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Mindy Hong,1 Jeffrey Krauss,1 Grace Wang,2 Ken Cohen,3 Christine E Chaisson,4 Amitabh Gulati5 1Hinge Health, San Francisco, CA, USA; 2Weitzman Institute, Middletown, CT, USA; 3Optum Care Center for Research and Innovation, Eden Prairie, MN, USA; 4Yale University Center for Clinical Investigation, New Haven, CT, USA; 5Memorial Sloan Kettering Cancer Center, New York, NY, USACorrespondence: Mindy Hong, Email mindy.hong@hingehealth.comPurpose: Physical therapy (PT) and conservative care are recommended first-line treatments for musculoskeletal (MSK) pain. While essential to high-quality care, these solutions often do not provide immediate or sufficient pain relief. Traditional transcutaneous electronic nerve stimulation (TENS) devices are often recommended; however, there is mixed evidence behind their effectiveness. A novel approach called hybrid form impulse therapy (HFIT) incorporates a priming pulse with a traditional TENS pulse width and frequency. This randomized controlled trial (RCT) aimed to compare the effectiveness of HFIT versus traditional TENS versus usual care among members of a digital MSK program.Patients and Methods: A three-arm RCT comparing HFIT versus TENS versus usual care was conducted. A total of 325 people with chronic back or knee pain who were members of a digital MSK program consisting of PT-guided exercise therapy, education, and coaching were randomized. Outcomes including pain, function, anxiety, and depression were examined at 1, 2, and 4 weeks (primary endpoint). Engagement was measured through exercise therapy (ET) sessions completed. Unadjusted and adjusted logistic generalized estimating equations were conducted.Results: Adjusted per-protocol results at 4 weeks showed significantly lower odds of achieving pain improvement for both TENS (OR: 0.42, 95% CI: [0.19, 0.92]) and usual care (OR: 0.35, 95% CI: [0.17, 0.72]) groups, compared to HFIT group. Both HFIT and usual care users had significantly higher engagement than the TENS users (p=0.026 and p=0.002, respectively). No adverse events were reported throughout the study.Conclusion: More participants of a digital MSK program who were randomized to the HFIT group experienced meaningful pain improvement at 4 weeks than participants who used TENS and usual care. HFIT can be an effective, non-pharmaceutical solution for relief as a complement to first-line treatments for patients with chronic back and knee pain.Keywords: HFIT, pain, chronic pain, neuromodulation, noninvasive treatment

Osteoarthritis is one of the most common joint disorders in the elderly, yet few studies have targeted symptomatic osteoarthritis, especially symptomatic hand osteoarthritis. The authors conducted a survey in 1992-1993 among an elderly population to estimate the prevalence of symptomatic hand osteoarthritis and to assess its impact on grip strength and functional activities. Framingham Study subjects received hand radiographs and answered queries on joint symptoms. Functional activities were assessed using an interviewer-administered questionnaire. Grip strength and observed functional performance were evaluated using standard procedures. A hand joint was defined as having symptomatic osteoarthritis if both symptoms and radiographic evidence of osteoarthritis were present. Of 1,041 subjects aged 71-100 years (36% men), the prevalence of symptomatic hand osteoarthritis was higher in women (26.2%) than in men (13.4%). Compared with those without symptomatic hand osteoarthritis, subjects with the disease had 10% reduced maximal grip strength, reported more difficulty writing, handling, or fingering small objects (odds ratio = 3.4), and showed more self-reported and observed difficulty carrying a 10-pound (4.5-kg) bundle (odds ratio = 1.7 and 1.6, respectively). In conclusion, in the context of a remarkable paucity of data on the epidemiology of symptomatic hand osteoarthritis, this study suggests that symptomatic hand osteoarthritis is a common disease among elders and frequently impairs hand function. [ABSTRACT FROM AUTHOR]

Objectives: We previously described a 6-item teamwork index (TEAM) with a strong relationship to provider experience, lower burnout, and intent to stay. We now sought to determine whether (1) TEAM relates to higher patient Net Promoter Score (NPS, or likelihood of patient referring to the organization) and (2) teamwork mediates a provider experience-NPS relationship., Study Design: A provider wellness survey was administered in the fall of 2019 in 6 care delivery organizations (CDOs) with patient NPS data., Methods: Measures included a validated burnout item, 6-item TEAM measure, provider experience metric, standard intent-to-stay question, and NPS data from 79,254 patients matched to CDO. Regression analyses modeled relationships among TEAM, provider experience, and NPS. Open-ended comments were reviewed to confirm patient NPS findings., Results: There were 1386 provider respondents (53% physicians, 47% advanced practice clinicians, 58% female, 62% White, 58% in primary care; response rate, 55.7%). Median NPS was 83%. TEAM was associated with patient NPS greater than the median (53% with high TEAM and high NPS vs 44% with low TEAM and high NPS; P < .001), as was provider experience (52% vs 45%; P < .05). In regression analyses, patient NPS was strongly related to TEAM (adjusted OR, 1.41; 95% CI, 1.25-1.60; P < .001). The provider experience-patient NPS relationship was partly mediated by TEAM. Open-ended comments confirmed positive or negative sentiments related to NPS., Conclusions: Teamwork and provider experience relate to patient NPS, and the provider experience-NPS relationship appears to be mediated by teamwork.

Objective: Implantable loop recorders (ILRs) are increasingly used for long-term rhythm monitoring after ischaemic and cryptogenic stroke, with the goal of detecting atrial fibrillation (AF) and subsequent initiation of oral anticoagulation to reduce risk of adverse clinical outcomes. There is a need to determine the effectiveness of different rhythm monitoring strategies in this context., Methods: We conducted a retrospective cohort analysis of individuals with commercial and Medicare Advantage insurance in Optum Labs Data Warehouse who had incident ischaemic or cryptogenic stroke and no prior cardiovascular implantable electronic device from 1 January 2016 to 30 June 2021. Patients were stratified by rhythm monitoring strategy: ILR, long-term continuous external cardiac monitor (>48 hours to 30 days) or Holter monitor (≤48 hours). The primary outcome was risk-adjusted all-cause mortality at 12 months. Secondary outcomes included new diagnosis of AF and oral anticoagulation, bleeding, and costs., Results: Among 48 901 patients with ischaemic or cryptogenic stroke, 9235 received an ILR, 29 103 long-term continuous external monitor and 10 563 Holter monitor only. Mean age was 69.9 (SD 11.9) years and 53.5% were female. During the 12-month follow-up period, patients who received ILRs compared with those who received long-term continuous external monitors had a higher odds of new diagnosis of AF and oral anticoagulant initiation (adjusted OR 2.27, 95% CI 2.09 to 2.48). Compared with patients who received long-term continuous external monitors, those who received ILRs had similar 12-month mortality (HR 1.00; 95% CI 0.89 to 1.12), with approximately $13 000 higher costs at baseline (including monitor cost) and $2500 higher costs during 12-month follow-up., Conclusions: In this large real-world study of patients with ischaemic or cryptogenic stroke, ILR placement resulted in more diagnosis of AF and initiation of oral anticoagulation, but no difference in mortality compared with long-term continuous external monitors., Competing Interests: Competing interests: SSD also receives research support from the Department of Veterans Affairs. SSD and RFR report serving on the Institute for Clinical and Economic Review (ICER) California Technology Assessment Forum. JM is a full-time employee of UnitedHealth Group and OA and KC (currently) and CEC (previously) are full-time employees of Optum Health, an arm of UnitedHealth Group and own stock in the company. OA had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis., (© 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.)

Objectives: To develop a brief teamwork measure and determine how teamwork relates to provider experience, burnout, and work intentions., Study Design: Survey of clinicians., Methods: We analyzed data from Optum's 2019 biannual clinician survey, including a validated burnout measure and measures of provider experience and intent to stay. A 6-item measure of team effectiveness (TEAM) focused on efficiency, communication, continuous improvement, and leadership. Construct validity was assessed with content, reliability, and correlation with burnout. Generalized estimating equations with robust SEs determined relationships among TEAM score, provider experience, and intent to stay, controlling for demographics, clustering, and practice factors., Results: Of 1500 physicians and advanced practice clinicians (1387 with complete data; response rate 56%), there were 58% in primary care; 57% were women, and 38% identified as Asian, Black/Hispanic, or another race/ethnicity other than White non-Hispanic. Burnout was present in 30%. The Cronbach α was excellent (0.86), and TEAM correlated with the validated burnout measure (adjusted odds ratio [OR] of lower burnout with high TEAM score, 0.28; 95% CI, 0.19-0.40; P < .0001). Clinicians with TEAM scores of at least 4 were more likely to have positive provider experiences (79% favorable vs 24% with low TEAM score; P < .001), had lower burnout rates (17% vs 44%%; P < .001), and more often intended to stay (93% vs 65%; P < .001). TEAM index score was strongly associated with provider experience (adjusted OR, 11.72; 95% CI, 8.11-16.95; P < .001) and intent to stay (adjusted OR, 7.24; 95% CI, 5.34-9.83; P < .001)., Conclusions: The TEAM index is related to provider experience, burnout, and intent to stay, and it may help organizations optimize clinical work environments.

Background: Likelihood of Neisseria gonorrhoeae infection in women exposed to male sex partners with increasing N. gonorrhoeae burdens and enhancement by Chlamydia trachomatis is not defined., Methods: We identified men with urethritis and their regular female sex partners. Exposure to N. gonorrhoeae burdens in men was compared in N. gonorrhoeae-infected versus -uninfected partners. Association of N. gonorrhoeae infection in women with burdens in male partners was estimated using logistic regression. Association of C. trachomatis coinfection and N. gonorrhoeae burdens in women adjusted for burdens in male partners was estimated by linear regression., Results: In total, 1816 men were enrolled; 202 had ≥2 partners, 91 who confirmed monogamy and were enrolled; 77% were married. Seventy were partners of N. gonorrhoeae-infected men; 58 (83%) were N. gonorrhoeae infected, 26 (45%) C. trachomatis coinfected. Infected women had partners with 9.3-fold higher N. gonorrhoeae burdens than partners of uninfected women (P = .0041). Association of N. gonorrhoeae infection in women with upper quartiles of N. gonorrhoeae burdens in partners increased (odds ratios ≥ 2.97)compared to the first quartile (P = .032). N. gonorrhoeae burdens in C. trachomatis-coinfected women were 2.82-fold higher than in C. trachomatis-uninfected women (P = .036)., Conclusions: N. gonorrhoeae infections increased in women whose partners were infected with higher N. gonorrhoeae burdens. C. trachomatis coinfection was associated with increased N. gonorrhoeae burdens in women., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Importance: Medicare Advantage is associated with improved health outcomes, increased care efficiency, and lower out-of-pocket costs compared with fee-for-service (FFS) Medicare. When engaged in 2-sided risk arrangements, physicians are incented to offer high value for patients; however, no studies have explored the quality and efficiency outcomes in 2-sided risk Medicare Advantage models compared with FFS Medicare., Objective: To compare quality and efficiency of care between physicians using a Medicare Advantage 2-sided risk model and FFS Medicare., Design, Setting, and Participants: This retrospective cohort analysis with exact and propensity score-matched design used claims data from January 1, 2018, to December 31, 2019. Participants included beneficiaries enrolled in a Medicare Advantage 2-sided risk model (ie, physicians assumed the financial risk of total costs of care) and those in an FFS Medicare program in a 5% limited data set with part A and B coverage residing in 6 states (Arizona, California, Florida, Nevada, Texas, and Utah). Data were analyzed from February 1 to June 15, 2022., Exposures: Medicare Advantage 2-sided risk model seen in practices that are part of a nationwide health care delivery organization compared with traditional FFS Medicare., Main Outcomes and Measures: Comparative analysis of 8 quality and efficiency metrics in populations enrolled in a 2-sided risk-model Medicare Advantage program and 5% FFS Medicare., Results: In this analytic cohort of 316 312 individuals (158 156 in each group), 46.11% were men and 53.89% were women; 32.72% were aged 65-69 years, 29.44% were aged 70-74 years, 19.05% were aged 75-79 years, 10.84% were aged 80-85 years, and 7.95% were 85 years or older. The Medicare Advantage model was associated with care of higher quality and efficiency in all 8 metrics compared with the FFS model. This included lower odds of inpatient admission (-18%; odds ratio [OR], 0.82 [95% CI, 0.79-0.84]), inpatient admission through the emergency department (ED) (-6%; OR, 0.94 [95% CI, 0.91-0.97]), ED visits (-11%; OR, 0.89 [95% CI, 0.86-0.91]), avoidable ED visits (-14%; OR, 0.86 [95% CI, 0.82-0.89]), 30-day inpatient readmission (-9%; rate ratio, 0.91 [95% CI, 0.86-0.98]), admission for stroke or myocardial infarction (-10%; OR, 0.90 [95% CI, 0.83-0.98]), and hospitalization for chronic obstructive pulmonary disease or asthma exacerbation (-44%; OR, 0.56 [95% CI, 0.50-0.62])., Conclusions and Relevance: The improvements observed in this study may be partly or fully attributed to the Medicare Advantage model. The Medicare Advantage risk adjustment system appears to be meeting its intended goal by aligning the capitation payments to the health care burden of the individual beneficiary and aggregate population served, thus providing revenue to develop infrastructure that supports improvements in quality and efficiency for the patients enrolled in Medicare Advantage models with 2-sided risk.

Introduction: This study aimed to examine all-cause mortality, 1- and 2-year major cardiovascular events, and major adverse limb events in individuals aged ≥65 years who received an in-home health visit with peripheral artery disease screening. In addition, we compared 1-year healthcare utilization before and after peripheral artery disease screening for those who screened positive., Setting/participants: Medicare Advantage beneficiaries aged ≥65 years participating in the Optum HouseCalls program in the U.S. between April 1, 2017 and February 1, 2019 were included., Intervention: The intervention consisted of a peripheral artery disease screening program using a plethysmography system., Main Outcome Measures: One-year all-cause mortality as a landmark analysis, 1- and 2-year major cardiovascular events, and major adverse limb events after screening were compared by peripheral artery disease screen status using claims data. We compared cardiovascular medications and revascularization procedures between the year before and after the peripheral artery disease screening event for those with peripheral artery disease., Results: Of 192,500 beneficiaries, 27.7% screened positive. One-year all-cause mortality rates for those who screened positive for peripheral artery disease versus those who screened negative were higher (1.51% vs 0.89%; p <0.001; adjusted hazard ratio=1.21; 95% CI=1.08, 1.36) as well as 1-year major cardiovascular events (5.54% vs 3.60%; adjusted hazard ratio= 1.22; 95% CI=1.15, 1.30) and major adverse limb events (0.23% vs 0.04%; adjusted hazard ratio=3.15; 95% CI=2.10, 4.73). Similar risks were observed for 2-year results. Before and after peripheral artery disease screening, medications remained stable for those who screened positive (e.g., statin therapy=54.2% vs 56.6%); rates of peripheral vascular interventions remained stable (0.0% vs 0.1%)., Conclusions: A national peripheral artery disease screening effort is feasible. Detecting previously undiagnosed peripheral artery disease is a way to risk stratify a population that would benefit from further cardiovascular risk management., (© 2022 The Authors.)

Background: The association between cost-sharing and receipt of medication for opioid use disorder (MOUD) is unknown., Methods: We constructed a cohort of 10,513 commercially insured individuals with a new diagnosis of opioid use disorder and information on insurance cost-sharing in a large national deidentified claims database. We examined 4 cost-sharing measures: (1) pharmacy deductible; (2) medical service deductible; (3) pharmacy medication copay; and (4) medical office copay. We measured MOUD (naltrexone, buprenorphine, or methadone) initiation (within 14 d of diagnosis), engagement (second receipt within 34 d of first), and 6-month retention (continuous receipt without 14-d gap). We used multivariable logistic regression to assess the association between cost-sharing and MOUD initiation, engagement, and retention. We calculated total out-of-pocket costs in the 30 days following MOUD initiation for each type of MOUD., Results: Of 10,513 individuals with incident opioid use disorder, 1202 (11%) initiated MOUD, 742 (7%) engaged, and 253 (2%) were retained in MOUD at 6 months. A high ($1000+) medical deductible was associated with a lower odds of initiation compared with no deductible (odds ratio: 0.85, 95% confidence interval: 0.74-0.98). We found no significant associations between other cost-sharing measures for initiation, engagement, or retention. Median initial 30-day out-of-pocket costs ranged from $100 for methadone to $710 for extended-release naltrexone., Conclusions: Among insurance plan cost-sharing measures, only medical services deductible showed an association with decreased MOUD initiation. Policy and benefit design should consider ways to reduce cost barriers to initiation and retention in MOUD., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Despite the importance of prenatal care, quality measurement efforts have focused on the number of prenatal visits, or prenatal care adequacy, rather than the services received. It is unknown whether attending more prenatal visits is associated with receiving more guideline-based prenatal care services. The relationship between guideline-based prenatal care and patients' clinical and sociodemographic characteristics has also not been studied., Objective: This study aimed to measure the receipt of guideline-based prenatal care among pregnant patients and to describe the association between guideline-based prenatal care and the number of prenatal visits and other patient characteristics., Study Design: This was a retrospective descriptive cohort study of 176,092 pregnancy episodes between 2016 and 2019. We used de-identified administrative claims data on commercial enrollees across the United States from the OptumLabs Data Warehouse. We identified the following 8 components of prenatal care that are universally recommended by the American College of Obstetricians and Gynecologists and other guideline-issuing organizations: testing for sexually transmitted infections, obstetric laboratory test panel, urine culture, urinalysis, anatomy scan ultrasound, oral glucose tolerance test, tetanus, diphtheria, and pertussis vaccine, and group B Streptococcus test. We measured the proportion of pregnant patients who received each of these guideline-based services at the appropriate gestational age. We measured the association between guideline-based services and the number of prenatal visits and prenatal care adequacy. We described variation of guideline-based care according to patient age, comorbidities, high deductible health plan enrollment, and their county's rurality, health professional shortage area status, racial composition, median income, and educational attainment., Results: The 176,092 pregnancy episodes were mostly among patients aged 25 to 34 years (63%) with few pregnancy comorbidities (81%) and living in urban areas (92%). Guideline-based care varied by service, from 51% receiving a timely urinalysis to 90% receiving an anatomy scan and 91% completing testing for sexually transmitted infections. Patients with at least 4 prenatal visits received, on average, 6 of the 8 guideline-based services. Guideline-based care did not increase with additional prenatal visits and varied by patient characteristics. Rates of tetanus, diphtheria, and pertussis vaccination were lower in counties with high proportions of minoritized populations, lower education, and lower income., Conclusion: In this commercially insured population, receipt of guideline-based care was not universal, did not increase with the number of prenatal visits, and varied by patient- and area-level characteristics. Measuring guideline-based care is feasible and may capture quality of prenatal care better than visit count or adequacy alone., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Medications for opioid use disorder (MOUD) are highly effective, but barriers along the cascade of care for opioid use disorder (OUD) from diagnosis to treatment limit their reach. For individuals desiring MOUD, the final step in the cascade is filling a written prescription, and fill rates have not been described., Methods: We used data from a large de-identified database linking individuals' electronic medical records (EMR) and administrative claims data and employed a previously developed algorithm to identify individuals with a new diagnosis of OUD. We included individuals with a prescription for buprenorphine or naltrexone recorded in the EMR. The outcome was a prescription fill within 30 days as reported in claims data. We compared demographic and clinical characteristics between those who did and did not fill the prescription and used a Kaplan-Meier curve to assess whether fill rates differed based on patient copay., Results: We identified 264 individuals with a new diagnosis of OUD who had a prescription written for buprenorphine or oral naltrexone. Of these, 70% (184) filled the prescription within 30 days, and more than half (57%) filled the prescription on the day it was written. Individuals with prescription copay at or below the mean had a 75% fill rate at 30 days compared with 63% for those with copay above the mean (p < 0.05) and this difference was consistent across fill times (log rank p-value <0.05)., Conclusions: It is alarming that nearly 1 in 3 MOUD prescriptions go unfilled. More research is needed to understand and reduce barriers to this final step of the OUD cascade of care., (Copyright © 2021. Published by Elsevier Inc.)

Many severe maternal morbidities (SMMs) are preventable, and understanding circumstances in which complications occur is crucial. The objective was to evaluate a framework for SMM benchmarking and quality improvement opportunities. Building upon metrics defined by the Centers for Disease Control and Prevention on the basis of an inpatient sample, analysis included indicators across 5 domains (Hemorrhage/Transfusion, Preeclampsia/Eclampsia, Cardiovascular, Sepsis, and Thromboembolism/Cerebrovascular). Morbidity rates per 10 000 deliveries were calculated using de-identified administrative claims in commercially insured women in the United States. Longitudinal data linked inpatient delivery episodes and 6-week postpartum period, and SMMs were assessed for present on admission and geographic variation. This retrospective analysis of 356 838 deliveries identified geographic variation in SMMs. For example, hemorrhage rates per 10 000 varied 3-fold across states from 279.7 in Alabama to 964.69 in Oregon. Administrative claims can be used to calculate SMM rates, identify geographic variations, and assess problems locally, nationally, and across payers. Identifying conditions present on admission and a postpartum window is valuable in differentiating events occurring during preadmission, inpatient stay, and postpartum periods. Targeting preventable SMMs through local and hospital-level interventions and limiting SMM progression through postdischarge monitoring may reduce the prevalence of SMM and postpartum complications., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc.)

Aim: The aim of this study was to characterize quality of buprenorphine care for opioid use disorder (OUD) by quantifying buprenorphine initiation, engagement, and maintenance for individuals in a large, diverse, real-world cohort in the United States., Design: This was a retrospective cohort analysis., Setting: OUD treatment in the outpatient setting., Participants: A total of 45,210 commercially insured and Medicare Advantage (MA) enrollees 18 years or older in the OptumLabs Data Warehouse with an index diagnosis of OUD between January 1, 2018 and December 31, 2018., Interventions: Treatment with buprenorphine., Measurements: We calculated 6 measures of buprenorphine treatment quality. We conducted survival analyses to characterize treatment duration and logistic regressions to evaluate the association between clinical and sociodemographic characteristics and quality., Findings: Of 45,210 eligible individuals with OUD, ∼1 in 10 (n=4600, 10.2%) initiated buprenorphine within 365 days following diagnosis (Measure #1) and 2850 individuals (6.3%) initiated buprenorphine within 14 days of diagnosis (Measure #2). Of individuals initiating treatment within 14 days of diagnosis, 1769 (62.1%) had 2 or more buprenorphine claims within 34 days of initiation (Measure #3). Of the 4600 individuals who received buprenorphine, 2300 (50.0%) were maintained in care with 180 days or more of covered buprenorphine treatment during 365 days after diagnosis (Measure #4). Finally, of the 4600 individuals who received buprenorphine, 2543 (55.3%) did not fill any other concurrent opioid analgesic (Measure #5) and 2951 (64.2%) did not fill any concurrent benzodiazepine (Measure #6). Quality was generally lower for individuals with MA compared with commercial coverage and among Hispanic and Black adults compared with White adults., Conclusion: Widespread gaps exist in quality of buprenorphine treatment initiation, engagement, and maintenance among commercially insured and MA enrollees with OUD., Competing Interests: C.E.C. is an employee of OptumLabs. S.H.S. is an employee of NCQA, a not-for-profit organization that develops and maintains quality measures. This work builds on quality measures developed by NCQA. L.N. is an employee of NCQA, a not-for-profit organization that develops and maintains quality measures. This work builds on quality measures developed by NCQA. G.C.A. is past Chair of FDA’s Peripheral and Central Nervous System Advisory Committee; has served as a paid advisor to IQVIA; is a co-founding Principal and equity holder in Monument Analytics, a health care consultancy whose clients include the life sciences industry as well as plaintiffs in opioid litigation; and is a past member of OptumRx’s National P&T Committee. This arrangement has been reviewed and approved by Johns Hopkins University in accordance with its conflict of interest policies. The remaining authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The long-term neurologic consequences of exposure to repetitive head impacts (RHI) are not well understood. This study used magnetic resonance spectroscopy (MRS) to examine later-life neurochemistry and its association with RHI and clinical function in former National Football League (NFL) players. The sample included 77 symptomatic former NFL players and 23 asymptomatic individuals without a head trauma history. Participants completed cognitive, behavior, and mood measures. N-acetyl aspartate, glutamate/glutamine, choline, myo-inositol, creatine, and glutathione were measured in the posterior (PCG) and anterior (ACG) cingulate gyrus, and parietal white matter (PWM). A cumulative head impact index (CHII) estimated RHI. In former NFL players, a higher CHII correlated with lower PWM creatine (r = -0.23, p = 0.02). Multivariate mixed-effect models examined neurochemical differences between the former NFL players and asymptomatic individuals without a history of head trauma. PWM N-acetyl aspartate was lower among the former NFL players (mean diff. = 1.02, p = 0.03). Between-group analyses are preliminary as groups were recruited based on symptomatic status. The ACG was the only region associated with clinical function, including positive correlations between glutamate (r = 0.32, p = 0.004), glutathione (r = 0.29, p = 0.02), and myo-inositol (r = 0.26, p = 0.01) with behavioral/mood symptoms. Other positive correlations between ACG neurochemistry and clinical function emerged (i.e., behavioral/mood symptoms, cognition), but the positive directionality was unexpected. All analyses controlled for age, body mass index, and education (for analyses examining clinical function). In this sample of symptomatic former NFL players, there was a direct effect between RHI and reduced cellular energy metabolism (i.e., lower creatine). MRS neurochemicals associated with neuroinflammation also correlated with behavioral/mood symptoms.

Background: Relative costs of care among treatment options for opioid use disorder (OUD) are unknown., Methods: We identified a cohort of 40,885 individuals with a new diagnosis of OUD in a large national de-identified claims database covering commercially insured and Medicare Advantage enrollees. We assigned individuals to 1 of 6 mutually exclusive initial treatment pathways: (1) Inpatient Detox/Rehabilitation Treatment Center; (2) Behavioral Health Intensive, intensive outpatient or Partial Hospitalization Services; (3) Methadone or Buprenorphine; (4) Naltrexone; (5) Behavioral Health Outpatient Services, or; (6) No Treatment. We assessed total costs of care in the initial 90 day treatment period for each strategy using a differences in differences approach controlling for baseline costs., Results: Within 90 days of diagnosis, 94.8% of individuals received treatment, with the initial treatments being: 15.8% for Inpatient Detox/Rehabilitation Treatment Center, 4.8% for Behavioral Health Intensive, Intensive Outpatient or Partial Hospitalization Services, 12.5% for buprenorphine/methadone, 2.4% for naltrexone, and 59.3% for Behavioral Health Outpatient Services. Average unadjusted costs increased from $3250 per member per month (SD $7846) at baseline to $5047 per member per month (SD $11,856) in the 90 day follow-up period. Compared with no treatment, initial 90 day costs were lower for buprenorphine/methadone [Adjusted Difference in Differences Cost Ratio (ADIDCR) 0.65; 95% confidence interval (CI), 0.52-0.80], naltrexone (ADIDCR 0.53; 95% CI, 0.42-0.67), and behavioral health outpatient (ADIDCR 0.54; 95% CI, 0.44-0.66). Costs were higher for inpatient detox (ADIDCR 2.30; 95% CI, 1.88-2.83)., Conclusion: Improving health system capacity and insurance coverage and incentives for outpatient management of OUD may reduce health care costs.

Importance: Opioid-tolerant only (OTO) medications, such as transmucosal immediate-release fentanyl products and certain extended-release opioid analgesics, require prior opioid tolerance for safe use, as patients without tolerance may be at increased risk of overdose. Studies using insurance claims have found that many patients initiating these medications do not appear to be opioid tolerant., Objectives: To measure prevalence of opioid tolerance in patients initiating OTO medications and to determine whether linked electronic health record (EHR) data contribute evidence of opioid tolerance not found in insurance claims data., Design, Setting, and Participants: This retrospective cohort study used a national database of deidentified longitudinal health information, including medical and pharmacy claims, insurance enrollment, and EHR data, from January 1, 2007, to December 31, 2016. Data included 131 756 US residents with at least 183 days of continuous enrollment in commercial or Medicare Advantage insurance (including medical and pharmacy benefits) who had received an OTO medication and who had no inpatient stays in the 30 days prior to starting an OTO medication; of these, 20 044 individuals had linked EHR data within the prior 183 days. Data were analyzed from July 1, 2017, to August 31, 2018., Exposures: Initiating an OTO medication., Main Outcomes and Measures: Prior opioid tolerance demonstrated through pharmacy fills or EHR data on prescriptions written., Results: Among 153 385 OTO use episodes identified, 89 029 (58.0%) occurred among women, 62 900 (41.0%) occurred among patients with Medicare Advantage insurance, 39 394 (25.7%) occurred in the Midwest, 17 366 (11.3%) occurred in the Northeast, 73 316 (47.8%) occurred in the South, and 23 309 (15.2%) occurred in the West. Less than half of use episodes (73 117 episodes [47.7%]) involved patients with evidence in claims data of opioid tolerance prior to initiating therapy with an OTO medication, including 31 392 of 101 676 episodes (30.9%) involving transdermal fentanyl, 1561 of 2440 episodes (64.0%) involving transmucosal fentanyl, 36 596 of 43 559 episodes (84.0%) involving extended-release oxycodone, and 3568 of 5710 episodes (62.5%) involving extended-release hydromorphone. Among 20 044 OTO use episodes with linked EHR and claims data, less than 1% of OTO episodes identified in claims had evidence of opioid tolerance in structured EHR data that was not present in claims data (108 episodes [0.5%]). After limiting the sample to OTO episodes identified in claims with a matching OTO prescription within 14 days in the structured EHR data, only 40 of 939 episodes (4.0%) occurred among patients with evidence of tolerance that was not present in claims data., Conclusions and Relevance: This cohort study found that most patients initiating OTO medications did not have evidence of prior opioid tolerance, suggesting they were at increased risk of opioid-related harms, including fatal overdose. Data from EHRs did not contribute substantial additional evidence of opioid tolerance beyond the data found in prescription claims. Future research is needed to understand the clinical rationale behind these observed prescribing patterns and to quantify the risk of harm to patients associated with potentially inappropriate prescribing.

Importance: Although clinical trials demonstrate the superior effectiveness of medication for opioid use disorder (MOUD) compared with nonpharmacologic treatment, national data on the comparative effectiveness of real-world treatment pathways are lacking., Objective: To examine associations between opioid use disorder (OUD) treatment pathways and overdose and opioid-related acute care use as proxies for OUD recurrence., Design, Setting, and Participants: This retrospective comparative effectiveness research study assessed deidentified claims from the OptumLabs Data Warehouse from individuals aged 16 years or older with OUD and commercial or Medicare Advantage coverage. Opioid use disorder was identified based on 1 or more inpatient or 2 or more outpatient claims for OUD diagnosis codes within 3 months of each other; 1 or more claims for OUD plus diagnosis codes for opioid-related overdose, injection-related infection, or inpatient detoxification or residential services; or MOUD claims between January 1, 2015, and September 30, 2017. Data analysis was performed from April 1, 2018, to June 30, 2019., Exposures: One of 6 mutually exclusive treatment pathways, including (1) no treatment, (2) inpatient detoxification or residential services, (3) intensive behavioral health, (4) buprenorphine or methadone, (5) naltrexone, and (6) nonintensive behavioral health., Main Outcomes and Measures: Opioid-related overdose or serious acute care use during 3 and 12 months after initial treatment., Results: A total of 40 885 individuals with OUD (mean [SD] age, 47.73 [17.25] years; 22 172 [54.2%] male; 30 332 [74.2%] white) were identified. For OUD treatment, 24 258 (59.3%) received nonintensive behavioral health, 6455 (15.8%) received inpatient detoxification or residential services, 5123 (12.5%) received MOUD treatment with buprenorphine or methadone, 1970 (4.8%) received intensive behavioral health, and 963 (2.4%) received MOUD treatment with naltrexone. During 3-month follow-up, 707 participants (1.7%) experienced an overdose, and 773 (1.9%) had serious opioid-related acute care use. Only treatment with buprenorphine or methadone was associated with a reduced risk of overdose during 3-month (adjusted hazard ratio [AHR], 0.24; 95% CI, 0.14-0.41) and 12-month (AHR, 0.41; 95% CI, 0.31-0.55) follow-up. Treatment with buprenorphine or methadone was also associated with reduction in serious opioid-related acute care use during 3-month (AHR, 0.68; 95% CI, 0.47-0.99) and 12-month (AHR, 0.74; 95% CI, 0.58-0.95) follow-up., Conclusions and Relevance: Treatment with buprenorphine or methadone was associated with reductions in overdose and serious opioid-related acute care use compared with other treatments. Strategies to address the underuse of MOUD are needed.

Objective: To determine whether the Linking Infectious and Narcology Care strengths-based case management intervention was more effective than usual care for linking people who inject drugs (PWID) to HIV care and improving HIV outcomes., Design: Two-armed randomized controlled trial., Setting: Participants recruited from a narcology hospital in St. Petersburg, Russia., Participants: A total of 349 HIV-positive PWID not on antiretroviral therapy (ART)., Intervention: Strengths-based case management over 6 months., Main Outcome Measures: Primary outcomes were linkage to HIV care and improved CD4 cell count. We performed adjusted logistic and linear regression analyses controlling for past HIV care using the intention-to-treat approach., Results: Participants (N = 349) had the following baseline characteristics: 73% male, 12% any past ART use, and median values of 34.0 years of age and CD4 cell count 311 cells/μl. Within 6 months of enrollment 51% of the intervention group and 31% of controls linked to HIV care (adjusted odds ratio 2.34; 95% confidence interval: 1.49-3.67; P < 0.001). Mean CD4 cell count at 12 months was 343 and 354 cells/μl in the intervention and control groups, respectively (adjusted ratio of means 1.14; 95% confidence interval: 0.91, 1.42, P = 0.25)., Conclusion: The Linking Infectious and Narcology Care strengths-based case management intervention was more effective than usual care in linking Russian PWID to HIV care, but did not improve CD4 cell count, likely due to low overall ART initiation. Although case management can improve linkage to HIV care, specific approaches to initiate and adhere to ART are needed to improve clinical outcomes (e.g., increased CD4 cell count) in this population.

Objective: Neuropsychological test performance can provide insight into functional abilities in patients with dementia, particularly in the absence of an informant. The relationship between neuropsychological measures and instrumental activities of daily living (IADLs) is unclear due to hetereogeneity in cognitive domains assessed and neuropsychological tests administered. Practical and ecologically valid performance-based measures of IADLs are also limited. The Neuropsychological Assessment Battery (NAB) is uniquely positioned to provide a dual-purpose assessment of cognitive and IADL function, as it includes Daily Living tests that simulate real-world functional tasks. We examined the utility of select NAB tests in predicting informant-reported IADLs in mild cognitive impairment and dementia., Methods: The sample of 327 participants included 128 normal controls, 97 individuals with mild cognitive impairment, and 102 individuals with Alzheimer's disease dementia from the Boston University Alzheimer's Disease Center research registry. Informants completed the Lawton Brody Instrumental Activities of Daily Living Scale, and study participants were administered selected NAB tests that were complementary to the existing protocol., Results: ROC curves showed strongest prediction of IADL (AUC > 0.90) for memory measures (List Learning delayed recall and Daily Living Memory delayed recall) and Daily Living Driving Scenes. At a predetermined level of specificity (95%), List Learning delayed recall (71%) and Daily Living Memory delayed recall (88%) were the most sensitive. The Daily Living Memory and Driving Scenes tests strongly predicted IADL status, and the other Daily Living tests contributed unique variance., Conclusions: NAB memory measures and Daily Living Tests may have clinical utility in detecting informant-rated functional impairment in dementia.

Background Russia continues to have an uncontrolled HIV epidemic and its per capita alcohol consumption is among the highest in the world. Alcohol use among HIV-positive individuals is common and is associated with worse clinical outcomes. Alcohol use and HIV each lead to microbial translocation, which in turn results in inflammation. Zinc supplementation holds potential for lowering levels of biomarkers of inflammation, possibly as a consequence of its impact on intestinal permeability. This paper describes the protocol of a double-blinded randomized placebo-controlled trial of zinc supplementation in St. Petersburg, Russia. Methods Participants (n = 254) were recruited between October 2013 and June 2015 from HIV and addiction clinical care sites, and non-clinical sites in St. Petersburg, Russia. Participants were randomly assigned, to receive either zinc (15 mg for men; 12 mg for women) or placebo, daily for 18 months. The following outcomes were assessed at 6, 12, and 18 months: (1) mortality risk (primary outcome at 18 months); (2) HIV disease progression; (3) cardiovascular risk; and (4) microbial translocation and inflammation. Adherence was assessed using direct (riboflavin) and indirect (pill count, self-report) measures. Conclusion Given the limited effectiveness of current interventions to reduce alcohol use, zinc supplementation merits testing as a simple, low-cost intervention to mitigate the consequences of alcohol use in HIV-positive persons despite ongoing drinking.

Objective: To examine the effect of age of first exposure to tackle football on chronic traumatic encephalopathy (CTE) pathological severity and age of neurobehavioral symptom onset in tackle football players with neuropathologically confirmed CTE., Methods: The sample included 246 tackle football players who donated their brains for neuropathological examination. Two hundred eleven were diagnosed with CTE (126 of 211 were without comorbid neurodegenerative diseases), and 35 were without CTE. Informant interviews ascertained age of first exposure and age of cognitive and behavioral/mood symptom onset., Results: Analyses accounted for decade and duration of play. Age of exposure was not associated with CTE pathological severity, or Alzheimer's disease or Lewy body pathology. In the 211 participants with CTE, every 1 year younger participants began to play tackle football predicted earlier reported cognitive symptom onset by 2.44 years (p < 0.0001) and behavioral/mood symptoms by 2.50 years (p < 0.0001). Age of exposure before 12 predicted earlier cognitive (p < 0.0001) and behavioral/mood (p < 0.0001) symptom onset by 13.39 and 13.28 years, respectively. In participants with dementia, younger age of exposure corresponded to earlier functional impairment onset. Similar effects were observed in the 126 CTE-only participants. Effect sizes were comparable in participants without CTE., Interpretation: In this sample of deceased tackle football players, younger age of exposure to tackle football was not associated with CTE pathological severity, but predicted earlier neurobehavioral symptom onset. Youth exposure to tackle football may reduce resiliency to late-life neuropathology. These findings may not generalize to the broader tackle football population, and informant-report may have affected the accuracy of the estimated effects. Ann Neurol 2018;83:886-901., (© 2018 American Neurological Association.)

Objectives: To determine whether or not automated FreeSurfer segmentation of brain regions considered important in repetitive head trauma can be analyzed accurately without manual correction., Materials and Methods: 3 T MR neuroimaging was performed with automated FreeSurfer segmentation and manual correction of 11 brain regions in former National Football League (NFL) players with neurobehavioral symptoms and in control subjects. Automated segmentation and manually-corrected volumes were compared using an intraclass correlation coefficient (ICC). Linear mixed effects regression models were also used to estimate between-group mean volume comparisons and to correlate former NFL player brain volumes with neurobehavioral factors., Results: Eighty-six former NFL players (55.2 ± 8.0 years) and 22 control subjects (57.0 ± 6.6 years) were evaluated. ICC was highly correlated between automated and manually-corrected corpus callosum volumes (0.911), lateral ventricular volumes (right 0.980, left 0.967), and amygdala-hippocampal complex volumes (right 0.713, left 0.731), but less correlated when amygdalae (right -0.170, left -0.090) and hippocampi (right 0.539, left 0.637) volumes were separately delineated and also less correlated for cingulate gyri volumes (right 0.639, left 0.351). Statistically significant differences between former NFL player and controls were identified in 8 of 11 regions with manual correction but in only 4 of 11 regions without such correction. Within NFL players, manually corrected brain volumes were significantly associated with 3 neurobehavioral factors, but a different set of 3 brain regions and neurobehavioral factor correlations was observed for brain region volumes segmented without manual correction., Conclusions: Automated FreeSurfer segmentation of the corpus callosum, lateral ventricles, and amygdala-hippocampus complex may be appropriate for analysis without manual correction. However, FreeSurfer segmentation of the amygdala, hippocampus, and cingulate gyrus need further manual correction prior to performing group comparisons and correlations with neurobehavioral measures.

Background/aims: Reproducible outcomes in clinical trials depend on adherence to study protocol. Short message service (also known as text message) reminders have been shown to improve clinical trial adherence in the United States and elsewhere. However, due to systematic differences in mobile data plans, languages, and technology, these systems are not easily translated to international settings., Methods: To gauge technical capabilities for international projects, we developed SMSMessenger, an automated Android application that uses a US server to send medication reminders to participants in a clinical trial in St. Petersburg, Russia (Zinc for HIV disease among alcohol users-a randomized controlled trial in the Russia Alcohol Research Collaboration on HIV/AIDS cohort). The application is downloaded once onto an Android study phone. When it is time for the text message reminders to be sent, study personnel access the application on a local phone, which in turn accesses the existing clinical trial database hosted on a US web server. The application retrieves a list of participants with the following information: phone number, whether a message should be received at that time, and the appropriate text of the message. The application is capable of storing multiple outgoing messages. With a few clicks, text messages are sent to study participants who can reply directly to the message. Study staff can check the local phone for incoming messages. The SMSMessenger application uses an existing clinical trial database and is able to receive real-time updates. All communications between the application and server are encrypted, and phone numbers are stored in a secure database behind a firewall. No sensitive data are stored on the phone, as outgoing messages are sent through the application and not by messaging features on the phone itself. Messages are sent simultaneously to study participants, which reduces the burden on local study staff. Costs and setup are minimal. The only local requirements are an Android phone and data plan., Conclusion: The SMSMessenger technology could be modified to be applied anywhere in the world, in any language, script, or alphabet, and for many different purposes. The novel application of this existing low-cost technology can improve the usefulness of text messaging in advancing the goals of international clinical trials.

Thalamic atrophy has been associated with exposure to repetitive head impacts (RHI) in professional fighters. The aim of this study is to investigate whether or not age at first exposure (AFE) to RHI is associated with thalamic volume in symptomatic former National Football League (NFL) players at risk for chronic traumatic encephalopathy (CTE). Eighty-six symptomatic former NFL players (mean age = 54.9 ± 7.9 years) were included. T1-weighted data were acquired on a 3T magnetic resonance imager, and thalamic volumes were derived using FreeSurfer. Mood and behavior, psychomotor speed, and visual and verbal memory were assessed. The association between thalamic volume and AFE to playing football and to number of years playing was calculated. Decreased thalamic volume was associated with more years of play (left: p = 0.03; right: p = 0.03). Younger AFE was associated with decreased right thalamic volume (p = 0.014). This association remained significant after adjusting for total years of play. Decreased left thalamic volume was associated with worse visual memory (p = 0.014), whereas increased right thalamic volume was associated with fewer mood and behavior symptoms (p = 0.003). In our sample of symptomatic former NFL players at risk for CTE, total years of play and AFE were associated with decreased thalamic volume. The effect of AFE on right thalamic volume was almost twice as strong as the effect of total years of play. Our findings confirm previous reports of an association between thalamic volume and exposure to RHI. They suggest further that younger AFE may result in smaller thalamic volume later in life.

Introduction: Later-life brain alterations in former tackle football players are poorly understood, particularly regarding their relationship with repetitive head impacts (RHIs) and clinical function. We examined white matter signal abnormalities (WMSAs) and their association with RHIs and clinical function in former National Football League (NFL) players., Methods: Eighty-six clinically symptomatic former NFL players and 23 same-age reportedly asymptomatic controls without head trauma exposure underwent magnetic resonance imaging and neuropsychological testing. FreeSurfer calculated WMSAs. A cumulative head impact index quantified RHIs., Results: In former NFL players, increased volume of WMSAs was associated with higher cumulative head impact index scores ( P  = .043) and worse psychomotor speed and executive function ( P  = .015). Although former NFL players had greater WMSA volume than controls ( P  = .046), these findings are inconclusive due to recruitment of controls based on lack of clinical symptoms and head trauma exposure., Discussion: In former NFL players, WMSAs may reflect long-term microvascular and nonmicrovascular pathologies from RHIs that negatively impact cognition.

Previous research suggests that age of first exposure (AFE) to football before age 12 may have long-term clinical implications; however, this relationship has only been examined in small samples of former professional football players. We examined the association between AFE to football and behavior, mood and cognition in a large cohort of former amateur and professional football players. The sample included 214 former football players without other contact sport history. Participants completed the Brief Test of Adult Cognition by Telephone (BTACT), and self-reported measures of executive function and behavioral regulation (Behavior Rating Inventory of Executive Function-Adult Version Metacognition Index (MI), Behavioral Regulation Index (BRI)), depression (Center for Epidemiologic Studies Depression Scale (CES-D)) and apathy (Apathy Evaluation Scale (AES)). Outcomes were continuous and dichotomized as clinically impaired. AFE was dichotomized into <12 and ⩾12, and examined continuously. Multivariate mixed-effect regressions controlling for age, education and duration of play showed AFE to football before age 12 corresponded with >2 × increased odds for clinically impaired scores on all measures but BTACT: (odds ratio (OR), 95% confidence interval (CI): BRI, 2.16,1.19-3.91; MI, 2.10,1.17-3.76; CES-D, 3.08,1.65-5.76; AES, 2.39,1.32-4.32). Younger AFE predicted increased odds for clinical impairment on the AES (OR, 95% CI: 0.86, 0.76-0.97) and CES-D (OR, 95% CI: 0.85, 0.74-0.97). There was no interaction between AFE and highest level of play. Younger AFE to football, before age 12 in particular, was associated with increased odds for impairment in self-reported neuropsychiatric and executive function in 214 former American football players. Longitudinal studies will inform youth football policy and safety decisions.

The link between HIV stigma with substance use is understudied. We characterized individuals with high HIV stigma and examined whether HIV stigma contributes to substance use among HIV-positive Russians reporting risky alcohol use. We analyzed data from HERMITAGE, a randomized controlled trial of 700 people living with HIV/AIDS (PLWHA) with past 6-month risky sex and risky alcohol use in St. Petersburg, Russia (2007-2011). Participants who were female and reported depressive symptoms and lower social support were more likely to endorse high HIV stigma (all p's < 0.001). In adjusted models, high HIV stigma was not significantly associated with the primary outcome unhealthy substance use and was not consistently associated with secondary substance use outcomes. Interventions to enhance social and mental health support for PLWHA, particularly women, may reduce stigma, though such reductions may not correspond to substantial decreases in substance use among this population.

Importance: Players of American football may be at increased risk of long-term neurological conditions, particularly chronic traumatic encephalopathy (CTE)., Objective: To determine the neuropathological and clinical features of deceased football players with CTE., Design, Setting, and Participants: Case series of 202 football players whose brains were donated for research. Neuropathological evaluations and retrospective telephone clinical assessments (including head trauma history) with informants were performed blinded. Online questionnaires ascertained athletic and military history., Exposures: Participation in American football at any level of play., Main Outcomes and Measures: Neuropathological diagnoses of neurodegenerative diseases, including CTE, based on defined diagnostic criteria; CTE neuropathological severity (stages I to IV or dichotomized into mild [stages I and II] and severe [stages III and IV]); informant-reported athletic history and, for players who died in 2014 or later, clinical presentation, including behavior, mood, and cognitive symptoms and dementia., Results: Among 202 deceased former football players (median age at death, 66 years [interquartile range, 47-76 years]), CTE was neuropathologically diagnosed in 177 players (87%; median age at death, 67 years [interquartile range, 52-77 years]; mean years of football participation, 15.1 [SD, 5.2]), including 0 of 2 pre-high school, 3 of 14 high school (21%), 48 of 53 college (91%), 9 of 14 semiprofessional (64%), 7 of 8 Canadian Football League (88%), and 110 of 111 National Football League (99%) players. Neuropathological severity of CTE was distributed across the highest level of play, with all 3 former high school players having mild pathology and the majority of former college (27 [56%]), semiprofessional (5 [56%]), and professional (101 [86%]) players having severe pathology. Among 27 participants with mild CTE pathology, 26 (96%) had behavioral or mood symptoms or both, 23 (85%) had cognitive symptoms, and 9 (33%) had signs of dementia. Among 84 participants with severe CTE pathology, 75 (89%) had behavioral or mood symptoms or both, 80 (95%) had cognitive symptoms, and 71 (85%) had signs of dementia., Conclusions and Relevance: In a convenience sample of deceased football players who donated their brains for research, a high proportion had neuropathological evidence of CTE, suggesting that CTE may be related to prior participation in football.

The King-Devick (K-D) test is a 1 to 2 minute, rapid number naming test, often used to assist with detection of concussion, but also has clinical utility in other neurological conditions (eg, Parkinson disease). The K-D involves saccadic eye and other eye movements, and abnormalities thereof may be an early indicator of Alzheimer disease (AD)-associated cognitive impairment. No study has tested the utility of the K-D in AD and we sought to do so. The sample included 206 [135 controls, 39 mild cognitive impairment (MCI), and 32 AD dementia] consecutive subjects from the Boston University Alzheimer's Disease Center registry undergoing their initial annual evaluation between March 2013 and July 2015. The K-D was administered during this period. Areas under the receiver operating characteristic curves generated from logistic regression models revealed the K-D test distinguished controls from subjects with cognitive impairment (MCI and AD dementia) [area under the curve (AUC)=0.72], MCI (AUC=0.71) and AD dementia (AUC=0.74). K-D time scores between 48 and 52 seconds were associated with high sensitivity (>90.0%) and negative predictive values (>85.0%) for each diagnostic group. The K-D correlated strongly with validated attention, processing speed, and visual scanning tests. The K-D test may be a rapid and simple effective screening tool to detect cognitive impairment associated with AD.

Background: Prompt entry into HIV care is often hindered by personal and structural barriers. Our objective was to evaluate the impact of self-perceived barriers to health care on 1-year mortality among newly diagnosed HIV-infected individuals in Durban, South Africa., Methods: Before HIV testing at 4 outpatient sites, adults (≥18 years) were surveyed regarding perceived barriers to care including (1) service delivery, (2) financial, (3) personal health perception, (4) logistical, and (5) structural. We assessed deaths via phone calls and the South African National Population Register. We used multivariable Cox proportional hazards models to determine the association between number of perceived barriers and death within 1 year., Results: One thousand eight hundred ninety-nine HIV-infected participants enrolled. Median age was 33 years (interquartile range: 27-41 years), 49% were females, and median CD4 count was 192/μL (interquartile range: 72-346/μL). One thousand fifty-seven participants (56%) reported no, 370 (20%) reported 1-3, and 460 (24%) reported >3 barriers to care. By 1 year, 250 [13%, 95% confidence interval (CI): 12% to 15%] participants died. Adjusting for age, sex, education, baseline CD4 count, distance to clinic, and tuberculosis status, participants with 1-3 barriers (adjusted hazard ratio: 1.49, 95% CI: 1.06 to 2.08) and >3 barriers (adjusted hazard ratio: 1.81, 95% CI: 1.35 to 2.43) had higher 1-year mortality risk compared with those without barriers., Conclusions: HIV-infected individuals in South Africa who reported perceived barriers to medical care at diagnosis were more likely to die within 1 year. Targeted structural interventions, such as extended clinic hours, travel vouchers, and streamlined clinic operations, may improve linkage to care and antiretroviral therapy initiation for these people.

Professional American football players incur thousands of repetitive head impacts (RHIs) throughout their lifetime. The long-term consequences of RHI are not well characterized, but may include olfactory dysfunction. RHI has been associated with changes to brain regions involved in olfaction, and olfactory impairment is common after traumatic brain injury. Olfactory dysfunction is a frequent early sequelae of neurodegenerative diseases (e.g., Alzheimer's disease), and RHI is associated with the neurodegenerative disease, chronic traumatic encephalopathy (CTE). We examined olfaction, and its association with clinical measures, in former National Football League (NFL) players. Ninety-five former NFL players (ages 40-69) and 28 same-age controls completed a neuropsychological and neuropsychiatric evaluation as part of a National Institutes of Health-funded study. The Brief Smell Identification Test (B-SIT) assessed olfaction. Principal component analysis generated a four-factor structure of the clinical measures: behavioral/mood, psychomotor speed/executive function, and verbal and visual memory. Former NFL players had worse B-SIT scores relative to controls (p = 0.0096). A B-SIT cutoff of 11 had the greatest accuracy (c-statistic = 0.61) and specificity (79%) for discriminating former NFL players from controls. In the former NFL players, lower B-SIT scores correlated with greater behavioral/mood impairment (p = 0.0254) and worse psychomotor speed/executive functioning (p = 0.0464) after controlling for age and education. Former NFL players exhibited lower olfactory test scores relative to controls, and poorer olfactory test performance was associated with worse neuropsychological and neuropsychiatric functioning. Future work that uses more-comprehensive tests of olfaction and structural and functioning neuroimaging may improve understanding on the association between RHI and olfaction.

The term "repetitive head impacts" (RHI) refers to the cumulative exposure to concussive and subconcussive events. Although RHI are believed to increase risk for later-life neurological consequences (including chronic traumatic encephalopathy), quantitative analysis of this relationship has not yet been examined because of the lack of validated tools to quantify lifetime RHI exposure. The objectives of this study were: 1) to develop a metric to quantify cumulative RHI exposure from football, which we term the "cumulative head impact index" (CHII); 2) to use the CHII to examine the association between RHI exposure and long-term clinical outcomes; and 3) to evaluate its predictive properties relative to other exposure metrics (i.e., duration of play, age of first exposure, concussion history). Participants included 93 former high school and collegiate football players who completed objective cognitive and self-reported behavioral/mood tests as part of a larger ongoing longitudinal study. Using established cutoff scores, we transformed continuous outcomes into dichotomous variables (normal vs. impaired). The CHII was computed for each participant and derived from a combination of self-reported athletic history (i.e., number of seasons, position[s], levels played), and impact frequencies reported in helmet accelerometer studies. A bivariate probit, instrumental variable model revealed a threshold dose-response relationship between the CHII and risk for later-life cognitive impairment (p < 0.0001), self-reported executive dysfunction (p < 0.0001), depression (p < 0.0001), apathy (p = 0.0161), and behavioral dysregulation (p < 0.0001). Ultimately, the CHII demonstrated greater predictive validity than other individual exposure metrics., Competing Interests: Author Disclosure Statement Dr. Stern is a paid consultant to Amarantus Bioscience, Avanir Pharmaceuticals, and Biogen. He also serves as an expert advisor to attorneys for cases pertaining to the long-term consequences of repetitive brain trauma. He receives royalties from Psychological Assessment Resources for the publication of neuropsychological tests. Dr. Cantu receives compensation from the National Football League as Senior Advisor to the Head, Neck, and Spine Committee; from the National Operating Committee on Safety of Athletic Equipment as Chairman of the Scientific Advisory Committee; and from Concussion Legacy Foundation as co-founder and medical director for some talks given and research conducted. He receives royalties from Houghton Mifflin Harcourt and compensation from expert legal opinion. All other authors report no competing financial interests.

The relationship between late-life body mass index (BMI) and Alzheimer's disease (AD) is poorly understood due to the lack of research in samples with autopsy-confirmed AD neuropathology (ADNP). The role of cerebrovascular disease (CVD) in the interplay between late-life BMI and ADNP is unclear. We conducted a retrospective longitudinal investigation and used joint modeling of linear mixed effects to investigate causal relationships among repeated antemortem BMI measurements, CVD (quantified neuropathologically), and ADNP in an autopsy sample of subjects across the AD clinical continuum. The sample included 1,421 subjects from the National Alzheimer's Coordinating Center's Uniform Data Set and Neuropathology Data Set with diagnoses of normal cognition (NC; n = 234), mild cognitive impairment (MCI; n = 201), or AD dementia (n = 986). ADNP was defined as moderate to frequent neuritic plaques and Braak stageIII-VI. Ischemic Injury Scale (IIS) operationalized CVD. Joint modeling examined relationships among BMI, IIS, and ADNP in the overall sample and stratified by initial visit Clinical Dementia Rating score. Subject-specific random intercept for BMI was the predictor for ADNP due to minimal BMI change (p = 0.3028). Analyses controlling for demographic variables and APOE ɛ4 showed lower late-life BMI predicted increased odds of ADNP in the overall sample (p < 0.001), and in subjects with CDR of 0 (p = 0.0021) and 0.5 (p = 0.0012), but not ≥1.0 (p = 0.2012). Although higher IIS predicted greater odds of ADNP (p < 0.0001), BMI did not predict IIS (p = 0.2814). The current findings confirm lower late-life BMI confers increased odds for ADNP. Lower late-life BMI may be a preclinical indicator of underlying ADNP.

Objectives: Among Russians living with HIV/AIDS who inject drugs, we examined the incidence of fatal and non-fatal overdoses following discharge from a narcology hospital and the associations with more advanced HIV infection., Design: Prospective cohort study of data collected at baseline, 3 and 6 months from HIV-infected patients with a history of injection drug use who were not treated with anti-retroviral therapy. Participants were recruited between 2012-2014 from a narcology (addiction) hospital in St. Petersburg, Russia., Methods: Fatal overdose was determined based on contact reports to study staff in the year after discharge. Non-fatal overdose was self-reported at the 3- and 6-month assessments. The main independent variable for HIV severity was CD4 cell count at the baseline interview (<200cells/mm 3 ≥200cells/mm 3 ). Secondary analyses assessed time since HIV diagnosis and treated with anti-retroviral treatment (ART) prior to enrolment as independent variables. We fit Cox proportional hazards models to assess whether HIV severity is associated with either fatal or non-fatal overdose., Results: Among 349 narcology patients, 18 participants died from overdose within one year after discharge (8.7%, 95% CI 3.4-14.2 by Kaplan-Meier); an estimated 51% [95% CI 34-68%] reported at least one non-fatal overdose within 6 months of discharge. HIV severity, time since HIV diagnosis and ever ART were not significantly associated with either fatal or non-fatal overdose events., Conclusion: Fatal and non-fatal overdose are common among Russians living with HIV/AIDS who inject drugs after narcology hospital discharge. Overdose prevention interventions are urgently warranted among Russian narcology patients with HIV infection., Competing Interests: No conflict declared., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Introduction: Blood protein analysis of total tau (t-tau) may be a practical screening biomarker for chronic traumatic encephalopathy (CTE), a neurodegenerative tauopathy associated with repetitive head impact (RHI) exposure. We examined plasma t-tau in symptomatic former National Football League (NFL) players compared with controls and the relationship between RHI exposure and later-life plasma t-tau., Methods: Ninety-six former NFL players (age 40-69) and 25 same-age controls underwent blood draw to determine plasma t-tau levels. The cumulative head impact index (CHII) quantified RHI exposure. Subjects completed measures of clinical function., Results: A higher CHII predicted greater plasma t-tau in the former NFL players ( P  = .0137). No group differences in plasma t-tau emerged, but a concentration ≥3.56 pg/mL was 100% specific to former NFL players. Plasma t-tau did not predict clinical function., Discussion: Greater RHI exposure predicted higher later-life plasma t-tau concentrations, and further study on plasma t-tau as a candidate screening biomarker for CTE is warranted.

Two of the most commonly used methods to assess memory functioning in studies of cognitive aging and dementia are story memory and list learning tests. We hypothesized that the most commonly used story memory test, Wechsler's Logical Memory, would generate more pronounced practice effects than a well validated but less common list learning test, the Neuropsychological Assessment Battery (NAB) List Learning test. Two hundred eighty-seven older adults, ages 51 to 100 at baseline, completed both tests as part of a larger neuropsychological test battery on an annual basis. Up to five years of recall scores from participants who were diagnosed as cognitively normal (n = 96) or with mild cognitive impairment (MCI; n = 72) or Alzheimer's disease (AD; n = 121) at their most recent visit were analyzed with linear mixed effects regression to examine the interaction between the type of test and the number of times exposed to the test. Other variables, including age at baseline, sex, education, race, time (years) since baseline, and clinical diagnosis were also entered as fixed effects predictor variables. The results indicated that both tests produced significant practice effects in controls and MCI participants; in contrast, participants with AD declined or remained stable. However, for the delayed-but not the immediate-recall condition, Logical Memory generated more pronounced practice effects than NAB List Learning (b = 0.16, p < .01 for controls). These differential practice effects were moderated by clinical diagnosis, such that controls and MCI participants-but not participants with AD-improved more on Logical Memory delayed recall than on delayed NAB List Learning delayed recall over five annual assessments. Because the Logical Memory test is ubiquitous in cognitive aging and neurodegenerative disease research, its tendency to produce marked practice effects-especially on the delayed recall condition-suggests a threat to its validity as a measure of new learning, an essential construct for dementia diagnosis., Competing Interests: BEG has received compensation for expert opinion. RAS has received research funding from Avid Radiopharmaceuticals, Inc. (Philadelphia, PA, USA). He is a member of the Mackey-White Committee of the NFL Players Association. He is a paid consultant to Amarantus BioScience Holdings, Inc. (San Francisco, CA, USA), Avanir Pharmaceuticals, Inc. (Aliso Viejo, CA), and Biogen (Cambridge, MA). He receives royalties for published neuropsychological tests (including the Neuropsychological Assessment Battery) from Psychological Assessment Resources, Inc. (Lutz, FL, USA), as well as compensation from expert legal opinion. All of the other authors declare that they have no competing interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: A fraction of HIV-diagnosed individuals promptly initiate antiretroviral therapy (ART). We evaluated the efficacy of health system navigators for improving linkage to HIV and tuberculosis (TB) care among newly diagnosed HIV-infected outpatients in Durban, South Africa., Methods: We conducted a randomized controlled trial (Sizanani Trial, NCT01188941) among adults (≥18 years) at 4 sites. Participants underwent TB screening and randomization into a health system navigator intervention or usual care. Intervention participants had an in-person interview at enrollment and received phone calls and text messages over 4 months. We assessed 9-month outcomes via medical records and the National Population Registry. Primary outcome was completion of at least 3 months of ART or 6 months of TB treatment for coinfected participants., Results: Four thousand nine hundred three participants were enrolled and randomized; 1899 (39%) were HIV-infected, with 1146 (60%) ART-eligible and 523 (28%) TB coinfected at baseline. In the intervention, 212 (39% of outcome-eligible) reached primary outcome compared to 197 (42%) in usual care (RR 0.93, 95% CI: 0.80 to 1.08). One hundred thirty-one (14%) HIV-infected intervention participants died compared to 119 (13%) in usual care; death rates did not differ between arms (RR 1.06, 95% CI: 0.84 to 1.34). In the as-treated analysis, participants reached for ≥5 navigator calls were more likely to achieve study outcome., Conclusions: ∼40% of ART-eligible participants in both study arms reached the primary outcome 9 months after HIV diagnosis. Low rates of engagement in care, high death rates, and lack of navigator efficacy highlight the urgency of identifying more effective strategies for improving HIV and TB care outcomes., Competing Interests: The authors have no conflicts of interests to disclose.

Background: Russia and Eastern Europe have one of the fastest growing HIV epidemics in the world. While countries in this region have implemented HIV testing within addiction treatment systems, linkage to HIV care from these settings is not yet standard practice. The Linking Infectious and Narcology Care (LINC) intervention utilized peer-led strengths-based case management to motivate HIV-infected patients in addiction treatment to obtain HIV care. This paper describes the protocol of a randomized controlled trial evaluating the effectiveness of the LINC intervention in St. Petersburg, Russia., Methods/design: Participants (n = 349) were recruited from the inpatient wards at the City Addiction Hospital in St. Petersburg, Russia. After completing a baseline assessment, participants were randomly assigned to receive either the LINC intervention or standard of care. Participants returned for research assessments 6 and 12 months post-baseline. Primary outcomes were assessed via chart review at HIV treatment locations., Discussion: LINC holds the potential to offer an effective approach to coordinating HIV care for people who inject drugs in Russia. The LINC intervention utilizes existing systems of care in Russia, minimizing adoption of substantial infrastructure for implementation. Trial Registration NCT01612455.

Background: The human immunodeficiency virus (HIV) epidemic in Russia, driven by injection drug use, has seen a steady rise in the past two decades. Hepatitis C virus (HCV) infection is highly prevalent in people who inject drugs (PWID). The study aimed to describe the current frequency of HCV testing and treatment among HIV-infected PWID in St. Petersburg, Russia., Methods: This study examined baseline data from the "Linking Infectious and Narcology Care" (LINC) and "Russia Alcohol Research Collaboration on HIV/AIDS" (Russia ARCH) studies. Participants included in this analysis were HIV-infected with a history of injection drug use. Descriptive statistics were performed to assess frequency of HCV testing and treatment., Results: Participants (n=349 [LINC], 207 [Russia ARCH]) had a mean age of 33.8 years (IQR: 31-37) in LINC and 33.0 (IQR: 30-36) in Russia ARCH; 26.6% (LINC) and 29.0% (Russia ARCH) were female; 100% were Caucasian. Nearly all participants had been tested for HCV (98.9% in LINC, 97.1% in Russia ARCH). Almost all reported being diagnosed HCV positive (98.9% in LINC, 97.1% in Russia ARCH). Only 2.3% of LINC and 5.0% of Russia ARCH participants reported ever receiving HCV treatment., Conclusions: Among these cohorts of HIV-infected PWID in St. Petersburg, Russia, as of 2015 nearly all reported being tested for HCV and testing positive, while only 3.3% received any HCV treatment. In this new era of effective HCV pharmacotherapy, an enormous chasm in the HCV treatment cascade in Russia exists providing substantial opportunities for curing HCV in HIV-infected Russians with a history of injection drug use.

Aims: This study assessed the effectiveness of HERMITAGE (HIV's Evolution in Russia-Mitigating Infection Transmission and Alcoholism in a Growing Epidemic), an adapted secondary HIV prevention intervention, compared with an attention control condition in decreasing sexually transmitted infections (STIs) and sex and drug risk behaviors among Russian HIV-infected heavy drinkers., Design: We conducted a single-blinded, two-armed, randomized controlled trial with 12-month follow-up., Setting: The study was conducted in St Petersburg, Russia. Participants were recruited from four HIV and addiction clinical sites. The intervention was conducted at Botkin Infectious Disease Hospital., Participants: HIV-infected individuals with past 6-month risky sex and heavy alcohol consumption (n = 700) were randomized to the HERMITAGE intervention (n = 350) or an attention control condition (n = 350)., Intervention: A Healthy Relationships Intervention stressing disclosure of HIV serostatus and condom use, adapted for a Russian clinical setting with two individual sessions and three small group sessions., Measurements: The primary outcome was incident STI by laboratory test at 12-month follow-up. Secondary outcomes included change in unprotected sex and several alcohol and injection drug use (IDU) variables., Findings: Participants had the following baseline characteristics: 59.3% male, mean age 30.1, 60.4% past year IDU, 15.4% prevalent STI and mean CD4 cell count 413.3/μl. Assessment occurred among 75 and 71% of participants at 6 and 12 months, respectively. STIs occurred in 20 subjects (8.1%) in the intervention group and 28 subjects (12.0%) in the control group at 12-month follow-up; logistic regression analyses found no significant difference between groups (adjusted odds ratio 0.63; 95% confidence interval = 0.34-1.18; P = 0.15). Both groups decreased unsafe behaviors, although no significant differences were found between groups., Conclusions: The HERMITAGE HIV risk reduction intervention does not appear to reduce sexually transmitted infections and HIV risk behaviors in Russian HIV-infected heavy drinkers compared with attention controls., (© 2014 Society for the Study of Addiction.)

Importance: The United States has invested substantially in screening and brief intervention for illicit drug use and prescription drug misuse, based in part on evidence of efficacy for unhealthy alcohol use. However, it is not a recommended universal preventive service in primary care because of lack of evidence of efficacy., Objective: To test the efficacy of 2 brief counseling interventions for unhealthy drug use (any illicit drug use or prescription drug misuse)-a brief negotiated interview (BNI) and an adaptation of motivational interviewing (MOTIV)-compared with no brief intervention., Design, Setting, and Participants: This 3-group randomized trial took place at an urban hospital-based primary care internal medicine practice; 528 adult primary care patients with drug use (Alcohol, Smoking, and Substance Involvement Screening Test [ASSIST] substance-specific scores of ≥4) were identified by screening between June 2009 and January 2012 in Boston, Massachusetts., Interventions: Two interventions were tested: the BNI is a 10- to 15-minute structured interview conducted by health educators; the MOTIV is a 30- to 45-minute intervention based on motivational interviewing with a 20- to 30-minute booster conducted by master's-level counselors. All study participants received a written list of substance use disorder treatment and mutual help resources., Main Outcomes and Measures: Primary outcome was number of days of use in the past 30 days of the self-identified main drug as determined by a validated calendar method at 6 months. Secondary outcomes included other self-reported measures of drug use, drug use according to hair testing, ASSIST scores (severity), drug use consequences, unsafe sex, mutual help meeting attendance, and health care utilization., Results: At baseline, 63% of participants reported their main drug was marijuana, 19% cocaine, and 17% opioids. At 6 months, 98% completed follow-up. Mean adjusted number of days using the main drug at 6 months was 12 for no brief intervention vs 11 for the BNI group (incidence rate ratio [IRR], 0.97; 95% CI, 0.77-1.22) and 12 for the MOTIV group (IRR, 1.05; 95% CI, 0.84-1.32; P = .81 for both comparisons vs no brief intervention). There were also no significant effects of BNI or MOTIV on any other outcome or in analyses stratified by main drug or drug use severity., Conclusions and Relevance: Brief intervention did not have efficacy for decreasing unhealthy drug use in primary care patients identified by screening. These results do not support widespread implementation of illicit drug use and prescription drug misuse screening and brief intervention., Trial Registration: clinicaltrials.gov Identifier: NCT00876941.

Overdoses and HIV infection are common among Russians who inject drugs, yet risk factors have not been studied. We analyzed baseline data of 294 participants with 30-day injection drug use from an HIV secondary prevention trial for persons reporting "heavy" alcohol use (National Institute on Alcohol Abuse and Alcoholism [NIAAA] risky drinking definition) and risky sex in the past 6 months. The outcome was any self-reported overdose in the previous 3 months. We examined demographic, HIV-related, criminal justice, mental health, substance use, and injection risk factors. Participants' characteristics included median age 29 years, 117/294 (40%) female, and median CD4 cell count 345/µl. Over three quarters 223/294 (76%) reported a history of overdose and 47/294 (16%) reported overdose in the past 3 months. Past month injection frequency (adjusted odds ratio [AOR] 4.77, 95% confidence interval [CI]: 1.63-14.0 highest vs. lowest quartile; AOR 3.58, 95% CI: 1.20-10.69 second highest vs. lowest quartile) and anti-retroviral therapy (ART) at time of interview (AOR 3.96 95% CI: 1.33-11.83) were associated with 3-month overdose. Nonfatal overdose among HIV-infected Russians who inject drugs is common. Risk factors include injection frequency and anti-retroviral therapy (ART), which warrant further study. Overdose prevention efforts are needed among HIV-infected Russians who inject drugs.

Background: Although anecdotal evidence suggests that the risk of recurrent gout attack increases with hospitalization, no study has formally tested this hypothesis., Methods: We conducted an online case-crossover study of individuals with gout. We obtained information on gout attacks over a 1-year period, including onset date, symptoms and signs, medications, and exposure to potential risk factors, including hospitalization, during the 2-day hazard period before each gout attack. The same exposure information also was obtained over 2-day intercritical gout control periods. We performed conditional logistic regression to examine the relationship of hospitalization with recurrent gout attacks and whether such a relationship was modified by concomitant use of anti-gout medications., Results: Of 724 participants (mean age, 54.5 years; 78.5% male), 35 hospitalizations occurred during a hazard or control period. The adjusted odds of gout attacks was increased 4-fold with hospitalization (odds ratio, 4.05; 95% confidence interval, 1.78-9.19) compared with no hospitalization. The effect of hospitalization tended to attenuate with the use of allopurinol, colchicine, or nonsteroidal anti-inflammatory drugs, but not statistically significantly., Conclusions: Our study confirmed that the risk of gout attacks increases among patients with gout during hospitalization. Appropriate measures should be considered for prevention of gout attacks during hospitalization for patients with preexisting gout., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Despite increases in HIV testing, only a fraction of people newly diagnosed with HIV infection enter the care system and initiate antiretroviral therapy (ART) in South Africa. We report on the design and initial enrollment of a randomized trial of a health system navigator intervention to improve linkage to HIV care and TB treatment completion in Durban, South Africa., Methods/design: We employed a multi-site randomized controlled trial design. Patients at 4 outpatient sites were enrolled prior to HIV testing. For all HIV-infected participants, routine TB screening with sputum for mycobacterial smear and culture were collected. HIV-infected participants were randomized to receive the health system navigator intervention or usual care. Participants in the navigator arm underwent a baseline interview using a strengths-based case management approach to assist in identifying barriers to entering care and devising solutions to best cope with perceived barriers. Over 4 months, participants in the navigator arm received scheduled phone and text messages. The primary outcome of the study is linkage and retention in care, assessed 9 months after enrollment. For ART-eligible participants without TB, the primary outcome is 3 months on ART as documented in the medical record; participants co-infected with TB are also eligible to meet the primary outcome of completion of 6 months of TB treatment, as documented by the TB clinic. Secondary outcomes include mortality, receipt of CD4 count and TB test results, and repeat CD4 counts for those not ART-eligible at baseline. We hypothesize that a health system navigator can help identify and positively affect modifiable patient factors, including self-efficacy and social support, that in turn can improve linkage to and retention in HIV and TB care., Discussion: We are currently evaluating the clinical impact of a novel health system navigator intervention to promote entry to and retention in HIV and TB care for people newly diagnosed with HIV. The details of this study protocol will inform clinicians, investigators, and policy makers of strategies to best support HIV-infected patients in resource-limited settings., Trial Registration: Clinicaltrials.gov. unique identifier: NCT01188941.

Background: Whether arthroscopic partial meniscectomy for symptomatic patients with a meniscal tear and knee osteoarthritis results in better functional outcomes than nonoperative therapy is uncertain., Methods: We conducted a multicenter, randomized, controlled trial involving symptomatic patients 45 years of age or older with a meniscal tear and evidence of mild-to-moderate osteoarthritis on imaging. We randomly assigned 351 patients to surgery and postoperative physical therapy or to a standardized physical-therapy regimen (with the option to cross over to surgery at the discretion of the patient and surgeon). The patients were evaluated at 6 and 12 months. The primary outcome was the difference between the groups with respect to the change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) physical-function score (ranging from 0 to 100, with higher scores indicating more severe symptoms) 6 months after randomization., Results: In the intention-to-treat analysis, the mean improvement in the WOMAC score after 6 months was 20.9 points (95% confidence interval [CI], 17.9 to 23.9) in the surgical group and 18.5 (95% CI, 15.6 to 21.5) in the physical-therapy group (mean difference, 2.4 points; 95% CI, -1.8 to 6.5). At 6 months, 51 active participants in the study who were assigned to physical therapy alone (30%) had undergone surgery, and 9 patients assigned to surgery (6%) had not undergone surgery. The results at 12 months were similar to those at 6 months. The frequency of adverse events did not differ significantly between the groups., Conclusions: In the intention-to-treat analysis, we did not find significant differences between the study groups in functional improvement 6 months after randomization; however, 30% of the patients who were assigned to physical therapy alone underwent surgery within 6 months. (Funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases; METEOR ClinicalTrials.gov number, NCT00597012.).

Background: Shared decision making (SDM) is a widely recommended yet unproven strategy for increasing colorectal cancer (CRC) screening uptake. Previous trials of decision aids to increase SDM and CRC screening uptake have yielded mixed results., Purpose: To assess the impact of decision aid-assisted SDM on CRC screening uptake., Design: RCT., Setting/participants: The study was conducted at an urban, academic safety-net hospital and community health center between 2005 and 2010. Participants were asymptomatic, average-risk patients aged 50-75 years due for CRC screening., Intervention: Study participants (n=825) were randomized to one of two intervention arms (decision aid plus personalized risk assessment or decision aid alone) or control arm. The interventions took place just prior to a routine office visit with their primary care providers., Main Outcome Measures: The primary outcome was completion of a CRC screening test within 12 months of the study visit. Logistic regression was used to identify predictors of test completion and mediators of the intervention effect. Analysis was completed in 2011., Results: Patients in the decision-aid group were more likely to complete a screening test than control patients (43.1% vs 34.8%, p=0.046) within 12 months of the study visit; conversely, test uptake for the decision aid and decision aid plus personalized risk assessment arms was similar (43.1% vs 37.1%, p=0.15). Assignment to the decision-aid arm (AOR=1.48, 95% CI=1.04, 2.10), black race (AOR=1.52, 95% CI=1.12, 2.06) and a preference for a patient-dominant decision-making approach (AOR=1.55, 95% CI=1.02, 2.35) were independent determinants of test completion. Activation of the screening discussion and enhanced screening intentions mediated the intervention effect., Conclusions: Decision aid-assisted SDM has a modest impact on CRC screening uptake. A decision aid plus personalized risk assessment tool is no more effective than a decision aid alone., Trial Registration: This study is registered at www.clinicaltrials.govNCT00251862., (Copyright © 2012 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

This paper presents the rationale and design features of the MeTeOR Trial (Meniscal Tear in Osteoarthritis Research; Clinical Trials.gov NCT00597012). MeTeOR is an NIH-funded seven-center prospective randomized controlled trial (RCT) designed to establish the efficacy of arthroscopic partial meniscectomy combined with a standardized physical therapy program as compared with a standardized physical therapy program alone in patients with a symptomatic meniscal tear in the setting of mild to moderate knee osteoarthritic change (OA). The design and execution of a trial that compares surgery with a nonoperative treatment strategy presents distinctive challenges. The goal of this paper is to provide the clinical rationale for MeTeOR and to highlight salient design features, with particular attention to those that present clinical and methodologic challenges., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objectives: To evaluate the feasibility of conducting an online case-crossover study of triggers for recurrent disease flares., Methods: We conducted an online case-crossover study of triggers for recurrent flares using gout as a paradigm. We constructed a Web site and recruited individuals with history of gout via the Internet. We confirmed gout diagnosis by reviewing each subject's medical records. We collected via the Internet exposure information during the intercritical period using a scheduled Control-period Questionnaire, and prior to recurrent gout attacks using a Hazard-period Questionnaire., Results: Over 10 months we recruited 197 subjects with a history of gout from 41 states and the District of Columbia. We obtained medical records from 172 subjects. All participants had experienced at least one recurrent attack and filled out required questionnaires. The median time between the date of an attack and the date of logging on to the Web site was 2 days. The incidence rate of recurrent gout attacks was 1.03 per person-year. Longer disease duration and presence of comorbidities appeared to increase the risk of recurrent flares., Conclusion: The results of this study demonstrate that a case-crossover study can be successfully conducted through the Internet. This approach has broad applicability to other diseases typified by recurrent attacks.