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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.

Background Research on risk factors for neuropsychiatric adverse events (NAEs) in smoking cessation with pharmacotherapy is scarce. We aimed to identify predictors and develop a prediction model for risk of NAEs in smoking cessation with medications using Bayesian regularization. Methods Bayesian regularization was implemented by applying two shrinkage priors, Horseshoe and Laplace, to generalized linear mixed models on data from 1203 patients treated with nicotine patch, varenicline or placebo. Two predictor models were considered to separate summary scores and item scores in the psychosocial instruments. The summary score model had 19 predictors or 26 dummy variables and the item score model 51 predictors or 58 dummy variables. A total of 18 models were investigated. Results An item score model with Horseshoe prior and 7 degrees of freedom was selected as the final model upon model comparison and assessment. At baseline, smokers reporting more abnormal dreams or nightmares had 16% greater odds of experiencing NAEs during treatment (regularized odds ratio (rOR) = 1.16, 95% credible interval (CrI) = 0.95 – 1.56, posterior probability P(rOR > 1) = 0.90) while those with more severe sleep problems had 9% greater odds (rOR = 1.09, 95% CrI = 0.95 – 1.37, P(rOR > 1) = 0.85). The prouder a person felt one week before baseline resulted in 13% smaller odds of having NAEs (rOR = 0.87, 95% CrI = 0.71 – 1.02, P(rOR Conclusions Worse sleep-related symptoms reported at baseline resulted in 85%—90% probability of being more likely to experience NAEs during smoking cessation with pharmacotherapy. Treatment for sleep disturbance should be incorporated in smoking cessation program for smokers with sleep disturbance at baseline. Bayesian regularization with Horseshoe prior permits including more predictors in a regression model when there is a low number of events per variable.

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.

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.

Background Evidence for effective pain management and opioid minimization of intravenous ketamine in elective surgery has been extrapolated to acutely injured patients, despite limited supporting evidence in this population. This trial seeks to determine the effectiveness of the addition of sub-dissociative ketamine to a pill-based, opioid-minimizing multi-modal pain regimen (MMPR) for post traumatic pain. Methods This is a single-center, parallel-group, randomized, controlled comparative effectiveness trial comparing a MMPR to a MMPR plus a sub-dissociative ketamine infusion. All trauma patients 16 years and older admitted following a trauma which require intermediate (IMU) or intensive care unit (ICU) level of care are eligible. Prisoners, patients who are pregnant, patients not expected to survive, and those with contraindications to ketamine are excluded from this study. The primary outcome is opioid use, measured by morphine milligram equivalents (MME) per patient per day (MME/patient/day). The secondary outcomes include total MME, pain scores, morbidity, lengths of stay, opioid prescriptions at discharge, and patient centered outcomes at discharge and 6 months. Discussion This trial will determine the effectiveness of sub-dissociative ketamine infusion as part of a MMPR in reducing in-hospital opioid exposure in adult trauma patients. Furthermore, it will inform decisions regarding acute pain strategies on patient centered outcomes. Trial registration The Ketamine for Acute Pain Management After Trauma (KAPT) with registration # NCT04129086 was registered on October 16, 2019.

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

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.

Background Incorporating physical movement in the teaching of academic content (active learning) is a promising approach to improve children’s health and academic performance. Despite documented benefits, implementation of active learning remains challenging for schools. The aims of this study are to develop an implementation strategy to support the delivery of active learning in elementary schools and examine the impact of the developed implementation strategy on the implementation and effectiveness of active learning. Methods Aim 1 will use Implementation Mapping, which is a multi-step approach that guides the use of theory, stakeholder input, and existing literature to develop a scientifically based implementation strategy for active learning in elementary schools. Aim 2 will feature a feasibility study to examine the impact of the implementation strategy on both implementation and effectiveness outcomes, consistent with a Hybrid Type 2 design. Acceptability and implementation fidelity will be the primary implementation outcomes, and student physical activity levels will be the primary effectiveness outcome. We will recruit two elementary schools within our partner district, and one will be randomly assigned to receive usual support while the other will receive the newly developed implementation strategy. Participants from each school will complete baseline, 6-, and 12-month assessments. Bayesian statistical approaches will quantitatively examine preliminary effectiveness outcomes. We will also use an embedded mixed methods approach to triangulate findings. Discussion This study’s innovative overarching conceptual framework (centered on Implementation Mapping) will inform the development and testing of the implementation strategy. This study also uses methodological approaches optimal for feasibility studies, including mixed methods and Bayesian statistics. As a result, we will be able to gain a thorough understanding about the feasibility and preliminary effectiveness of the implementation strategy, which will inform subsequent research and practice for implementing active learning in schools. Trial registration ClinicalTrials.gov, NCT05048433, registered on September 8, 2021.

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.

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.

INTRODUCTION: In 2013, we implemented a pill-based, multi-modal pain regimen (MMPR) in order to decrease in-hospital opioid exposure after injury at our trauma center. We hypothesized that the MMPR would decrease inpatient oral morphine milligram equivalents (MME), decrease opioid prescriptions at discharge, and result in similar Numerical Rating Scale (NRS) pain scores. METHODS: Adult patients admitted to a level-1 trauma center with ≥1 rib fracture from 2010–2017 were included – spanning 3 years before and 4 years after MMPR implementation. MME were summarized as medians and interquartile range (IQR) by year of admission. The effect of the MMPR on daily total MME was estimated using Bayesian generalized linear model. RESULTS: Over the 8 year study period, 6,933 patients who met study inclusion criteria were included. No significant differences between years were observed in Abbreviated Injury Scale (AIS) Chest or Injury Severity Scores (ISS). After introduction of the MMPR, there was a significant reduction in median total MME administered per patient day from 60 MME/ patient day (IQR 36–91 MME/patient day) pre-MMPR implementation to 37 MME/patient day (IQR 18–61 MME/patient day) in 2017, p

BackgroundEvidence for effective pain management and opioid minimization of intravenous ketamine in elective surgery has been extrapolated to acutely injured patients, despite limited supporting evidence in this population. This trial seeks to determine the effectiveness of the addition of sub-dissociative ketamine to a pill-based, opioid-minimizing multi-modal pain regimen (MMPR) for post traumatic pain.MethodsThis is a single-center, parallel-group, randomized, controlled comparative effectiveness trial comparing a MMPR to a MMPR plus a sub-dissociative ketamine infusion. All trauma patients 16 years and older admitted following a trauma which require intermediate (IMU) or intensive care unit (ICU) level of care are eligible. Prisoners, patients who are pregnant, patients not expected to survive, and those with contraindications to ketamine are excluded from this study. The primary outcome is opioid use, measured by morphine milligram equivalents (MME) per patient per day (MME/patient/day). The secondary outcomes include total MME, pain scores, morbidity, lengths of stay, opioid prescriptions at discharge, and patient centered outcomes at discharge and six months.DiscussionThis trial will determine the effectiveness of sub-dissociative ketamine infusion as part of a MMPR in reducing in-hospital opioid exposure in adult trauma patients. Furthermore, it will inform decisions regarding acute pain strategies on patient centered outcomes.Trial Registration:The Ketamine for Acute Pain Management After Trauma (KAPT) with registration # NCT04129086 was registered on 10/16/2019 and is available at https://clinicaltrials.gov/ct2/show/NCT04129086?term=ketamine+injury&draw=2&rank=6

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

Background: This study investigated the association between drug use and Hepatitis C Virus (HCV) infection in HIV-negative men who have sex with men (MSM) who reported drug use but not injection drug use. Methods: This cross-sectional study analyzed the data of 118 HIV-negative MSM who reported drug use but not injection drug use recruited from two inner-city communities between 2004 and 2007. Latent class analysis (LCA) was used to identify drug use latent classes. Multinomial logistic regression analysis was used to evaluate the association between drug use latent class and HCV infection. Results: Four distinct latent classes of drug use were identified: (1) persons >=42 years old who used only crack cocaine, (2) persons about 42 years old who used >2 drugs, (3) persons 5 drugs, and (4) persons >=42 years old who used >6 drugs. Class 4, persons >= 42 years old who used >6 drugs were significantly associated with HCV infection. Compared with persons about 42 years old who used >2 drugs, persons >=42 years old who used >6 drugs had more than 16 times the odds of having HCV infection (adjusted OR = 16.9, 95%CI: 1.4-205.4), and compared with persons 5 drugs, persons >=42 years old who used >6 drugs were about 22 times as likely to have HCV infection (adjusted OR=21.8, 95%CI: 1.5-322.8). Conclusions: The subgroup of MSM >=42 years old with non-injection but multiple use of heroin, speedball, and methamphetamine, in addition to crack cocaine and marijuana, had high probability of HCV infection. Public health and education programs, as well as drug treatment and rehabilitation programs, should be developed for this high-risk subgroup to prevent HCV acquisition and transmission.

Evidence supporting specific therapies for late-life treatment-resistant depression (LL-TRD) is necessary. This study used Bayesian adaptive randomization to determine the optimal dose for the probability of treatment response (≥50% improvement from baseline on the Montgomery-Asberg Depression Rating Scale) 7 days after a 40 min intravenous (IV) infusion of ketamine 0.1 mg/kg (KET 0.1), 0.25 mg/kg (KET 0.25), or 0.5 mg/kg (KET 0.5), compared to midazolam 0.03 mg/kg (MID) as an active placebo. The goal of this study was to identify the best dose to carry forward into a larger clinical trial. Response durability at day 28, safety and tolerability, and effects on cortical excitation/inhibition (E/I) ratio using resting electroencephalography gamma and alpha power, were also determined. Thirty-three medication-free US military veterans (mean age 62; range: 55-72; 10 female) with LL-TRD were randomized double-blind. The trial was terminated when dose superiority was established. All interventions were safe and well-tolerated. Pre-specified decision rules terminated KET 0.1 (N = 4) and KET 0.25 (N = 5) for inferiority. Posterior probability was 0.89 that day-seven treatment response was superior for KET 0.5 (N = 11; response rate = 70%) compared to MID (N = 13; response rate = 46%). Persistent treatment response at day 28 was superior for KET 0.5 (response rate = 82%) compared to MID (response rate = 37%). KET 0.5 had high posterior probability of increased frontal gamma power (posterior probability = 0.99) and decreased posterior alpha power (0.89) during infusion, suggesting an acute increase in E/I ratio. These results suggest that 0.5 mg/kg is an effective initial IV ketamine dose in LL-TRD, although further studies in individuals older than 75 are required.

Research has indicated that mental health disorders, particularly anxiety, predicts poorer antiretroviral medication adherence among persons living with HIV/AIDS (PLWHA). The present study tests a novel six-session Cognitive-Behavioral Therapy-based integrated treatment/management program for PLWHA with concurrent anxiety delivered in community health clinics Houston, Texas. Twenty-Seven PLWHA (

Background: Good collateral flow has been shown to have better outcomes after acute ischemic stroke (AIS), including for patients receiving IV thrombolysis (IVT) and mechanical thrombectomy (MT). Hypothesis: In patients with AIS who undergo MT, good collateral flow is associated with better functional independence measure (FIM) change. Design/Methods: Data was collected retrospectively for patients who presented with AIS and were treated with MT. A total of 54 patients from 4 inpatient rehabilitation facility (IRF) locations between April 2017 and August 2019 were included. Collateral score was collected from angiograms and CT angiogram (CTA) in cases where an angiogram was not available. FIM change was defined as the difference in FIM at admission to IRF and discharge from IRF. Regression analyses were conducted to estimate the relationship between collateral score and FIM change. The predictors in the model included collateral score, FIM at admission to IRF, age at onset, and gender. Logistic regression was used for categorical variables and linear regression was applied for continuous variables. Statistical significance level was set at 0.05. Collaterals were scored from 0 to 4, with 0 to 2 being poor and good collateral flow defined as scores 3 and 4. The primary outcome of this study was FIM change. Results: The mean age was 70.4 years, and 54.5% was female. Regression analyses did not show any significant differences in FIM change in patients with collaterals ranging from poor to good p = 0.807 (Table 1), when adjusted for age, gender, and severity as represented by FIM at admission to IRF. Conclusion: In this patient cohort, good collateral flow was not associated with improvement in FIM change.

Introduction: We sought to predict the course and rate of functional improvement and length of stay (LOS) in patients with ischemic and hemorrhagic strokes admitted to inpatient rehabilitation facilities(IRF). Aim: To study the course and associating factors affecting functional outcomes among a large cohort of stroke patients admitted to IRFs. Methods: The cohort consists of stroke patients admitted to 5 IRFs in Houston, between 4/17-8/19. Higher order polynomial (quartic, cubic, quadratic) regressions were fitted to predict the temporal relationship between FIM score improvement and LOS, and based on goodness of fit statistics, cubic polynomial fit was selected. Effects of interactions were tested and later dropped from the final model because of non-statistical significance. Models were adjusted for age, gender, stroke type (hemorrhagic vs ischemic), and stroke severity based on NIHSS. Results: The demographics of patients are presented in table 1. Among 679 patients, the univariate analyses reflected that age (F=24.2, p p p Conclusion: Patient’s age, ischemic vs hemorrhagic stroke were the most significant predictors when deriving the relationship between total FIM score and LOS while adjusting for stroke severity and patient’s gender, which plateaued after 2 weeks of IRF stay.

Introduction: We asked whether intracerebral hemorrhage (ICH) patients admitted to inpatient rehabilitation facilities(IRF) improve differently based on their involvement of the corticospinal tract(CST). Aim: To predict associating radiological factors affecting discharge FIM score. Methods: We reviewed the patients’ characteristics and their respective imaging findings presenting with ICH between 4/17 to 8/19. The ICH volume and edema around the ICH were measured using analyze software. The main outcome measure was FIM score at time of discharge. Statistical significance was set at 0.05. Results: Among the 53 patients included, 49% were female. The median age of the patients was 62 years (IQR 25,89). The median length of stay at IRF was 22days (IQR 14,26). In univariate analysis, FIM score at the time of discharge FIM score at the time of discharge admission were significantly associated with NIHSS (estimate -1.26, pp = 0.008), gender ( p p p =0.02). Conclusion: This preliminary study suggests that functional improvement declines in ICH patients with CST involvement.

Introduction Thirdhand smoke (THS) is ultrafine particulate matter and residue resulting from tobacco combustion, with implications for health-related harm (eg, impaired wound healing), particularly among hospitalized infants. Project aims were to characterize nicotine (THS proxy) transported on neonatal intensive care unit (NICU) visitors and deposited on bedside furniture, as well as infant exposure. Methods Cross-sectional data were collected from participants in a metropolitan NICU. Participants completed a survey and carbon monoxide breath sample, and 41.9% (n = 88) of participants (n = 210) were randomly selected for finger-nicotine wipes during a study phase when all bedside visitors were screened for nicotine use and finger-nicotine levels. During an overlapping study phase, 80 mother–infant dyads consented to bedside furniture-nicotine wipes and an infant urine sample (for cotinine analyses). Results Most nonstaff visitors’ fingers had nicotine above the limit of quantification (>LOQ; 61.9%). Almost all bedside furniture surfaces (93.8%) and infant cotinine measures (93.6%) had values >LOQ, regardless of household nicotine use. Participants who reported using (or lived with others who used) nicotine had greater furniture-nicotine contamination (Mdn = 0.6 [interquartile range, IQR = 0.2–1.6] µg/m2) and higher infant cotinine (Mdn = 0.09 [IQR = 0.04–0.25] ng/mL) compared to participants who reported no household-member nicotine use (Mdn = 0.5 [IQR = 0.2–0.7] µg/m2; Mdn = 0.04 [IQR = 0.03–0.07] ng/mL, respectively). Bayesian univariate regressions supported hypotheses that increased nicotine use/exposure correlated with greater nicotine contamination (on fingers/furniture) and infant THS exposure. Conclusions Potential furniture-contamination pathways and infant-exposure routes (eg, dermal) during NICU hospitalization were identified, despite hospital prohibitions on tobacco/nicotine use. This work highlights the surreptitious spread of nicotine and potential THS-related health risks to vulnerable infants during critical stages of development. Implications THS contamination is underexplored in medical settings. Infants who were cared for in the NICU are vulnerable to health risks from THS exposure. This study demonstrated that 62% of nonstaff NICU visitors transport nicotine on their fingers to the NICU. Over 90% of NICU (bedside) furniture was contaminated with nicotine, regardless of visitors’ reported household-member nicotine use or nonuse. Over 90% of infants had detectable levels of urinary cotinine during NICU hospitalizations. Results justify further research to better protect infants from unintended THS exposure while hospitalized.

Background Posttraumatic stress disorder (PTSD) is associated with hyperarousal and stress reactivity, features consistent with behavioral sensitization. In this Phase 1b, parallel-arm, randomized, double-blind, placebo-controlled trial, we tested whether the selective low-trapping N-methyl-D-aspartate receptor (NMDAR) antagonist [Lanicemine (BHV-5500)] blocks expression of behavioral sensitization. Methods Twenty-four participants with elevated anxiety potentiated startle (APS) and moderate-to-severe PTSD symptoms received three infusions of lanicemine 1.0 mg/ml (100 mg) or matching placebo (0.9% saline) (1:1 ratio), over a 5-day period. The primary outcome was change in APS from baseline to end of third infusion. We also examined changes in EEG gamma-band oscillatory activity as measures of NMDAR target engagement and explored Clinician-Administered PTSD Scale (CAPS-5) hyperarousal scores. Results Lanicemine was safe and well-tolerated with no serious adverse events. Using Bayesian statistical inference, the posterior probability that lanicemine outperformed placebo on APS T-score after three infusions was 38%. However, after the first infusion, there was a 90% chance that lanicemine outperformed placebo in attenuating APS T-score by a standardized effect size more than 0.4. Conclusion We demonstrated successful occupancy of lanicemine on NMDAR using gamma-band EEG and effects on hyperarousal symptoms (Cohen's d = 0.75). While lanicemine strongly attenuated APS following a single infusion, differential changes from placebo after three infusions was likely obscured by habituation effects. To our knowledge, this is the first use of APS in the context of an experimental medicine trial of a NMDAR antagonist in PTSD. These findings support selective NMDAR antagonism as a viable pharmacological strategy for salient aspects of PTSD.

An effective strategy to manage acute pain and minimize opioid exposure is needed for injured patients. In this trial, we aimed to compare 2 multimodal pain regimens (MMPRs) for minimizing opioid exposure and relieving acute pain in a busy, urban trauma center.This was an unblinded, pragmatic, randomized, comparative effectiveness trial of all adult trauma admissions except vulnerable patient populations and readmissions. The original MMPR (IV administration, followed by oral, acetaminophen, 48 hours of celecoxib and pregabalin, followed by naproxen and gabapentin, scheduled tramadol, and as-needed oxycodone) was compared with an MMPR of generic medications, termed the Multi-Modal Analgesic Strategies for Trauma (MAST) MMPR (ie oral acetaminophen, naproxen, gabapentin, lidocaine patches, and as-needed opioids). The primary endpoint was oral morphine milligram equivalents (MMEs) per day and secondary outcomes included total MMEs during hospitalization, opioid prescribing at discharge, and pain scores.During the trial, 1,561 patients were randomized, 787 to receive the original MMPR and 774 to receive the MAST MMPR. There were no differences in demographic characteristics, injury characteristics, or operations performed. Patients randomized to receive the MAST MMPR had lower MMEs per day (34 MMEs/d; interquartile range 15 to 61 MMEs/d vs 48 MMEs/d; interquartile range 22 to 74 MMEs/d; p0.001) and fewer were prescribed opioids at discharge (62% vs 67%; p = 0.029; relative risk 0.92; 95% credible interval, 0.86 to 0.99; posterior probability relative risk1 = 0.99). No clinically significant difference in pain scores were seen.The MAST MMPR was a generalizable and widely available approach that reduced opioid exposure after trauma and achieved adequate acute pain control.

Neonatal ICU (NICU) hospitalizations provide opportunities to engage individuals/families who smoke with evidence-based cessation treatments to protect infants from tobacco smoke exposure. The aim of this pilot study was to establish the feasibility and potential efficacy of providing motivational advice and NRT (MA+NRT) to families of NICU infants. RCT methodology equally allocated participants who reported ≥1 household smoker (N=32) from a large NICU to MA+NRT or referral to a Quitline. The primary outcome was accepting NRT patches (MA+NRT) and use of NRT. Bayesian analyses modeled NRT use as a function of treatment group. Most MA+NRT participants (81.3%; n=13) accepted the patches. No Quitline participants called the Quitline. NRT use differed across groups, indicating a 0.907 posterior probability that a positive effect for MA+NRT exists (RR=2.32, 95% CI=[0.68-11.34]). This study demonstrated feasibility and acceptability for offering NRT and motivational advice to NICU parents and supports further intervention refinement with NICU families.

Opioid misuse and opioid-related death are a growing public health concern. One population of interest is recent trauma and/or surgery patients, who are at increased risk of developing an opioid use disorder (OUD). Although a variety of assessments have been developed to screen for risk of opioid misuse, each has limitations and prediction needs improvement. One promising measure is drug demand, a behavioral economic measure assessing drug consumption at different price points. In the current proposal, we assessed the utility of a brief assessment of opioid demand. Demand and various pain-related self-report measures among trauma-surgery patients (N = 103) were assessed at 4 weeks post-discharge. Opioid demand was significantly associated with self-report measures of pain and amount of morphine milligram equivalents (MME) received during the hospital stay. The current result support the utility of the opioid demand as an adjunctive and complementary measure to assess risk of opioid misuse. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Senior financial exploitation (FE) is prevalent and harmful. Its often insidious nature and co-occurrence with other forms of mistreatment make detection and substantiation challenging. A secondary data analysis of N = 8,800 Adult Protective Services substantiated senior mistreatment cases, using machine learning algorithms, was conducted to determine when pure FE versus hybrid FE was occurring. FE represented N = 2514 (29%) of the cases with 78% being pure FE. Victim suicidal ideation and threatening behaviors, injuries, drug paraphernalia, contentious relationships, caregiver stress, and burnout and victims needing assistance were most important for differentiating FE vs non-FE-related mistreatment. The inability to afford housing, medications, food, and medical care as well as victims suffering from intellectual disability disorder(s) predicted hybrid FE. This study distinguishes socioecological factors strongly associated with the presence of FE during protective service investigations. These findings support existing and new indicators of FE and could inform protective service investigation practices.

Importance The Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NRN) extremely preterm birth outcome model is widely used for prognostication by practitioners caring for families expecting extremely preterm birth. The model provides information on mean outcomes from 1998 to 2003 and does not account for substantial variation in outcomes among US hospitals. Objective To update and validate the NRN extremely preterm birth outcome model for most extremely preterm infants in the United States. Design, Setting, and Participants This prognostic study included 3 observational cohorts from January 1, 2006, to December 31, 2016, at 19 US centers in the NRN (derivation cohort) and 637 US centers in Vermont Oxford Network (VON) (validation cohorts). Actively treated infants born at 22 weeks’ 0 days’ to 25 weeks’ 6 days’ gestation and weighing 401 to 1000 g, including 4176 in the NRN for 2006 to 2012, 45 179 in VON for 2006 to 2012, and 25 969 in VON for 2013 to 2016, were studied. VON cohorts comprised more than 85% of eligible US births. Data analysis was performed from May 1, 2017, to March 31, 2019. Exposures Predictive variables used in the original model, including infant sex, birth weight, plurality, gestational age at birth, and exposure to antenatal corticosteroids. Main Outcomes and Measures The main outcome was death before discharge. Secondary outcomes included neurodevelopmental impairment at 18 to 26 months’ corrected age and measures of hospital resource use (days of hospitalization and ventilator use). Results Among 4176 actively treated infants in the NRN cohort (48% female; mean [SD] gestational age, 24.2 [0.8] weeks), survival was 63% vs 62% among 3702 infants in the era of the original model (47% female; mean [SD] gestational age, 24.2 [0.8] weeks). In the concurrent (2006-2012) VON cohort, survival was 66% among 45 179 actively treated infants (47% female; mean [SD] gestational age, 24.1 [0.8] weeks) and 70% among 25 969 infants from 2013 to 2016 (48% female; mean [SD] gestational age, 24.1 [0.8] weeks). Model C statistics were 0.74 in the 2006-2012 validation cohort and 0.73 in the 2013-2016 validation cohort. With the use of decision curve analysis to compare the model with a gestational age–only approach to prognostication, the updated model showed a predictive advantage. The birth hospital contributed equally as much to prediction of survival as gestational age (20%) but less than the other factors combined (60%). Conclusions and Relevance An updated model using well-known factors to predict survival for extremely preterm infants performed moderately well when applied to large US cohorts. Because survival rates change over time, the model requires periodic updating. The hospital of birth contributed substantially to outcome prediction.

OBJECTIVE, To assess whether an asthma intervention program reduces treatment days outside the home among children with severe asthma receiving comprehensive care (CC) in our center. METHODS, Between October 21, 2014 and September 28, 2016, children with severe asthma were randomized to receive CC alone (n=29) or CC plus the asthma intervention program (n=34) which involved collaboration with pharmacists and school nurses, motivational interviewing, and tracking the one-second forced expiratory volume at home. All patients were followed through March 31, 2017. Frequentist and Bayesian intent-to-treat analyses were performed. RESULTS, The asthma intervention program doubled the telephone calls between the staff and families (753 vs 356 per 100 child years for the intervention group vs. control group; Rate Ratio [RR], 2.11 [95% confidence interval, 1.29–3.45]). Yet, we found no evidence that it reduced the composite number of days of healthcare outside home which includes, clinic visits, ED visits, and hospital admissions (1179 vs 958 per 100 child-years in the intervention group vs. control group; [RR], 1.23 [95% CI, 0.82–1.84]) or secondary outcomes which are individual components (clinic visits, ED visits, hospitalizations, PICU admissions and school absences; RR 1.15 – 2.30; p>0.05). Bayesian analysis indicated a 67% probability that the intervention program increases total treatment days outside the home and only a 14% probability of a true decrease of >20% as originally hypothesized. CONCLUSION, A multi-component intervention program provided to children with severe asthma failed to reduce and may have increased days of healthcare outside home and school absenteeism.

Objective: Substance use disorders and posttraumatic stress symptoms are commonly comorbid. Previous studies have established that those with substance use disorders or posttraumatic stress disorder (PTSD) have lower high frequency-heart rate variability (HF-HRV) compared to controls, suggesting that low HF-HRV may be a biomarker of a common physiological mechanism underlying both disorders. We evaluated HF-HRV as a potential biomarker of a common underlying process by testing whether lower HF-HRV related to greater severity of substance use and PTSD symptoms in individuals with both substance use disorders and at least four symptoms of PTSD. Methods: HF-HRV was measured in 49 adults with substance use disorders and at least four symptoms of PTSD. We performed a series of regressions controlling for age to test whether low HF-HRV was associated with greater substance use disorder and PTSD symptom severity. Substance use disorder symptoms were measured by the Addiction Severity Index and PTSD symptoms were measured by the Clinician-Administered PTSD Scale and the PTSD Checklist. Results: After controlling for age, low resting HF-HRV was significantly associated with drug and alcohol symptom severity but not PTSD symptom severity. Conclusions: HF-HRV may be more sensitive to the severity of drug and alcohol use rather than PTSD. Findings may suggest that in PTSD populations, HF-HRV may primarily index comorbid substance use disorder symptoms. HF-HRV could serve as an objective measure of substance use severity and should be further investigated as a predictor of outcomes in treatment for substance use disorders.

Background Machine-learning can elucidate complex relationships/provide insight to important variables for large datasets. This study aimed to develop an accurate model to predict neonatal surgical site infections (SSI) using different statistical methods. Methods The 2012–2015 National Surgical Quality Improvement Program-Pediatric for neonates was utilized for development and validations models. The primary outcome was any SSI. Models included different algorithms: full multiple logistic regression (LR), a priori clinical LR, random forest classification (RFC), and a hybrid model (combination of clinical knowledge and significant variables from RF) to maximize predictive power. Results 16,842 patients (median age 18 days, IQR 3–58) were included. 542 SSIs (4%) were identified. Agreement was observed for multiple covariates among significant variables between models. Area under the curve for each model was similar (full model 0.65, clinical model 0.67, RF 0.68, hybrid LR 0.67); however, the hybrid model utilized the fewest variables (18). Conclusions The hybrid model had similar predictability as other models with fewer and more clinically relevant variables. Machine-learning algorithms can identify important novel characteristics, which enhance clinical prediction models.

Background and aims Despite the availability of several efficacious smoking cessation treatments, fewer than 25% of smokers who quit remain abstinent 1 year post-treatment. This study aimed to determine if varenicline and bupropion combination treatment would result in higher abstinence rates than varenicline alone. Design A double-blind, randomized, parallel-group smoking cessation clinical trial in which participants were exposed to 12 weeks of treatment and followed for 12 months. Setting Hospital-based out-patient clinic in Texas, USA specializing in cancer prevention. Participants A total of 385 community smokers (58.44% male) who smoked 1 pack of cigarettes/day [mean = 19.66 cigarettes/day, standard deviation (SD) = 9.45]; had average carbon monoxide (CO) of 26.43 parts per million (SD = 13.74); and were moderately dependent (Fagerstrom Test for Cigarette Dependence = 4.79; SD = 2.07). Interventions and comparator Smokers were randomized in a 3 : 1 (active: Placebo) ratio to 12 weeks of treatment as follows: placebo (n = 56), varenicline (Var; n = 166), and varenicline + bupropion (Combo; n = 163). Measurements A priori primary outcome: prolonged abstinence at 12 months. Secondary outcomes 7-day point prevalence abstinence and continuous abstinence; all abstinence measures at end of treatment and 6-month follow-ups. Findings Intention-to-treat analysis: the Combo group (n = 163) failed to demonstrate superiority to the Var group (n = 166) for prolonged abstinence at 12 months [odds ratio (OR) = 0.91, 95% confidence interval (CI) = 0.50-1.64], supported by Bayes factor = 0.06. Both the Var (OR = 6.66, 95% CI = 1.61-59.27) and Combo groups (OR = 6.06, 95% CI = 1.45-54.09) demonstrated superiority to the Placebo group (n = 56; score = 8.38, P Conclusions The addition of bupropion to varenicline treatment does not appear to increase smoking abstinence rates above that of varenicline alone. The findings support previous research showing a consistently favorable effect of both varenicline and the combination of varenicline and bupropion on smoking cessation compared with placebo.

Posttraumatic stress disorder (PTSD) and substance use disorders (SUD) are complex psychiatric conditions that commonly co-occur. No evidence-based, ‘gold standard’ treatments for PTSD/SUD comorbidity are currently available. The present pilot randomized clinical trial was designed to evaluate the feasibility and preliminary efficacy of a novel, integrated cognitive-behavioral treatment approach for PTSD/SUD, entitled Treatment of Integrated Posttraumatic Stress and Substance Use (TIPSS), as compared to standard cognitive-behavioral treatment (CBT) for SUD. The TIPSS program integrates cognitive processing therapy with CBT for SUD for the treatment of co-occurring PTSD/SUD. Both treatment conditions are comprised of 12, 60-minute individual psychotherapy sessions, delivered twice-weekly over six weeks. Primary aims examine whether TIPSS, compared to standard CBT for SUD, reduces: (1) PTSD symptoms and (2) substance use outcomes (i.e., self-report, objective). Secondary aims examine whether (a) trauma- and substance cue reactivity and (b) distress tolerance (i.e., actual or perceived ability to withstand uncomfortable emotional or physical states) are significant mechanisms of change. The study was recently closed to new enrollment. Participants included adults with substance dependence and at least four symptoms of PTSD.

Drug addiction is a chronic, devastating, but treatable disorder. A core principle of drug addiction treatment states that no single treatment is appropriate for everyone (NIDA, 2012); treatments need to adjust based on patient characteristics and response in order to be maximally effective. For cocaine use disorders (CUD), specifically, the most potent intervention currently available for initiating abstinence is behavior therapy using contingency management (CM) procedures, with early cessation being a robust predictor of future abstinence. This raises two key questions for treatment development research: First, can we significantly improve initial CM response rates with targeted adjunctive interventions? Second, for individuals who fail to achieve initial abstinence with CM, is pharmacotherapy an effective augmentation strategy? This paper describes how a sequential, multiple assignment, randomized trial (SMART) design has advantages over a fixed-intervention approach when it comes to collecting data needed to answer both questions. The first aim will examine whether Acceptance and Commitment Therapy (ACT) in combination with CM increases initial abstinence response rates (i.e., 2 consecutive weeks of cocaine-negative urine screens). The second aim will examine whether ACT+CM in combination with modafinil promotes abstinence achievement in initial non-responders. Results are expected to inform how we tailor treatment of CUD to maximize outcomes.

Cocaine use continues to be a significant public health problem with limited treatment options and no approved pharmacotherapies. Cognitive-behavioral therapy (CBT) remains the mainstay treatment for preventing relapse, however, people with chronic cocaine use display cognitive impairments that are associated with poor response to CBT. Emerging evidence in animal and human studies suggests that the peroxisome proliferator-activated receptor-gamma (PPAR- γ) agonist, pioglitazone, improves white matter integrity that is essential for cognitive function. This project will determine whether adjunctive use of pioglitazone enhances the effect of CBT in preventing relapse during the early phase of recovery from cocaine use disorder. This paper describes the design of a mechanism-focused phase 2 randomized clinical trial that aims first to evaluate the effects of pioglitazone on targeted mechanisms related to white matter integrity, cognitive function, and cocaine craving; and second, to evaluate the extent to which improvements on target mechanisms predict CBT response. Positive results will support pioglitazone as a potential cognitive enhancing agent to advance to later stage medication development research.

Introduction Varenicline and bupropion are two effective smoking cessation pharmacotherapies. Researchers have hypothesized that they might be effective, in part, because they reduce cue reactivity and cue-induced cravings. Here, we used event-related potentials (ERPs) to directly measure brain responses to cigarette-related and other motivationally relevant images during a pharmacologically aided quit attempt. Methods Smokers involved in a 12-week placebo-controlled double-blind clinical trial of smoking cessation medications (varenicline, bupropion, placebo) took part in the study. We assessed participants at two time points: 24 h (n = 140) and 4 weeks (n = 176) after the quit date. At both sessions, we measured the amplitude of the late positive potential (LPP), an ERP component reliably associated with motivational relevance, and self-reported tonic craving using the brief version of the Questionnaire of Smoking Urges (QSU-Brief). Results At both sessions, emotional and cigarette-related images evoked significantly larger LPPs than neutral images. Neither drug type nor smoking abstinence altered this effect at either session. At both sessions, varenicline and bupropion significantly reduced self-reported tonic craving relative to the placebo condition. Conclusions While both varenicline and bupropion reduced self-reported tonic craving, neither medication altered the amplitude of the LPP to cigarette-related or emotional pictures in smokers attempting to quit. These medications may influence abstinence by means other than by reducing neuroaffective responses to cigarette-related cues. Smokers should be prepared for the likelihood that even after several weeks of successful abstinence, once treatment ends, cigarette-related cues may remain motivationally relevant and trigger cravings that might lead to relapse. Implications Bupropion and varenicline do not alter electrophysiological responses, as measured by the LPP, to cigarette-related and emotional images. These findings help explain why cigarette-related cues can trigger relapse when smoking cessation medication treatments end.

Introduction Traditionally, opioids have been the mainstay of treatment for background, breakthrough, procedural, and postoperative pain after burns. However, in addition to an impetus to reduce provider-driven opioid exposure, there is increasing evidence that opioids can worsen acute pain through induction of hyperalgesia. In 2019, we implemented a pill-based, opioid-minimizing pain protocol and protocolized moderate sedation for dressing changes. We hypothesized that these protocols would reduce inpatient opioid exposure without increasing acute pain scores. Methods Two groups of consecutive patients admitted to the burn service were compared: Pre (01/2018 to 07/2019) and Post (01/2020 to 06/2020) implementation of the protocols (08/2019 to 12/2019). Patient demographics, burn characteristics, and lengths of stay were abstracted from the burn registry. Opioid exposure and pain scale scores were obtained from the electronic medical record. The primary outcome was total morphine milligram equivalents (MME). Secondary outcomes included MME/day, pain domain specific MME, pain scores, and lengths of stay. Pain was estimated by creating a normalized pain score (range 0–1) from three different pain scales (Numeric Rating Scale, Behavioral Pain Scale, and Behavioral Pain Assessment Scale). Groups were compared using Wilcoxon Rank Sum and Chi Square. Treatment effect was estimated using Bayesian generalized linear models. Results There were no differences in demographics or burn characteristics between the Pre (n=495) and Post groups (n=174), including TBSA burn (Pre 4% [2, 10] versus Post 5% [2, 10], p=0.898). The Post group had significantly lower total MME (IRR 0.72, 95% CrI 0.57–0.93, posterior probability 99%), MME/day (IRR 0.76, 95% CrI 0.65–0.90, posterior probability 99%), and domain-specific total MME (Table). No difference in average normalized pain scores was seen. The Pre group were hospitalized longer than the Post group (5 days [2, 14] versus 4 days [1, 9], p=0.012). Conclusions Implementation of opioid-minimizing protocols for acute burn pain were associated with a significant reduction in inpatient opioid exposure without increased pain scores. More information is needed to understand the association with reduced hospital days.

Background Medication development research for cocaine use disorder (CUD) has been a longstanding goal in addiction research, but has not resulted in an FDA-approved treatment. Rising cocaine use rates underscore the need for efficient adaptive designs. This study compared differences between two doses of the selective serotonin reuptake inhibitor (SSRI) citalopram (versus placebo) on duration of cocaine abstinence and applied adaptive decision rules to select the ‘best efficacy’ dose. Methods A double-blind, placebo-controlled, randomized Bayesian drop-the-loser (DTL) trial with three arms compared placebo to citalopram 20 mg and 40 mg. Adults (N = 107) with CUD attended thrice-weekly clinic visits for 9 weeks. The primary outcome was longest duration of abstinence (LDA), based on continuous cocaine-negative urine drug screens (UDS). The secondary outcome was probability of cocaine-negative UDS during treatment. A planned interim analysis performed at approximately 50% of recruitment dropped the least-effective active medication. Bayesian inference was used for all analyses with a pre-specified posterior probability (PP) threshold PP ≥ 95% considered statistically reliable evidence Results Citalopram 40 mg satisfied interim efficacy criteria and was retained for the second half of the trial. For LDA, analyses indicated PP = 82% and PP = 65% of benefit for 40 mg and 20 mg, respectively (each relative to placebo). The odds of having cocaine-negative UDS decreased in all groups over 9 weeks but remained higher for 40 mg (PP = 97.4%) Conclusions Neither dose met the 95% PP threshold for the primary outcome; however, 40 mg provided moderate-to-strong evidence for positive effects on LDA and cocaine-negative UDS. The 40 mg dose was declared the “winner” in this DTL trial.

OBJECTIVE: To evaluate the effects of early treatment with CPAP on nutritional intake and in-hospital growth rates of extremely preterm (EPT) infants. STUDY DESIGN: EPT infants (24–0/7 to 27–6/7 weeks of gestation) enrolled in the Surfactant Positive Airway Pressure and Pulse Oximetry Trial (SUPPORT) were included. EPT infants who died before 36 weeks’ postmenstrual age (PMA) were excluded. The growth rates from birth to 36 weeks’ PMA and follow-up outcomes at 18–22 months’ corrected age of EPT infants randomized at birth to either early CPAP (intervention group) or early intubation for surfactant administration (control group) were analyzed. RESULTS: 810 of 1316 infants enrolled in SUPPORT (414 in intervention group, 396 in control group) had growth data analyzed. Median gestational age was 26 weeks and mean birthweight was 839 grams. Baseline characteristics, total nutritional intake, and in-hospital comorbidities were not significantly different between groups. In a regression model, growth rates between birth and 36 weeks’ PMA as well as growth rates during multiple intervals from birth to day 7, day 7 to14, day 14 to 21, day 21 to 28, day 28 to 32 weeks’ PMA, and 32 weeks’ PMA to 36 weeks’ PMA did not differ between treatment groups. Independent of treatment group, higher growth rates from day 21 to day 28 were associated with a lower risk of Bayley III cognitive score

Background Chronic cocaine users show impairments in cognitive processes associated with dopamine (DA) circuitry. Medications aimed at bolstering cognitive functions via DA modulation might enhance treatment outcome. Methods The trial used a double-blind, double-dummy, parallel-group design with four treatment arms comparing placebo (PLC) to levodopa/carbidopa 800 mg/200 mg alone (LR0), levodopa plus extended release (XR) ropinirole 2 mg (LR2) or XR ropinirole 4 mg (LR4). Adults (n = 110) with cocaine use disorder attended thrice weekly clinic visits for 10 weeks. Potential cognitive mediators assessed at week 5 consisted of measures of decision-making (Iowa Gambling Task, Risky Decision-Making Task), attention/impulsivity (Immediate Memory Task), motivation (Progressive Ratio task), and cognitive control (Cocaine Stoop task). The primary outcome measure was the treatment effectiveness score (TES) calculated as the number of cocaine-negative urines collected from weeks 6–10. Results Bayesian mediation examined indirect and total effects of the relationships between each active treatment (compared to PLC) and TES. Total (direct) effects were supported for LR0 and LR2, but not for LR4. Indirect effects were tested for each mediator. Notably, 22.3 % and 35.4 % of the total effects of LR0 and LR2 on TES were mediated by changes in attention/impulsivity. Conclusions The hypothesized mediation effect was strongest for levodopa plus 2 mg ropinirole, indicating that this DA medication combination predicted change (improvement) in attention/impulsivity, which in turn predicted change (reduction) in cocaine use. This finding provides modest support for cognitive enhancement as a target for medications to treat cocaine use disorder.