Oxytocin's anti-inflammatory and proimmune functions in COVID-19: a transcriptomic signature-based approach.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a worldwide pandemic, infecting over 16 million people worldwide with a significant mortality rate. However, there is no current Food and Drug Administration-approved drug that treats coronavirus disease 2019 (COVID-19). Damage to T lymphocytes along with the cytokine storm are important factors that lead to exacerbation of clinical cases. Here, we are proposing intravenous oxytocin (OXT) as a candidate for adjunctive therapy for COVID-19. OXT has anti-inflammatory and proimmune adaptive functions. Using the Library of Integrated Network-Based Cellular Signatures (LINCS), we used the transcriptomic signature for carbetocin, an OXT agonist, and compared it to gene knockdown signatures of inflammatory (such as interleukin IL-1ß and IL-6) and proimmune markers (including T cell and macrophage cell markers like CD40 and ARG1). We found that carbetocin's transcriptomic signature has a pattern of concordance with inflammation and immune marker knockdown signatures that are consistent with reduction of inflammation and promotion and sustaining of immune response. This suggests that carbetocin may have potent effects in modulating inflammation, attenuating T cell inhibition, and enhancing T cell activation. Our results also suggest that carbetocin is more effective at inducing immune cell responses than either lopinavir or hydroxychloroquine, both of which have been explored for the treatment of COVID-19.

Ketamine for acute suicidal ideation. An emergency department intervention: A randomized, double-blind, placebo-controlled, proof-of-concept trial.

BACKGROUND: Depressed patients presenting to emergency departments with acute suicidal ideation are a major public health concern. Ketamine, a rapidly acting antidepressant with antisuicidal properties, might offer relief. METHODS: In a randomized, double-blind, placebo-controlled, proof-of-concept trial, 18 depressed subjects with acute suicidal ideation, who required hospitalization, were randomized to either an intravenous ketamine 0.2 mg/kg group or a saline placebo group. Safety and efficacy evaluations were scheduled for 15, 30, 60, 90, 120, 180, and 240 min, and on Days 1, 2, 3, 7, and 14 after infusion. The main outcome measure was suicidal ideation with secondary measures of depression. RESULTS: Nine subjects were randomized to each group. There were no differences between groups at baseline in any demographic or assessment scales. A reduction in suicidal ideation was noted at 90-180 min (p < .05). Ninety minutes after infusion, 88% of the ketamine group had achieved remission of suicidal ideation compared with 33% in the placebo group (p < .05). No serious adverse events were noted. CONCLUSIONS: Ketamine was safe and effective for rapid reduction in suicidal ideation in depressed, highly suicidal subjects presenting to the emergency department. Our results support further study of ketamine for acute suicidal ideation.

The Effect of Antidepressants on Depression After Traumatic Brain Injury: A Meta-analysis.

OBJECTIVE: Following traumatic brain injury (TBI), depressive symptoms are common and may influence recovery. We performed a meta-analysis to estimate the benefit of antidepressants following TBI and compare the estimated effects between antidepressants and placebo. PARTICIPANTS: Multiple databases were searched to find prospective pharmacological treatment studies of major depressive disorder (MDD) in adults following TBI. MAIN MEASURES: Effect sizes for antidepressant medications in patients with TBI were calculated for within-subjects designs that examined change from baseline after receiving medical treatment and treatment/placebo designs that examined the differences between the antidepressants and placebo groups. DESIGN: A random-effects model was used for both analyses. RESULTS: Of 1028 titles screened, 11 were included. Pooled estimates showed nonsignificant difference in reduction of depression scores between medications and placebo (standardized mean difference of 5 trials = -0.3; 95% CI, -0.6 to 0.0; I = 17%), and a significant reduction in depression scores for individuals after pharmacotherapy (mean change = -11.2; 95% CI, -14.7 to -7.6 on the Hamilton Depression Scale; I = 87%). CONCLUSIONS: This meta-analysis found no significant benefit of antidepressant over placebo in the treatment of MDD following TBI. Pooled estimates showed a high degree of bias and heterogeneity. Prospective studies on the impact of antidepressants in well-defined cohorts of TBI patients are warranted.

Ketamine for Treatment of Suicidal Ideation and Reduction of Risk for Suicidal Behavior.

Ketamine, an NMDA receptor antagonist with efficacy as a rapid anti-depressant, has early evidence for action to reduce suicidal ideation. This review will explore several important questions that arise from these studies. First, how do we measure reductions in suicidal ideation that occur over minutes to hours? Second, are the reductions in suicidal ideation after ketamine treatment solely a result of its rapid anti-depressant effect? Third, is ketamine only effective in reducing suicidal ideation in patients with mood disorders? Fourth, could ketamine's action lead us to a greater understanding of the neurobiology of suicidal processes? Last, do the reductions in depression and suicidal ideation after ketamine treatment translate into decreased risk for suicidal behavior? Our review concludes that ketamine treatment can be seen as a double-edged sword, clinically to help provide treatment for acutely suicidal patients and experimentally to explore the neurobiological nature of suicidal ideation and suicidal behavior.

Efficacy of venlafaxine XR for the treatment of pain in patients with spinal cord injury and major depression: a randomized, controlled trial.

OBJECTIVES: To (1) determine the efficacy of venlafaxine XR for the treatment of pain (secondary aim) in individuals with spinal cord injury (SCI) enrolled in a randomized controlled trial (RCT) on the efficacy of venlafaxine XR for major depressive disorder (MDD) (primary aim); and (2) test the hypothesis that venlafaxine XR would be effective for both neuropathic and nociceptive pain. DESIGN: Multisite, double-blind, randomized (1:1) controlled trial with subjects block randomized and stratified by site, lifetime history of substance abuse, and prior history of MDD. SETTING: Six Departments of Physical Medicine and Rehabilitation in university-based medical schools. PARTICIPANTS: Individuals (N=123) with SCI and major depression between 18 and 64 years of age, at least 1 month post-SCI who also reported pain. INTERVENTION: Twelve-week trial of venlafaxine XR versus placebo using a flexible titration schedule. OUTCOME MEASURES: A 0-to-10 numeric rating scale for pain, pain interference items of the Brief Pain Inventory; 30% and 50% responders. RESULTS: The effect of venlafaxine XR on neuropathic pain was similar to that of placebo. However venlafaxine XR resulted in statistically significant and clinically meaningful reductions in nociceptive pain site intensity and interference even after controlling for anxiety, depression, and multiple pain sites within the same individual. For those who achieved a minimally effective dose of venlafaxine XR, some additional evidence of effectiveness was noted for those with mixed (both neuropathic and nociceptive) pain sites. CONCLUSIONS: Venlafaxine XR could complement current medications and procedures for treating pain after SCI and MDD that has nociceptive features. Its usefulness for treating central neuropathic pain is likely to be limited. Research is needed to replicate these findings and determine whether the antinociceptive effect of venlafaxine XR generalizes to persons with SCI pain without MDD.

Novel risk factors associated with current suicidal ideation and lifetime suicide attempts in individuals with spinal cord injury.

OBJECTIVE: To determine unique associations of suicidal ideation (SI) and lifetime suicide attempts (SAs) in individuals with spinal cord injury (SCI). DESIGN: Cross-sectional analysis. SETTING: Outpatient. PARTICIPANTS: Individuals with SCI (N=2533) who were 18 years or older with a history of traumatic SCI. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Any SI in the past 2 weeks (9-item Patient Health Questionnaire) and any lifetime SA. RESULTS: Three hundred twenty-three individuals (13.3%) reported SI in the past 2 weeks and 179 (7.4%) reported lifetime SA. After controlling for other factors, both lifetime SA and current SI were associated with study site and current level of depression. In addition, SA was associated with less education, younger age at injury, having current or past treatment of depression, and having bipolar disorder or schizophrenia. SI was associated with more years since injury and lifetime SA. Several psychological factors were associated with current SI and lifetime SAs, including lower environmental reward and less positive affect. In addition, control of one's community activities and spiritual well-being were associated with current SI. In bivariate comparisons, severity of SCI was also associated with the 47% of the SAs that occurred after injury. CONCLUSIONS: Several unique associations of SI and lifetime SA in individuals with SCI were identified, including level of environmental reward and control, spiritual well-being, and severity of SCI. These factors bear further investigation as prospective risk factors for suicidal behavior after SCI.

Rapid follow-up for patients after psychiatric crisis.

Patients in psychiatric crisis often lack connection to community resources and present to emergency departments (EDs) for care. A transitional psychiatry clinic (TPC) bridged patients after ED visit. These retrospective chart review data of 390 patients were analyzed by ANOVA, logistic regression and survival analysis. Predictors of ED return included psychosis, personality disorder and increased number of prior ED visits. Longer wait for the TPC was associated strongly with non-attendance. TPC appointment within 3 days was associated with significantly longer time in the community without ED presentation. Rapid follow-up after ED visits increased attendance at aftercare and lengthens community tenure.

Post-traumatic growth following spinal cord injury.

CONTEXT/OBJECTIVE: Examine the relationship of post-traumatic psychological growth (PTG), depression, and personal and injury characteristics in persons with spinal cord injury (SCI). DESIGN: Cross-sectional survey. SETTING: Community. PARTICIPANTS: Eight hundred and twenty-four adults with SCI. INTERVENTIONS: None. OUTCOME MEASURES: Five items from the Post-traumatic Growth Inventory, reflecting positive change after injury in life priorities, closeness to others, new opportunities being available, stronger faith, and personal strength. RESULTS: Initial structural equation model testing of a conceptual model of personal and injury characteristics, violent etiology, depression, and PTG resulted in a poor fit. Model modifications resulted in an improved fit, but explained only 5% of the variance in PTG. Being female, younger, having less formal education, and less time since injury had significant relationships with PTG, whereas depression, violent etiology, and injury level/severity did not. In each PTG domain, between 54 and 79% of the sample reported at least some positive change after injury. CONCLUSIONS: The results of this study, while promising, explained only a small portion of the variance in PTG. A majority of the sample experienced some positive change after injury, with the greatest change in discovering that they were stronger than they thought they were. Comparing means previously reported in a non-SCI sample of those who experienced trauma, positive change after injury was comparable for each PTG item except for new opportunities being available, which was significantly lower for those with SCI. Future directions of research include the development of theoretical models of PTG after SCI.

Routine depression screening in an HIV clinic cohort identifies patients with complex psychiatric co-morbidities who show significant response to treatment.

This study described characteristics, psychiatric diagnoses and response to treatment among patients in an outpatient HIV clinic who screened positive for depression. Depressed (25 %) were less likely to have private insurance, less likely to have suppressed HIV viral loads, had more anxiety symptoms, and were more likely to report current substance abuse than not depressed. Among depressed, 81.2 % met diagnostic criteria for a depressive disorder; 78 % for an anxiety disorder; 61 % for a substance use disorder; and 30 % for co-morbid anxiety, depression, and substance use disorders. Depressed received significantly more treatment for depression and less HIV primary care than not depressed patients. PHQ-9 total depression scores decreased by 0.63 from baseline to 6-month follow-up for every additional attended depression treatment visit. HIV clinics can routinely screen and treat depressive symptoms, but should consider accurate psychiatric diagnosis as well as co-occurring mental disorders.

Patient reported outcomes in routine care: advancing data capture for HIV cohort research.

INTRODUCTION: Computerized collection of standardized measures of patient reported outcomes (PROs) provides a novel paradigm for data capture at the point of clinical care. Comparisons between data from PROs and Electronic Health Records (EHR) are lacking. We compare EHR and PRO for capture of depression and substance abuse and their relationship to adherence to antiretroviral therapy (ART). METHODS: This retrospective study includes HIV-positive patients at an HIV clinic who completed an initial PRO assessment April 2008-July 2009. The questionnaire includes measures of depression (PHQ-9) and substance abuse (ASSIST). Self-reported ART adherence was modeled using separate logistic regression analyses (EHR vs PRO). RESULTS: The study included 782 participants. EHR vs PRO diagnosis of current substance abuse was 13% (n = 99) vs 6% (n = 45) (P < .0001), and current depression was 41% (n = 317) vs 12% (n = 97) (P < .0001). In the EHR model, neither substance abuse (OR = 1.25; 95% CI = 0.70-2.21) nor depression (OR = 0.93; 95% CI = 0.62-1.40) was significantly associated with poor ART adherence. Conversely, in the PRO model, current substance abuse (OR = 2.78; 95% CI = 1.33-5.81) and current depression (OR = 1.93; 95% CI = 1.12-3.33) were associated with poor ART adherence. DISCUSSIONS: The explanatory characteristics of the PRO model correlated best with factors known to be associated with poor ART adherence (substance abuse; depression). The computerized capture of PROs as a part of routine clinical care may prove to be a complementary and potentially transformative health informatics technology for research and patient care.

Single, Fixed-Dose Intranasal Ketamine for Alleviation of Acute Suicidal Ideation. An Emergency Department, Trans-Diagnostic Approach: A Randomized, Double-Blind, Placebo-Controlled, Proof-of-Concept Trial.

BACKGROUND: Suicidal patients often present to the emergency department, where specific anti-suicidal treatment is lacking. Ketamine, a Glutamate modulator and a rapidly acting antidepressant with anti-suicidal properties, might offer relief. AIMS: Evaluation of single, fixed-dosed intranasal ketamine for acute suicidal ideation in the emergency department. METHODS: Between August 2016 and April 2018, 30 eligible suicidal subjects, scheduled for psychiatric hospitalization, independently of their psychiatric diagnosis, were randomized to intranasal ketamine 40 mg or saline placebo. Safety and efficacy evaluations were scheduled for 30, 60, 120 and 240 min post administration and on days 1, 2, 3, 4, 5, 7, 21 and 28. Primary outcome was suicidal ideation. RESULTS: Fifteen subjects were randomized for each study group. All were analyzed for primary and secondary outcomes. Four hours post administration, the mean difference in suicidal symptoms between the groups, measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) item of suicidal thoughts (MADRS-SI), was 1.267 (95% confident interval 0.1-2.43, p < 0.05) favoring treatment. Remission from suicidal ideation was evident in 80% for the ketamine group compared with 33% for the controls (p < 0.05). The mean difference in depressive symptoms, measured by MADRS, at the same time was 9.75 (95% confident interval 0.72-18.79, p < 0.05) favoring ketamine. Treatment was safe and well-tolerated. CONCLUSIONS: Single, fixed-dose, intranasal ketamine alleviated suicidal ideation and improved depressive symptoms four hours post administration. We present here an innovative paradigm for emergency department management of suicidal individuals. Future larger-scale studies are warranted. ClinicalTrials.gov Identifier: NCT02183272.

SIBAT-A Computerized Assessment Tool for Suicide Ideation and Behavior: Development and Psychometric Properties.

Objective: Most assessments of suicidal ideation and behavior (SIB) are limited by reliance on a single assessor, typically a clinician or patient, with scant detail on patient-related drivers of SIB and inability to detect rapid change in SIB. Furthermore, many techniques do not include a semistructured interview, increasing rater variability. The Suicide Ideation and Behavior Assessment Tool (SIBAT) addresses these limitations. Design: More than 30 experts in scale development, statistics, and clinical management of suicidal patients collaborated over a greater than four-year period to develop the SIBAT. Input for content and validity was received from patients, clinicians, and regulatory authorities in the United States (US) and Europe. Psychometric properties of the SIBAT were evaluated in validation studies. Results: The SIBAT is organized into eight independent patient- or clinician-rated modules with branching logic and scoring algorithms, which necessitates computerization. Patient-reported information is first captured in Modules 1 to 5. Thereafter, an experienced clinician reviews the patient's report, conducts a semistructured interview (Module 6), and assesses the patient's suicide risk (Module 7) and optimal antisuicide management (Module 8). Input from cognitive interviews of diverse adult, adolescent, and clinician participants was incorporated into the final version of the SIBAT. Psychometric testing demonstrated good inter-rater reliability (intraclass coefficient range: 0.68-0.82), intra-rater reliability (weighted-kappa range: 0.64-0.76), and concurrent validity with other instruments for assessing SIB. Conclusion: Patient- and clinician-based assessments and the psychometric studies summarized in this report support the validity and reliability of the SIBAT for capturing critical information related to assessment of SIB in adolescents and adults at risk for suicide.

SSRIs: Applications in inflammatory lung disease and implications for COVID-19.

Selective serotonin reuptake inhibitors (SSRIs) have anti-inflammatory properties that may have clinical utility in treating severe pulmonary manifestations of COVID-19. SSRIs exert anti-inflammatory effects at three mechanistic levels: (a) inhibition of proinflammatory transcription factor activity, including NF-κB and STAT3; (b) downregulation of lung tissue damage and proinflammatory cell recruitment via inhibition of cytokines, including IL-6, IL-8, TNF-α, and IL-1ß; and (c) direct suppression inflammatory cells, including T cells, macrophages, and platelets. These pathways are implicated in the pathogenesis of COVID-19. In this review, we will compare the pathogenesis of lung inflammation in pulmonary diseases including COVID-19, ARDS, and chronic obstructive pulmonary disease (COPD), describe the anti-inflammatory properties of SSRIs, and discuss the applications of SSRIS in treating COVID-19-associated inflammatory lung disease.

Fluoxetine as an anti-inflammatory therapy in SARS-CoV-2 infection.

Hyperinflammatory response caused by infections such as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) increases organ failure, intensive care unit admission, and mortality. Cytokine storm in patients with Coronavirus Disease 2019 (COVID-19) drives this pattern of poor clinical outcomes and is dependent upon the activity of the transcription factor complex nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) and its downstream target gene interleukin 6 (IL6) which interacts with IL6 receptor (IL6R) and the IL6 signal transduction protein (IL6ST or gp130) to regulate intracellular inflammatory pathways. In this study, we compare transcriptomic signatures from a variety of drug-treated or genetically suppressed (i.e. knockdown) cell lines in order to identify a mechanism by which antidepressants such as fluoxetine demonstrate non-serotonergic, anti-inflammatory effects. Our results demonstrate a critical role for IL6ST and NF-kappaB Subunit 1 (NFKB1) in fluoxetine's ability to act as a potential therapy for hyperinflammatory states such as asthma, sepsis, and COVID-19.

Routine, self-administered, touch-screen, computer-based suicidal ideation assessment linked to automated response team notification in an HIV primary care setting.

BACKGROUND: Human immunodeficiency virus (HIV) and AIDS continue to be associated with an underrecognized risk for suicidal ideation, attempted suicide, and completed suicide. Suicidal ideation represents an important predictor for subsequent attempted and completed suicide. We sought to implement routine screening of suicidal ideation and associated conditions using computerized patient-reported outcome (PRO) assessments. METHODS: Two geographically distinct academic HIV primary care clinics enrolled patients who attended scheduled visits from December 2005 through February 2009. Touch-screen, computer-based PRO assessments were implemented into routine clinical care. Substance abuse, alcohol consumption, depression, and anxiety were assessed. The 9-item Patient Health Questionnaire assesses the frequency of suicidal ideation in the preceding 2 weeks. A response of "nearly every day" triggered an automated page to predetermined clinic personnel, who completed more detailed self-harm assessments. RESULTS: Overall, 1216 patients (740 from the University of Alabama at Birmingham and 476 from the University of Washington) completed the initial PRO assessment during the study period. Patients were predominantly white (646 [53%]) and male (959 [79%]), with a mean age (+/- standard deviation) of 44 +/- 10 years. Among surveyed patients, 170 (14%) endorsed some level of suicidal ideation, whereas 33 (3%) admitted suicidal ideation nearly every day. In multivariable analysis, suicidal ideation risk was lower with advancing age (odds ratio [OR], 0.74 per 10 years; 95% confidence interval [CI], 0.58-0.96) and was increased with current substance abuse (OR, 1.88; 95% CI, 1.03-3.44) and more-severe depression (OR, 3.91 for moderate depression [95% CI, 2.12-7.22] and 25.55 for severe depression [95% CI, 12.73-51.30]). DISCUSSION: Suicidal ideation was associated with current substance abuse and depression. The use of novel technologies to incorporate routine self-reported screening for suicidal ideation and other health domains allows for timely detection and intervention for this life-threatening condition.

Willingness of Mentally Ill Individuals to Sign Up for a Novel Proposal to Prevent Firearm Suicide.

The study goal was to determine whether a significant number of high suicide risk individuals would confidentially put their own names onto a list to prevent future gun purchases. An anonymous written survey was administered in an inpatient psychiatric unit and two outpatient psychiatric clinics at an academic medical center. Two hundred forty individuals were approached to fill out the survey, of whom 200 (83.3%) did so. Forty-six percent of participants stated that they would put their own name onto the list. This novel suicide prevention proposal, a Do-Not-Sell List, would appeal to many people at high risk for suicide.

Assessment of the relationship of spiritual well-being to depression and quality of life for persons with spinal cord injury.

OBJECTIVE: This study sought to describe the association between spiritual well-being, demographic characteristics, quality of life (QOL) and depressive symptoms following spinal cord injury (SCI). We hypothesized QOL and depressed mood would both be explained by extent of spiritual well-being, and meaning-focused (M&P) spirituality would have a stronger impact than faith-focused spirituality. METHODS: 210 individuals with SCI were screened as part of a randomized control trial of venlafaxine XR for major depressive disorder (MDD). 204 completed all measures: Patient Health Questionniare-9 (PHQ-9) assessed depression, the FACIT-Sp assessed spiritual well-being, the Neuro-QOL PAWB scale assessed QOL, and the PANAS assessed affect. RESULTS: Approximately 26% had major depression. Bivariate correlations of scores on PAWB and PANAS and FACIT-Sp showed that all four scales had strong associations with those on PAWB (p < 0.0005). As hypothesized, both the M&P and Faith scales of the FACIT-Sp were significant predictors of QOL (ß = 0.544; p < 0.0005 and ß = 0.151; p = 0.004), though only the M&P scale was an independently significant predictor of likely MDD. CONCLUSION: The findings support that spirituality, as measured by the FACIT-Sp, is strongly associated with QOL and likelihood of MDD. Assessment of spirituality should be included along with more traditional psychological measurements to better inform treatment. Implications for Rehabilitation Spiritual beliefs can contribute to quality of life and may help moderate depressive symptoms that accompany chronic illness and disability, suggesting that rehabilitation professionals should address spirituality in working with their patients with spinal cord injury (SCI). While spiritual issues are often deferred to pastoral counselors during hospitalization, it is clear that addressing these is not the domain of one discipline and does not end upon inpatient discharge. In addressing spirituality, clinicians should tap the spiritual strengths present in their clients, whether meaning/peace-focused or religious, understanding that spirituality involves more than religiosity and also that having a sense of meaning and peace appears to be of great importance.

A Machine Learning Approach to Identifying the Thought Markers of Suicidal Subjects: A Prospective Multicenter Trial.

Death by suicide demonstrates profound personal suffering and societal failure. While basic sciences provide the opportunity to understand biological markers related to suicide, computer science provides opportunities to understand suicide thought markers. In this novel prospective, multimodal, multicenter, mixed demographic study, we used machine learning to measure and fuse two classes of suicidal thought markers: verbal and nonverbal. Machine learning algorithms were used with the subjects' words and vocal characteristics to classify 379 subjects recruited from two academic medical centers and a rural community hospital into one of three groups: suicidal, mentally ill but not suicidal, or controls. By combining linguistic and acoustic characteristics, subjects could be classified into one of the three groups with up to 85% accuracy. The results provide insight into how advanced technology can be used for suicide assessment and prevention.

Cigarette Smokers are Less Likely to Have Undetectable Viral Loads: Results From Four HIV Clinics.

BACKGROUND: The prevalence of smoking among HIV-infected individuals is 2-3 times that of the general population, increasing the risk of smoking-related morbidity and mortality. We examined characteristics associated with smoking behavior among a large cohort of HIV-infected individuals in care in the United States. METHODS: A convenience sample of 2952 HIV-infected patients in the Centers for AIDS Research (CFAR) Network of Integrated Clinical Systems (CNICS) was assessed during routine clinic visits and was included. Multinomial logistic regression was used to examine the relationship between smoking status, depression/panic symptoms, alcohol/substance use, and demographic and clinical characteristics. RESULTS: Compared with never-smokers, current smokers were more likely to have moderate to severe depression (odds ratio [OR] 1.37), endorse current substance use (OR 14.09), and less likely to report low-risk alcohol use on the Alcohol Use Disorders Identification Test (AUDIT-C) (OR 0.73). Current smokers were less likely to have an undetectable viral load (OR 0.75), and more likely to have current substance abuse (OR 2.81) and moderate to severe depression (OR 1.50), relative to smokers who had quit smoking. CONCLUSIONS: HIV-infected smokers are less likely to have undetectable viral loads and frequently have psychosocial comorbidities including depression and substance abuse that impact antiretroviral therapy adherence and viral load suppression. To be effective, smoking-cessation interventions need to address the complex underlying concurrent risks in this population.

Disclosing the potential impact of placebo controls in antidepressant trials.

BACKGROUND: Although placebo-control clinical trials that withhold effective treatments can be permissible, how best to inform participants of the placebo design has received little attention. AIMS: To determine the effect of disclosing quantitative outcome estimates of individual treatment v. entering placebo-control randomised control trial (RCT) on willingness to enrol in such an RCT. METHOD: We randomised 278 adult patients at a depression clinic to receive standard disclosure (n = 129) or enhanced (n = 149) quantitative outcome estimates (based on decision analysis) of individual treatment v. RCT, and assessed their willingness to enrol in the RCT. RESULTS: A greater proportion of those in the standard arm preferred enrolling in RCT (41.3% v. 23.8%, P = 0.002). Those in the standard arm preferred RCT more for direct benefit than altruism reasons, whereas the opposite was true in the enhanced arm. CONCLUSIONS: Disclosing the quantitative outcome implications of placebos may select for fewer but more altruistic participants. DECLARATION OF INTEREST: S.Y.H.K. was a DSMB member of a clinical trial sponsored by Hoffman-LaRoche and he receives royalties from Oxford University Press for his book Evaluation of Capacity to Consent to Treatment and Research. C.M. has served in the past year on a scientific advisory board and as a consultant for Janssen Pharmaceuticals. COPYRIGHT AND USAGE: This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.