Publications

In psychiatry and medicine, there is a long history of framing placebo effects primarily as nuisance factors and focusing on how they should be minimised in clinical trials. However, a new view on placebo effects has emerged with advances in understanding their complex neurobiology and observations of unexpectedly large placebo responses in recent psychiatric trials. In particular, novel therapeutic device trials for depression have shown placebo-group remission rates nearing 50%. Instead of considering these studies as a failure and moving on, questions should be raised on how such responses are possible and how these effects can be harnessed for the benefit of patients. There have also been important new insights into the mechanisms of nocebo effects and analogous questions on how best to mitigate the effect of negative expectations on symptoms and medication side-effects. In this Review, paper 1 of 2 on reconceptualising placebo and nocebo effects, we discuss the rationale, strategies, and ethical considerations related to harnessing placebo effects and mitigating nocebo effects in clinical practice, including discussion of target patient populations, traditional pure and impure placebos, authorised deception, honest open-label placebo, pharmacotherapy dose reduction via conditioned placebo, nocebo education, nocebo reframing, and other ways to apply principles underlying placebo and nocebo effects, such as shifting mindsets and enhancing the therapeutic context. Lastly, we highlight the centrality of this topic to psychiatry, but explore how better understanding the interactions of mind, brain, and body-epitomised by placebo and nocebo effects-has crucial relevance across medicine.

Adults with cancer are at risk for complications from vaccine-preventable diseases, yet vaccine adherence in this population remains poorly characterized. This cross-sectional study used the National Health Interview Survey 2019 to 2023 to examine trends in influenza, pneumococcal, and shingles vaccines among adults aged ≥50 years with cancer. Of the 6,533 respondents included, only 30.6% (95% confidence interval [CI; 29.3%, 31.9%]) reported receiving all three recommended vaccines. Factors associated with lower vaccination adherence included younger age (odds ratio [OR] comparing ages ≥75 to 50 to 64 years 5.39; 95% CI [4.70, 6.18]), male sex (OR 0.81; 95% CI [0.73, 0.90]), Black (OR 0.59; 95% CI [0.47, 0.73]) or Hispanic race/ethnicity (OR 0.69; 95% CI [0.52, 0.92]), Medicaid insurance (OR 0.79; 95% CI [0.65, 0.96]), and lower educational attainment (OR 0.65; 95% CI [0.58, 0.73]). Preventable disease vaccination remains subpar in the adult cancer population, and further efforts including targeted interventions are necessary to improve preventative health efforts in these patients.

BACKGROUND: Risks related to long-term opioid therapy for chronic pain are high and may increase over time with aging. Deprescribing may be a beneficial intervention for older adults prescribed chronic opioids.

METHODS: Semi-structured interviews with hypothetical clinical cases of older adults prescribed opioids for chronic pain: (1) low-risk case: a patient prescribed low-dose opioids without concerns; (2) moderate-risk case: a patient with multimorbidity and concurrent benzodiazepine use prescribed moderate opioid doses; (3) high-risk case: a patient prescribed high-dose opioids with signs of an opioid use disorder (OUD). PCPs were asked, in an open-ended fashion, to discuss whether they would initiate a deprescribing conversation, how they would approach deprescribing, and how they would approach a patient who declined recommendations to deprescribe.

PARTICIPANTS AND SETTING: PCPs from a Massachusetts health system.

RESULTS: 18 PCPs participated (56% female, 78% academic). More than half of PCPs would initiate a deprescribing conversation across the three cases. PCPs' approach to deprescribing and mitigating risks differed based on clinical risk. In low and moderate-risk cases, PCPs emphasized a patient-directed taper plan and education on opioid risks. In the high-risk case, some PCPs were uncertain about initiating a deprescribing conversation due to concerns about the patient's mental health and the risk of illicit opioid use. Naloxone was infrequently recommended across the three cases, but in the high-risk case, approximately half of PCPs suggested medications for OUD.

CONCLUSIONS: PCPs reported that they would often initiate opioid deprescribing conversations with older adults, but were less confident in managing older adults with signs of OUD. PCPs require additional support to implement successful conversations on opioid deprescribing with older adults.

OBJECTIVE: This retrospective cohort study assessed the association between aneurysm diameter and 1 year sac behaviour.

METHODS: All endovascular aneurysm repairs (EVARs) with 1 year imaging follow up in the Vascular Quality Initiative (2003 - 2024) were included. Sac behaviour was defined as expansion (≥ 5 mm enlargement), regression (≥ 5 mm shrinkage), or stable (< 5 mm change). Aneurysm diameter was categorised by sex specific thresholds (female/male): < 45/< 50 mm, 45 - 50/50 - 55 mm, 50 - 55/55 - 60 mm, 55 - 60/60 - 65 mm, 60 - 65/65 - 70 mm, and > 65/> 70 mm. Sac behaviour was estimated using multinomial logistic regression, with sac stability and 50 - 55/55 - 60 mm as reference categories. Restricted cubic splines (RCS) were incorporated to explore the continuous relationship.

RESULTS: A total of 28 275 patients were included. At 1 year, 48.5% had sac regression, 45.4% stability, and 6.1% expansion. Using 50 - 55/55 - 60 mm as the diameter reference and sac stability as the outcome reference, adjusted odds ratios (95% confidence interval) for sac regression were 0.40 (0.37 - 0.43) for < 45/< 50 mm, 0.82 (0.77 - 0.86) for 45 - 50/50 - 55 mm, 1.25 (1.17 - 1.33) for 55 - 60/60 - 65 mm, 1.38 (1.29 - 1.48) for 60 - 65/65 - 70 mm, and 1.46 (1.37 - 1.57) for > 65/> 70 mm. Corresponding odds ratios for expansion were 1.92 (1.88 - 1.95), 1.03 (1.02 - 1.04), 1.20 (1.18 - 1.21), 1.43 (1.41 - 1.45), and 1.67 (1.64 - 1.69), respectively. RCS demonstrated that regression increased steeply with diameter up to ∼55 mm, while stability declined progressively. Expansion was most common in small aneurysms and least likely near 55 mm.

CONCLUSION: Pre-operative aneurysm diameter showed a non-linear association with 1 year sac behaviour. Sac regression increased up to ∼55 mm, where the predicted probability of expansion was lowest. Small aneurysms had nearly twofold higher odds of expansion relative to stability. In larger aneurysms, higher odds of expansion reflected lower stability rather than a meaningful rise in absolute expansion risk. Further investigation is needed to clarify the mechanisms underlying sac expansion in small aneurysms. These findings suggest that patients treated at small diameters may require closer surveillance.

BACKGROUND AND AIMS: Heart failure with preserved ejection fraction (HFpEF) is increasingly recognized as a syndrome of reserve dysfunction. However, integrated assessment of biventricular (LV/RV) volumetric reserve under physiological stress remains underexplored. We aimed to investigate whether exercise cardiac magnetic resonance (Ex-CMR) can reveal distinct volumetric reserve profiles across the HFpEF spectrum.

METHODS: In this retrospective analysis of a prospective observational, multicentre study, supine ergometer Ex-CMR was performed in HFpEF patients across early to advanced stages (stage B, exercise-induced, stage C), along with healthy controls and a non-cardiac dyspnoea (NCD) group. Percentage changes in LV/RV end-diastolic (ΔEDV%) and end-systolic volumes (ΔESV%) from rest to stress defined EDV reserve and ESV reserve, respectively. Ventricular efficiency index (EI) was defined as ΔEDV%-ΔESV%; biventricular EI as LVEI + RVEI. Group comparisons were performed using ANOVA and post hoc testing. Multivariable general linear model analyses adjusted for age, sex, BMI, and exercise response. A composite phenotyping assessment incorporating all four key reserve parameters was explored.

RESULTS: Among 140 participants (40 healthy, 27 NCD, and 73 HFpEF), all HFpEF subgroups showed impaired LVEDV reserve and reduced LVEI (P < .0001). LVESV reserve was impaired only in stage C (P < .0001). Exercise-induced RV dysfunction was a hallmark of HFpEF with pulmonary hypertension (P < .0001). Biventricular EI declined progressively with advancing HFpEF stage (P < .0001) and was significantly lower in NYHA > II (P = .0006). Six distinct reserve phenotypes emerged.

CONCLUSION: Ex-CMR-based assessment of LV/RV volumetric reserve reveals progressive biventricular dysfunction across HFpEF stages and supports biventricular volumetric reserve-based phenotyping for characterizing HFpEF pathophysiology.

KEY QUESTION: Can the integration of left and right ventricular end-diastolic and end-systolic volume reserve under physiological stress reveal distinct profiles across the HFpEF spectrum and enhance our understanding of its haemodynamic heterogeneity?

KEY FINDINGS: Non-invasive assessment of biventricular volumetric reserve, along with their intra- and interventricular interactions using exercise CMR, revealed a significant, stepwise deterioration across HFpEF subgroups, worsening with NYHA class > II. Exercise CMR enabled composite volumetric reserve-based phenotyping and identified six distinct reserve phenotypes.

TAKE HOME MESSAGE: Biventricular volumetric reserve assessment is feasible through exercise CMR and may support future precision therapy strategies.