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To determine whether concurrent posttraumatic stress disorder (PTSD) should affect whether to augment or switch medications when major depressive disorder (MDD) has not responded to a prior antidepressant trial. Patients at 35 Veterans Health Administration medical centers from December 2012 to May 2015 with nonpsychotic MDD (N = 1,522) and a suboptimal response to adequate antidepressant treatment were randomly assigned to 3 "next step" treatments: switching to bupropion, augmenting the current antidepressant with bupropion, and augmenting with the antipsychotic aripiprazole. Blinded ratings with the 16-item Quick Inventory of Depressive Symptomatology-Clinician Rated (QIDS-C₁₆) determined remission and response by 12 weeks and relapse after remission. Survival analyses compared treatment effects in patients with concurrent PTSD diagnosed with the Mini-International Neuropsychiatric Interview (n = 717, 47.1%) and those without PTSD (n = 805, 52.9%). Patients diagnosed with PTSD showed more severe depressive symptoms at baseline and were less likely to achieve either remission or response by 12 weeks. Augmentation with aripiprazole was associated with greater likelihood of achieving response (68.4%) than switching to bupropion (57.7%) in patients with PTSD (relative risk [RR] = 1.26; 95% CI, 1.01-1.59) as well as in patients without PTSD (RR = 1.29; 95% CI, 1.05-1.97) (78.9% response with aripiprazole augmentation vs 66.9% with switching to bupropion). Treatment comparisons with the group receiving augmentation with bupropion were not significant. There was no significant interaction between treatment group and PTSD on remission (P = .70), response (P = .98), or relapse (P = .15). Although PTSD was associated with poorer overall outcomes, the presence of concurrent PTSD among Veterans in this trial did not affect the comparative effectiveness of medications on response, remission, or relapse after initial remission. ClinicalTrials.gov identifier: NCT01421342.

ObjectiveIn this secondary analysis of data from the Veterans Affairs Augmentation and Switching Treatments for Improving Depression Outcomes (VAST-D) study, the authors sought to determine the effectiveness of early improvement (or lack thereof) for predicting remission from depression with antidepressant therapy.MethodsThis study used data from the VAST-D study, a multisite, randomized, single-blind trial with parallel assignment to one of three medication interventions for 1,522 veterans whose major depressive disorder was unresponsive to at least one course of antidepressant treatment meeting minimal standards for dosage and duration. The authors calculated the positive predictive value (PPV) and negative predictive value (NPV) of early improvement on remission, response, or greater than minimal improvement from depression for various degrees of improvement (10%-50%) on the Quick Inventory of Depressive Symptomatology-Clinician Rated (QIDS-C) at 1, 2, 4, and 6 weeks.ResultsThe end of week 2 of treatment was identified as the best time to evaluate early improvement. The presence of a ≥20% drop from the baseline QIDS-C score by the end of week 2 resulted in a PPV for remission of 38% and an NPV of 93% by week 12. Extending the observational window to week 6 minimally improved NPV (97%). This association did not differ across treatment groups.ConclusionsA lack of early improvement at the end of week 2 of antidepressant therapy can be used to inform clinical decisions on the likelihood of nonremission of depression during the subsequent 10 weeks, even when dosage optimization is incomplete.

ImportanceLess than one-third of patients with major depressive disorder (MDD) achieve remission with their first antidepressant.ObjectiveTo determine the relative effectiveness and safety of 3 common alternate treatments for MDD.Design, setting, and participantsFrom December 2012 to May 2015, 1522 patients at 35 US Veterans Health Administration medical centers who were diagnosed with nonpsychotic MDD, unresponsive to at least 1 antidepressant course meeting minimal standards for treatment dose and duration, participated in the study. Patients were randomly assigned (1:1:1) to 1 of 3 treatments and evaluated for up to 36 weeks.InterventionsSwitch to a different antidepressant, bupropion (switch group, n = 511); augment current treatment with bupropion (augment-bupropion group, n = 506); or augment with an atypical antipsychotic, aripiprazole (augment-aripiprazole group, n = 505) for 12 weeks (acute treatment phase) and up to 36 weeks for longer-term follow-up (continuation phase).Main outcomes and measuresThe primary outcome was remission during the acute treatment phase (16-item Quick Inventory of Depressive Symptomatology-Clinician Rated [QIDS-C16] score ≤5 at 2 consecutive visits). Secondary outcomes included response (≥50% reduction in QIDS-C16 score or improvement on the Clinical Global Impression Improvement scale), relapse, and adverse effects.ResultsAmong 1522 randomized patients (mean age, 54.4 years; men, 1296 [85.2%]), 1137 (74.7%) completed the acute treatment phase. Remission rates at 12 weeks were 22.3% (n = 114) for the switch group, 26.9% (n = 136)for the augment-bupropion group, and 28.9% (n = 146) for the augment-aripiprazole group. The augment-aripiprazole group exceeded the switch group in remission (relative risk [RR], 1.30 [95% CI, 1.05-1.60]; P = .02), but other remission comparisons were not significant. Response was greater for the augment-aripiprazole group (74.3%) than for either the switch group (62.4%; RR, 1.19 [95% CI, 1.09-1.29]) or the augment-bupropion group (65.6%; RR, 1.13 [95% CI, 1.04-1.23]). No significant treatment differences were observed for relapse. Anxiety was more frequent in the 2 bupropion groups (24.3% in the switch group [n = 124] vs 16.6% in the augment-aripiprazole group [n = 84]; and 22.5% in augment-bupropion group [n = 114]). Adverse effects more frequent in the augment-aripiprazole group included somnolence, akathisia, and weight gain.Conclusions and relevanceAmong a predominantly male population with major depressive disorder unresponsive to antidepressant treatment, augmentation with aripiprazole resulted in a statistically significant but only modestly increased likelihood of remission during 12 weeks of treatment compared with switching to bupropion monotherapy. Given the small effect size and adverse effects associated with aripiprazole, further analysis including cost-effectiveness is needed to understand the net utility of this approach.Trial registrationclinicaltrials.gov Identifier: NCT01421342.

BackgroundThe Shingles Prevention Study (SPS) demonstrated zoster vaccine efficacy through 4 years postvaccination. A Short-Term Persistence Substudy (STPS) demonstrated persistence of vaccine efficacy for at least 5 years. A Long-Term Persistence Substudy (LTPS) was undertaken to further assess vaccine efficacy in SPS vaccine recipients followed for up to 11 years postvaccination. Study outcomes were assessed for the entire LTPS period and for each year from 7 to 11 years postvaccination.MethodsSurveillance, case determination, and follow-up were comparable to those in SPS and STPS. Because SPS placebo recipients were offered zoster vaccine before the LTPS began, there were no unvaccinated controls. Instead, SPS and STPS placebo results were used to model reference placebo groups.ResultsThe LTPS enrolled 6867 SPS vaccine recipients. Compared to SPS, estimated vaccine efficacy in LTPS decreased from 61.1% to 37.3% for the herpes zoster (HZ) burden of illness (BOI), from 66.5% to 35.4% for incidence of postherpetic neuralgia, and from 51.3% to 21.1% for incidence of HZ, and declined for all 3 outcome measures from 7 through 11 years postvaccination. Vaccine efficacy for the HZ BOI was significantly greater than zero through year 10 postvaccination, whereas vaccine efficacy for incidence of HZ was significantly greater than zero only through year 8.ConclusionsEstimates of vaccine efficacy decreased over time in the LTPS population compared with modeled control estimates. Statistically significant vaccine efficacy for HZ BOI persisted into year 10 postvaccination, whereas statistically significant vaccine efficacy for incidence of HZ persisted only through year 8.

This issue of Politics and the Life Sciences includes an article, ten commentaries, and three responses on the subject of birth order and rebelliousness, focusing in particular on Frank Sulloway's Born to Rebel (1996, 1997). Extraordinary events have surrounded the publication of this roundtable, including threats of legal action, accusations of misconduct, letters to university officials, termination of the journal's publishing contract, and an almost five-year delay in publication. This editorial reviews these events and goes on to assess Frank Sulloway's responses (published in this issue), as well as parts of Born to Rebel. It also reports the results of a replication of Sulloway's study of Reformation martyrs. The replication generated markedly different data than those reported by Sulloway. Data from an expanded sample were also inconsistent with the relationship that Sulloway reported finding between birth order and religious commitment among Reformation martyrs. The editorial supports the suggestion by Frederic Townsend that an independent review of Born to Rebel would be appropriate. It concludes with a call for establishment of a multidisciplinary legal defense fund that would reduce the likelihood that legal threats can succeed in stifling research and publication in the natural and social sciences.

By Mike Hawkins. New York: Cambridge University Press, 1997. 344p. $69.95 cloth, $27.95 paper. Gary R. Johnson, Lake Superior State University 'Social Darwinism' is a moral and political indictment in [...]

Scientific, philosophical, and moral problems related to claiming crime is caused by genetic factors raise questions about the prospects of explaining neurobiological sciences. These raise questions regarding the possibility of providing genetic explanation to socially defined behavior. Another issue is related to social and ethical implications of genetics and crime research. Proponents of genetics and crime research are optimistic about the use of this knowledge in preventing crime while critics are apprehensive that the research will lead to social inequalities and abuse.

The article discusses a study on the effects of planting depth on tree stability and growth for various species of trees including Whitesphire birch, green ash, snowdrift crabapple and bicolor oak. Of the four species, birch demonstrated the greatest instability when not planted deep enough. Perceived benefits of planting deep in containers to improve stability was observed only in birch and at the expense of significantly reduced root volume increase.

The article discusses a study which determined the relationship between local urban forestry activity and the urban and community forestry (U&CF) programs implemented by states. It cites the reasons for the failure and success of urban forestry programs in managing urban tree populations including championing a forestry cause, funding, staff experience, and political support. Data from the Performance Measures and Accountability System (PMAS) of the U.S. Forestry Service (USFS) were used.

The article describes the enabling legislation for technical and financial assistance, types and frequency of technical and financial assistance and funding of urban and community forestry programs in the United States. It reveals that nearly one-third believed their state program would end and nearly half believed a severe reduction in the state program would occur if federal funding was eliminated.

The article focuses on the derivation of urban and community forestry (U&CF) program capacity within the 50 United States through four indicator areas that included the U&CF program coordinator, volunteer coordination, state U&CF council and strategic plan. Occasionally, non-U&CF duties were conducted by U&CF staff with fire control, forest stewardship, special objects and forest health most commonly given as other areas conducted by U&CF staff.

The article explores mechanical root-disruption practices and their impact on circling roots of pot-bound Tilia cordata Mill. and Salix alba L. Niobe. Roots growing beyond the original root ball were measured for diameter growth to assess the effectiveness of the root pruning techniques. All root disruption treatments resulted in increased fibrous root growth. No mechanical root disruption method was better than root balls left undisturbed.

Reports on the eighteen meeting of the Association for Politics and the Life Sciences held in Boston, Massachusetts on September 3-6, 1998. Conference features; Keynote address by Harvard biologist Edward O. Wilson; Reflections of a panel organizer; Biological warfare and weapons panels; Population, fertility and policy panels; Challenge of attending all panels.

National and international regulations require that chemicals must be properly classified, labeled, packaged, and transported based on their ability to damage or destroy tissue, e.g., skin. Traditionally, skin corrosion assessments were based on tests involving topical application of test substances to the skin of rabbits. In the present work, an in vitro skin corrosion test based on the use of reconstructed human skin cultures was developed as a potential replacement for in vivo rabbit skin tests for corrosion. In the in vitro method, test substances were applied topically to the stratum corneum surface of human skin cultures. Skin culture damage or cytotoxicity was measured as decreased 3-[4,5-dimethylthiazol-2-yl] 2,5-diphenyltetrazolium bromide (MTT) vital dye metabolism. In time-course experiments, the time (in minutes) of test material exposure eliciting a 50% reduction of MTT metabolism (i.e., t50 value) was calculated. Using this method we evaluated 24 chemicals and found that the 9 corrosive chemicals were accurately distinguished from 15 strong, moderate, or mild skin irritants, using an in vitro cutoff of t50 < 3 min. Histologic examination of the cultures indicated gradations of epidermal necrosis quantitated using a specially designed grading scale, which correlated well with the corrosivity of treatment chemicals and cytotoxicity measurements. The predictivity of the method was confirmed and was consistent in skin culture models from two suppliers. Thus, the utility of human skin equivalent cultures as a screening tool for prediction of skin corrosivity appears to be independent of the commercial source of the cultures. We conclude that the in vitro assay using human skin equivalent cultures is a promising alternative to in vivo rabbit skin corrosion tests for assessment of the corrosivity of chemicals to human skin. [ABSTRACT FROM AUTHOR]