Adopting the RE-AIM analytic framework for rural program evaluation: experiences from the Advance Care Planning via Group Visits (ACP-GV) national evaluation.

Introduction: To support rigorous evaluation across a national portfolio of grants, the United States Department of Veterans Affairs (VA) Office of Rural Health (ORH) adopted an analytic framework to guide their grantees' evaluation of initiatives that reach rural veterans and to standardize the reporting of outcomes and impacts. Advance Care Planning via Group Visits (ACP-GV), one of ORH's Enterprise-Wide Initiatives, also followed the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework. ACP-GV is a national patient-centered intervention delivered in a large, veterans integrated healthcare system. This manuscript describes how RE-AIM was used to evaluate this national program and lessons learned from ORH's annual reporting feedback to ACP-GV on their use of the framework to describe evaluation impacts. Methods: We used patient, provider, and site-level administrative health care data from the VA Corporate Data Warehouse and national program management databases for federal fiscal years (FY) spanning October 1, 2018-September 30, 2023. Measures included cumulative and past FY metrics developed to assess program impacts. Results: RE-AIM constructs included the following cumulative and annual program evaluation results. ACP-GV reached 54,167 unique veterans, including 19,032 unique rural veterans between FY 2018 to FY 2023. During FY 2023, implementation adherence to the ACP-GV model was noted in 91.7% of program completers, with 55% of these completers reporting a knowledge increase and 14% reporting a substantial knowledge increase (effectiveness). As of FY 2023, 66 ACP-GV sites were active, and 1,556 VA staff were trained in the intervention (adoption). Of the 66 active sites in FY 2023, 27 were sites previously funded by ORH and continued to offer ACP-GV after the conclusion of three years of seed funding (maintenance). Discussion: Lessons learned developing RE-AIM metrics collaboratively with program developers, implementers, and evaluators allowed for a balance of clinical and scientific input in decision-making, while the ORH annual reporting feedback provided specificity and emphasis for including both cumulative, annual, and rural specific metrics. ACP-GV's use of RE-AIM metrics is a key step towards improving rural veteran health outcomes and describing real world program impacts.

Impact of Implementation Facilitation on the REACH VET Clinical Program for Veterans at Risk for Suicide.

OBJECTIVE: In 2017, the Veterans Health Administration (VHA) implemented a national suicide prevention program, called Recovery Engagement and Coordination for Health-Veterans Enhanced Treatment (REACH VET), that uses a predictive algorithm to identify, attempt to reach, assess, and care for patients at the highest risk for suicide. The authors aimed to evaluate whether facilitation enhanced implementation of REACH VET at VHA facilities not meeting target completion rates. METHODS: In this hybrid effectiveness-implementation type 2 program evaluation, a quasi-experimental pre-post design was used to assess changes in implementation outcome measures evaluated 6 months before and 6 months after onset of facilitation of REACH VET implementation at 23 VHA facilities. Measures included percentages of patients with documented coordinator and provider acknowledgment of receipt, care evaluation, and outreach attempt. Generalized estimating equations were used to compare differences in REACH VET outcome measures before and after facilitation. Qualitative interviews were conducted with personnel and were explored via template analysis. RESULTS: Time had a significant effect in all outcomes models (p<0.001). An effect of facilitation was significant only for the outcome of attempted outreach. Patients identified by REACH VET had significantly higher odds of having a documented outreach attempt after facilitation of REACH VET implementation, compared with before facilitation. Site personnel felt supported and reported that the external facilitators were helpful and responsive. CONCLUSIONS: Facilitation of REACH VET implementation was associated with an improvement in outreach attempts to veterans identified as being at increased risk for suicide. Outreach is critical for engaging veterans in care.

Healthy food delivery for type 2 diabetes management in rural clinics' patients: A comparative effectiveness randomized controlled trial protocol.

BACKGROUND: Rural populations experience a higher prevalence of both food insecurity and type 2 diabetes mellitus (T2DM) than metropolitan populations and face many challenges in accessing resources essential to optimal T2DM self-management. This study aims to address these challenges by delivering a T2DM-appropriate food box and recipes directly to rural participants' homes. METHODS: This is a comparative effectiveness randomized controlled trial including 400 English- or Spanish-speaking rural adult participants with T2DM (HbA1c ≥6.5%) experiencing food insecurity. Participants are randomly assigned to a 3-month Healthy Food Delivery Intervention (HFDI) plus one 60-min virtual consultation with a diabetes educator or consultation only. The HFDI includes a weekly food box delivery with recipes. Data are collected at pre-intervention, 3-months (post-intervention), 9-months, and 15-months. The primary outcome is change in HbA1c, with secondary measures including diet quality (Healthy Eating Index-2015, calculated from one 24-h dietary recall at each data collection time point), cardio-metabolic risk factors (i.e., blood pressure, lipids, body mass index, glucose), and patient-centered outcomes (e.g., T2DM self-efficacy, T2DM-related distress). Process evaluation data (e.g., successful food box deliveries, diabetes educator consultation attendance, intervention satisfaction) are collected during and post-intervention (3-months). A cost-effectiveness analysis based on traditional cost per quality-adjusted life year gain thresholds will be conducted to estimate the incremental cost-effectiveness between HFDI plus consultation and consultation alone. CONCLUSION: Findings from this study will provide evidence regarding the effectiveness of an intervention that promotes participant adherence and improves access to healthy food. CLINICAL TRIAL REGISTRATION: NCT04876053.

Opioid therapy trajectories of patients with chronic non-cancer pain over 1 year of follow-up after initiation of short-acting opioid formulations.

OBJECTIVE: This study compared opioid utilization trajectories of persons initiating tramadol, short-acting hydrocodone, or short-acting oxycodone, and it characterized opioid dose trajectories and type of opioid in persistent opioid therapy subsamples. METHODS: A retrospective cohort study of adults with chronic non-cancer pain who were initiating opioid therapy was conducted with the IQVIA PharMetrics® Plus for Academics data (2008-2018). Continuous enrollment was required for 6 months before ("baseline") and 12 months after ("follow-up") the first opioid prescription ("index date"). Opioid therapy measures were assessed every 7 days over follow-up. Group-based trajectory modeling (GBTM) was used to identify trajectories for any opioid and total morphine milligram equivalent measures, and longitudinal latent class analysis was used for opioid therapy type. RESULTS: A total of 40 276 tramadol, 141 023 hydrocodone, and 45 221 oxycodone initiators were included. GBTM on any opioid therapy identified 3 latent trajectories: early discontinuers (tramadol 39.0%, hydrocodone 54.1%, oxycodone 61.4%), late discontinuers (tramadol 37.9%, hydrocodone 39.4%, oxycodone 33.3%), and persistent therapy (tramadol 6.7%, hydrocodone 6.5%, oxycodone 5.3%). An additional fourth trajectory, intermittent therapy (tramadol 16.4%), was identified for tramadol initiators. Of those on persistent therapy, 2687 individuals were on persistent therapy with tramadol, 9169 with hydrocodone, and 2377 with oxycodone. GBTM on opioid dose resulted in 6 similar trajectory groups in each persistent therapy group. Longitudinal latent class analysis on opioid therapy type identified 6 latent classes for tramadol and oxycodone and 7 classes for hydrocodone. CONCLUSION: Opioid therapy patterns meaningfully differed by the initial opioid prescribed, notably the presence of intermittent therapy among tramadol initiators and higher morphine milligram equivalents and prescribing of long-acting opioids among oxycodone initiators.

Engaging stakeholders to retrospectively discern implementation strategies to support program evaluation: Proposed method and case study.

BACKGROUND: Availability of evidence-based practices (EBPs) is critical for improving health care outcomes, but diffusion can be challenging. Implementation activities increase the adoption of EBPs and support sustainability. However, when implementation activities are a part of quality improvement processes, evaluation of the time and cost associated with these activities is challenged by the need for a correct classification of these activities to a known taxonomy of implementation strategies by implementation actors. DESIGN: Observational study of a four-stage, stakeholder-engaged process for identifying implementation activities and estimating the associated costs. RESULTS: A national initiative in the Veterans Health Administration (VHA) to improve Advance Care Planning (ACP) via Group Visits (ACP-GV) for rural veterans identified 49 potential implementation activities. Evaluators translated and reduced these to 14 strategies used across three groups with the aid of implementation actors. Data were collected to determine the total implementation effort and applied cost estimates to estimate the budget impact of implementation for VHA. LIMITATIONS: Recall bias may influence the identification of potential implementation activities. CONCLUSIONS: This process improved understanding of the implementation effort and allowed estimation of ACP-GV 's budget impact. IMPLICATIONS: A four-stage, stakeholder-engaged methodology can be applied to other initiatives when a pragmatic evaluation of implementation efforts is needed.

An Integrative Review of Micro-Credentials and Digital Badges for Pharmacy Educators.

Micro-credentials (MCs) and digital badges (DBs) have gained popularity in recent years as a means to supplement traditional degrees and certifications. MCs and DBs can play a significant role in supporting student-centered learning by offering personalized and flexible learning pathways, emphasizing real-world relevance and practical skills, and fostering a culture of continuous learning and growth. However, barriers currently exist within health professions education, including pharmacy education, that could limit the full adoption and implementation of MCs and DBs. Research on the use of MCs and DBs in Doctor of Pharmacy degree programs is sparse. In this integrative review, literature on the use of MCs and DBs in health professions education is reviewed, and perspectives on the benefits, issues, and potential future uses within Doctor of Pharmacy degree programs are presented.

Clinical Review of Risk of Nephrotoxicity with Acyclovir Use for Treatment of Herpes Simplex Virus Infections in Neonates and Children.

OBJECTIVE: This study aims to clarify the risk of nephrotoxicity with intravenous use of acyclovir (ACV) for the treatment of neonates (ages <3 months) and children (ages ≥3 months to <12 years) with herpes simplex virus (HSV) infections and to identify gaps in knowledge that could be further investigated. METHODS: Multiple databases were searched to identify studies on risk of nephrotoxicity with ACV use for treatment of invasive HSV infections, defined as any neonatal infection or HSV encephalitis (HSE) in children. RESULTS: There were 5 and 14 studies that evaluated the risk of ACV-associated nephrotoxicity in neonates and children, respectively. The US Food and Drug Administration (FDA) delayed the approval of high (HD; 60 mg/kg/day) ACV in neonates secondary to risk of toxicity. Based on our review, the risk of ACV-associated nephrotoxicity was lower in the neonatal compared with the pediatric population. Acyclovir dose >1500 mg/m2, older age, and concomitant use of nephrotoxic drugs were identified as variables that increased the risk of ACV nephrotoxicity in children. Although the FDA has approved the use of HD ACV for the treatment of HSE in children, the American Academy of Pediatrics recommends a lower dose to minimize the risk of toxicity. The efficacy and safety of high vs lower doses of ACV for the management of HSE in children has yet to be evaluated. CONCLUSIONS: The risk of ACV-associated nephrotoxicity was lower among neonates compared with older children. Future studies are needed to identify the optimal dosage that minimizes toxicities and maximizes the efficacy of ACV in children with HSE.

Addressing COVID-19 vaccine hesitancy in rural community pharmacies: a protocol for a stepped wedge randomized clinical trial.

BACKGROUND: Uptake of COVID-19 vaccines remains problematically low in the USA, especially in rural areas. COVID-19 vaccine hesitancy is associated with lower uptake, which translates to higher susceptibility to SARS-CoV-2 variants in communities where vaccination coverage is low. Because community pharmacists are among the most accessible and trusted health professionals in rural areas, this randomized clinical trial will examine implementation strategies to support rural pharmacists in delivering an adapted evidence-based intervention to reduce COVID-19 vaccine hesitancy. METHODS: We will use an incomplete stepped wedge trial design in which we will randomize 30 rural pharmacies (unit of analysis) to determine the effectiveness and incremental cost-effectiveness of a standard implementation approach (consisting of online training that describes the vaccine hesitancy intervention, live webinar, and resource website) compared to adding on a virtual facilitation approach (provided by a trained facilitator in support of the delivery of the vaccine hesitancy counseling intervention by pharmacists). The intervention (ASORT) has been adapted from an evidence-based vaccine communication intervention for HPV vaccines through a partnership with rural pharmacies in a practice-based research network in seven southern US states. ASORT teaches pharmacists how to identify persons eligible for COVID-19 vaccination (including a booster), solicit and address vaccine concerns in a non-confrontational way, recommend the vaccine, and repeat the steps later if needed. The primary trial outcome is fidelity to the ASORT intervention, which will be determined through ratings of recordings of pharmacists delivering the intervention. The secondary outcome is the effectiveness of the intervention, determined by rates of patients who agree to be vaccinated after receiving the intervention. Other secondary outcomes include feasibility, acceptability, adoption, reach, and cost. Cost-effectiveness and budget impact analyses will be conducted to maximize the potential for future dissemination and sustainability. Mixed methods will provide triangulation, expansion, and explanation of quantitative findings. DISCUSSION: This trial contributes to a growing evidence base on vaccine hesitancy interventions and virtual-only facilitation of evidenced-based practices in community health settings. The trial will provide the first estimate of the relative value of different implementation strategies in pharmacy settings. TRIAL REGISTRATION: NCT05926544 (clinicaltrials.gov); 07/03/2023.

Food Insecurity and Health Outcomes of Children With Intellectual and Developmental Disabilities in the United States.

We aimed to (a) provide nationally representative estimates of food insecurity (FI) among children with intellectual and developmental disabilities (IDD), and (b) determine the association between FI and four health outcomes (overall health, problem behavior, activities of daily living, functional limitations) in 5,657 children with IDD compared to 1:1 propensity score matched children without IDD. Mixed-effects ordered logistic regression models were used. Children with IDD were more likely to experience FI than children without IDD (43.3% vs. 30.0%, p < 0.001). FI and IDD were independently associated with worse scores on all four health outcomes. Having both FI and IDD further exacerbated the adverse impacts on these health outcomes. The association was stronger among children with moderate-to-severe FI than those with mild FI.

Orai inhibition modulates pulmonary ILC2 metabolism and alleviates airway hyperreactivity in murine and humanized models.

Ca2+ entry via Ca2+ release-activated Ca2+ (CRAC) channels is a predominant mechanism of intracellular Ca2+ elevation in immune cells. Here we show the immunoregulatory role of CRAC channel components Orai1 and Orai2 in Group 2 innate lymphoid cells (ILC2s), that play crucial roles in the induction of type 2 inflammation. We find that blocking or genetic ablation of Orai1 and Orai2 downregulates ILC2 effector function and cytokine production, consequently ameliorating the development of ILC2-mediated airway inflammation in multiple murine models. Mechanistically, ILC2 metabolic and mitochondrial homeostasis are inhibited and lead to the upregulation of reactive oxygen species production. We confirm our findings in human ILC2s, as blocking Orai1 and Orai2 prevents the development of airway hyperreactivity in humanized mice. Our findings have a broad impact on the basic understanding of Ca2+ signaling in ILC2 biology, providing potential insights into the development of therapies for the treatment of allergic and atopic inflammatory diseases.

Real-World Survival of First-Line Immune Checkpoint Inhibitor Treatment Versus Chemotherapy in Older Patients With Non-Small-Cell Lung Cancer and Synchronous Brain Metastases.

PURPOSE: This study assessed real-world survival among older patients with non-small-cell lung cancer (NSCLC) and brain metastases (BMs) at diagnosis (synchronous BM [SBM]) receiving first-line immune checkpoint inhibitors (ICIs) compared with chemotherapy only. METHODS: Patients with NSCLC and SBM age 65 years or older at diagnosis from 2010 to 2019 SEER-Medicare database and received US Food and Drug Administration-approved ICIs (pembrolizumab/nivolumab/ipilimumab/atezolizumab/durvalumab/cemiplimab) and/or chemotherapy (platinum-based doublets/taxane/pemetrexed/gemcitabine) as first-line systemic treatment were included, excluding those with no cranial radiation or ever being treated with targeted therapies. Overall survival time was from the start of systemic treatment (ICI/chemotherapy) to death, censored at disenrollment from Medicare part A/B, enrollment in part C, or end of the study period (December 31, 2019). Kaplan-Meier (KM) survival curves were compared between treatment groups using the log-rank test. Multivariable Cox proportional hazards (CPH) model was used to estimate hazard ratio (HR) between groups, adjusting for patients' sociodemographic and clinical characteristics. RESULTS: The study included 1,481 patients (1,303 chemotherapy and 178 ICI). The median (range) age was 71 (65-91) years. First-line ICI patients were more likely to be older, live in urban areas, and less likely to be non-White than the chemotherapy group. KM estimates showed that survival curves initially overlapped but diverged approximately 6 months after initiating first-line systemic treatment (median survival [95% CI]: ICI, 190 [131 to 303] days versus chemotherapy, 189 [177 to 201] days), with ICI showing a better survival than the chemotherapy group (log-rank test P < .0001). First-line ICI was associated with a lower risk of death compared with chemotherapy in adjusted CPH model (HR [95% CI], 0.67 [0.55 to 0.80]; P < .0001). CONCLUSION: Among older patients with NSCLC and SBM, first-line ICI use was associated with improved survival occurring 6 months after treatment initiation compared with chemotherapy only.

Factors Associated With Guideline-Concordant Pharmacological Treatment for Neuropathic Pain Among Breast Cancer Survivors.

PURPOSE: To identify factors associated with receiving guideline-concordant treatment among breast cancer survivors with neuropathic pain. MATERIALS AND METHODS: A retrospective case-control study was conducted using the SEER-Medicare linked database. We included female breast cancer survivors diagnosed with non-metastatic breast cancer (stages 0-III) between 2007 and 2015 who developed treatment-related neuropathic pain during their survivorship period. Guideline-concordant treatment was defined based on NCCN guidelines. Factors associated with receiving guideline-concordant treatment were assessed using multivariable logistic regression and backward selection was used to identify potential associated factors. RESULTS: Around 16.7% of breast cancer survivors in the study developed a neuropathic pain condition. The mean time to develop neuropathic pain was 1.4 years after beginning adjuvant treatment. On average, patients who developed neuropathic pain and received guideline-concordant treatment did so at 2.4 months after their neuropathic pain diagnosis. We found that survivors that are black and of other races were less likely to receive guideline-concordant treatment for breast cancer treatment-related neuropathic pain. Whereas survivors with diabetes, mental health disorders, hemiplegia, prior continuous opioid use, benzodiazepine use, nonbenzodiazepine CNS depressant use, or antipsychotic medication use were less likely to receive guideline-concordant treatment. CONCLUSION: This study suggests that minority races, prior medication use, and comorbid conditions are associated with guideline-concordant treatment among breast cancer survivors with neuropathic pain. These findings warrant attention towards minority races to prescribe them guideline-concordant treatment as well as caution when prescribing concurrent pain medications to survivors with comorbidities and prior medication use.

Retrospective Cohort Study of Safety Outcomes Associated with Opioid Rotations to Buprenorphine.

The objective of this study was to understand the effect buprenorphine rotations have on respiratory risk and other safety outcomes. This was a retrospective observational study evaluating Veterans who underwent an opioid rotation from full-agonist opioids to buprenorphine products or to alternative opioids. The primary endpoint was change in the Risk Index for Overdose or Serious Opioid-induced Respiratory Depression (RIOSORD) score from baseline to six months post-rotation. Median baseline RIOSORD scores were 26.0 and 18.0 in the Buprenorphine Group and the Alternative Opioid Group, respectively. There was no statistically significant difference between groups in baseline RIOSORD score. At six months post-rotation, median RIOSORD scores were 23.5 and 23.0 in the Buprenorphine Group and Alternative Opioid Group, respectively. The difference in change in RIOSORD scores between groups was not statistically significant (p = 0.23). However, based on changes in RIOSORD risk class, an 11% and 0% decrease in respiratory risk was observed in the Buprenorphine and Alternative Opioid groups, respectively. This finding may be considered clinically significant given a change in risk was observed as predicted by RIOSORD score. Further research is needed to clarify the effect that opioid rotations have on respiratory depression risk and other safety outcomes.

The use of gabapentinoids and opioids and risk of developing opioid-induced respiratory depression among older breast cancer survivors with neuropathic pain.

PURPOSE: To estimate the combined effect of gabapentinoid and opioid therapy compared to opioid monotherapy on the risk of developing opioid-induced respiratory depression among breast cancer survivors with neuropathic pain. METHOD: A nested case-control study of Medicare female breast cancer survivors with neuropathic pain receiving both opioids and gabapentinoids, opioid monotherapy, gabapentinoid monotherapy, and none of these drugs was conducted using SEER-Medicare between 2007 and 2015. Cases were survivors with respiratory depression and were matched with controls on the event date (± 1 year), age at diagnosis (± 5 years), and stage at diagnosis. Exposure to opioids and gabapentinoids was assessed 120 days before the event date. Conditional logistic regression was used to assess the impact of exposure among cases and controls. RESULTS: A total of 657 cases and 11,471 controls were identified. After matching, 656 cases and 5612 controls were retained, and cases were more likely to be diagnosed with mental health disorders (24.4% vs 10.5%, p < 0.0001) than controls. In the primary adjusted analysis, combined opioids and gabapentin use were associated with an increased risk of respiratory depression compared to opioid monotherapy (Adj. OR: 1.513; 95% CI: 1.473-2.350). Additionally, under secondary analysis, combined opioids and gabapentin use were associated with an increased risk of respiratory depression compared to receiving neither of these classes. (Adj. OR: 1.595; 95% CI: 1.050-2.421). CONCLUSION: There is a need for dose titration strategies of gabapentinoids and caution when co-prescribing opioids and gabapentinoids in older cancer survivors.

Comparative Study of Opioid Initiation With Tramadol, Short-acting Hydrocodone, or Short-acting Oxycodone on Opioid-related Adverse Outcomes Among Chronic Noncancer Pain Patients.

OBJECTIVE: To compare the safety profiles of low and high-dose tramadol, short-acting hydrocodone, and short-acting oxycodone therapies among chronic noncancer pain individuals. MATERIALS AND METHODS: A retrospective cohort study of individuals with back/neck pain/osteoarthritis with an initial opioid prescription for tramadol, hydrocodone, or oxycodone was conducted using IQVIA PharMetrics Plus claims for Academics database (2006 to 2020). Two cohorts were created for separately studying opioid-related adverse events (overdoses, accidents, self-inflicted injuries, and violence-related injuries) and substance use disorders (opioid and nonopioid). Patients were followed from the index date until an outcome event, end of enrollment, or data end. Time-varying exposure groups were constructed and Cox regression models were estimated. RESULTS: A total of 1,062,167 (tramadol [16.5%], hydrocodone [61.1%], and oxycodone [22.4%]) and 986,809 (tramadol [16.5%], hydrocodone [61.3%], and oxycodone [22.2%]) individuals were in the adverse event and substance use disorder cohorts. All high-dose groups had elevated risk of nearly all outcomes, compared with low-dose hydrocodone. Compared with low-dose hydrocodone, low-dose oxycodone was associated with a higher risk of opioid overdose (hazard ratio: 1.79 [1.37 to 2.33]). No difference in risk was observed between low-dose tramadol and low-dose hydrocodone (hazard ratio: 0.85 [0.64 to 1.13]). Low-dose oxycodone had higher risks of an opioid use disorder, and low-dose tramadol had a lower risk of accidents, self-inflicted injuries, and opioid use disorder compared with low-dose hydrocodone. DISCUSSION: Low-dose oxycodone had a higher risk of opioid-related adverse outcomes compared with low-dose tramadol and hydrocodone. This should be interpreted in conjunction with the benefits of pain control and functioning associated with oxycodone use in future research.

Healthcare costs and utilization associated with pain among breast cancer survivors: a propensity score matched cohort study using SEER-Medicare data.

PURPOSE: To assess healthcare costs and utilization of treatment-related pain among breast cancer survivors. METHODS: A retrospective matched cohort study using Surveillance Epidemiology and End Results SEER-Medicare linked data was conducted. The study population included older breast cancer survivors continuously enrolled in Medicare parts A, B, and D in the baseline and 1-year follow-up periods. Survivors with pain were matched to survivors without pain using PSM. Incremental all-cause healthcare costs associated with pain were calculated using a two-part model. Incremental healthcare utilization of inpatient hospitalizations, ER, outpatient, and physician services were estimated using the negative binomial model. RESULTS: The study included 101,120 non-metastatic breast cancer patients between July 2007 and September 2013. The final analytical cohort after matching included 5891 survivors in both groups. The incremental annual all-cause total healthcare costs per patient were higher in survivors with pain as compared to survivors without pain (Δ = 4379.00 (95% CI: 4308.00-4448.80). The main cost drivers were hospitalizations at 71%, followed by ER at 16% and physician services at 9% for survivors diagnosed with pain. Annual all-cause healthcare resource utilization was also found to be higher in survivors with pain as compared to survivors without pain across all categories of use. Similar trends were observed when stratified by surgery type and subgrouped by pain type and pain-related costs. CONCLUSION: This study provided baseline data that can be used for future cost-effectiveness analysis studies and burden of illness studies. IMPLICATION FOR CANCER SURVIVORS: Treatment-related costs have a substantial burden on healthcare costs and the utilization of Medicare.

"Advancing" Advance Care Planning to Veterans in the Veterans Health Administration.

INTRODUCTION: The completion rate of Advance Directive (ADs) in the Veterans Health Administration (VHA) is unknown. There is substantial literature on the need for effective Advance Care Planning (ACP) that leads to an AD to ensure that health care preferences for patients are known. Advance Directive are essential to consider since ACP, which explains and plans Advance Directive, does not reach all individuals. Health inequities, such as those experienced in rural areas, continue to exist. While ACP may disproportionately affect rural-residing veterans and their providers, a VHA program was specifically designed to increase ACP engagement with rural veterans and to address several systemic barriers to ACP. MATERIALS AND METHODS: This descriptive analysis seeks to identify patient, provider, and geographic characteristics associated with higher rates of ACP participation in VHA. An observational examination of the profile of veterans and the types of ACP (e.g., individual or in groups) using administrative data for all beneficiaries receiving VHA health care services in federal fiscal year (FY) 2020 was conducted as part of a national program evaluation. The measures include patient-level data on demographics (e.g., race, ethnicity, gender), unique patient identifiers (e.g., name, social security number), geographic characteristics of patient's location (e.g., rurality defined as Rural-Urban Commuting Areas [RUCA]), VHA priority group; provider-level data (e.g., type of document definition, clinic stop codes, visit date used to verify Advance Care Planning via Group Visits [ACP-GV] attendance; data not shown), and electronic health record note titles that indicated the presence of ACP in VHA (e.g., "Advance Directive [AD] Discussion" note title, "ACP-GV CHAR 4 code"). Pearson's chi-square statistics were used for between-group comparisons based on a two-sided test with a significance level of 0.05. RESULTS: The overall rate of AD discussions among unique VHA users in FY2020 was 5.2% (95% CI: 5.2%-5.2%) and for Advance Care Planning via Group Visits, which targets rural veterans using groups, it was 1.8% (95% CI: 1.8%-1.9%). Advance Directive discussions in VHA are more successful at reaching middle age (M = 64; SD = 16), African Americans, males, veterans living in urban areas, and veterans with a VA disability (Priority Group 1-4). Advance Care Planning delivered in groups is reaching slightly younger veterans under the age of 75 years (M = 62; SD = 15), African Americans, females, disabled veterans (e.g., Priority Group 1-4), and more veterans residing in rural communities compared to the national population of VHA users. CONCLUSION: Advance Directive discussion rates are low across VHA, yet intentional efforts with ACP via group visits are reaching veterans who are considered underserved owing to residing in rural areas. Advance Care Planning needs to be a well-informed clinical priority for VHA to engage with the entire veteran population and to support the completion of ADs.

Depression and diabetes distress in patients with diabetes.

We aimed to identify the prevalence of comorbid depression, diabetes, and diabetes distress and assess glycemic control and rates of diabetes-related complications. While the presence of either depression or distress did not predict the level of glycemic control, certain macro- and microvascular complications were more prevalent with depression.

The Impact of Continuous Infusion Compared to Intravenous Bolus Administration of Pantoprazole on Length of Intensive Care Unit Stay in Critically Ill Patients.

Purpose: To determine if intravenous (IV) bolus pantoprazole increases intensive care unit (ICU) length of stay compared to IV infusion pantoprazole for treatment of gastrointestinal (GI) bleeding in critically ill patients. Methods: This retrospective cohort study included adult patients admitted to the ICU with GI bleeds. Patients treated with IV pantoprazole from January 1, 2017 to December 31, 2017 were analyzed in the continuous infusion group, and patients treated from March 1, 2018 to February 28, 2019 were analyzed in the bolus only group. Patients with pregnancy, variceal bleeds, or lower GI bleeds were excluded. Intensive care unit length of stay was compared between the two cohorts using the Mann Whitney U test. Adjusted analysis was conducted using the generalized linear model with gamma log link to estimate the effect of type of infusion on ICU length of stay. Results: A total of 145 patients were included in the analysis, with 72 patients in the continuous infusion group and 73 patients in the bolus only group. The median ICU length of stay was 70.5 hours for continuous infusion and 64 hours for bolus only pantoprazole (P-value = .577). In the adjusted analysis, there was no difference in ICU length of stay between the continuous infusion and bolus only groups (RR, 1.06; 95% CI, .76-1.47). Conclusion: Intensive care unit length of stay was not prolonged with the use of IV bolus only compared to continuous infusion pantoprazole. Intravenous bolus only pantoprazole may be used in critically ill patients for treatment of upper GI bleeding.

Human PD-1 agonist treatment alleviates neutrophilic asthma by reprogramming T cells.

BACKGROUND: Neutrophilic asthma is associated with disease severity and corticosteroid insensitivity. Novel therapies are required to manage this life-threatening asthma phenotype. Programmed cell death protein-1 (PD-1) is a key homeostatic modulator of the immune response for T-cell effector functions. OBJECTIVE: We sought to investigate the role of PD-1 in the regulation of acute neutrophilic inflammation in a murine model of airway hyperreactivity (AHR). METHODS: House dust mite was used to induce and compare neutrophilic AHR in wild-type and PD-1 knockout mice. Then, the therapeutic potential of a human PD-1 agonist was tested in a humanized mouse model in which the PD-1 extracellular domain is entirely humanized. Single-cell RNA sequencing and flow cytometry were mainly used to investigate molecular and cellular mechanisms. RESULTS: PD-1 was highly induced on pulmonary T cells in our inflammatory model. PD-1 deficiency was associated with an increased neutrophilic AHR and high recruitment of inflammatory cells to the lungs. Consistently, PD-1 agonist treatment dampened AHR, decreased neutrophil recruitment, and modulated cytokine production in a humanized PD-1 mouse model. Mechanistically, we demonstrated at the transcriptional and protein levels that the inhibitory effect of PD-1 agonist is associated with the reprogramming of pulmonary effector T cells that showed decreased number and activation. CONCLUSIONS: PD-1 agonist treatment is efficient in dampening neutrophilic AHR and lung inflammation in a preclinical humanized mouse model.