Excess Death Rates by State During the COVID-19 Pandemic: United States, 2020‒2023.

Objectives. To estimate state-level excess death rates during 2020 to 2023 and examine differences by region and partisan orientation. Methods. We modeled death and population counts from the Centers for Disease Control and Prevention to estimate excess death rates for the United States, 9 census divisions, and 50 states. We compared excess death rates for states with different partisan orientations, measured by the party of the seated governor and the level of partisan representation in state legislatures. Results. The United States experienced 1 277 697 excess deaths between March 2020 and July 2023. Almost 90% of these deaths were attributed to COVID-19, and 51.5% occurred after vaccines were available. The highest excess death rates first occurred in the Northeast and then shifted to the South and Mountain states. Between weeks ending June 20, 2020, through March 19, 2022, excess death rates were higher in states with Republican governors and greater Republican representation in state legislatures. Conclusions. Excess death rates during the COVID-19 pandemic varied considerably across the US states and were associated with partisan representation in state government, although the influence of confounding variables cannot be excluded. (Am J Public Health. Published online ahead of print July 18, 2024:e1-e10. https://doi.org/10.2105/AJPH.2024.307731).

Screening for Unhealthy Alcohol Use Among Patients With Multiple Chronic Conditions in Primary Care.

Introduction: Unhealthy alcohol use increases the risk for and exacerbation of chronic health conditions. As such, screening, prevention, and management of unhealthy alcohol use is especially critical to improving health outcomes for patients with multiple chronic health conditions. It is unclear to what extent multiple chronic condition status is a barrier to screening for unhealthy alcohol use in the primary care setting. The authors hypothesized that patients with multiple chronic conditions would be at lower odds of being screened for unhealthy alcohol use than patients without multiple chronic conditions. Methods: The authors performed a secondary analysis of electronic health record data for patients from 67 primary care practices in Virginia (2020-2023). Using the Center for Medicare and Medicaid Services' chronic disease framework, they classified patients by multiple chronic condition status: no multiple chronic conditions, physical multiple chronic conditions, mental health multiple chronic conditions, and physical and mental health multiple chronic conditions. They used multiple logistic regressions with an added practice-level random effect to analyze the relationship between multiple chronic condition status and the odds of receiving an alcohol-related assessment, of being screened for unhealthy alcohol use with a U.S. Preventive Services Task Force-recommended instrument, and of screening positive for unhealthy alcohol use within the past 2 years. Results: Within a final cohort of n=11,789, a total of 6,796 patients (58%) had multiple chronic conditions (29% physical multiple chronic conditions, 4% mental health multiple chronic conditions, and 25% physical and mental health multiple chronic conditions). In all, 69% of patients were screened for unhealthy alcohol use, whereas 16% were screened with a U.S. Preventive Services Task Force-recommended instrument, and 7% screened positive for unhealthy alcohol use. Patients with physical and mental health multiple chronic conditions had 0.9 times lower odds of receiving any screening for unhealthy alcohol use than those with no multiple chronic conditions (95% CI=0.8, 1.0; p=0.0240), whereas patients with only physical multiple chronic conditions or only mental health multiple chronic conditions had similar odds. There was no difference in the odds of being screened with a U.S. Preventive Services Task Force-recommended instrument on the basis of multiple chronic condition status. Patients with mental health multiple chronic conditions and physical and mental health multiple chronic conditions had 1.8 and 1.5 times greater odds of screening positive for unhealthy alcohol use, respectively (95% CI=1.3, 2.7; p=0.0014 and 95% CI=1.2, 1.8; p=0.0003). Conclusions: Although patients with chronic mental health conditions were more likely to screen positive for unhealthy alcohol use than patients without multiple chronic conditions, Virginia primary care patients with physical and mental health multiple chronic conditions were less likely to receive an alcohol-related assessment during the past 2 years. Given the overall modest rate of screening with a U.S. Preventive Services Task Force-recommended instrument, further efforts are needed to create the conditions for high-quality alcohol-related preventive service delivery in primary care, particularly for patients with high complexity and/or mental health conditions.

Quality Gap in Long-Stay Antipsychotic Quality Measure Performance Widens Over the Pandemic, Reversing Past Gains.

The Centers for Medicare & Medicaid Services (CMS) grades nursing home performance in antipsychotic prescribing quarterly, publishing findings as a quality measure. While scores have improved since 2011, marked performance variation between facilities persists. To assess quality gap changes between best- and worst-performing deciles, we compared quarterly prescribing changes between these groups pre-pandemic (April 2011 to March 2020) and during the pandemic (April 2020 to March 2022). Antipsychotic quality measure scores, improving pre-pandemic, deteriorated during the pandemic. The pre-pandemic quality gap between the best- and worst-performing deciles narrowed as the worst-performing decile improved faster than the best-performing decile. During the pandemic, the quality gap widened as the worst-performing decile relapsed more than the best-performing decile (p < .0001). The pandemic disrupted quality performance gains and compounded disparities between facilities. A better understanding of the factors allowing high performers to weather pandemic stressors better than poor performers may reveal opportunities to improve nursing home quality and equity for all residents.

School Closure and Child Maltreatment During the COVID-19 Pandemic.

It is not known how school closure affected child maltreatment. We conducted a retrospective cohort, linear mixed-models study of 133 counties (comprising 8,582,479 children) in Virginia between 2018 and 2021. Exposure was the opening of schools at least 2 days a week. Outcomes were referrals and incidence of child maltreatment reported to the Department of Social Services. In 2020-2021, there were descriptively more referrals (in-person: 50.9 per 10,000 [95% CI: 47.9, 54.0]; virtual: 45.8 per 10,000 [95% CI: 40.7, 50.9]) and incidence (in-person: 3.7 per 10,000 [95% CI: 3.3, 4.2]; virtual: 2.9 per 10,000 [95% CI: 2.3, 3.5]) of child maltreatment in counties with in-person schooling, though these differences did not reach statistical significance. The referral rate variations (between pandemic and pre-pandemic eras) of counties with in-person schooling was significantly greater than rate changes in counties with virtual schooling during the summer period. There were no differences in incidence in any quarter. Higher poverty within a county was associated with both higher referrals and incidence. Our findings suggest that child maltreatment is driven primarily by underlying differences in counties (namely, poverty) rather than the type of schooling children receive.

Increased Organizational Stress in Primary Care: Understanding the Impact of the COVID-19 Pandemic, Medicaid Expansion, and Practice Ownership.

BACKGROUND: Primary care is the foundation of health care, resulting in longer lives and improved equity. Primary care was the frontline of the COVID-19 pandemic public response and essential for access to care. Yet primary care faces substantial structural and systemic challenges. As part of a longitudinal analysis to track the capacity and health of primary care, we surveyed every primary care practice in Virginia in 2018 and again in 2022. METHODS: Surveys were emailed or mailed up to 6 times and nonresponders received a phone call. Questions assessed organizational characteristics, scope of care, capacity, and organizational stress in the prior year. From respondents, 39 clinicians, nurses, staff, administrators, and practice managers were interviewed. RESULTS: 526 out of 2296 primary care practices (23% response rate) completed the survey, with broad representation across geography, ownership, and payer mix. Compared with 2018, in 2022 there were increases in practices owned by health systems (25% vs 43%, P < .0001) and average percent of patients with Medicaid per practice (12% vs 22%, P < .0001). The percent of practices reporting any major stressor increased from 34% to 53% (P < .0001). The main increased stress was losing a clinician, with 13% of practices in 2018 versus 42% in 2022 reporting losing a clinician (P < .0001). CONCLUSIONS: Primary care practices are resilient and continue to serve their communities, including a broad scope of services and care for underserved people. However, the COVID-19 pandemic caused significant stress. With an increase in clinicians leaving clinical practice, we anticipate worsening access to primary care.

Neighborhood Predictors of Poor Prenatal Care and Well-Child Visit Attendance.

PURPOSE: Women and children continue to miss preventive visits. Which neighborhood factors predict inadequate prenatal care (PNC) and well-child visit (WCV) attendance remain unclear. DESCRIPTION: In a retrospective case-control study at Virginia Commonwealth University Health System, mothers with less than 50% adherence or initiation after 5 months gestation were eligible as cases and those with ≥ 80% adherence and initiation before 5 months were eligible as controls. Children in the lowest quintile of adherence were eligible as cases and those with ≥ 80% of adherence were eligible as controls. Cases and controls were randomly selected at a 1:2 ratio and matched on birth month. Covariates were derived from the 2018 American Community Survey. A hotspot was defined as a zip code tabulation area (ZCTA) with a proportion of controls less than 0.66. ZCTAs with fewer than 5 individuals were excluded. Weighted quantile regression was used to determine which covariates were most associated with inadequate attendance. ASSESSMENT: We identified 38 and 35 ZCTAs for the PNC and WCV analyses, respectively. Five of 11 hotspots for WCV were also hotspots for PNC. Education and income predicted 51% and 34% of the variation in missed PNCs, respectively; language, education and transportation difficulties explained 33%, 29%, and 17% of the variation in missed WCVs, respectively. Higher proportions of Black residents lived in hotspots of inadequate PCV and WCV attendance. CONCLUSION: Neighborhood-level factors performed well in predicting inadequate PCV and WCV attendance. The disproportionate impact impact of inadequate PCV and WCV in neighborhoods where higher proportions of Black people lived highlights the potential influence of systemic racism and segregation on healthcare utilization.

Fibrosis-4 (FIB-4) index as a predictor for mechanical ventilation and 30-day mortality across COVID-19 variants.

Background: The Fibrosis-4 (FIB-4) index, a simple index that includes age, liver enzymes, and platelet count has been studied as a tool to identify patients at a risk of requiring mechanical ventilation due to its high negative predictive value. It is unknown if FIB-4 remains useful to predict the severity of respiratory disease requiring mechanical ventilation amongst new Coronavirus disease 2019 (COVID-19) variants and whether a relationship also exists between FIB-4 and 30-day mortality. The main objective was to determine if FIB-4 can predict mechanical ventilation requirements and 30-day mortality from COVID-19 across variants including Alpha, Delta, and Omicron. Methods: This was a population-based, retrospective cohort analysis of 232,364 hospitalized patients in the National COVID-19 Cohort Collaborative between the age of 18-90 who tested positive for COVID-19 between April 27, 2020 and June 25, 2022. The primary outcome was association between FIB-4 and need for mechanical ventilation. Secondary measures included the association of FIB-4 with 30-day mortality. Results: A FIB-4 > 2.67 had 1.8 times higher odds of requiring mechanical ventilation across all variants of COVID-19 (OR 1.81; 95% CI: [1.76, 1.86]). The area under the ROC curve showed high diagnostic accuracy with values ranging between 0.79 (Omicron wave) and 0.97 (delta wave). Increased FIB-4 was associated with 30-day mortality across the variates. Conclusion: The FIB-4 was consistently associated with both increased utilization of mechanical ventilation and 30-day mortality among COVID-19 patients across all waves in both adjusted and unadjusted models. This provides a simple tool for risk-stratification for front-line health care professionals.

INTRAVENOUS VITAMIN C SUPPLEMENTATION IN ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANT RECIPIENTS: SALUTARY IMPACT ON CLINICAL OUTCOMES.

Intravenous (IV) vitamin C improves organ function and reduces inflammation in sepsis, an inflammatory state like the post-hematopoietic stem cell transplant (SCT) milieu. The safety and efficacy of parenteral vitamin C after allogeneic hematopoietic stem cell transplant (HSCT) were evaluated in a phase I/II trial and clinical outcomes compared with a propensity score - matched historical control. Methods: Patients with advanced hematologic malignancies were enrolled in a phase 2 clinical trial, receiving IV vitamin C, 50mg/kg/d, divided into 3 doses given on days 1-14 after HSCT, followed by 500 mg bid oral from day 15 until 6 months post-SCT. Results: 55 patients received IV vitamin C: these include 10/10 HLA-MRD and MUD (n=48) and 9/10 HLA MUD recipients (n=7). All patients enrolled were deficient in vitamin C at day 0 and had restoration to normal levels for the remainder of the course. Vitamin C recipients had lower non-relapse mortality (11% vs. 25%, p-value = 0.07) and consequently, improved survival compared to historical controls (82% vs 62% p=0.06), with no attributable grade 3 and 4 toxicities to vitamin C. Patients with myeloid malignancies had improved survival (83% vs. 54%, p=0.02) and non-relapse mortality (NRM) (10% vs. 37%, p=0.009), as well as chronic GVHD, with similar relapse rates compared to controls. Conclusions: In patients undergoing allogeneic HSCT the administration of IV vitamin C is safe and reduces non-relapse mortality improving overall survival. Randomized trials are needed to confirm the utility of this easily available and inexpensive therapy.

Intravenous Vitamin C Supplementation in Allogeneic Hematopoietic Cell Transplant Recipients: Salutary Impact on Clinical Outcomes.

Intravenous (IV) vitamin C improves organ function and reduces inflammation in sepsis, an inflammatory state like the post-hematopoietic stem cell transplant (HCT) milieu. The safety and efficacy of parenteral vitamin C after allogeneic HCT were evaluated in a phase I/II trial. Clinical outcomes were compared with a propensity score - matched historical control. Methods: Patients with advanced hematologic malignancies received IV vitamin C, 50mg/kg/d, divided into 3 doses given on days 1-14 after HCT, followed by 500 mg bid oral from day 15 until 6 months post-SCT. Results: 55 patients received IV vitamin C. All patients were deficient in vitamin C at day 0. Vitamin C recipients had lower non-relapse mortality (NRM) (p = 0.07) and improved survival compared to historical controls (p=0.06), with no attributable grade 3 and 4 toxicities. Vitamin C recipients had similar relapse rate and acute graft versus host disease (GVHD) (p=0.35), but lower severe chronic GVHD (p=0.35). Patients with myeloid malignancies had improved survival (p=0.02) and NRM (p=0.009), as well as chronic GVHD, with similar relapse rates compared to controls. Conclusions: In patients undergoing allogeneic HCT the administration of IV vitamin C is safe and reduces non-relapse mortality and chronic GVHD improving overall survival.

Rising Racial Disparities in Opioid Mortality and Undertreatment of Opioid Use Disorder and Mental Health Comorbidities in Virginia.

Introduction: There were more than 100,000 fatal drug overdoses in the U.S. in 2021 alone. In recent years, there has been a shift in opioid mortality from predominantly White rural communities to Black urban communities. This study aimed to identify the Virginia communities disproportionately affected by the overdose crisis and to better understand the systemic factors contributing to disparities in opioid mortality. Methods: Using the state all-payer claims database, state mortality records, and census data, we created a multivariate model to examine the community-level factors contributing to racial disparities in opioid mortality. We used generalized linear mixed models to examine the associations between socioecologic factors and fatal opioid overdoses, opioid use disorder diagnoses, opioid-related emergency department visits, and mental health diagnoses. Results: Between 2015 and 2020, racial disparities in mortality widened. In 2020, Black males were 1.5 times more likely to die of an opioid overdose than White males (47.3 vs 31.6 per 100,000; p<0.001). The rate of mental health disorders strongly correlated with mortality (ß=0.53, p<0.001). Black individuals are not more likely to be diagnosed with opioid use disorder (ß=0.01, p=0.002) or with mental health disorders (ß= -0.12, p<0.001), despite higher fatal opioid overdoses. Conclusions: There are widening racial disparities in opioid mortality. Untreated mental health disorders are a major risk factor for opioid mortality. Findings show pathways to address inequities, including early linkage to care for mental health and opioid use disorders. This analysis shows the use of comprehensive socioecologic data to identify the precursors to fatal overdoses, which could allow earlier intervention and reallocation of resources in high-risk communities.

Postpartum medication for opioid use disorder outcomes associated with prenatal treatment and neighborhood-level social determinants.

BACKGROUND: Opioid use disorder is a leading cause of death through the year postpartum. OBJECTIVE: This study aimed to identify the association of neighborhood-level social determinants of health and prenatal opioid use disorder treatment receipt with the outcomes of medication treatment for opioid use disorder through the year postpartum among a cohort of birthing people. STUDY DESIGN: This was a population-based retrospective cohort study that used state Medicaid claims and enrollment data for the 1690 individuals who delivered a live infant between July 1, 2016 and December 31, 2020 and received medication for opioid use disorder at delivery. The primary exposure was the state Health Opportunity Index, a composite measure of social determinants of health linked at the census-tract level. Secondary exposures included comprehensiveness of opioid use disorder treatment and duration of medication treatment for opioid use disorder received prenatally. Outcomes included the duration and continuity of postpartum medication treatment for opioid use disorder, operationalized as the time from delivery to the discontinuation of medication treatment for opioid use disorder, and percentage of days covered by medication treatment for opioid use disorder within the 12 months after delivery, respectively. RESULTS: Within the study sample, 711 deliveries were to birthing people in the lowest state Health Opportunity Index tercile (indicating high burden of negative social determinants of health), 647 in the middle state Health Opportunity Index tercile, and 332 in the highest state Health Opportunity Index tercile. Using stepwise multivariable regression (Cox proportional hazards and negative binomial models) guided by a socioecological framework, prenatal receipt of more comprehensive opioid use disorder treatment and/or longer duration of prenatal medication treatment for opioid use disorder was associated with improved 1-year postpartum opioid use disorder treatment outcomes (duration and continuity of medication treatment for opioid use disorder). When the state Health Opportunity Index was added to the models, these significant associations remained stable, with the state Health Opportunity Index not demonstrating an association with the outcomes (duration hazard ratio, 1.39; 95% confidence interval, 0.551-3.512; continuity relative risk, 1.024; 95% confidence interval, 0.323-3.247). CONCLUSION: Targeted efforts at expanding access to and quality of evidence-based opioid use disorder treatments for reproductive-age people across the life course should be prioritized within the spectrum of work aimed at eradicating disparities in pregnancy-related mortality.

Association Between Partisan Affiliation of State Governments and State Mortality Rates Before and During the COVID-19 Pandemic.

Policy Points The increasing political polarization of states reached new heights during the COVID-19 pandemic, when response plans differed sharply across party lines. This study found that states with Republican governors and larger Republican majorities in legislatures experienced higher death rates during the COVID-19 pandemic-and in preceding years-but these associations often lost statistical significance after adjusting for the average income and health status of state populations and for the policy orientations of the states. Future research may help clarify whether the higher death rates in these states result from policy choices or have other explanations, such as the tendency of voters with lower incomes or poorer health to elect Republican candidates. CONTEXT: Increasing polarization of states reached a high point during the COVID-19 pandemic, when the party affiliation of elected officials often predicted their policy response. The health consequences of these divisions are unclear. Prior studies compared mortality rates based on presidential voting patterns, but few considered the partisan orientation of state officials. This study examined whether the partisan orientation of governors or legislatures was associated with mortality outcomes during the COVID-19 pandemic. METHODS: Data on deaths and the partisan orientation of governors and legislators were obtained from the Centers for Disease Control and Prevention and the National Conference of State Legislatures, respectively. Linear regression was used to measure the association between Republican representation (percentage of seats held) in legislatures and (1) age-adjusted, all-cause mortality rates (AAMRs) in 2015-2021 and (2) excess death rates during three phases of the COVID-19 pandemic, controlling for median household income, the prevalence of four risk factors (obesity, chronic obstructive pulmonary disease, heart attack, stroke), and state policy orientation. Associations between excess death rates and the governor's party were also examined. FINDINGS: States with Republican governors or greater Republican representation in legislatures experienced higher AAMRs during 2015-2021, lower excess death rates during Phase 1 of the COVID-19 pandemic (weeks ending March 28, 2020, through June 13, 2020), and higher excess death rates in Phases 2 and 3 (weeks ending June 20, 2020, through April 30, 2022; p < 0.05). Most associations lost statistical significance after adjustment for control variables. CONCLUSIONS: Mortality was higher in states with Republican governors and greater Republican legislative representation before and during much of the pandemic. Observed associations could be explained by the adverse effects of policy choices, reverse causality (e.g., popularity of Republican candidates in states with lower socioeconomic and health status), or unmeasured factors that predominate in states with Republican leaders.

Trends in Antiseizure Medication Prescribing Among Nursing Home Residents With and Without a Seizure Diagnosis.

OBJECTIVES: Evaluate current prevalence and changes in prescribing of antiseizure medications (ASMs) in Virginia nursing homes for residents with and without seizures. METHODS: Retrospective cohort. De-identified claims extracted from the Virginia All-Payers-Claims-Database defined annual and biennial cohorts of all insured long-stay residents with and without any claims-based seizure diagnoses. ASM prescribing prevalence rates for these cohorts were analyzed from 2011 to 2016. Multiple logistic regression compared prescribing prevalence rates within and between these 2 groups. RESULTS: Annual cohorts averaged 57,190. 65.6% Female, 38% white. 80% public insurance, 20% commercial secondary. Between 2011 and 2016, the claims-based prevalence of seizure diagnoses decreased (17.1% to 10.5%). However, ASM prescribing prevalence increased (10.4% to 11.6%). Increases were entirely among residents who never had any seizure-epilepsy claim, whereas ASM prescribing among residents with seizures decreased. Different drugs were used for patients with and without seizures. For residents without seizures, 85% of ASMs prescribed have alternative indications for mood or pain symptoms, and large gains in gabapentin and modest but significant increases in valproate, lamotrigine, carbamazepine, and topiramate prescribing were detected. Among residents with seizures, ASMs without alternative indications were more common (59%), with marked reductions in phenobarbital and phenytoin but significant increases in levetiracetam and lacosamide use observed. CONCLUSIONS: Long-stay ASM use is changing. ASM gains are unrelated to seizure-epilepsy prevalence. ASM prescribing increased only among residents without seizures, where ASMs with expanded indications were preferred. Long-stay ASM prescribing and prescribing indication should be included in mandatory CMS reporting similar to other CNS-active medications.

Allogeneic haematopoietic cell transplants as dynamical systems: influence of early-term immune milieu on long-term T-cell recovery.

Objectives: Immune recovery following haematopoietic cell transplantation (HCT) functions as a dynamical system. Reducing the duration of intense immune suppression and augmenting antigen presentation has the potential to optimise T-cell reconstitution, potentially influencing long-term outcomes. Methods: Based on donor-derived T-cell recovery, 26 patients were adaptively randomised between mycophenolate mofetil (MMF) administered for 30-day post-transplant with filgrastim for cytokine support (MMF30 arm, N = 11), or MMF given for 15 days with sargramostim (MMF15 arm, N = 15). All patients underwent in vivo T-cell depletion with 5.1 mg kg-1 antithymocyte globulin (administered over 3 days, Day -9 through to Day -7) and received reduced intensity 450 cGy total body irradiation (3 fractions on Day -1 and Day 0). Patients underwent HLA-matched related and unrelated donor haematopoietic cell transplantation (HCT). Results: Clinical outcomes were equivalent between the two groups. The MMF15 arm demonstrated superior T-cell, as well as T-cell subset recovery and a trend towards superior T-cell receptor (TCR) diversity in the first month with this difference persisting through the first year. T-cell repertoire recovery was more rapid and sustained, as well as more diverse in the MMF15 arm. Conclusion: The long-term superior immune recovery in the MMF15 arm, administered GMCSF, is consistent with a disproportionate impact of early interventions in HCT. Modifying the 'immune-milieu' following allogeneic HCT is feasible and may influence long-term T-cell recovery.

Recent innovations in adaptive trial designs: A review of design opportunities in translational research.

Clinical trials are constantly evolving in the context of increasingly complex research questions and potentially limited resources. In this review article, we discuss the emergence of "adaptive" clinical trials that allow for the preplanned modification of an ongoing clinical trial based on the accumulating evidence with application across translational research. These modifications may include terminating a trial before completion due to futility or efficacy, re-estimating the needed sample size to ensure adequate power, enriching the target population enrolled in the study, selecting across multiple treatment arms, revising allocation ratios used for randomization, or selecting the most appropriate endpoint. Emerging topics related to borrowing information from historic or supplemental data sources, sequential multiple assignment randomized trials (SMART), master protocol and seamless designs, and phase I dose-finding studies are also presented. Each design element includes a brief overview with an accompanying case study to illustrate the design method in practice. We close with brief discussions relating to the statistical considerations for these contemporary designs.

Use of population health data to promote equitable recruitment for a primary care practice implementation trial addressing unhealthy alcohol use.

Background: Recruiting underrepresented people and communities in research is essential for generalizable findings. Ensuring representative participants can be particularly challenging for practice-level dissemination and implementation trials. Novel use of real-world data about practices and the communities they serve could promote more equitable and inclusive recruitment. Methods: We used a comprehensive primary care clinician and practice database, the Virginia All-Payers Claims Database, and the HealthLandscape Virginia mapping tool with community-level socio-ecological information to prospectively inform practice recruitment for a study to help primary care better screen and counsel for unhealthy alcohol use. Throughout recruitment, we measured how similar study practices were to primary care on average, mapped where practices' patients lived, and iteratively adapted our recruitment strategies. Results: In response to practice and community data, we adapted our recruitment strategy three times; first leveraging relationships with residency graduates, then a health system and professional organization approach, followed by a community-targeted approach, and a concluding approach using all three approaches. We enrolled 76 practices whose patients live in 97.3% (1844 of 1907) of Virginia's census tracts. Our overall patient sample had similar demographics to the state for race (21.7% vs 20.0% Black), ethnicity (9.5% vs 10.2% Hispanic), insurance status (6.4% vs 8.0% uninsured), and education (26.0% vs 32.5% high school graduate or less). Each practice recruitment approach uniquely included different communities and patients. Discussion: Data about primary care practices and the communities they serve can prospectively inform research recruitment of practices to yield more representative and inclusive patient cohorts for participation.

Rapid induction onto extended-release injectable buprenorphine following opioid overdose: A case series.

Background: Buprenorphine treatment has been associated with reduced non-prescribed opioid use and opioid related overdose (OD). We evaluated initial outcomes of rapid induction onto extended-release injectable buprenorphine (BUP-XR) within 7 days of emergency department presentation for unintentional OD. Methods: Between February 2019-February 2021, N = 19 patients with opioid use disorder received buprenorphine/naloxone (4/1 mg), followed by BUP-XR (300 mg) at induction and continued BUP-XR outpatient for 6 months. Primary outcomes included adverse events, repeat OD, and death. Results: For patients who received at least one dose of BUP-XR, there were no treatment related serious adverse events or symptoms of precipitated withdrawal. In addition, there were no repeat visits for ODs or deaths within 6 months of the initial OD. Discussion: These preliminary findings support the need for larger controlled clinical trials to examine the safety and efficacy of rapid induction of BUP-XR in patients with opioid use disorder at high risk of opioid OD. Rapid induction onto long-lasting injectable buprenorphine may be a promising and protective treatment approach in the future.

Cell-free next-generation sequencing impacts diagnosis and antimicrobial therapy in immunocompromised hosts: A retrospective study.

BACKGROUND: Cell-free next-generation sequencing (cfNGS) may have a unique role in the diagnosis of infectious complications in immunocompromised hosts. The rapid turnaround time and non-invasive nature make it a promising supplement to standard of care. METHODS: This retrospective, observational single-center study at a tertiary care medical center in Virginia investigated the use of cfNGS in clinical practice. Patients over age 18 years with cfNGS performed for any indication were included. The primary outcome was detection of bacteria and/or fungi on cfNGS. The secondary outcomes were concordance, and abundance of fungal and bacterial organism concentration detected over time from symptom onset, and clinical impact. RESULTS: Thirty-six patients (92% immunosuppressed) were identified and included. Twenty-one (58%) tests detected one to five organisms (14/21 bacteria, 8/21 fungi, and 6/21 viruses). The clinical impact of cfNGS was positive in 52.8% of cases, negative in 2.8%, and negligible in 44.4%. Positive tests prompted therapy changes in 12 of 21 patients; six of 20 bacteria and seven of eight fungi identified were considered clinically pathogenic. Three bacteria identifications and six fungi identifications prompted targeted treatment. When fungal species were not identified by cNFGS, antifungal de-escalation occurred in seven patients. CONCLUSION: cfNGS assisted in critical management changes, including initiation of treatment for identified organisms and antimicrobial de-escalation. Its non-invasive nature and rapid turnaround time make this an important adjunct to standard of care testing that may assist in providing earlier, targeted therapy, especially when opportunistic pathogens remain high on the differential diagnosis.

High dose valacyclovir for cytomegalovirus prophylaxis following allogeneic hematopoietic cell transplantation.

INTRODUCTION: Cytomegalovirus (CMV) is one of the most common and clinically significant viral infections following allogeneic hematopoietic cell transplantation (HCT). Currently available options for CMV prophylaxis and treatment present challenges related to side effects and cost. METHODS: In this retrospective medical record review, the incidence of clinically significant CMV infection (CMV disease or reactivation requiring preemptive treatment) following allogeneic HCT was compared in patients receiving valacyclovir 1 g three times daily versus acyclovir 400 mg every 12 h for viral prophylaxis. RESULTS: Forty-five patients who received valacyclovir were matched based on propensity scoring to 35 patients who received acyclovir. All patients received reduced-intensity conditioning regimens containing anti-thymocyte globulin. Clinically significant CMV infection by day + 180 was lower in the valacyclovir group compared to the acyclovir group (18% vs. 57%, p = 0.0004). Patients receiving valacyclovir prophylaxis also had less severe infection evidenced by a reduction in CMV disease, lower peak CMV titers, delayed CMV reactivation, and less secondary neutropenia. CONCLUSION: Prospective evaluation of valacyclovir 1 g three times daily for viral prophylaxis following allogeneic HCT is warranted. Due to valacyclovir's favorable toxicity profile and affordable cost, it has the potential to benefit patients on a broad scale as an option for CMV prophylaxis.