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.
Publications
2022
IMPORTANCE: The dramatic rise in use of telehealth accelerated by COVID-19 created new telehealth-specific challenges as patients and clinicians adapted to technical aspects of video visits.
OBJECTIVE: To evaluate a telehealth patient navigator pilot program to assist patients in overcoming barriers to video visit access.
DESIGN, SETTING, AND PARTICIPANTS: This quality improvement study investigated visit attendance outcomes among those who received navigator outreach (intervention group) compared with those who did not (comparator group) at 2 US academic primary care clinics during a 12-week study period from April to July 2021. Eligible participants had a scheduled video visit without previous successful telehealth visits.
INTERVENTIONS: The navigator contacted patients with next-day scheduled video appointments by phone to offer technical assistance and answer questions on accessing the appointment.
MAIN OUTCOMES AND MEASURES: The primary outcome was appointment attendance following the intervention. Return on investment (ROI) accounting for increased clinic adherence and costs of implementation was examined as a secondary outcome.
RESULTS: A total 4066 patients had video appointments scheduled (2553 [62.8%] women; median [IQR] age: intervention, 55 years [38-66 years] vs comparator, 52 years [36-66 years]; P = .02). Patients who received the navigator intervention had significantly increased odds of attending their appointments (odds ratio, 2.0; 95% CI, 1.6-2.6) when compared with the comparator group, with an absolute increase of 9% in appointment attendance for the navigator group (949 of 1035 patients [91.6%] vs 2511 of 3031 patients [82.8%]). The program's ROI was $11 387 over the 12-week period.
CONCLUSIONS AND RELEVANCE: In this quality improvement study, we found that a telehealth navigator program was associated with significant improvement in video visit adherence with a net financial gain. Our findings have relevance for efforts to reduce barriers to telehealth-based health care and increase equity.
BACKGROUND: In 2014, hypertension guidelines for older adults endorsed increased use of fixed-dose combinations, prioritized thiazide diuretics and calcium channel blockers (CCBs) for Black patients, and no longer recommend beta-blockers as first-line therapy.
OBJECTIVE: To evaluate older adults' antihypertensive use following guideline changes.
DESIGN: Time series analysis.
PATIENTS: Twenty percent national sample of Medicare Part D beneficiaries aged 66 years and older with hypertension.
INTERVENTION: Eighth Joint National Committee (JNC8) guidelines MAIN MEASURES: Quarterly trends in prevalent and initial antihypertensive use were examined before (2008 to 2013) and after (2014 to 2017) JNC8. Analyses were conducted among all beneficiaries with hypertension, beneficiaries without chronic conditions that might influence antihypertensive selection (hypertension-only cohort), and among Black patients, given race-based guideline recommendations.
KEY RESULTS: The number of beneficiaries with hypertension increased from 1,978,494 in 2008 to 2,809,680 in 2017, the proportions using antihypertensives increased from 80.3 to 81.2%, and the proportion using multiple classes and fixed-dose combinations declined (60.8 to 58.1% and 20.7 to 15.1%, respectively, all P<.01). Prior to JNC8, the use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and CCBs was increasing. Use of CCBs as initial therapy increased more rapidly following JNC8 (relative change in quarterly trend 0.15% [95% CI, 0.13-0.18%), especially among Black beneficiaries (relative change 0.44% [95% CI, 0.21-0.68%]). Contrary to guidelines, the use of thiazides and combinations as initial therapy consistently decreased in the hypertension-only cohort (13.8 to 8.3% and 25.1 to 15.7% respectively). By 2017, 65.9% of Black patients in the hypertension-only cohort were initiated on recommended first-line or combination therapy compared to 80.3% of non-Black patients.
CONCLUSIONS: Many older adults, particularly Black patients, continue to be initiated on antihypertensive classes not recommended as first-line, indicating opportunities to improve the effectiveness and equity of hypertension care and potentially reduce antihypertensive regimen complexity.
BACKGROUND: Patients with dementia are frequently hospitalized and may face barriers in post-discharge care.
OBJECTIVE: To determine whether patients with dementia have an increased risk of adverse outcomes following discharge.
DESIGN: Retrospective cohort study.
SUBJECTS: Medicare beneficiaries hospitalized in 2016.
MAIN MEASURES: Co-primary outcomes were mortality and readmission within 30 days of discharge. Multivariable logistic regression models were estimated to assess the risk of each outcome for patients with and without dementia accounting for demographics, comorbidities, frailty, hospitalization factors, and disposition.
KEY RESULTS: The cohort included 1,089,109 hospitalizations of which 211,698 (19.3%) were of patients with diagnosed dementia (median (IQR) age 83 (76-89); 61.5% female) and 886,411 were of patients without dementia (median (IQR) age 76 (79-83); 55.0% female). At 30 days following discharge, 5.7% of patients with dementia had died compared to 3.1% of patients without dementia (adjusted odds ratio (aOR) 1.21; 95% CI 1.17 to 1.24). At 30 days following discharge, 17.7% of patients with dementia had been readmitted compared to 13.1% of patients without dementia (aOR 1.02; CI 1.002 to 1.04). Dementia was associated with an increased odds of readmission among patients discharged to the community (aOR 1.07, CI 1.05 to 1.09) but a decreased odds of readmission among patients discharge to nursing facilities (aOR 0.93, CI 0.90 to 0.95). Patients with dementia who were discharged to the community were more likely to be readmitted than those discharged to nursing facilities (18.9% vs 16.0%), and, when readmitted, were more likely to die during the readmission (20.7% vs 4.4%).
CONCLUSIONS: Diagnosed dementia was associated with a substantially increased risk of mortality and a modestly increased risk of readmission within 30 days of discharge. Patients with dementia discharged to the community had particularly elevated risk of adverse outcomes indicating possible gaps in post-discharge services and caregiver support.
IMPORTANCE: Medicare Advantage health plans covered 37% of beneficiaries in 2018, and coverage increased to 48% in 2022. Whether Medicare Advantage plans provide similar care for patients presenting with specific clinical conditions is unknown.
OBJECTIVE: To compare 30-day mortality and treatment for Medicare Advantage and traditional Medicare patients presenting with acute myocardial infarction (MI) from 2009 to 2018.
DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study that included 557 309 participants with ST-segment elevation [acute] MI (STEMI) and 1 670 193 with non-ST-segment elevation [acute] MI (NSTEMI) presenting to US hospitals from 2009-2018 (date of final follow up, December 31, 2019).
EXPOSURES: Enrollment in Medicare Advantage vs traditional Medicare.
MAIN OUTCOMES AND MEASURES: The primary outcome was adjusted 30-day mortality. Secondary outcomes included age- and sex-adjusted rates of procedure use (catheterization, revascularization), postdischarge medication prescriptions and adherence, and measures of health system performance (intensive care unit [ICU] admission and 30-day readmissions).
RESULTS: The study included a total of 2 227 502 participants, and the mean age in 2018 ranged from 76.9 years (Medicare Advantage STEMI) to 79.3 years (traditional Medicare NSTEMI), with similar proportions of female patients in Medicare Advantage and traditional Medicare (41.4% vs 41.9% for STEMI in 2018). Enrollment in Medicare Advantage vs traditional Medicare was associated with significantly lower adjusted 30-day mortality rates in 2009 (19.1% vs 20.6% for STEMI; difference, -1.5 percentage points [95% CI, -2.2 to -0.7] and 12.0% vs 12.5% for NSTEMI; difference, -0.5 percentage points [95% CI, -0.9% to -0.1%]). By 2018, mortality had declined in all groups, and there were no longer statically significant differences between Medicare Advantage (17.7%) and traditional Medicare (17.8%) for STEMI (difference, 0.0 percentage points [95% CI, -0.7 to 0.6]) or between Medicare Advantage (10.9%) and traditional Medicare (11.1%) for NSTEMI (difference, -0.2 percentage points [95% CI, -0.4 to 0.1]). By 2018, there was no statistically significant difference in standardized 90-day revascularization rates between Medicare Advantage and traditional Medicare. Rates of guideline-recommended medication prescriptions were significantly higher in Medicare Advantage (91.7%) vs traditional Medicare patients (89.0%) who received a statin prescription (difference, 2.7 percentage points [95% CI, 1.2 to 4.2] for 2018 STEMI). Medicare Advantage patients were significantly less likely to be admitted to an ICU than traditional Medicare patients (for 2018 STEMI, 50.3% vs 51.2%; difference, -0.9 percentage points [95% CI, -1.8 to 0.0]) and significantly more likely to be discharged to home rather than to a postacute facility (for 2018 STEMI, 71.5% vs 70.2%; difference, 1.3 percentage points [95% CI, 0.5 to 2.1]). Adjusted 30-day readmission rates were consistently lower in Medicare Advantage than in traditional Medicare (for 2009 STEMI, 13.8% vs 15.2%; difference, -1.3 percentage points [95% CI, -2.0 to -0.6]; and for 2018 STEMI, 11.2% vs 11.9%; difference, 0.6 percentage points [95% CI, -1.5 to 0.0]).
CONCLUSIONS AND RELEVANCE: Among Medicare beneficiaries with acute MI, enrollment in Medicare Advantage, compared with traditional Medicare, was significantly associated with modestly lower rates of 30-day mortality in 2009, and the difference was no longer statistically significant by 2018. These findings, considered with other outcomes, may provide insight into differences in treatment and outcomes by Medicare insurance type.
PURPOSE: We examined the prevalence of, and factors associated with, serious opioid-related adverse drug events (ORADEs) that led to an emergency department (ED) visit or hospitalization among patients with chronic gastrointestinal (GI) symptoms and disorders dually enrolled in the Department of Veterans Affairs (VA) and Medicare Part D.
METHODS: In this retrospective cohort study, we used linked national patient-level data (April 1, 2011, to October 31, 2014) from the VA and Centers for Medicare and Medicaid Services to identify serious ORADEs among dually enrolled veterans with a chronic GI symptom or disorder. Outcome measures included serious ORADEs, defined as an ED visit attributed to an ORADE or a hospitalization where the principal or secondary reason for admission involved an opioid. We used multiple logistic regression models to determine factors independently associated with a serious ORADE.
RESULTS: We identified 3,430 veterans who had a chronic GI symptom or disorder; were dually enrolled in the VA and Medicare Part D; and had a serious ORADE that led to an ED visit, hospitalization, or both. The period prevalence of having a serious ORADE was 2.4% overall and 4.4% among veterans with chronic opioid use (≥90 consecutive days). Veterans with serious ORADEs were more likely to be less than 40 years old, male, white, and to have chronic abdominal pain, functional GI disorders, chronic pancreatitis, or Crohn's disease. They were also more likely to have used opioids chronically and at higher daily doses.
CONCLUSION: There may be a considerable burden of serious ORADEs among patients with chronic GI symptoms and disorders. Future quality improvement efforts should target this vulnerable population.
BACKGROUND: Atrial fibrillation (AF) is strongly associated with clinical adversity, including increased hospitalization and bleeding and stroke events. We examined the effect of the SARS-2 Coronavirus 2019 (COVID-19) pandemic on such events in individuals with AF receiving oral anticoagulation.
METHODS: We employed medical and pharmacy claims spanning 2018-2020 from a nationally representative U.S. database (IQVIA Longitudinal Prescription, Medical Claims, and Institutional Claims). We selected individuals receiving oral anticoagulation in 2018 for AF and followed them from 1/1/2019-7/8/2020 for clinical events. We constructed interrupted time-series analyses across 30-day intervals with Poisson regression models to determine the effect of the COVID-19 pandemic on clinical events.
RESULTS: The dataset included 1,439,145 individuals (half with age ≥75 years; 47.6% women) receiving oral anticoagulation. We determined a 19% decrease in emergency room visits following the pandemic declaration and 8% decrease in inpatient admissions. In contrast admissions for stroke and bleeding were not affected by the declaration of the pandemic.
DISCUSSION: These results describe the temporal effect of the COVID-19 pandemic on clinical adversity - hospitalizations, strokes, and bleeding events - in individuals receiving oral anticoagulation for AF. Our analysis quantifies the decrease in clinical adversity accompanying COVID-19 in a large, highly representative U.S. health claims database.