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Background: Apathy is among the neuropsychiatric symptoms frequently observed in people with cognitive impairment. It has been postulated to be a potential predictor of conversion from mild cognitive impairment (MCI) to Alzheimer’s disease (AD). Objective: To detect conversion rates from MCI to AD, and to determine the effect of apathy on the progression to AD in patients with MCI enrolled in the Texas Alzheimer’s Research and Care Consortium (TARCC) cohort. Methods: Apathy was determined by a positive response to the respective item in the Neuropsychiatric Inventory –Questionnaire (NPI-Q) completed by family members or caregivers. The final dataset included 2,897 observations from 1,092 individuals with MCI at the baseline. Kaplan-Meier survival curves were estimated to provide indices of the probability of conversion to AD over time across all individuals as well as between those with and without apathy. Cox proportional hazards regression measured the hazard associated with apathy and several other predictors of interest. Results: Over a period of 8.21 years, 17.3% of individuals had conversion from MCI to AD (n = 190 of 1,092 total individuals) across observations. The median time-to-conversion across all participants was 6.41 years. Comparing individuals with apathy (n = 158) versus without apathy (n = 934), 36.1% and 14.2% had conversion to AD, respectively. The median time-to-conversion was 3.79 years for individuals with apathy and 6.83 years for individuals without apathy. Cox proportional hazards regression found significant effects of several predictors, including apathy, on time-to-conversion. Age and cognitive performance were found to moderate the relationship between apathy and time-to-conversion. Conclusions: Apathy is associated with progression from MCI to AD, suggesting that it might improve risk prediction and aid targeted intervention delivery.

Smokers with stronger neuroaffective responses to drug-related cues compared to nondrug-related pleasant images (C > P) are more vulnerable to compulsive smoking than individuals with the opposite brain reactivity profile (P > C). However, it is unknown if these neurobehavioral profiles exist in individuals abusing other drugs. We tested whether individuals with cocaine use disorder (CUD) show similar neuroaffective profiles to smokers. We also monitored eye movements to assess attentional bias toward cues and we further performed exploratory analyses on demographics, personality, and drug use between profiles. Participants with CUD (n = 43) viewed pleasant, unpleasant, cocaine, and neutral images while we recorded electroencephalogram. For each picture category, we computed the amplitude of the late positive potential (LPP), an event-related potential component that reflects motivational relevance. k-means clustering classified participants based on their LPP responses. In line with what has been observed in smokers, clustering participants using LPP responses revealed the presence of two groups: one with larger LPPs to pleasant images compared to cocaine images (P > C) and one group with larger LPPs to cocaine images compared to pleasant images (C > P). Individuals with the C > P reactivity profile also had higher attentional bias toward drug cues. The two groups did not differ on demographic and drug use characteristics, however individuals with the C > P profile reported lower distress tolerance, higher anhedonia, and higher posttraumatic stress symptoms compared to the P > C group. This is the first study to report the presence of these neuroaffective profiles in individuals with CUD, indicating that this pattern may cut across addiction populations. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The death of a spouse is associated with maladaptive immune alterations; grief severity may exacerbate this link. We investigated whether high grief symptoms were associated with an amplified inflammatory response to subsequent stress among 111 recently bereaved older adults. Participants completed a standardized psychological stressor and underwent a blood draw before, 45 min after, and 2 hr after the stressor. Those experiencing high grief symptoms (i.e., scoring > 25 on the Inventory of Complicated Grief) experienced a 45% increase in interleukin-6 (IL-6; a proinflammatory cytokine) per hour, whereas those experiencing low grief symptoms demonstrated a 26% increase. In other words, high grief was related to a 19% increase in IL-6 per hour relative to low grief. The grief levels of recently bereaved people were associated with the rate of change in IL-6 following a subsequent stressor, above and beyond depressive symptoms. This is the first study to demonstrate that high grief symptoms promote inflammation following acute stress.

Objective: To evaluate a non-invasive surrogate imaging marker for blood evacuation in patients with IVH. Clinical Relevance: Extension of intracerebral hemorrhage (ICH) to the ventricles increases the 48 hours mortality by 43%, requiring external ventricular drains (EVD) to mitigate hydrocephalus and monitor intracranial pressures. Blood increases CSF viscosity, altering the diffusion coefficient. We hypothesize change in lateral ventricle (LV) DTI metrics, fractional anisotropy (FA) and mean diffusivity (MD), can be used as a marker for blood removal after IVH. Methods: A sub-cohort of 20 patients in SHRINC trial with ICH and IVH were serially imaged at day 1 (T1=20), 14 (T1=20), 28 (T3=16), and 42 (T4=13) on a 3T MRI system. The serial T1w, segmented LV (JHU WM atlas) volumes, FA, and MD maps were registered. The FA and MD of ipsi and contralesional LV were recorded. Clinical assessment (NIHSS) was associated with the change in FA and MD of LV. A mixed model statistical analysis was performed. Results: We serially imaged 11M/9F with average age 55.4±8.7 years. The baseline hematoma volume and NIHSS were 22.1±18.5 cc and 16.1±8.7 respectively. The patients had basal ganglia (n=12) and thalamic (n=8) ICH extended into LV. The ipsilesional FA was significantly (T1=0.24, T4=0.15, p-3 mm 2 /sec, T4 = 2.37 *10 -3 mm 2 /sec, p-5 mm 2 /sec/day). At T4, there was no relationship (p=0.919) between ipsilesional and contra-MD of LV (Fig-1). Patients with higher baseline NIHSS had a significant temporal decline in FA than those with lower NIHSS (p Conclusion: The data suggest that DTI metrics of FA and MD are associated with blood clearance from the ipsilesional ventricle.

Objective: Prescription opioids are an effective pain treatment strategy but can lead to long-term opioid misuse. Identifying at risk patients during hospitalization can inform the development of prevention interventions post-discharge. Using the Opioid Risk Tool (ORT) as a screening measure, this study predicted factors associated with pain and opioid use at 2 weeks post-discharge in trauma patients.Design: A quality improvement prospective study design was used.Setting: Participant recruitment took place at an inpatient Level 1 trauma center in Houston, Texas.Participants: Participants (n = 103) were patients admitted to the adult trauma service. Patients completed the ORT in the hospital and a survey at 2 weeks post-discharge.Main outcome measure: The survey assessed pain intensity and interference, injury-related stress, medication use, and need for additional pain treatment. Wilcoxon–Mann–Whitney U test, the Spearman rank-order correlation, and chi-square test of independence tested the ORT as a predictor of follow-up outcomes. Post hoc analyses relied on logistic and quantile regression.Results: The ORT identified 15.5 percent of patients at high risk for opioid-related aberrant behavior. Survey results indicated high percentages of patients reporting moderate to severe pain (79.6 percent), pain interference (77.9 percent), taking pain pills (59.6 percent), experiencing stress (76.9 percent), and needing pain treatment (52.4 percent). The ORT predicted injury-related stress with the high-risk category having higher stress levels than low risk (Z = 2.518, p = 0.012).Conclusion: Risk of opioid misuse assessed in hospitalized trauma patients was associated with injury-related stress reported post-discharge. This highlights the importance of including stress assessments in follow-up appointments.

The behavioral economic measure drug demand and the neural measure late positive potential (LPP) are two measures of motivational value that have been associated with drug relapse risk and treatment outcomes. Despite having overlapping themes, no studies have directly compared drug demand and LPP. Participants (

Pre-exposure prophylaxis (PrEP) is an effective HIV prevention method, but it has been underutilized by women. Anticipated stigma regarding use of PrEP is a contributing factor in the underutilization of this prevention strategy. The current study explored the relationships among PrEP stigma, sex risk (i.e., inconsistent condom use, condomless sex with persons of unknown serostatus, or sex in exchange for money or drugs), substance use, attitudes toward HIV testing, and medical mistrust. Participants were 106 primarily ethnic-minority women who reported recent substance use and agreed to participate in a study exploring HIV prevention attitudes. Within this sample, the majority of participants had one or more CDC-defined PrEP indications. Findings indicate that medical mistrust was associated with perceived PrEP stereotypes and HIV testing attitudes. These results provide some insight into reasons for low PrEP uptake among women at risk for HIV. Implications for HIV prevention with women are discussed.

Objectives Previous work has shown effects of transcranial direct current stimulation (tDCS) on clinical pain measures, qualitative sensory testing measures, and peripheral inflammation. The present report extends this research to investigate the effect of tDCS on brain-derived neurotrophic factor (BDNF) levels. Materials and methods This secondary analysis examined a sample of 40 older adults (50 to 70 y old) with symptomatic knee osteoarthritis randomly assigned in a 1:1 fashion to active (n=20) or sham (n=20) tDCS for 20 minutes on 5 consecutive days. BDNF was measured before the first session and after the final treatment session. Generalized linear modeling evaluated BDNF plasma levels as a function of tDCS group, adjusted for baseline. Bayesian statistical inference was used to quantify the probability that effects of the treatment exist. Results Generalized linear modeling indicated a 90.4% posterior probability that the sham condition had 49.9% higher BDNF at the end of treatment, controlling for baseline. Follow-up analyses within the active TDCS group supported an association between change in BDNF and change in clinical pain, and exploratory analyses found an effect of tDCS on irisin. Discussion Results indicated that tDCS could be a potential nonpharmacological treatment to decrease BDNF levels, which may in turn decrease pain. This study adds to a growing literature suggesting that tDCS affects cortical excitability, and consequentially, the neural circuits implicated in pain modulation. In addition to a direct connection to analgesia, BDNF changes may reflect tDCS-induced changes in different cortical areas and/or neural circuits.

IntroductionApproved pharmacological treatments for smoking cessation are modestly effective, underscoring the need for improved pharmacotherapies. Glucagon-like peptide-1 receptor (GLP-1R) agonists attenuate the rewarding effects of nicotine in preclinical studies. We examined the efficacy of extended-release exenatide, a GLP-1R agonist, combined with nicotine replacement therapy (NRT, patch) for smoking cessation, craving, and withdrawal symptoms, with post-cessation body weight as a secondary outcome.MethodsEighty-four prediabetic and/or overweight smokers were randomized (1 : 1) to once-weekly placebo or exenatide, 2 mg, subcutaneously. All participants received NRT (21 mg) and brief smoking cessation counseling. Seven-day point prevalence abstinence (expired CO level ≤5 ppm), craving, withdrawal, and post-cessation body weight were assessed following 6 weeks of treatment. A Bayesian approach for analyzing generalized linear models yielded posterior probabilities (PP) to quantify the evidence favoring hypothesized effects of treatment on the study outcomes.ResultsExenatide increased the risk for smoking abstinence compared to placebo (46.3% and 26.8%, respectively), (risk ratio [RR] = 1.70; 95% credible interval = [0.96, 3.27]; PP = 96.5%). Exenatide reduced end-of-treatment craving in the overall sample and withdrawal among abstainers. Post-cessation body weight was 5.6 pounds lower in the exenatide group compared to placebo (PP = 97.4%). Adverse events were reported in 9.5% and 2.3% of participants in the exenatide and placebo groups, respectively.ConclusionsExenatide, in combination with the NRT improved smoking abstinence, reduced craving and withdrawal symptoms, and decreased weight gain among abstainers. Findings suggest that the GLP-1R agonist strategy is worthy of further research in larger, longer duration studies.ImplicationsDespite considerable progress in tobacco control, cigarette smoking remains the leading cause of preventable disease, disability, and death. In this pilot study, we showed that extended-release exenatide, a glucagon-like peptide-1 receptor agonist, added to the nicotine patch, improved abstinence and mitigated post-cessation body weight gain compared to patch alone. Further research is needed to confirm these initial positive results.

Despite a persistent link between homelessness, mental illness, and increased psychiatric hospitalizations, there is a dearth of research examining risk factors for higher utilization of mental hea...

Background: The response time speed-accuracy trade-off (SATO) is an established index of information processing ability, but rarely examined as a variable in association with treatment of substance use disorder (SUD). Aim: The purpose of this study was to test baseline information-processing ability differences between individuals who respond to treatment for cocaine use disorder v. those who do not. Methods: Eighty patients enrolled in a clinical trial for cocaine use disorder completed a baseline drug-specific eye-tracking (anti-saccade) assessment prior to treatment, which included trials with both cocaine-related and neutral stimuli. SATO functions were computed for treatment responders v. non-responders. Results: Unexpectedly, responders demonstrated statistically different SATO functions, showing poorer accuracy when executing faster response times. This difference was present on trials that presented cocaine stimuli only. Conclusions: SATO during performance of an eye-movement task may be useful for predicting differential response to substance use disorder treatment. However, in the present study, results were specific to cocaine cues rather than an overall SATO performance decrement.

For non-treatment-seeking women who use substances during pregnancy, immediately postpartum may be an optimum time for intervention. Our study tested a novel, brief, hospital-initiated, adaptive motivational interviewing plus acceptance and commitment therapy (MIACT) intervention to facilitate treatment initiation and reproductive planning postpartum among mothers who used substances during pregnancy.Mothers (N = 64) with an infant admitted to a neonatal intensive care unit were enrolled if they or their infant tested positive for an illicit substance at delivery or had a documented positive drug screen during pregnancy. A parallel group, randomized controlled design assigned participants to MIACT or conventional care (CC), with assessments at week 2 and 4 during treatment and follow-up at 2 and 6 months post treatment. Bayesian generalized linear modeling was used to evaluate outcomes as a function of treatment.Results indicated that during treatment the MIACT group demonstrated an 84% probability of benefit relative to CC with regard to initiating treatment (RR=1.5), however the effect was not seen at follow-up. MIACT was also associated with an increased probability of attending a postpartum obstetrics visit (RR=1.4), and receiving contraception during treatment and at both follow-ups, with posterior probabilities of 96% or higher and relative risks ranging from 1.5 to 5.1 at varying timepoints. Substance use rates for the MIACT versus CC were higher at follow-up.Brief, hospital-initiated interventions can assist postpartum mothers who use substances to enter treatment and obtain contraception in order to reduce future substance-exposed pregnancies.

The objective of the current meta-analysis was to assess the effect size of the Late Positive Potential (LPP) to drug and emotional cues in substance users compared to controls. The secondary objective was to test for moderation by: age, gender, years of use, use status, and substance type. Search was performed in August 2021 using PubMed. Inclusion criteria were: substance use disorder/dependence or validated self-report, LPP means, healthy control comparison, non-acute drug study, data available, peer-reviewed journal, English, and human participants. Selection bias was tested through modified Egger's regression and exploratory 3-parameter selection model tests. Results (k = 11) indicated LPP to drug cues was larger in substance use compared to control group, with a large effect size (Hedges' g=1.66, 95%CI [0.64,2.67], p = 0.005). There were no overall differences for emotional cues. Though threats of selection bias were not severe, inclusion of more studies with larger sample sizes in future meta-analyses will allow more robust tests of publication bias and more accurate measures of effect size.

Research indicates that high utilizers of the health care system are more likely to have mental illness, to be from socially disadvantaged groups, and to have limited access to community-based services. In this retrospective study, three definitions of high utilization were examined: (1) across time: non-high utilization versus high-utilization, (2) single year versus multi-year, and (3) year-to-year. Univariate logistic regression models were fit to a set of 20 theory-selected predictors of high utilization. An optimal multiple predictor model was then derived via penalized multiple logistic regression (via elastic net, a machine learning algorithm). Three factors were identified in the optimized model as increasing the likelihood of high utilization: having a diagnosis of schizophrenia, having a co-occurring personality disorder diagnosis, and having less than a high school education. Given the complex needs of psychiatric high utilizers, innovative approaches should be considered to improve patient outcomes and reduce costly psychiatric hospitalizations.

Aims To test a model of psychosocial/cultural/biological risk factors for poor birth outcomes in Latina pregnant women. Design An observational study measuring acculturation, progesterone, cortisol, cotinine, age, marital status, income, stress, depressive symptoms and coping. We tested a structural equation model to predict risk. Methods We obtained a convenience sample (N = 515) of low medical risk pregnant Mexican American Hispanic women at 22–24 weeks of gestation. Bilingual research nurses collected data from blood, urine and questionnaires. Self‐report measures were the Beck Depression Inventory‐II, the Perceived Stress Scale, the Acculturation Rating Scale for Mexican Americans‐II and the Brief Cope. We measured progesterone and cortisol in plasma and cotinine levels in urine by enzyme‐linked immunoassays. Results A PLS‐SEM model revealed that Mexican American Hispanic pregnant women who were younger, single, lower income, more acculturated and who had greater negative coping, stress and depression were most at risk for having earlier and smaller babies.

Dysregulated kynurenine (KYN) pathway has been implicated in the pathophysiology of depression. In this systematic review, we examined the relationship between kynurenine pathway metabolites (KYN, kynurenic acid KYNA, tryptophan TRP, quinolinic acid QUIN, KYN to TRP ratio) and depression symptoms in the context of pro-inflammatory activation and immune response. Out of 5,082 articles, fifteen studies were suitable; ten studies (N=315 medically ill patients treated with Interferon-alpha IFN-α) reported baseline and post-intervention plasma KYN, TRP and KYN/TRP ratios which were included in quantitative meta-analysis. Data from five studies were summarized (Interferon-alpha IFN-α, Interferon-beta IFN-β, and lipopolysaccharide LPS). We found that IFN-αtreatment in patients with chronic illnesses was associated with decreased TRP, increased levels of KYN and KYN/TRP ratio and depression scores from baseline to follow-up at both 4 and 24 weeks. Our findings suggest that increased risk of depression observed after immune-activating agents in patients with chronic medical illnesses likely is mediated by the kynurenine pathway. Further prospective studies are required to investigate the exact pathophysiology of the KYN pathway in depression.

Background Inflammation is implicated in cocaine use and associated problems, including depression and cognitive impairment. Objective We assessed 18 cytokines, cocaine use, cognition, and depression in individuals with Cocaine Use Disorder. Our general hypothesis was that higher pro-inflammatory cytokines would relate to more cocaine use, poorer cognition, and more depression, while higher anti-inflammatory cytokines would relate to less cocaine use, better cognition, and less depression. Methods Data were collected from 85 individuals (76.5% male, 80% African American) aged 18-65. The ASI, Shipley-2, and BDI-II assessed frequency and duration of cocaine use, cognition, and depression. Cytokines were tested using Bio-Plex Pro™ assays. Elastic net regression identified which cytokines related to each measure, controlling for confounds. Results Lower IL-29 (B = -0.08, bootstrapped 95%CI = [-0.24,0.07]), scD163 (B = -0.11, bootstrapped 95%CI = [-0.27,0.04]), Eotaxin-1 CCL11 (B = -0.11, bootstrapped 95%CI = [-0.30,0.08]), and higher APRIL/TNFSF13 (B = 0.11, bootstrapped 95%CI = [-0.08,0.30]) related to more frequent cocaine use. Lower IL-29 (B = -0.24, bootstrapped 95% CI = [-2.26,1.79]) and IL-20 (B = -1.62, bootstrapped 95%CI = [-3.53,0.29]) related to longer duration of cocaine use. Higher Eotaxin-2 CCL24 (B = 2.79, bootstrapped 95%CI = [-0.59,6.17]) and TWEAK (B = 2.83, bootstrapped 95%CI = [-0.80,6.45]) related to better cognition. Finally, higher IL-20 (B = -1.83, bootstrapped 95%CI = [-3.70,0.04]) and Osteocalcin (B = -1.56, bootstrapped 95%CI = [-3.81,0.70]) related to lower depressive symptoms. However, none of these relationships survived bootstrapped analyses. Conclusion Pro- and anti-inflammatory cytokines may relate to cocaine use, cognition, and depression, but inconsistent with our hypotheses, higher pro-inflammatory cytokines related to better functioning in several domains. Additionally, cytokines were selected at low frequencies and demonstrated weak relationships with outcomes. These preliminary findings suggest complex relationships between inflammation and cocaine use.

Background Acceptance and mindfulness processes indicating psychological flexibility may be important mechanisms in chronic pain adaptation; however, their association with opioid analgesic misuse (OA) risk is unclear. The present study investigated the extent to which psychological flexibility is associated with OA misuse risk within a chronic low back pain population on long-term opioid therapy. Methods Participants were 156 patients presenting for treatment at an academic pain clinic. Aspects of psychological flexibility were assessed using the Mindfulness Attention Awareness Scale (MAAS) and the Acceptance and Action Questionnaire II (AAQ II). The Current Opioid Misuse Measure (COMM) determined heightened risk of opioid analgesic misuse. Participants were 59% female, 48.3 years old on average (SD = 9.8), and largely White, Hispanic. Results Nested multiple linear regression indicated that the higher mindfulness levels predicted opioid misuse risk while controlling for pain severity, pain-related interference, pain anxiety, and acceptance. The full regression model predicted 54% of the variance in OA misuse risk. Conclusion Results suggest that psychological flexibility, particularly mindfulness processes, may be important in predicting and mitigating OA misuse risks among chronic pain patients. Non-pharmacological interventions are critical to addressing the current opioid misuse crisis.

BACKGROUND Breast milk has many benefits for infants, but initiating breastfeeding/pumping can be difficult for mothers of preterm infants, especially those who smoke (or live with individuals who smoke). The primary aim of this study was to identify risks for breastfeeding/pumping cessation with neonatal intensive care unit (NICU) infants' mothers who smoke or live with individuals who smoke, using a novel survival-analytic approach. METHODS/DESIGN Mothers (N = 360) were recruited for a secondhand smoke prevention intervention during infants' NICU hospitalizations and followed for ~6 months after infant discharge. Data were obtained from medical records and participant self-report/interviews. RESULTS The sample was predominantly ethnic/racial minorities; mean age was 26.8 (SD = 5.9) years. One-fifth never initiated breastfeeding/pumping (n = 67; 18.9%) and mean time-to-breastfeeding cessation was 48.1 days (SD = 57.2; median = 30.4 [interquartile range: 6.0-60.9]). Education, length of stay, employment, race/ethnicity, number of household members who smoke, and readiness-to-protect infants from tobacco smoke were significantly associated with breastfeeding cessation. Further, infants fed breast milk for ≥4 months had 42.7% more well-child visits (p

Objective The present study examined the effects of home-based remotely supervised transcranial direct current stimulation on quantitative sensory testing measurements in older adults with knee osteoarthritis. Participants were hypothesized to experience improved pain measurements over time. Design Open-label, single-arm trial. Setting Southeast Texas between March and November 2018 at a nursing school and participant homes. Subjects Older adults (aged 50–85 years) with self-reported unilateral or bilateral knee osteoarthritis pain who met eligibility criteria set by the American College of Rheumatology. Methods The intervention was applied with a constant current intensity for 20 minutes every weekday for two weeks (10 total sessions). Quantitative measures of pain were collected three times over 10 days (days 1, 5, and 10) and included heat threshold and tolerance, pressure pain threshold, punctate mechanical pain, pain, and conditioned pain modulation. Analyses used nonparametric tests to evaluate differences between day 1 and day 10. Generalized linear mixed models were then used to evaluate change across all three time points for each measure. Bayesian inference was used to provide the posterior probability of longitudinal effects. Results Nonparametric tests found improvements in seven measures, and longitudinal models supported improvements in 10 measures, with some nonlinear effects. Conclusions The home-based, remotely supervised intervention improved quantitative measurements of pain in older adults with knee osteoarthritis. This study contributes to the growing body of literature supporting home-based noninvasive stimulation interventions.

Cocaine use disorder (CUD) is a significant public health issue. Behavioral interventions such as contingency management (CM) have been demonstrated to be highly effective in promoting cocaine abstinence. However, identifying individual characteristics associated with cocaine relapse may help improve treatment outcomes. Cocaine demand is a behavioral economic measure that shares a scientific foundation with CM. In the current study, we assessed baseline cocaine demand using a hypothetical cocaine purchasing task. Participants (N = 58) consisted of treatment-seeking individuals with CUD. All participants received 1 month of CM treatment for cocaine abstinence, and treatment responders were defined as presenting 6 consecutive cocaine negative urine samples from thrice weekly clinic visits. Demand data were well described by the exponentiated demand model. Indices of demand (intensity of demand [Q₀], elasticity [α]) were significantly associated with recent (last 30 days) cocaine use. Importantly, linear regression revealed that CM treatment nonresponders presented significantly higher Q₀ (p = .025). Subsequent quantile regression analyses examining the relationship between CM treatment response and Q₀ revealed statistically reliable effects of being a nonresponder across 3 of the lower percentiles (i.e., 15, 25, and 30). Overall, these findings provide further support for the utility of exponentiated demand model. To our knowledge, this is the first study to demonstrate an association between baseline demand and contingency management response and systematically extend the findings of prior demand research to a novel drug class, cocaine. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Objective The neutrophil to lymphocyte ratio (NLR) is a non-specific, easy-to-obtain marker of inflammation associated with morbidity and mortality in systemic, psychiatric, and age-related inflammatory conditions. Given the growing trend of substance use disorder (SUD) in older adults, and the relationship between inflammation and SUD elevated NLR may serve as a useful inflammatory biomarker of the combined burden of aging and SUD. The present study focused on cocaine use disorder (CUD) to examine if cocaine adds further inflammatory burden among older adults, by comparing NLR values between older adults with CUD and a non-cocaine using, aged-matched, nationally representative sample. Methods The dataset included 107 (86% male) participants (aged 50-65 years) with cocaine use disorder. NLR was derived from complete blood count tests by dividing the absolute value of peripheral neutrophil concentration by lymphocyte concentration. For comparison, we extracted data from age-matched adults without CUD using the National Health and Nutrition Examination Survey. Individuals with immunocompromising conditions were excluded (e.g., rheumatoid arthritis and sexually transmitted infections such as HIV). A doubly-robust inverse probability-weighted regression adjustment (IPWRA) propensity score method was used to estimate group differences on NLR while controlling for potential confounding variables (age, gender, race, income, nicotine, marijuana and alcohol use). Results The IPWRA model revealed that the CUD sample had significantly elevated NLR in comparison to non-cocaine users, with a moderate effect size (β weight = 0.67). Conclusion Although non-specific, NLR represents a readily obtainable inflammatory marker for SUD research. CUD may add further inflammatory burden to aging cocaine users.

Bipolar disorder (BD) has been previously associated with clinical signs of premature aging, including accelerated epigenetic aging in blood and brain, and a steeper age-related decline in cognitive function. However, the clinical drivers and cognitive correlates of epigenetic aging in BD are still unknown. We aimed to investigate the relationship between multiple measures of epigenetic aging acceleration with clinical, functioning, and cognitive outcomes in patients with BD and controls. Blood genome-wide DNA methylation levels were measured in BD patients (n = 153) and matched healthy controls (n = 50) with the Infinium MethylationEPIC BeadChip (Illumina). Epigenetic age estimates were calculated using an online tool, including the recently developed lifespan predictor GrimAge, and analyzed with generalized linear models controlling for demographic variables and blood cell proportions. BD was significantly associated with greater GrimAge acceleration (AgeAccelGrim, β=0.197, p = 0.009), and significant group-dependent interactions were found between AgeAccelGrim and blood cell proportions (CD4+ T-lymphocytes, monocytes, granulocytes, and B-cells). Within patients, higher AgeAccelGrim was associated with worse cognitive function in multiple domains (short-term affective memory (β=-0.078, p = 0.030), short-term non-affective memory (β=-0.088, p = 0.018), inhibition (β=0.064, p = 0.046), and problem solving (β=-0.067, p = 0.034)), age of first diagnosis with any mood disorder (β=-0.076, p = 0.039) or BD (β=-0.102, p = 0.016), as well as with current non-smoking status (β=-0.392, p 0.001). Overall, our findings support the contribution of epigenetic factors to the aging-related cognitive decline and premature mortality reported in BD patients, with an important driving effect of smoking in this population.

Background: Apathy is among the most frequent neuropsychiatric syndromes in Alzheimer’s disease (AD). Objective: To determine the prevalence of apathy and the associated clinical and laboratorial parameters (focus on inflammatory biomarkers) in patients with dementia enrolled at the Texas Alzheimer’s Research and Care Consortium (TARCC) study. Methods: This is a cross-sectional analysis of TARCC baseline. Participants were evaluated through different clinical tools, including the Mini-Mental State Examination (MMSE) and the Lawton-Brody Instrumental Activities of Daily Life (IADL)/Physical Self-Maintenance Scale (PSMS). Apathy was defined by a positive response to the respective item in the Neuropsychiatric Inventory–Questionnaire applied to caregivers. Serum levels of 16 biomarkers were determined by HumanMap multiplex immunoassay. Comparisons between apathy versus non-apathy groups were carried out with non-parametric tests. Logistic regression and the least absolute shrinkage and selection operator (LASSO) were used to separately model apathy as a function of each biomarker, adjusted for the potential confounders. Results: From 1,319 patients with AD (M/F: 579/740, mean age ± SD: 75.3 ± 8.4), 373 (28.3%) exhibited apathy. When categorized according to the presence of apathy, the groups had significant differences in sex, diabetes diagnosis, and tobacco use. The apathy group also had worse cognitive performance and daily functioning than the non-apathy group as assessed, respectively, by MMSE and IADL/PSMS. Higher levels of interleukin-6, interleukin-10, and leptin were associated with higher odds of apathy. Conclusion: Apathy is associated with cognitive and functional status in AD. The association between apathy and peripheral inflammatory mediators deserves further investigation.

Bipolar disorder (BD) is a highly variable and burdensome disease for patients and caregivers. A BD diagnosis almost triples the likelihood of developing dementia as the disease progresses. Neurocognitive reserve appears to be one of the most important influences on lifelong functional outcomes and quality of life in BD. Though several prior studies have assessed the effects of lithium on regional gray and white matter volumes in this population, representative cohorts are typically middle-aged, have a more severe pathology, and are not as commonly assessed in the depressive phase (which represents the majority of most patients' lifespans outside of remission). Here we have shown that positive adaptations with lithium can be observed throughout the brain after only six weeks of monotherapy at low-therapeutic serum levels. Importantly, these results remove some confounders seen in prior studies (patients were treatment free at time of enrollment and mostly treatment naïve). This cohort also includes underrepresented demographics in the literature (young adult patients, mostly bipolar II, and exclusively in the depressed phase). These findings bolster the extensive body of evidence in support of long-term lithium therapy in BD, furthering the possibility of its expanded use to wider demographics.

Objective Tobacco residue, also known as third-hand smoke (THS), contains toxicants and lingers in dust and on surfaces and clothes. THS also remains on hands of individuals who smoke, with potential transfer to infants during visitation while infants are hospitalized in neonatal intensive care units (NICUs), raising concerns (e.g., hindered respiratory development) for vulnerable infants. Previously unexplored, this study tested handwashing (HW) and sanitization efficacy for finger-nicotine removal in a sample of adults who smoked and were visiting infants in an NICU. Study Design A cross-sectional sample was recruited to complete an interview, carbon monoxide breath samples, and three nicotine wipes of separate fingers (thumb, index, and middle). Eligible participants (n = 14) reported current smoking (verified with breath samples) and were randomly assigned to 30 seconds of HW (n = 7) or alcohol-based sanitization (n = 7), with the order of finger wipes both counterbalanced and randomly assigned. After randomization, the first finger was wiped for nicotine. Participants then washed or sanitized their hands and finger two was wiped 5 minutes later. An interview assessing tobacco/nicotine use and exposure was then administered, followed by a second breath sample and the final finger wipe (40–60 minutes after washing/sanitizing). Results Generalized linear mixed models found that HW was more effective than sanitizer for nicotine removal but failed to completely remove nicotine. Conclusions Without proper protections (e.g., wearing gloves and gowns), NICU visitors who smoke may inadvertently expose infants to THS. Research on cleaning protocols are needed to protect vulnerable medical populations from THS and associated risks. Key Points

IntroductionPost-stroke depression (PSD) is a severe complication of cerebrovascular stroke affecting about one-third of stroke survivors. Moreover, PSD is associated with functional recovery and quality of life (QOL) in stroke survivors. Screening for PSD is recommended. There are, however, differences in the literature on the impact of early screening on functional outcomes. In this systematic review, we synthesise the currently available literature regarding the associations between timing and setting of PSD screening and mortality, QOL and functional outcomes in stroke survivors.Methods and analysisWe will systematically search electronic databases including PubMed, Embase, APA PsycINFO, Web of Science, Scopus and CINAHL from inception to August 2021. Four reviewers will screen the title and abstract and full-text level records identified in the search in a blinded fashion to determine the study eligibility. Any selection disagreements between the reviewers will be resolved by the study investigator. Data extraction of eligible studies will be conducted by two reviewers using a predefined template. We will complete the quality assessment of included articles independently by two reviewers using the Newcastle Ottawa Scale. Eventual discrepancies will be resolved by the principal investigator.Ethics and disseminationDue to the nature of the study design, ethical approval is not required. The systematic review and meta-analysis findings will be published and disseminated in a peer-reviewed journal. Our results will also be disseminated through posters and presentations at appropriate scientific conferences.PROSPERO registration numberCRD42021235993.

Transcranial direct current stimulation (tDCS) has demonstrated effectiveness in reducing clinical and experimental measures of pain in patients with chronic pain; however, research examining the mechanisms of action for the effects of tDCS has been lacking. The present study investigated the effect of active tDCS on measures of inflammation and stress. Older adults (aged 50–70 years) with knee osteoarthritis (OA) were randomly assigned to receive daily 20-min sessions of either tDCS ( n = 20) or sham tDCS ( n = 20) for 5 consecutive days. Participants provided blood samples at baseline and the end of treatment. The following measures of immune function and stress were collected: interleukin (IL)-6 and 10, tumor necrosis factor-α (TNF-α), C-reactive protein, cortisol, and β-endorphin. Generalized linear modeling evaluated each posttreatment measure as a function of tDCS group, controlling for baseline (measuring residual change, analogous to analysis of covariance). Bayesian statistical inference was used to directly quantify the probability of the effect of active tDCS. IL-6, IL-10, TNF-α, and β-endorphin demonstrated lower levels of stress and inflammation in the active tDCS group. These findings provide preliminary evidence that active (relative to sham) tDCS is associated with reduced levels of inflammation.

Background: Hydrocodone-combination analgesics were changed from Schedule III to Schedule II to discourage the prescribing of these analgesics. Our primary aim was to explore the effect of hydrocodone rescheduling on opioid prescribing within an urban safety-net health care system. Methods and Design: Data were extracted from electronic records of ambulatory patients (N = 82,432 patients) prescribed hydrocodone-combination, codeine-combination, or tramadol opioid analgesics (N = 200,675 prescriptions) between October 6, 2013 and October 6, 2015. Data analyses modeled predicted probabilities of hydrocodone-combination prescriptions (HCPs). Chronic opioid therapy (COT) for chronic pain (ie, ≥3 opioid prescriptions/12 months) and morphine milligram equivalency (MME) levels were also examined. Results: The probability of providers writing HCPs decreased significantly from pre- to postrescheduling (0.525 vs 0.158, respectively, P Discussion: Significant declines in HCPs occurred after rescheduling; however, one third of patients prescribed opioids remained on doses ≥20 MME/day. Codeine- and tramadol-prescription probabilities increased significantly and providers may have an increased perception of safety about these medications. Physicians and health care systems must reduce their overreliance on opioids in treating pain, especially chronic pain, as all opioids incur some level of risk.

A hypothetical cocaine purchasing task (CocPT) was used to assess changes in cocaine demand in the context of contingency management (CM) treatment for cocaine use disorder (CUD). Participants (N = 89) were treatment-seeking individuals with CUD receiving 4 weeks of abstinence-based, high-magnitude CM. Treatment response (vs. non-response) was operationally defined as the submission of 6 consecutive cocaine-negative urine samples across two weeks. The CPT was assessed at baseline, week 2, and week 5. Demand data were well described by the exponentiated demand model, and baseline demand indices (Q0, Pmax, breakpoint, essential value) were significantly associated with self-report measures of cocaine use. The probability of being a zero-responder reporting zero cocaine consumption at all prices significantly increased over the course of treatment, and was greater among treatment responders vs. non-responders. Among non-zero demand data, decreases in Omax, Pmax, breakpoint, and essential value were observed over the course of CM treatment, favoring responders. To our knowledge, this is the first study to assess change in cocaine demand in the context of CM treatment targeting cocaine abstinence. Our results support the utility of cocaine demand as a measure for both identifying individuals with greater treatment need and tracking relapse risk over the course of treatment.

Background Out-of-hospital cardiac arrest (OHCA) data debriefing and clinical research often require the retrospective analysis of large datasets containing defibrillator files from different vendors and clinical annotations by the emergency medical services. Aim To introduce and evaluate a methodology to automatically extract cardiopulmonary resuscitation (CPR) quality data in a uniform and systematic way from OHCA datasets from multiple heterogeneous sources. Methods A dataset of 2236 OHCA cases from multiple defibrillator models and manufacturers was analyzed. Chest compressions were automatically identified using the thoracic impedance and compression depth signals. Device event time-stamps and clinical annotations were used to set the start and end of the analysis interval, and to identify periods with spontaneous circulation. A manual audit of the automatic annotations was conducted and used as gold standard. Chest compression fraction (CCF), rate (CCR) and interruption ratio were computed as CPR quality variables. The unsigned error between the automated procedure and the gold standard was calculated. Results Full-episode median errors below 2% in CCF, 1 min−1 in CCR, and 1.5% in interruption ratio, were measured for all signals and devices. The proportion of cases with large errors ( > 10% in CCF and interruption ratio, and > 10 min−1 in CCR) was below 10%. Errors were lower for shorter sub-intervals of interest, like the airway insertion interval. Conclusions An automated methodology was validated to accurately compute CPR metrics in large and heterogeneous OHCA datasets. Automated processing of defibrillator files and the associated clinical annotations enables the aggregation and analysis of CPR data from multiple sources.

Cocaine demand is a behavioral economic measure assessing drug reward value and motivation to use drug. The purpose of the current study was to develop a brief assessment of cocaine demand (BACD). Results from the BACD were compared with self-report measures of cocaine use. Participants consisted of treatment-seeking individuals with cocaine use disorder (CUD: N = 22). Results revealed that indices of brief demand were significantly associated with various self-report measures of cocaine use. Overall, these results support the utility of a BACD for assessing cocaine demand.