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Competing Interests: Competing interests: None declared.

Objectives: We report the safety, tolerability and efficacy of tofacitinib in patients with juvenile idiopathic arthritis (JIA) in an ongoing long-term extension (LTE) study., Methods: Patients (2-<18 years) with JIA who completed phase 1/3 index studies or discontinued for reasons excluding treatment-related serious adverse events (AEs) entered the LTE study and received tofacitinib 5 mg two times per day or equivalent weight-based doses. Safety outcomes included AEs, serious AEs and AEs of special interest. Efficacy outcomes included improvement since tofacitinib initiation per the JIA-American College of Rheumatology (ACR)70/90 criteria, JIA flare rate and disease activity measured by Juvenile Arthritis Disease Activity Score (JADAS)27, with inactive disease corresponding to JADAS ≤1.0., Results: Of 225 patients with JIA (median (range) duration of treatment, 41.6 (1-103) months), 201 (89.3%) had AEs; 34 (15.1%) had serious AEs. 10 patients developed serious infections; three had herpes zoster. Two patients newly developed uveitis. Among patients with polyarticular course JIA, JIA-ACR70/90 response rates were 60.0% (78 of 130) and 33.6% (47 of 140), respectively, at month 1, and generally improved over time. JIA flare events generally occurred in <5% of patients through to month 48. Observed mean (SE) JADAS27 was 22.0 (0.6) at baseline, 6.2 (0.7) at month 1 and 2.8 (0.5) at month 48, with inactive disease in 28.8% (36 of 125) of patients at month 1 and 46.8% (29 of 82) at month 48., Conclusions: In this interim analysis of LTE study data in patients with JIA, safety findings were consistent with the known profile of tofacitinib, and efficacy was maintained up to month 48., Trial Registration Number: NCT01500551., Competing Interests: Competing interests: HIB has received research grants from Bristol Myers Squibb, Novartis and Pfizer; is an employee of Cincinnati Children’s Hospital Medical Center; has received consulting fees or other remuneration from AbbVie, AstraZeneca/MedImmune, Bayer, Biocon, Boehringer Ingelheim, Bristol Myers Squibb, Cerecor, Eli Lilly, EMD Serono, Janssen, Novartis, Pfizer, Roche, R-Pharm and Sobi; and is a member of speaker bureaus for Novartis and Pfizer. JDA has received honorarium from Novartis. JFB has received research grants from AbbVie, Bristol Myers Squibb, Janssen, Pfizer and Roche. ALB is a member of speaker bureaus for AbbVie, Novartis and Roche. RC has received consulting fees or other remuneration from AbbVie, Bristol Myers Squibb, Eli Lilly, GSK, Novartis, Pfizer, Roche and Sanofi. GS has received consulting fees or other remuneration from Novartis and Sobi and research support from IpiNovyx. CN has received research grants from AbbVie, AstraZeneca, Bristol Myers Squibb, Eli Lilly, GSK, Pfizer and UCB. MV-DM is an employee of Clínica de Investigacion en Reumatologia y Obesidad, SC. HP, CC, CWh, KeK and SL are employees and stockholders of Pfizer. AW was an employee and stockholder of Pfizer at the time of this analysis. AM has received consulting fees or other remuneration from Aurinia, Bristol Myers Squibb, Eli Lilly, EMD Serono, Janssen and Pfizer. DL’s institution, the Cincinnati Children’s Hospital Medical Center, has received research grants from Bristol Myers Squibb, Janssen, Novartis, Pfizer, Roche and UBC; and has received consulting fees or other remuneration from AstraZeneca, Boehringer Ingelheim, GSK, Roche, Novartis, Pfizer, Takeda and UBC. DL is also a data safety and monitoring board member or chairperson for the National Institutes of Health and the Canadian Arthritis Society. NR has received honoraria for consultancies or speaker bureaus from Ablynx, AstraZeneca/MedImmune, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, EMD Serono, F Hoffmann-La Roche, GS, Janssen, MSD, Novartis, Pfizer, R-Pharm, Sanofi, Servier, Sinergie and Sobi. The IRCCS Istituto Giannina Gaslini, where NR works as a full-time public employee, has received contributions from Bristol Myers Squibb, Eli Lilly, F Hoffmann-La Roche, GS, Janssen, Novartis, Pfizer and Sobi; this funding has been reinvested for the research activities of the hospital in a fully independent manner, without any commitment with third parties. EA-A, GC, WDLP, LJ, ÖK, KaK, RR-C, JCRR, LW-W, JEW and CWo have declared no conflicts., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.)

Introduction: The Pediatric Rheumatology Care and Outcomes Improvement Network (PR-COIN) is a North American learning health network focused on improving outcomes of children with juvenile idiopathic arthritis (JIA). JIA is a chronic autoimmune disease that can lead to morbidity related to persistent joint and ocular inflammation. PR-COIN has a shared patient registry that tracks twenty quality measures including ten outcome measures of which six are related to disease activity. The network's global aim, set in 2021, was to increase the percent of patients with oligoarticular or polyarticular JIA that had an inactive or low disease activity state from 76% to 80% by the end of 2023., Methods: Twenty-three hospitals participate in PR-COIN, with over 7,200 active patients with JIA. The disease activity outcome measures include active joint count, physician global assessment of disease activity, and measures related to validated composite disease activity scoring systems including inactive or low disease activity by the 10-joint clinical Juvenile Arthritis Disease Activity Score (cJADAS10), inactive or low disease activity by cJADAS10 at 6 months post-diagnosis, mean cJADAS10 score, and the American College of Rheumatology (ACR) provisional criteria for clinical inactive disease. Data is collated to measure network performance, which is displayed on run and control charts. Network-wide interventions have included pre-visit planning, shared decision making, self-management support, population health management, and utilizing a Treat to Target approach to care., Results: Five outcome measures related to disease activity have demonstrated significant improvement over time. The percent of patients with inactive or low disease activity by cJADAS10 surpassed our goal with current network performance at 81%. Clinical inactive disease by ACR provisional criteria improved from 46% to 60%. The mean cJADAS10 score decreased from 4.3 to 2.6, and the mean active joint count declined from 1.5 to 0.7. Mean physician global assessment of disease activity significantly improved from 1 to 0.6., Conclusions: PR-COIN has shown significant improvement in disease activity metrics for patients with JIA. The network will continue to work on both site-specific and collaborative efforts to improve outcomes for children with JIA with attention to health equity, severity adjustment, and data quality., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Harris, Bingham, Vora, Yildirim-Toruner, Batthish, Bullock, Burnham, Fair, Ferraro, Ganguli, Gilbert, Gottlieb, Halyabar, Hazen, Laxer, Lee, Liu, Lovell, Mannion, Oberle, Pan, Shishov, Weiss and Morgan.)

Objective: Intra-articular corticosteroid injections (IACI) have been shown to be effective at improving arthritis across juvenile idiopathic arthritis (JIA) categories. The American College of Rheumatology (ACR) recommends IACI use as primary and adjunctive therapy for JIA patients. However, there remains minimal data describing actual IACI use in North America. The objective of this study was to describe and to evaluate IACI use in JIA, utilizing the Pediatric Rheumatology Care and Outcomes Improvement Network (PR-COIN) registry., Methods: Study participants from 13 sites were enrolled in the PR-COIN registry from 2011 to 2015. Demographic and clinical variables were summarized and Chi-squared and t -tests were used to evaluate differences between participants who did or did not receive IACI. Multiple logistic regression models were used to evaluate characteristics associated with IACI treatment., Results: Our study included 3,241 participants, the majority of whom were white (85%), female (71%) and had oligoarticular JIA (39%). IACI was administered at least once in 23% of participants, the majority of whom had oligoarticular disease (52.5%), but overall use in oligoarticular participants was low at 30.8%. IACI use varied significantly between treatment centers and use was associated with oligoarticular disease, ANA positivity, and use of other systemic medications., Conclusion: This study demonstrates that participants with JIA enrolled in the PR-COIN registry between 2011 and 2015 with persistent oligoarticular disease, ANA positivity, and use of other systemic medications were more likely to receive IACI. However, IACI use was lower than expected for oligoarticular participants., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Balay-Dustrude, Weiss, Goh, Rubin and Bullock.)

Objective: To determine the influence of structural racism, vis-à-vis neighborhood socioeconomic trajectory, on colorectal and breast cancer diagnosis and treatment., Background: Inequities in cancer care are well-documented in the United States but less is understood about how historical policies like residential redlining and evolving neighborhood characteristics influence current gaps in care., Methods: This retrospective cohort study included adult patients diagnosed with colorectal or breast cancer between 2010 and 2015 in 7 Indiana cities with available historic redlining data. Current neighborhood socioeconomic status was determined by the Area Deprivation Index. Based on historic redlining maps and the current Area Deprivation Index, we created 4 "neighborhood trajectory" categories: advantage stable, advantage reduced, disadvantage stable, and disadvantage reduced. Modified Poisson regression models estimated the relative risks (RRs) of neighborhood trajectory on cancer stage at diagnosis and receipt of cancer-directed surgery (CDS)., Results: A final cohort derivation identified 4862 cancer patients with colorectal or breast cancer. Compared with "advantage stable" neighborhoods, "disadvantage stable" neighborhood was associated with a late-stage diagnosis for both colorectal and breast cancer [RR = 1.30 (95% CI: 1.05-1.59); RR = 1.41 (1.09-1.83), respectively]. Black patients had a lower likelihood of receiving CDS in "disadvantage reduced" neighborhoods [RR = 0.92 (0.86-0.99)] than White patients., Conclusions: Disadvantage stable neighborhoods were associated with late-stage diagnoses of breast and colorectal cancer. "Disadvantage reduced" (gentrified) neighborhoods were associated with racial inequity in CDS. Improved neighborhood socioeconomic conditions may improve timely diagnosis but could contribute to racial inequities in surgical treatment., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The role of historic residential redlining on health inequities is intertwined with policy changes made before and after the 1930s that influence current neighborhood characteristics and shape ongoing structural racism in the United States (U.S.). We developed Neighborhood Trajectories which combine historic redlining data and the current neighborhood socioeconomic characteristics as a novel approach to studying structural racism. Home Owners' Loan Corporation (HOLC) neighborhoods for the entire U.S. were used to map the HOLC grades to the 2020 U.S. Census block group polygons based on the percentage of HOLC areas in each block group. Each block group was also assigned an Area Deprivation Index (ADI) from the Neighborhood Atlas®. To evaluate changes in neighborhoods from historic HOLC grades to present degree of deprivation, we aggregated block groups into "Neighborhood Trajectories" using historic HOLC grades and current ADI. The Neighborhood Trajectories are "Advantage Stable"; "Advantage Reduced"; "Disadvantage Reduced"; and "Disadvantage Stable." Neighborhood Trajectories were established for 13.3% (32,152) of the block groups in the U.S., encompassing 38,005,799 people. Overall, the Disadvantage-Reduced trajectory had the largest population (16,307,217 people). However, the largest percentage of non-Hispanic/Latino Black residents (34%) fell in the Advantage-Reduced trajectory, while the largest percentage of Non-Hispanic/Latino White residents (60%) fell in the Advantage-Stable trajectory. The development of the Neighborhood Trajectories affords a more nuanced mechanism to investigate dynamic processes from historic policy, socioeconomic development, and ongoing marginalization. This adaptable methodology may enable investigation of ongoing sociopolitical processes including gentrification of neighborhoods (Disadvantage-Reduced trajectory) and "White flight" (Advantage Reduced trajectory)., (© 2024. The New York Academy of Medicine.)

Objective: To describe the selection, development, and implementation of quality measures (QMs) for juvenile idiopathic arthritis (JIA) by the Pediatric Rheumatology Care and Outcomes Improvement Network (PR-COIN), a multihospital learning health network using quality improvement methods and leveraging QMs to drive improved outcomes across a JIA population since 2011., Methods: An American College of Rheumatology-endorsed multistakeholder process previously selected initial process QMs. Clinicians in PR-COIN and parents of children with JIA collaboratively selected outcome QMs. A committee of rheumatologists and data analysts developed operational definitions. QMs were programmed and validated using patient data. Measures are populated by registry data, and performance is displayed on automated statistical process control charts. PR-COIN centers use rapid-cycle quality improvement approaches to improve performance metrics. The QMs are revised for usefulness, to reflect best practices, and to support network initiatives., Results: The initial QM set included 13 process measures concerning standardized measurement of disease activity, collection of patient-reported outcome assessments, and clinical performance measures. Initial outcome measures were clinical inactive disease, low pain score, and optimal physical functioning. The revised QM set has 20 measures and includes additional measures of disease activity, data quality, and a balancing measure., Conclusion: PR-COIN has developed and tested JIA QMs to assess clinical performance and patient outcomes. The implementation of robust QMs is important to improve quality of care. PR-COIN's set of JIA QMs is the first comprehensive set of QMs used at the point-of-care for a large cohort of JIA patients in a variety of pediatric rheumatology practice settings., (© 2023 The Authors. Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

The early COVID-19 pandemic was associated with cessation of screening services, but the prevalence of ongoing delays in cancer screening into the third year of the pandemic are not well-characterized. In February/March 2022, a population-based survey assessed cancer needs in New Hampshire and Vermont. The associations between cancer screening delays (breast, cervical, colorectal or lung cancer) and social determinants of health, health care access, and cancer attitudes and beliefs were tested. Distributions and Rao-Scott chi-square tests were used for hypothesis testing and weighted to represent state populations. Of 1717 participants, 55% resided in rural areas, 96% identified as White race, 50% were women, 36% had high school or less education. Screening delays were reported for breast cancer (28%), cervical cancer (30%), colorectal cancer (24%), and lung cancer (30%). Delays were associated with having higher educational attainment (lung), urban living (colorectal), and having Medicaid insurance (breast, cervical). Low confidence in ability to obtain information about cancer was associated with screening delays across screening types. The most common reason for delay was the perception that the screening test was not urgent (31% breast, 30% cervical, 28% colorectal). Cost was the most common reason for delayed lung cancer screening (36%). COVID-19 was indicated as a delay reason in 15-29% of respondents; 12-20% reported health system capacity during the pandemic as a reason for delay, depending on screening type. Interventions that address sub-populations and reasons for screening delays are needed to mitigate the impact of the COVID-19 pandemic on cancer burden and mortality., Competing Interests: Declaration of Competing Interest No authors have conflicts of interest to report., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Compared with urban areas, rural areas have higher cancer mortality and have experienced substantially smaller declines in cancer incidence in recent years. In a New Hampshire (NH) and Vermont (VT) survey, we explored the roles of rurality and educational attainment on cancer risk behaviors, beliefs, and other social drivers of health. In February-March 2022, two survey panels in NH and VT were sent an online questionnaire. Responses were analyzed by rurality and educational attainment. Respondents ( N = 1,717, 22%) mostly lived in rural areas (55%); 45% of rural and 25% of urban residents had high school education or less and this difference was statistically significant. After adjustment for rurality, lower educational attainment was associated with smoking, difficulty paying for basic necessities, greater financial difficulty during the COVID-19 pandemic, struggling to pay for gas ( P < 0.01), fatalistic attitudes toward cancer prevention, and susceptibility to information overload about cancer prevention. Among the 33% of respondents who delayed getting medical care in the past year, this was more often due to lack of transportation in those with lower educational attainment (21% vs. 3%, P = 0.02 adjusted for rurality) and more often due to concerns about catching COVID-19 among urban than rural residents (52% vs. 21%; P < 0.001 adjusted for education). In conclusion, in NH/VT, smoking, financial hardship, and beliefs about cancer prevention are independently associated with lower educational attainment but not rural residence. These findings have implications for the design of interventions to address cancer risk in rural areas., Significance: In NH and VT, the finding that some associations between cancer risk factors and rural residence are more closely tied to educational attainment than rurality suggest that the design of interventions to address cancer risk should take educational attainment into account., (© 2023 The Authors; Published by the American Association for Cancer Research.)

We tested the hypotheses that adult cancer incidence and mortality in the Northeast region and in Northern New England (NNE) were different than the rest of the United States, and described other related cancer metrics and risk factor prevalence. Using national, publicly available cancer registry data, we compared cancer incidence and mortality in the Northeast region with the United States and NNE with the United States overall and by race/ethnicity, using age-standardized cancer incidence and rate ratios (RR). Compared with the United States, age-adjusted cancer incidence in adults of all races combined was higher in the Northeast (RR, 1.07; 95% confidence interval [CI] 1.07-1.08) and in NNE (RR 1.06; CI 1.05-1.07). However compared with the United States, mortality was lower in the Northeast (RR, 0.98; CI 0.98-0.98) but higher in NNE (RR, 1.05; CI 1.03-1.06). Mortality in NNE was higher than the United States for cancers of the brain (RR, 1.16; CI 1.07-1.26), uterus (RR, 1.32; CI 1.14-1.52), esophagus (RR, 1.36; CI 1.26-1.47), lung (RR, 1.12; CI 1.09-1.15), bladder (RR, 1.23; CI 1.14-1.33), and melanoma (RR, 1.13; CI 1.01-1.27). Significantly higher overall cancer incidence was seen in the Northeast than the United States in all race/ethnicity subgroups except Native American/Alaska Natives (RR, 0.68; CI 0.64-0.72). In conclusion, NNE has higher cancer incidence and mortality than the United States, a pattern that contrasts with the Northeast region, which has lower cancer mortality overall than the United States despite higher incidence., Significance: These findings highlight the need to identify the causes of higher cancer incidence in the Northeast and the excess cancer mortality in NNE., (© 2023 The Authors; Published by the American Association for Cancer Research.)

Background: Juvenile idiopathic arthritis (JIA) is a common pediatric rheumatic condition and is associated with symptoms such as joint pain that can negatively impact health-related quality of life. To effectively manage pain in JIA, young people, their families, and health care providers (HCPs) should be supported to discuss pain management options and make a shared decision. However, pain is often under-recognized, and pain management discussions are not optimal. No studies have explored decision-making needs for pain management in JIA using a shared decision making (SDM) model. We sought to explore families' decision-making needs with respect to pain management among young people with JIA, parents/caregivers, and HCPs., Methods: We conducted semi-structured virtual or face-to-face individual interviews with young people with JIA 8-18 years of age, parents/caregivers and HCPs using a qualitative descriptive study design. We recruited participants online across Canada and the United States, from a hospital and from a quality improvement network. We used interview guides based on the Ottawa Decision Support Framework to assess decision-making needs. We audiotaped, transcribed verbatim and analyzed interviews using thematic analysis., Results: A total of 12 young people (n = 6 children and n = 6 adolescents), 13 parents/caregivers and 11 HCPs participated in interviews. Pediatric HCPs were comprised of rheumatologists (n = 4), physical therapists (n = 3), rheumatology nurses (n = 2) and occupational therapists (n = 2). The following themes were identified: (1) need to assess pain in an accurate manner; (2) need to address pain in pediatric rheumatology consultations; (3) need for information on pain management options, especially nonpharmacological approaches; (4) importance of effectiveness, safety and ease of use of treatments; (5) need to discuss young people/families' values and preferences for pain management options; and the (6) need for decision support. Themes were similar for young people, parents/caregivers and HCPs, although their respective importance varied., Conclusions: Findings suggest a need for evidence-based information and communication about pain management options, which would be addressed by decision support interventions and HCP training in pain and SDM. Work is underway to develop such interventions and implement them into practice to improve pain management in JIA and in turn lead to better health outcomes., (© 2023. The Author(s).)

Purpose: Geographic access to cancer care is known to significantly impact utilization and outcomes. Longer travel times have negative impacts for patients requiring highly specialized care, such as for rare cancers, and for those in rural areas. Scant population-based research informs geographic access to care for rare cancers and whether rurality impacts that access., Methods: Using Medicare data (2014-2015), we identified prevalent cancers and cancer-directed surgeries, chemotherapy, and radiation. We classified cancers as rare (incidence <6/100,000/year) or common (incidence ≥6/100,000/year) using previously published thresholds and categorized rurality from ZIP code of beneficiary residence. We estimated travel time between beneficiaries and providers for each service based on ZIP code. Descriptive statistics summarized travel time by rare versus common cancers, service type, and rurality., Findings: We included 1,169,761 Medicare beneficiaries (21.9% in nonmetropolitan areas), 87,399; 7.5% had rare cancers, with 9,133,003 cancer-directed services. Travel times for cancer services ranged from approximately 29 minutes (25th percentile) to 68 minutes (75th percentile). Travel times were similar for rare and common cancers overall (median: 45 vs 43 minutes) but differed by service type; 13.4% of surgeries were >2 hours away for rare cancers, compared to 8.3% for common cancers. Increasing rurality disproportionately increased travel time to surgical care for rare compared to common cancers., Conclusions: Travel times to cancer services are longest for surgery, especially among rural residents, yet not markedly longer overall between rare versus common cancers. Understanding geographic access to cancer care for patients with rare cancers is important to delivering specialized care., (© 2022 National Rural Health Association.)

Objective: To evaluate the proportion of children with juvenile idiopathic arthritis (JIA) who met criteria for comorbid juvenile fibromyalgia (FM) using the Pain and Symptom Assessment Tool (PSAT), and to identify clinical and demographic differences among JIA patients with and without juvenile FM., Methods: Patients ages 11-17 years with JIA were recruited from 4 North American pediatric rheumatology centers. Each patient completed the PSAT. Additional clinical and disease activity measures included pain visual analog scale, patient global assessment of disease activity (PtGA) and physician global assessment of disease activity (PhGA), the Functional Disability Inventory (FDI), and the Pain Catastrophizing Scale in children., Results: Of 129 patients, 11 met criteria for juvenile FM. FDI scores were markedly higher in patients who tested positive for juvenile FM, with a mean of 24.8 compared to 6.9 in patients without juvenile FM (P < 0.001). Pain catastrophizing scores were also significantly higher, by ~14 points, in patients with juvenile FM. There was a significant tendency for patients to give higher disease activity scores than physicians, which was more marked among patients with juvenile FM. In patients with juvenile FM, PtGA scores exceeded PhGA scores by a mean of 3.7, compared to a mean of 0.7 among patients without juvenile FM (P < 0.001)., Conclusion: A minority of JIA patients (8.5%) met criteria for juvenile FM. This group demonstrated markedly more functional impairment. PtGA scores were strikingly higher than PhGA scores among patients with JIA who met juvenile FM criteria, suggesting that providers might consider a more expansive approach to chronic pain and non-musculoskeletal symptom assessment and treatment in JIA patients., (© 2021 American College of Rheumatology.)

Background: In a 2018 descriptive study, cancer incidence in children (age 0-19) in diagnosis years 2003 to 2014 was reported as being highest in New Hampshire and in the Northeast region., Methods: Using the Cancer in North America (CiNA) analytic file, we tested the hypotheses that incidence rates in the Northeast were higher than those in other regions of the United States either overall or by race/ethnicity group, and that rates in New Hampshire were higher than the Northeast region as a whole., Results: In 2003 to 2014, pediatric cancer incidence was significantly higher in the Northeast than other regions of the United States overall and among non-Hispanic Whites and Blacks, but not among Hispanics and other racial minorities. However, there was no significant variability in incidence in the states within the Northeast overall or by race/ethnicity subgroup. Overall, statistically significantly higher incidence was seen in the Northeast for lymphomas [RR, 1.15; 99% confidence interval (CI), 1.10-1.19], central nervous system neoplasms (RR, 1.12; 99% CI, 1.07-1.16), and neuroblastoma (RR, 1.13; 99% CI, 1.05-1.21)., Conclusions: Pediatric cancer incidence is statistically significantly higher in the Northeast than in the rest of the United States, but within the Northeast, states have comparable incidence. Differences in cancer subtypes by ethnicity merit further investigation., Impact: Our analyses clarify and extend previous reports by statistically confirming the hypothesis that the Northeast has the highest pediatric cancer rates in the country, by providing similar comparisons stratified by race/ethnicity, and by assessing variability within the Northeast., (©2022 American Association for Cancer Research.)

Background: This study evaluated the influence that social determinants of health had on stage at diagnosis and receipt of cancer-directed surgery for patients with lung and colorectal cancer in the North Carolina Central Cancer Registry (2010-2015)., Methods: This study examined non-Hispanic uninsured or privately-insured patients 18 to 64 years of age. Multivariable logistic regression models, including two-way interaction terms, assessed the influence of race, insurance status, rurality, and Social Deprivation Index on stage at diagnosis and receipt of surgery., Results: 6574 lung cancer patients and 5355 colorectal cancer patients were included. Among the lung cancer patients, the uninsured patients had higher odds of having stage IV disease (odds ratio [OR] = 1.46; 95 % confidence interval [CI] = 1.22-1.76) and lower odds of receiving surgery (OR = 0.48; 95 % CI = 0.34-0.69) than the privately-insured patients. Among the colorectal cancer patients, uninsured status was associated with higher odds of stage IV disease (OR = 1.53; 95 % CI = 1.17-2.00) than privately-insured status. A significant insurance status and rurality interaction (p = 0.03) was found in the colorectal model for receipt of surgery. In the privately-insured group, non-Hispanic Black and rural patients had lower odds of receiving colorectal surgery (OR = 0.69; 95 % CI = 0.50-0.94 and OR = 0.68; 95 % CI = 0.52-0.89; respectively) than their non-Hispanic White and urban counterparts., Conclusions: After controlling for confounding and evaluation of interactions between patient-, community-, and geographic-level factors, uninsured status remained the strongest driver of patients' presentation with late-stage lung and colorectal cancer. As policy and care delivery transformation targets uninsured and vulnerable populations, explicit recognition, and measurement of intersectionality should be considered., (© 2022. Society of Surgical Oncology.)

Objective: Treat to target (T2T) is a strategy of adjusting treatment until a target is reached. An international task force recommended T2T for juvenile idiopathic arthritis (JIA) treatment. Implementing T2T in a standard and reliable way in clinical practice requires agreement on critical elements of (1) target setting, (2) T2T strategy, (3) identifying barriers to implementation, and (4) patient eligibility. A consensus conference was held among Pediatric Rheumatology Care and Outcomes Improvement Network (PR-COIN) stakeholders to inform a statement of understanding regarding the PR-COIN approach to T2T., Methods: PR-COIN stakeholders including 16 healthcare providers and 4 parents were invited to form a voting panel. Using the nominal group technique, 2 rounds of voting were held to address the above 4 areas to select the top 10 responses by rank order., Results: Incorporation of patient goals ranked most important when setting a treatment target. Shared decision making (SDM), tracking measurable outcomes, and adjusting treatment to achieve goals were voted as the top elements of a T2T strategy. Workflow considerations, and provider buy-in were identified as key barriers to T2T implementation. Patients with JIA who had poor prognostic factors and were at risk for high disease burden were leading candidates for a T2T approach., Conclusion: This consensus conference identified the importance of incorporating patient goals as part of target setting and of the influence of patient stakeholder involvement in drafting treatment recommendations. The network approach to T2T will be modified to address the above findings, including solicitation of patient goals, optimizing SDM, and better workflow integration., (Copyright © 2022 by the Journal of Rheumatology.)

Background: Considerable gaps in knowledge remain regarding the intersectionality between race, insurance status, rurality, and community-level socioeconomic status that contribute in concert to disparities in breast cancer care delivery., Methods: Women age 18-64 y old with either private, Medicaid, or no insurance coverage and a diagnosis of breast cancer from the North Carolina Central Cancer Registry (2010-2015) were identified and reviewed. Logistic regression models examined the impact of race, insurance status, rurality, and the Social Deprivation Index (SDI) on advanced stage disease at diagnosis (III, IV) and receipt of cancer directed surgery (CDS). Models tested two-way interactions between race, insurance status, rurality, and SDI., Results: Of the study population (n = 23,529), 14.6% were diagnosed with advanced stage disease (III, IV), and 97.1% of women with non-metastatic breast cancer (n = 22,438) received cancer directed surgery (CDS). Twenty percent of women were non-Hispanic Black (NHB), 3.0% Hispanic, 10.9% Medicaid insured, 5.9% uninsured, 20.0% of women resided in rural areas, and 20.0% resided in communities of the highest quartile SDI. NHB race, Medicaid or uninsured status, and residence in rural or socially deprived areas were associated with advanced stage breast cancer at diagnosis. NHB and Medicaid or uninsured women were significantly less likely to receive CDS. There were no statistically significant interactions found influencing stage at diagnosis or receipt of cancer directed surgery., Conclusions: In a heterogeneous population across the state of North Carolina, non-Hispanic Black race, Medicaid or uninsured status, and residence in rural or high social deprivation communities are independently associated with advanced stage breast cancer at diagnosis, while non-Hispanic Black race and Medicaid or uninsured status are associated with lower odds to receive cancer directed surgery., (Copyright © 2021. Published by Elsevier Inc.)

Juvenile fibromyalgia is a common referral in pediatric rheumatology settings. Providing a clear diagnosis and explanation of altered pain processing offers reassurance that pain has a biologic basis and the symptoms are part of a recognized pain syndrome. Physicians should acknowledge the impact of chronic pain and associated symptoms on patient's lives and take time to understand contributing factors including stress, mood, inactivity, and lifestyle factors. The optimal treatment for juvenile fibromyalgia is multidisciplinary, focusing on education about juvenile fibromyalgia, along with physical therapy, cognitive behavioral therapy, sleep hygiene, healthy lifestyle habits, and medications for symptom management as appropriate., Competing Interests: Disclosure S. Kashikar-Zuck receives funding for her research in JFM from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) of the National Institutes of Health, USA. Drs J.E. Weiss and S. Kashikar-Zuck receive support from the Arthritis Foundation for their work on the Steering Committee of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) of North America., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: To determine s.c. tocilizumab (s.c.-TCZ) dosing regimens for systemic JIA (sJIA) and polyarticular JIA (pJIA)., Methods: In two 52-week phase 1 b trials, s.c.-TCZ (162 mg/dose) was administered to sJIA patients every week or every 2 weeks (every 10 days before interim analysis) and to pJIA patients every 2 weeks or every 3 weeks with body weight ≥30 kg or <30 kg, respectively. Primary end points were pharmacokinetics, pharmacodynamics and safety; efficacy was exploratory. Comparisons were made to data from phase 3 trials with i.v. tocilizumab (i.v.-TCZ) in sJIA and pJIA., Results: Study participants were 51 sJIA patients and 52 pJIA patients aged 1-17 years who received s.c.-TCZ. Steady-state minimum TCZ concentration (Ctrough) >5th percentile of that achieved with i.v.-TCZ was achieved by 49 (96%) sJIA and 52 (100%) pJIA patients. In both populations, pharmacodynamic markers of disease were similar between body weight groups. Improvements in Juvenile Arthritis DAS-71 were comparable between s.c.-TCZ and i.v.-TCZ. By week 52, 53% of sJIA patients and 31% of pJIA patients achieved clinical remission on treatment. Safety was consistent with that of i.v.-TCZ except for injection site reactions, reported by 41.2% and 28.8% of sJIA and pJIA patients, respectively. Infections were reported in 78.4% and 69.2% of patients, respectively. Two sJIA patients died; both deaths were considered to be related to TCZ., Conclusion: s.c.-TCZ provides exposure and risk/benefit profiles similar to those of i.v.-TCZ. S.c. administration provides an alternative administration route that is more convenient for patients and caregivers and that has potential for in-home use., Trial Registration: ClinicalTrials.gov, http://clinicaltrials.gov, NCT01904292 and NCT01904279., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Importance: Treatment delays are associated with increased morbidity and cost of disease, although the extent to which cost sharing influences timely presentation and management of acute surgical disease remains unknown. Given recent policy changes using cost sharing to modify health care behavior, this study examines the association of cost sharing with the health of the patient at presentation and with receipt of optimal or minimally invasive surgery., Objective: To assess whether cost sharing is associated with the likelihood of early, uncomplicated patient presentation or with surgical management of 2 representative emergency general surgery diagnoses: acute appendicitis and acute diverticulitis., Design Setting and Participants: This cohort study used Health Care Cost Institute claims from January 1, 2013, through December 31, 2017, to analyze data of commercially insured individuals hospitalized for acute appendicitis or diverticulitis. In total, 151 852 patients in the data set aged 18 to 64 years and presenting with acute appendicitis or diverticulitis were included as identified using the International Classification of Diseases, Ninth Revision and the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision . Data were analyzed from January 2020 through February 2021., Exposures: The primary exposure was patient total cost sharing incurred for the index hospitalization, defined as their summed deductible, copayments, and coinsurance., Main Outcomes and Measures: The primary outcome was early, uncomplicated disease presentation. Secondary outcomes were receipt of optimal surgical care and minimally invasive surgery if undergoing an operation. Analyses were conducted with multivariable logistic regression models to adjust for patient characteristics and community-level socioeconomic and geographic factors. High cost sharing was defined as quartile 4 (>$3082), and low cost sharing as quartile 1 ($0-$502)., Results: Among 151 852 patients, 52.4% were men, and the total cost-sharing median was $1725 (interquartile range, $503-$3082). Higher cost sharing was associated with lower odds of early, uncomplicated disease presentation (odds ratio, 0.63; 95% CI, 0.61-0.65). Patients with higher cost sharing were less likely to receive optimal surgical care (odds ratio, 0.96; 95% CI, 0.93-0.99) or minimally invasive surgery (odds ratio, 0.89; 95% CI, 0.84-0.95)., Conclusions and Relevance: The findings of this cohort study suggest that, as policymakers debate the degree of cost sharing in public and private insurance plans, attention should be given to the clinical and financial implications associated with care delays., Competing Interests: Conflict of Interest Disclosures: Dr Loehrer reported receiving grants from the Robert Wood Johnson Foundation during the conduct of the study. Mr Wengle reported receiving nonfinancial support from a Robert Wood Johnson Foundation grant for data access during the conduct of the study. Dr Zuckerman reported receiving grants from the Robert Wood Johnson Foundation during the conduct of the study. No other disclosures were reported., (Copyright 2021 Loehrer AP et al. JAMA Health Forum.)

Background: Cancer is the second leading cause of death globally, and researchers seek to identify modifiable risk factors Over the past several decades, there has been ongoing debate whether opioids are associated with cancer development, metastasis, or recurrence. Basic science, clinical, and observational studies have produced conflicting results. The authors examined the association between prescription opioids and incident cancers using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. A complex relation was observed between prescription opioids and incident cancer, and cancer site may be an important determinant., Methods: By using linked SEER cancer registry and Medicare claims from 2008 through 2013, a case-control study was conducted examining the relation between cancer onset and prior opioid exposure. Logistic regression was used to account for differences between cases and controls for 10 cancer sites., Results: Of the population studied (n = 348,319), 34% were prescribed opioids, 79.5% were white, 36.9% were dually eligible (for both Medicare and Medicaid), 13% lived in a rural area, 52.7% had ≥1 comorbidity, and 16% had a smoking-related diagnosis. Patients exposed to opioids had a lower odds ratio (OR) associated with breast cancer (adjusted OR, 0.96; 95% CI, 0.92-0.99) and colon cancer (adjusted OR, 0.90; 95% CI, 0.86-0.93) compared with controls. Higher ORs for kidney cancer, leukemia, liver cancer, lung cancer, and lymphoma, ranging from lung cancer (OR, 1.04; 95% CI, 1.01-1.07) to liver cancer (OR, 1.19; 95% CI, 1.08-1.31), were present in the exposed population., Conclusions: The current results suggest that an association exists between prescription opioids and incident cancer and that cancer site may play an important role. These findings can direct future research on specific patient populations that may benefit or be harmed by prescription opioid exposure., (© 2020 American Cancer Society.)

This is a case of an 11-year-old female who was admitted with respiratory failure, requiring intubation while testing positive for SARS-CoV-2. During her recovery, she had new onset fevers and uptrending inflammatory markers. After an evaluation of infectious causes, the diagnosis of MIS-C was made approximately 1 month after her initial symptoms.

Background and Aims: National guidelines for colonoscopy screening and surveillance assume adequate bowel preparation. We used New Hampshire Colonoscopy Registry (NHCR) data to investigate the influence of bowel preparation quality on endoscopist recommendations for follow-up intervals in average-risk patients following normal screening colonoscopies., Methods: The analysis included 9170 normal screening colonoscopies performed on average risk individuals aged 50 and above between February 2005 and September 2013. The NHCR Procedure Form instructs endoscopists to score based on the worst prepped segment after clearing all colon segments, using the following categories: excellent (essentially 100% visualization), good (very unlikely to impair visualization), fair (possibly impairing visualization), and poor (definitely impairing visualization). We categorized examinations into 3 preparation groups: optimal (excellent/good) (n=8453), fair (n=598), and poor (n=119). Recommendations other than 10 years for examinations with optimal preparation, and >1 year for examinations with poor preparation, were considered nonadherent., Results: Of all examinations, 6.2% overall received nonadherent recommendations, including 5% of examinations with optimal preparation and 89.9% of examinations with poor preparation. Of normal examinations with fair preparation, 20.7% of recommendations were for an interval <10 years. Among those examinations with fair preparation, shorter-interval recommendations were associated with female sex, former/nonsmokers, and endoscopists with adenoma detection rate ≥20%., Conclusions: In 8453 colonoscopies with optimal preparations, most recommendations (95%) were guideline-adherent. No guideline recommendation currently exists for fair preparation, but in this investigation into community practice, the majority of the fair preparation group received 10-year follow-up recommendations. A strikingly high proportion of examinations with poor preparation received a follow-up recommendation greater than the 1-year guideline recommendation. Provider education is needed to ensure that patients with poor bowel preparation are followed appropriately to reduce the risk of missing important lesions.

Purpose: This study examined the concordance between individuals' self-reported rural-urban category of their community and ZIP Code-derived Rural-Urban Commuting Area (RUCA) category., Methods: An Internet-based survey, administered from August 2017 through November 2017, was used to collect participants' sociodemographic characteristics, self-reported ZIP Code of residence, and perception of which RUCA category best describes the community in which they live. We calculated weighted kappa (ĸ) coefficients (95% confidence interval [CI]) to test for concordance between participants' ZIP Code-derived RUCA category and their selection of RUCA descriptor. Descriptive frequency distributions of participants' demographics are presented., Findings: A total of 622 survey participants, residents of New Hampshire (63%) and Vermont (37%), responded to the survey's self-reported rural-urban category. The overall ĸ was 0.33 (95% CI: 0.27-0.38). The highest concordance was found among those living in a small rural area (N = 81, 13%): 62% of this group identified their communities as small rural. Sixty-five percent (300/459) of participants residing in urban or large rural areas reported their community as more rural (small rural or isolated). Sixty-eight percent (111/163) of participants living in small rural or isolated areas identified their community as more urban (large rural or urban)., Conclusions: Discordance was found between self-report of rural-urban category and ZIP Code-derived RUCA designation. Caution is warranted when attributing rural-urban designation to individuals based on geographic unit, since perceived rurality/urbanicity of their community that relates to health behaviors may not be reflected., (© 2019 National Rural Health Association.)

Following publication of the original article [1], we have been notified that the corresponding author's given name is spelled incorrectly.

Background: Severe pain and impairments in functioning are commonly reported for youth with juvenile fibromyalgia. The prevalence and impact of pain in other diseases commonly managed in pediatric rheumatology comparatively have been rarely systematically studied. The objective of the current study was to determine the extent to which high levels of pain and functional limitations, and the strength of their association, are unique to youth with juvenile primary fibromyalgia syndrome/JPFS) relative to other pediatric rheumatic diseases., Methods: Using data from 7753 patients enrolled in the multinational Childhood Arthritis and Rheumatology Research Alliance (CARRA) Legacy Registry, we compared the levels and association of pain and functional limitations between youth with JPFS and those with other rheumatic diseases., Results: Pain levels were rated highest among youth with JPFS (M = 6.4/10, SD = 2.4) and lowest for juvenile dermatomyositis (M = 1.7/10, SD = 2.2), with pain significantly higher in the JPFS group than any other pediatric rheumatic disease (effect sizes = .22 to 1.05). Ratings on measures of functioning and well-being also were significantly worse for patients with JPFS than patients with any other rheumatic disease (effect sizes = .62 to 1.06). The magnitude of association between pain intensity and functional disability, however, generally was higher in other rheumatic diseases than in JPFS. Pain was most strongly associated with functional limitations in juvenile dermatomyositis, juvenile idiopathic arthritis, and mixed connective tissue disease., Conclusions: JPFS is unique among conditions seen in pediatric rheumatology with regard to ratings of pain and disability. However, pain appears to be comparably or more highly associated with level of functional impairment in other pediatric rheumatic diseases. Pain in childhood rheumatic disease thus would benefit from increased prioritization for research and treatment.

Background and study aims  Adenoma detection rate (ADR), the proportion of an endoscopist's screening colonoscopies in which at least one adenoma is found, is an established quality metric. Several publications have suggested that a technique referred to as "one and done," where less attention is paid to additional polyp detection following discovery of one likely adenoma, may be occurring 1 2 3 . To investigate whether this practice occurs and provide additional context to the significance of ADR, we examined ADR by single and multiple adenomas in the statewide New Hampshire Colonoscopy Registry (NHCR). Patients and methods  A total of 25,324 NHCR patients receiving screening colonoscopies between 2009 and 2014 by 69 endoscopists were analyzed. ADR was dichotomized into high (≥ 20 %) and low (< 20 %) based on 2006 recommended targets in place during the time of the study. ADR-plus (the average number of adenomas in colonoscopies with > 1 adenoma) was dichotomized at mean values into high (≥ 1.5) and low (< 1.5). As suggested by others, a high ADR but low ADR-plus was used to indicate the "one and done" approach. Results  Among endoscopists with an ADR ≥ 20 %, only 5 (7.2 %) had low ADR-plus values and were classified as "one and done." Results for serrated polyp detection were similar. ADR and ADR-plus decreased monotonically with increasing years since residency ( P values for trend ADR = 0.02; ADR-plus = 0.003) after adjusting for patient risk factors. Conclusion  "One and done" infrequently occurred among endoscopists with high ADR in a large statewide registry. The need to replace ADR with other polyp detection metrics (such as ADR-plus) to accurately ascertain performance quality is not supported by these findings.

Background: To describe the demographic, clinical, and treatment characteristics of youth diagnosed with juvenile primary fibromyalgia syndrome (JPFS) who are seen in pediatric rheumatology clinics., Methods: Information on demographics, symptoms, functioning, and treatments recommended and tried were obtained on patients with JPFS as part of a multi-site patient registry (the Childhood Arthritis and Rheumatology Research Alliance Legacy Registry). Data were summarized using descriptive statistics. In a subset of patients completing registry follow-up visits, changes in symptoms, pain, and functioning were evaluated using growth modeling., Results: Of the 201 patients with JPFS enrolled in the registry, most were Caucasian/White (85%), non-Hispanic (83%), and female (84%). Ages ranged from 9 to 20 years (M = 15.4 + 2.2). The most common symptoms reported were widespread musculoskeletal pain (91%), fatigue (84%), disordered sleep (82%), and headaches (68%). Pain intensity was rated as moderate to severe (M = 6.3 + 2.4/10). Scores on measures of functioning indicated mild to moderate impairment, with males observed to report significantly greater impairments. For the 37% of the initial cohort having follow-up data available, indicators of function and well-being were found to either worsen over time or remain relatively unchanged., Conclusions: The symptoms of JPFS remained persistent and disabling for many patients treated by pediatric rheumatologists. Further study appears warranted to elucidate gender differences in the impact of JPFS symptoms. Work also is needed to identify accessible and effective outpatient treatment options for JPFS that can be routinely recommended or implemented by pediatric rheumatology providers.

Objective: To determine the relationship between serum levels of S100A8/A9 and S100A12 and the maintenance of clinically inactive disease during anti-tumor necrosis factor (anti-TNF) therapy and the occurrence of disease flare following withdrawal of anti-TNF therapy in patients with polyarticular forms of juvenile idiopathic arthritis (JIA)., Methods: In this prospective, multicenter study, 137 patients with polyarticular-course JIA whose disease was clinically inactive while receiving anti-TNF therapy were enrolled. Patients were observed for an initial 6-month phase during which anti-TNF treatment was continued. For those patients who maintained clinically inactive disease over the 6 months, anti-TNF was withdrawn and they were followed up for 8 months to assess for the occurrence of flare. Serum S100 levels were measured at baseline and at the time of anti-TNF withdrawal. Spearman's rank correlation test, Mann-Whitney U test, Kruskal-Wallis test, receiver operating characteristic (ROC) curve, and Kaplan-Meier survival analyses were used to assess the relationship between serum S100 levels and maintenance of clinically inactive disease and occurrence of disease flare after anti-TNF withdrawal., Results: Over the 6-month initial phase with anti-TNF therapy, the disease state reverted from clinically inactive to clinically active in 24 (18%) of the 130 evaluable patients with polyarticular-course JIA; following anti-TNF withdrawal, 39 (37%) of the 106 evaluable patients experienced a flare. Serum levels of S100A8/A9 and S100A12 were elevated in up to 45% of patients. Results of the ROC analysis revealed that serum S100 levels did not predict maintenance of clinically inactive disease during anti-TNF therapy nor did they predict disease flare after treatment withdrawal. Elevated levels of S100A8/A9 were not predictive of the occurrence of a disease flare within 30 days, 60 days, 90 days, or 8 months following anti-TNF withdrawal, and elevated S100A12 levels had a modest predictive ability for determining the risk of flare within 30, 60, and 90 days after treatment withdrawal. Serum S100A12 levels at the time of anti-TNF withdrawal were inversely correlated with the time to disease flare (r = -0.36)., Conclusion: Serum S100 levels did not predict maintenance of clinically inactive disease or occurrence of disease flare in patients with polyarticular-course JIA, and S100A12 levels were only moderately, and inversely, correlated with the time to disease flare., (© 2018, American College of Rheumatology.)

Studies have identified abnormalities in the microbiota of patients with arthritis. To evaluate the pathogenicity of human microbiota, we performed fecal microbial transplantation from children with spondyloarthritis and controls to germ-free KRN/B6xNOD mice. Ankle swelling was equivalent in those that received patient vs. control microbiota. Principal coordinates analysis revealed incomplete uptake of the human microbiota with over-representation of two genera (Bacteroides and Akkermansia) among the transplanted mice. The microbiota predicted the extent of ankle swelling (R2 = 0.185, p = 0.018). The abundances of Bacteroides (r = -0.510, p = 0.010) inversely and Akkermansia (r = 0.367, p = 0.078) directly correlated with ankle swelling. Addition of Akkermansia muciniphila to Altered Schaedler's Flora (ASF) resulted in small but statistically significant increased ankle swelling as compared to mice that received ASF alone (4.0 mm, 3.9-4.1 vs. 3.9 mm, IQR 3.6-4.0, p = 0.041), as did addition of A. muciniphila cultures to transplanted human microbiota as compared to mice that received transplanted human microbiota alone (4.5 mm, IQR 4.3-5.5 vs. 4.1 mm, IQR 3.9-4.3, p = 0.019). This study supports previous findings of an association between A. muciniphila and arthritis.

Objective: To determine the frequency, time to flare, and predictors of disease flare upon withdrawal of anti-tumor necrosis factor (anti-TNF) therapy in children with polyarticular forms of juvenile idiopathic arthritis (JIA) who demonstrated ≥6 months of continuous clinically inactive disease., Methods: In 16 centers 137 patients with clinically inactive JIA who were receiving anti-TNF therapy (42% of whom were also receiving methotrexate [MTX]) were prospectively followed up. If the disease remained clinically inactive for the initial 6 months of the study, anti-TNF was stopped and patients were assessed for flare at 1, 2, 3, 4, 6, and 8 months. Life-table analysis, t-tests, chi-square test, and Cox regression analysis were used to identify independent variables that could significantly predict flare by 8 months or time to flare., Results: Of 137 patients, 106 (77%) maintained clinically inactive disease while receiving anti-TNF therapy for the initial 6 months and were included in the phase of the study in which anti-TNF therapy was stopped. Stopping anti-TNF resulted in disease flare in 39 (37%) of 106 patients by 8 months. The mean/median ± SEM time to flare was 212/250 ± 9.77 days. Patients with shorter disease duration at enrollment, older age at onset and diagnosis, shorter disease duration prior to experiencing clinically inactive disease, and shorter time from onset of clinically inactive disease to enrollment were found to have significantly lower hazard ratios for likelihood of flare by 8 months (P < 0.05)., Conclusion: Over one-third of patients with polyarticular JIA with sustained clinically inactive disease will experience a flare by 8 months after discontinuation of anti-TNF therapy. Several predictors of lower likelihood of flare were identified., (© 2018, American College of Rheumatology.)

Chronic musculoskeletal pain (CMP) is one of the main reasons for referral to a pediatric rheumatologist and is the third most common cause of chronic pain in children and adolescents. Causes of CMP include amplified musculoskeletal pain, benign limb pain of childhood, hypermobility, overuse syndromes, and back pain. CMP can negatively affect physical, social, academic, and psychological function so it is essential that clinicians know how to diagnose and treat these conditions. This article provides an overview of the epidemiology and impact of CMP, the steps in a comprehensive pain assessment, and the management of the most common CMPs., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: The survival benefit from detecting additional breast cancers by preoperative magnetic resonance imaging (MRI) continues to be controversial., Methods: We followed a cohort of 4454 women diagnosed with non-metastatic breast cancer (stage I-III) from 2/2005-6/2010 in five registries of the breast cancer surveillance consortium (BCSC). BCSC clinical and registry data were linked to Medicare claims and enrollment data. We estimated the cumulative probability of breast cancer-specific and all-cause mortality. We tested the association of preoperative MRI with all-cause mortality using a Cox proportional hazards model., Results: 917 (20.6%) women underwent preoperative MRI. No significant difference in the cumulative probability of breast cancer-specific mortality was found. We observed no significant difference in the hazard of all-cause mortality during the follow-up period after adjusting for sociodemographic and clinical factors among women with MRI (HR 0.90; 95% CI 0.72-1.12) compared to those without MRI., Conclusion: Our findings of no breast cancer-specific or all-cause mortality benefit supplement prior results that indicate a lack of improvement in surgical outcomes associated with use of preoperative MRI. In combination with other reports, the results of this analysis highlight the importance of exploring the benefit of preoperative MRI in patient-reported outcomes such as women's decision quality and confidence levels with decisions involving treatment choices.

Background: A history of proliferative breast disease with atypia (PBDA) may be indicative of an increased risk not just of breast cancer but also of a more aggressive form of breast cancer., Methods: Multifocal breast cancer (MFBC), defined as 2 or more tumors in the same breast upon a diagnosis of cancer, is associated with a poorer prognosis than unifocal (single-tumor) breast cancer. PBDA, including atypical ductal hyperplasia and atypical lobular hyperplasia, is a known risk factor for breast cancer. Using New Hampshire Mammography Network data collected for 3567 women diagnosed with incident breast cancer from 2004 to 2014, this study assessed the risk of MFBC associated with a previous diagnosis of PBDA., Results: Women with a history of PBDA were found to be twice as likely to be subsequently diagnosed with MFBC as women with no history of benign breast disease (BBD; odds ratio [OR], 2.23; 95% confidence interval [CI], 1.08-4.61). Ductal carcinoma in situ on initial biopsy was associated with a 2-fold increased risk of MFBC in comparison with invasive cancer (OR, 2.13; 95% CI, 1.58-2.88). BBD and proliferative BBD without atypia were not associated with MFBC., Conclusions: Women with a history of previous PBDA may be at increased risk for MFBC. Women with a history of PBDA may benefit from additional presurgical clinical workup. Cancer 2018;124:1350-7. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

Background: Prior studies have demonstrated abnormalities in the composition of the gastrointestinal microbiota in pediatric and adult patients with spondyloarthritis (SpA). In particular, diminished fecal abundance of Faecalibacterium prausnitzii and abnormalities in both directions in the abundance of the Bacteroides genus have been identified., Methods: We obtained fecal specimens from 30 children with treatment-naïve enthesitis-related arthritis (ERA) and 19 healthy controls, as well as specimens from 11 adult patients with longstanding SpA and 10 adult healthy controls. All of the samples underwent sequencing of the 16S ribosomal DNA. A subset of the pediatric fecal samples was subjected to shotgun metagenomics sequencing., Results: ERA patients had decreased abundance of the anti-inflammatory F. prausnitzii A2-165 strain (41 ± 28% versus 54 ± 20% of all sequences matching F. prausnitzii, p = 0.084) and an increased abundance of the control F. prausnitzii L2/6 strain (28 ± 28% versus 15 ± 15%, p = 0.038). Similar trends were observed in adults with longstanding SpA (n = 11) and controls (n = 10). In contrast, the fecal abundance of Bacteroides fragilis was increased in ERA subjects (2.0 ± 4.0% versus 0.45 ± 0.7% of all sequences, p = 0.045), yet was diminished in adult subjects (0.2 ± % versus 1.0 ± % of all sequences, p = 0.106). Shotgun metagenomics sequencing of the fecal DNA in the pediatric subjects revealed diminished coverage of the butanoate pathway (abundance normalized to controls of 1 ± 0.48 versus 0.72 ± 0.33 in ERA, p = 0.037)., Conclusions: The anti-inflammatory F. prausnitzii A2-165 strain appears to be depleted in both pediatric and adult SpA. In contrast, B. fragilis may be depleted in adult disease yet abundant in pediatric SpA, suggesting developmental effects on the immune system.

Background & Aims: Surveillance guidelines for serrated polyps (SPs) are based on limited data on longitudinal outcomes of patients. We used the New Hampshire Colonoscopy Registry to evaluate risk of clinically important metachronous lesions associated with SPs detected during index colonoscopies., Methods: We collected data from a population-based colonoscopy registry that has been collecting and analyzing data on colonoscopies across the state of New Hampshire since 2004, including rates of adenoma and SP detection. Patients completed a questionnaire to determine demographic characteristics, health history, and risk factors for colorectal cancer, and were followed from index colonoscopy through all subsequent surveillance colonoscopies. Our analyses included 5433 participants (median age, 61 years; 49.7% male) with 2 colonoscopies (median time to surveillance, 4.9 years). We used multivariable logistic regression models to assess effects of index SPs (n = 1016), high-risk adenomas (HRA, n = 817), low-risk adenomas (n = 1418), and no adenomas (n = 3198) on subsequent HRA or large SPs (>1 cm) on surveillance colonoscopy (metachronous lesions). Synchronous SPs, within each index risk group, were assessed for size and by histology. SPs comprise hyperplastic polyps, sessile serrated adenomas/polyps (SSA/Ps), and traditional serrated adenomas. In this study, SSA/Ps and traditional serrated adenomas are referred to collectively as STSAs., Results: HRA and synchronous large SP (odds ratio [OR], 5.61; 95% confidence interval [CI], 1.72-18.28), HRA with synchronous STSA (OR, 16.04; 95% CI, 6.95-37.00), and HRA alone (OR, 3.86; 95% CI, 2.77-5.39) at index colonoscopy significantly increased the risk of metachronous HRA compared to the reference group (no index adenomas or SPs). Large index SPs alone (OR, 14.34; 95% CI, 5.03-40.86) or index STSA alone (OR, 9.70; 95% CI, 3.63-25.92) significantly increased the risk of a large metachronous SP., Conclusions: In an analysis of data from a population-based colonoscopy registry, we found index large SP or index STSA with no index HRA increased risk of metachronous large SPs but not metachronous HRA. HRA and synchronous SPs at index colonoscopy significantly increased risk of metachronous HRA. Individuals with HRA and synchronous large SP or any STSA could therefore benefit from close surveillance., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: More extensive surgical treatments for early stage breast cancer are increasing. The patterns of preoperative MRI overall and by stage for this trend has not been well established., Methods: Using Breast Cancer Surveillance Consortium registry data from 2010 through 2014, we identified women with an incident non-metastatic breast cancer and determined use of preoperative MRI and initial surgical treatment (mastectomy, with or without contralateral prophylactic mastectomy (CPM), reconstruction, and breast conserving surgery ± radiation). Clinical and sociodemographic covariates were included in multivariable logistic regression models to estimate adjusted odds ratios and 95% confidence intervals., Results: Of the 13 097 women, 2217 (16.9%) had a preoperative MRI. Among the women with MRI, results indicated 32% higher odds of unilateral mastectomy compared to breast conserving surgery and of mastectomy with CPM compared to unilateral mastectomy. Women with preoperative MRI also had 56% higher odds of reconstruction., Conclusion: Preoperative MRI in women with DCIS and early stage invasive breast cancer is associated with more frequent mastectomy, CPM, and reconstruction surgical treatment. Use of more extensive surgical treatment and reconstruction among women with DCIS and early stage invasive cancer whom undergo MRI warrants further investigation., (© 2017 Wiley Periodicals, Inc.)

Goal: To examine screening adenoma detection rates (ADR) and serrated detection rates (SDR) among smokers and obese adults in the New Hampshire Colonoscopy Registry., Background: ADR, a quality measure for screening colonoscopies, is associated with protection from interval colorectal cancer. Currently, only sex-specific ADR benchmarks are reported. However, obesity and smoking ≥20 pack-years are strong predictors for colorectal neoplasia, as highlighted by the 2009 American College of Gastroenterology CRC Screening Guidelines. Data comparing ADR in smokers and obese adults to those without these risks are limited., Study: We calculated ADR, SDR, and 95% confidence intervals for screening colonoscopies in participants ≥50 years. Sex-specific and sex-age-specific rates were compared by smoking exposure (never vs. <20 vs. ≥20 pack-years) and body mass index (<30 vs. ≥30)., Results: A total of 21,539 screening colonoscopies were performed by 77 endoscopists at 20 facilities (April 2009 to September 2013). The difference in ADR between nonsmokers and smokers with ≥20 pack-years was 8.8% (P<0.0001) and between obesity groups 5.0% (P<0.0001). Significant sex-specific and sex-age-specific increases in ADR and SDR were found among smokers and obese participants., Conclusions: ADR and SDR for smokers and obese adults were significantly higher than their counterparts without those risks. Endoscopists should consider the prevalence of these risks within their screening population when comparing their rates to established benchmarks. Calculating sex-specific or sex-age-specific ADR and SDR based on smoking and obesity may provide optimal protection for populations with a particularly high prevalence of smokers and obese adults.

Background: The prognosis of children with juvenile dermatomyositis (JDM) has improved remarkably since the 1960's with the use of corticosteroid and immunosuppressive therapy. Yet there remain a minority of children who have refractory disease. Since 2003 the sporadic use of biologics (genetically-engineered proteins that usually are derived from human genes) for inflammatory myositis has been reported. In 2011-2016 we investigated our collective experience of biologics in JDM through the Childhood Arthritis and Rheumatology Research Alliance (CARRA)., Methods: The JDM biologic study group developed a survey on the CARRA member experience using biologics for Juvenile DM utilizing Delphi consensus methods in 2011-2012. The survey was completed online by the CARRA members interested in JDM in 2012. A second survey was similarly developed that provided more opportunity to describe their experiences with biologics in JDM in detail and was completed by CARRA members in Feb 2013. During three CARRA meetings in 2013-2015, nominal group techniques were used for achieving consensus on the current choices of biologic drugs. A final survey was performed at the 2016 CARRA meeting., Results: One hundred and five of a potential 231 pediatric rheumatologists (42%) responded to the first survey in 2012. Thirty-five of 90 had never used a biologic for Juvenile DM at that time. Fifty-five of 91 (denominators vary) had used biologics for JDM in their practice with 32%, 5%, and 4% using rituximab, etanercept, and infliximab, respectively, and 17% having used more than one of the three drugs. Ten percent used a biologic as monotherapy, 19% a biologic in combination with methotrexate (mtx), 52% a biologic in combination with mtx and corticosteroids, 42% a combination of a biologic, mtx, corticosteroids (steroids), and an immunosuppressive drug, and 43% a combination of a biologic, IVIG and mtx. The results of the second survey supported these findings in considerably more detail with multiple combinations of drugs used with biologics and supported the use of rituximab, abatacept, anti-TNFα drugs, and tocilizumab in that order. One hundred percent recommended that CARRA continue studying biologics for JDM. The CARRA meeting survey in 2016 again supported the study and use of these four biologic drug groups., Conclusions: Our CARRA JDM biologic work group developed and performed three surveys demonstrating that pediatric rheumatologists in North America have been using multiple biologics for refractory JDM in numerous scenarios from 2011 to 2016. These survey results and our consensus meetings determined our choice of four biologic therapies (rituximab, abatacept, tocilizumab and anti-TNFα drugs) to consider for refractory JDM treatment when indicated and to evaluate for comparative effectiveness and safety in the future. Significance and Innovations This is the first report that provides a substantial clinical experience of a large group of pediatric rheumatologists with biologics for refractory JDM over five years. This experience with biologic therapies for refractory JDM may aid pediatric rheumatologists in the current treatment of these children and form a basis for further clinical research into the comparative effectiveness and safety of biologics for refractory JDM.

Background and Aims: Similar to achieving adenoma detection rate (ADR) benchmarks to prevent colorectal cancer (CRC), achieving adequate serrated polyp detection rates (SDRs) may be essential to the prevention of CRC associated with the serrated pathway. Previous studies have been based on data from high-volume endoscopists at single academic centers. Based on a hypothesis that ADR is correlated with SDR, we stratified a large, diverse group of endoscopists (n = 77 practicing at 28 centers) into high performers and low performers, based on ADR, to provide data for corresponding target SDR benchmarks., Methods: By using colonoscopies in adults aged ≥50 years (4/09-12/14), we stratified endoscopists by high and low ADRs (<15%, 15%-<25%, 25%-<35%, ≥35%) to determine corresponding SDRs by using 2 SDR measures, for screening and surveillance colonoscopies separately: (1) Clinically significant SDR (CSSDR), meaning colonoscopies with any sessile serrated adenoma/polyp (SSA/P), traditional serrated adenoma (TSA), or hyperplastic polyp (HP) >1 cm anywhere in the colon or HP >5 mm in the proximal colon only divided by the total number of screening and surveillance colonoscopies, respectively. (2) Proximal SDR (PSDR) meaning colonoscopies with any serrated polyp (SSA/P, HP, TSA) of any size proximal to the sigmoid colon divided by the total number of screening and surveillance colonoscopies, respectively., Results: A total of 45,996 (29,960 screening) colonoscopies by 77 endoscopists (28 facilities) were included. Moderately strong positive correlation coefficients were observed for screening ADR/CSSDR (P = .69) and ADR/PSDR (P = .79) and a strong positive correlation (P = .82) for CSSDR/PSDR (P < .0001 for all) was observed. For ADR ≥25%, endoscopists' median (interquartile range) screening CSSDR was 6.8% (4.3%-8.6%) and PSDR was 10.8% (8.6%-16.1%)., Conclusions: Derived from ADR, the primary colonoscopy quality indicator, our results suggest potential SDR benchmarks (CSSDR = 7% and PSDR = 11%) that may guide adequate serrated polyp detection. Because CSSDR and PSDR are strongly correlated, endoscopists could use the simpler PSDR calculation to assess quality., (Published by Elsevier Inc.)

Digital breast tomosynthesis (DBT) has shown potential to improve breast cancer screening and diagnosis compared to digital mammography (DM). The FDA approved DBT use in conjunction with conventional DM in 2011, but coverage was approved by CMS recently in 2015. Given changes in coverage policies, it is important to monitor diffusion of DBT by insurance type. This study examined DBT trends and estimated associations with insurance type. From June 2011 to September 2014, DBT use in 22 primary care centers in the Dartmouth -Brigham and Women's Hospital Population-based Research Optimizing Screening through Personalized Regimens research center (PROSPR) was examined among women aged 40-89. A longitudinal repeated measures analysis estimated the proportion of DBT performed for screening or diagnostic indications over time and by insurance type. During the study period, 93,182 mammograms were performed on 48,234 women. Of these exams, 16,506 DBT tests were performed for screening (18.1%) and 2537 were performed for diagnosis (15.7%). Between 2011 and 2014, DBT utilization increased in all insurance groups. However, by the latest observed period, screening DBT was used more frequently under private insurance (43.4%) than Medicaid (36.2%), Medicare (37.8%), other (38.6%), or no insurance (32.9%; P < 0.0001). No sustained differences in use of DBT for diagnostic testing were seen by insurance type. DBT is increasingly used for breast cancer screening and diagnosis. Use of screening DBT may be associated with insurance type. Surveillance is required to ensure that disparities in breast cancer screening are minimized as DBT becomes more widely available., (© 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objectives: To assess the feasibility of studying the comparative effectiveness of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) consensus treatment plans (CTPs) for systemic Juvenile Idiopathic Arthritis (JIA) using an observational registry., Methods: Untreated systemic JIA patients enrolled in the CARRA Registry were begun on one of 4 CTPs chosen by the treating physician and patient/family (glucocorticoid [GC] alone; methotrexate [MTX] ± GC; IL1 inhibitor [IL1i] ± GC; IL6 inhibitor [IL6i] ± GC). The primary outcome of clinical inactive disease (CID) without current GC use was assessed at 9 months., Trial Registration: clinicaltrials.gov NCT01697254; first registered 9/28/12 (retrospectively enrolled)., Results: Thirty patients were enrolled at 13 sites; eight patients were started on a non-biologic CTP (2 GC, 6 MTX) and 22 patients on a biologic CTP (12 IL1i, 10 IL6i) at disease onset. Demographic and disease features were similar between CTP groups. CTP choice appeared to segregate by site preference. CID off GC was achieved by 37% (11 of 30) including 11/22 (50%) starting a biologic CTP compared to 0/8 starting a non-biologic CTP (p = 0.014). There were four serious adverse events: two infections, one appendicitis and one macrophage activation syndrome., Conclusions: The CARRA systemic JIA CTP pilot study demonstrated successful implementation of CTPs using the CARRA registry infrastructure. Having demonstrated feasibility, a larger study using CTP response to better determine the relative effectiveness of treatments for new-onset systemic JIA is now underway.

Purpose: To assess indication for examination for four breast imaging modalities and describe the complexity and heterogeneity of data sources and ascertainment methods., Methods: Indication was evaluated among the Population-based Research Optimizing Screening through Personalized Regimens (PROSPR) breast cancer research centers (PRCs). Indication data were reported overall and separately for four breast imaging modalities: digital mammography (DM), digital breast tomosynthesis (DBT), ultrasound (US), and magnetic resonance imaging (MRI)., Results: The breast PRCs contributed 236,262 women with 607,735 breast imaging records from 31 radiology facilities. We found a high degree of heterogeneity for indication within and across six data sources. Structured codes within a data source were used most often to identify indication for mammography (59% DM, 85% DBT) and text analytics for US (45%) and MRI (44%). Indication could not be identified for 17% of US and 26% of MRI compared with 2% of mammography examinations (1% DM, 3% DBT)., Conclusions: Multiple and diverse data sources, heterogeneity of ascertainment methods, and nonstandardization of codes within and across data systems for determining indication were found. Consideration of data sources and standardized methodology for determining indication is needed to assure accurate measurement of cancer screening rates and performance in clinical practice and research., Competing Interests: All authors have no conflicts of interest related to the material presented in this manuscript., (Copyright © 2016 American College of Radiology. Published by Elsevier Inc. All rights reserved.)