Drugs, guns, and violent crime in California.

BACKGROUND: There is evidence linking use of controlled substances with perpetration of interpersonal violence. While the United States constitution protects the right to own a firearm, federal law prohibits firearm purchase and possession by persons believed to be at high risk for violence, including those who use controlled substances unlawfully. METHODS: We report here the results of a 13-year prospective observational study on the risk of violent crime associated with a history of criminal drug charges in a cohort of 79,678 legal purchasers of handguns in California in 2001. The main outcomes were post-purchase charges for any violent crime, violent Crime Index crimes (murder, rape, robbery, aggravated assault), and firearm-related violent crimes. The main exposure of interest was a history of pre-purchase charge(s) for drug-related offenses; we examined as a secondary exposure a history of marijuana-related charges. We estimated adjusted hazard ratios (aHR) with 95 % confidence intervals (CI) using Cox proportional hazards multiple events models. RESULTS: We found that legal handgun purchasers in California with a history of drug-related charges, even those with marijuana charges only, had triple the risk of a post-purchase violent crime charge compared to purchasers with no criminal charges (drug charges only: aHR=2.9, 95 % CI 2.2-3.8; marijuana charges only: aHR=3.3, 95 % CI 1.8-6.0). In addition, a criminal history of drug charges only vs. no criminal history was associated with increased risk of one or more violent crime charges after the first post-purchase arrest event (aHR=1.6, 95 % CI 1.2-2.3). CONCLUSION: It is incumbent on researchers and policy makers to understand the nature and causes of this risk in order to take effective steps towards mitigation.

International recommendations for screening and preventative practices for long-term survivors of transplantation and cellular therapy: a 2023 update.

As hematopoietic cell transplantation (HCT) and cellular therapy expand to new indications and international access improves, the volume of HCT performed annually continues to rise. Parallel improvements in HCT techniques and supportive care entails more patients surviving long-term, creating further emphasis on survivorship needs. Survivors are at risk for developing late complications secondary to pre-, peri- and post-transplant exposures and other underlying risk-factors. Guidelines for screening and preventive practices for HCT survivors were originally published in 2006 and updated in 2012. To review contemporary literature and update the recommendations while considering the changing practice of HCT and cellular therapy, an international group of experts was again convened. This review provides updated pediatric and adult survivorship guidelines for HCT and cellular therapy. The contributory role of chronic graft-versus-host disease (cGVHD) to the development of late effects is discussed but cGVHD management is not covered in detail. These guidelines emphasize special needs of patients with distinct underlying HCT indications or comorbidities (e.g., hemoglobinopathies, older adults) but do not replace more detailed group, disease, or condition specific guidelines. Although these recommendations should be applicable to the vast majority of HCT recipients, resource constraints may limit their implementation in some settings.

International Recommendations for Screening and Preventative Practices for Long-Term Survivors of Transplantation and Cellular Therapy: A 2023 Update.

As hematopoietic cell transplantation (HCT) and cellular therapy expand to new indications and international access improves, the number of HCTs performed annually continues to rise. Parallel improvements in HCT techniques and supportive care entails more patients surviving long term, creating further emphasis on survivorship needs. Survivors are at risk for developing late complications secondary to pretransplantation, peritransplantation, and post-transplantation exposures and other underlying risk factors. Guidelines for screening and preventive practices for HCT survivors were originally published in 2006 and then updated in 2012. An international group of experts was convened to review the contemporary literature and update the recommendations while considering the changing practices of HCT and cellular therapy. This review provides updated pediatric and adult survivorship guidelines for HCT and cellular therapy. The contributory role of chronic graft-versus-host disease (cGVHD) to the development of late effects is discussed, but cGVHD management is not covered in detail. These guidelines emphasize the special needs of patients with distinct underlying HCT indications or comorbidities (eg, hemoglobinopathies, older adults) but do not replace more detailed group-, disease-, or condition-specific guidelines. Although these recommendations should be applicable to the vast majority of HCT recipients, resource constraints may limit their implementation in some settings.

Comparison of record linkage software for deduplicating patient identities in California's Prescription Drug Monitoring Program.

BACKGROUND: To help prevent overdose deaths involving prescription drugs, accurate linkage of prescription drug monitoring program (PDMP) records for individual patients is essential. OBJECTIVES: To compare the accuracy of the linkage program used by California's PDMP against various record linkage programs with respect to accuracy in deduplicating patient identities in the PDMP, with implications for identifying high-risk opioid use and outlier behaviors. RESEARCH DESIGN: We evaluated California's program, Link Plus, LinkSolv, and The Link King on 557 861 PDMP identity records with addresses in two 3-digit zip code areas for patients who filled a controlled substance prescription in 2013. Manual review was performed on a stratified sample of 720 paired records identified as matches by at least one program. MEASURES: We estimated sensitivity and positive predictive value, and computed PDMP patient alerts for the patient entities identified by each program. RESULTS: Sensitivity was 95% for LinkSolv and The Link King, 84% for Link Plus, and 73% for California's program; positive predictive value was ≥93% for all programs. The number of patient entities prompting a PDMP alert was similar among the programs for all alerts except multiple provider episodes (obtaining prescriptions from ≥6 prescribers or ≥6 pharmacies in the last 6 months), which were 10.9%, 26.6%, and 16.9% greater using The Link King, Link Plus, and LinkSolv, respectively, compared to California's program. CONCLUSIONS: PDMPs should assess the accuracy of record linkage algorithms and the impacts of these algorithms on patient safety alerts and develop national best practices for PDMP record linkage.

Impact of 30-day prescribed opioid dose trajectory on fatal overdose risk: A population-based, statewide cohort study.

BACKGROUND: Both increases and decreases in patients' prescribed daily opioid dose have been linked to increased overdose risk, but associations between 30-day dose trajectories and subsequent overdose risk have not been systematically examined. OBJECTIVE: To examine the associations between 30-day prescribed opioid dose trajectories and fatal opioid overdose risk during the subsequent 15 days. DESIGN: Statewide cohort study using linked prescription drug monitoring program and death certificate data. We constructed a multivariable Cox proportional hazards model that accounted for time-varying prescription-, prescriber-, and pharmacy-level factors. PARTICIPANTS: All patients prescribed an opioid analgesic in California from March to December, 2013 (5,326,392 patients). MAIN MEASURES: Dependent variable: fatal drug overdose involving opioids. Primary independent variable: a 16-level variable denoting all possible opioid dose trajectories using the following categories for current and 30-day previously prescribed daily dose: 0-29, 30-59, 60-89, or ≥90 milligram morphine equivalents (MME). KEY RESULTS: Relative to patients prescribed a stable daily dose of 0-29 MME, large (≥2 categories) dose increases and having a previous or current dose ≥60 MME per day were associated with significantly greater 15-day overdose risk. Patients whose dose decreased from ≥90 to 0-29 MME per day had significantly greater overdose risk compared to both patients prescribed a stable daily dose of ≥90 MME (aHR 3.56, 95%CI 2.24-5.67) and to patients prescribed a stable daily dose of 0-29 MME (aHR 7.87, 95%CI 5.49-11.28). Patients prescribed benzodiazepines also had significantly greater overdose risk; being prescribed Z-drugs, carisoprodol, or psychostimulants was not associated with overdose risk. CONCLUSIONS: Large (≥2 categories) 30-day dose increases and decreases were both associated with increased risk of fatal opioid overdose, particularly for patients taking ≥90 MME whose opioids were abruptly stopped. Results align with 2022 CDC guidelines that urge caution when reducing opioid doses for patients taking long-term opioid for chronic pain.

Application of the Childbirth Supporter Study to Advance the Birth Unit Design Spatial Evaluation Tool.

OBJECTIVE: Translational research to advance design criteria and apply the Childbirth Supporter Study (CSS) findings to practice. BACKGROUND: The physical design of birth environments has not undergone substantial improvements in layout or ambiance since the initial move to hospitals. Cooperative, continuously present childbirth supporters are beneficial and are an expectation for most modern birth practices, yet the built environment does not offer support for the supporter. METHODS: To advance design criteria, we use a comparative case study approach to create translational findings. Specifically, CSS findings were used as indicators to advance the Birth Unit Design Spatial Evaluation Tool (BUDSET) design characteristics in pursuit of better support for childbirth supporters in the built hospital birth environment. RESULTS: This comparative case study provides eight new BUDSET design domain suggestions to benefit the supporter-woman dyad, and subsequently the baby and care providers. CONCLUSIONS: Research-informed design imperatives are needed to guide the inclusion of childbirth supporters as both a supporter and as an individual in the birth space. Increased understanding of relationships between specific design features and childbirth supporters' experiences and reactions are provided. Suggestions to enhance the applicability of the BUDSET for birth unit design facility development are made, specifically ones that will better accommodate childbirth supporters.

Disparities in treatment and survival in early-stage hepatocellular carcinoma in California.

BACKGROUND AND OBJECTIVES: Curative intent therapy is the standard of care for early-stage hepatocellular carcinoma (HCC). However, these therapies are under-utilized, with several treatment and survival disparities. We sought to demonstrate whether the type of facility and distance from treatment center (with transplant capabilities) contributed to disparities in curative-intent treatment and survival for early-stage HCC in California. METHODS: We performed a retrospective analysis of the California Cancer Registry for patients diagnosed with stage I or II primary HCC between 2005 and 2017. Primary and secondary outcomes were receipt of treatment and overall survival, respectively. Multivariable logistic regression and Multivariable Cox proportional hazards regression were used to evaluate associations. RESULTS: Of 19 059 patients with early-stage HCC, only 36% (6778) received curative-intent treatment. Compared to Non-Hispanic White patients, Hispanic patients were less likely, and Asian/Pacific Islander patients were more likely to receive curative-intent treatment. Our results showed that rural residence, public insurance, lower neighborhood SES, and care at non-National Cancer Institute-designated cancer center were associated with not receiving treatment and decreased survival. CONCLUSIONS: Although multiple factors influence receipt of treatment for early-HCC, our findings suggest that early intervention programs should target travel barriers and access to specialist care to help improve oncologic outcomes.

Intra- and Intertumoral Microglia/Macrophage Infiltration and Their Associated Molecular Signature Is Highly Variable in Canine Oligodendroglioma: A Preliminary Evaluation.

The goal of this study was to define the glioma-associated microglia/macrophage (GAM) response and associated molecular landscape in canine oligodendrogliomas. Here, we quantified the intratumoral GAM density of low- and high-grade oligodendrogliomas compared to that of a normal brain, as well as the intratumoral concentration of several known GAM-derived pro-tumorigenic molecules in high-grade oligodendrogliomas compared to that in a normal brain. Our analysis demonstrated marked intra- and intertumoral heterogeneity of GAM infiltration. Correspondingly, we observed significant variability in the intratumoral concentrations of several GAM-associated molecules, unlike what we previously observed in high-grade astrocytomas. However, high-grade oligodendroglioma tumor homogenates (n = 6) exhibited an increase in the pro-tumorigenic molecules hepatocyte growth factor receptor (HGFR) and vascular endothelial growth factor (VEGF), as we observed in high-grade astrocytomas. Moreover, neoplastic oligodendrocytes displayed robust expression of GAL-3, a chimeric galectin implicated in driving immunosuppression in human glioblastoma. While this work identifies shared putative therapeutic targets across canine glioma subtypes (HGFR, GAL-3), it highlights several key differences in the immune landscape. Therefore, a continued effort to develop a comprehensive understanding of the immune microenvironment within each subtype is necessary to inform therapeutic strategies going forward.

Patient-Reported Outcomes of Kinematic vs Mechanical Alignment in Total Knee Arthroplasty: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Background: Total knee arthroplasty (TKA) is an effective treatment method for severe osteoarthritis of the knee. Poor alignment of a knee replacement has been associated with suboptimal clinical results. Traditionally, mechanical alignment (MA) has been considered the gold standard. In light of reports of decreased satisfaction with TKA, a new technique called kinematic alignment (KA) has been developed. The purpose of this study is to (1) review the results of KA and MA for TKA in randomized controlled trials based on the Western Ontario and McMaster Universities Arthritis Index score, the Oxford Knee Score, and the Knee Society Scores, (2) perform a meta-analyses of the randomized controlled trials with baseline and follow-up values of these parameters, and (3) discuss other shortcomings of this literature from the perspective of study design and execution. Methods: Two independent reviewers performed a systematic review of the English literature using the Embase, Scopus, and PubMed databases searching for randomized controlled trials of MA vs KA in TKA. Of the initial 481 published reports, 6 studies were included in the final review for meta-analysis. The individual studies were then analyzed to evaluate for risks of bias and inconsistencies of methodology. Results: A majority of studies demonstrated low risk of bias. All studies had fundamental technical issues by utilizing different techniques to achieve KA vs MA. There was no significant difference between KA and MA in these studies. Conclusions: There is no significant difference in any outcomes measured between KA and MA in TKA. Both statistical and methodological factors diminish the value of these conclusions.

Meta-analysis of the Modified Checklist for Autism in Toddlers, Revised/Follow-up for Screening.

CONTEXT: The Modified Checklist for Autism in Toddlers, Revised with Follow-up (M-CHAT-R/F) is used worldwide to screen for autism spectrum disorder (ASD). OBJECTIVE: To calculate psychometric properties of the M-CHAT-R/F for subsequent diagnosis of ASD. DATA SOURCES: Systematic searches of Medline, Embase, SCOPUS, and Trip Pro databases from January 2014 to November 2021. STUDY SELECTION: Studies were included if they (1) used the M-CHAT-R/F (2) applied standard scoring protocol, (3) used a diagnostic assessment for ASD, and (4) reported at least 1 psychometric property of the M-CHAT-R/F. DATA EXTRACTION: Two independent reviewers completed screening, full-text review, data extraction, and quality assessment, following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. A random-effects model was used to derive pooled estimates and assess for between-study heterogeneity. RESULTS: Of 667 studies identified, 15 with 18 distinct samples from 10 countries (49 841 children) were used in the meta-analysis. Pooled positive predictive value (PPV), was 57.7% (95% confidence interval [CI] 48.6-66.8, τ2 = 0.031). PPV was higher among high-risk (75.6% [95% CI 66.0-85.2]) than low-risk samples (51.2% [95% CI 43.0-59.5]). Pooled negative predictive value was 72.5% (95% CI 62.5-82.4 τ2 = 0.031), sensitivity was 82.6% (95% CI 76.2-88.9) and specificity 45.7% (95% CI 25.0-66.4). LIMITATIONS: Negative predictive value, sensitivity, and specificity were calculated based on small sample sizes because of limited or no evaluation of screen-negative children. CONCLUSIONS: These results support use of the M-CHAT-R/F as a screening tool for ASD. Caregiver counseling regarding likelihood of an ASD diagnosis after positive screen should acknowledge the moderate PPV.

Impact of Chronic Graft-versus-Host Disease on Patient Employment, Income, and Informal Caregiver Burden: Findings From the Living With Chronic GVHD Patient Survey.

The development of chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT) results in impaired physical function and quality of life. However, limited data exist regarding the employment and financial impact on patients and caregivers. The objective of this study was to examine the impact of chronic GVHD on patient employment, disability leave, income, reliance on caregivers, and effects on caregiver employment. The Living With Chronic GVHD Patient Survey was a cross-sectional online survey administered from May to August 2020 in the United States to adult HSCT survivors diagnosed with chronic GVHD within the past 5 years. Data on respondent demographics and disease characteristics and the effects of chronic GVHD on employment, income, and need for caregiver assistance were collected. Respondents also were asked to report on the impact of their chronic GVHD on their caregivers' employment. All data were summarized using descriptive statistics; no formal statistical comparisons were conducted. A total of 165 respondents completed the survey (median age, 57.0 years; 63.6% women; 83.0% white). The respondents had been experiencing chronic GVHD for a median of 4.5 years (range, .1 to 36.7 years), with a median of .5 years (range, 0 to 3.6 years) from the most recent transplantation to chronic GVHD diagnosis. Among those employed full- or part-time at the time of their most recent transplantation (n = 80), 61.3% reported taking disability leave, 58.8% worked reduced hours, 27.5% took a less demanding job, and 33.8% left a job because of chronic GVHD. Additionally, 71.3% believed they had lost income due to chronic GVHD. Among all respondents, 72.1% reported receiving regular caregiver assistance. Respondents commonly reported employment changes among unpaid caregivers; 34.5% reduced their working hours, and 16.6% left a job). HSCT survivors who develop chronic GVHD are vulnerable to employment changes and financial hardship. This analysis highlights the need for effective therapies and improved symptom management to reduce the multifaceted burden of chronic GVHD on patients and their caregivers and ultimately improve long-term HSCT outcomes.

Osimertinib in NSCLC With Atypical EGFR-Activating Mutations: A Retrospective Multicenter Study.

Introduction: EGFR mutations drive a subset of NSCLC. Patients harboring the common EGFR mutations, deletion of exon 19 and L858R, respond well to osimertinib, a third-generation tyrosine kinase inhibitor. Nevertheless, the effect of osimertinib on NSCLC with atypical EGFR mutations is not well described. This multicenter retrospective study evaluates the efficacy of osimertinib among patients with NSCLC harboring atypical EGFR mutations. Methods: Patients with metastatic NSCLC treated with osimertinib, harboring at least one atypical EGFR mutation, excluding concurrent deletion of exon 19, L858R, or T790M mutations, from six U.S. academic cancer centers were included. Baseline clinical characteristics were collected. The primary end point was the time to treatment discontinuation (TTD) of osimertinib. Objective response rate by the Response Evaluation Criteria in Solid Tumors version 1.1 was also assessed. Results: A total of 50 patients with NSCLC with uncommon EGFR mutations were identified. The most frequent EGFR mutations were L861Q (40%, n = 18), G719X (28%, n = 14), and exon 20 insertion (14%, n = 7). The median TTD of osimertinib was 9.7 months (95% confidence interval [CI]: 6.5-12.9 mo) overall and 10.7 months (95% CI: 3.2-18.1 mo) in the first-line setting (n = 20). The objective response rate was 31.7% (95% CI: 18.1%-48.1%) overall and 41.2% (95% CI: 18.4%-67.1%) in the first-line setting. The median TTD varied among patients with L861Q (17.2 mo), G719X (7.8 mo), and exon 20 insertion (1.5 mo) mutations. Conclusions: Osimertinib has activity in patients with NSCLC harboring atypical EGFR mutations. Osimertinib activity differs by the type of atypical EGFR-activating mutation.

Patient-reported symptom burden and impact on daily activities in chronic graft-versus-host disease.

BACKGROUND: Chronic graft-versus-host disease (GVHD) is a potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation (HSCT) treatment for hematologic malignancies. There are limited patient-reported data concerning symptom burden and effects on activities of daily living (ADL). METHODS: The cross-sectional Living With Chronic GVHD Patient Survey was administered online in the United States (May-August 2020) to participants aged ≥18 years who underwent allogeneic HSCT, were diagnosed with chronic GVHD by a healthcare provider, and self-reported active chronic GVHD (within past 5 years). Information on patient demographics, disease characteristics, symptom burden, and ability to perform ADL was collected. Symptom burden was assessed using the validated Lee Symptom Scale (range from 0-100 with higher scores indicating greater burden). All data were summarized using descriptive statistics; no formal statistical comparisons were conducted. RESULTS: Out of 580 participants who entered the survey screener, 165 participants (28.4%) across 33 states fulfilled all study eligibility criteria, completed the entire survey, and were included (age: mean [SD], 53.7 (13.8) years; median [range], 57.0 [18-78] years; female, n = 105 [63.6%]; White, n = 137 [83.0%]). Respondents described their chronic GVHD severity primarily as moderate (n = 54 [32.7%]) or severe (n = 102 [61.8%]) at the time when symptoms were at their worst. One-third of respondents (33.9%) indicated that their chronic GVHD symptoms were at their worst for ≥1 year in duration. Mean (SD; range) Lee Symptom Scale score was 44.8 (19.4; 2-100); 44% of respondents considered "dry eye" the most burdensome symptom. Almost half of respondents (n = 73 [44.2%]) rated their overall quality of life (QoL) as poor. Participants reported a detrimental impact of symptoms on ADL, including basic activities (eg, eating, personal hygiene, dressing). CONCLUSIONS: Survey respondents self-reported high chronic GVHD symptom burden and felt that their symptoms severely interfered with physical function and ADL. Effective strategies to mitigate chronic GVHD symptoms are needed to improve QoL among HSCT survivors.

The Effect of Peer-to-Peer Education about the Significance of Specialty Certification on Empowering Nurses Working in Dialysis.

Specialty certification demonstrates knowledge and expertise in an area of nursing practice resulting in significant benefits to nurses, patients, public, and hiring organizations, empowering professional practice, and improving nurse retention and patient outcomes. However, a large majority of nurses working in dialysis have never validated their knowledge and skills through specialty certification. A one-group pre- and post-intervention study was conducted, with a sample group of registered nurses working in dialysis, using an asynchronous peer-to-peer education regarding empowering practice through specialty certification. The effect on psychological empowerment was measured using a 2-tailed t test with a comparison of enrollments in pre-certification courses. Results showed a 25% increase in course enrollments, but no statistical significance in psychological empowerment. Future study is needed on how nephrology nursing certification impacts patient outcomes, empowerment, workplace environment, and staff retention in nephrology.

Enabling Healthy Aging to AVOID Frailty in Community Dwelling Older Canadians.

The Canadian population is aging. With aging, biological and social changes occur increasing the risk of developing chronic conditions and functional loss leading to frailty. Older adults living with frailty are more vulnerable to minor stressors, take longer to recover from illness, and have difficulty participating in daily activities. The Canadian Frailty Network's (CFN) mission is to improve the lives of older adults living with frailty. In September 2019, CFN launched the Activity & Exercise, Vaccination, Optimization of medications, Interaction & Socialization, and Diet & Nutrition (AVOID) Frailty public health campaign to promote assessing and reducing risk factors leading to the development of frailty. As part of the campaign, CFN held an Enabling Healthy Aging Symposium with 36 stakeholders from across Canada. Stakeholders identified individual and community-level opportunities and challenges for the enablement of healthy aging and frailty mitigation, as part of a focused consultative process. Stakeholders ranked the three most important challenges and opportunities at the individual and community levels for implementing AVOID Frailty recommendations. Concrete actions, further research areas, policy changes, and existing resources/programs to enhance the AVOID Frailty campaign were identified. The results will help inform future priorities and behaviour change strategies for healthy aging in Canada.

Inhaled recombinant human IL-15 in dogs with naturally occurring pulmonary metastases from osteosarcoma or melanoma: a phase 1 study of clinical activity and correlates of response.

PURPOSE: Although recombinant human interleukin-15 (rhIL-15) has generated much excitement as an immunotherapeutic agent for cancer, activity in human clinical trials has been modest to date, in part due to the risks of toxicity with significant dose escalation. Since pulmonary metastases are a major site of distant failure in human and dog cancers, we sought to investigate inhaled rhIL-15 in dogs with naturally occurring lung metastases from osteosarcoma (OSA) or melanoma. We hypothesized a favorable benefit/risk profile given the concentrated delivery to the lungs with decreased systemic exposure. EXPERIMENTAL DESIGN: We performed a phase I trial of inhaled rhIL-15 in dogs with gross pulmonary metastases using a traditional 3+3 cohort design. A starting dose of 10 µg twice daily × 14 days was used based on human, non-human primate, and murine studies. Safety, dose-limiting toxicities (DLT), and maximum tolerated dose (MTD) were the primary objectives, while response rates, progression-free and overall survival (OS), and pharmacokinetic and immune correlative analyses were secondary. RESULTS: From October 2018 to December 2020, we enrolled 21 dogs with 18 dogs reaching the 28-day response assessment to be evaluable. At dose level 5 (70 µg), we observed two DLTs, thereby establishing 50 µg twice daily × 14 days as the MTD and recommended phase 2 dose. Among 18 evaluable dogs, we observed one complete response >1 year, one partial response with resolution of multiple target lesions, and five stable disease for an overall clinical benefit rate of 39%. Plasma rhIL-15 quantitation revealed detectable and sustained rhIL-15 concentrations between 1-hour and 6 hour postnebulization. Decreased pretreatment lymphocyte counts were significantly associated with clinical benefit. Cytotoxicity assays of banked peripheral blood mononuclear cells revealed significant increases in peak cytotoxicity against canine melanoma and OSA targets that correlated with OS. CONCLUSIONS: In this first-in-dog clinical trial of inhaled rhIL-15 in dogs with advanced metastatic disease, we observed promising clinical activity when administered as a monotherapy for only 14 days. These data have significant clinical and biological implications for both dogs and humans with refractory lung metastases and support exploration of combinatorial therapies using inhaled rhIL-15.

The impact of California wildfires on patient access to prescription opioids.

BACKGROUND: Patients on long-term opioid therapy are particularly vulnerable to disruptions in medication access, especially during traumatic and chaotic events such as wildfires and other natural disasters. OBJECTIVES: To determine whether past highly destructive California wildfires were associated with disrupted access to prescription opioids for patients receiving long-term, and therefore physically dependent on, opioid medications. METHODS: Using California prescription drug monitoring program data, this retrospective study selected patients with long-term prescription opioid use episodes residing in ZIP code tabulation areas impacted by either the Camp Fire or Tubbs Fire. Autoregressive integrated moving average time series models were fit to pre-fire data to forecast post-fire expected values and then compared with observed post-fire data, specifically for weekly proportions of long-term episodes with early fills, late fills, changes in patients' prescriber and pharmacy, and fills within a different ZIP code tabulation area than the patient's residence. RESULTS: After the Camp Fire, there were significant spikes in the proportions of early fills (peak at 56% of total, week 1 after fire), late fills (peak at 29%, week 6), and immediate significant increases in prescriber (peak at 37%, week 3) and pharmacy changes (peak at 71%, week 1) in high-impact ZIP code tabulation areas. Low-impact ZIP code tabulation areas experienced no similar disruptions. Disruptions due to the Tubbs Fire were far less severe. CONCLUSION: Access to prescription opioids was greatly disrupted for patients living in areas most impacted by the Camp Fire. Future research should explore effectiveness of current state and federal controlled substance prescribing policies to determine what improvements are needed to minimize disruptions in medication access due to wildfires and other natural disasters.

Are We Making PROGRESS in Preventing Graft-versus-Host Disease and Improving Clinical Outcomes? Impact of BMT CTN 1301 Study Results on Clinical Practice.

The need for prospective randomized clinical trials investigating novel graft-versus-host disease (GVHD) prevention strategies that include other clinical outcomes impacted by GVHD has been highlighted as a priority for the field of hematopoietic cell transplantation. A recently completed study through the Blood and Marrow Transplant Clinical Trials Network (BMT CTN 1301) comparing CD34+ selection and post-transplantation cyclophosphamide with tacrolimus/methotrexate (Tac/MTX) for GVHD prevention demonstrated no significant differences in the primary endpoint of chronic GVHD relapse-free survival among the 3 approaches. The trial did not demonstrate a superior approach compared with Tac/MTX; however, it did highlight several challenges in determining the best and most relevant approaches to clinical trial design, particularly in the context of current and ongoing changes in real-world practices. Here we review the results of BMT CTN 1301 and their implications for clinical practice and future clinical trial design.