Effectiveness of Hybrid Form Impulse Therapy (HFIT) Compared to Traditional Transcutaneous Electronic Nerve Stimulation (TENS) in Patients with Chronic Low Back and Knee Pain: A Randomized Controlled Trial.

Purpose: 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.

Effectiveness, utilisation and cost associated with implantable loop recorders versus external monitors after ischaemic or cryptogenic stroke.

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.

Teamwork measure relates to provider experience, burnout, and intent to stay.

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.

Comparison of Care Quality Metrics in 2-Sided Risk Medicare Advantage vs Fee-for-Service Medicare Programs.

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.

Neisseria gonorrhoeae Infection in Women Increases With Rising Gonococcal Burdens in Partners: Chlamydia Coinfection in Women Increases Gonococcal Burden.

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.

Variation in Initiation, Engagement, and Retention on Medications for Opioid Use Disorder Based on Health Insurance Plan Design.

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.

Peripheral Artery Disease Screening in the Community and 1-Year Mortality, Cardiovascular Events, and Adverse Limb Events.

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.

Variation in guideline-based prenatal care in a commercially insured population.

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.

Potential barriers to filling buprenorphine and naltrexone prescriptions among a retrospective cohort of individuals with opioid use disorder.

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.

Using a Claims-Based Framework to Identify Severe Maternal Morbidities in a Commercially Insured US Population.

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.

Quality of Buprenorphine Care for Insured Adults With Opioid Use Disorder.

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.

Relative Cost Differences of Initial Treatment Strategies for Newly Diagnosed Opioid Use Disorder: A Cohort Study.

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.

Assessment of Potentially Inappropriate Prescribing of Opioid Analgesics Requiring Prior Opioid Tolerance.

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.

Comparative Effectiveness of Different Treatment Pathways for Opioid Use Disorder.

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.

Mycoplasma genitalium in Symptomatic Male Urethritis: Macrolide Use Is Associated With Increased Resistance.

BACKGROUND: Mycoplasma genitalium (MG) causes symptomatic urethritis in men, and can infect alone or together with other sexually transmitted infection (STI) agents. METHODS: The prevalence of MG and other STIs was determined in 1816 men with symptomatic urethritis. Resistance of MG to macrolides and fluoroquinolones was determined by sequencing; the impact of recent antimicrobial usage on the distribution of MG single or mixed infections was determined. RESULTS: Overall, prevalence of MG infection was 19.7% (358/1816). Fifty-four percent (166/307) of MG infections occurred alone in the absence of other STI agents. Men with single MG infection self-administered or were prescribed antibiotics more often in the 30 days prior to enrollment than subjects with urethritis caused by MG coinfection (P < .0001). Higher rates (96.7%) of infection with macrolide resistance in MG were identified in men who had taken macrolides prior to enrollment (P < .03). Overall, 88.9% (303/341) of 23S ribosomal RNA (rRNA) genes contained mutations responsible for macrolide resistance; 89.5% (308/344) of parC and 12.4% (42/339) of gyrA genes had mutations responsible for fluoroquinolone resistance. Approximately 88% (270/308) of MG had combined mutations in 23S rRNA and parC genes; 10.4% (32/308) had mutations in all 3 genes. CONCLUSIONS: MG was the single pathogen identified in 11% of men with symptomatic urethritis. Overall, nearly 90% of MG infections were resistant to macrolides and fluoroquinolones. Men who took macrolides in the 30 days prior to enrollment had higher rates (97%) of macrolide-resistant MG. Resistance was associated with numerous mutations in 23SrRNA, parC, and gyrA genes.

A magnetic resonance spectroscopy investigation in symptomatic former NFL players.

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.

Risk of gout flares after vaccination: a prospective case cross-over study.

OBJECTIVES: The recombinant zoster vaccine (RZV) containing a strong non-aluminium adjuvant is associated with increased risk of gout flares, presumably via NLRP3 inflammasome activation. We tested the possibility that other vaccines may also be associated with gout flares. METHODS: We conducted an online case-crossover study of patients with gout to examine the association between vaccination and gout flares. We collected information through the Internet on exposures to potential risk factors, including vaccinations, during 2-day hazard periods prior to gout flare and 2-day control periods without a flare. Conditional logistic regression was used to adjust for covariates. RESULTS: There were 517 participants with gout (mean age 55 years, 79% male) who experienced gout flares during follow-up. There were 28 vaccinations during 990 hazard periods and 21 vaccinations during 1407 control periods. Vaccination was associated with twofold higher odds of gout flare (adjusted OR 1.99; 95% CI 1.01 to 3.89). CONCLUSION: Our findings suggest vaccines other than RZV are associated with increased odds of gout flares, potentially through a shared pathogenetic mechanism like NLRP3 inflammasome. However, the absolute magnitude of increased odds of gout flares with vaccinations remains small and must be interpreted within the context of the overwhelming benefits of vaccinations.

Study protocol for the targeting effective analgesia in clinics for HIV (TEACH) study - a cluster randomized controlled trial and parallel cohort to increase guideline concordant care for long-term opioid therapy among people living with HIV.

Background: People living with HIV (PLWH) frequently experience chronic pain and receive long-term opioid therapy (LTOT). Adherence to opioid prescribing guidelines among their providers is suboptimal. Objective: This paper describes the protocol of a cluster randomized trial, targeting effective analgesia in clinics for HIV (TEACH), which tested a collaborative care intervention to increase guideline-concordant care for LTOT among PLWH. Methods: HIV physicians and advanced practice providers (n = 41) were recruited from September 2015 to December 2016 from two HIV clinics in Boston and Atlanta. Patients receiving LTOT from participating providers were enrolled through a waiver of informed consent (n = 187). After baseline assessment, providers were randomized to the control group or the year-long TEACH intervention involving: (1) a nurse care manager and electronic registry to assist with patient management; (2) opioid education and academic detailing; and (3) facilitated access to addiction specialists. Randomization was stratified by site and LTOT patient volume. Primary outcomes (≥2 urine drug tests, early refills, provider satisfaction) were collected at 12 months. In parallel, PLWH receiving LTOT (n = 170) were recruited into a longitudinal cohort at both clinics and underwent baseline and 12-month assessments. Secondary outcomes were obtained through patient self-report among participants enrolled in both the cohort and the RCT (n = 117). Conclusions: TEACH will report the effects of an intervention on opioid prescribing for chronic pain on both provider and patient-level outcomes. The results may inform delivery of care for PLWH on LTOT for chronic pain at a time when opioid practices are being questioned in the US.

A strengths-based case management intervention to link HIV-positive people who inject drugs in Russia to HIV care.

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.

Limbic system structure volumes and associated neurocognitive functioning in former NFL players.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with exposure to repetitive head impacts. CTE has been linked to disruptions in cognition, mood, and behavior. Unfortunately, the diagnosis of CTE can only be made post-mortem. Neuropathological evidence suggests limbic structures may provide an opportunity to characterize CTE in the living. Using 3 T magnetic resonance imaging, we compared select limbic brain regional volumes - the amygdala, hippocampus, and cingulate gyrus - between symptomatic former National Football League (NFL) players (n = 86) and controls (n = 22). Moreover, within the group of former NFL players, we examined the relationship between those limbic structures and neurobehavioral functioning (n = 75). The former NFL group comprised eighty-six men (mean age = 55.2 ± 8.0 years) with at least 12 years of organized football experience, at least 2 years of active participation in the NFL, and self-reported declines in cognition, mood, and behavior within the last 6 months. The control group consisted of men (mean age = 57.0 ± 6.6 years) with no history of contact-sport involvement or traumatic brain injury. All control participants provided neurobehavioral data. Compared to controls, former NFL players exhibited reduced volumes of the amygdala, hippocampus, and cingulate gyrus. Within the NFL group, reduced bilateral cingulate gyrus volume was associated with worse attention and psychomotor speed (r = 0.4 (right), r = 0.42 (left); both p < 0.001), while decreased right hippocampal volume was associated with worse visual memory (r = 0.25, p = 0.027). Reduced volumes of limbic system structures in former NFL players are associated with neurocognitive features of CTE. Volume reductions in the amygdala, hippocampus, and cingulate gyrus may be potential biomarkers of neurodegeneration in those at risk for CTE.