Microbial Translocation Is Associated with Increased Monocyte Activation and Dementia in AIDS Patients

Elevated plasma lipopolysaccharide (LPS), an indicator of microbial translocation from the gut, is a likely cause of systemic immune activation in chronic HIV infection. LPS induces monocyte activation and trafficking into brain, which are key mechanisms in the pathogenesis of HIV-associated dementia (HAD). To determine whether high LPS levels are associated with increased monocyte activation and HAD, we obtained peripheral blood samples from AIDS patients and examined plasma LPS by Limulus amebocyte lysate (LAL) assay, peripheral blood monocytes by FACS, and soluble markers of monocyte activation by ELISA. Purified monocytes were isolated by FACS sorting, and HIV DNA and RNA levels were quantified by real time PCR. Circulating monocytes expressed high levels of the activation markers CD69 and HLA-DR, and harbored low levels of HIV compared to CD4+ T-cells. High plasma LPS levels were associated with increased plasma sCD14 and LPS-binding protein (LBP) levels, and low endotoxin core antibody levels. LPS levels were higher in HAD patients compared to control groups, and were associated with HAD independently of plasma viral load and CD4 counts. LPS levels were higher in AIDS patients using intravenous heroin and/or ethanol, or with Hepatitis C virus (HCV) co-infection, compared to control groups. These results suggest a role for elevated LPS levels in driving monocyte activation in AIDS, thereby contributing to the pathogenesis of HAD, and provide evidence that cofactors linked to substance abuse and HCV co-infection influence these processes

Development and Characterization of Boron-Nitride Reinforced Nickel Matrix Composites

In this work, pure nickel was reinforced with various contents of h-BN (4 & 8wt.%) and SiC (2, 4, 6 & 8wt.%) prepared via PM route. The synergistic effect of h-BN and SiC on mechanical and microstructural behaviour was investigated. The microstructure and crystal structure were characterized by scanning electron microscope and X-ray diffractometer. The density and microhardness were eveluated via He pycnometer and microhardness tester. SEM results revealed that the exfoliation reduced the particle size of h-BN from approximately 105 nm to 30-40 nm. Furthermore, the addition of h-BN and SiC improved the mechanical properties of the composite. The maximum hardness value of 420 HV was obtained for Ni-8BN-6SiC. This improvement in hardness was attributed to uniform dispersion and high hardness of h-BN and SiC. However, more addition of SiC (>6 wt.%) deteriorated the hardness of the composite due to generated porosity

A national study of clinical discussions about cannabis use among Veteran patients prescribed opioids.

BACKGROUND: The Veterans Health Administration tracks urine drug tests (UDTs) among patients on long-term opioid therapy (LTOT) and recommends discussing the health effects of cannabis use. OBJECTIVE: To determine the occurrence of cannabis-related discussions between providers and patients on LTOT during six months following UDT positive for cannabis, and examine factors associated with documenting cannabis use. DESIGN: We identified patients prescribed LTOT with a UDT positive for cannabis in 2019. We developed a text-processing tool to extract discussions around cannabis use from their charts. SUBJECTS: Twelve thousand seventy patients were included. Chart review was conducted on a random sample of 1,946 patients. MAIN MEASURES: The presence of a cannabis term in the chart suggesting documented cannabis use or cannabis-related discussions. Content of those discussions was extracted in a subset of patients. Logistic regression was used to examine the association between patient factors, including state of residence legal status, with documentation of cannabis use. KEY RESULTS: Among the 12,070 patients, 65.8% (N = 7,948) had a cannabis term, whereas 34.1% (N = 4,122) of patients lacked a cannabis term, suggesting that no documentation of cannabis use or discussion between provider and patient took place. Among the subset of patients who had a discussion documented, 47% related to cannabis use for medical reasons, 35% related to a discussion of VA policy or legal issues, and 17% related to a discussion specific to medical risks or harm reduction strategies. In adjusted analyses, residents of states with legalized recreational cannabis were less likely to have any cannabis-related discussion compared to patients in non-legal states [OR 0.73, 95% CI 0.64-0.82]. CONCLUSIONS: One-third of LTOT patients did not have documentation of cannabis use in the chart in the 6 months following a positive UDT for cannabis. Discussions related to the medical risks of cannabis use or harm reduction strategies were uncommon

A national population-based study of cannabis use and correlates among U.S. veterans prescribed opioids in primary care.

Cannabis is marketed as a treatment for pain. There is limited data on the prevalence of cannabis use and its correlates among Veterans prescribed opioids. To examine the prevalence and correlates of cannabis use among Veterans prescribed opioids. Cross-sectional study. Veterans with a urine drug test (UDT) from Primary Care 2014-2018, in 50 states, Washington, D.C., and Puerto Rico. A total of 1,182,779 patients were identified with an opioid prescription within 90 days prior to UDT. Annual prevalence of cannabis positive UDT by state. We used multivariable logistic regression to assess associations of demographic factors, mental health conditions, substance use disorders, and pain diagnoses with cannabis positive UDT. Annual prevalence of cannabis positive UDT ranged from 8.5% to 9.7% during the study period, and in 2018 was 18.15% in Washington, D.C. and 10 states with legalized medical and recreational cannabis, 6.1% in Puerto Rico and 25 states with legalized medical cannabis, and 4.5% in non-legal states. Younger age, male sex, being unmarried, and marginal housing were associated with use (p < 0.001). Post-traumatic stress disorder (adjusted odds ratio [AOR] 1.17; 95% confidence interval [CI] 1.13-1.22, p < 0.001), opioid use disorder (AOR 1.14; CI 1.07-1.22, p < 0.001), alcohol use disorder or positive AUDIT-C (AOR 1.34; 95% CI 1.28-1.39, p < 0.001), smoking (AOR 2.58; 95% CI 2.49-2.66, p < 0.001), and other drug use disorders (AOR 1.15; 95% CI 1.03-1.29, p = 0.02) were associated with cannabis use. Positive UDT for amphetamines AOR 1.41; 95% CI 1.26-1.58, p < 0.001), benzodiazepines (AOR 1.41; 95% CI 1.31-1.51, p < 0.001) and cocaine (AOR 2.04; 95% CI 1.75-2.36, p < 0.001) were associated with cannabis positive UDT. Cannabis use among Veterans prescribed opioids varied by state and by legalization status. Veterans with PTSD and substance use disorders were more likely to have cannabis positive UDT. Opioid-prescribed Veterans using cannabis may benefit from screening for these conditions, referral to treatment, and attention to opioid safety

A national population-based study of cannabis use and correlates among U.S. veterans prescribed opioids in primary care

BACKGROUND: Cannabis is marketed as a treatment for pain. There is limited data on the prevalence of cannabis use and its correlates among Veterans prescribed opioids. OBJECTIVE: To examine the prevalence and correlates of cannabis use among Veterans prescribed opioids. DESIGN: Cross-sectional study. PARTICIPANTS: Veterans with a urine drug test (UDT) from Primary Care 2014-2018, in 50 states, Washington, D.C., and Puerto Rico. A total of 1,182,779 patients were identified with an opioid prescription within 90 days prior to UDT. MAIN MEASURES: Annual prevalence of cannabis positive UDT by state. We used multivariable logistic regression to assess associations of demographic factors, mental health conditions, substance use disorders, and pain diagnoses with cannabis positive UDT. RESULTS: Annual prevalence of cannabis positive UDT ranged from 8.5% to 9.7% during the study period, and in 2018 was 18.15% in Washington, D.C. and 10 states with legalized medical and recreational cannabis, 6.1% in Puerto Rico and 25 states with legalized medical cannabis, and 4.5% in non-legal states. Younger age, male sex, being unmarried, and marginal housing were associated with use (p \u3c 0.001). Post-traumatic stress disorder (adjusted odds ratio [AOR] 1.17; 95% confidence interval [CI] 1.13-1.22, p \u3c 0.001), opioid use disorder (AOR 1.14; CI 1.07-1.22, p \u3c 0.001), alcohol use disorder or positive AUDIT-C (AOR 1.34; 95% CI 1.28-1.39, p \u3c 0.001), smoking (AOR 2.58; 95% CI 2.49-2.66, p \u3c 0.001), and other drug use disorders (AOR 1.15; 95% CI 1.03-1.29, p = 0.02) were associated with cannabis use. Positive UDT for amphetamines AOR 1.41; 95% CI 1.26-1.58, p \u3c 0.001), benzodiazepines (AOR 1.41; 95% CI 1.31-1.51, p \u3c 0.001) and cocaine (AOR 2.04; 95% CI 1.75-2.36, p \u3c 0.001) were associated with cannabis positive UDT. CONCLUSIONS: Cannabis use among Veterans prescribed opioids varied by state and by legalization status. Veterans with PTSD and substance use disorders were more likely to have cannabis positive UDT. Opioid-prescribed Veterans using cannabis may benefit from screening for these conditions, referral to treatment, and attention to opioid safety

Association of a positive drug screening for cannabis with mortality and hospital visits among veterans affairs enrollees prescribed opioids.

Importance: Cannabis has been proposed as a therapeutic with potential opioid-sparing properties in chronic pain, and its use could theoretically be associated with decreased amounts of opioids used and decreased risk of mortality among individuals prescribed opioids. Question: Is cannabis use associated with increased risk of mortality among patients prescribed opioid analgesics? Findings: In this cohort study among 297 620 patients in the Veterans Affairs health system treated with opioids in the prior 90 days, cannabis use was not associated with increased mortality among participants aged less than 65 years, but was associated with increased 90-day mortality among those aged 65 years and older receiving long-term opioid therapy. No increase in mortality was found at 180 days. Meaning: This study found that cannabis use was associated with increased short-term mortality risk among adults aged 65 years and older receiving long-term prescription opioids

Association of a Positive Drug Screening for Cannabis With Mortality and Hospital Visits Among Veterans Affairs Enrollees Prescribed Opioids

IMPORTANCE: Cannabis has been proposed as a therapeutic with potential opioid-sparing properties in chronic pain, and its use could theoretically be associated with decreased amounts of opioids used and decreased risk of mortality among individuals prescribed opioids. OBJECTIVE: To examine the risks associated with cannabis use among adults prescribed opioid analgesic medications. DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted among individuals aged 18 years and older who had urine drug screening in 2014 to 2019 and received any prescription opioid in the prior 90 days or long-term opioid therapy (LTOT), defined as more than 84 days of the prior 90 days, through the Veterans Affairs health system. Data were analyzed from November 2020 through March 2022. EXPOSURES: Biologically verified cannabis use from a urine drug screen. MAIN OUTCOMES AND MEASURES: The main outcomes were 90-day and 180-day all-cause mortality. A composite outcome of all-cause emergency department (ED) visits, all-cause hospitalization, or all-cause mortality was a secondary outcome. Weights based on the propensity score were used to reduce confounding, and hazard ratios [HRs] were estimated using Cox proportional hazards regression models. Analyses were conducted among the overall sample of patients who received any prescription opioid in the prior 90 days and were repeated among those who received LTOT. Analyses were repeated among adults aged 65 years and older. RESULTS: Among 297 620 adults treated with opioids, 30 514 individuals used cannabis (mean [SE] age, 57.8 [10.5] years; 28 784 [94.3%] men) and 267 106 adults did not (mean [SE] age, 62.3 [12.3] years; P \u3c .001; 247 684 [92.7%] men; P \u3c .001). Among all patients, cannabis use was not associated with increased all-cause mortality at 90 days (HR, 1.07; 95% CI, 0.92-1.22) or 180 days (HR, 1.00; 95% CI, 0.90-1.10) but was associated with an increased hazard of the composite outcome at 90 days (HR, 1.05; 95% CI, 1.01-1.07) and 180 days (HR, 1.04; 95% CI, 1.01-1.06). Among 181 096 adults receiving LTOT, cannabis use was not associated with increased risk of all-cause mortality at 90 or 180 days but was associated with an increased hazard of the composite outcome at 90 days (HR, 1.05; 95% CI, 1.02-1.09) and 180 days (HR, 1.05; 95% CI, 1.02-1.09). Among 77 791 adults aged 65 years and older receiving LTOT, cannabis use was associated with increased 90-day mortality (HR, 1.55; 95% CI, 1.17-2.04). CONCLUSIONS AND RELEVANCE: This study found that cannabis use among adults receiving opioid analgesic medications was not associated with any change in mortality risk but was associated with a small increased risk of adverse outcomes and that short-term risks were higher among older adults receiving LTOT