Publications

2022

Herzig, Shoshana J, Timothy S Anderson, Yoojin Jung, Long H Ngo, and Ellen P McCarthy. (2022) 2022. “Risk Factors for Opioid-Related Adverse Drug Events Among Older Adults After Hospital Discharge.”. Journal of the American Geriatrics Society 70 (1): 228-34. https://doi.org/10.1111/jgs.17453.

BACKGROUND: Although opioids are initiated on hospital discharge in millions of older adults each year, there are no studies examining patient- and prescribing-related risk factors for opioid-related adverse drug events (ADEs) after hospital discharge among medical patients.

METHODS: A retrospective cohort study of a national sample of Medicare beneficiaries aged 65 years and older, hospitalized for a medical reason, with at least one claim for an opioid within 2 days of hospital discharge. We excluded patients receiving hospice care and patients admitted from or discharged to a facility. We used administrative billing codes and medication claims to define potential opioid-related ADEs within 30 days of hospital discharge, and competing risks regression to identify risk factors for these events.

RESULTS: Among 22,879 medical hospitalizations (median age 74, 36.9% female) with an opioid claim within 2 days of hospital discharge, a potential opioid-related ADE occurred in 1604 (7.0%). Independent risk factors included age of 80 years and older (HR 1.18, 95% CI 1.05-1.33); clinical conditions, including kidney disease (HR 1.22, 95% CI 1.08-1.37), dementia/delirium (HR 1.38, 95% CI 1.22-1.56), anxiety disorder (HR 1.20, 95% CI 1.06-1.36), opioid use disorder (HR 1.20, 95% CI 1.03-1.39), intestinal disorders (HR 1.31, 95% CI 1.15-1.49), pancreaticobiliary disorders (HR 1.32, 95% CI 1.09-1.61), and musculoskeletal and nervous system injuries (HR 1.35, 95% CI 1.17-1.54); red flags for opioid misuse (HR 1.37, 95% CI 1.04-1.80); opioid use in the 30 days before hospitalization (HR 1.20, 95% CI 1.08-1.34); and prescription of long-acting opioids (HR 1.34, 95% CI 1.06-1.70).

CONCLUSIONS: Potential opioid-related ADEs occurred within 30 days of hospital discharge in 7.0% of older adults discharged from a medical hospitalization with an opioid prescription. Identified risk factors can be used to inform physician decision-making, conversations with older adults about risk, and development and targeting of harm reduction strategies.

Vitarello, John A, Clara J Fitzgerald, Jennifer L Cluett, Stephen P Juraschek, and Timothy S Anderson. (2022) 2022. “Prevalence of Medications That May Raise Blood Pressure Among Adults With Hypertension in the United States.”. JAMA Internal Medicine 182 (1): 90-93. https://doi.org/10.1001/jamainternmed.2021.6819.

This cross-sectional study characterizes the prevalent use of medications that may raise BP and examine their associations with BP control and antihypertensive use.

Anderson, Timothy S, Ashley O’Donoghue, Oren Mechanic, Tenzin Dechen, and Jennifer Stevens. (2022) 2022. “Administration of Anti-SARS-CoV-2 Monoclonal Antibodies After US Food and Drug Administration Deauthorization.”. JAMA Network Open 5 (8): e2228997. https://doi.org/10.1001/jamanetworkopen.2022.28997.

This cross-sectional study uses time-series data to evaluate the administration of bamlanivimab-etesevimab and casirivimab-imdevimab monoclonal antibody treatments for SARS-CoV-2 infection after the US Food and Drug Administration deauthorized their use in early 2022.

Juraschek, Stephen P, Jennifer L Cluett, Matthew J Belanger, Timothy S Anderson, Anthony Ishak, Shivani Sahni, Courtney Millar, et al. (2022) 2022. “Effects of Antihypertensive Deprescribing Strategies on Blood Pressure, Adverse Events, and Orthostatic Symptoms in Older Adults: Results From TONE.”. American Journal of Hypertension 35 (4): 337-46. https://doi.org/10.1093/ajh/hpab171.

BACKGROUND: The Trial of Nonpharmacologic Interventions in the Elderly (TONE) demonstrated the efficacy of weight loss and sodium reduction to reduce hypertension medication use in older adults. However, the longer-term effects of drug withdrawal (DW) on blood pressure (BP), adverse events, and orthostatic symptoms were not reported.

METHODS: TONE enrolled adults, ages 60-80 years, receiving treatment with a single antihypertensive and systolic BP (SBP)/diastolic BP <145/<85 mm Hg. Participants were randomized to weight loss, sodium reduction, both, or neither (usual care) and followed up to 36 months;  3 months postrandomization, the antihypertensive was withdrawn and only restored if needed for uncontrolled hypertension. BP and orthostatic symptoms (lightheadedness, feeling faint, imbalance) were assessed at randomization and throughout the study. Two physicians independently adjudicated adverse events, masked to intervention, classifying symptomatic (lightheadedness, dizziness, vertigo), or clinical events (fall, fracture, syncope).

RESULTS: Among the 975 participants (mean age 66 years, 48% women, 24% black), mean (±SD) BP was 128 ± 9/71 ± 7 mm Hg. Independent of assignment, DW increased SBP by 4.59 mm Hg (95% confidence interval [CI]: 3.89, 5.28) compared with baseline. There were 113 adverse events (84 symptomatic, 29 clinical), primarily during DW. Compared with usual care, combined weight loss and sodium reduction mitigated the effects of DW on BP (β = -4.33 mm Hg; 95% CI: -6.48, -2.17) and reduced orthostatic symptoms long term (odds ratio = 0.62; 95% CI: 0.41, 0.92), without affecting adverse events (hazard ratio = 1.81; 95% CI: 0.90, 3.65). In contrast, sodium reduction alone increased risk of adverse events (hazard ratio = 1.75; 95% CI: 1.04, 2.95), mainly during DW.

CONCLUSIONS: In older adults, antihypertensive DW may increase risk of symptomatic adverse events, highlighting the need for caution in withdrawing their antihypertensive medications.

CLINICAL TRIALS REGISTRATION: Trial Number NCT00000535.

Anderson, Trevor S, Amanda L Wooster, Savanna L Piersall, Izuchukwu F Okpalanwaka, and Devin B Lowe. (2022) 2022. “Disrupting Cancer Angiogenesis and Immune Checkpoint Networks for Improved Tumor Immunity.”. Seminars in Cancer Biology 86 (Pt 3): 981-96. https://doi.org/10.1016/j.semcancer.2022.02.009.

Immune checkpoint inhibitors (ICIs) have advanced the field of cancer immunotherapy in patients by sustaining effector immune cell activity within the tumor microenvironment. However, the approach in general is still faced with issues related to ICI response duration/resistance, treatment eligibility, and safety, which indicates a need for further refinements. As immune checkpoint upregulation is inextricably linked to cancer-induced angiogenesis, newer clinical efforts have demonstrated the feasibility of disrupting both tumor-promoting networks to mediate enhanced immune-driven protection. This review focuses on such key evidence stipulating the necessity of co-applying ICI and anti-angiogenic strategies in cancer patients, with particular interest in highlighting newer engineered antibody approaches that may provide theoretically superior multi-pronged and safe therapeutic combinations.