Publications

BACKGROUND: Chronic benzodiazepine use remains common among older adults, despite limited evidence of benefit and substantial risks. Evidence-based approaches that are feasible in primary care settings are needed to support benzodiazepine deprescribing for older adults.

OBJECTIVES: To determine the feasibility, acceptability, and exploratory patient-centered outcomes of a team-based approach to benzodiazepine deprescribing in primary care.

DESIGN: Single-arm prospective clinical trial.

PARTICIPANTS: Adults age 65 and older prescribed long-term benzodiazepines recruited from four primary care clinics in an academic health system.

INTERVENTIONS: Ten-week virtual primary care embedded program consisting of pharmacist-guided tapering and three psychologist-led mindfulness-informed cognitive behavioral therapy (CBT) sessions.

MAIN MEASURES: Feasibility outcomes included enrollment, retention, and intervention adherence. Acceptability outcomes were collected through qualitative interviews. Exploratory efficacy outcomes included change in mean daily benzodiazepine dose, change in PROMIS anxiety score, and change in PROMIS sleep disturbance score.

KEY RESULTS: Seventeen participants (mean age 72, 29% female, mean 17 years of benzodiazepine use) enrolled and completed all six study visits (100% fidelity). Participants' mean (SD) baseline daily benzodiazepine dose was 9.0 (8.6) diazepam milligram equivalents. At completion, participants had a mean 60.5 percentage point reduction in benzodiazepine use (95% CI -69.9% to -51.3%; p < .001), with all participants reducing their dose and 3 stopping completely. Mean PROMIS anxiety scores decreased from 55.2 to 51.8 (-3.5 point change, 95% CI -6.5 to -0.7; p = 0.02) and mean PROMIS sleep disturbance scores were unchanged at week 10 (-1.7 point change, 95% CI -4.9 to 1.5; p = 0.30). Qualitative interviews indicated the program may target increased self-efficacy to reduce benzodiazepines and endorsed utility from both pharmacist- and psychologist-led components.

CONCLUSIONS: A primary care embedded virtual intervention involving pharmacist-led tapering and mindfulness-informed CBT sessions to support benzodiazepine deprescribing is feasible, acceptable, may reduce older adults' benzodiazepine use, and warrants multi-site testing.

GOV TRIAL NUMBER: NCT06119308.

GOV REGISTRATION DATE: 10/27/2023.

BACKGROUND: Few studies have examined how multiple types of adverse pregnancy outcomes across women's reproductive lives relate to long-term cardiovascular disease.

METHODS: In 59 154 parous participants in Nurses' Health Study II, lifetime history of gestational diabetes, gestational hypertension, preeclampsia, preterm delivery, and low birthweight was self-reported, and cardiovascular events, including myocardial infarction, stroke, and coronary revascularization, were identified through June 2017. We used Cox proportional hazards models to estimate associations between adverse pregnancy outcomes and cardiovascular disease and quantified the extent to which these associations were explained by the later development of hypertension, diabetes, and hypercholesterolemia. We evaluated whether adding adverse pregnancy outcomes improved prediction of premature cardiovascular disease beyond established risk factors such as systolic blood pressure and diabetes.

RESULTS: Each adverse pregnancy outcome was associated with a higher risk of long-term cardiovascular disease. Only gestational hypertension (hazard ratio, 1.62 [95% CI, 1.36-1.92]) and preeclampsia (1.31 [1.11-1.55]) retained independent associations after accounting for the cooccurrence of other adverse pregnancy outcomes. Postpregnancy hypertension, diabetes, and hypercholesterolemia jointly accounted for substantial attenuation (58.4% [38.7%-75.8%]) of the association between adverse pregnancy outcomes in the first pregnancy and later cardiovascular disease. Adding adverse pregnancy outcomes only modestly improved discrimination and slightly improved reclassification.

CONCLUSIONS: Common adverse pregnancy outcomes, especially gestational hypertension and preeclampsia, are associated with higher future cardiovascular risk, with much of this association attenuated after accounting for subsequent cardiovascular risk factors. However, given the limited predictive gains, more nuanced integration of adverse pregnancy outcomes is needed to enhance their clinical utility in cardiovascular risk prediction.

BackgroundPatients with Alzheimer's disease and related dementias (ADRD) have an increased risk for delirium and subsequent complications. Rating delirium severity in the presence of co-occurring dementia is challenging due to overlapping features of delirium and ADRD. The multi-site prospective Better ASsessment of ILlness (BASIL)-II study will develop and validate a new delirium severity instrument for use in patients with and without ADRD.ObjectiveDescribe an expert panel process used to rate delirium severity.MethodsClinical assessors conducted standardized cognitive tests. A separate panel of experts independently reviewed assessors' reports, rated delirium severity using a 0-10 scale, and assigned dementia diagnoses using DSM-5 criteria. Panel agreement was defined using a priori criteria. Cases without agreement after initial review were discussed as a group and re-rated using a modified Delphi approach until achieving consensus.ResultsPatients (N = 488) were on average 79 years old, 58% female, and 75% White. After initial review, 80% of cases were in agreement for delirium severity. Kappa was 0.86 (95% CI, 0.78, 0.82) before expert panel discussion and 0.90 (95%CI, 0.89, 0.92) after consensus. Final delirium severity ratings were no delirium (48%); subsyndromal (22%), mild-moderate (25%), or severe (6%). Disagreement in delirium severity was associated with ADRD (OR 3.02), nursing home setting (2.63), and vision impairment (2.42).ConclusionsThis rigorous process provides confidence that delirium severity can be rated accurately in patients with and without ADRD. We will use this expert panel adjudication to provide the reference standard for validation of a future delirium severity instrument.

UNLABELLED: Background. The use of colorectal cancer (CRC) screening decision aids (DAs) increases patient knowledge and engagement in decision making. Thus, we aimed to implement a CRC DA in a Boston-area health system informed by the Theory of Change quality improvement framework. Methods. Following international standards, an interdisciplinary working group developed a 2-page CRC screening DA, readable on smartphones, for adults ages 45 to 75 y. Prior to DA implementation, we texted a study survey to 8,641 adults age 45 to 75 y seen in primary care at our health system (baseline). Between January 2022 and April 2023, we texted the DA to 21,522 patients due for CRC screening and scheduled with their primary care provider (PCP). In August 2022 and in May 2023 (follow-up), we texted a study survey to patients who had been texted the DA in prior months. We used linear regression to examine the DA's effects on shared decision-making (SDM) quality (using the 4-item SDM Process Scale, for which scores range from 0-4), knowledge (2 questions), and reported discussions with PCPs of screening modalities. Results. Of 30,163 texted study surveys, 1,692 (5.6%, 697 baseline and 995 follow-up) were completed; 77.1% of participants were non-Hispanic White and 45.3% were aged 60 to 75 y. Overall, 30.6% (n = 304) of follow-up survey respondents reported reviewing the DA. Compared with baseline participants, these patients reported higher SDM quality (SDM process scores = 2.5 v. 2.1, P < 0.001) and more knowledge about CRC screening and were more likely to have discussed stool-based testing with PCPs. Limitations. Low response rate with no sociodemographic data for nonresponders. Conclusions/Implications. Patients who read a CRC screening DA texted to them before primary care visits may experience improved SDM quality. However, a more intensive implementation strategy may be needed for more patients to read DAs.

HIGHLIGHTS: It is feasible for large health systems to automatize text messaging of colorectal cancer (CRC) screening decision aids (DAs) to patients due for CRC screening before a visit with their primary care practitioner.Patients who review a texted CRC screening DA report higher shared decision-making quality and knowledge about CRC screening.Use of CRC DAs may decrease screening via colonoscopy but not overall screening rates.A more intensive intervention than text messaging is likely needed to increase the number of patients who review a CRC screening DA.

IMPORTANCE: There is limited research on the long-term associations of plasma phosphorylated tau 217 (p-tau217) with mild cognitive impairment (MCI) and dementia. No study has evaluated whether such associations vary by race or hormone therapy (HT) use.

OBJECTIVE: To examine associations of baseline plasma p-tau217 with incident MCI and dementia and determine whether associations vary by age, race, APOE ε4 carrier status, or HT use.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study examined women recruited from 39 US clinical sites between 1996 and 1999 into the Women's Health Initiative Memory Study who were randomized to either estrogen alone vs placebo or estrogen plus progestin vs placebo. Women were assessed for up to 25 years through 2021. Baseline plasma p-tau217 was measured in 2024 and analyzed between February and August 2025. Women aged 65 to 79 years who were cognitively unimpaired at baseline were included for this analysis.

EXPOSURE: Plasma p-tau217, quantified using the ALZpath Simoa assay.

MAIN OUTCOMES AND MEASURES: The primary outcome was the combined end point of incident MCI or probable dementia. Secondary outcomes included MCI and dementia examined separately. Cause-specific hazard ratios (HRs) and 95% CIs for the association of p-tau217 with MCI or dementia were estimated using Cox proportional hazards regression models.

RESULTS: Among 2766 participants (mean [SD] age, 69.9 [3.8] years; 486 [17.9%] Black, 196 [7.1%] Hispanic, and 2007 [73.9%] White), 1311 developed the combined end point of MCI or dementia (849 participants with MCI and 752 participants with dementia). Every 1-SD increase in log2-transformed p-tau217 was associated with incident MCI or dementia (HR, 2.43; 95% CI, 2.18-2.71) and each individual outcome (MCI: HR, 1.94; 95% CI, 1.72-2.20; dementia: HR, 3.17; 95% CI, 2.79-3.61). Associations of p-tau217 with dementia were larger in magnitude for women randomized to estrogen plus progestin (HR, 4.18; 95% CI, 3.41-5.13) vs placebo (HR, 3.07; 95% CI, 2.41-3.91) (P for interaction = .04) but did not significantly vary by estrogen alone vs placebo. P-tau217 associations with MCI or dementia were larger in magnitude for women older than 70 years (P for interaction = .04), APOE ε4 carriers (P for interaction = .02), and White women compared with Black women (P for interaction < .001). However, the combination of p-tau217 and age performed similarly in White women (area under the curve = 72.0%; 95% CI, 70.3%-73.6%) and Black women (area under the curve = 70.4%; 95% CI, 64.0%-78.0%). P-tau217 was not associated with incident MCI in Black women.

CONCLUSIONS AND RELEVANCE: In this cohort study of cognitively unimpaired older women, p-tau217 was associated with incident MCI or dementia up to 25 years later. These findings suggest that age, race, APOE ε4, and HT use should be considered when examining associations of p-tau217 with cognitive outcomes.

BACKGROUND: Resistant hypertension is associated with adverse cardiovascular outcomes and mortality. In the past decade, management guidelines have shifted to target lower blood pressures (BP). Current prevalence and prescribing patterns among adults with resistant hypertension are not well characterized.

METHODS: We used data from the National Health and Nutrition Examination Survey from 2003 to 2020. Apparent treatment-resistant hypertension (aTRH) was defined as patients on a diuretic, either with a systolic BP ≥130 or diastolic BP ≥80 mm Hg while on 3 medications or those on ≥4 medications regardless of BP. Medications were identified through pill bottle review.

RESULTS: Of 24 579 adults with hypertension, 1939 had aTRH (42.4% male, 19.9% Black), corresponding to a weighted total of 6 989 821 US patients. Among hypertensive adults, the prevalence of aTRH was 6.41% (95% CI, 5.97%-6.88%) and remained stable over time. Over the study duration, aTRH prevalence among adults on treatment decreased from 17.7% to 12.6%. The overall prevalence of hypertension rose from 50.1% to 54.0%, while the prevalence of uncontrolled BP decreased from 75.0% to 68.7%. Over time, use of 3 drug regimens for aTRH decreased (57.8%-42.9%), while 4 drug regimens increased (34.0%-51.8%). aTRH was most strongly associated with older patients, those of Black race, higher body mass index, and more advanced cardiovascular comorbidities.

CONCLUSION: The prevalence of aTRH has remained stable over the past 2 decades despite the rising incidence of hypertension. Use of multidrug treatment regimens has increased, aligning with national guidelines. However, uncontrolled hypertension remains high.