Research

Estimating the magnitude of placebo responses across pharmacological and nonpharmacological trials is important for understanding their influence on trial outcomes. Yet, the extent to which more intense placebo interventions like sham acupuncture yield larger analgesic responses than placebo pills, and the factors predicting these responses, remain unclear. This meta-analysis investigated the magnitude and predictors of placebo analgesia responses in pharmacological vs acupuncture trials. Analyses included individual patient data from the placebo arm of 11 randomized controlled trials (RCTs): 9 pharmacological RCTs using placebo pills (N = 2021) and 2 acupuncture RCTs using sham acupuncture (N = 747). All trials were conducted in patients with chronic nociceptive pain (osteoarthritis, N = 2068; low back pain, N = 700). The placebo response was calculated as the change in pain intensity (0-100) between baseline and week 12. A random effects model demonstrated that placebo pills and patients with osteoarthritis exhibited smaller placebo responses than sham acupuncture and patients with low back pain (both P < 0.001, marginal effects). A mixed effects model showed that route of administration interacted significantly with baseline pain, premature termination, and the presence of adverse events. Together, predictors explained 20% to 25% of the individual variance in placebo responses, whereas 75% to 80% remained unaccounted for. In summary, sham acupuncture accounted for slightly larger placebo responses than placebo pills. Since basic trial and patient parameters explained only a small portion of this variability, we might need to start considering the patient's perception of the treatment-including cognition and emotions-to better predict placebo analgesia responses.

BACKGROUND: Age-related cognitive decline results in significant clinical and public health costs. Cognitive decline predisposes individuals to dementia and leads to difficulties with activities of daily living and increased hospitalizations. While a few dietary interventions have shown considerable promise at delaying cognitive decline, studies of the effects of long-term blueberry consumption on brain health among older adults have been limited and equivocal.

OBJECTIVE: To test the hypothesis that a 24-week intervention with blueberry powder versus placebo will improve (i) plasma biomarkers of brain health and (ii) cognitive performance in older adults.

METHODS: This randomized, double-blind, placebo-controlled trial will be conducted in older Americans aged 65-99 years old. Sixty-seven participants will be randomly assigned to receive either blueberry powder (20 g/d - equivalent of one (1) cup of fresh blueberries) or a placebo powder (20 g/d) for 24 weeks. Participants will undergo four clinic visits (baseline and 8 weeks, 16 weeks, and 24 weeks after randomization) for cognitive assessments, blood pressure measurements, and blood sample collections. Primary outcomes will be plasma levels of neurofilament light chain (NFL) and phosphorylated tau protein (pTau-181). Secondary outcomes will be plasma levels of glial fibrillary acidic protein (GFAP) and non-esterified fatty acids (NEFA); blood pressure during visits; and cognitive function.

CONCLUSION: Findings from this trial will answer the question whether a long-term intervention with blueberry powder can improve (i) plasma biomarkers of brain health and (ii) cognitive function in older adults.

INTRODUCTION: Triple-negative breast cancer (TNBC) often shows significant response to neoadjuvant chemotherapy (NACT), creating opportunities for axillary de-escalation. This study investigates axillary de-escalation and the factors influencing its use in TNBC.

METHODS: Patients with cT1-cT2, cN1 TNBC treated between 2012 and 2020 were identified from the National Cancer Database. Nodal response rates, including achievement of ypN0, were analyzed. Logistic regression identified clinical and sociodemographic factors associated with axillary management.

RESULTS: Among 12,742 patients undergoing axillary lymph node dissection (ALND), 31.7% achieved nodal pathologic complete response (pCR). These patients were more also likely to achieve breast tumor pCR. Treatment across multiple facilities was associated with a higher likelihood of attempted axillary de-escalation. ALND rates steadily declined between 2014 and 2020.

CONCLUSION: Despite achieving nodal pCR after NACT, many patients with TNBC underwent ALND. These findings underscore the need to refine criteria and increase adoption of axillary de-escalation strategies in TNBC.

BACKGROUND: Mechanisms of injury due to hypertension (HTN) in pregnancy remain poorly characterized. This study examined trends in markers of cardiac injury (high-sensitivity troponin I, hs-cTnI), strain (N-terminal pro-B-type natriuretic peptide, NT-proBNP), and inflammation (high-sensitivity C-reactive protein, hs-CRP) in pregnancies with and without HTN.

METHODS: This prospective, 1:1 case-control study enrolled pregnant women with and without HTN (24-32 weeks gestation) from 2019-2022. HTN was defined by a clinical diagnosis of HTN or baseline blood pressure (BP)≥140/90 mmHg. Serum was collected at baseline, pre-delivery, and postpartum day 1. Mixed effects tobit models compared log-transformed hs-cTnI, NT-proBNP, and hs-CRP across HTN groups and over time, adjusted for age and BMI.

RESULTS: Mean baseline BP was 130.5 (17.5)/88.2 (13.5) mmHg for the HTN group (n=38, 86.8% chronic, 13.2% gestational HTN), and 112.0 (9.8)/70.9 (8.2) mmHg for those without HTN (n=38). Over pregnancy, the HTN group had higher hs-cTnI than those without HTN (2.12 [0.43] vs. 1.07 [0.25], Δ1.05 [95%CI: 0.07-2.03] ng/L). Compared to baseline, hs-cTnI increased at pre-delivery and postpartum for both groups. Overall, the two groups had similar NT-proBNP (HTN: 39.0 [4.5] vs. no HTN: 35.6 [4.3] pg/mL) and hs-CRP (HTN: 12.0 [1.7] vs. no HTN: 9.9 [1.5] mg/L). For both groups, NT-proBNP and hs-CRP increased from baseline to postpartum (NT-proBNP, HTN: 127% [58-227%], no HTN: 120% [51-219%]; hs-CRP: HTN: 550% [343-853%], no HTN: 664% [415-1034%]).

CONCLUSION: HTN was associated with markers of cardiac injury during pregnancy, while delivery alone led to increases in markers of strain and inflammation. These biomarker changes associated with HTN in pregnancy may represent potential mechanisms to explain adverse cardiovascular events.

BackgroundAdvance care planning (ACP) helps older adults make end-of-life medical decisions. While ACP discussions are associated with improved patient outcomes, overall engagement remains low in the emergency department (ED).ObjectivesThis study assessed ACP engagement in older ED patients.MethodsWe conducted a questionnaire study among adults ≥65 in a Boston ED (July-Oct 2023). Our primary outcome was ACP Engagement as measured by a validated 9-item instrument with three ACP self- efficacy and six ACP readiness questions. Secondary outcomes included participants' preferences for learning about five ACP topics in the ED-medical decision makers, what matters most, leeway and flexibility for decision makers, sharing wishes, and asking questions)-as well as their favored learning formats (eg, pamphlets, videos, clinician conversations). Each was rated on a 5-point Likert scale. We examined the relationship between ACP engagement and existing electronic health record (EHR) documentation.ResultsNinety-nine older adults participated (mean age 75.5; 53.5% women). On the 9-item ACP Engagement Survey, participants reported high overall scores with a mean of 4.1 (95% CI: 4.0-4.2). Among ACP readiness topics, 80 (81.6%) named a decision-maker; 37 (40.2%) discussed end-of-life wishes with doctors. Participants preferred ED team conversations. Among the 51 participants who reported having signed paperwork regarding end-of-life wishes, only 7 (13.7%) had forms documented in the EHR.ConclusionsAmong older adults in a large Boston-based ED, ACP engagement was high, but few patients had documentation of end-of-life wishes available in the EHR. Findings highlight the need for better ACP documentation in EDs.

PURPOSE OF THE REVIEW: Hypertension remains a major public health concern globally and in the United States with significant racial/ethnic disparities in prevalence, treatment, and control. Despite effective treatments, undiagnosed or uncontrolled hypertension persists, leading to an increased risk of cardiovascular disease and substantial healthcare costs. Addressing hypertension disparities requires a comprehensive approach, integrating clinical interventions with community-based strategies. This review examines the current landscape of clinic-and community-based interventions designed to improve hypertension management and reduce disparities.

RECENT FINDINGS: Clinic-based approaches highlighted include implementing evidence-based guidelines, using treatment algorithms, promoting self-management, integrating digital health technologies, and incorporating team-based care approaches. Community interventions discussed involve lifestyle modification programs, faith-based initiatives, trusted community spaces, culturally-tailored health education, engaging community health workers, and collaborative care models linking clinics and communities. This review stresses the importance of addressing SDoH, fostering community engagement, and delivering culturally competent care. Strengthening clinic-community linkages, evaluating long-term effectiveness and cost-effectiveness, leveraging technology and innovation, and addressing gaps in research for underrepresented groups are key priorities for advancing health equity in hypertension management.

SUMMARY: To effectively close the widening gap in hypertension disparities, collaborative multi-level efforts integrating clinical excellence and community empowerment are essential to mitigate the disproportionate burden of hypertension among racial/ethnic minority populations.