Managing differential performance of polygenic risk scores across groups: Real-world experience of the eMERGE Network.

The differential performance of polygenic risk scores (PRSs) by group is one of the major ethical barriers to their clinical use. It is also one of the main practical challenges for any implementation effort. The social repercussions of how people are grouped in PRS research must be considered in communications with research participants, including return of results. Here, we outline the decisions faced and choices made by a large multi-site clinical implementation study returning PRSs to diverse participants in handling this issue of differential performance. Our approach to managing the complexities associated with the differential performance of PRSs serves as a case study that can help future implementers of PRSs to plot an anticipatory course in response to this issue.

Prospective, multi-site study of healthcare utilization after actionable monogenic findings from clinical sequencing.

As large-scale genomic screening becomes increasingly prevalent, understanding the influence of actionable results on healthcare utilization is key to estimating the potential long-term clinical impact. The eMERGE network sequenced individuals for actionable genes in multiple genetic conditions and returned results to individuals, providers, and the electronic health record. Differences in recommended health services (laboratory, imaging, and procedural testing) delivered within 12 months of return were compared among individuals with pathogenic or likely pathogenic (P/LP) findings to matched individuals with negative findings before and after return of results. Of 16,218 adults, 477 unselected individuals were found to have a monogenic risk for arrhythmia (n = 95), breast cancer (n = 96), cardiomyopathy (n = 95), colorectal cancer (n = 105), or familial hypercholesterolemia (n = 86). Individuals with P/LP results more frequently received services after return (43.8%) compared to before return (25.6%) of results and compared to individuals with negative findings (24.9%; p < 0.0001). The annual cost of qualifying healthcare services increased from an average of $162 before return to $343 after return of results among the P/LP group (p < 0.0001); differences in the negative group were non-significant. The mean difference-in-differences was $149 (p < 0.0001), which describes the increased cost within the P/LP group corrected for cost changes in the negative group. When stratified by individual conditions, significant cost differences were observed for arrhythmia, breast cancer, and cardiomyopathy. In conclusion, less than half of individuals received billed health services after monogenic return, which modestly increased healthcare costs for payors in the year following return.

Trabecular bone ontogeny tracks neural development and life history among humans and non-human primates.

Trabecular bone-the spongy bone inside marrow cavities-adapts to its mechanical environment during growth and development. Trabecular structure can therefore be interpreted as a functional record of locomotor behavior in extinct vertebrates. In this paper, we expand upon traditional links between form and function by situating ontogenetic trajectories of trabecular bone in four primate species into the broader developmental context of neural development, locomotor control, and ultimately life history. Our aim is to show that trabecular bone structure provides insights into ontogenetic variation in locomotor loading conditions as the product of interactions between increases in body mass and neuromuscular maturation. Our results demonstrate that age-related changes in trabecular bone volume fraction (BV/TV) are strongly and linearly associated with ontogenetic changes in locomotor kinetics. Age-related variation in locomotor kinetics and BV/TV is in turn strongly associated with brain and body size growth in all species. These results imply that age-related variation in BV/TV is a strong proxy for both locomotor kinetics and neuromuscular maturation. Finally, we show that distinct changes in the slope of age-related variation in bone volume fraction correspond to the age of the onset of locomotion and the age of locomotor maturity. Our findings compliment previous studies linking bone development to locomotor mechanics by providing a fundamental link to brain development and life history. This implies that trabecular structure of fossil subadults can be a proxy for the rate of neuromuscular maturation and major life history events like locomotor onset and the achievement of adult-like locomotor repertoires.

Post-hospitalization Care Transition Strategies for Patients with Substance Use Disorders: A Narrative Review and Taxonomy.

Hospitalizations represent important opportunities to engage individuals with substance use disorders (SUD) in treatment. For those who engage with SUD treatment in the hospital setting, tailored supports during post-discharge transitions to longitudinal care settings may improve care linkages, retention, and treatment outcomes. We updated a recent systematic review search on post-hospitalization SUD care transitions through a structured review of published literature from January 2020 through June 2023. We then added novel sources including a gray literature search and key informant interviews to develop a taxonomy of post-hospitalization care transition models for patients with SUD. Our updated literature search generated 956 abstracts not included in the original systematic review. We selected and reviewed 89 full-text articles, which yielded six new references added to 26 relevant articles from the original review. Our search of five gray literature sources yielded four additional references. Using a thematic analysis approach, we extracted themes from semi-structured interviews with 10 key informants. From these results, we constructed a taxonomy consisting of 10 unique SUD care transition models in three overarching domains (inpatient-focused, transitional, outpatient-focused). These models include (1) training and protocol implementation; (2) screening, brief intervention, and referral to treatment; (3) hospital-based interdisciplinary consult team; (4) continuity-enhanced interdisciplinary consult team; (5) peer navigation; (6) transitional care management; (7) outpatient in-reach; (8) post-discharge outreach; (9) incentivizing follow-up; and (10) bridge clinic. For each model, we describe design, scope, approach, and implementation strategies. Our taxonomy highlights emerging models of post-hospitalization care transitions for patients with SUD. An established taxonomy provides a framework for future research, implementation efforts, and policy in this understudied, but critically important, aspect of SUD care.

Integrating Buprenorphine for Opioid Use Disorder into Rural, Primary Care Settings.

BACKGROUND: Medications for opioid use disorder (MOUD) including buprenorphine are effective, but underutilized. Rural patients experience pronounced disparities in access. To reach rural patients, the US Department of Veterans Affairs (VA) has sought to expand buprenorphine prescribing beyond specialty settings and into primary care. OBJECTIVE: Although challenges remain, some rural VA health care systems have begun offering opioid use disorder (OUD) treatment with buprenorphine in primary care. We conducted interviews with clinicians, leaders, and staff within these systems to understand how this outcome had been achieved. DESIGN: Using administrative data from the VA Corporate Data Warehouse (CDW), we identified rural VA health care systems that had improved their rate of primary care-based buprenorphine prescribing over the period 2015-2020. We conducted qualitative interviews (n = 30) with staff involved in implementing or prescribing buprenorphine in these systems to understand the processes that had facilitated implementation. PARTICIPANTS: Clinicians, staff, and leaders embedded within rural VA health care systems located in the Northwest, West, Midwest (2), South, and Northeast. APPROACH: Qualitative interviews were analyzed using a mixed inductive/deductive approach. KEY RESULTS: Interviews revealed the processes through which buprenorphine was integrated into primary care, as well as processes insufficient to enact change. Implementation was often initially catalyzed through a targeted hire. Champions then engaged clinicians and leaders one-on-one to "pitch" the case, describe concordance between buprenorphine prescribing and existing goals, and delineate the supportive role that they could provide. Sites were prepared for implementation by developing new clinical teams and redesigning clinical processes. Each of these processes was made possible with the active, instrumental support of leadership. CONCLUSIONS: Results suggest that rural systems seeking to improve buprenorphine accessibility in primary care may need to alter primary care structures to accommodate buprenorphine prescribing, whether through new hires, team development, or clinical redesign.

Internal Medicine Resident Addiction Training at the Veteran's Health Administration: A Qualitative Evaluation of Site Directors' Response to the 2022 ACGME Requirements.

BACKGROUND: Substance use disorders (SUDs) are prevalent in the USA yet remain dramatically undertreated. To address this care gap, the Accreditation Council for Graduate Medical Education (ACGME) approved revisions to the Program Requirements for Graduate Medical Education (GME) in Internal Medicine, effective July 1, 2022, requiring addiction medicine training for all internal medicine (IM) residents. The Veterans Health Administration (VHA) is a clinical training site for many academic institutions that sponsor IM residencies. This focus group project evaluated VHA IM residency site directors' perspectives about providing addiction medical education within VHA IM training sites. OBJECTIVE: To better understand the current state, barriers to, and facilitators of IM resident addiction medicine training at VHA sites. DESIGN: This was a qualitative evaluation based on semi-structured video-based focus groups. PARTICIPANTS: Participants were VHA IM site directors based at a VHA hospital or clinic throughout the USA. APPROACH: Focus groups were conducted using a semi-structured group interview guide. Two investigators coded each focus group independently, then met to create a final adjudicated coding scheme. Thematic analysis was used to identify key themes. KEY RESULTS: Forty-three participants from 38 VHA sites participated in four focus groups (average size: 11 participants). Six themes were identified within four pre-defined categories. Current state of training: most VHA sites offered no formal training in addiction medicine for IM residents. Barriers: addiction experts are often located outside of IM settings, and ACGME requirements were non-specific. Facilitators: clinical champions help support addiction training. Desired next steps: participants desired incentives to train or hire local champions and a pre-packaged didactic curriculum. CONCLUSIONS: Developing competent clinical champions and leveraging VHA addiction specialists from non-IM settings would create more addiction training opportunities for IM trainees at VHA sites. These insights can likely be applied to IM training at non-VHA sites.

Impact of the COVID-19 pandemic on hospital episodes for falls and fractures associated with new-onset disability and frailty in England: a national cohort study.

BACKGROUND: Older people with frailty are at risk of harm from immobility or isolation, yet data about how COVID-19 lockdowns affected them are limited. Falls and fractures are easily measurable adverse outcomes correlated with frailty. We investigated whether English hospital admission rates for falls and fractures varied from the expected trajectory during the COVID-19 pandemic, and how these varied by frailty status. METHODS: NHS England Hospital Episode Statistics Admitted Patient Care data were analysed for observed versus predicted outcome rates for 24 January 2020 to 31 December 2021. An auto-regressive integrated moving average time-series model was trained using falls and fracture incidence data from 2013 to 2018 and validated using data from 2019. Models included national and age-, sex- and region-stratified forecasts. Outcome measures were hospital admissions for falls, fractures, and falls and fractures combined. Frailty was defined using the Hospital Frailty Risk Score. RESULTS: 144,148,915 pre-pandemic hospital admissions were compared with 42,267,318 admissions after pandemic onset. For the whole population, falls and fracture rates were below predicted for the first period of national lockdown, followed by a rapid return to rates close to predicted. Thereafter, rates followed expected trends. For people living with frailty, however, falls and fractures increased above expected rates during periods of national lockdown and remained elevated throughout the study period. Effects of frailty were independent of age. CONCLUSIONS: People living with frailty experienced increased fall and fracture rates above expected during and following periods of national lockdown. These remained persistently elevated throughout the study period.

Post-COVID-19 patients in geriatric rehabilitation substantially recover in daily functioning and quality of life.

BACKGROUND: After an acute infection, older persons may benefit from geriatric rehabilitation (GR). OBJECTIVES: This study describes the recovery trajectories of post-COVID-19 patients undergoing GR and explores whether frailty is associated with recovery. DESIGN: Multicentre prospective cohort study. SETTING: 59 GR facilities in 10 European countries. PARTICIPANTS: Post-COVID-19 patients admitted to GR between October 2020 and October 2021. METHODS: Patients' characteristics, daily functioning (Barthel index; BI), quality of life (QoL; EQ-5D-5L) and frailty (Clinical Frailty Scale; CFS) were collected at admission, discharge, 6 weeks and 6 months after discharge. We used linear mixed models to examine the trajectories of daily functioning and QoL. RESULTS: 723 participants were included with a mean age of 75 (SD: 9.91) years. Most participants were pre-frail to frail (median [interquartile range] CFS 6.0 [5.0-7.0]) at admission. After admission, the BI first steeply increased from 11.31 with 2.51 (SE 0.15, P < 0.001) points per month and stabilised around 17.0 (quadratic slope: -0.26, SE 0.02, P < 0.001). Similarly, EQ-5D-5L first steeply increased from 0.569 with 0.126 points per month (SE 0.008, P < 0.001) and stabilised around 0.8 (quadratic slope: -0.014, SE 0.001, P < 0.001). Functional recovery rates were independent of frailty level at admission. QoL was lower at admission for frailer participants, but increased faster, stabilising at almost equal QoL values for frail, pre-frail and fit patients. CONCLUSIONS: Post-COVID-19 patients admitted to GR showed substantial recovery in daily functioning and QoL. Frailty at GR admission was not associated with recovery and should not be a reason to exclude patients from GR.

Exploratory factor analysis and Rasch analysis to assess the structural validity of the Adult Social Care Outcomes Toolkit Proxy version (ASCOT-Proxy) completed by care home staff.

PURPOSE: Rasch analysis and exploratory factor analysis (EFA) were used to evaluate the structural validity of the ASCOT-Proxy measures completed by staff on behalf of older adults resident in care homes, by comparison to the ASCOT-SCT4, the measure of social care-related quality of life (SCRQoL) from which the ASCOT-Proxy was developed. METHODS: EFA was conducted on the ASCOT-SCT4 and the two ASCOT-Proxy measures (Proxy-Proxy, Proxy-Resident), to determine if they retained the single factor of the original ASCOT-SCT4 measure found in samples of older community-dwelling adults. Rasch analysis was also applied to measures with a single factor structure in the EFA. RESULTS: ASCOT-Proxy-Resident had a single factor structure, as did the original ASCOT-SCT4 (also, found in this analysis when completed by care home staff). The ASCOT-Proxy-Proxy had a two factor structure. Rasch analysis of ASCOT-Proxy-Resident and ASCOT-SCT4 had an acceptable model fit, internal consistency and met the assumptions of unidimensionality and local independence. There was evidence of less than optimal distinguishability at some thresholds between responses, and low frequency of rating of the 'high level needs'. CONCLUSION: The ASCOT-Proxy-Resident is a valid instrument of SCRQoL for older adults resident in care homes, completed by staff proxies. Due to the two-factor structure, which differs from the original ASCOT-SCT4, we do not recommend the use of the ASCOT-Proxy-Proxy measure, although collecting data as part of the ASCOT-Proxy questionnaire may support its feasibility and acceptability. Further qualitative study of how care home staff complete and perceive the ASCOT-Proxy is encouraged for future studies.

Frailty identification and management among Brazilian healthcare professionals: a survey.

BACKGROUND: National and international guidelines on frailty assessment and management recommend frailty screening in older people. This study aimed to determine how Brazilian healthcare professionals (HCPs) identify and manage frailty in practice. METHODS: An anonymous online survey on the assessment and management of frailty was circulated virtually through HCPs across Brazil. RESULTS: Most of the respondants used non-specific criteria such as gait speed (45%), handgrip strength (37.6%), and comprehensive geriatric assessment (33.2%). The use of frailty-specific criteria was lower than 50%. The most frequently used criteria were the Frailty Index (19.1%), Frailty Phenotype (13.2%), and FRAIL (12.5%). Only 43.5% felt confident, and 40% had a plan to manage frailty. In the multivariate-adjusted models, training was the most crucial factor associated with assessing frailty, confidence, and having a management plan (p < 0.001 for all). Those with fewer years of experience were more likely to evaluate frailty (p = 0.009). Being a doctor increased the chance of using a specific tool; the opposite was true for dietitians (p = 0.03). Those who assisted more older people had a higher likelihood of having a plan (p = 0.011). CONCLUSION: Frailty assessment was heterogeneous among healthcare professions groups, predominantly using non-specific criteria. Training contributed to frailty assessment, use of specific criteria, confidence, and having a management plan. This data informs the need for standardized screening criteria and management plans for frailty, in association with increasing training at the national level for all the HCPs who assist older people.

A Nationwide Analysis of the Impact of Socioeconomic Status on Complications and Health Care Utilizations After Total Knee Arthroplasty Using the Area Deprivation Index: Consideration of the Disadvantaged Patient.

BACKGROUND: Socioeconomic status has been demonstrated to be an important prognostic risk factor among patients undergoing total joint arthroplasty. We evaluated patients living near neighborhoods with higher socioeconomic risk undergoing total knee arthroplasty (TKA) and if they were associated with differences in the following: (1) medical complications; (2) emergency department (ED) utilizations; (3) readmissions; and (4) costs of care. METHODS: A query of a national database from 2010 to 2020 was performed for primary TKAs. The Area Deprivation Index (ADI) is a weighted index comprised of 17 census-based markers of material deprivation and poverty. Higher numbers indicate a greater disadvantage. Patients undergoing TKA in zip codes associated with high ADI (90%+) were 1:1 propensity-matched to a comparison group by age, sex, and Elixhauser Comorbidity Index. This yielded 225,038 total patients, evenly matched between cohorts. Outcomes studied included complications, ED utilizations, readmission rates, and 90-day costs. Logistic regression models computed the odds ratios (OR) of ADI on the dependent variables. P values less than .003 were significant. RESULTS: High ADI led to higher rates and odds of any medical complications (11.7 versus 11.0%; OR: 1.05, P = .0006), respiratory failures (0.4 versus 0.3%; OR: 1.28, P = .001), and acute kidney injuries (1.7 versus 1.5%; OR: 1.15, P < .0001). Despite lower readmission rates (2.9 versus 3.5%), high ADI patients had greater 90-day ED visits (4.2 versus 4.0%; OR: 1.07, P = .0008). The 90-day expenditures ($15,066 versus $12,459; P < .0001) were higher in patients who have a high ADI. CONCLUSIONS: Socioeconomically disadvantaged patients have increased complications and ED utilizations. Neighborhood disadvantage may inform health care policy and improve postdischarge care. The socioeconomic status metrics, including ADI (which captures community effects), should be used to adequately risk-adjust or risk-stratify patients so that access to care for deprived regions and patients is not lost. LEVEL OF EVIDENCE: III.

Inconsistent Classification of "Outpatient" Surgeries Leads to Different Outcomes Following Total Hip Arthroplasty in Medicare Beneficiaries: A Critical Analysis.

BACKGROUND: With rising utilization of outpatient total hip arthroplasty (THA) in older patients including Medicare beneficiaries, the objective was to compare differences in definition including (1) patient demographics; (2) lengths of stay (LOS); and (3) outcomes of "outpatient" (stated status) versus "same-day discharge" (SDD) (actual LOS = 0 days) utilizing a nationwide database. METHODS: A national database from 2015 to 2019 was queried for Medicare-aged patients undergoing outpatient THA. Total outpatient THAs (N = 6,072) were defined in one of 2 ways: either "outpatient" by the hospital (N = 2,003) or LOS = 0 days (N = 4,069). Demographics, LOS, discharge destinations, and complications were compared between groups. Logistic regression models computed odds ratios (ORs) for factors leading to complications, readmissions, and nonhome discharges. P values < .008 were significant. RESULTS: Women (OR: 1.19, P = .002), diabetes mellitus (OR: 1.31, P = .003), general anesthesia (OR: 1.24, P = .001), and longer operative times (≥95 minutes) (OR: 1.82, P < .001) were associated with 'outpatient' designation versus SDD. Within the hospital-defined 'outpatient' cohort, 49.1% (983 of 2,003) were discharged the same day (LOS = 0 days), and 21.8% had LOS 2 or more days. The hospital-defined 'outpatient' cohort had greater odds of nonhome discharges (6.3 versus 2.8%; OR: 1.88, P < .001) compared to SDD surgeries. The incidence was higher for any complication among hospital-defined 'outpatient' designated patients compared to SDD (5.5 versus 3.9%, P = .007). CONCLUSIONS: Outpatient surgeries may be misleading and often do not correlate with SDD, as over 20% remain in the hospital 2 or more days. Investigators should quantitatively define the "outpatient" status by actual LOS to allow standardization and results comparison. LEVEL OF EVIDENCE: III.

Preoperative Depression Screening for Primary Total Knee Arthroplasty: An Evaluation of Its Modifiability on Outcomes in Patients Who Have Depression.

INTRODUCTION: Few studies have evaluated preoperative depression screenings in patients who have depression. We studied whether depression screenings before total knee arthroplasty (TKA) were associated with lower: 1) medical complications; 2) emergency department (ED) utilizations and readmissions; 3) implant complications; and 4) costs. METHODS: A nationwide sample from January 1, 2010 to April 30, 2021 was collected using an insurance database. Depression patients were 1:1 propensity-score matched based on those who had (n=29,009) and did not have (n=29,009) pre-operative depression screenings or psychotherapy visits within 3 months of TKA. A case-matched population who did not have depression was compared (n=144,994). A 90-day period was used to compare complications and healthcare utilization and 2-year follow-up for periprosthetic joint infections (PJIs) and implant survivorship. Costs were 90-day reimbursements. Logistic regression models computed odds ratios (OR) of depression screening on dependent variables. P-values less than 0.001 were significant. RESULTS: Patients who did not receive preoperative screening were associated with higher medical complications (18.7 versus 5.2%, OR:4.15, P < 0.0001) and ED utilizations (11.5 versus 3.2%, OR: 3.93, P < 0.0001) than depressed patients who received screening. Patients who had screening had lower medical complications (5.2 versus 5.9%, OR: 0.88, P < 0.0001) and ED utilizations compared to patients who did not have depression (3.2 versus 3.8%, OR: 0.87, P = 0.0001). Two-year PJI incidences (3.0 versus 1.3%, OR: 2.63, P < 0.0001) and TKA revisions (4.3 versus 2.1%, OR: 2.46, P < 0.0001) were greater in depression patients who were not screened preoperatively versus screened patients. Depression patients who had screening had lower PJIs (1.3 versus 1.8%, OR: 0.74, P < 0.0001) compared to non-depressed patients. Reimbursements ($13,949 versus $11,982; P < 0.0001) were higher in depression patients who did not have screening. CONCLUSIONS: Pre-operative screening was associated with improved outcomes in depression patients.

The Association of Dental Caries or Dental Implant Placement Within One Year of Primary Total Hip Arthroplasty on Medical and Implant Complications.

BACKGROUND: Total hip arthroplasty (THA) adverse events among patients who have dental diagnoses remain unclear. We sought to determine if dental caries or dental implant placements increased (1) 90-day medical complications, (2) 90-day readmissions, and (3) 2-year implant-related complications, including periprosthetic joint infections (PJIs) after THA. METHODS: A nationwide database for primary THAs from 2010 to 2021 was queried to compare 3 patient cohorts. Patients who had a history of dental implants or caries within 12 months prior to THA (n = 1,179) or 12 months after THA (n = 1,218) were case-matched to patients who did not have dental history (n = 6,090) by age and comorbidities. Outcomes included 90-day complications, 90-day readmissions, and 2-year implant-related complications. Logistic regression models computed the odds ratios (ORs) of complications and readmissions. P values less than .006 were significant. RESULTS: Patients who had dental caries or implant placement 12 months before or after THA experienced 1.6-fold greater odds of 90-day medical complications compared to case-matched patients. Readmissions within 90 days increased for patients who had a dental history before (11.7% versus 8.3%; OR: 1.49, P < .0001) and after (14.2% versus 8.3%; OR: 1.84, P < .0001) THA compared to case-matched patients. A dental caries diagnosis or dental implant placement within 12 months following THA increased 2-year implant complications compared to case-matched patients (15.2% versus 9.3%; OR: 1.69, P < .0001), including PJIs (5.3% versus 2.8%; OR: 1.98, P < .0001), dislocations (4.4% versus 2.7%; OR: 1.63, P = .002), and THA revisions (3.9% versus 2.5%; OR: 1.61, P = .005). CONCLUSIONS: Dental diagnoses within 12 months of THA are associated with increased medical complications. Dental diagnoses occurring 12 months after THA are associated with greater implant-related complications, including PJIs. Delaying invasive dental procedures for 12 months after THA may be advisable.

Preoperative Opioid Use Disorder is Associated with Longer Length of Stay, Infection Rate, and Healthcare Expenditure Following Primary Shoulder Arthroplasty.

Recent research efforts have focused on the complications and outcomes associated with opioid use disorder (OUD). However, there is a lack of evidence on the associated risks respective to each primary shoulder arthroplasty procedure. After separating patients by total shoulder arthroplasty (TSA) and reverse shoulder arthroplasty (RSA) and matching to controls, our study demonstrated significant association with longer LOS in both groups, higher risk of SSI and PJI in the TSA group, PJI in the RSA group, and higher costs regardless of procedure. Efforts to appropriately recognize OUD, optimize patients pre-operatively, and apply targeted surveillance postoperatively should be made. (Journal of Surgical Orthopaedic Advances 33(2):117-121, 2024).

Exercise as Medicine for People with a Substance Use Disorder: An ACSM Call to Action Statement.

ABSTRACT: Over 20 million Americans are living with a substance use disorder (SUD) and nearly 100,000 die annually from drug overdoses, with a majority involving an opioid. Many people with SUD have co-occurring chronic pain and/or a mental health disorder. Exercise is a frontline treatment for chronic pain and is an effective strategy for reducing depression and anxiety and improving overall mental health. Several studies have shown that exercise improves SUD-related outcomes including abstinence; however, there is limited large-scale randomized clinical trial evidence to inform integration of exercise into practice. In this Call to Action, we aim to raise awareness of the specific issues that should be addressed to advance exercise as medicine in people with SUD including the challenges of co-occurring chronic pain, mental illness, and cardiopulmonary health conditions. In addition, specialized training for exercise professionals and other support staff should be provided on these issues, as well as on the multiple dimensions of stigma that can impair engagement in treatment and overall recovery in people with SUD.

Arrhythmia Variant Associations and Reclassifications in the eMERGE-III Sequencing Study.

BACKGROUND: Sequencing Mendelian arrhythmia genes in individuals without an indication for arrhythmia genetic testing can identify carriers of pathogenic or likely pathogenic (P/LP) variants. However, the extent to which these variants are associated with clinically meaningful phenotypes before or after return of variant results is unclear. In addition, the majority of discovered variants are currently classified as variants of uncertain significance, limiting clinical actionability. METHODS: The eMERGE-III study (Electronic Medical Records and Genomics Phase III) is a multicenter prospective cohort that included 21 846 participants without previous indication for cardiac genetic testing. Participants were sequenced for 109 Mendelian disease genes, including 10 linked to arrhythmia syndromes. Variant carriers were assessed with electronic health record-derived phenotypes and follow-up clinical examination. Selected variants of uncertain significance (n=50) were characterized in vitro with automated electrophysiology experiments in HEK293 cells. RESULTS: As previously reported, 3.0% of participants had P/LP variants in the 109 genes. Herein, we report 120 participants (0.6%) with P/LP arrhythmia variants. Compared with noncarriers, arrhythmia P/LP carriers had a significantly higher burden of arrhythmia phenotypes in their electronic health records. Fifty-four participants had variant results returned. Nineteen of these 54 participants had inherited arrhythmia syndrome diagnoses (primarily long-QT syndrome), and 12 of these 19 diagnoses were made only after variant results were returned (0.05%). After in vitro functional evaluation of 50 variants of uncertain significance, we reclassified 11 variants: 3 to likely benign and 8 to P/LP. CONCLUSIONS: Genome sequencing in a large population without indication for arrhythmia genetic testing identified phenotype-positive carriers of variants in congenital arrhythmia syndrome disease genes. As the genomes of large numbers of people are sequenced, the disease risk from rare variants in arrhythmia genes can be assessed by integrating genomic screening, electronic health record phenotypes, and in vitro functional studies. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier; NCT03394859.

Prevalence of Testing for Human Immunodeficiency Virus, Hepatitis B Virus, and Hepatitis C Virus Among Medicaid Enrollees Treated With Medications for Opioid Use Disorder in 11 States, 2016-2019.

BACKGROUND: Limited information exists about testing for human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) among Medicaid enrollees after starting medication for opioid use disorder (MOUD), despite guidelines recommending such testing. Our objectives were to estimate testing prevalence and trends for HIV, HBV, and HCV among Medicaid enrollees initiating MOUD and examine enrollee characteristics associated with testing. METHODS: We conducted a serial cross-sectional study of 505 440 initiations of MOUD from 2016 to 2019 among 361 537 Medicaid enrollees in 11 states. Measures of MOUD initiation; HIV, HBV, and HCV testing; comorbidities; and demographics were based on enrollment and claims data. Each state used Poisson regression to estimate associations between enrollee characteristics and testing prevalence within 90 days of MOUD initiation. We pooled state-level estimates to generate global estimates using random effects meta-analyses. RESULTS: From 2016 to 2019, testing increased from 20% to 25% for HIV, from 22% to 25% for HBV, from 24% to 27% for HCV, and from 15% to 19% for all 3 conditions. Adjusted rates of testing for all 3 conditions were lower among enrollees who were male (vs nonpregnant females), living in a rural area (vs urban area), and initiating methadone or naltrexone (vs buprenorphine). Associations between enrollee characteristics and testing varied across states. CONCLUSIONS: Among Medicaid enrollees in 11 US states who initiated medications for opioid use disorder, testing for human immunodeficiency virus, hepatitis B virus, hepatitis C virus, and all 3 conditions increased between 2016 and 2019 but the majority were not tested.

Returning integrated genomic risk and clinical recommendations: The eMERGE study.

PURPOSE: Assessing the risk of common, complex diseases requires consideration of clinical risk factors as well as monogenic and polygenic risks, which in turn may be reflected in family history. Returning risks to individuals and providers may influence preventive care or use of prophylactic therapies for those individuals at high genetic risk. METHODS: To enable integrated genetic risk assessment, the eMERGE (electronic MEdical Records and GEnomics) network is enrolling 25,000 diverse individuals in a prospective cohort study across 10 sites. The network developed methods to return cross-ancestry polygenic risk scores, monogenic risks, family history, and clinical risk assessments via a genome-informed risk assessment (GIRA) report and will assess uptake of care recommendations after return of results. RESULTS: GIRAs include summary care recommendations for 11 conditions, education pages, and clinical laboratory reports. The return of high-risk GIRA to individuals and providers includes guidelines for care and lifestyle recommendations. Assembling the GIRA required infrastructure and workflows for ingesting and presenting content from multiple sources. Recruitment began in February 2022. CONCLUSION: Return of a novel report for communicating monogenic, polygenic, and family history-based risk factors will inform the benefits of integrated genetic risk assessment for routine health care.

Trends in Health Service Utilization After Enrollment in an Interdisciplinary Primary Care Clinic for Veterans with Addiction, Social Determinants of Health, or Other Vulnerabilities.

BACKGROUND: Models of interdisciplinary primary care (IPC) may improve upon traditional primary care approaches in addressing addiction and social determinants of health. OBJECTIVE: To compare the trends in health care utilization in the year before and after enrollment in an IPC clinic model, and explore the variations in temporal patterns for patients with histories of high emergency department (ED) use, homelessness, and/or substance use disorders (SUDs). DESIGN AND PARTICIPANTS: Interrupted time series study of utilization among IPC patients. MAIN MEASURES: Quarterly ED, inpatient, primary care, and behavioral health visits were abstracted from administrative data before and after IPC enrollment. Negative binomial segmented regressions estimated changes in health care utilization over time. We used interactions to test for statistical differences in temporal patterns for IPC subgroups. RESULTS: Among IPC patients (n=994), enrollment was associated with overall reductions in ED, inpatient, and behavioral health visits (p's<0.001) and increases in primary care (p's<0.001). Temporal patterns of ED visits, hospitalizations, and behavioral health differed across IPC subgroups (interaction p's<0.001). For those with histories of high ED use (n=265), ED, inpatient, and behavioral health visits decreased after enrollment (level change incidence rate ratios [IRRs]=0.57-0.69) and continued to decline over time (post-enrollment IRRs=0.80-0.88). Among other patients with homeless experiences (n=123), there were initial declines in hospitalizations (IRR=0.33) and overall declines in behavioral health visits (level change and post-enrollment IRRs=0.46-0.94). Other patients with SUDs had initial declines in hospitalizations (IRR=0.46), and post-enrollment declines in rates of specialty SUD visits (IRR=0.92). For all patients, primary care visits initially increased (level change IIRs=2.47-1.34) then gradually declined (post-enrollment IRRs=0.92-0.92). CONCLUSIONS: An IPC model of care reduces acute care and behavioral health service use, particularly for patients with historically high ED use. IPC models may improve patient and system outcomes of vulnerable patient populations with social, clinical, and addiction morbidities.