Online mindfulness as a promising method to improve exercise capacity in heart disease: 12-month follow-up of a randomized controlled trial

<div><p>There is increasing evidence that mindfulness can reduce stress, and thereby affect other psychological and physiological outcomes as well. Earlier, we reported the direct 3-month results of an online modified mindfulness-based stress reduction training in patients with heart disease, and now we evaluate the effect at 12-month follow-up. 324 patients (mean age 43.2 years, 53.7% male) were randomized in a 2:1 ratio to additional 3-month online mindfulness training or to usual care alone. The primary outcome was exercise capacity measured with the 6 minute walk test (6MWT). Secondary outcomes were blood pressure, heart rate, respiratory rate, NT-proBNP, cortisol levels (scalp hair sample), mental and physical functioning (SF-36), anxiety and depression (HADS), perceived stress (PSS), and social support (PSSS12). Differences between groups on the repeated outcome measures were analyzed with linear mixed models. At 12-months follow-up, participants showed a trend significant improvement exercise capacity (6MWT: 17.9 meters, p = 0.055) compared to UC. Cohen’s D showed significant but small improvement on exercise capacity (d = 0.22; 95%CI 0.05 to 0.39), systolic blood pressure (d = 0.19; 95%CI 0.03 to 0.36), mental functioning (d = 0.22; 95%CI 0.05 to 0.38) and depressive symptomatology (d = 0.18; 95%CI 0.02 to 0.35). All other outcome measures did not change statistically significantly. In the as-treated analysis, systolic blood pressure decreased significantly with 5.5 mmHg (p = 0.045; d = 0.23 (95%CI 0.05–0.41)). Online mindfulness training shows favorable albeit small long-term effects on exercise capacity, systolic blood pressure, mental functioning, and depressive symptomatology in patients with heart disease and might therefore be a beneficial addition to current clinical care.</p><p><b>Trial registration:</b><a href="http://www.trialregister.nl" target="_blank">www.trialregister.nl</a><a href="https://clinicaltrials.gov/ct2/show/NTR3453" target="_blank">NTR3453</a></p></div

Therapeutic Drug Monitoring of Endoxifen for Tamoxifen Precision Dosing: Feasible in Patients with Hormone-Sensitive Breast Cancer

Background: Endoxifen is the most important active metabolite of tamoxifen. Several retrospective studies have suggested a minimal or threshold endoxifen systemic concentration of 14–16 nM is required for a lower recurrence rate. The aim of this study was to investigate the feasibility of reaching a predefined endoxifen level of ≥ 16 nM (5.97 ng/mL) over time using therapeutic drug monitoring (TDM). Methods: This prospective open-label intervention study enrolled patients who started treatment with a standard dose of tamoxifen 20 mg once daily for early breast cancer. An outpatient visit was combined with a TDM sample at 3, 4.5, and 6 months after initiation of the tamoxifen treatment. The tamoxifen dose was escalated to a maximum of 40 mg if patients had an endoxifen concentration < 16 nM. The primary endpoint of the study was the percentage of patients with an endoxifen level ≥ 16 nM at 6 months after the start of therapy compared with historical data, in other words, 80% of patients with endoxifen levels ≥ 16 nM with standard therapy. Results: In total, 145 patients were included. After 6 months, 89% of the patients had endoxifen levels ≥ 16 nM, compared with a literature-based 80% of patients with endoxifen levels ≥ 16 nM at baseline (95% confidence interval 82–94; P = 0.007). In patients with an affected CYP2D6 allele, it was not always feasible to reach the predefined endoxifen level of ≥ 16 nM. No increase in tamoxifen-related adverse events was reported after dose escalation. Conclusion: This study demonstrated that it is feasible to increase the percentage of patients with endoxifen levels ≥ 16 nM using TDM. TDM is a safe strategy that offers the possibility of nearly halving the number of patients with endoxifen levels < 16 nM

Linear mixed models results.

<p>Plot showing Linear Mixed Models results: the mean distance walked in meters by the Intervention group (red) and the Control group (blue) at each of the three measurement moments.</p

Flowchart of mindfulness intervention group and control group.

<p>*Linear mixed effects models use all available data and obtains valid inferences under the missing at random assumption.</p

Outcomes at baseline and 12 months, and linear mixed models-based estimated difference (β) of intervention group compared to control over time.

<p>Outcomes at baseline and 12 months, and linear mixed models-based estimated difference (β) of intervention group compared to control over time.</p

Cohen’s D in as-treated analysis.

<p>Plot showing Cohen’s D effect measures of online mindfulness compared to treatment as usual in the As-Treated analysis. All values lower than 0 indicate a significant difference in favour of mindfulness. The breadth of the line indicates the 95%CI. Values between 0 and -0.2 indicate negligible effect; between -0.2 and -0.5 small effect; between -0.5 and -0.8 medium effect and lower than -0.8 a large effect. *: log transformed values.</p

Cohen’s D in intention-to-treat analysis.

<p>Plot showing Cohen’s D effect measures of online mindfulness compared to treatment as usual in the Intention-To-Treat analysis. All values lower than 0 indicate a significant difference in favour of mindfulness. The breadth of the line indicates the 95%CI. Values between 0 and -0.2 indicate negligible effect; between -0.2 and -0.5 small effect; between -0.5 and -0.8 medium effect and lower than -0.8 a large effect. *: log transformed values.</p