Publications

Despite the availability of efficacious direct-acting antiviral (DAA) therapy, the number of people infected with hepatitis C virus (HCV) continues to rise, and HCV remains a leading cause of liver-related morbidity, liver transplantation, and mortality. We developed and validated machine learning (ML) algorithms to predict DAA treatment failure. Using the HCV-TARGET registry of adults who initiated all-oral DAA treatment, we developed elastic net (EN), random forest (RF), gradient boosting machine (GBM), and feedforward neural network (FNN) ML algorithms. Model performances were compared with multivariable logistic regression (MLR) by assessing C statistics and other prediction evaluation metrics. Among 6525 HCV-infected adults, 308 patients (4.7%) experienced DAA treatment failure. ML models performed similarly in predicting DAA treatment failure (C statistic [95% CI]: EN, 0.74 [0.69-0.79]; RF, 0.74 [0.69-0.80]; GBM, 0.72 [0.67-0.78]; FNN, 0.75 [0.70-0.80]), and all 4 outperformed MLR (C statistic [95% CI]: 0.51 [0.46-0.57]), and EN used the fewest predictors (n = 27). With Youden index, the EN had 58.4% sensitivity and 77.8% specificity, and nine patients were needed to evaluate to identify 1 DAA treatment failure. Over 60% treatment failure were classified in top three risk decile subgroups. EN-identified predictors included male sex, treatment < 8 weeks, treatment discontinuation due to adverse events, albumin level < 3.5 g/dL, total bilirubin level > 1.2 g/dL, advanced liver disease, and use of tobacco, alcohol, or vitamins. Addressing modifiable factors of DAA treatment failure may reduce the burden of retreatment. Machine learning algorithms have the potential to inform public health policies regarding curative treatment of HCV.

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.

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

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.

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.

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.