Fatigue and Pain Severity in Gulf War Illness Is Associated With Changes in Inflammatory Cytokines and Positive Acute Phase Proteins.

OBJECTIVE: The aim of the study is to investigate relationships between inflammatory analytes and symptoms of pain and fatigue in Gulf War illness (GWI). METHODS: In this preliminary study, 12 male veterans meeting GWI criteria provided daily blood samples and symptom ratings over 25 days. Linear mixed models were used to analyze associations between symptoms and sera concentrations of cytokines, acute phase proteins, insulin, and brain-derived neurotropic factor. RESULTS: Analyses included 277 days with both blood draws and self-reports. Days with worse fatigue severity were associated with higher C-reactive protein and serum amyloid A, and lower eotaxin 1. Muscle pain and joint pain were associated with leptin, monocyte chemoattractant protein 1, and interferon γ-induced protein. Joint pain was further associated with serum amyloid A and eotaxin 3. CONCLUSIONS: Gulf War illness involves fatigue and pain associated with inflammation. Conventional and novel anti-inflammatories should be further explored for the treatment of GWI.

A Placebo-Controlled, Pseudo-Randomized, Crossover Trial of Botanical Agents for Gulf War Illness: Reishi Mushroom (Ganoderma lucidum), Stinging Nettle (Urtica dioica), and Epimedium (Epimedium sagittatum).

This report is third in a three-part clinical trial series screening potential treatments for Gulf War Illness (GWI). The goal of the project was to rapidly identify agents to prioritize for further efficacy research. We used a placebo-controlled, pseudo-randomized, crossover design to test the effects of reishi mushroom (Ganoderma lucidum), stinging nettle (Uritca dioica), and epimedium (Epimedium sagittatum) in 29 men with GWI. Participants completed 30 days of symptom reports for baseline, then a botanical line consisting of 30 days of placebo, followed by 30 days each of lower-dose and higher-dose botanical. After completing a botanical line, participants were randomized to complete the protocol with another botanical, until they completed three botanical trials. GWI symptom severity, pain, and fatigue were contrasted between the four conditions (baseline, placebo, lower-dose, higher dose) using linear mixed models. GWI symptom severity was unchanged from placebo in the reishi lower-dose condition (p = 0.603), and was higher in the higher-dose condition (p = 0.012). Symptom severity was not decreased from placebo with lower-dose stinging nettle (p = 0.604), but was significantly decreased with higher-dose stinging nettle (p = 0.048). Epimedium showed no significant decreases of GWI symptoms in the lower (p = 0.936) or higher (p = 0.183) dose conditions. Stinging nettle, especially at higher daily dosages, may help reduce the symptoms of GWI. Epimedium does not appear to beneficially affect GWI symptom severity, and reishi may exaggerate symptoms in some GWI sufferers. These results are in a small sample and are preliminary. Further research is required to determine if stinging nettle is indeed helpful for the treatment of GWI, and what dosage is optimal. This trial was registered on ClinicalTrials.gov (NCT02909686).

A Placebo-Controlled, Pseudo-Randomized, Crossover Trial of Botanical Agents for Gulf War Illness: Curcumin (Curcuma longa), Boswellia (Boswellia serrata), and French Maritime Pine Bark (Pinus pinaster).

This report is part of a larger study designed to rapidly and efficiently screen potential treatments for Gulf War Illness (GWI) by testing nine different botanicals. In this placebo-controlled, pseudo-randomized, crossover clinical trial of 20 men with GWI, we tested three botanical agents with putative peripheral and central anti-inflammatory actions: curcumin (Curcuma longa), boswellia (Boswellia serrata), and French maritime pine bark extract (Pinus pinaster). Participants completed 30 +/- 3 days of baseline symptom reports, followed by 30 +/- 3 days of placebo, 30 +/- 3 days of lower-dose botanical, and 30 +/- 3 days of higher-dose botanical. Participants then repeated the process with a new botanical until completing up to three botanical cycles. Data were analyzed using linear mixed models. Curcumin reduced GWI symptom severity significantly more than placebo at both the lower (p < 0.0001) and higher (p = 0.0003) dosages. Boswellia was not more effective than placebo at reducing GWI symptoms at either the lower (p = 0.726) or higher (p = 0.869) dosages. Maritime pine was not more effective than placebo at the lower dosage (p = 0.954) but was more effective than placebo at the higher dosage (p = 0.006). This study provides preliminary evidence that curcumin and maritime pine may help alleviate symptoms of GWI. As a screening study, a final determination of the efficacy of these compounds for all individuals with GWI cannot be made, and further studies will need to be conducted to determine strength and durability of effects, as well as optimal dosage. These results suggest that GWI may, at least in part, involve systemic inflammatory processes. This trial was registered on ClinicalTrials.gov (NCT02909686) on 13 September 2016.

A Placebo-Controlled, Pseudo-Randomized, Crossover Trial of Botanical Agents for Gulf War Illness: Resveratrol (Polygonum cuspidatum), Luteolin, and Fisetin (Rhus succedanea).

A chronic multi-symptom illness of unknown etiology, Gulf War Illness (GWI) affects 175,000 to 250,000 veterans of the Gulf War. Because inflammation has suspected involvement in the pathophysiology of GWI, botanical treatments that target inflammation may be beneficial in reducing symptoms. No FDA-approved treatments currently exist for GWI, and rapid prioritization of agents for future efficacy testing is important. This study is part of a larger project that screened nine different botanical compounds with purported anti-inflammatory properties for potential treatment of GWI. We tested three botanicals (resveratrol [Polygonum cuspidatum], luteolin, and fisetin [Rhus succedanea]) on symptom severity of GWI in this placebo-controlled, pseudo-randomized clinical trial. Twenty-one male veterans with GWI completed the study protocol, which consisted of 1 month (30 days ± 3) of baseline symptom reports, 1 month of placebo, 1 month of lower-dose botanical, and 1 month of higher-dose botanical. Participants completed up to 3 different botanicals, repeating the placebo, lower-dose, and higher-dose cycle for each botanical assigned. Linear mixed models were used for analyses. Resveratrol reduced GWI symptom severity significantly more than placebo at both the lower (p = 0.035) and higher (p = 0.004) dosages. Luteolin did not decrease symptom severity more than placebo at either the lower (p = 0.718) or higher dosages (p = 0.492). Similarly, fisetin did not reduce symptom severity at either the lower (p = 0.504) or higher (p = 0.616) dosages. Preliminary findings from this screening study suggest that resveratrol may be beneficial in reducing symptoms of GWI and should be prioritized for future testing. Larger trials are required to determine efficacy, response rates, durability of effects, safety, and optimal dosage. This trial was registered on ClinicalTrials.gov (NCT02909686) on 13 September 2016.

Differences among cigarette-only smokers compared to dual users of cigarettes and little cigars/cigarillos in the criminal justice population.

INTRODUCTION: The FDA has restrictions on cigarettes; however, little cigars and cigarillos (LCCs) remain largely absent from these regulations. Due to their low prices and flavoring, many engage in dual use of both LCCs and cigarettes. Dual use is particularly prevalent among low income racial/ethnic minority groups. The purpose of this study was to (U.S. Department of Health and Human Services, 2014) conduct an exploratory examination among cigarette users compared to dual users on smoking characteristics; and (Centers for Disease Control and Prevention, 2016) to examine racial differences (White and Black) among cigarette users compared to dual users. METHODS: Participants (N = 500) were recruited from community corrections (i.e., parole/probation) and categorized as either cigarette-only (66.4%) or dual users (33.6%) if they used little cigars or cigarillos over a one-year period during a smoking cessation clinical trial. RESULTS: Dual users were more likely to be younger, Black, males with lower educational attainment compared to cigarette-only smokers. Smokers with increased nicotine dependence were 17% more likely to be cigarette-only smokers compared to dual users. Racial differences revealed that White/cigarette-only smokers were more likely to report non-menthol use and higher cigarette consumption at the end of treatment compared to Black/cigarette-only or Black/dual users. CONCLUSIONS: This study contributes to our understanding of dual use among a disenfranchised group of smokers. Overall, dual users were more likely to be younger, Black, and male with lower reported nicotine dependence compared to cigarette-only users. Racial differences revealed that non-menthol smokers as well as smokers with greater cigarettes smoked at the end of treatment were more likely White/cigarette-only smokers.

Medical, psychosocial, and treatment predictors of opioid overdose among high risk opioid users.

INTRODUCTION: Drug overdoses are the leading cause of accidental death in the United States. It is imperative to explore predictors of opioid overdose in order to facilitate targeted treatment and prevention efforts. The present study was conducted as an exploratory examination of the factors associated with having a past opioid overdose. METHODS: Participants (N = 244) from substance treatment facilities, inpatient services following ER admittance, or involved within the drug court system and who reported opioid use in the past 6 months were recruited in this study. Measures of opioid use and history were used to determine characteristics associated with previous experience of a non-fatal opioid overdose. RESULTS: Opioid users who were Caucasian and used a combination of prescription opioids and heroin were more likely to have experienced a prior overdose. Opioid user characteristics associated with greater odds of experiencing a prior overdose included: witnessing a friend overdose (OR 4.21), having chronic hepatitis C virus (HCV) infection (OR 2.44), reporting a higher frequency of buprenorphine treatment episodes (OR 1.55), and having a higher frequency of witnessing others overdose (OR 1.42). Greater frequency of methadone treatment episodes was related to decreased odds of experiencing an overdose (OR 0.67). CONCLUSION: Overall, this study demonstrated certain demographic and drug use factors associated with elevated risk for an overdose. Understanding the risk factors associated with drug overdose can lead to targeted naloxone training and distribution to prevent fatal overdoses.