Abstract Funding Acknowledgements Type of funding sources: None. Objective Depression is common in patients with coronary artery disease (CAD) and is associated with poor outcomes. Although different treatments are available, it is unclear which are best or most acceptable to patients, so we conducted a network meta-analysis of evidence from randomized controlled trials (RCTs) of different depression treatments to ascertain relative efficacy. Methods We searched for systematic reviews of RCTs of depression treatments in CAD and updated these with a comprehensive search for recent individual RCTs. RCTs comparing depression treatments (pharmacological, psychotherapeutic, combined pharmacological/psychotherapeutic, exercise, collaborative care) were included. Primary outcomes were acceptability (dropout rate) and change in depressive symptoms 8-weeks post-treatment commencement. Change in 26-week depression and mortality were secondary outcomes. Frequentist, random effects network meta-analysis synthesized the evidence. GRADE was used to assess evidence quality. Results Thirty-three RCTs (7240 participants) provided analysable data. All treatments were equally acceptable. At 8-weeks, combination therapy (1 study), exercise (1 study), and antidepressants (10 studies) yielded the strongest effects versus comparators. At 26-weeks, antidepressants were consistently effective, but psychotherapy was only effective versus usual care. There were no differences in treatment groups for mortality. GRADE ratings ranged from very low to low. Conclusions All treatments were equally acceptable, while antidepressants appeared to have the most robust evidence base for post-CAD depression. The evidence base was limited and biased; conclusions based on this literature should be drawn cautiously and considered to be tentative. Rigorous, multi-arm intervention trials, including trials of combination therapies and exercise, are urgently needed.
Some of the methodological and conceptual issues relevant to behavior therapy treatment outcome studies for anxiety disorders are presented. The practice among behavioral researchers of measuring anxiety from 3 response systems (verbal, physiological and motoric-behavioral) is discussed. It is emphasized that many of the popular methods used to assess the 3 response systems have unknown or poor reliability or validity. From the point of view of treatment variables, it is noted that many behavioral treatment procedures are not reported in sufficient detail to allow replication or comparisons to be made across studies. In addition, it is argued that in order to improve the existing treatment procedures, it will be necessary for each study to assess the subjects' adherence to the treatment regimen, as well as their proficiency with any skills required to carry out the treatment plan. Finally, the importance of 'placebo' control groups is discussed in the context of identifying the specific factors in behavioral treatments which are responsible for change in the targeted symptoms. It is concluded that behavior therapy holds promise as an effective treatment for the anxiety disorders.
Introduction Late-onset Alzheimer’s disease (LOAD, onset age > 60 years) is the most prevalent dementia in the elderly 1 , and risk is partially driven by genetics 2 . Many of the loci responsible for this genetic risk were identified by genome-wide association studies (GWAS) 3–8 . To identify additional LOAD risk loci, the we performed the largest GWAS to date (89,769 individuals), analyzing both common and rare variants. We confirm 20 previous LOAD risk loci and identify four new genome-wide loci ( IQCK , ACE , ADAM10 , and ADAMTS1 ). Pathway analysis of these data implicates the immune system and lipid metabolism, and for the first time tau binding proteins and APP metabolism. These findings show that genetic variants affecting APP and Aβ processing are not only associated with early-onset autosomal dominant AD but also with LOAD. Analysis of AD risk genes and pathways show enrichment for rare variants ( P = 1.32 × 10 −7 ) indicating that additional rare variants remain to be identified.
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