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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).

Background Blood pressure (BP) is often inadequately controlled in children treated for hypertension, and personalized (n-of-1) trials show promise for tailoring treatment choices. We assessed whether patients whose treatment choices are informed by an n-of-1 trial have improved BP control compared to usual care. Methods A randomized clinical trial was conducted in a pediatric hypertension clinic in Houston from April 2018 to September 2020. Hypertensive adolescents and young adults 10–22 years old were randomized 1:1 to a strategy of n-of-1 trial using ambulatory BP monitoring to inform treatment choice or usual care, with treatment selected by physician preference. The primary outcome was the proportion of patients with ambulatory BP control at 6 months in a Bayesian analysis. Results Among 49 participants (23 randomized to n-of-1 trials and 26 to usual care), mean age was 15.6 years. Using skeptical priors, we found a 69% probability that n-of-1 trials increased BP control at 6 months (Bayesian odds ratio (OR) 1.24 (95% credible interval (CrI) 0.51, 2.97), and 74% probability using neutral informed priors (OR 1.45 (95% CrI 0.48, 4.53)). Systolic BP was reduced in both groups, with a 93% probability of greater reduction in the n-of-1 trial group (mean difference between groups = −3.6 mm Hg (95% CrI −8.3, 1.28). There was no significant difference in side effect experience or caregiver satisfaction. Conclusions Among hypertensive adolescents and young adults, n-of-1 trials with ambulatory BP monitoring likely increased the probability of BP control. A large trial is needed to assess their use in clinical practice. ClinicalTrials.gov NCT03461003 Clinical trial registry ClinicalTrials.gov; NCT 03461003

BackgroundAge is a significant risk factor for functional decline and disease of the musculoskeletal system, yet few biomarkers exist to facilitate ageing research in musculoskeletal tissues. Multivariate models based on DNA methylation, termed epigenetic clocks, have shown promise as markers of biological age. However, the accuracy of existing epigenetic clocks in musculoskeletal tissues are no more, and often less accurate than a randomly sampled baseline model.ResultsWe developed a highly accurate epigenetic clock, Msk-Age, that is specific to tissues and cells of the musculoskeletal system. MskAge was built using a penalised genetic algorithm islands model that addresses multi-tissue clock bias. The final model was trained on the transformed principal components of CpGs selected by the genetic algorithm, which are significantly enriched for pathways terms related to the skeletal system and mesenchyme development. We show that MskAge tracks epigenetic ageingex vivoandin vitro. Epigenetic age estimates are rejuvenated to zero with cellular reprogramming and are accelerated at a rate of 0.45 years per population doubling. Remarkably, MskAge explains more variance associated within vitroageing of fibroblasts than the purpose-developed skin and blood clock.ConclusionThe precision of MskAge and its ability to capture perturbations in biological ageing make it a promising research tool for musculoskeletal and ageing biologists.

IMPORTANCE: Improving treatment outcomes for smokers with Major Depressive Disorder (MDD) can have significant public health implications. OBJECTIVE: To evaluate the safety and efficacy of smoking cessation pharmacotherapy among smokers with MDD. DESIGN: Secondary analysis of a randomized, double-blind, active- (nicotine patch) and placebo-controlled trial of 12 weeks of either varenicline or bupropion with 12-week follow-up. PARTICIPANTS: Community volunteers 18-75 years of age; smoke 10+ cigarettes/day; with clinically stable MDD(N=2635) or no psychiatric disorder(N=4028), from 140 sites in 16 countries. INTERVENTION: 12 weeks of pharmacotherapy (placebo, PLA; nicotine replacement therapy, NRT; bupropion, BUP; varenicline, VAR) plus brief cessation counseling. MEASURE(S): Primary safety outcome: the occurrence of ≥ 1 treatment-emergent, moderate to severe Neuropsychiatric Adverse Event (NPSAE). Primary efficacy outcome: biochemically confirmed continuous abstinence (CA) during the final 4 weeks of treatment (Weeks 9–12). RESULTS: 6,653 participants (56% female; 39% MDD) ~47 years old. Risk of NPSAEs did not differ by medication for MDD. MDD had higher risk (p

Introduction: Persistent pain after stroke significantly impacts patients’ function, ability to participate in rehabilitation, and quality of life. We examined characteristics of stroke survivors discharged with pain. Methods: The sample consisted of 824 stroke patients admitted to a large, urban university based acute care facility in Texas with a completed pain assessment (numeric rating scale or Behavior Pain Scale) at discharge. Descriptive analysis of means and frequency distributions was conducted using a two-sided t-test for continuous variables and a Chi-squared test for categorical variables. Univariable and multivariable logistic regression models were used to determine the association between pain at discharge and type of stroke, adjusting for age, sex, race, smoking status, prevalent hypertension, BMI, and length of stay (LOS). We also tested for statistical interactions between stroke type and age, sex, and race. Results: The mean age was 64 years, with 56% (n=462) being males. Of the 824 stroke patients, 584 (71%) had ischemic stroke while 237 (29%) had hemorrhagic (ICH) stroke. At discharge, 43% (n=358) reported pain. In unadjusted analyses, those reporting pain were younger (p Conclusions: Our study finds that 43% of stroke survivors reported pain at discharge. Younger females with an increased BMI and an increased LOS were more likely to report pain. Our model AUC suggests that post stroke pain may be a complicated phenomenon that requires more complex models.

Objective: Serially measure the rate of hematoma volume (HV) and edema volume (EV) resolution in patients with acute-to-early chronic ICH Background: After ICH, the primary cause of brain injury is the mechanical force from the compression of the brain tissue. The secondary damage involves (bio)chemical injury produced by the toxicity of components of extravasated blood, which directly compromises surrounding tissue by oxidative stress, cell death, neuroinflammation, and brain edema. There is very little known about the rate of HV and EV resolution within one month of ictus. Methods: Twelves patients, a placebo sub-cohort of a previous clinical trial, were serially imaged on day-1, 14, and 28 of initial ictus. Anatomical (FLAIR, T1W, and T2W) images were obtained on a 3T MRI system. HV and EV were segmented using semiautomated seed growing algorithm. The prediction of HV and EV resolution rate was calculated using the Bayesian model and compared across the different time points. Results: There were 7M/5F with the average age of 57 ± 9y. The baseline average HV/NIHSS 22,998 mm 3 /11. All patients with deep ICH and 6 extended to IVH. The multilevel Bayesian analysis showed the rate of HV resolution -327.90 mm 3 (95% CrI = -475.37- -181.86; Posterior Probability b < 0 ≥ 0.99) with 14 days acceleration of -17.67 mm 3 (95% CrI = -35.89- 1.21; Posterior Probability b < 0 = 0.97). The rate of EV resolution -341.44 mm 3 (95% CrI = -736.32- 60.98; Posterior Probability b < 0 = 0.96) with 14 days acceleration -34.63 mm 3 (95% CrI = -85.47- 16.61; Posterior Probability b < 0 = 0.91). Overall the decrease in HV over time was an offsetting deceleration which increases over time. The overall trend of HV resolution is shown in Fig-1 Conclusion: There was a high variance in the rate of HV and EV resolution, but overall all the patients exhibited a similar trend. The rates of HV and EV resolution can help us provide optimal patient care.

Acute cerebral stroke is a leading cause of disability and death, which could be reduced with a prompt diagnosis during patient transportation to the hospital. A portable retina imaging system could enable this by measuring vascular information and blood perfusion in the retina and, due to the homology between retinal and cerebral vessels, infer if a cerebral stroke is underway. However, the feasibility of this strategy, the imaging features, and retina imaging modalities to do this are not clear. In this work, we show initial evidence of the feasibility of this approach by training machine learning models using feature engineering and self-supervised learning retina features extracted from OCT-A and fundus images to classify controls and acute stroke patients. Models based on macular microvasculature density features achieved an area under the receiver operating characteristic curve (AUC) of 0.87–0.88. Self-supervised deep learning models were able to generate features resulting in AUCs ranging from 0.66 to 0.81. While further work is needed for the final proof for a diagnostic system, these results indicate that microvasculature density features from OCT-A images have the potential to be used to diagnose acute cerebral stroke from the retina.

Background Patients with sickle cell disease (SCD) have vaso-occlusive crises (VOCs). Infusion centers (ICs) are alternatives to emergency department (ED) care and may improve patient outcomes. Objective To assess whether care in ICs or EDs leads to better outcomes for the treatment of uncomplicated VOCs. Design Prospective cohort. (ClinicalTrials.gov: NCT02411396). Setting 4 U.S. sites, with recruitment between April 2015 and December 2016. Participants Adults with SCD living within 60 miles of a study site. Measurements Participants were followed for 18 months after enrollment. Outcomes of interest were time to first dose of parenteral pain medication, whether pain reassessment was completed within 30 minutes after the first dose, and patient disposition on discharge from the acute care visit. Treatment effects for ICs versus EDs were estimated using a time-varying propensity score adjustment. Results Researchers enrolled 483 participants; the 269 who had acute care visits on weekdays are included in this report. With inverse probability of treatment-weighted adjustment, the mean time to first dose was 62 minutes in ICs and 132 minutes in EDs; the difference was 70 minutes (95% CI, 54 to 98 minutes; E-value, 2.8). The probability of pain reassessment within 30 minutes of the first dose of parenteral pain medication was 3.8 times greater (CI, 2.63 to 5.64 times greater; E-value, 4.7) in the IC than the ED. The probability that a participant's visit would end in admission to the hospital was smaller by a factor of 4 (0.25 [CI, 0.18 to 0.33]) with treatment in an IC versus an ED. Limitation The study was restricted to participants with uncomplicated VOCs. Conclusion In adults with SCD having a VOC, treatment in an IC is associated with substantially better outcomes than treatment in an ED. Primary funding source Patient-Centered Outcomes Research Institute.

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.

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.

Background Neuroinflammation plays a key role in PD pathogenesis, and allogeneic bone marrow–derived mesenchymal stem cells can be used as an immunomodulatory therapy. Objective The objective of this study was to prove the safety and tolerability of intravenous allogeneic bone marrow–derived mesenchymal stem cells in PD patients. Methods This was a 12‐month single‐center open‐label dose‐escalation phase 1 study of 20 subjects with mild/moderate PD assigned to a single intravenous infusion of 1 of 4 doses: 1, 3, 6, or 10 × 106 allogeneic bone marrow–derived mesenchymal stem cells/kg, evaluated 3, 12, 24, and 52 weeks postinfusion. Primary outcome safety measures included transfusion reaction, study‐related adverse events, and immunogenic responses. Secondary outcomes included impact on peripheral markers, PD progression, and changes in brain perfusion. Results There were no serious adverse reactions related to the infusion and no responses to donor‐specific human leukocyte antigens. Most common treatment‐emergent adverse events were dyskinesias (20%, n = 4) with 1 emergent and 3 exacerbations; and hypertension (20%, n = 4) with 3 transient episodes and 1 requiring medical intervention. One possibly related serious adverse event occurred in a patient with a 4‐year history of lymphocytosis who developed asymptomatic chronic lymphocytic leukemia. Peripheral inflammation markers appear to be reduced at 52 weeks in the highest dose including, tumor necrosis factor‐α (P

Background: In 2019, an estimated 7.3 US million adults had used stimulants in the past year. Stimulant use is associated with increased stroke risk, yet the prevalence of common stroke risk factors (RFs) in patients who use stimulants is not well described. We sought to examine the association between stimulant use and the presence of stroke risk factors (RFs) in stroke patients. Methods: We conducted an IRB approved retrospective review of ischemic and hemorrhagic stroke patients admitted 9/2019 through 9/2020. Inclusion criteria were age ≥18 and completion of a urine drug screen (UDS) on admission. Logistic regression was used to model the association of RFs (hypertension, type 2 diabetes (DMII), hyperlipidemia, atrial fibrillation, and coronary disease) to acute stimulant use, adjusting for socio-demographic characteristics. Results: Among 1878 patients screened, 814 (43.3%) had a UDS. UDS was more common in younger (median age 60 vs 67), male (60.4% vs 47.6%) and Black (35.6% vs 27.5%) and Hispanic (22.0% vs 21.6%) patients. Of those with UDS, 72(8.84%) had cocaine and/or amphetamine detected and 660 (81.08%) were UDS negative. After controlling for age, sex, race, and insurance status, hypertension (OR 2.28, 95%CI 1.17-4.41) was positively associated with stimulant use while DMII was negatively associated (OR 0.39, 95%CI 0.19-0.81). Other RFs were not associated with stimulant use. Conclusion: Despite being younger, stroke patients with stimulant-positive UDS had a higher prevalence of hypertension, a leading risk factor for recurrent stroke, than UDS-negative patients. This group may represent a high-risk population that may benefit from targeted interventions for secondary stroke prevention. Differences in screening by sex, race, and age may lead to missed opportunities for assessment of recurrent stroke risk. A standard approach to drug screening may eliminate these biases.

Background: Enteral tube feeding is required for adequate nutrition in post-stroke patients with dysphagia. Nasogastric tube (NGT) feeding is used short-term, while percutaneous endoscopic gastrostomy (PEG) is utilized when dysphagia persists. Furthermore, most post-acute care facilities, including inpatient rehabilitation (IR), do not accept patients with NGT. We assessed factors associated with quick recovery of swallowing function, to identify which patients may avoid unnecessary PEG placement during hospitalization and reduce associated complications. Methods: Using a prospectively collected registry of stroke patients admitted in our system of 5 IRs, we found 806 patients with stroke (1/2018 to 6/2019). At discharge from hospitalization or IR, 83 patients had either a PEG or NGT. We divided patients into two groups based on whether PEG was used for nutrition at discharge from IR or if dysphagia improved and they were able to resume a PO diet. We performed predictive modeling with RIDGE regression analysis using age, sex, marital status, initial NIHSS, infarct location, change in dysphagia outcome and screening scale (DOSS) at first two evaluations, and days hospitalized. Results: Median age was 65 (IQR 60-71) years and 28 (34%) were female. Twenty-eight patients (34%) required nutritional support upon IR discharge. Mean initial NIHSS for patients who passed swallow testing prior to IR discharge was 15 (7.3), similar to patients who failed swallow testing prior to discharge 13.7 (8.0) (p=0.50). Patients who passed swallow testing prior to IR discharge had comparable median length of hospitalization to those who did not (14.9 and 14.3, respectively, p=0.84). Predictive modeling indicated that age, sex, marital status, initial NIHSS, location of infarct, change in DOSS and length of hospitalization can predict passing swallow evaluation satisfactorily (AUC=0.673). Of the 12 patients with NGT at discharge from hospital, no patients required PEG placement. Conclusion: Our model shows that age, sex, marital status, initial NIHSS, location of infarct, change in DOSS and length of hospitalization can satisfactorily predict passing swallow evaluations. However, additional factors involved in the process will be explored to improve the model.

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

Background Efforts to reduce opioid use in trauma patients are currently hampered by an incomplete understanding of the baseline opioid exposure and variation in United States. The purpose of this project was to obtain a global estimate of opioid exposure following injury and to quantify the variability of opioid exposure between and within United States trauma centers. Study design Prospective observational study was performed to calculate opioid exposure by converting all sources of opioids to oral morphine milligram equivalents (MMEs). To estimate variation, an intraclass correlation was calculated from a multilevel generalized linear model adjusting for the a priori selected variables Injury Severity Score and prior opioid use. Results The centers enrolled 1,731 patients. The median opioid exposure among all sites was 45 MMEs per day, equivalent to 30 mg of oxycodone or 45 mg of hydrocodone per day. Variation in opioid exposure was identified both between and within trauma centers with the vast majority of variation (93%) occurring within trauma centers. Opioid exposure increased with injury severity, in male patients, and patients suffering penetrating trauma. Conclusion The overall median opioid exposure was 45 MMEs per day. Despite significant differences in opioid exposure between trauma centers, the majority of variation was actually within centers. This suggests that efforts to minimize opioid exposure after injury should focus within trauma centers and not on high-level efforts to affect all trauma centers. Level of evidence Epidemiological, level III.