Antidepressants may not assist recovery in practice: a naturalistic prospective survey.

A total of 130 people attending psychiatric hospitals within 6 months of onset or relapse of an episode of depressive disorder were interviewed about their symptoms and treatment at the time of their initial contact. After a mean 4-month interval, 119 were reassessed to test the hypothesis that patients treated with antidepressants would be significantly more likely to be clinically improved compared with those untreated. Severity and duration of the episode emerged as the only significant clinical predictors of clinical improvement. Patients on treatment with antidepressants at the start of the study showed a nonsignificant trend for a lesser degree of clinical improvement, even when clinical severity and compliance were taken into account. Those who were not commenced on treatment until later in the study also fared no better than those who were never prescribed antidepressants. The effect of low doses of antidepressants (almost always a tricyclic) appeared to be less beneficial than either higher doses or clinical management without antidepressant drugs. The need for further experimental and naturalistic studies conducted over various periods of time and the implications for clinical practice, medical audit and the appropriate use of health outcome indicators are discussed.     

V-region mutation in vitro,in vivo,and in silico reveal the importance of the enzymatic properties of AID and the sequence environment

The somatic hypermutation of Ig variable regions requires the activity of activation-induced cytidine deaminase (AID) which has previously been shown to preferentially deaminate WRC (W = A/T, R = A/G) motif hot spots in in vivo and in vitro assays. We compared mutation profiles of in vitro assays for the 3′ flanking intron of VhJ558-Jh4 region to previously reported in vivo profiles for the same region in the Msh2^−/−Ung^−/− mice that lack base excision and mismatch repair. We found that the in vitro and in vivo mutation profiles were highly correlated for the top (nontranscribed) strand, while for the bottom (transcribed) strand the correlation is far lower. We used an in silico model of AID activity to elucidate the relative importance of motif targeting in vivo. We found that the mutation process entails substantial complexity beyond motif targeting, a large part of which is captured in vitro. To elucidate the contribution of the sequence environment to the observed differences between the top and bottom strands, we analyzed intermutational distances. The bottom strand shows an approximately exponential distribution of distances in vivo and in vitro, as expected from a null model. However, the top strand deviates strongly from this distribution in that mutations approximately 50 nucleotides apart are greatly reduced, again both in vivo and in vitro, illustrating an important strand asymmetry. While we have confirmed that AID targeting of hot and cold spots is a key part of the mutation process, our results suggest that the sequence environment plays an equally important role.     

The HIV care cascade: models,measures and moving forward

Introduction

This article seeks to identify where delays occur along the adult HIV care cascade (“the cascade”), to improve understanding of what constitutes “delay” at each stage of the cascade and how this can be measured across a range of settings and to inform service delivery efforts. Current metrics are reviewed, measures informed by global guidelines are suggested and areas for further clarification are underscored.

Discussion

Questions remain on how best to evaluate late entry into each stage of the cascade. The delayed uptake of HIV testing may be more consistently measured once rapid CD4 testing is administered at the time of HIV testing. For late enrolment, preliminary research has begun to determine how different time intervals for linking to HIV care affect individual health. Regarding treatment, since 2013, the World Health Organization (WHO) and UNAIDS recommend treatment initiation when CD4 <500 cells/mm³; these guidelines provide a useful albeit evolving threshold to define late treatment initiation. Finally, WHO guidelines for high-, low- and middle-income countries also could be used to standardize measures for achieving viral suppression.

Conclusions

There is no “one size fits all” model as the provision of services may differ based on a range of factors. Nonetheless, measures informed by global guidelines are needed to more consistently evaluate the scope of and factors associated with delays to each stage of the cascade. Doing so will help identify how practitioners can best deliver services and facilitate access to and continued engagement in care.     

Posttraumatic stress disorder and odds of major invasive procedures among U.S. Veterans Affairs patients

Objectives

Although individuals with posttraumatic stress disorder (PTSD) are at heightened risk for several serious health conditions, research has not examined how having PTSD impacts receipt of invasive procedures that may alleviate these problems. We examined whether PTSD, after controlling for major depression, was associated with odds of receiving common types of major invasive procedures, and whether race, ethnicity, and gender was associated with odds of procedures.

Methods

Veterans Health Administration patients with PTSD and/or depression were age-matched with patients without these disorders. The odds of invasive hip/knee, digestive system, coronary artery bypass graft/percutaneous coronary intervention (CABG/PCI), and vascular procedures during FY2006–2009 were modeled for the full sample of 501,489 patients and for at-risk subsamples with medical conditions alleviated by the procedures examined.

Results

Adjusting for demographic covariates and medical comorbidity, PTSD without depression was associated with decreased odds of all types of procedures (odds ratios [OR] range 0.74–0.82), as was depression without PTSD (OR range 0.59–0.77). In analyses of at-risk patients, those with PTSD only were less likely to undergo hip/knee (OR = 0.78) and vascular procedures (OR = 0.73) but not CABG/PCI. African-Americans and women at-risk patients were less likely to undergo hip/knee, vascular, and CABG/PCI procedures (OR range 0.31–0.82).

Conclusion

With the exception of CABG/PCI among at-risk patients, Veterans with PTSD and/or depression were less likely to undergo all types of procedures examined. Future studies should examine the reasons for this disparity and whether it is associated with subsequent adverse outcomes.