Ethnic differences in the adaptation rate of HIV gp120 from a vaccine trial

Differences in HIV-1 gp120 sequence variation were examined in North American volunteers who became infected during a phase III vaccine trial using the rgp120 vaccine. Molecular adaptation of the virus in vaccine and placebo recipients from different ethnic subgroups was compared by estimating the d(N)/d(S )ratios in viruses sampled from each individual using three different methods. ANOVA analyses detected significant differences in d(N)/d(S )ratios among races (P < 0.02). gp120 sequences from the black individuals showed higher mean d(N)/d(S )ratios for all estimators (1.24–1.45) than in other races (0.66–1.35), and several pairwise comparisons involving blacks remained significant (P < 0.05) after correction for multiple tests. In addition, black-placebo individuals showed significantly (P < 0.02) higher mean d(N)/d(S )ratios (1.3–1.66) than placebo individuals from the other races (0.65–1.56). These results suggest intrinsic differences among races in immune response and highlight the need for including multiple ethnicities in the design of future HIV-1 vaccine studies and trials

Longitudinal Development of Reasons for Living and Dying With Suicide Attempters: A 2-Year Follow-Up Study

Background: Clinical interventions for patients after a suicide attempt might include a focus on Reasons for Living (RFL) and/or Reasons for Dying (RFD). The present study examined the longitudinal development of RFL and RFD in patients with and without a suicide-specific intervention - the Attempted Suicide Short Intervention Program (ASSIP). Methods: In this secondary analysis of a 2-year follow-up randomized controlled study, participants completed the Suicide Status Form II to assess RFL and RFD, at baseline, as well as at 6-, 12-, 18-, and 24-months follow-up. Growth models and latent class analysis were used to investigate longitudinal developments in RFL and RFD. Regression models were used to test the association between RFL, RFD and suicidal reattempts and ideation. Results: Cross-sectionally and longitudinally, RFD, but not RFL, were associated with suicide reattempts and suicidal ideation. The number of RFD decreased significantly across the 24 month period (from 1.90 at t1 to 1.04 at t5 in the control group and from 2.32 at t1 to 0.51 at t5 in the intervention group), and this decrease was stronger (b = −0.02; p = 0.004) in the ASSIP group than in the control group. There was no overall change in RFL. Three latent trajectories of RFD were identified: a decreasing (n = 77), a steady high (n = 17) and a trajectory with first increasing and then decreasing RFD (n = 26). The proportion of patients in the ASSIP intervention was highest in the decreasing trajectory and lowest in the steady high trajectory. Patients in the steady high trajectory were characterized by worse mental health and fewer social obligations (partner, children) at baseline. Conclusion: The results confirm the importance of RFD within the suicidal process and show that the number of RFD can be further reduced over the period of 24 months with short interventions such as ASSIP. The relevance of number of RFL in the suicidal process, as protective factor, was not confirmed. In the subgroup of patients whose RFD did not decrease over a long period of time, there is a particularly high risk of suicidal ideation/behavior. Clinical interventions should focus more closely on RFD, their etiology and maintenance

Collaborative Assessment and Management of Suicidality (CAMS) compared to enhanced treatment as usual (E-TAU) for suicidal patients in an inpatient setting: study protocol for a randomized controlled trial

Santel M, Beblo T, Neuner F, et al. Collaborative Assessment and Management of Suicidality (CAMS) compared to enhanced treatment as usual (E-TAU) for suicidal patients in an inpatient setting: study protocol for a randomized controlled trial. BMC Psychiatry. 2020;20(1): 183.Background The Collaborative Assessment and Management of Suicidality (CAMS) is a therapeutic framework that has been shown to reduce suicidal ideation and overall symptom distress. CAMS has not been previously evaluated in a standard acute inpatient mental health care setting with only short treatment times for suicidal patients. In this randomized controlled trial (RCT) we are investigating whether CAMS is more effective than Enhanced-Treatment as Usual (E-TAU) in reducing suicidal thoughts as primary outcome variable. We are also investigating depressive symptoms, general symptom relief, and the quality of the therapeutic alliance as secondary outcomes. Methods/Design This RCT is designed as a single-center, two-armed, parallel group observer-blinded clinical effectiveness investigation. We are recruiting and randomizing 60 participants with different diagnoses, who are admitted as inpatients because of acute suicidal thoughts or behaviors into the Clinic for Psychiatry and Psychotherapy, Ev. Hospital Bethel in Bielefeld, Germany. The duration of treatment will vary depending on patients’ needs and clinical assessments ranging between 10 and 40 days. Patients are assessed four times, at admission, discharge, 1 month, and 5 months post-discharge. The primary outcome measure is the Beck Scale for Suicide Ideation. Other outcome measures are administered as assessment timepoints including severity of psychiatric symptoms, depression, reasons for living, and therapeutic relationship. Discussion This effectiveness study is being conducted on an acute ward in a psychiatric clinic where patients have multiple problems and diagnoses. Treatment is somewhat limited, and therapists have a large caseloads. The results of this study can thus be generalizable to a typical inpatient psychiatric hospital settings

Development of a Clinical Guide to Enhance Care for Suicidal Patients

Suicidal thoughts and behavior are common among mental health patients and are a source of stress for clinicians, who typically receive limited formal training on suicide. The U.S. Air Force initiated a project to enhance care and increase practitioner confidence when working with suicidal patients. A clinical guide was developed containing 18 recommendations for assessing and managing suicidality, strategies for meeting the recommendations, and clinical tools to facilitate quality care. Training opportunities and marketing efforts accompanied distribution of the guide. This initial article reviews the guide\u27s development, content, and evaluation plan as a model that other health care systems, clinics, or training programs can follow to enhance care for suicidal patients. Outcome data will be presented in a follow-up article

Longitudinal population analysis of dual infection with recombination in two strains of HIV type 1 subtype B in an individual from a phase 3 HIV vaccine efficacy trial

This study documents a case of coinfection (simultaneous infection of an individual with two or more strains) of two HIV-1 subtype B strains in an individual from a Phase 3 HIV-1 vaccine efficacy trial, conducted in North American and the Netherlands. We examined 86 full-length gp120 (env) gene sequences from this individual collected from nine different time points over a 20-month period. We estimated evolutionary relationships using maximum likelihood and Bayesian methods and inferred recombination breakpoints and recombinant sequences using phylogenetic and substitutional methods. These analyses identified two strongly supported monophyletic clades (clades A and B) of 14 and 69 sequences each and a small paraphyletic recombinant clade of three sequences. We then studied the genetic characteristics of these lineages by comparing estimates of genetic diversity generated by mutation and recombination and adaptive selection within a coalescent and maximum likelihood framework. Our results suggest significant differences on the evolutionary dynamics of these strains. We then discuss the implications of these results for vaccine development

Reasons for Living and Dying in Suicide Attempters: A Two-year Prospective Study

Background: The aim of this study was to explore Reasons for Living (RFL) and Reasons for Dying (RFD) of suicide attempters and their association with current and future suicidal ideation and behavior. Method: The sample consisted of 60 patients who were admitted at a psychiatric emergency unit in Switzerland following an attempted suicide. They received treatment as usual, participated in an assessment interview and completed self-report questionnaires including written RFL and RFD responses, depressive symptoms, and suicide ideation at baseline and 6, 12 and 24 months follow-ups. Outcome measures were suicide ideation and repeated suicide attempts. Multiple imputations were used in order to address missing data. Results: The number of RFD responses was the strongest predictor for increased suicide ideation at baseline. The number of RFL responses was not associated with suicide ideation and reattempts. RFD, depressive symptoms, and baseline suicide ideation predicted subsequent suicide reattempt up to 12 months later in simple regression analyses. Mediation analyses suggested that RFD mediated the effect of depressive symptoms at baseline on suicide ideation at 12-months follow-up. Conclusion: RFL were unrelated to the mental health of study participants and did not function as protective factor against suicide risk. RFD may be an important motivational driver in the suicidal process. Clinical interventions should focus more on the reduction of RFD than on RFL in suicidal individuals

Using a Tablet-Based App to Deliver Evidence-Based Practices for Suicidal Patients in the Emergency Department: Pilot Randomized Controlled Trial

BACKGROUND: Emergency departments (EDs) have the potential to provide evidence-based practices for suicide prevention to patients who are acutely suicidal. However, few EDs have adequate time and personnel resources to deliver recommended evidence-based assessment and interventions. To raise the clinical standard of care for patients who are suicidal and seeking psychiatric crisis services in the ED, we developed Jaspr Health, a tablet-based app for direct use by such patients, which enables the delivery of 4 evidence-based practices. OBJECTIVE: This study aims to evaluate the feasibility, acceptability, and effectiveness of Jaspr Health among suicidal adults in EDs. METHODS: Patients who were acutely suicidal and seeking psychiatric crisis services participated in an unblinded pilot randomized controlled trial while in the ED. Participants were randomly assigned to Jaspr Health (n=14) or care as usual (control; n=17) groups. Participants were assessed at baseline, and a 2-hour posttest using self-report measures and a semistructured interview were conducted. RESULTS: Conditions differed significantly at baseline with regard to age but not other demographic variables or baseline measures. On average, participants had been in the ED for 17 hours before enrolling in the study. Over their lifetime, 84% (26/31) of the sample had made a suicide attempt (mean 3.4, SD 6.4) and 61% (19/31) had engaged in nonsuicidal self-injurious behaviors, with an average rate of 8.8 times in the past 3 months. All established feasibility and acceptability criteria were met: no adverse events occurred, participants\u27 app use was high, Jaspr Health app user satisfaction ratings were high, and all participants using Jaspr Health recommended its use for other suicidal ED patients. Comparisons between study conditions provide preliminary support for the effectiveness of the app: participants using Jaspr Health reported a statistically significant increase in receiving 4 evidence-based suicide prevention interventions and overall satisfaction ratings with their ED experience. In addition, significant decreases in distress and agitation, along with significant increases in learning to cope more effectively with current and future suicidal thoughts, were observed among participants using Jaspr Health compared with those receiving care as usual. CONCLUSIONS: Even with limited statistical power, the results showed that Jaspr Health is feasible, acceptable, and clinically effective for use by ED patients who are acutely suicidal and seeking ED-based psychiatric crisis services. TRIAL REGISTRATION: ClinicalTrials.gov NCT03584386; https://clinicaltrials.gov/ct2/show/NCT03584386

Stress-Induced Reinstatement of Drug Seeking: 20 Years of Progress

In human addicts, drug relapse and craving are often provoked by stress. Since 1995, this clinical scenario has been studied using a rat model of stress-induced reinstatement of drug seeking. Here, we first discuss the generality of stress-induced reinstatement to different drugs of abuse, different stressors, and different behavioral procedures. We also discuss neuropharmacological mechanisms, and brain areas and circuits controlling stress-induced reinstatement of drug seeking. We conclude by discussing results from translational human laboratory studies and clinical trials that were inspired by results from rat studies on stress-induced reinstatement. Our main conclusions are (1) The phenomenon of stress-induced reinstatement, first shown with an intermittent footshock stressor in rats trained to self-administer heroin, generalizes to other abused drugs, including cocaine, methamphetamine, nicotine, and alcohol, and is also observed in the conditioned place preference model in rats and mice. This phenomenon, however, is stressor specific and not all stressors induce reinstatement of drug seeking. (2) Neuropharmacological studies indicate the involvement of corticotropin-releasing factor (CRF), noradrenaline, dopamine, glutamate, kappa/dynorphin, and several other peptide and neurotransmitter systems in stress-induced reinstatement. Neuropharmacology and circuitry studies indicate the involvement of CRF and noradrenaline transmission in bed nucleus of stria terminalis and central amygdala, and dopamine, CRF, kappa/dynorphin, and glutamate transmission in other components of the mesocorticolimbic dopamine system (ventral tegmental area, medial prefrontal cortex, orbitofrontal cortex, and nucleus accumbens). (3) Translational human laboratory studies and a recent clinical trial study show the efficacy of alpha-2 adrenoceptor agonists in decreasing stress-induced drug craving and stress-induced initial heroin lapse

Phylodynamics of HIV-1 from a Phase III AIDS Vaccine Trial in Bangkok, Thailand

In 2003, a phase III placebo-controlled trial (VAX003) was completed in Bangkok, Thailand. Of the 2,546 individuals enrolled in the trial based on high risk for infection through injection drug use (IDU), we obtained clinical samples and HIV-1 sequence data (envelope glycoprotein gene gp120) from 215 individuals who became infected during the trial. Here, we used these data in combination with other publicly available gp120 sequences to perform a molecular surveillance and phylodynamic analysis of HIV-1 in Thailand.Phylogenetic and population genetic estimators were used to assess HIV-1 gp120 diversity as a function of vaccination treatment, viral load (VL) and CD4(+) counts, to identify transmission clusters and to investigate the timescale and demographics of HIV-1 in Thailand. Three HIV-1 subtypes were identified: CRF01_AE (85% of the infections), subtype B (13%) and CRF15_AE (2%). The Bangkok IDU cohort showed more gp120 diversity than other Asian IDU cohorts and similar diversity to that observed in sexually infected individuals. Moreover, significant differences (P<0.02) in genetic diversity were observed in CRF01_AE IDU with different VL and CD4(+) counts. No phylogenetic structure was detected regarding any of the epidemiological and clinical factors tested, although high proportions (35% to 50%) of early infections fell into clusters, which suggests that transmission chains associated with acute infection play a key role on HIV-1 spread among IDU. CRF01_AE was estimated to have emerged in Thailand in 1984.5 (1983-1986), 3-6 years before the first recognition of symptomatic patients (1989). The relative genetic diversity of the HIV-1 population has remained high despite decreasing prevalence rates since the mid 1990s.Our study and recent epidemiological reports indicate that HIV-1 is still a major threat in Thailand and suggest that HIV awareness and prevention needs to be strengthened to avoid AIDS resurgence