History and current status of contingency management programs in the Department of Veterans Affairs.

OBJECTIVE: This article describes the Department of Veterans Affairs (VA) national implementation of contingency management within VA substance use disorder (SUD) treatment programs. METHODS: The rationale for implementing CM, role of VA leadership, and training and supervision procedures are detailed. The role of the Veterans Canteen Service (VCS) in sustaining the CM implementation through the donation of incentives is outlined. Updated outcomes from the primary program, CM to incentivize stimulant abstinence, are provided. Data presented were gathered from June 2011 to January 2023, from VA facilities across the country. RESULTS: More than 6000 Veterans from 119 VA facilities have received CM in a 12-week program in which two urine samples are obtained per week, with 92% of the samples negative for the targeted substance. Two other CM pilot projects are described. The first incentivizes adherence to injectable medications for opioid and alcohol use disorders, with over 580 veterans from 27 VA sites participating to date. The second incentivized smoking cessation in 312 patients from four sites. A new initiative in which CM is implemented in smaller community-based VA facilities through use of onsite prize cabinets is presented and the possibility of providing CM remotely in VA is discussed. CONCLUSIONS: It has proved feasible to implement abstinence CM and several other CM pilot programs at many VA facilities. Factors that contributed to the success of the VA CM rollout, challenges that were encountered along the way, and lessons learned that may facilitate wider use of CM outside VA are discussed.

A Real-World Evaluation of a Smokeless Tobacco Cessation Text Message Program for Veterans: Outcomes and Comparison to Cigarette Smokers.

INTRODUCTION: Smokeless tobacco (ST) use and cessation rates have remained unchanged while cigarette smoking has declined, and cessation rates have increased. Text message programs have proved effective for cigarette smokers but have not been evaluated for ST users. The Veterans Health Administration (VHA) created a ST-specific arm of its SmokefreeVET automated text message program to help veteran ST users quit. AIMS AND METHODS: A retrospective evaluation was conducted on a real-world sample of veteran ST users (n = 1139) who subscribed to SmokefreeVET between 2017 and 2020. Time in program, abstinence, and nicotine replacement therapy (NRT) use were evaluated and compared to 9764 cigarette smokers who subscribed to SmokefreeVET. RESULTS: Younger subscribers were more likely to opt out early; 54% of ST users and 60% of cigarette smokers completed the 6-week program. ST users were more likely to report abstinence than cigarette smokers at all time points: the primary outcome, 30-day abstinence at 6 months, was 3.9% in ST users and 2.6% in cigarette smokers (p = .05) and the secondary outcome, abstinence at 3 months, was 5.3% in ST users and 3.4% in cigarette smokers (p = .03). NRT was used by 17% of ST users and was associated with a trend toward higher abstinence compared to ST users who did not use NRT. CONCLUSION: A real-world sample of ST users were more likely to report abstinence after using the SmokefreeVET text program than cigarette smokers. Automated text message programs may be effective for increasing cessation among ST users and warrant further investigation. IMPLICATIONS: Smokeless tobacco (ST) cessation is an important public health priority and of importance for veteran and military populations that have higher rates of ST use. There have been relatively few studies conducted investigating the effectiveness of text message interventions for ST cessation, despite the proven efficacy for cigarette smokers. This study provides evidence from a large, real-world sample that text message programs may be effective for ST users and suggests that further research into this treatment modality for ST users is needed.

Real-World Utilization and Outcomes of the Veterans Health Administration's Smoking Cessation Text Message Program.

INTRODUCTION: Smoking cessation mobile health (mHealth) programs are effective and have been recommended for integration into health care services but have not been evaluated in real-world health care settings. The Veterans Health Administration, a safety net health care provider, provides health care for 9 million US military veterans. Veterans Health Administration implemented the SmokefreeVET text message program in 2013. METHODS: A retrospective evaluation of 6153 SmokefreeVET subscribers was conducted. The primary outcome was 30-day self-reported abstinence at 6 months. Secondary outcomes included percentage of opt outs, program completers, and 30-day self-reported abstinence at 3 months. RESULTS: SmokefreeVET subscribers were on average 47.5 years old and 71.4% male. Smoking cessation medication use was reported by 11.5% of subscribers at the start of their quit attempt and subscribers enrolled in the program for an average of 29 days. Subscribers who were younger, female, and heavier smokers were more likely to opt out of the six-week program early. The abstinence rate for the primary outcome, self-reported 30-day abstinence at 6 months among all subscribers was 3.7%. CONCLUSIONS: SmokefreeVET enrolled a younger and more female population of subscribers than other studies of veterans interested in tobacco treatment. The mHealth program was generally acceptable to veterans, yet strategies to increase retention may improve completion rates and outcomes. In this real-world setting, nearly half of the mHealth program subscribers combined use of the text program with smoking cessation medication. Further study of the optimal combination of mHealth with smoking cessation treatments is needed. IMPLICATIONS: mHealth smoking cessation programs can be effectively implemented within real-world health care settings, even in those serving disadvantaged populations. Further research to improve mHealth program efficacy and integration into clinical settings will increase the population-level impact of these effective smoking cessation programs.

Death-domain dimerization-mediated activation of RIPK1 controls necroptosis and RIPK1-dependent apoptosis.

RIPK1 is a critical mediator of cell death and inflammation downstream of TNFR1 upon stimulation by TNFα, a potent proinflammatory cytokine involved in a multitude of human inflammatory and degenerative diseases. RIPK1 contains an N-terminal kinase domain, an intermediate domain, and a C-terminal death domain (DD). The kinase activity of RIPK1 promotes cell death and inflammation. Here, we investigated the involvement of RIPK1-DD in the regulation of RIPK1 kinase activity. We show that a charge-conserved mutation of a lysine located on the surface of DD (K599R in human RIPK1 or K584R in murine RIPK1) blocks RIPK1 activation in necroptosis and RIPK1-dependent apoptosis and the formation of complex II. Ripk1K584R/K584R knockin mutant cells are resistant to RIPK1 kinase-dependent apoptosis and necroptosis. The resistance of K584R cells, however, can be overcome by forced dimerization of RIPK1. Finally, we show that the K584R RIPK1 knockin mutation protects mice against TNFα-induced systematic inflammatory response syndrome. Our study demonstrates the role of RIPK1-DD in mediating RIPK1 dimerization and activation of its kinase activity during necroptosis and RIPK1-dependent apoptosis.

Engagement and abstinence among users of a smoking cessation text message program for veterans.

BACKGROUND: SmokefreeVET is a text messaging smoking cessation program available to veterans enrolled in the Veterans Health Administration. SmokefreeVET was developed in collaboration with the National Cancer Institute as part of the SmokefreeTXT initiative. PURPOSE: To evaluate the real world use of and effectiveness of the SmokefreeVET program for SmokefreeVET users who enrolled between 2013 and 2014. METHODS: Demographics and smoking behavior of 1470 SmokefreeVET users who enrolled between 2013 and 2014 were analyzed. Latent growth mixture modeling was used to identify discrete classes of SmokefreeVET users based on engagement patterns. Multi-level modeling determined class differences in abstinence. RESULTS: The average age of the SmokefreeVET user was 48, 75% of users were male, and 84% were daily smokers. After five weeks, 13% of all users reported abstinence from smoking. Five statistically distinct engagement classes of SmokefreeVET users were identified. Highly engaged classes were significantly less likely to opt-out and more likely to report abstinence. Over 60% of users who were classified as high engagers throughout the program reported abstinence 5weeks after their quit date. Users were more likely to report abstinence after two weeks if they used smoking cessation medication than those that did not use medication (OR=9.01, p<0.001). CONCLUSIONS: SmokefreeVET may be effective at supporting abstinence among a real world group of highly engaged users. Smoking cessation medication use was also associated with abstinence in SmokefreeVET users. Engagement appears to be a critical component when assessing the efficacy of a text messaging smoking cessation intervention.

Cigarette Smoking and Sociodemographic, Military, and Health Characteristics of Operation Enduring Freedom and Operation Iraqi Freedom Veterans: 2009-2011 National Health Study for a New Generation of US Veterans.

OBJECTIVE: We examined the sociodemographic, military, and health characteristics of current cigarette smokers, former smokers, and nonsmokers among Operation Enduring Freedom (OEF) / Operation Iraqi Freedom (OIF) veterans and estimated smoking prevalence to better understand cigarette use in this population. METHODS: We analyzed data from the US Department of Veterans Affairs (VA) 2009-2011 National Health Study for a New Generation of US Veterans. On the basis of a stratified random sample of 60 000 OEF/OIF veterans, we sought responses to a 72-item questionnaire via mail, telephone, or Internet. Cigarette smoking status was based on self-reported cigarette use in the past year. We used multinomial logistic regression to evaluate associations between smoking status and sociodemographic, military, and health characteristics. RESULTS: Among 19 911 veterans who provided information on cigarette smoking, 5581 were current smokers (weighted percentage: 32.5%, 95% confidence interval [CI]: 31.7-33.2). Current smokers were more likely than nonsmokers or former smokers to be younger, to have less education or income, to be separated/divorced or never married/single, and to have served on active duty or in the army. Comparing current smokers and nonsmokers, some significant associations from adjusted analyses included the following: having a Mental Component Summary score (a measure of overall mental health) above the mean of the US population relative to below the mean (adjusted odds ratio [aOR] = 0.81, 95% CI: 0.73-0.90); having physician-diagnosed depression (aOR = 1.52, 95% CI: 1.33-1.74), respiratory conditions (aOR = 1.16, 95% CI: 1.04-1.30), or repeated seizures/blackouts/convulsions (aOR = 1.80, 95% CI: 1.22-2.67); heavy alcohol use vs never use (aOR = 5.49, 95% CI: 4.57-6.59); a poor vs excellent perception of overall health (aOR = 3.79, 95% CI: 2.60-5.52); and being deployed vs nondeployed (aOR = 0.87, 95% CI: 0.78-0.96). Using health care services from the VA protected against current smoking. CONCLUSION: Mental and physical health, substance use, and military service characteristics shape cigarette-smoking patterns in OEF/OIF veterans.

Suicide Prevention Referrals in a Mobile Health Smoking Cessation Intervention.

Automated mobile health (mHealth) programs deliver effective smoking cessation interventions through text message platforms. Smoking is an independent risk factor for suicide, so the Department of Veterans Affairs incorporated information about the Veterans Crisis Line into its SmokefreeVET smoking cessation text messaging program. Almost 7% of all SmokefreeVET enrollees have accessed this information. Because of the reach and automated nature of this and similar programs, we recommend including a referral to a suicide prevention hotline for all smoking cessation mHealth interventions.

No wrong door to smoking cessation care: a Veterans Affairs Chaplain survey.

Cigarette smoking disproportionately affects veterans, particularly those with psychiatric diagnoses. Chaplains working within the Department of Veterans Affairs (VA) play key roles in emotional, physical, and spiritual health care of veterans, and veterans often turn to chaplains with mental health concerns. The VA/Department of Defense Integrated Mental Health Care Strategy is working to understand how collaboration between chaplains and mental health professionals may improve services to veterans, and one interest area is the role chaplains might play in facilitating the dissemination of smoking cessation programs. We report the survey results of 321 VA chaplains regarding their interest and willingness to be involved in smoking cessation efforts. Results indicated that over 80% of responding chaplains would feel "somewhat" or "very comfortable" providing information to veterans about VA smoking cessation programs, and that a smaller majority (between 55% and 85%) would feel this level of comfort engaging in smoking cessation-related activities. Findings suggest the potential for collaboration among chaplains and mental health providers in smoking cessation efforts, and also point to the need for further discussion and deeper mutual understanding between these professionals in how they view their roles in contributing to the overall health and well-being of veterans.

Control of life-or-death decisions by RIP1 kinase.

RIP1 kinase, a multifunctional protein that contains an N-terminal Ser/Thr kinase and a C-terminal death domain, has emerged as a key regulatory molecule involved in regulating both cell death and cell survival. When the proinflammatory cytokine TNFα stimulates its receptor, TNFR1, RIP1 regulates whether the cell lives by activating NF-κB or dies by apoptosis or necroptosis, two distinct pathways of programmed cell death that may be activated to eliminate unwanted cells. The kinase domain of RIP1 is involved in regulating necroptosis, and the death domain regulates RIP1 recruitment to the intracellular domain of TNFR1. The intermediate domain of RIP1 activates NF-κB and also interacts with RIP3 kinase, a downstream mediator of RIP1 in the execution of necroptosis. This review focuses on the functional roles of RIP1 in regulating multiple cellular mechanisms, the dynamic regulation of RIP1, and the physiological and pathological roles of RIP1 kinase in human health and disease.

Necroptosis as an alternative form of programmed cell death.

The family of death receptors plays a critical role in regulating cell number and eliminating harmful or virally infected cells. Agonistic stimulation of death receptors is known to lead two alternative cell fates by either activating NF-kappaB to promote cell survival or inducing apoptosis to lead to cell death; and now a third pathway, termed necroptosis or programmed necrosis has been identified. Interestingly, a death-domain containing kinase, RIP1, is involved in mediating all three pathways, with its kinase activity specifically involved in regulating necroptosis. The availability of necrostatin-1, a specific inhibitor of RIP1 kinase, made it possible to dissect the distinct functional domains of RIP1. Recent genome-wide siRNA screens have identified multiple players of necroptosis that may interact with and/or regulate RIP1 kinase and mediate the signaling pathway and execution of necroptosis. Necroptosis and necrostatins provide an exciting new opportunity for developing new treatments for multiple human diseases involving necrosis and inflammation.

Identification of a molecular signaling network that regulates a cellular necrotic cell death pathway.

Stimulation of death receptors by agonists such as FasL and TNFalpha activates apoptotic cell death in apoptotic-competent conditions or a type of necrotic cell death dependent on RIP1 kinase, termed necroptosis, in apoptotic-deficient conditions. In a genome-wide siRNA screen for regulators of necroptosis, we identify a set of 432 genes that regulate necroptosis, a subset of 32 genes that act downstream and/or as regulators of RIP1 kinase, 32 genes required for death-receptor-mediated apoptosis, and 7 genes involved in both necroptosis and apoptosis. We show that the expression of subsets of the 432 genes is enriched in the immune and nervous systems, and cellular sensitivity to necroptosis is regulated by an extensive signaling network mediating innate immunity. Interestingly, Bmf, a BH3-only Bcl-2 family member, is required for death-receptor-induced necroptosis. Our study defines a cellular signaling network that regulates necroptosis and the molecular bifurcation that controls apoptosis and necroptosis.

A genome-wide RNAi screen reveals multiple regulators of caspase activation.

Apoptosis is an evolutionally conserved cellular suicide mechanism that can be activated in response to a variety of stressful stimuli. Increasing evidence suggests that apoptotic regulation relies on specialized cell death signaling pathways and also integrates diverse signals from additional regulatory circuits, including those of cellular homeostasis. We present a genome-wide RNA interference screen to systematically identify regulators of apoptosis induced by DNA damage in Drosophila melanogaster cells. We identify 47 double- stranded RNA that target a functionally diverse set of genes, including several with a known function in promoting cell death. Further characterization uncovers 10 genes that influence caspase activation upon the removal of Drosophila inhibitor of apoptosis 1. This set includes the Drosophila initiator caspase Dronc and, surprisingly, several metabolic regulators, a candidate tumor suppressor, Charlatan, and an N-acetyltransferase, ARD1. Importantly, several of these genes show functional conservation in regulating apoptosis in mammalian cells. Our data suggest a previously unappreciated fundamental connection between various cellular processes and caspase-dependent cell death.