67 research outputs found
Does publication bias inflate the apparent efficacy of psychological treatment for major depressive disorder? A systematic review and meta-analysis of US national institutes of health-funded trials
Background The efficacy of antidepressant medication has been shown empirically to be overestimated due to publication bias, but this has only been inferred statistically with regard to psychological treatment for depression. We assessed directly the extent of study publication bias in trials examining the efficacy of psychological treatment for depression. Methods and Findings We identified US National Institutes of Health grants awarded to fund randomized clinical trials comparing psychological treatment to control conditions or other treatments in patients diagnosed with major depressive disorder for the period 1972–2008, and we determined whether those grants led to publications. For studies that were not published, data were requested from investigators and included in the meta-analyses. Thirteen (23.6%) of the 55 funded grants that began trials did not result in publications, and two others never started. Among comparisons to control conditions, adding unpublished studies (Hedges’ g = 0.20; CI95% -0.11~0.51; k = 6) to published studies (g = 0.52; 0.37~0.68; k = 20) reduced the psychotherapy effect size point estimate (g = 0.39; 0.08~0.70) by 25%. Moreover, these findings may overestimate the "true" effect of psychological treatment for depression as outcome reporting bias could not be examined quantitatively. Conclusion The efficacy of psychological interventions for depression has been overestimated in the published literature, just as it has been for pharmacotherapy. Both are efficacious but not to the extent that the published literature would suggest. Funding agencies and journals should archive both original protocols and raw data from treatment trials to allow the detection and correction of outcome reporting bias. Clinicians, guidelines developers, and decision makers should be aware that the published literature overestimates the effects of the predominant treatments for depression
Lipid Motif of a Bacterial Antigen Mediates Immune Responses via TLR2 Signaling
The cross-talk between the innate and the adaptive immune system is facilitated
by the initial interaction of antigen with dendritic cells. As DCs express a
large array of TLRs, evidence has accumulated that engagement of these molecules
contributes to the activation of adaptive immunity. We have evaluated the
immunostimulatory role of the highly-conserved outer membrane lipoprotein P6
from non-typeable Haemophilus influenzae (NTHI) to determine
whether the presence of the lipid motif plays a critical role on its
immunogenicity. We undertook a systematic analysis of the role that the lipid
motif plays in the activation of DCs and the subsequent stimulation of
antigen-specific T and B cells. To facilitate our studies, recombinant P6
protein that lacked the lipid motif was generated. Mice immunized with
non-lipidated rP6 were unable to elicit high titers of anti-P6 Ig. Expression of
the lipid motif on P6 was also required for proliferation and cytokine secretion
by antigen-specific T cells. Upregulation of T cell costimulatory molecules was
abrogated in DCs exposed to non-lipidated rP6 and in
TLR2−/− DCs exposed to native P6, thereby resulting
in diminished adaptive immune responses. Absence of either the lipid motif on
the antigen or TLR2 expression resulted in diminished cytokine production from
stimulated DCs. Collectively; our data suggest that the lipid motif of the
lipoprotein antigen is essential for triggering TLR2 signaling and effective
stimulation of APCs. Our studies establish the pivotal role of a bacterial lipid
motif on activating both innate and adaptive immune responses to an otherwise
poorly immunogenic protein antigen
The Validity of Using Analogue Patients in Practitioner–Patient Communication Research: Systematic Review and Meta-Analysis
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