Piloting a Hospital-Based Rapid Methadone Initiation Protocol for Fentanyl.

OBJECTIVES: Treating acute opioid withdrawal and offering medications for opioid use disorder (OUD) is critical. Hospitalization offers a unique opportunity to rapidly initiate methadone for OUD; however, little clinical guidance exists. This report describes our experience during the first 9 months following introduction of a hospital-based rapid methadone initiation protocol. METHODS: We conducted a retrospective chart review of hospitalized patients with OUD seen by our interprofessional addiction medicine consult service at an urban academic center between December 2022 and August 2023. We identified patients who initiated methadone using the rapid methadone initiation protocol, which includes dose recommendations (maximum 60 mg day 1, 70 mg day 2, 80 mg day 3, 100 mg days 4-7) and strict inclusion and exclusion criteria (end organ failure, arrhythmia, concurrent benzodiazepine or alcohol use, age >65). RESULTS: There were 171 patients that received methadone for OUD during the study period. Of those, 25 patients (15%) received rapid methadone initiation. The average total daily dose of methadone on days 1-7 was 53.0 mg, 69.2 mg, 75.4 mg, 79.5 mg, 87.1 mg, 92.2 mg, and 96.6 mg, respectively. There were no adverse events requiring holding a dose of scheduled methadone, naloxone administration, or transfer to higher level of care. CONCLUSIONS: A rapid methadone initiation protocol for OUD can be implemented in the inpatient setting. Patients up-titrated their methadone doses quicker than with traditional induction methods, and there were no serious adverse events. Appropriate patient selection may be important to avoid harms.

Cost Analysis of Bladder Catheterization After Pelvic Floor Surgery.

IMPORTANCE: Approximately 15-45% of female patients develop transient postoperative urinary retention (POUR) following pelvic reconstructive surgery. Catheter options for bladder drainage include transurethral indwelling catheter (TIC), intermittent self-catheterization (ISC), and suprapubic tube (SPT). Each strategy has risks and benefits; none have been shown to be clinically superior, and to date, no comprehensive comparative economic analysis has been published. OBJECTIVE: The objective of this study was to evaluate the cost of these different bladder catheterization strategies after transvaginal pelvic surgery. STUDY DESIGN: A Canadian universal single-payer (government funded) health system perspective was taken, and a decision tree model was constructed to evaluate the costs associated with each catheterization strategy over a 6-week horizon. Base-cases were set based on recently published clinical data of our institutions, 2 academic tertiary care centers, and based on systematic reviews and meta-analyses. Costs were established in consultation with process stakeholders, in addition to published values. RESULTS: The average cost calculated for management of transient POUR after outpatient pelvic reconstructive surgery was 150.69 CAD (median 154.86; interquartile range [IQR] 131.30-176.33) for TIC, 162.28 CAD (median 164.72; IQR 144.36-189.39) for ISC and 255.67 CAD (median 270.63; IQR 234.32-276.82) for SPT. In costing inpatient surgical data, the average cost calculated was 134.22 CAD (median 123.61; IQR 108.87-151.85) for TIC and 224.61 CAD (median 216.07; IQR 203.86-231.23) for SPT. CONCLUSION: TIC and ISC were found to be significantly less costly than SPT in managing transient POUR following transvaginal pelvic reconstructive surgery.

Activity-driven chromatin organization during interphase: Compaction, segregation, and entanglement suppression.

In mammalian cells, the cohesin protein complex is believed to translocate along chromatin during interphase to form dynamic loops through a process called active loop extrusion. Chromosome conformation capture and imaging experiments have suggested that chromatin adopts a compact structure with limited interpenetration between chromosomes and between chromosomal sections. We developed a theory demonstrating that active loop extrusion causes the apparent fractal dimension of chromatin to cross-over between two and four at contour lengths on the order of 30 kilo-base pairs. The anomalously high fractal dimension [Formula: see text] is due to the inability of extruded loops to fully relax during active extrusion. Compaction on longer contour length scales extends within topologically associated domains (TADs), facilitating gene regulation by distal elements. Extrusion-induced compaction segregates TADs such that overlaps between TADs are reduced to less than 35% and increases the entanglement strand of chromatin by up to a factor of 50 to several Mega-base pairs. Furthermore, active loop extrusion couples cohesin motion to chromatin conformations formed by previously extruding cohesins and causes the mean square displacement of chromatin loci during lag times ([Formula: see text]) longer than tens of minutes to be proportional to [Formula: see text]. We validate our results with hybrid molecular dynamics-Monte Carlo simulations and show that our theory is consistent with experimental data. This work provides a theoretical basis for the compact organization of interphase chromatin, explaining the physical reason for TAD segregation and suppression of chromatin entanglements which contribute to efficient gene regulation.

Characterizing fitness and immune escape of SARS-CoV-2 EG.5 sublineage using elderly serum and nasal organoid.

SARS-CoV-2 Omicron variant has evolved into sublineages. Here, we compared the neutralization susceptibility and viral fitness of EG.5.1 and XBB.1.9.1. Serum neutralization antibody titer against EG.5.1 was 1.71-fold lower than that for XBB.1.9.1. However, there was no significant difference in virus replication between EG.5.1 and XBB.1.9.1 in human nasal organoids and TMPRSS2/ACE2 over-expressing A549 cells. No significant difference was observed in competitive fitness and cytokine/chemokine response between EG.5.1 and XBB.1.9.1. Both EG.5.1 and XBB.1.9.1 replicated more robustly in the nasal organoid from a younger adult than that from an older adult. Our findings suggest that enhanced immune escape contributes to the dominance of EG.5.1 over earlier sublineages. The combination of population serum susceptibility testing and viral fitness evaluation with nasal organoids may hold promise in risk assessment of upcoming variants. Utilization of serum specimens and nasal organoid derived from older adults provides a targeted risk assessment for this vulnerable population.

Bioactive coating provides antimicrobial protection through immunomodulation and phage therapeutics.

Medical implant-associated infections (IAI) is a growing threat to patients undergoing implantation surgery. IAI prevention typically relies on medical implants endowed with bactericidal properties achieved through surface modifications with antibiotics. However, the clinical efficacy of this traditional paradigm remains suboptimal, often necessitating revision surgery and posing potentially lethal consequences for patients. To bolster the existing anti-IAI arsenal, we propose herein a chitosan-based bioactive coating, i.e., ChitoAntibac, which exerts bacteria-inhibitory effects either through immune modulation or phage-directed microbial clearance, without relying on conventional antibiotics. The immuno-stimulating effects and phage-induced bactericidal properties can be tailored by engineering the loading dynamic of macrophage migration inhibitory factor (MIF), which polarizes macrophages towards the proinflammatory subtype (M1) with enhanced bacterial phagocytosis, and Staphylococcal Phage K, resulting in rapid and targeted pathogenic clearance (>99.99%) in less than 8 h. Our innovative antibacterial coating opens a new avenue in the pursuit of effective IAI prevention through immuno-stimulation and phage therapeutics.

Exploring knowledge and implementation gaps of activity-based therapy in centers lacking specialized spinal cord injury services: understanding therapists' perspectives.

STUDY DESIGN: Qualitative exploratory OBJECTIVES: Rehabilitation following spinal cord injury (SCI) is a life-long process involving healthcare in a variety of settings, including facilities lacking SCI-specific services (i.e., non-SCI-specialized centers). Activity-based therapy (ABT) is a neurorestorative approach involving intensive, task-specific movement practice below the injury level. This study explored the existing knowledge, perceptions, and implementation of ABT among physical and occupational therapists working in non-SCI-specialized centers. SETTING: Canadian hospitals and community clinics DESIGN/METHODS: Semi-structured interviews were conducted with Canadian therapists who worked at non-SCI-specialized centers and treated at least one patient with SCI within the last 18 months. The Theoretical Domains Framework was used to develop interview questions that queried therapists' experiences in delivering SCI rehabilitation, their understanding of ABT and experience with its implementation. Interviews were audio-recorded, transcribed verbatim and analyzed using interpretive description. RESULTS: Four physical therapists and three occupational therapists, from diverse settings (i.e., acute care, inpatient rehabilitation, long-term care, outpatient rehabilitation, rural outpatient clinic) participated. Three themes were identified: (1) Available knowledge, resources and therapy time in non-SCI-specialized centers challenge ABT implementation, (2) How current therapy practices in non-SCI-specialized centers align with ABT and (3) Desire for ABT knowledge. Although participants were not familiar with the term ABT, it was identified that they were unknowingly incorporating some components of ABT into their practice. Participants expressed a keenness to learn more about ABT. CONCLUSION: Current knowledge and implementation of ABT in non-SCI-specialized centers is limited. Tailoring ABT education to therapists at non-SCI-specialized centers may increase ABT implementation.

Activity-driven chromatin organization during interphase: compaction, segregation, and entanglement suppression.

In mammalian cells, the cohesin protein complex is believed to translocate along chromatin during interphase to form dynamic loops through a process called active loop extrusion. Chromosome conformation capture and imaging experiments have suggested that chromatin adopts a compact structure with limited interpenetration between chromosomes and between chromosomal sections. We developed a theory demonstrating that active loop extrusion causes the apparent fractal dimension of chromatin to cross over between two and four at contour lengths on the order of 30 kilo-base pairs (kbp). The anomalously high fractal dimension D=4 is due to the inability of extruded loops to fully relax during active extrusion. Compaction on longer contour length scales extends within topologically associated domains (TADs), facilitating gene regulation by distal elements. Extrusion-induced compaction segregates TADs such that overlaps between TADs are reduced to less than 35% and increases the entanglement strand of chromatin by up to a factor of 50 to several Mega-base pairs. Furthermore, active loop extrusion couples cohesin motion to chromatin conformations formed by previously extruding cohesins and causes the mean square displacement of chromatin loci during lag times (Δt) longer than tens of minutes to be proportional to Δt1/3. We validate our results with hybrid molecular dynamics - Monte Carlo simulations and show that our theory is consistent with experimental data. This work provides a theoretical basis for the compact organization of interphase chromatin, explaining the physical reason for TAD segregation and suppression of chromatin entanglements which contribute to efficient gene regulation.

The genome of Litomosoides sigmodontis illuminates the origins of Y chromosomes in filarial nematodes.

Heteromorphic sex chromosomes are usually thought to have originated from a pair of autosomes that acquired a sex-determining locus and subsequently stopped recombining, leading to degeneration of the sex-limited chromosome. The majority of nematode species lack heteromorphic sex chromosomes and determine sex using an X-chromosome counting mechanism, with males being hemizygous for one or more X chromosomes (XX/X0). Some filarial nematode species, including important parasites of humans, have heteromorphic XX/XY karyotypes. It has been assumed that sex is determined by a Y-linked locus in these species. However, karyotypic analyses suggested that filarial Y chromosomes are derived from the unfused homologue of an autosome involved in an X-autosome fusion event. Here, we generated a chromosome-level reference genome for Litomosoides sigmodontis, a filarial nematode with the ancestral filarial karyotype and sex determination mechanism (XX/X0). By mapping the assembled chromosomes to the rhabditid nematode ancestral linkage (or Nigon) elements, we infer that the ancestral filarial X chromosome was the product of a fusion between NigonX (the ancestrally X-linked element) and NigonD (ancestrally autosomal). In the two filarial lineages with XY systems, there have been two independent X-autosome chromosome fusion events involving different autosomal Nigon elements. In both lineages, the region shared by the neo-X and neo-Y chromosomes is within the ancestrally autosomal portion of the X, confirming that the filarial Y chromosomes are derived from the unfused homologue of the autosome. Sex determination in XY filarial nematodes therefore likely continues to operate via the ancestral X-chromosome counting mechanism, rather than via a Y-linked sex-determining locus.

Healthcare utilization for asthma exacerbation among children of migrant and seasonal farmworkers.

Latino children of Migrant and Seasonal Farmworkers (MSFWs) with asthma are at risk for poor health outcomes due to medical access barriers. We compared differences in acute care utilization for asthma exacerbations among migrant and non-migrant Latino and non-Hispanic white (NHW) children at U.S. community health centers. A retrospective observational study utilizing electronic health record data from the ADVANCE Clinical Research Network of United States community health centers included 13,423 children ages 3-17 with a primary care visit between 2005 and 2017 from eight states. Emergency department (ED) and hospitalization data came from Oregon Medicaid claims. Outcomes included acute clinic visits, ED visits, and hospitalizations for asthma exacerbation. Regression analyses adjusted for patient-level covariates. Latino children had higher odds of acute clinic visits for asthma exacerbation compared to NHW children (MSFW odds ratio [OR] = 1.17, 95 % CI = 1.03-1.33; without migrant status OR = 1.13, 95 % CI = 1.03-1.23). MSFW children using Oregon Medicaid had fewer ED visits (rate ratio [RR] = 0.72, 95 % CI = 0.52-0.99) and hospitalizations (RR = 0.47, 95 % CI = 0.26-0.86) compared to NHW children. Increased community health center visits may help mitigate disparities in acute asthma care for MSFW children.

Associations between stimulant use and return to illicit opioid use following initiation onto medication for opioid use disorder.

AIM: The aim of this study was to estimate how ongoing stimulant use affects return to illicit opioid use after initiation onto medication for opioid use disorder (MOUD). DESIGN: This was a secondary analysis of pooled data from two clinical trials comparing buprenorphine (BUP-NX) and extended-release naltrexone (XR-NTX). SETTING: Thirteen opioid treatment programs and HIV clinics across 10 states in the United States from 2014 to 2019 took part in this study. PARTICIPANTS: A total of 528 participants who initiated MOUD as part of trial participation were included. Nearly half (49%) were between 30 and 49 years of age, 69% were male and 66% were non-Hispanic White. MEASUREMENTS: The primary outcome was first self-reported day of non-prescribed opioid use following MOUD initiation, and the exposure of interest was daily stimulant use (methamphetamine, amphetamines or cocaine). Both were defined using time-line follow-back. Among participants reporting at least 1 day of illicit opioid use, we also examined relapse to ongoing use, defined as (1) 7 days of continuous opioid use or (2) 4 consecutive weeks with self-reported opioid use, one or more positive urine drug screens (UDS) for opioids or one or more missing UDS. FINDINGS: Forty-seven per cent of participants reported stimulant use following MOUD initiation, 58% returned to illicit opioid use and 66% of those relapsed to ongoing use. Stimulant use was strongly associated with increased risk of misusing opioids after MOUD initiation when measured daily [adjusted hazard ratio (aHR) = 9.23, 95% confidence interval (CI) = 6.80-12.50, P < 0.001] and over a 7-day period (aHR = 1.27 for each additional day, CI = 1.18-1.37, P < 0.001). Using stimulants weekly or more often was associated with increased likelihood of relapse to ongoing opioid use compared with less than weekly or no stimulant use (adjusted odds ratio = 2.30, CI = 1.05-5.39, P = 0.044). CONCLUSIONS: People initiated on medication for opioid use disorder who subsequently use stimulants appear to be more likely to return to and continue using non-prescribed opioids compared with those without stimulant use. The association appears to be stronger among patients who initiate buprenorphine compared with those who initiate extended-release naltrexone.

Autoantibodies against angiotensin-converting enzyme 2 (ACE2) after COVID-19 infection or vaccination.

Autoantibodies against angiotensin-converting enzyme 2 (ACE2) are frequently reported in patients during coronavirus disease 2019 (COVID-19) with evidence for a pathogenic role in severe infection. However, little is known of the prevalence or clinical significance of ACE2 autoantibodies in late convalescence or following COVID-19 vaccination. In this study, we measured ACE2 autoantibodies in a cohort of 182 COVID-19 convalescent patients, 186 COVID-19 vaccine recipients, and 43 adolescents with post-mRNA vaccine myopericarditis using two ACE2 enzymatic immunoassays (EIAs). ACE2 IgM autoantibody EIA median optical densities (ODs) were lower in convalescent patients than pre-COVID-19 control samples with only 2/182 (1.1%) convalescents testing positive. Similarly, only 3/182 (1.6%) convalescent patients tested positive for ACE2 IgG, but patients with history of moderate-severe COVID-19 tended to have significantly higher median ODs than controls and mild COVID-19 patients. In contrast, ACE2 IgG antibodies were detected in 10/186 (5.4%) COVID-19 vaccine recipients after two doses of vaccination. Median ACE2 IgG EIA ODs of vaccine recipients were higher than controls irrespective of the vaccine platform used (inactivated or mRNA). ACE2 IgG ODs were not correlated with surrogate neutralizing antibody levels in vaccine recipients. ACE2 IgG levels peaked at day 56 post-first dose and declined within 12 months to baseline levels in vaccine recipients. Presence of ACE2 antibodies was not associated with adverse events following immunization including myopericarditis. One convalescent patient with ACE2 IgG developed Guillain-Barre syndrome, but causality was not established. ACE2 autoantibodies are observed in COVID-19 vaccine recipients and convalescent patients, but are likely innocuous.

Humoral and cellular immunity against different SARS-CoV-2 variants in patients with chronic kidney disease.

Chronic kidney disease (CKD) patients are at higher risk of severe COVID-19. Humoral and cellular immunity from prior infection or vaccination are important for protection, but the neutralizing antibody (nAb) response against SARS-CoV-2 variants is impaired. We investigated the variant-specific nAb and T cell immunity among CKD patients. Adult CKD patients were recruited between August and October 2022. nAb against the SARS-CoV-2 (ancestral strains and four Omicron sublineages) and T cell response were measured using the live virus neutralization assay and interferon-gamma release assay (IGRA). The correlation between nAb/T-cell response and subsequent infection after recruitment were also determined. Among the 88 recruited patients, 95.5% had prior infection or had completed the primary vaccine series. However, only 77.3% had detectable nAb against at least one SARS-CoV-2 strains, 59.1% tested positive in IGRA, and 52.3% had detectable nAb and tested positive in the IGRA. The nAb geometic mean titers (GMTs) against XBB.1, BA.5 and BA.2.3.20 were significantly lower than those against BA.2 and ancestral strain. Prior SARS-CoV-2 infection was associated with elevated nAb and T cell response. More kidney transplant recipients (KTRs) showed absent nAb and T cell response (36.8% vs. 10.1%), despite a higher prevalence of vaccine booster in this population (94.7% vs. 50.7%). Lower levels of nAb titer and T cell response were significantly associated with subsequent infection. A considerable proportion of CKD patients, especially KTRs, showed absence of humoral and cellular protective immunity against SARS-CoV-2. Strategies to improve immunogenicity in this population are urgently needed.

Ambulatory Intensive Care for Medically Complex Patients at a Health Care Clinic for Individuals Experiencing Homelessness: The SUMMIT Randomized Clinical Trial.

Importance: Intensive primary care interventions have been promoted to reduce hospitalization rates and improve health outcomes for medically complex patients, but evidence of their efficacy is limited. Objective: To assess the efficacy of a multidisciplinary ambulatory intensive care unit (A-ICU) intervention on health care utilization and patient-reported outcomes. Design, Setting, and Participants: The Streamlined Unified Meaningfully Managed Interdisciplinary Team (SUMMIT) randomized clinical trial used a wait-list control design and was conducted at a health care clinic for patients experiencing homelessness in Portland, Oregon. The first patient was enrolled in August 2016, and the last patient was enrolled in November 2019. Included patients had 1 or more hospitalizations in the prior 6 months and 2 or more chronic medical conditions, substance use disorder, or mental illness. Data analysis was performed between March and May 2021. Intervention: The A-ICU included a team manager, a pharmacist, a nurse, care coordinators, social workers, and physicians. Activities included comprehensive 90-minute intake, transitional care coordination, and flexible appointments, with reduced panel size. Enhanced usual care (EUC), consisting of team-based primary care with access to community health workers and mental health, addiction treatment, and pharmacy services, served as the comparator. Participants who received EUC joined the A-ICU intervention after 6 months. Main Outcomes and Measures: The main outcome was the difference in rates of hospitalization (primary outcome), emergency department (ED) visits, and primary care physician (PCP) visits per person over 6 months (vs the prior 6 months). Patient-reported outcomes included changes in patient activation, experience, health-related quality of life, and self-rated health at 6 months (vs baseline). We performed an intention-to-treat analysis using a linear mixed-effects model with a random intercept for each patient to examine the association between study group and outcomes. Results: This study randomized 159 participants (mean [SD] age, 54.9 [9.8] years) to the A-ICU SUMMIT intervention (n = 80) or to EUC (n = 79). The majority of participants were men (102 [65.8%]) and most were White (121 [76.1%]). A total of 64 participants (41.0%) reported having unstable housing at baseline. Six-month hospitalizations decreased in both the A-ICU and EUC groups, with no difference between them (mean [SE], -0.6 [0.5] vs -0.9 [0.5]; difference, 0.3 [95% CI, -1.0 to 1.5]). Emergency department use did not differ between groups (mean [SE], -2.0 [1.0] vs 0.9 [1.0] visits per person; difference, -1.1 [95% CI, -3.7 to 1.6]). Primary care physician visits increased in the A-ICU group (mean [SE], 4.2 [1.6] vs -2.0 [1.6] per person; difference, 6.1 [95% CI, 1.8 to 10.4]). Patients in the A-ICU group reported improved social functioning (mean [SE], 4.7 [2.0] vs -1.1 [2.0]; difference, 5.8 [95% CI, 0.3 to 11.2]) and self-rated health (mean [SE], 0.7 [0.3] vs -0.2 [0.3]; difference, 1.0 [95% CI, 0.1 to 1.8]) compared with patients in the EUC group. No differences in patient activation or experience were observed. Conclusions and Relevance: The A-ICU intervention did not change hospital or ED utilization at 6 months but increased PCP visits and improved patient well-being. Longer-term studies are needed to evaluate whether these observed improvements lead to eventual changes in acute care utilization. Trial Registration: ClinicalTrials.gov Identifier: NCT03224858.

Screening for Hepatitis C Among Community Health Center Patients by Ethnicity and Language Preference.

Introduction: Hepatitis C virus is associated with high morbidity and mortality-chronic liver disease is a leading cause of death among Latinos in the U.S. Screening for hepatitis C virus in community health center settings, which serve a disproportionate percentage of Latinos, is essential to eradicating hepatitis C virus infection. We assessed hepatitis C virus screening disparities in adults served by community health centers by ethnicity and language preference. Methods: This was an observational cohort study (spanning 2013-2017) of adults born in 1945-1965 in the Accelerating Data Value Across a National Community Health Center Network electronic health record data set. Our exposure of interest was race/ethnicity and language preference (non-Hispanic White, Latino English preferred, Latino Spanish preferred). Our primary outcome was the relative hazard of hepatitis C virus screening, estimated using multivariate Cox proportional hazards regression. Results: A total of 182,002 patients met the study criteria and included 60% non-Hispanic Whites, 29% Latino Spanish preferred, and 11% Latino English preferred. In total, 9% received hepatitis C virus screening, and 2.4% were diagnosed with hepatitis C virus. Latino English-preferred patients had lower rates of screening than both non-Hispanic Whites and Latino Spanish preferred (5.5% vs 9.4% vs 9.6%, respectively). Latino English preferred had lower hazards of hepatitis C virus screening than non-Hispanic Whites (adjusted hazard ratio=0.56, 95% CI=0.44, 0.72), and Latino Spanish preferred had similar hazards of hepatitis C virus screening (adjusted hazard ratio=1.11, 95% CI=0.88, 1.41). Conclusions: We found that in a large community health center network, adult Latinos who preferred English had lower hazards of hepatitis C virus screening than non-Hispanic Whites, whereas Latinos who preferred Spanish had hazards of screening similar to those of non-Hispanic Whites. The overall prevalence of hepatitis C virus screening was low. Further work on the role of language preference in hepatitis C virus screening is needed to better equip primary care providers to provide this recommended preventive service in culturally relevant ways.

The IL-17A-neutrophil axis promotes epithelial cell IL-33 production during nematode lung migration.

The early migratory phase of pulmonary helminth infections is characterized by tissue injury leading to the release of the alarmin interleukin (IL)-33 and subsequent induction of type 2 immune responses. We recently described a role for IL-17A, through suppression of interferon (IFN)-γ, as an important inducer of type 2 responses during infection with the lung-migrating rodent nematode Nippostrongylus brasiliensis. Here, we aimed to investigate the interaction between IL-17A and IL-33 during the early lung migratory stages of N. brasiliensis infection. In this brief report, we demonstrate that deficiency of IL-17A leads to impaired IL-33 expression and secretion early in infection, independent of IL-17A suppression of IFN-γ. Neutrophil-depletion experiments, which dramatically reduce lung injury, revealed that neutrophils are primarily responsible for the IL-17A-dependent release of IL-33 into the airways. Taken together, our results reveal an IL-17A-neutrophil-axis that can drive IL-33 during helminth infection, highlighting an additional pathway by which IL-17A regulates pulmonary type 2 immunity.

Finding the Optimal Resistance Training Intensity for Your Bones: Protocol for a Randomized Controlled Trial.

OBJECTIVE: The purpose of this trial is to evaluate the effect of twice-weekly, moderate-to-high intensity progressive resistance training (PRT) for 1 year on lumbar spine bone mineral density (BMD) in individuals with low BMD, compared to attention control. Secondary analyses will examine if resistance training improves other health outcomes; if high intensity is more effective than moderate intensity resistance training for all outcomes; the cost of intervention versus benefit; the willingness to pay; and harms. METHODS: For this study, 324 men or postmenopausal women aged ≥50 years with a femoral neck, total hip, or lumbar spine BMD T-score of ≤-1, or a Fracture Risk Assessment Tool probability of ≥20% for major osteoporotic fracture or ≥ 3% for hip fracture are being recruited to participate in a randomized controlled trial with 1:1:1 randomization. Participants will be stratified by site (3 centers) to twice-weekly, supervised PRT at moderate intensity (about 10 repetitions maximum), to high intensity PRT (≤6 repetitions maximum), or to a home posture and balance exercise program (attention control) for 1 year (resistance training to comparator allocation ratio of 2:1). The primary outcome is lumbar spine BMD via dual-energy X-ray absorptiometry. Secondary outcomes include trabecular bone score, proximal femur and total hip BMD and structure, bone-free and appendicular lean mass, physical functioning, falls, fractures, glucose metabolism, cost per life-year gained, adverse events, and quality of life. Between-group differences will be tested in intention-to-treat and per-protocol analyses using analysis of covariance, chi-square tests, or negative binomial or logistic regression, adjusting for site and baseline values. IMPACT: The Finding the Optimal Resistance Training Intensity For Your Bones trial will support decision making on resistance training for people at risk of fracture.

The Complexity of Transferring Remote Monitoring and Virtual Care Technology Between Countries: Lessons From an International Workshop.

International deployment of remote monitoring and virtual care (RMVC) technologies would efficiently harness their positive impact on outcomes. Since Canada and the United Kingdom have similar populations, health care systems, and digital health landscapes, transferring digital health innovations between them should be relatively straightforward. Yet examples of successful attempts are scarce. In a workshop, we identified 6 differences that may complicate RMVC transfer between Canada and the United Kingdom and provided recommendations for addressing them. These key differences include (1) minority groups, (2) physical geography, (3) clinical pathways, (4) value propositions, (5) governmental priorities and support for digital innovation, and (6) regulatory pathways. We detail 4 broad recommendations to plan for sustainability, including the need to formally consider how highlighted country-specific recommendations may impact RMVC and contingency planning to overcome challenges; the need to map which pathways are available as an innovator to support cross-country transfer; the need to report on and apply learnings from regulatory barriers and facilitators so that everyone may benefit; and the need to explore existing guidance to successfully transfer digital health solutions while developing further guidance (eg, extending the nonadoption, abandonment, scale-up, spread, sustainability framework for cross-country transfer). Finally, we present an ecosystem readiness checklist. Considering these recommendations will contribute to successful international deployment and an increased positive impact of RMVC technologies. Future directions should consider characterizing additional complexities associated with global transfer.

Methamphetamine use and utilization of medications for opioid use disorder among rural people who use drugs.

BACKGROUND: Methamphetamine use is common among persons with opioid use disorder. This study evaluated associations between methamphetamine use and treatment with agonist medications for opioid use disorder (MOUD, specifically buprenorphine, and/or methadone) in U.S. rural communities. METHODS: The Rural Opioid Initiative (ROI) is a consortium spanning 10 states and 65 rural counties that included persons who reported past 30-day use of opioids and/or injection drug use between 1/2018 and 3/2020. Analyses were restricted to participants who had ever used opioids and had data on past 30-day methamphetamine use. Multivariable models examined the relationship between methamphetamine use and utilization of agonist MOUD. RESULTS: Among 2899 participants, 2179 (75.2%) also reported recent methamphetamine use. Persons with methamphetamine use compared to those without were younger, more likely to have injected drugs, be unhoused, criminal justice involved, and less likely to have health insurance. Adjusted for age, sex, race, and study site, recent methamphetamine use was associated with lower relative odds of past 30-day methadone treatment (aOR=0.66; 95% CI: 0.45-0.99) and fewer methadone treatment days (aIRR=0.76; 0.57-0.99), but not past 30-day buprenorphine receipt (aOR=0.90; 0.67-1.20), buprenorphine treatment days in past 6 months: aIRR=0.88; 0.69-1.12) or perceived inability to access buprenorphine (aOR=1.12; 0.87-1.44) or methadone (aOR=1.06; 0.76-1.48). CONCLUSION: Methamphetamine use is common among persons who use opioids in rural U.S. areas and negatively associated with current treatment and retention on methadone but not buprenorphine. Future studies should examine reasons for this disparity and reduce barriers to methadone for persons who use opioids and methamphetamine.

The role of language in mammography orders among low-income Latinas over a 10-year period.

INTRODUCTION: Latinas in the United States have higher mortality from breast cancer, but longitudinal studies of mammography ordering (a crucial initial step towards screening) in primary care are lacking. METHODS: We conducted an analysis of mammography order rates in Latinas (by language preference) and non-Latina white women (N = 181,755) over a > 10 year period in a multi-state network of community health centers (CHCs). We evaluated two outcomes (ever having a mammogram order and annual rate of mammography orders) using generalized estimating equation modeling. RESULTS: Approximately one-third of all patients had ever had a mammogram order. Among those receiving mammogram orders, English-preferring Latinas had lower mammogram order rates than non-Hispanic white women (RR = 0.92, 95% CI = 0.89-0.95). Spanish-preferring Latinas had higher odds of ever having a mammogram ordered than non-Hispanic whites (odds ratio = 2.12, 95% CI = 2.06-2.18) and, if ever ordered, had a higher rate of annual mammogram orders (rate ratio = 1.53, 95% CI = 1.50-1.56). CONCLUSION: These findings suggest that breast cancer detection barriers in low-income Latinas may not stem from a lack of orders in primary care, but in the subsequent accessibility of receiving ordered services.

A cost-utility analysis of thrombopoietin receptor agonists for treating pediatric immune thrombocytopenia purpura after failure of first-line therapies.

BACKGROUND: Thrombopoietin receptor agonists (TPO-RAs) have emerged as a recommended treatment for children with persistent and/or chronic immune thrombocytopenic purpura (ITP). The purpose of this study was to evaluate the cost-effectiveness of TPO-RAs relative to treatment without TPO-RAs (non-TPO-RAs/usual care) for ITP in children who do not respond to first-line therapy and in whom splenectomy is not recommended in Ontario, Canada, from a hospital payer perspective. PROCEDURE: A 2-year Markov model with an embedded decision tree was used. Data on medications used, dose, response rate, bleeding, and emergency treatment events were collected from the Hospital for Sick Children in Toronto. The health outcomes were described in quality-adjusted life-years (QALYs). Health-state utilities were derived from the peer-reviewed literature. Scenario analyses, deterministic, and probabilistic sensitivity analyses were conducted. Economic costs were measured in 2021 Canadian dollars ($1.00 = US$0.80) RESULTS: TPO-RAs are estimated to result in an increased cost of $27,118 and a QALY gain of 0.21 compared to non-TPO-RAs over a 2-year horizon, resulting in an incremental cost-effectiveness ratio (ICER) of $129,133. In a 5-year scenario analysis, the ICER fell to $76,403. In the probabilistic sensitivity analysis, TPO-RAs exhibit a 40.0% probability of being cost-effective at a conventional ($100,000) willingness-to-pay threshold per QALY gained. CONCLUSIONS: Further assessment of the long-term efficacy of TPO-RAs is warranted to obtain more precise long-term estimates. As the costs of TPO-RAs decline with the introduction of generic formulations, TPO-RAs may be increasingly cost-effective.