenous cohort from 2006 to 2019. Smoking status was defined as current, former, or never. All pregnancies were reviewed to identify cessation interventions and cessation events. The primary outcome was smoking prevalence during pregnancy, with secondary outcomes measuring uptake of smoking cessation interventions and cessation. RESULTS: The Indigenous cohort included 57 people with 81 pregnancies, compared to 226 non-Indigenous people with 358 pregnancies. Smoking was identified during 45.7% of Indigenous pregnancies versus 11.2% of non-Indigenous pregnancies (RR: 3.25, 95% CI = 1.98-5.31, p ≤ .0001). Although there was no difference in uptake of cessation interventions between cohorts, smoking cessation was significantly less likely during Indigenous pregnancies compared to non-Indigenous pregnancies (OR: 0.23, 95% CI = 0.07-0.72, p = .012). CONCLUSIONS: Indigenous pregnant people in Olmsted County, Minnesota were more than three times as likely to smoke cigarettes during pregnancy compared to the non-indigenous cohort. Despite equivalent uptake of cessation interventions, Indigenous people were less likely to quit than non-Indigenous people. Understanding why conventional smoking cessation interventions were ineffective at promoting cessation during pregnancy among Indigenous women warrants further study. IMPLICATIONS: Indigenous pregnant people in Olmsted County, Minnesota, were greater than three times more likely to smoke during pregnancy compared to a regional age matched non-Indigenous cohort. Although Indigenous and non-Indigenous pregnant people had equivalent uptake of cessation interventions offered during pregnancy, Indigenous people were significantly less likely to quit smoking before fetal delivery. This disparity in the effectiveness of standard of care interventions highlights the need for further study to understand barriers to cessation in pregnant Indigenous people.

The Incidence and Outcomes of Breast Implants Among 1696 Women over more than 50 Years.

OBJECTIVE: To investigate the incidence of women with breast implants in 1964-2017 MATERIALS AND METHODS: All women with breast implants in Olmsted County, MN between January 1, 1992 and December 31, 2017 were identified, and a comprehensive review of individual medical records was performed, adding to a previously identified cohort of women with breast implants in 1964-1991. Incidence rates were calculated and were age- and sex-adjusted to the US white female 2010 population. RESULTS: In 1992-2017, 948 women with breast implants were identified, totaling 1696 Olmsted County, MN women with breast implants in 1964-2017. Overall incidence was 63.3 (95% CI 60.2-66.4) per 100,000 women, but incidence varied significantly over time. Women in 1964-1991 were more likely to have implants for cosmetic reasons and more likely to have silicone implants compared to the 1992-2017 cohort. The overall standardized mortality ratio was 1.17 (95% CI 0.99-1.38) in 1964-1991 and 0.94 (95% CI 0.66-1.29) in 1992-2017. In 1992-2017, breast reconstruction patients had a significantly elevated risk of implant rupture and implant removal versus breast augmentation patients. CONCLUSION: The incidence of breast implants among women in Olmsted County, MN has varied drastically over the past five decades, with significant changes in the trends for implant type and reason. The findings of this study may provide further insight regarding how risks associated with implants may vary over time. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Health Care Utilization in Systemic Lupus Erythematosus in the Community: The Lupus Midwest Network.

OBJECTIVE: The aim of this study was to determine inpatient health care utilization in an incident cohort of patients with systemic lupus erythematosus (SLE) compared with the general population. METHODS: This was a population-based cohort study in the upper Midwest, United States. We included patients fulfilling the European League Against Rheumatism/American College of Rheumatology SLE classification criteria between 1995 and 2018. They were 1:1 age-, sex-, county-matched with individuals without SLE. All hospital admissions and emergency department (ED) visits were electronically retrieved for 1995-2020. Rates for hospital admission, length of stay, readmission, ED visits, and discharge destination were compared between groups. RESULTS: Three hundred forty-one patients with SLE and 341 comparators without SLE were included (mean age, 48.6 years at diagnosis; 79.2% female). Rates of hospitalization for patients with SLE and comparators were 29.8 and 9.9 per 100 person-years, respectively. These differences were present across sexes and age groups. Hospitalization rates were higher in patients with SLE after diagnosis and remained higher than comparators for the first 15 years of the disease. Patients with SLE were more likely than comparators to visit the ED (hazard ratio, 2.71; 95% confidence interval, 2.05-3.59). Readmission rates (32% vs. 21%, p = 0.017) were higher in patients with SLE. Length of stay and discharge destination were similar between both groups. CONCLUSION: Patients with SLE were more likely to be hospitalized and to visit the ED than individuals without SLE, highlighting important inpatient care needs. Increased hospitalization rates were observed in both male and female patients and all age groups.

Baricitinib for relapsing giant cell arteritis: a prospective open-label 52-week pilot study.

BACKGROUND/PURPOSE: Preclinical vascular inflammation models have demonstrated effective suppression of arterial wall lesional T cells through inhibition of Janus kinase 3 and JAK1. However, JAK inhibition in patients with giant cell arteritis (GCA) has not been prospectively investigated. METHODS: We performed a prospective, open-label, pilot study of baricitinib (4 mg/day) with a tiered glucocorticoid (GC) entry and accelerated taper in patients with relapsing GCA. RESULTS: 15 patients were enrolled (11, 73% female) with a mean age at entry of 72.4 (SD 7.2) years, median duration of GCA of 9 (IQR 7-21) months and median of 1 (1-2) prior relapse. Four (27%) patients entered the study on prednisone 30 mg/day, 6 (40%) at 20 mg/day and 5 (33%) at 10 mg/day. Fourteen patients completed 52 weeks of baricitinib. At week 52, 14/15 (93%) patients had ≥1 adverse event (AE) with the most frequent events, including infection not requiring antibiotics (n=8), infection requiring antibiotics (n=5), nausea (n=6), leg swelling (n=2), fatigue (n=2) and diarrhoea (n=1). One subject required baricitinib discontinuation due to AE. One serious adverse event was recorded. Only 1 of 14 (7%) patients relapsed during the study. The remaining 13 patients achieved steroid discontinuation and remained in disease remission during the 52-week study duration. CONCLUSION: In this proof-of-concept study, baricitinib at 4 mg/day was well tolerated and discontinuation of GC was allowed in most patients with relapsing GCA. Larger randomised clinical trials are needed to determine the utility of JAK inhibition in GCA. TRIAL REGISTRATION NUMBER: NCT03026504.

Rising incidence and prevalence of systemic lupus erythematosus: a population-based study over four decades.

OBJECTIVES: To determine the trends in incidence, prevalence and mortality of systemic lupus erythematosus (SLE) in a US population over four decades. METHODS: We identified all the patients with SLE in Olmsted County, Minnesota who fulfilled the European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) criteria for SLE during 1976-2018. Age-specific and sex-specific incidence and prevalence rates were adjusted to the standard 2000 projected US population. The EULAR/ACR score was used as a proxy for disease severity. Standardised mortality ratio (SMR) was estimated. RESULTS: There were 188 incident SLE cases in 1976-2018 (mean age 46.3±SD 16.9; 83% women). Overall age-adjusted and sex-adjusted annual SLE incidence per 100 000 population was 4.77 (95% CI 4.09 to 5.46). Incidence was higher in women (7.58) than men (1.89). The incidence rate increased from 3.32 during 1976-1988 to 6.44 during 2009-2018. Incidence rates were higher among the racial and ethnic minority populations than non-Hispanic whites. The EULAR/ACR score did not change significantly over time. Overall prevalence increased from 30.6 in 1985 to 97.4 in 2015. During the study period, there was no improvement in SMR over time (p=0.31). CONCLUSIONS: The incidence and prevalence of SLE are increasing in this US population. The increase in incidence may be at least partially explained by the rising ethnic/racial diversity of the population. There was no evidence that the severity of SLE has changed over time. The survival gap between SLE and the general population remains unchanged. As the US population grows more diverse, we might continue to see an increase in the incidence of SLE.

Population-based incidence and time to classification of systemic lupus erythematosus by three different classification criteria: a Lupus Midwest Network (LUMEN) study.

OBJECTIVE: To estimate the incidence and time-to-classification of SLE by the 1997 ACR (ACR97) criteria, the SLICC criteria, and the European Alliance of Associations for Rheumatology/ACR (EULAR/ACR) criteria. METHODS: We identified all incident SLE cases from 2000-2018 in the well-defined Olmsted County population. Clinical data included in the ACR97, SLICC and EULAR/ACR criteria were manually abstracted from medical records. All incident cases met at least one of the three classification criteria. Time-to-classification was estimated from the first documented lupus-attributable disease manifestation to the time of criteria fulfilment by each of the three definitions. Annual incidence rates were age or age/sex adjusted to the 2000 US population. RESULTS: Of 139 incident cases there were 126 cases by the EULAR/ACR criteria, corresponding to an age/sex-adjusted incidence of 4.5 per 100 000 population (95% CI: 3.7, 5.2). The age/sex-incidence was higher than that of the SLICC criteria (113 cases; 4.0 per 100 000 [95% CI: 3.3, 4.7], P = 0.020) and the ACR97 (92 cases; 3.3 per 100 000 [95% CI: 2.6, 3.9], P < 0.001). The median time from first disease manifestation to criteria fulfilment was shorter for the EULAR/ACR criteria (29.4 months) than the ACR97 criteria (47.0 months, P < 0.001) and similar to the SLICC criteria (30.6 months, P = 0.83). CONCLUSION: The incidence of SLE was higher by the EULAR/ACR criteria compared with the ACR97 and the SLICC criteria, and the EULAR/ACR criteria classified patients earlier that the ACR97 criteria but similar to the SLICC criteria.

Batch enrollment for an artificial intelligence-guided intervention to lower neurologic events in patients with undiagnosed atrial fibrillation: rationale and design of a digital clinical trial.

BACKGROUND: Clinical trials are a fundamental tool to evaluate medical interventions but are time-consuming and resource-intensive. OBJECTIVES: To build infrastructure for digital trials to improve efficiency and generalizability and test it using a study to validate an artificial intelligence algorithm to detect atrial fibrillation (AF). DESIGN: We will prospectively enroll 1,000 patients who underwent an electrocardiogram for any clinical reason in routine practice, do not have a previous diagnosis of AF or atrial flutter and would be eligible for anticoagulation if AF is detected. Eligible patients will be identified using digital phenotyping algorithms, including natural language processing that runs on the electronic health records. Study invitations will be sent in batches via patient portal or letter, which will direct patients to a website to verify eligibility, learn about the study (including video-based informed consent), and consent electronically. The method aims to enroll participants representative of the general patient population, rather than a convenience sample of patients presenting to clinic. A device will be mailed to patients to continuously monitor for up to 30 days. The primary outcome is AF diagnosis and burden; secondary outcomes include patients' experience with the trial conduct methods and the monitoring device. The enrollment, intervention, and follow-up will be conducted remotely, ie, a patient-centered site-less trial. SUMMARY: This is among the first wave of trials to adopt digital technologies, artificial intelligence, and other pragmatic features to create efficiencies, which will pave the way for future trials in a broad range of disease and treatment areas. Clinicaltrials.gov: NCT04208971.

The phenotype of a phospholipase C (plc-1) mutant in a filamentous fungus, Neurospora crassa.

In the filamentous fungus Neurospora crassa, phospholipase C may play a role in hyphal extension at the growing tips as part of a growth-sensing mechanism that activates calcium release from internal stores to mediate continued expansion of the hyphal tip. One candidate for a tip-localized phospholipase C is PLC-1. We characterized morphology and growth characteristics of a knockout mutant (KO plc-1) and a RIP mutated strain (RIP plc-1) (missense mutations and a nonsense mutation render the gene product non-functional). Growth and hyphal cytology of wildtype and KO plc-1 were similar, but the RIP plc-1 mutant grew slower and exhibited abnormal membrane structures at the hyphal tip, imaged using the fluorescence dye FM4-64. To test for causes of the slower growth of the RIP plc-1 mutant, we examined its physiological poise compared to wildtype and the KO plc-1 mutant. The electrical properties of all three strains and the electrogenic contribution of the plasma membrane H(+)-ATPase (identified by cyanide inhibition) were the same. Responses to high osmolarity were also similar. However, the RIP plc-1 mutant had a significantly lower turgor, a possible cause of its slower growth. While growth of all three strains was inhibited by the phospholipase C inhibitor 3-nitrocoumarin, the RIP plc-1 mutant did not exhibit hyphal bursting after addition of the inhibitor, observed in both wildtype and the KO plc-1 mutant. Although the plc-1 gene is not obligatory for tip growth, the phenotype of the RIP plc-1 mutant - abnormal tip cytology, lower turgor and resistance to inhibitor-induced hyphal bursting - suggest it does play a role in tip growth. The expression of a dysfunctional plc-1 gene may cause a shift to alternative mechanism(s) of growth sensing in hyphal extension.

Incidence, Prevalence, and Mortality of Lupus Nephritis: A Population-Based Study Over Four Decades Using the Lupus Midwest Network.

OBJECTIVE: There is a paucity of population-based studies investigating the epidemiology of lupus nephritis (LN) in the US and long-term secular trends of the disease and its outcomes. We aimed to examine the epidemiology of LN in a well-defined 8-county region in the US. METHODS: Patients with incident LN between 1976 and 2018 in Olmsted County, Minnesota (1976-2009) and an 8-county region in southeast Minnesota (2010-2018) were identified. Age- and sex-specific incidence rates and point prevalence over 4 decades, adjusted to the projected 2000 US population, were determined. Standardized mortality ratios (SMRs), survival rates, and time to end-stage renal disease (ESRD) were estimated. RESULTS: There were 72 patients with incident LN between 1976 and 2018, of whom 76% were female and 69% were non-Hispanic White. Mean ± SD age at diagnosis was 38.4 ± 16.24 years. Average annual LN incidence per 100,000 population between 1976 and 2018 was 1.0 (95% CI 0.8-1.3) and was highest in patients ages 30-39 years. Between the 1976-1989 and 2000-2018 time periods, overall incidence of LN increased from 0.7 to 1.3 per 100,000, but this was not statistically significant. Estimated LN prevalence increased from 16.8 per 100,000 in 1985 to 21.2 per 100,000 in 2015. Patients with LN had an SMR of 6.33 (95% CI 3.81-9.89), with no improvement in the mortality gap in the last 4 decades. At 10 years, survival was 70%, and 13% of LN patients had ESRD. CONCLUSION: The incidence and prevalence of LN in this area increased in the last 4 decades. LN patients have poor outcomes, with high rates of ESRD and mortality rates 6 times that of the general population.

Financial Toxicity in the Clinical Encounter: A Paired Survey of Patient and Clinician Perceptions.

Objective: To compare the agreement between patient and clinician perceptions of care-related financial issues. Patients and Methods: We surveyed patient-clinician dyads immediately after an outpatient medical encounter between September 2019 and May 2021. They were asked to separately rate (1-10) patient's level of difficulty in paying medical bills and the importance of discussing cost issues with that patient during clinical encounters. We calculated agreement between patient-clinician ratings using the intraclass correlation coefficient and used random effects regression models to identify patient predictors of paired score differences in difficulty and importance of ratings. Results: 58 pairs of patients (n=58) and clinicians (n=40) completed the survey. Patient-clinician agreement was poor for both measures, but higher for difficulty in paying medical bills (intraclass correlation coefficient=0.375; 95% CI, 0.13-0.57) than for the importance of discussing cost (-0.051; 95% CI, -0.31 to 0.21). Agreement on difficulty in paying medical bills was not lower in encounters with conversations about the cost of care. In adjusted models, poor patient-clinician agreement on difficulty in paying medical bills was associated with lower patient socioeconomic status and education level, whereas poor agreement on patient-perceived importance of discussing cost was significant for patients who were White, married, reported 1 or more long-term conditions, and had higher education and income levels. Conclusion: Even in encounters where cost conversations occurred, there was poor patient-clinician agreement on ratings of the patient's difficulty in paying medical bills and perceived importance of discussing cost issues. Clinicians need more training and support in detecting the level of financial burden and tailoring cost conversations to the needs of individual patients.

The point of no return? Functional disability transitions in patients with and without rheumatoid arthritis: A population-based cohort study.

OBJECTIVE: To assess transition probability between different levels of functional disability (FD) and time spent with FD in patients with versus without rheumatoid arthritis (RA) after RA incidence/index date. METHODS: This retrospective population-based cohort study included Olmsted County, Minnesota residents (1987 ACR criteria met in 1999-2013) and comparators without RA from the same area with similar age, sex and RA incidence/index date. Activities of Daily Living (ADL) were obtained by self-report questionnaires annually since 1999. FD was defined as having difficulty with ≥1 ADL. Multistate modeling was used to estimate the probability of transitioning between FD states. RESULTS: Five hundred fifty-eight patients with RA and 457 comparators completed ≥2 questionnaires and were included. Patients with RA had increased risk of transitioning from no FD to FD: Hazard Ratio (HR) 2.4; 95%CI:1.9-3.0. Each additional FD at RA onset reduced the probability of returning to no FD by 14%. However, the probability of having ≥1 FD was stable between RA incidence and 10-year follow-up. In the first 15 years of disease, patients with RA spent on average 10.1 years without FD and 3.4 years with ≥1 FD versus 11.6 years and 2.0 years (p<0.001) in comparators. CONCLUSION: Patients with RA remain functionally disadvantaged compared to individuals without RA. The likelihood of returning to no FD in RA decreases with each additional preexisting FD. However, the probability of FD does not increase within 10 years of RA onset, potentially reflective of the benefits of disease-modifying treatments in RA.

Body mass index trend and variability in rheumatoid arthritis.

OBJECTIVE: To characterize and compare trends in body mass index (BMI) and variability in BMI between subjects with rheumatoid arthritis (RA) and matched non-RA subjects and to determine predictors of BMI trends and variability within RA subjects. METHODS: This retrospective population-based cohort study included 1114 Olmsted County, Minnesota residents, 558 with incident RA (age ≥ 18 years, 1987 ACR criteria met in 1995-2009) and 556 non-RA subjects from the same underlying population with similar age, sex, and index calendar year. All subjects were followed until death, migration, or 12/31/2018. Generalized linear models with smoothing splines and random effects to account for multiple measurements per subject were used to examine trends in BMI measurements over time. RESULTS: Mean BMI of patients with incident RA (28.8 kg/m2) was not significantly different from that of non-RA subjects (28.9 kg/m2). There was no significant difference in BMI trends over time between RA and non-RA cohorts, or between seropositive for rheumatoid factor (RF) and/or citrullinated antibody (CCP-antibody) and seronegative RA patients, or between male and female subjects. RA subjects were noted to have significantly higher BMI variability following diagnosis compared to non-RA subjects [difference in standard deviation between RA and non-RA subjects prior to index (p = 0.12), 0-5 years after index (p = 0.044), and 5-15 years after index (p = 0.013)]. CONCLUSION: The BMI trajectory of the RA population is not significantly different compared to that of the non-RA population, but patients with RA demonstrate higher variability in BMI following diagnosis compared to the non-RA population. Key Points • This study uniquely characterizes longitudinal trajectory in BMI measures and their variability in the RA population versus the non-RA population • This study suggests that RA patients have greater BMI variability compared to the non-RA population, which is highly relevant as BMI variability is increasingly understood as a cardiovascular risk factor.

The development of ultra-high field MRI guidance technology for neuronavigation.

OBJECTIVE: Magnetic resonance imaging at 7T offers improved image spatial and contrast resolution for visualization of small brain nuclei targeted in neuromodulation. However, greater image geometric distortion and a lack of compatible instrumentation preclude implementation. In this report, the authors detail the development of a stereotactic image localizer and accompanying imaging sequences designed to mitigate geometric distortion, enabling accurate image registration and surgical planning of basal ganglia nuclei. METHODS: Magnetization-prepared rapid acquisition with gradient echo (MPRAGE), fast gray matter acquisition T1 inversion recovery (FGATIR), T2-weighted, and T2*-weighted sequences were optimized for 7T in 9 human subjects to visualize basal ganglia nuclei, minimize image distortion, and maximize target contrast-to-noise and signal-to-noise ratios. Extracranial spatial distortions were mapped to develop a skull-contoured image localizer embedded with spherical silicone fiducials for improved MR image registration and target guidance. Surgical plan accuracy testing was initially performed in a custom-developed MRI phantom (n = 5 phantom studies) and finally in a human trial. RESULTS: MPRAGE and T2*-weighted sequences had the best measures among global measures of image quality (3.8/4, p < 0.0001; and 3.7/4, p = 0.0002, respectively). Among basal ganglia nuclei, FGATIR outperformed MPRAGE for globus pallidus externus (GPe) visualization (2.67/4 vs 1.78/4, p = 0.008), and FGATIR, T2-weighted imaging, and T2*-weighted imaging outperformed MPRAGE for substantia nigra visualization (1.44/4 vs 2.56/4, p = 0.04; vs 2.56/4, p = 0.04; vs 2.67/4, p = 0.003). Extracranial distortion was lower in the head's midregion compared with the base and apex ( 1.17-1.33 mm; MPRAGE and FGATIR, p < 0.0001; T2-weighted imaging, p > 0.05; and T2*-weighted imaging, p = 0.013). Fiducial placement on the localizer in low distortion areas improved image registration (fiducial registration error, 0.79-1.19 mm; p < 0.0001) and targeting accuracy (target registration error, 0.60-1.09 mm; p = 0.04). Custom surgical software and the refined image localizer enabled successful surgical planning in a human trial (fiducial registration error = 1.0 mm). CONCLUSIONS: A skull-contoured image localizer that accounts for image distortion is necessary to enable high-accuracy 7T imaging-guided targeting for surgical neuromodulation. These results may enable improved clinical efficacy for the treatment of neurological disease.

Indigenous Smoking Behaviors in Olmsted County, Minnesota: A Longitudinal Population-Based Study.

OBJECTIVE: To describe smoking behaviors and pharmaceutical cessation aid uptake in a population-based Indigenous cohort compared with an age- and sex-matched non-Indigenous cohort. PATIENTS AND METHODS: Using the health record-linkage system of the Rochester Epidemiology Project (January 1, 2006, to December 31, 2019), smoking data of Indigenous residents of Olmsted County in Minnesota were abstracted to define the smoking prevalence, incidence, cessation, relapse after cessation, and pharmaceutical smoking cessation aid uptake compared with a matched non-Indigenous cohort. Prevalence was analyzed with a modified Poisson regression; cessation and relapse were evaluated with generalized estimating equations. Incidence was evaluated with a Cox proportional hazards model. RESULTS: Smoking prevalence was higher in the Indigenous cohort (39.0% to 47.0%; n=898) than the matched cohort (25.6% to 30.3%; n=1780). Pharmaceutical uptake was higher among the Indigenous cohort (35.8% of n=584 ever smokers vs 16.3% of n=778 ever smokers; P<.001). Smoking cessation events occurred more frequently in the Indigenous cohort (relative risk, 1.10; 95% CI, 1.06 to 1.13; P<.001). Indigenous former smokers were more likely to resume smoking (relative risk, 3.03; 95% CI, 2.93 to 3.14; P<.001) compared with the matched cohort. These findings were independent of socioeconomic status, age, and sex. CONCLUSION: Smoking in this Indigenous cohort was more prevalent compared with a sex- and age-matched non-Indigenous cohort despite more smoking cessation events and higher use of smoking cessation aids in the Indigenous cohort. The relapse rate after achieving cessation in the Indigenous cohort was more than three times higher than the non-Indigenous cohort. This finding has not been previously described and represents a potential target for relapse prevention efforts in US Indigenous populations.

Epidemiology of Childhood-Onset Systemic Lupus Erythematosus: A Population-Based Study.

OBJECTIVE: To characterize the incidence and prevalence of childhood-onset systemic lupus erythematosus (SLE), and to estimate the proportion of patients who are diagnosed with SLE during childhood. METHODS: A cohort of patients with incident childhood-onset SLE from 1976 to 2018 from an 8-county region in the US were identified based on comprehensive medical record review. All patients met the European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) classification criteria for SLE or the ACR SLE classification criteria from 1997 at or before age 18 years. Incidence rates were estimated using Poisson methods. We estimated the childhood-onset SLE point prevalence for January 1, 2015. Results were sex and age adjusted to the US 2000 population. Among all the SLE patients living in the 8-county region on January 1, 2015, the proportion of patients diagnosed at ≤18 years was estimated. RESULTS: A total of 13 children were diagnosed with childhood-onset SLE during the study period (using the EULAR/ACR definition; mean age at diagnosis 15.1 years, 85% female, 69% White). Childhood-onset SLE overall adjusted incidence rate was 0.7 (95% confidence interval [95% CI] 0.2-1.1) per 100,000 children. The incidence rate in girls was 1.2 (95% CI 0.5-1.9) per 100,000 children, while in boys it was 0.2 (95% CI 0.0-0.5) per 100,000. The adjusted prevalence of childhood-onset SLE was 1.1 (95% CI 0.0-3.1) per 100,000 children. The proportion of patients with SLE diagnosed as children was 9% (95% CI 6-13%). CONCLUSION: In this population-based study, both the incidence and prevalence rates of childhood-onset SLE were ~1 per 100,000 children. One in 10 adults with SLE was diagnosed in childhood. More studies are needed to further characterize the epidemiology of childhood-onset SLE in minorities.

Incidence of Clinically Relevant Thyroid Cancers Remains Stable for Almost a Century: A Population-Based Study.

OBJECTIVE: To examine the trends in incidence of clinically relevant thyroid cancers within the overall rising incidence of thyroid cancers. PATIENTS AND METHODS: This is a population-based cohort study conducted using the Rochester Epidemiology Project database to identify all new cases of thyroid cancer in Olmsted County, Minnesota, between January 1, 1935, and December 31, 2018. We extracted information about demographics and tumor pathologic type, size, and invasiveness. Clinically relevant cancers included aggressive histology or presence of metastatic disease, size larger than 4 cm, and gross extrathyroidal tumor invasion. RESULTS: Between 1935 and 2018, 596 thyroid cancer cases were diagnosed (mean age, 46.4 years; 72% female; 87% papillary cancers; and median tumor size, 1.5 cm). The sex- and age-adjusted incidence of thyroid cancer increased from 1.3 per 100,000 person-years (p-y) from 1935-1949 to 12.0 per 100,000 p-y in 2010-2018, corresponding to an absolute change per decade of 1.4 (95% CI, 0.7 to 2.2). There was a nonsignificant period absolute change for patients with tumor greater than 4 cm (0.03; 95% CI, -0.2 to 0.3), with evidence of tumor invasion (0.1; 95% CI, -0.1 to 0.4), and with aggressive histology or presence of metastatic disease (0.2; 95% CI, -0.1 to 0.6). Thyroid cancer mortality was unchanged over the observation period. CONCLUSION: Incidence rates of clinically relevant thyroid cancers, as defined by histology, size, and invasiveness, have not changed significantly in 80 years. The rising thyroid cancer incidence is driven by indolent thyroid cancers.

Association Between Area-Level Socioeconomic Deprivation and Diabetes Care Quality in US Primary Care Practices.

Importance: Diabetes management operates under a complex interrelationship between behavioral, social, and economic factors that affect a patient's ability to self-manage and access care. Objective: To examine the association between 2 complementary area-based metrics, area deprivation index (ADI) score and rurality, and optimal diabetes care. Design, Setting, and Participants: This cross-sectional study analyzed the electronic health records of patients who were receiving care at any of the 75 Mayo Clinic or Mayo Clinic Health System primary care practices in Minnesota, Iowa, and Wisconsin in 2019. Participants were adults with diabetes aged 18 to 75 years. All data were abstracted and analyzed between June 1 and November 30, 2020. Main Outcomes and Measures: The primary outcome was the attainment of all 5 components of the D5 metric of optimal diabetes care: glycemic control (hemoglobin A1c <8.0%), blood pressure (BP) control (systolic BP <140 mm Hg and diastolic BP <90 mm Hg), lipid control (use of statin therapy according to recommended guidelines), aspirin use (for patients with ischemic vascular disease), and no tobacco use. The proportion of patients receiving optimal diabetes care was calculated as a function of block group-level ADI score (a composite measure of 17 US Census indicators) and zip code-level rurality (calculated using Rural-Urban Commuting Area codes). Odds of achieving the D5 metric and its components were assessed using logistic regression that was adjusted for demographic characteristics, coronary artery disease history, and primary care team specialty. Results: Among the 31 934 patients included in the study (mean [SD] age, 59 [11.7] years; 17 645 men [55.3%]), 13 138 (41.1%) achieved the D5 metric of optimal diabetes care. Overall, 4090 patients (12.8%) resided in the least deprived quintile (quintile 1) of block groups and 1614 (5.1%) lived in the most deprived quintile (quintile 5), while 9193 patients (28.8%) lived in rural areas and 2299 (7.2%) in highly rural areas. The odds of meeting the D5 metric were lower for individuals residing in quintile 5 vs quintile 1 block groups (odds ratio [OR], 0.72; 95% CI, 0.67-0.78). Patients residing in rural (OR, 0.84; 95% CI, 0.73-0.97) and highly rural (OR, 0.81; 95% CI, 0.72-0.91) zip codes were also less likely to attain the D5 metric compared with those in urban areas. Conclusions and Relevance: This cross-sectional study found that patients living in more deprived and rural areas were significantly less likely to attain high-quality diabetes care compared with those living in less deprived and urban areas. The results call for geographically targeted population health management efforts by health systems, public health agencies, and payers.

Association of Neighborhood Measures of Social Determinants of Health With Breast, Cervical, and Colorectal Cancer Screening Rates in the US Midwest.

Importance: Despite advances in cancer treatment and cancer-related outcomes, disparities in cancer mortality remain. Lower rates of cancer prevention screening and consequent delays in diagnosis may exacerbate these disparities. Better understanding of the association between area-level social determinants of health and cancer screening may be helpful to increase screening rates. Objective: To examine the association between area deprivation, rurality, and screening for breast, cervical, and colorectal cancer in patients from an integrated health care delivery system in 3 US Midwest states (Minnesota, Iowa, and Wisconsin). Design, Setting, and Participants: In this cross-sectional study of adults receiving primary care at 75 primary care practices in Minnesota, Iowa, and Wisconsin, rates of recommended breast, cervical, and colorectal cancer screening completion were ascertained using electronic health records between July 1, 2016, and June 30, 2017. The area deprivation index (ADI) is a composite measure of social determinants of health composed of 17 US Census indicators and was calculated for all census block groups in Minnesota, Iowa, and Wisconsin (11 230 census block groups). Rurality was defined at the zip code level. Using multivariable logistic regression, this study examined the association between the ADI, rurality, and completion of cancer screening after adjusting for age, Charlson Comorbidity Index, race, and sex (for colorectal cancer only). Main Outcomes and Measures: Completion of recommended breast, cervical, and colorectal cancer screening. Results: The study cohorts were composed of 78 302 patients eligible for breast cancer screening (mean [SD] age, 61.8 [7.1] years), 126 731 patients eligible for cervical cancer screening (mean [SD] age, 42.6 [13.2] years), and 145 550 patients eligible for colorectal cancer screening (mean [SD] age, 62.4 [7.0] years; 52.9% [77 048 of 145 550] female). The odds of completing recommended screening were decreased for individuals living in the most deprived (highest ADI) census block group quintile compared with the least deprived (lowest ADI) quintile: the odds ratios were 0.51 (95% CI, 0.46-0.57) for breast cancer, 0.58 (95% CI, 0.54-0.62) for cervical cancer, and 0.57 (95% CI, 0.53-0.61) for colorectal cancer. Individuals living in rural areas compared with urban areas also had lower rates of cancer screening: the odds ratios were 0.76 (95% CI, 0.72-0.79) for breast cancer, 0.81 (95% CI, 0.79-0.83) for cervical cancer, and 0.93 (95% CI, 0.91-0.96) for colorectal cancer. Conclusions and Relevance: Individuals living in areas of greater deprivation and rurality had lower rates of recommended cancer screening, signaling the need for effective intervention strategies that may include improved community partnerships and patient engagement to enhance access to screening in highest-risk populations.

Optimization of flare management in patients with rheumatoid arthritis: results of a randomized controlled trial.

INTRODUCTION/OBJECTIVES: To evaluate the effect of a flare management intervention guided by non-physician providers versus usual care between rheumatology visits on flare occurrence and rheumatoid arthritis (RA) disease activity. METHODS: Adult patients with established RA (per 2010 ACR criteria, n = 150) were randomized to the intervention arm (n = 75) versus usual care (n = 75). The Flare Assessment in Rheumatoid Arthritis (FLARE-RA) questionnaire was administered monthly during 24 months to all patients in the intervention arm to assess flare status. Telephone nurse-led counseling or an expedited visit with a rheumatology provider was offered to patients in the intervention arm who indicated they were in flare. RESULTS: Patients in the intervention arm completed a median of 8.5 (range 1-24) questionnaires. RA flare was reported on 122 (19%) of these questionnaires; average FLARE-RA score, 4.72 on 0 (no flare) to 10 (maximum flare) scale. Patients preferred an expedited clinic visit with a rheumatology provider during 39 (32%) of flares. The majority of patients preferred to self-manage their flare (76, 62%); some patients received nursing advice on flare management over the phone (7, 6%). There were no differences in RA flare by OMERACT9 definition, DAS28-CRP, CDAI, SDAI, anti-rheumatic treatment change by rheumatology provider, or remission by CDAI between the study arms over 24-month follow-up. CONCLUSIONS: The flare management intervention did not have any major effect on flare occurrence or RA disease activity metrics over the 24-month follow-up. The majority of patients in the intervention arm preferred self-management to an expedited visit with their rheumatology provider. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02382783 ( https://clinicaltrials.gov/ct2/show/NCT02382783 ) Key Points • The flare management intervention had no effect on rheumatoid arthritis (RA) disease activity. • Patients preferred self-management of their RA flares to expedited rheumatology provider visits.