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

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

Iatrogenic Spinal Cord Injury Resulting From Cervical Spine Surgery.

STUDY DESIGN: Retrospective cohort study of prospectively collected data. OBJECTIVE: To examine the incidence of iatrogenic spinal cord injury following elective cervical spine surgery. METHODS: A retrospective multicenter case series study involving 21 high-volume surgical centers from the AOSpine North America Clinical Research Network was conducted. Medical records for 17 625 patients who received cervical spine surgery (levels from C2 to C7) between January 1, 2005, and December 31, 2011, were reviewed to identify occurrence of iatrogenic spinal cord injury. RESULTS: In total, 3 cases of iatrogenic spinal cord injury following cervical spine surgery were identified. Institutional incidence rates ranged from 0.0% to 0.24%. Of the 3 patients with quadriplegia, one underwent anterior-only surgery with 2-level cervical corpectomy, one underwent anterior surgery with corpectomy in addition to posterior surgery, and one underwent posterior decompression and fusion surgery alone. One patient had complete neurologic recovery, one partially recovered, and one did not recover motor function. CONCLUSION: Iatrogenic spinal cord injury following cervical spine surgery is a rare and devastating adverse event. No standard protocol exists that can guarantee prevention of this complication, and there is a lack of consensus regarding evaluation and treatment when it does occur. Emergent imaging with magnetic resonance imaging or computed tomography myelography to evaluate for compressive etiology or malpositioned instrumentation and avoidance of hypotension should be performed in cases of intraoperative and postoperative spinal cord injury

Predictors of suboptimal CD4 response among women achieving virologic suppression in a randomized antiretroviral treatment trial, Africa

Background: A subset of HIV-1 infected patients starting highly active antiretroviral treatment (HAART) experience suboptimal CD4 response (SCR) despite virologic suppression. We studied the rate of and risk factors for SCR among women starting HAART in the ACTG A5208 study conducted in 7 African countries. 741 HAART-naive women with screening CD4 count <200 cells/μL were randomized to start HAART with Tenofovir/Emtricitabine plus either Nevirapine or Lopinavir/Ritonavir. Methods: This analysis includes the 625 women who remained on-study through 48 weeks without experiencing protocol-defined virologic failure. We defined SCR as < 100 CD4 cells/μL increase from baseline and absolute CD4 cell count < 350 cells/μL, both at 48 weeks after HAART initiation. Results: The baseline characteristics for the 625 women prior to HAART initiation were: median age 33 years, screening CD4 count 134 cells/μL, and HIV-1 RNA 5.1 log10 copies/mL; 184 (29%) were WHO Stage 3 or 4. Seventy one (11%) of these 625 women experienced SCR. Baseline factors independently associated with increased odds of SCR included older age, lower HIV-1 RNA, positive Hepatitis B surface antigen, and site location. At 96 weeks, only 6% of the SCR group had CD4 ≥ 350 cells/μL compared with 67% in the non SCR group. Conclusion: After starting HAART, 11% of women with virologic suppression through 48 weeks experienced SCR. These patients were also less likely to achieve CD4 ≥ 350 cells/μL by 96 weeks. The underlying causes and long term clinical implications of SCR deserve further investigation. Trial registration Clinicaltrials.gov Identifier: NCT0008950

Comparative gender analysis of the efficacy and safety of atazanavir/ritonavir and lopinavir/ritonavir at 96 weeks in the CASTLE study.

OBJECTIVES: To examine whether the overall results of the CASTLE study pertain to both genders, we analysed the efficacy and safety of atazanavir/ritonavir and lopinavir/ritonavir in 277 female and 606 male patients in the open-label, multinational trial over 96 weeks. The trial is registered with ClinicalTrials.gov, number NCT00272779. METHODS: Treatment-naive patients aged ≥ 18 years with HIV-1 RNA ≥ 5000 copies/mL were randomized to receive either atazanavir/ritonavir 300/100 mg once daily or lopinavir/ritonavir 400/100 mg twice daily, with fixed-dose tenofovir/emtricitabine 300/200 mg once daily. RESULTS: At week 96, confirmed virological response rates (HIV RNA \u3c50 copies\u3e/mL; intent-to-treat analysis) were higher in women and men receiving atazanavir/ritonavir than those receiving lopinavir/ritonavir and lower in women than men in both treatment arms (67% of women and 77% of men on atazanavir/ritonavir and 63% of women and 71% of men on lopinavir/ritonavir). These differences were not observed in the on-treatment analysis. Mean change in CD4 cell count from baseline to week 96 was 265 cells/mm(3) for women and 269 cells/mm(3) for men on atazanavir/ritonavir and 298 cells/mm(3) for women and 286 cells/mm(3) for men on lopinavir/ritonavir. Discontinuation rates were higher in women than men in each treatment arm (22% of women and 15% of men on atazanavir/ritonavir and 29% of women and 18% of men on lopinavir/ritonavir). In women and men, grade 2-4 nausea and diarrhoea were more frequent in the lopinavir/ritonavir group; jaundice and hyperbilirubinaemia occurred more frequently in the atazanavir/ritonavir group. CONCLUSIONS: Once-daily atazanavir/ritonavir is an effective and well-tolerated therapeutic option for women and men with HIV-1 infection. The sex-based differences in response may be due to higher discontinuation rates in women

Topological Defects and Interactions in Nematic Emulsions

Inverse nematic emulsions in which surfactant-coated water droplets are dispersed in a nematic host fluid have distinctive properties that set them apart from dispersions of two isotropic fluids or of nematic droplets in an isotropic fluid. We present a comprehensive theoretical study of the distortions produced in the nematic host by the dispersed droplets and of solvent mediated dipolar interactions between droplets that lead to their experimentally observed chaining. A single droplet in a nematic host acts like a macroscopic hedgehog defect. Global boundary conditions force the nucleation of compensating topological defects in the nematic host. Using variational techniques, we show that in the lowest energy configuration, a single water droplet draws a single hedgehog out of the nematic host to form a tightly bound dipole. Configurations in which the water droplet is encircled by a disclination ring have higher energy. The droplet-dipole induces distortions in the nematic host that lead to an effective dipole-dipole interaction between droplets and hence to chaining.Comment: 17 double column pages prepared by RevTex, 15 eps figures included in text, 2 gif figures for Fig. 1

HIV-1 protease inhibitors and clinical malaria: A secondary analysis of the AIDS Clinical Trials Group A5208 study

HIV-1 protease inhibitors (PIs) have antimalarial activity in vitro and in murine models. The potential beneficial effect of HIV-1 PIs on malaria has not been studied in clinical settings. We used data from Adult AIDS Clinical Trials Group A5208 sites where malaria is endemic to compare the incidence of clinically diagnosed malaria among HIV-infected adult women randomized to either lopinavir/ritonavir (LPV/r)-based antiretroviral therapy (ART) or to nevirapine (NVP)-based ART. We calculated hazard ratios and 95% confidence intervals. We conducted a recurrent events analysis that included both first and second clinical malarial episodes and also conducted analyses to assess the sensitivity of results to outcome misclassification. Among the 445 women in this analysis, 137 (31%) received a clinical diagnosis of malaria at least once during follow-up. Of these 137, 72 (53%) were randomized to LPV/r-based ART. Assignment to the LPV/r treatment group (n = 226) was not consistent with a large decrease in the hazard of first clinical malarial episode (hazard ratio = 1.11 [0.79 to 1.56]). The results were similar in the recurrent events analysis. Sensitivity analyses indicated the results were robust to reasonable levels of outcome misclassification. In this study, the treatment with LPV/r compared to NVP had no apparent beneficial effect on the incidence of clinical malaria among HIV-infected adult women. Additional research concerning the effects of PI-based therapy on the incidence of malaria diagnosed by more specific criteria and among groups at a higher risk for severe disease is warranted. Copyrigh