Publications

IMPORTANCE: Asymptomatic blood pressure (BP) elevations are common in hospitalized older adults, and widespread heterogeneity in the clinical management of elevated inpatient BPs exists.

OBJECTIVE: To examine the association of intensive treatment of elevated inpatient BPs with in-hospital clinical outcomes of older adults hospitalized for noncardiac conditions.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study examined Veterans Health Administration data between October 1, 2015, and December 31, 2017, for patients aged 65 years or older hospitalized for noncardiovascular diagnoses and who experienced elevated BPs in the first 48 hours of hospitalization.

INTERVENTIONS: Intensive BP treatment following the first 48 hours of hospitalization, defined as receipt of intravenous antihypertensives or oral classes not used prior to admission.

MAIN OUTCOME AND MEASURES: The primary outcome was a composite of inpatient mortality, intensive care unit transfer, stroke, acute kidney injury, B-type natriuretic peptide elevation, and troponin elevation. Data were analyzed between October 1, 2021, and January 10, 2023, with propensity score overlap weighting used to adjust for confounding between those who did and did not receive early intensive treatment.

RESULTS: Among 66 140 included patients (mean [SD] age, 74.4 [8.1] years; 97.5% male and 2.6% female; 17.4% Black, 1.7% Hispanic, and 75.9% White), 14 084 (21.3%) received intensive BP treatment in the first 48 hours of hospitalization. Patients who received early intensive treatment vs those who did not continued to receive a greater number of additional antihypertensives during the remainder of their hospitalization (mean additional doses, 6.1 [95% CI, 5.8-6.4] vs 1.6 [95% CI, 1.5-1.8], respectively). Intensive treatment was associated with a greater risk of the primary composite outcome (1220 [8.7%] vs 3570 [6.9%]; weighted odds ratio [OR], 1.28; 95% CI, 1.18-1.39), with the highest risk among patients receiving intravenous antihypertensives (weighted OR, 1.90; 95% CI, 1.65-2.19). Intensively treated patients were more likely to experience each component of the composite outcome except for stroke and mortality. Findings were consistent across subgroups stratified by age, frailty, preadmission BP, early hospitalization BP, and cardiovascular disease history.

CONCLUSIONS AND RELEVANCE: The study's findings indicate that among hospitalized older adults with elevated BPs, intensive pharmacologic antihypertensive treatment was associated with a greater risk of adverse events. These findings do not support the treatment of elevated inpatient BPs without evidence of end organ damage, and they highlight the need for randomized clinical trials of inpatient BP treatment targets.

IMPORTANCE: Dementia is a life-altering diagnosis that may affect medication safety and goals for chronic disease management.

OBJECTIVE: To examine changes in medication use following an incident dementia diagnosis among community-dwelling older adults.

DESIGN, SETTING, AND PARTICIPANTS: In this cohort study of adults aged 67 years or older enrolled in traditional Medicare and Medicare Part D, patients with incident dementia diagnosed between January 2012 and December 2018 were matched to control patients based on demographics, geographic location, and baseline medication count. The index date was defined as the date of first dementia diagnosis or, for controls, the date of the closest office visit. Data were analyzed from August 2021 to June 2023.

EXPOSURE: Incident dementia diagnosis.

MAIN OUTCOMES AND MEASURES: The main outcomes were overall medication counts and use of cardiometabolic, central nervous system (CNS)-active, and anticholinergic medications. A comparative time-series analysis was conducted to examine quarterly changes in medication use in the year before through the year following the index date.

RESULTS: The study included 266 675 adults with incident dementia and 266 675 control adults; in both groups, 65.1% were aged 80 years or older (mean [SD] age, 82.2 [7.1] years) and 67.8% were female. At baseline, patients with incident dementia were more likely than controls to use CNS-active medications (54.32% vs 48.39%) and anticholinergic medications (17.79% vs 15.96%) and less likely to use most cardiometabolic medications (eg, diabetes medications, 31.19% vs 36.45%). Immediately following the index date, the cohort with dementia had a greater increase in mean number of medications used (0.41 vs -0.06; difference, 0.46 [95% CI, 0.27-0.66]) and in the proportion of patients using CNS-active medications (absolute change, 3.44% vs 0.79%; difference, 2.65% [95% CI, 0.85%-4.45%]) owing to an increased use of antipsychotics, antidepressants, and antiepileptics. The cohort with dementia also had a modestly greater decline in use of anticholinergic medications (quarterly change in use, -0.53% vs -0.21%; difference, -0.32% [95% CI, -0.55% to -0.08%]) and most cardiometabolic medications (eg, quarterly change in antihypertensive use: -0.84% vs -0.40%; difference, -0.44% [95% CI, -0.64% to -0.25%]). One year after diagnosis, 75.2% of the cohort with dementia were using 5 or more medications (2.8% increase).

CONCLUSIONS AND RELEVANCE: In this cohort study of Medicare Part D beneficiaries, following an incident dementia diagnosis, patients were more likely to initiate CNS-active medications and modestly more likely to discontinue cardiometabolic and anticholinergic medications compared with the control group. These findings suggest missed opportunities to reduce burdensome polypharmacy by deprescribing long-term medications with high safety risks or limited likelihood of benefit or that may be associated with impaired cognition.

OBJECTIVES: Older adults undergoing orthopedic procedures are commonly discharged from the hospital on opioids, but risk factors for postdischarge opioid-related adverse drug events (ORADEs) have not been previously examined. We aimed to identify risk factors for ORADEs after hospital discharge following orthopedic procedures.

METHODS: This is a retrospective cohort study of a national sample of Medicare beneficiaries 65 years or older, who underwent major orthopedic surgery during hospitalization in 2016 and had an opioid fill within 2 days of discharge. We excluded beneficiaries with hospice claims and those admitted from or discharged to a facility. We used billing codes and medication claims to define potential ORADEs requiring a hospital revisit within 30 days of discharge.

RESULTS: Among 30,514 hospitalizations with a major orthopedic procedure (89.7% arthroplasty, 5.6% treatment of fracture of dislocation, 4.7% other) and an opioid claim, a potential ORADE requiring hospital revisit occurred in 750 (2.5%). Independent risk factors included age of 80 years or older (hazard ratio [HR], 1.65; 95% confidence interval, 1.38-1.97), female sex (HR, 1.34 [1.16-1.56]), and clinical conditions, including heart failure (HR, 1.34 [1.10-1.62]), respiratory illness (HR, 1.23 [1.03-1.46]), kidney disease (HR, 1.23 [1.04-1.47]), dementia/delirium (HR, 1.63 [1.26-2.10]), anxiety disorder (HR, 1.42 [1.18-1.71]), and musculoskeletal/nervous system injuries (HR, 1.54 [1.24-1.90]). Prior opioid use, coprescribed sedating medications, and opioid prescription characteristics were not associated with ORADEs after adjustment for patient characteristics.

CONCLUSIONS: Potential ORADEs occurred in 2.5% of older adults discharged with opioids after orthopedic surgery. These risk factors can inform clinician decision making, conversations with older adults, and targeting of harm reduction strategies.

Colorectal cancer (CRC) remains a leading cause of cancer-related mortality despite efforts to improve standard interventions. As CRC patients can benefit from immunotherapeutic strategies that incite effector T cell action, cancer vaccines represent a safe and promising therapeutic approach to elicit protective and durable immune responses against components of the tumor microenvironment (TME). In this study, we investigate the pre-clinical potential of a Listeria monocytogenes (Lm)-based vaccine targeting the CRC-associated vasculature. CRC survival and progression are reliant on functioning blood vessels to effectively mediate various metabolic processes and oxygenate underlying tissues. We, therefore, advance the strategy of initiating immunity in syngeneic mouse models against the endogenous pericyte antigen RGS5, which is a critical mediator of pathological vascularization. Overall, Lm-based vaccination safely induced potent anti-tumor effects that consisted of recruiting functional Type-1-associated T cells into the TME and reducing tumor blood vessel content. This study underscores the promising clinical potential of targeting RGS5 against vascularized tumors like CRC.

BACKGROUND: Atrial fibrillation is a common cause of stroke among older adults and is often first detected during hospitalization, given frequent use of cardiac telemetry.

METHODS: In a 20% national sample of Medicare fee-for-service beneficiaries, we identified patients aged 65-or-older newly diagnosed with atrial fibrillation while hospitalized in 2016. Our primary outcome was an oral anticoagulant claim within 7-days of discharge. Multivariable logistic regression analyses assessed relationships between anticoagulation initiation and thromboembolic and bleeding risk scores while controlling for demographics, frailty, comorbidities, and hospitalization characteristics.

RESULTS: Among 38,379 older adults newly diagnosed with atrial fibrillation while hospitalized (mean age 78.2 [SD 8.4]; 51.8% female; 83.3% white), 36,633 (95.4%) had an indication for anticoagulation and 24.6% (9011) of those initiated an oral anticoagulant following discharge. Higher CHA2 DS2 -VASc score was associated with a small increase in oral anticoagulant initiation (predicted probability 20.5% [95% CI, 18.7%-22.3%] for scores <2 and 24.9% [CI, 24.4%-25.4%] for ≥4). Elevated HAS-BLED score was associated with a small decrease in probability of anticoagulant initiation (25.4% [CI, 24.4%-26.4%] for score <2 and 23.1% [CI, 22.5%-23.8%] for ≥3). Frailty was associated with decreased likelihood of oral anticoagulant initiation (24.7% [CI, 23.2%-26.2%] for non-frail and 18.1% [CI, 16.6%-19.6%] for moderately-severely frail). Anticoagulant initiation varied by primary reason for hospitalization, with predicted probability highest among patients with a primary diagnosis of atrial fibrillation (46.1% [CI, 45.0%-47.3%]) and lowest among those with non-cardiovascular conditions (13.8% [CI, 13.3%-14.3%]) and bleeds (3.6% [CI, 2.4%-4.8%]).

CONCLUSIONS: Oral anticoagulant initiation is uncommon among older adults newly diagnosed with atrial fibrillation during hospitalization, even among patients hospitalized primarily for atrial fibrillation and patients with high thromboembolic risk. Clinicians should discuss risks and benefits of oral anticoagulants with all inpatients found to have atrial fibrillation.

IMPORTANCE: Use of telehealth has increased substantially in recent years. However, little is known about whether the likelihood of completing recommended tests and specialty referrals-termed diagnostic loop closure-is associated with visit modality.

OBJECTIVES: To examine the prevalence of diagnostic loop closure for tests and referrals ordered at telehealth visits vs in-person visits and identify associated factors.

DESIGN, SETTING, AND PARTICIPANTS: In a retrospective cohort study, all patient visits from March 1, 2020, to December 31, 2021, at 1 large urban hospital-based primary care practice and 1 affiliated community health center in Boston, Massachusetts, were evaluated.

MAIN MEASURES: Prevalence of diagnostic loop closure for (1) colonoscopy referrals (screening and diagnostic), (2) dermatology referrals for suspicious skin lesions, and (3) cardiac stress tests.

RESULTS: The study included test and referral orders for 4133 patients (mean [SD] age, 59.3 [11.7] years; 2163 [52.3%] women; 203 [4.9%] Asian, 1146 [27.7%] Black, 2362 [57.1%] White, and 422 [10.2%] unknown or other race). A total of 1151 of the 4133 orders (27.8%) were placed during a telehealth visit. Of the telehealth orders, 42.6% were completed within the designated time frame vs 58.4% of those ordered during in-person visits and 57.4% of those ordered without a visit. In an adjusted analysis, patients with telehealth visits were less likely to close the loop for all test types compared with those with in-person visits (odds ratio, 0.55; 95% CI, 0.47-0.64).

CONCLUSIONS: The findings of this study suggest that rates of loop closure were low for all test types across all visit modalities but worse for telehealth. Failure to close diagnostic loops presents a patient safety challenge in primary care that may be of particular concern during telehealth encounters.

OBJECTIVES: Pregnancy provides a critical opportunity to engage individuals with opioid use disorder in care. However, before the COVID-19 pandemic, there were multiple barriers to accessing buprenorphine/naloxone during pregnancy. Care disruptions during the pandemic may have further exacerbated these existing barriers. To quantify these changes, we examined trends in the number of individuals filling buprenorphine/naloxone prescriptions during the COVID-19 pandemic.

METHODS: We estimated an interrupted time series model using linked national pharmacy claims and medical claims data from prepandemic (May 2019 to February 2020) to the pandemic period (April 2020 to December 2020). We estimated changes in the growth rate in the monthly number of individuals filling buprenorphine/naloxone prescriptions in the 6 months preceding a delivery claim, per 100,000 pregnancies, during the COVID-19 pandemic.

RESULTS: We identified 2947 pregnant individuals filling buprenorphine/naloxone prescriptions. Before the pandemic, there was positive growth in the monthly number of individuals filling buprenorphine/naloxone prescriptions (4.83%; 95% confidence interval [CI], 3.82-5.84%). During the pandemic, this monthly growth rate declined for both individuals on commercial insurance and individuals on Medicaid (all payers: -5.53% [95% CI, -6.65% to -4.41%]; Medicaid: -7.66% [95% CI, -10.14% to -5.18%]; Commercial: -3.59% [95% CI, -5.32% to -1.87%]).

CONCLUSION: The number of pregnant individuals filling buprenorphine/naloxone prescriptions was increasing, but this growth has been lost during the pandemic.

Despite the availability of various treatment options, colorectal cancer (CRC) remains a significant contributor to cancer-related mortality. Current standard-of-care interventions, including surgery, chemotherapy, and targeted agents like immune checkpoint blockade and anti-angiogenic therapies, have improved short-term patient outcomes depending on disease stage, but survival rates with metastasis remain low. A promising strategy to enhance the clinical experience with CRC involves the use of dendritic cell (DC) vaccines that incite immunity against tumor-derived blood vessels, which are necessary for CRC growth and progression. In this report, we target tumor-derived pericytes expressing DLK1 with a clinically-relevant alpha type-1 polarized DC vaccine (αDC1) in a syngeneic mouse model of colorectal cancer. Our pre-clinical data demonstrate the αDC1 vaccine's ability to induce anti-tumor effects by facilitating cytotoxic T lymphocyte activity and ablating the tumor vasculature. This work, overall, provides a foundation to further interrogate immune-mediated mechanisms of protection in order to help devise efficacious αDC1-based strategies for patients with CRC.