Publications

Guidelines recommend against initiating long-acting opioids during acute hospitalization, owing to higher risk of overdose and morbidity compared to short-acting opioid initiation. We investigated the incidence of long-acting opioid initiation following hospitalization in a retrospective cohort of Medicare beneficiaries with an acute care hospitalization in 2016 who were ≥65 years old, did not have cancer or hospice care, and had not filled an opioid prescription within the preceding 90 days. Among 258,193 hospitalizations, 47,945 (18.6%) were associated with a claim for a new opioid prescription in the week after hospital discharge: 817 (0.3%) with both short- and long-acting opioids, 125 (0.1%) with long-acting opioids only, and 47,003 (18.2%) with short-acting opioids only. Most long-acting opioid claims occurred in surgical patients (770 out of 942; 81.7%). Compared with beneficiaries prescribed short-acting opioids only, beneficiaries prescribed long-acting opioids were younger, had a higher prevalence of diseases of the musculoskeletal system and connective tissue, and had more known risk factors for opioid-related adverse events, including anxiety disorders, opioid use disorder, prior long-term high-dose opioid use, and benzodiazepine co-prescription. These findings may help target quality-improvement initiatives.

Melanoma continues to be an aggressive and deadly form of skin cancer while therapeutic options are continuously developing in an effort to provide long-term solutions for patients. Immunotherapeutic strategies incorporating antibody-drug conjugates (ADCs) have seen varied levels of success across tumor types and represent a promising approach for melanoma. This review will explore the successes of FDA-approved ADCs to date compared to the ongoing efforts of melanoma-targeting ADCs. The challenges and opportunities for future therapeutic development are also examined to distinguish how ADCs may better impact individuals with malignancies such as melanoma.

This cohort study analyzes the trends in filled naloxone prescriptions during the COVID-19 pandemic in the United States and compare these to opioid prescriptions and overall prescriptions.

Background Only one third of patients recommended intensified treatment by the 2017 American College of Cardiology/American Heart Association (ACC/AHA) guideline for high blood pressure would have been eligible for the clinical trials on which recommendations were largely based. We sought to identify characteristics of adults who would have been trial-ineligible in order to inform clinical practice and research priorities. Methods and Results We examined the proportion of adults diagnosed with hypertension who met trial inclusion and exclusion criteria, stratified by age, diabetes mellitus status, and guideline recommendations in a cross-sectional study of the National Health and Nutrition Examination Survey, 2013-2016. Of the 107.7 million adults (95% CI, 99.3-116.0 million) classified as having hypertension by the ACC/AHA guideline, 23.1% (95% CI, 20.8%-25.5%) were below the target blood pressure of 130/80 mm Hg, 22.2% (95% CI, 20.1%-24.4%) would be recommended nonpharmacologic treatment, and 54.6% (95% CI, 52.5%-56.7%) would be recommended additional pharmacotherapy. Only 20.6% (95% CI, 18.8%-22.4%) of adults with hypertension would be trial-eligible. The majority of adults <50 years were excluded because of low cardiovascular risk and lack of access to primary care. The majority of adults aged ≥70 years were excluded because of multimorbidity and limited life expectancy. Reasons for trial exclusion were similar for patients with and without diabetes mellitus. Conclusions Intensive blood pressure treatment trials were not representative of many younger adults with low cardiovascular risk and older adults with multimorbidity who are now recommended more intensive blood pressure goals.

Colorectal cancer (CRC) remains a leading cause of cancer-related deaths in the United States despite an array of available treatment options. Current standard-of-care interventions for this malignancy include surgical resection, chemotherapy, and targeted therapies depending on the disease stage. Specifically, infusion of anti-vascular endothelial growth factor agents in combination with chemotherapy was an important development in improving the survival of patients with advanced colorectal cancer, while also helping give rise to other forms of anti-angiogenic therapies. Yet, one approach by which tumor angiogenesis may be further disrupted is through the administration of a dendritic cell (DC) vaccine targeting tumor-derived blood vessels, leading to cytotoxic immune responses that decrease tumor growth and synergize with other systemic therapies. Early generations of such vaccines exhibited protection against various forms of cancer in pre-clinical models, but clinical results have historically been disappointing. Sipuleucel-T (Provenge®) was the first, and to-date, only dendritic cell-based therapy to receive FDA approval after significantly increasing overall survival in prostate cancer patients. The unparalleled success of Sipuleucel-T has helped revitalize the clinical development of dendritic cell vaccines, which will be examined in this review. We also highlight the promise of these vaccines to instill anti-angiogenic immunity for individuals with advanced colorectal cancer.

BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) cause approximately 13 100 infections, with an 8% mortality rate in the United States annually. Carbapenemase-producing CRE (CP-CRE) a subset of CRE infections infections have much higher mortality rates (40%-50%). There has been little research on characteristics unique to CP-CRE. The goal of the current study was to assess differences between US veterans with non-CP-CRE and those with CP-CRE cultures.

METHODS: A retrospective cohort of veterans with CRE cultures from 2013-2018 and their demographic, medical, and facility level covariates were collected. Clustered multiple logistic regression models were used to assess independent factors associated with CP-CRE.

RESULTS: The study included 3096 unique patients with cultures positive for either non-CP-CRE or CP-CRE. Being African American (odds ratio, 1.44 [95% confidence interval, 1.15-1.80]), diagnosis in 2017 (3.11 [2.13-4.54]) or 2018 (3.93 [2.64-5.84]), congestive heart failure (1.35 [1.11-1.64]), and gastroesophageal reflux disease (1.39 [1.03-1.87]) were associated with CP-CRE cultures. There was no known antibiotic exposure in the previous year for 752 patients (24.3% of the included patients). Those with no known antibiotic exposure had increased frequency of prolonged proton pump inhibitor use (17.3%) compared to those with known antibiotic exposure (5.6%).

DISCUSSION: Among a cohort of patients with CRE, African Americans, patients with congestive heart failure, and those with gastroesophageal reflux disease had greater odds of having a CP-CRE culture. Roughly 1 in 4 patients with CP-CRE had no known antibiotic exposure in the year before their positive culture.

BACKGROUND: Ceftazidime/avibactam (C/A), ceftolozane/tazobactam (C/T), imipenem/relebactam (I/R), and meropenem/vaborbactam (M/V) combine either a cephalosporin (C/T and C/A) or a carbapenem antibiotic (M/V and I/R) with a β-lactamase inhibitor. They are used to treat carbapenem-resistant Enterobacterales (CRE) and/or multidrug-resistant Pseudomonas aeruginosa (MDRPA).

OBJECTIVE: We compared the pooled clinical success of these medications to older therapies.

METHODS: PubMed and EMBASE were searched from January 1, 2012, through September 2, 2020, for C/A, C/T, I/R, and M/V studies. The main outcome was clinical success, which was assessed using random-effects models. Stratified analyses were conducted for study drug, sample size, quality, infection source, study design, and multidrug-resistant gram-negative organism (MDRGNO) population. Microbiological success and 28- and 30-day mortality were assessed as secondary outcomes. Heterogeneity was determined using I2 values.

RESULTS: Overall, 25 articles met the inclusion criteria; 8 observational studies and 17 randomized control trials. We detected no difference in clinical success comparing new combination antibiotics with standard therapies for all included organisms (pooled OR, 1.21; 95% CI, 0.96-1.51). We detected a moderate level of heterogeneity among the included studies I2 = 56%. Studies that focused on patients with CRE or MDRPA infections demonstrated a strong association between treatment with new combination antibiotics and clinical success (pooled OR, 2.20; 95% CI, 1.60-3.57).

CONCLUSIONS: C/T, C/A, I/R, and M/V are not inferior to standard therapies for treating various complicated infections, but they may have greater clinical success for treating MDRPA and CRE infections. More studies that evaluate the use of these antibiotics for drug-resistant infections are needed to determine their effectiveness.

INTRODUCTION: Antibiotics and opioids are targeted by public health and stewardship communities for reductions in prescribing across the country. This study evaluates trends and factors associated with outpatient prescribing by dental and medical providers in a large integrated health system.

METHODS: This was a cross-sectional study of national dental and medical outpatient visits from Department of Veterans Affairs facilities in 2015-2017; analyzed in 2019-2020. Antibiotic and opioid prescribing rates were assessed by provider and facility characteristics. Multivariable Poisson regression adjusted for repeated measures by the provider was used to assess the independent association between facility and provider characteristics and rate of prescribing.

RESULTS: Over the study period, 4,625,840 antibiotic and 10,380,809 opioid prescriptions were identified for 115,625,890 visits. Physicians prescribed most antibiotics (67%). Dentists prescribed 6% of the antibiotics but had the highest per-visit antibiotic prescribing rate compared to medical providers (6.75 vs 3.90 prescriptions per 100 visits, p<0.0001), which was largely driven by dental specialists. By contrast, dentists had lower opioid prescribing than medical providers (3.02 vs 9.20 prescriptions per 100 visits, p<0.0001). Overall, antibiotic and opioid prescribing decreased over time, with opioids having the greatest decreases (-28.0%). In multivariable analyses, U.S. geographic region, rurality, and complexity were associated with prescribing for both drug classes. Opioid and antibiotic prescribing were positively correlated.

CONCLUSIONS: Although antibiotic and opioid prescribing has decreased, there are still important target areas for improvement. Interventions need to be tailored to community characteristics such as rurality and provider type.