Residential treatment for combat-related posttraumatic stress disorder: Identifying trajectories of change and predictors of treatment response

Background Combat-related posttraumatic stress disorder (PTSD) can be a difficult condition to treat and has been associated with serious medical and economic issues among U.S. military veterans. Distinguishing between treatment responders vs. non-responders in this population has become an important public health priority. This study was conducted to identify pre-treatment characteristics of U.S. veterans with combat-related PTSD that might contribute to favorable and unfavorable responses to high value treatments for this condition. Method This study focused on 805 patients who completed a VHA PTSD residential program between 2000 and 2007. These patients completed the PTSD Clinical Checklist at pre-treatment, post-treatment, and a four-month follow-up assessment. Latent growth curve analysis (LCGA) was incorporated to determine trajectories of changes in PTSD across these assessments and whether several key clinical concerns for this population were associated with their treatment responses. Study Findings LCGA indicated three distinct trajectories in PTSD outcomes and identified several clinical factors that were prospectively linked with changes in veterans\u27 posttraumatic symptomatology. When compared to a group with high PTSD symptom severity that decreased over the program but relapsed at follow-up (41%), the near half (48.8%) of the sample with an improving trajectory had less combat exposure and superior physical/mental health. However, when compared to a minority (10.2%) with relatively low symptomatology that also remained somewhat stable, patients in the improving group were younger and also reported greater combat exposure, poorer physical/mental health status, and more problems with substance abuse before the start of treatment. Conclusions Findings suggest that veterans are most likely to benefit from residential treatment in an intermediate range of symptoms and risk factors, including PTSD symptom severity, history of combat exposure, and comorbid issues with physical/mental health. Addressing these factors in an integrative manner could help to optimize the effectiveness of treatments of combat-related PTSD in many cases

Moral Injury and ICD-11 Complex PTSD (CPTSD) Symptoms among Treatment-Seeking Veterans in the United Kingdom

Military veterans often encounter events with chronic or repeated traumas of an interpersonal nature that might lead to emotional, relational, and spiritual suffering. Research is needed to assess whether and/or how emerging conceptions of moral injury (MI) align with existing trauma-related conditions. Focusing on 173 veterans from the United Kingdom who had recently pursued mental health treatment, we examined associations between self- and other-directed outcomes related to MI and World Health Organization International Classifcation System for Diseases, 11th version (ICD-11) criteria for posttraumatic stress disorder (PTSD) and Complex PTSD (CPTSD) in two ways. First, drawing on psychometrically validated tools for assessing MI (Currier et al., 2017) and PTSD/CPTSD (Cloitre et al., 2018), ANOVAs revealed the 57.2% of veterans in the sample who possibly met criteria for CPTSD reported greater MI related to both perpetration- and betrayal-based events compared to those with and without possible PTSD. Second, latent profile analysis revealed two distinct classes based on the symptom severity of MI and CPTSD. Specifically, when examining the six symptom clusters for CPTSD dimensionally, four in five of the veterans endorsed high levels of distress related to all indicators of MI and CPTSD symptoms compared to a group with consistently lower scores. Overall, the two sets of findings suggest the special relevance of MI among veterans who are struggling with CPTSD

A Cure for HIV Infection: "Not in My Lifetime" or "Just Around the Corner"?

With the advent and stunning success of combination antiretroviral therapy (ART) to prolong and improve quality of life for persons with HIV infection, HIV research has been afforded the opportunity to pivot towards studies aimed at finding "a cure." The mere idea that cure of HIV might be possible has energized researchers and the community towards achieving this goal. Funding agencies, both governmental and private, have targeted HIV cure as a high priority; many in the field have responded to these initiatives and the cure research agenda is robust. In this "salon" two editors of Pathogens and Immunity, Michael Lederman and Daniel Douek ask whether curing HIV is a realistic, scalable objective. We start with an overview perspective and have asked a number of prominent HIV researchers to add to the discussion

A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less

Background: The efficacy and safety of adding a protease inhibitor to two nucleoside analogues to treat human immunodeficiency virus type 1 (HIV-1) infection are not clear. We compared treatment with the protease inhibitor indinavir in addition to zidovudine and lamivudine with treatment with the two nucleosides alone in HIV-infected adults previously treated with zidovudine. Methods: A total of 1156 patients not previously treated with lamivudine or protease inhibitors were stratified according to CD4 cell count (50 or fewer vs. 51 to 200 cells per cubic millimeter) and randomly assigned to one of two daily regimens: 600 mg of zidovudine and 300 mg of lamivudine, or that regimen with 2400 mg of indinavir. Stavudine could be substituted for zidovudine. The primary end point was the time to the development of the acquired immunodeficiency syndrome (AIDS) or death. Results: The proportion of patients whose disease progressed to AIDS or death was lower with indinavir, zidovudine (or stavudine), and lamivudine (6 percent) than with zidovudine (or stavudine) and lamivudine alone (11 percent; estimated hazard ratio, 0.50; 95 percent confidence interval, 0.33 to 0.76; P�0.001). Mortality in the two groups was 1.4 percent and 3.1 percent, respectively (estimated hazard ratio, 0.43; 95 percent confidence interval, 0.19 to 0.99; P=0.04). The effects of treatment were similar in both CD4 cell strata. The responses of CD4 cells and plasma HIV-1 RNA paralleled the clinical results. Conclusions: Treatment with indinavir, zidovudine, and lamivudine as compared with zidovudine and lamivudine alone significantly slows the progression of HIV-1 disease in patients with 200 CD4 cells or fewer per cubic millimeter and prior exposure to zidovudine. (N Engl J Med 1997;337:725-33.

Variant-Specific Viral Kinetics in Acute COVID-19

Understanding variant-specific differences in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral kinetics may explain differences in transmission efficiency and provide insights on pathogenesis and prevention. We evaluated SARS-CoV-2 kinetics from nasal swabs across multiple variants (Alpha, Delta, Epsilon, Gamma) in placebo recipients of the ACTIV-2/A5401 trial. Delta variant infection led to the highest maximum viral load and shortest time from symptom onset to viral load peak. There were no significant differences in time to viral clearance across the variants. Viral decline was biphasic with first- and second-phase decays having half-lives of 11 hours and 2.5 days, respectively, with differences among variants, especially in the second phase. These results suggest that while variant-specific differences in viral kinetics exist, post-peak viral load all variants appeared to be efficiently cleared by the host. Clinical Trials Registration. NCT04518410

A Cure for HIV Infection: “Not in My Lifetime” or “Just Around the Corner”?

With the advent and stunning success of combination antiretroviral therapy (ART) to prolong and improve quality of life for persons with HIV infection, HIV research has been afforded the opportunity to pivot towards studies aimed at finding “a cure.” The mere idea that cure of HIV might be possible has energized researchers and the community towards achieving this goal. Funding agencies, both governmental and private, have targeted HIV cure as a high priority; many in the field have responded to these initiatives and the cure research agenda is robust. In this “salon” two editors of Pathogens and Immunity, Michael Lederman and Daniel Douek ask whether curing HIV is a realistic, scalable objective. We start with an overview perspective and have asked a number of prominent HIV researchers to add to the discussion

Statistical Challenges When Analyzing SARS-CoV-2 RNA Measurements Below the Assay Limit of Quantification in COVID-19 Clinical Trials

Most clinical trials evaluating coronavirus disease 2019 (COVID-19) therapeutics include assessments of antiviral activity. In recently completed outpatient trials, changes in nasal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA levels from baseline were commonly assessed using analysis of covariance (ANCOVA) or mixed models for repeated measures (MMRM) with single imputation for results below assay lower limits of quantification (LLoQ). Analyzing changes in viral RNA levels with singly imputed values can lead to biased estimates of treatment effects. In this article, using an illustrative example from the ACTIV-2 trial, we highlight potential pitfalls of imputation when using ANCOVA or MMRM methods, and illustrate how these methods can be used when considering value

Newborn Sequencing in Genomic Medicine and Public Health

The rapid development of genomic sequencing technologies has decreased the cost of genetic analysis to the extent that it seems plausible that genome-scale sequencing could have widespread availability in pediatric care. Genomic sequencing provides a powerful diagnostic modality for patients who manifest symptoms of monogenic disease and an opportunity to detect health conditions before their development. However, many technical, clinical, ethical, and societal challenges should be addressed before such technology is widely deployed in pediatric practice. This article provides an overview of the Newborn Sequencing in Genomic Medicine and Public Health Consortium, which is investigating the application of genome-scale sequencing in newborns for both diagnosis and screening