Why admixture matters in genetically-guided therapy: missed targets in the COAG and EU-PACT trials.
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ABSTRACT:
SUBMITTER: Duconge J
PROVIDER: S-EPMC4770896 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The vitamin D receptor is expressed in most tissues of the body - and the cancers that arise from those tissues. The vitamin D signaling pathway is active in those tissues and cancers. This is at least consistent with the hypothesis that perturbing this signaling may have a favorable effect on the genesis and growth of cancers. Epidemiologic data indicate that vitamin D signaling may be important in the initiation and outcome of a number of types of cancer. Many studies have shown that calcitriol (1,25 dihydroxycholecalciferol) and other vitamin D compounds have antiproliferative, pro-apoptotic, anti-cell migration and antiangiogenic activity in a number of preclinical studies in many different cancer types. Unfortunately, the assessment of the activity of calcitriol or other vitamin D analogues in the treatment of cancer, as single agents or in combination with other anticancer agents has been stymied by the failure to adhere to commonly accepted principles of drug development and clinical trials conduct.
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Project description:BACKGROUND:Perfectionism can become a debilitating condition that may negatively affect functioning in multiple areas, including mental health. Prior research has indicated that internet-based cognitive behavioral therapy can be beneficial, but few studies have included follow-up data. OBJECTIVE:The objective of this study was to explore the outcomes at follow-up of internet-based cognitive behavioral therapy with guided self-help, delivered as 2 separate randomized controlled trials conducted in Sweden and the United Kingdom. METHODS:In total, 120 participants randomly assigned to internet-based cognitive behavioral therapy were included in both intention-to-treat and completer analyses: 78 in the Swedish trial and 62 in the UK trial. The primary outcome measure was the Frost Multidimensional Perfectionism Scale, Concern over Mistakes subscale (FMPS CM). Secondary outcome measures varied between the trials and consisted of the Clinical Perfectionism Questionnaire (CPQ; both trials), the 9-item Patient Health Questionnaire (PHQ-9; Swedish trial), the 7-item Generalized Anxiety Disorder scale (GAD-7; Swedish trial), and the 21-item Depression Anxiety Stress Scale (DASS-21; UK trial). Follow-up occurred after 6 months for the UK trial and after 12 months for the Swedish trial. RESULTS:Analysis of covariance revealed a significant difference between pretreatment and follow-up in both studies. Intention-to-treat within-group Cohen d effect sizes were 1.21 (Swedish trial; 95% CI 0.86-1.54) and 1.24 (UK trial; 95% CI 0.85-1.62) for the FMPS CM. Furthermore, 29 (59%; Swedish trial) and 15 (43%; UK trial) of the participants met the criteria for recovery on the FMPS CM. Improvements were also significant for the CPQ, with effect sizes of 1.32 (Swedish trial; 95% CI 0.97-1.66) and 1.49 (UK trial; 95% CI 1.09-1.88); the PHQ-9, effect size 0.60 (95% CI 0.28-0.92); the GAD-7, effect size 0.67 (95% CI 0.34-0.99); and the DASS-21, effect size 0.50 (95% CI 0.13-0.85). CONCLUSIONS:The results are promising for the use of internet-based cognitive behavioral therapy as a way of targeting perfectionism, but the findings need to be replicated and include a comparison condition.
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Project description:Arterial hypertension (AH) may be related to fluid retention, increased vascular resistance or hyperdynamic heart function. Impedance cardiography (ICG) is shown to be useful in the individualization of antihypertensive therapy but little is known about who most benefits from this therapeutic approach. The aim of this analysis was to estimate the effectiveness of ICG-guided antihypertensive therapy with respect to baseline blood pressure (BP) from the perspective of 12 weeks' observation in randomized, prospective and controlled trials.This analysis involved 272 patients (average age: 44.1 ± 10.8 years) with AH. After baseline evaluation, including: office BP measurement (systolic, SBP; diastolic, DBP; mean, MBP) and ambulatory BP monitoring (mean 24-h SBP, mean 24-h DBP) the subjects were randomly assigned to groups of empiric [GE] and ICG-guided antihypertensive therapy [HD]. The results were evaluated separately in subgroups derived from median of MBP (110 mmHg): with slightly increased ('SI_BP') and more increased BP ('MI_BP'). The comparative analysis included absolute change in BP (d_OSBP, d_ODBP, d_24-h SBP, d_24-h DBP) and the percentage of patients with reduction of BP ? 10 mmHg (d10_OSBP, d10_ODBP, d10_24-h SBP, d10_24-h DBP).ICG-guided therapy was shown to be superior to the empiric approach, especially in MI_BP. In this subgroup, the BP reduction in HD was higher than in GE: d_OSBP (23.3 ± 10.8 versus 18.5 ± 13.9 mmHg; p = 0.035), d_ODBP (16.0 ± 6.3 versus 11.6 ± 9.6 mmHg; p = 0.003), d_24-h SBP (17.7 ± 10.8 versus 13.1 ± 13.1 mmHg; p = 0.035). This benefit was also confirmed by a higher percentage of patients with significant BP reduction: d10_OSBP (87.7% versus 69.1%; p = 0.012), d10_ODBP (69.2% versus 47.3%; p = 0.012) and d10_24-h SBP (72.3% versus 52.7%; p = 0.012). The comparison in the SI_BP subgroup did not reveal such significant differences.The hemodynamically guided pharmacotherapy results in greater BP reduction. This effect is more pronounced in patients with higher baseline BP, while in those with slightly increased BP the empiric approach seems comparable to ICG.
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