Smoking Cessation After Initial Treatment Failure With Varenicline or Nicotine Replacement: A Randomized Clinical Trial.

Importance: Most people who smoke do not quit on their initial attempt. Objective: To determine the best subsequent strategy for nonabstinence following initial treatment with varenicline or combined nicotine replacement therapy (CNRT). Design, Setting, and Participants: Using a double-blind, placebo-controlled, sequential multiple assignment randomized trial, 490 volunteers were randomized to receive 6 weeks of varenicline or CNRT. After 6 weeks, nonabstainers were rerandomized to continue, switch, or increase medication dosage for 6 additional weeks. The study was conducted from June 2015 through October 2019 in a Texas tobacco treatment clinic. Interventions: The initial treatment was 2 mg/d of varenicline or the combined replacement therapy of a 21-mg patch plus 2-mg lozenge. The rerandomized participants either continued with their initial therapies, switched between varenicline and CNRT, or increased dosages either to 3-mg or more of varenicline or to a 42-mg patch and lozenges. All received weekly brief counseling. Main Outcomes and Measures: Biochemically verified 7-day point prevalence abstinence at the end of treatment at 12 weeks. Results: The 490 randomized participants (210 female [43%], 287 non-Hispanic White [58%], mean age, 48.1 years) smoked an average of 20 cigarettes per day. After the first phase, 54 participants in the CNRT group were abstinent and continued their therapy; of the 191 who were not abstinent, 151 were rerandomized, and the 40 who did not return for rerandomization were assigned to continue their initial CNRT condition in phase 2. The end-of-treatment abstinence rate for the 191 phase 1 nonabstainers was 8% (95% credible interval [CrI], 6% to 10%) for the 90 (47%) who continued at the dosage condition, 14% (CrI, 10% to 18%) for the 50 (33%) who increased their dosage, and 14% (95% CrI, 10% to 18%) for the 51 (34%) who switched to varenicline (absolute risk difference [RD], 6%; 95% CrI, 6% to 11%) with more than 99% posterior probability that either strategy conferred benefit over continuing the initial dosage. After the first phase, 88 participants in the varenicline group were abstinent and continued their therapy; of the 157 who were not abstinent, 122 were rerandomized and 35 who did not return for rerandomization were assigned to continue with the varenicline condition. The end-of-treatment abstinence rate for the 157 phase 1 nonabstainers was 20% (95% CrI, 16% to 26%) for the 39 (32%) who increased their varenicline dosage, 0 (95% CrI, 0 to 0) for the 41 (34%) who switched CNRT, and 3% (95% CrI, 1% to 4%) for the 77 (49%) who were assigned to the continued varenicline condition (absolute RD, -3%; 95% CrI, -4% to -1%) with more than 99% posterior probability that continuing varenicline at the initial dosage was worse than switching to a higher dosage. Furthermore, increasing the varenicline dosage had an absolute RD of 18% (95% CrI, 13% to 24%) and a more than 99% posterior probability of conferring benefit. The secondary outcome of continuous abstinence at 6 months indicated that only increased dosages of the CNRT and varenicline provided benefit over continuation of the initial treatment dosages. Conclusions and Relevance: For individuals who smoked but did not achieve abstinence after treatment with varenicline, increasing the dosage enhanced abstinence vs continuing, whereas for nonabstainers initially treated with CNRT, a dosage increase or switch to varenicline enhanced abstinence and may be viable rescue strategies. Trial Registration: ClinicalTrials.gov Identifier: NCT02271919.

Bayesian regularization to predict neuropsychiatric adverse events in smoking cessation with pharmacotherapy.

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 < 1) = 0.94). Odds of NAEs were comparable across treatment groups. The final model did not perform well in the test set. 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.

A retrospective examination of pain in acute stroke at hospital discharge.

OBJECTIVES: Pain is an overlooked sequela of stroke. Persistent pain after stroke is an underrecognized experience and significantly impacts survivors' function, ability to participate in rehabilitation, and quality of life. The aim of this retrospective, observational study is to examine the incidence of pain at the acute hospitalization period immediately after stroke, to identify the characteristics of those reporting pain at discharge, and to compare pain reporting between stroke and non-stroke hospital controls. MATERIALS AND METHODS: Using discharge diagnosis, this retrospective review examined self- reports of pain during acute hospitalization for stroke compared to those with COPD (control group) admitted during the same time in the same facilities. Variables of interest included age, gender, body mass index (BMI), length of stay, pain assessment score (numeric rating scale [NRS], behavior pain scale [BPS], and medication administration record pain score total [MAR]), smoking history, prevalence of hypertension and race. 821 subjects were included from a total of three campuses from one large hospital system. 772 subjects were included in the comparative analysis with COPD patients from the same facilities during the same time. RESULTS: 43% of patients diagnosed with stroke reported pain at discharge. For stroke survivors reporting pain at discharge, the average BMI was higher (p=0.009), average arrival NIHSS was higher (p=0.044), and mean hospital length of stay was longer (p<0.001). CONCLUSIONS: The evidence demonstrated in this study highlights the critical need for the implementation of targeted objective pain assessment and effective pain interventions for stroke survivors beginning at initial hospitalization.

The effects of varenicline, bupropion, nicotine patch, and placebo on smoking cessation among smokers with major depression: A randomized clinical trial.

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 a 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: Twelve 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: A total of 6653 participants (56% female; 39% MDD) ~47 years old. Risk of NPSAEs did not differ by medication for MDD. MDD had higher risk (p < .0001) for NPSAEs than the NPC. Efficacy (6653; intent-to-treat): CA rates for MDD versus NPC respectively were 31.2% versus 38.0% VAR; 23.0% versus 26.1% BUP; 22.6% versus 26.4% NRT; and 13.4% versus 13.7% PLA but no differential treatment effect was noted within the cohorts. All active treatments differed from PLA but VAR showed the largest effect. CONCLUSIONS: Results suggest that for MDD smokers, inclusive of those with recurrent episode, varenicline plus counseling may be the best pharmacological option for the treatment of smoking given its greater efficacy effect size and similar risk of NPSAEs. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01456936. https://clinicaltrials.gov/ct2/show/NCT01456936.

Treatment of Acute Pain in Adults With Sickle Cell Disease in an Infusion Center Versus the Emergency Department : A Multicenter Prospective Cohort Study.

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.

Handwashing Results in Incomplete Nicotine Removal from Fingers of Individuals who Smoke: A Randomized Controlled Experiment.

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: · NICU infants may be exposed to THS via visitors.. · THS is not eliminated by HW or sanitizing.. · THS removal protections for NICU infants are needed..

Distress tolerance: prospective associations with cognitive-behavioral therapy outcomes in adults with posttraumatic stress and substance use disorders.

74Distress tolerance (DT; perceived or actual ability to tolerate aversive physical or emotional states) is related to both posttraumatic stress disorder (PTSD) symptoms and substance use disorders (SUD). This investigation evaluates self-report and behavioral measures of DT as potential predictors of PTSD and SUD cognitive-behavioral therapy outcomes. Participants included 41 treatment-seeking adults (53.7% women; 73.2% African American; Mage = 44.90, SD = 9.68) who met at least four symptoms of DSM-5 PTSD and DSM-IV substance dependence, assessed via structured interviews. At baseline (pre-treatment), participants completed the Distress Tolerance Scale (DTS), Mirror-Tracing Persistence Task (MTPT), Breath Holding task, and Paced Auditory Serial Addition Task. The Clinician-Administered PTSD Scale for DSM-5 severity scores and percent days of primary substance use, measured via Timeline Follow-back, were used as indicators of PTSD symptoms and substance use, respectively. Covariates included treatment condition, baseline PTSD symptom severity, and baseline substance use. Lower perceived DT at baseline (DTS total score) was associated with higher PTSD symptom severity at end-of-treatment. Lower behavioral DT at baseline (MTPT duration) was associated with higher substance use at the conclusion of treatment (i.e. proportion of number of use days to total number of days between two final treatment sessions).

Allogeneic Bone Marrow-Derived Mesenchymal Stem Cell Safety in Idiopathic Parkinson's Disease.

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 < 0.05), chemokine (C-C motif) ligand 22 (P < 0.05), whereas brain-derived neurotrophic factor (P < 0.05) increased. The highest dose seems to have demonstrated the most significant effect at 52 weeks, reducing the OFF state UPDRS motor, -14.4 (P < 0.01), and total, -20.8 (P < 0.05), scores. CONCLUSION: A single intravenous infusion of allogeneic bone marrow-derived mesenchymal stem cells at doses of 1, 3, 6, or 10 × 106 allogeneic bone marrow-derived mesenchymal stem cells/kg is safe, well tolerated, and not immunogenic in mild/moderate PD patients. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Duration of breastmilk feeding of NICU graduates who live with individuals who smoke.

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 < 0.001) and 50.0% fewer respiratory-related clinic visits (p < 0.05). CONCLUSIONS: One-quarter of infants admitted to NICUs will be discharged to households where individuals who smoke live; we demonstrated that smoking-related factors were associated with mothers' breastfeeding practices. Infants who received breast milk longer had fewer respiratory-related visits. IMPACT: One-quarter of NICU infants will be discharged to households where smokers live. Initiating/sustaining breastfeeding can be difficult for mothers of preterm NICU infants, especially mothers who smoke or live with others who smoke. Education, employment, race/ethnicity, length of stay, household member smoking, and readiness-to-protect infants from tobacco smoke were significantly associated with time-to-breastfeeding cessation. Infants fed breast milk for ≥4 months had 42.7% more well-child visits and 50.0% fewer respiratory-related clinic visits, compared to infants fed breast milk <4 months. Data support intervention refinements for mothers from smoking households and making NICU-based healthcare workers aware of risk factors for early breastfeeding cessation.

Neurophysiological and clinical effects of the NMDA receptor antagonist lanicemine (BHV-5500) in PTSD: A randomized, double-blind, placebo-controlled trial.

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.

Exenatide Adjunct to Nicotine Patch Facilitates Smoking Cessation and May Reduce Post-Cessation Weight Gain: A Pilot Randomized Controlled Trial.

INTRODUCTION: Approved 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. METHODS: Eighty-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. RESULTS: Exenatide 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. CONCLUSIONS: Exenatide, 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. IMPLICATIONS: Despite 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.

Thirdhand Smoke Contamination and Infant Nicotine Exposure in a Neonatal Intensive Care Unit: An Observational Study.

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.

Unexpected results of a randomized quality improvement program for children with severe asthma.

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.

Thirdhand smoke associations with the gut microbiomes of infants admitted to a neonatal intensive care unit: An observational study.

INTRODUCTION: Microbiome differences have been found in adults who smoke cigarettes compared to non-smoking adults, but the impact of thirdhand smoke (THS; post-combustion tobacco residue) on hospitalized infants' rapidly developing gut microbiomes is unexplored. Our aim was to explore gut microbiome differences in infants admitted to a neonatal ICU (NICU) with varying THS-related exposure. METHODS: Forty-three mother-infant dyads (household member[s] smoke cigarettes, n = 32; no household smoking, n = 11) consented to a carbon monoxide-breath sample, bedside furniture nicotine wipes, infant-urine samples (for cotinine [nicotine's primary metabolite] assays), and stool collection (for 16S rRNA V4 gene sequencing). Negative binomial regression modeled relative abundances of 8 bacterial genera with THS exposure-related variables (i.e., household cigarette use, surface nicotine, and infant urine cotinine), controlling for gestational age, postnatal age, antibiotic use, and breastmilk feeding. Microbiome-diversity outcomes were modeled similarly. Bayesian posterior probabilities (PP) ≥75.0% were considered meaningful. RESULTS: A majority of infants (78%) were born pre-term. Infants from non-smoking homes and/or with lower NICU-furniture surface nicotine had greater microbiome alpha-diversity compared to infants from smoking households (PP ≥ 75.0%). Associations (with PP ≥ 75.0%) of selected bacterial genera with urine cotinine, surface nicotine, and/or household cigarette use were evidenced for 7 (of 8) modeled genera. For example, lower Bifidobacterium relative abundance associated with greater furniture nicotine (IRR<0.01 [<0.01, 64.02]; PP = 87.1%), urine cotinine (IRR = 0.08 [<0.01,2.84]; PP = 86.9%), and household smoking (IRR<0.01 [<0.01, 7.38]; PP = 96.0%; FDR p < 0.05). CONCLUSIONS: THS-related exposure was associated with microbiome differences in NICU-admitted infants. Additional research on effects of tobacco-related exposures on healthy infant gut-microbiome development is warranted.

Reducing Tobacco Smoke Exposure in High-Risk Infants: A Randomized, Controlled Trial.

OBJECTIVE: To evaluate a hospital-initiated intervention to reduce tobacco smoke exposure in infants in the neonatal intensive care unit. STUDY DESIGN: A randomized, controlled trial compared motivational interviewing plus financial incentives with conventional care on infant urine cotinine at 1 and 4 months' follow-up. Mothers of infants in the neonatal intensive care unit (N = 360) who reported a smoker living in the home were enrolled. Motivational interviewing sessions were delivered in both the hospital and the home. Financial incentives followed session attendance and negative infant cotinine tests postdischarge. RESULTS: The intervention effect on infant cotinine was not significant, except among mothers who reported high baseline readiness/ability to protect their infant (P ≤ .01) and mothers who completed the study within 6 months postdischarge (per protocol; P ≤ .05). Fewer mothers in the motivational interviewing plus financial incentives condition were smoking postdischarge (P ≤ .01). More mothers in the motivational interviewing plus financial incentives group reported a total home and car smoking ban at follow-up (P ≤ .05). CONCLUSIONS: Motivational interviewing combined with financial incentives reduced infant tobacco smoke exposure in a subset of women who were ready/able to protect their infant. The intervention also resulted in less maternal smoking postpartum. More robust interventions that include maternal and partner/household smoking cessation are likely needed to reduce the costly effects of tobacco smoke exposure on children and their families. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01726062.

Socioecological indicators of senior financial exploitation: an application of data science to 8,800 substantiated mistreatment cases.

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.

Proactive delivery of nicotine replacement therapy to families of hospitalized infants in a NICU: A randomized controlled pilot trial.

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.

HIV Anxiety Reduction/Management Program (HAMRT): pilot randomized controlled trial.

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 (Mage = 48.5, SD = 8.9, 44.4% female) were recruited for a proof-of-concept study and randomized to either an active treatment condition, or a waitlist control condition of equal length. Participants were assessed pre-randomization, at the mid-treatment time point (after three sessions for the active participants and three weeks for the control participants) and post-treatment (six sessions for active participants, six weeks for control participants). Data were examined used Bayesian multilevel models. Results indicated a reliable (99.87% posterior probability of a moderating effect) interaction between active and control groups for depressive symptoms and reliable (99.65% probability) interaction for anxiety symptoms. Results indicated an unreliable interaction for combined antiretroviral therapy adherence. These findings are discussed in terms of the feasibility and potential utility of administering an anxiety-reduction therapy program designed for PLWHA with HIV medication adherence difficulties.

Brain Responses to Cigarette-Related and Emotional Images in Smokers During Smoking Cessation: No Effect of Varenicline or Bupropion on the Late Positive Potential.

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.

Change in physical activity and quality of life in endometrial cancer survivors receiving a physical activity intervention.

BACKGROUND: Endometrial cancer survivors are at an increased risk of poor quality of life outcomes. Physical activity is positively associated with general quality of life in this population, however, little is known about how changes in physical activity may be associated with changes in specific aspects of quality of life. The aim of this secondary data analysis was to explore the relationships between change in physical activity and change in physical, mental, social, and other aspects of quality of life in endometrial cancer survivors receiving a physical activity intervention. METHODS: Endometrial cancer survivors (N = 100) participated in a telephone-based physical activity intervention for six months. At baseline and post-intervention we measured physical activity via accelerometry and ecological momentary assessment, and quality of life via the Short Form Health Survey (SF-36), the Quality of Life of Adult Cancer Survivors instrument, the Brief Symptom Inventory, the Pittsburgh Sleep Quality Index, and the Perceived Stress Scale. We conducted structural equation modeling path analyses to investigate how physical activity post-intervention was associated with the quality of life measures' subscales post-intervention, adjusting for baseline levels and potentially confounding covariates. RESULTS: Increasing physical activity was positively associated with improvements in general health (p = .044), role limitation due to physical health (p = .005), pain (p = .041), and somatic distress (p = .023). There was no evidence to indicate that change in physical activity was associated with change in other aspects of quality of life. CONCLUSIONS: Endometrial cancer survivors are at higher risk for suffering from challenges to physical quality of life, and findings from this study suggest that increasing physical activity may alleviate some of these problems. Further research is needed to determine whether other aspects of quality of life are linked to change in physical activity. TRIAL REGISTRATION: Trial registration number: NCT00501761 Name of registry: clinicaltrials.gov Date of registration: July 16, 2007. Date of enrollment: June 16, 2005.