A Pilot Study to Test the Feasibility for a Randomized Controlled Trial of E-cigarettes as Harm Reduction Tools Among People Who Smoke and Previously Failed to Quit with Pharmacotherapy.

INTRODUCTION: We conducted a pilot study to test the feasibility of a future randomized controlled trial comparing e-cigarettes to traditional pharmacotherapy among people who smoke daily, were motivated to quit, and failed to quit within the past 5 years using pharmacotherapy. METHODS: Eligible participants were assigned to either: 1) an e-cigarette (n=20) or 2) combination nicotine replacement therapy (patches and lozenges) (n=10). Participants received 5 weeks of product and selected a quit date 1 week later. Assessments were completed weekly, and electronic diaries were completed each day. As a pilot randomized controlled trial, outcomes focus on effects sizes and not statistical significance. RESULTS: Participants in the e-cigarette and NRT groups had a mean age of 51 (SD=13) and 50 (SD=10) years old, were 55% and 60% female, and were 15% and 0% non-white, respectively. At least 90% of participants completed each weekly assessment, and 77% of participants completed at least 80% of daily diaries. Mean cigarettes smoked per day reduced from 18 (SD=6.2) to 2.4 (SD=4.4) per day in the e-cigarette group and 16.5 (SD=8.5) to 4.9 (SD=5.9) per day in the NRT group. Rates of biochemically confirmed 7-day point prevalence abstinence at the end of treatment were numerically, but not statistically, higher in the e-cigarette group than the NRT group (35% vs. 10%, OR=4.8, 95% CI=0.5-46.5). CONCLUSIONS: Among current daily cigarette smokers who have previously tried to quit and failed using standard pharmacotherapies, provision of an e-cigarette is a feasible intervention. A larger adequately powered trial is warranted. IMPLICATIONS: This pilot study suggests that e-cigarettes may serve as an acceptable harm reduction intervention for people who smoke who cannot quit smoking with traditional pharmacotherapy, but adequately powered randomized controlled trials are needed.

Opioid Dosing Deviation and Dose Banding Development in Young Hospitalized Children.

BACKGROUND AND OBJECTIVES: Individualized, weight-based opioid dosing poses safety risks and contributes to inefficient medication delivery processes. Dose banding is a patient safety strategy to reduce dosing errors through standardized doses based on weight ranges. Study objectives were (1) determine the frequency of dosing deviation from reference ranges of common intravenous (IV) and oral opioid medications, (2) evaluate the differences in dosing deviations by age, and (3) determine the potential reduction in dose variation that could be achieved by dose banding. METHODS: We conducted a cross-sectional analysis of hospitalized children ≥2 months to ≤24 months old who received IV morphine, oral methadone, or oral oxycodone at a single center. Dosing was categorized as no dosing deviation (within ±5% of the reference range), negative dosing deviation (>5% below the reference range), or positive dosing deviation (>5% above the reference range). Descriptive and bivariate analyses were conducted. RESULTS: A total of 3361 opioid doses met the inclusion criteria. A total of 2663 (79.2%) had no dosing deviation, 214 (6.3%) demonstrated negative deviations, and 484 (14.4%) demonstrated positive deviations. Dosing deviations were more frequent among subjects ≥2 months to ≤6 months old for oral methadone and oxycodone (P < .0001) and more frequent among older age group for IV morphine (P < .0001). Dose banding has the potential to reduce the number of unique doses prescribed for all medications by 75% while eliminating unintended dosing deviations. CONCLUSIONS: A total of 20% of opioid doses prescribed to children ≤24 months of age are outside the recommended ranges. Dose banding represents a promising method for simplifying opioid prescribing in the pediatric inpatient setting.

Associations Between Drug Overdose Mortality and Recovery Ecosystems in the United States: A County-Level Analysis Using a Novel Index.

BACKGROUND: Communities with robust recovery ecosystems could reduce negative outcomes associated with substance use disorders (SUDs) and facilitate the recovery process. This cross-sectional study examined the relationship between drug overdose mortality rates in the United States and the strength of county-level recovery ecosystems, as measured by the Recovery Ecosystem Index (REI). METHODS: The REI assesses the strength of county-level recovery ecosystems in the United States. Comprised of 14 indicators across 3 component classes, overall and component scores ranging from "one" (strongest) to "five" (weakest) were calculated for each county using standardized values of the indicators. County-level analyses included: (1) correlational analyses between drug overdose mortality rates (n = 2076) and REI scores (overall score and by component); and (2) quadrant analysis (n = 2076), dividing counties based on their drug overdose mortality rates and overall REI scores. RESULTS: Drug overdose mortality rates were inversely related to REI overall, SUD treatment component, and continuum of SUD support component scores, indicating that lower (stronger) scores corresponded to higher rates. Conversely, REI infrastructure and social component scores were positively related to rates. Counties were relatively evenly distributed across quadrants, with 26% (n = 537) with a strong REI score and high overdose mortality rate, 24% (n = 489) with a strong REI score and low overdose mortality rate, 20% (n = 409) with a weak REI and high overdose mortality rate, and 31% (n = 641) with a weak REI and low overdose mortality rate. CONCLUSIONS: REI scores were generally inversely associated with drug overdose mortality rates in US counties, suggesting that communities have stronger recovery systems and services as the burden of SUD increases. Given relative variation in the scale of drug overdose mortality and strength of recovery ecosystems among counties, results could guide the identification of communities where the need for expanded recovery systems and services may be particularly critical.

Individual Predictors of Response to A Behavioral Activation-Based Digital Smoking Cessation Intervention: A Machine Learning Approach.

Background: Depression is prevalent among individuals who smoke cigarettes and increases risk for relapse. A previous clinical trial suggests that Goal2Quit, a behavioral activation-based smoking cessation mobile app, effectively increases smoking abstinence and reduces depressive symptoms. Objective: Secondary analyses were conducted on these trial data to identify predictors of success in depression-specific digitalized cessation interventions. Methods: Adult who smoked cigarettes (age = 38.4 ± 10.3, 53% women) were randomized to either use Goal2Quit for 12 weeks (N = 103), paired with a 2-week sample of nicotine replacement therapy (patch and lozenge) or to a Treatment-As-Usual (TAU) control (N = 47). The least absolute shrinkage and selection operator was utilized to identify a subset of baseline variables predicting either smoking or depression intervention outcomes. The retained predictors were then fitted via linear regression models to determine relations to each intervention outcome. Results: Relative to TAU, only individuals who spent significant time using Goal2Quit (56 ± 46 min) were more likely to reduce cigarette use by at least 50% after 12 weeks, whereas those who spent minimal time using Goal2Quit (10 ± 2 min) did not exhibit significant changes. An interaction between educational attainment and treatment group revealed that, as compared to TAU, only app users with an educational degree beyond high school exhibited significant reductions in depression. Conclusions: The findings highlight the importance of tailoring depression-specific digital cessation interventions to individuals' unique engagement needs and educational level. This study provides a potential methodological template for future research aimed at personalizing technology-based treatments for cigarette users with depressive symptoms.

The prospective relationship between a-priori intentions for and patterns of e-cigarette use among adults who smoke cigarettes.

BACKGROUND: Electronic (e-)cigarettes may help adult cigarette smokers achieve cigarette cessation, depending on patterns of e-cigarette use. Among cigarette smokers who do not use e-cigarettes, it is unclear if and how a-priori intentions for use are related to uptake patterns. Longitudinal studies have focused on established e-cigarette users or adolescent and young adult populations exclusively. METHODS: Within a nationwide randomized clinical trial (N = 638), adult cigarette smokers not currently using e-cigarettes were randomized (2:1) to receive (or not) one-month sampling of e-cigarettes. An exploratory factor analysis (EFA) was performed on an established 15-item measure assessing a-priori intentions for e-cigarette use to identify latent variables. Among those receiving e-cigarette products, regression models examined relationships between intentions and: 1) uptake (yes/no), 2) frequency (number of days per week), and 3) amount (puffing episodes per day) of e-cigarette use at one-month follow-up. RESULTS: Two factors emerged from the EFA: 1) cigarette-related intentions (e.g., cigarette cessation, no smell) and 2) novel appeal of e-cigarettes (e.g., flavors). Three items remained and were treated as separate intentions: "feels like cigarette smoking", "curiosity", and "affordability". In the final multivariable models, "feel like cigarette smoking" predicted more frequent e-cigarette use (ß = 0.187, SE = 0.086, p = 0.03); however, none of the five factors/intentions were significantly associated with uptake or amount of use. CONCLUSIONS: For adult cigarette smokers not currently using e-cigarettes, a-priori intentions for using e-cigarettes might not be predictive of if or how these products will be used in the future, suggesting that motives may not drive use behavior.

Factors Affecting Postpartum Bone Mineral Density in a Clinical Trial of Vitamin D Supplementation.

Background: Few studies evaluate the effects of vitamin D status and supplementation on maternal bone mineral density (BMD) during lactation and further lack inclusion of diverse racial/ethnic groups, body mass index (BMI), or physical activity. Objective: Determine the effects of vitamin D treatment/status, feeding type, BMI, race/ethnicity, and physical activity on postpartum women's BMD to 7 months. Methods: Women with singleton pregnancies beginning 4-6 weeks' postpartum were randomized into two treatment groups (400 or 6400 IU vitamin D/day). Participant hip, spine, femoral neck, and whole-body BMD using Dual-energy X-ray absorptiometry (DXA Hologic), serum 25-hydroxyvitamin D [25(OH)D] (RIA; Diasorin), BMI, and physical activity were measured at 1, 4, and 7 months postpartum. A general linear mixed modeling approach was undertaken to assess the effects of vitamin D status [both serum 25(OH)D concentrations and treatment groups], feeding type, race/ethnicity, BMI, and physical activity on BMD in postpartum women. Results: During the 6-month study period, lactating women had 1-3% BMD loss in all regions compared with 1-3% gain in nonlactating women. Higher maternal BMI was associated with less bone loss in femoral neck and hip regions. Black American women had less BMD loss than White/Caucasian or Hispanic lactating women in spine and hip regions. Exclusively breastfeeding women in the 6400 IU vitamin D group had less femoral neck BMD loss than the 400 IU group at 4 months sustained to 7 months. Physical activity was associated with higher hip BMD. Conclusion: While there was BMD loss during lactation to 7 months, the loss rate was less than previously reported, with notable racial/ethnic variation. Breastfeeding was associated with loss in BMD compared with formula-feeding women who gained BMD. Higher BMI and physical activity independently appeared to protect hip BMD, whereas higher vitamin D supplementation appeared protective against femoral neck BMD loss.

Behavioral Activation-Based Digital Smoking Cessation Intervention for Individuals With Depressive Symptoms: Randomized Clinical Trial.

BACKGROUND: Depression is common among adults who smoke cigarettes. Existing depression-specific cessation interventions have limited reach and are unlikely to improve smoking prevalence rates among this large subgroup of smokers. OBJECTIVE: This study aimed to determine whether a mobile app-based intervention tailored for depression paired with a mailed sample of nicotine replacement therapy (NRT) is efficacious for treating depression and promoting smoking cessation. METHODS: A 2-arm nationwide remote randomized clinical trial was conducted in the United States. Adults (N=150) with elevated depressive symptoms (Patient Health Questionnaire-8≥10) who smoked were enrolled. The mobile app ("Goal2Quit") provided behavioral strategies for treating depression and quitting smoking based on Behavioral Activation Treatment for Depression. Goal2Quit participants also received a 2-week sample of combination NRT. Treatment as usual participants received a self-help booklet for quitting smoking that was not tailored for depression. Primary end points included Goal2Quit usability, change in depression (Beck Depression Inventory-II) across 12 weeks, and smoking cessation including reduction in cigarettes per day, incidence of 24-hour quit attempts, floating abstinence, and 7-day point prevalence abstinence (PPA). RESULTS: In total, 150 participants were enrolled between June 25, 2020, and February 23, 2022, of which 80 were female (53.3%) and the mean age was 38.4 (SD 10.3) years. At baseline, participants on average reported moderate depressive symptoms and smoked a mean of 14.7 (SD 7.5) cigarettes per day. Goal2Quit usability was strong with a mean usability rating on the System Usability Scale of 78.5 (SD 16.9), with 70% scoring above the ≥68 cutoff for above-average usability. Retention data for app use were generally strong immediately following trial enrollment and declined in subsequent weeks. Those who received Goal2Quit and the NRT sample reported lower mean depressive symptoms over the trial duration as compared to treatment as usual (difference of mean 3.72, SE 1.37 points less; P=.01). Across time points, all cessation outcomes favored Goal2Quit. Regarding abstinence, Goal2Quit participants reported significantly higher rates of 7-day PPA at weeks 4 (11% vs 0%; P=.02), 8 (7-day PPA: 12% vs 0%; P=.02), and 12 (16% vs 2%; P=.02). CONCLUSIONS: A mobile app intervention tailored for depression paired with a sample of NRT was effective for depression treatment and smoking cessation. Findings support the utility of this intervention approach for addressing the currently unmet public health treatment need for tailored, scalable depression-specific cessation treatments. TRIAL REGISTRATION: ClinicalTrials.gov NCT03837379; https://clinicaltrials.gov/ct2/show/NCT03837379.

A quality improvement study on the feasibility and potential benefits of a yogic breathing program for cancer survivors and caregivers during treatment in a lodging facility.

Background: Complementary and integrative health approaches with a focus on relieving side effects of cancer treatment are popular among cancer patients. Previous studies have investigated the combined effects of yoga postures, breathing, and meditation, but the specific effects of the breathing component are under-reported. Our previous studies indicate that yogic breathing can improve salivary biomarker expression related to stress, immune response, and tumor suppression. We aim to assess the acceptability and feasibility of a yogic breathing program in cancer patients and caregivers during the treatment period. Methods: In this quality improvement study, we designed a 20-minute yogic breathing regimen and introduced them to all-site cancer patients and their caregivers during the cancer treatment period at a lodging facility, Hope Lodge in Charleston, SC. All interested participants were included as there were no eligibility criteria set for the study. The availability of the class was advertised via intercom, displays, and word of mouth. Participants were taught five different breathing exercises, and after completion of the exercises in a single session, a self-reported quality improvement questionnaire was administered assessing sociodemographic/clinical factors, expectations about the session, and ratings of satisfaction with the session. Results: During the nine months of the data collection period, 52 participants provided feedback of which patients and caregivers were almost equal numbers. Participants' perception of intervention acceptance, symptom management, satisfaction with the sessions, and future needs for practice indicate that the yogic breathing sessions help improve some of the key symptoms of cancer experience such as stress. Conclusion: Findings indicate that yogic breathing is acceptable to patients and caregivers and may help alleviate some of the side effects resulting from cancer treatment, and the intervention is feasible at lodging facilities during treatment. Currently, the yogic breathing sessions are conducted on a weekly basis by Hope Lodge volunteers trained by the study team.

Rationale, design, and protocol for a hybrid type 1 effectiveness-implementation trial of a proactive smoking cessation electronic visit for scalable delivery via primary care: the E-STOP trial.

BACKGROUND: Cigarette smoking remains the leading cause of preventable disease and death in the United States. Primary care offers an ideal setting to reach adults who smoke cigarettes and improve uptake of evidence-based cessation treatment. Although U.S. Preventive Services Task Force Guidelines recommend the 5As model (Ask, Advise, Assess, Assist, Arrange) in primary care, there are many barriers to its implementation. Automated, comprehensive, and proactive tools are needed to overcome barriers. Our team developed and preliminarily evaluated a proactive electronic visit (e-visit) delivered via the Electronic Health Record patient portal to facilitate evidence-based smoking cessation treatment uptake in primary care, with promising initial feasibility and efficacy. This paper describes the rationale, design, and protocol for an ongoing Hybrid Type I effectiveness-implementation trial that will simultaneously assess effectiveness of the e-visit intervention for smoking cessation as well as implementation potential across diverse primary care settings. METHODS: The primary aim of this remote five-year study is to examine the effectiveness of the e-visit intervention vs. treatment as usual (TAU) for smoking cessation via a clinic-randomized clinical trial. Adults who smoke cigarettes are recruited across 18 primary care clinics. Clinics are stratified based on their number of primary care providers and randomized 2:1 to either e-visit or TAU. An initial baseline e-visit gathers information about patient smoking history and motivation to quit, and a clinical decision support algorithm determines the best evidence-based cessation treatment to prescribe. E-visit recommendations are evaluated by a patient's own provider, and a one-month follow-up e-visit assesses cessation progress. Main outcomes include: (1) cessation treatment utilization (medication, psychosocial cessation counseling), (2) reduction in cigarettes per day, and (3) biochemically verified 7-day point prevalence abstinence (PPA) at six-months. We hypothesize that patients randomized to the e-visit condition will have better cessation outcomes (vs. TAU). A secondary aim evaluates e-visit implementation potential at patient, provider, and organizational levels using a mixed-methods approach. Implementation outcomes include acceptability, adoption, fidelity, implementation cost, penetration, and sustainability. DISCUSSION: This asynchronous, proactive e-visit intervention could provide substantial benefits for patients, providers, and primary care practices and has potential to widely improve reach of evidence-based cessation treatment. TRIAL REGISTRATION: NCT05493254.

Remote Carbon Monoxide Capture via REDCap: Evaluation of an Integrated Mobile Application.

INTRODUCTION: To improve the feasibility of remote biochemical verification of smoking status, our team developed "COast", a mobile app integrated with REDCap that allows a research participant to complete self-report research assessments and provide a breath sample via the iCOQuit® Smokerlyzer® for the purposes of carbon monoxide (CO) testing. The aims of the present study were to examine: 1) the validity of remote CO data capture using COast as compared to gold standard approaches (salivary cotinine, stand-alone CO monitor) and 2) the feasibility of remote CO data capture using COast as applied to both daily and weekly CO collection schedules. METHODS: Participants (N=143, 59% Female), including recently quit (n=36) and current (n=107) smokers, completed a baseline video session to capture validity data, and then were randomized to daily or weekly CO monitoring for a period of one month. RESULTS: Balancing both sensitivity and specificity, optimal cut-points for defining abstinence using the COast system were < 4 parts per million (ppm) with salivary cotinine as the referent (Sensitivity = 100%, Specificity = 92.8%) and < 8ppm with the stand-alone CO monitor as the referent (Sensitivity = 100%, Specificity = 88.9%). Compliance across groups with CO monitoring was high with average compliance of 74% for the daily group and 84% for the weekly group. Self-reported feasibility and acceptability of using the system were strong. CONCLUSIONS: Pairing the iCOQuit with REDCap via the COast app was both valid and feasible among a sample of adults who smoke cigarettes enrolled remotely. This integration may help to improve the rigor of decentralized smoking cessation trials. IMPLICATIONS: With increasing prevalence of decentralized trial designs, innovative methods are needed to remotely capture biomarkers. Methods that leverage existing widely available research data capture platforms may be particularly useful for promoting adoption. The COast app, which integrates a Bluetooth-enabled carbon monoxide monitor with REDCap, is a fitting, valid, feasible solution to remotely biochemically verify smoking status.

Effect of unguided e-cigarette provision on uptake, use, and smoking cessation among adults who smoke in the USA: a naturalistic, randomised, controlled clinical trial.

Background: As summarised in the most recent Cochrane review, the few clinical trials on e-cigarettes are largely focused on smoking cessation. We aimed to determine the naturalistic uptake, use, and impact of e-cigarettes among adults who may or may not want to stop smoking. Methods: In this naturalistic, randomised, controlled clinical trial, adult smokers, across the motivational spectrum and with minimal history of e-cigarette use, were recruited online from the general community within 11 cities across the USA. Participants were randomly assigned (2:1) to either receive either a free 4-week supply of flavoured, tank-style e-cigarette, or not. E-cigarette group participants received a battery and device with up to 30 pre-filled tanks, offered among five flavours, with minimal instructions on use. The study's primary purpose was to descriptively assess naturalistic uptake and usage of the e-cigarette, and to secondarily assess its impact on smoking behavior. The latter, assessed through six months of follow-up, included: a) self-reported 7-day point prevalence abstinence, b) incidence of quit attempts, and c) smoking reduction. This trial is registered at ClinicalTrials.gov, NCT03453385. Findings: Between 5/2018 and 3/2022, 638 adult smokers were enrolled and randomly assigned (427 in the e-cigarette group and 211 in the no-product control group). Uptake of e-cigarettes was robust: approximately 70% of participants used the product, with average usage exceeding 4 days per week during the initial 30 days. Based on an intent-to-treat approach where missing data is imputed as smoking, almost all behavioral outcomes favored the e-cigarette group relative to no-product control, including point prevalence abstinence at six months (Odds Ratio [OR] = 1.8; 95% Confidence Interval [CI] = 1.0-3.1), cumulative incidence of 24-hr quit attempts (OR = 1.5; 95% CI = 1.0-2.2), and having reduced smoking by at least 50% since baseline (OR = 1.8; 95% CI = 1.2-2.7). Results were similar under an alternative imputation. Interpretation: Complementing cessation-focused trials, results suggest that unguided e-cigarette use also leads to smoking cessation, allaying the notion that causal effects of e-cigarettes on cessation are not reflective of real-world scenario of self-determined use. For smokers who may not be able to quit using existing pharmacologic approaches, e-cigarettes may be considered to achive that purpose. Funding: National Cancer Institute.

Measuring success: A comparison of ultrasound and landmark guidance for knee arthrocentesis in a cadaver model.

OBJECTIVE: Knee arthrocentesis can be performed by landmark (LM) or ultrasound (US) guidance. The goal of performing knee arthrocentesis is to obtain synovial fluid, however, it is also important to consider the number of attempts required and accidental bone contacts that occur. This study evaluates procedural success without bone contact in knee arthrocentesis and compares both LM and US guided techniques in a cadaver model. METHODS: This was a randomized crossover study comparing US vs LM guidance for arthrocentesis in a single academic center. Volunteers were randomized to perform both LM and US guided knee arthrocentesis on cadavers. The primary outcome was procedural success, defined as first attempt aspiration of synovial fluid without bone contact. Secondary outcomes included number of attempts, number of bone contacts, time to aspiration, and confidence. RESULTS: Sixty-one participants completed the study with a total of 122 procedures performed. Procedural success without bone contact was greater in the US group (84% vs 64% p = 0.02). Time to aspiration was longer for US (38.75 s vs 25.54 s p = 0.004). Participants were more confident with US compared to LM both before the procedure on a Visual Analog Scale from 1 to 100 (29 vs 21 p = 0.03) as well as after the procedure (83 vs 69 p = 0.0001). Participants had a greater median increase in confidence with US following training (44 vs 26 p = 0.01). CONCLUSIONS: Study participants had greater procedural success without bone contact when US guidance was used. The increase in confidence following training was greater for US guidance than the LM method. Use of US guidance may offer a benefit by allowing for better needle control and avoidance of sensitive structures for clinicians performing knee arthrocentesis.

"And then I found $5": Optimizing recruitment efficiency in remote clinical trials.

Introduction: As clinical trials adopt remote methodologies, there is need to optimize efficiency of remote enrollment. Within a remote clinical trial, we aim to (1) assess if sociodemographic factors differ among those consenting via mail vs. technology-based procedures (e-consent), (2) determine if, among those consenting via mail, a small unconditional monetary reward ($5) increases likelihood of subsequent enrollment, (3) economically evaluate additional cost per additional participant enrolled with $5 reward. Methods: In the parent nationwide randomized clinical trial of adult smokers (N = 638), participants could enroll via mail or e-consent. Logistic regression models assessed relationships between sociodemographics and enrollment via mail (vs e-consent). Mailed consent packets were randomized (1:4) to include $5 unconditional reward or not, and logistic regression modeling examined impact of reward on subsequent enrollment, allowing for a randomized study within a study. Incremental cost-effectiveness ratio analysis estimated additional cost per additional participant enrolled with $5 incentive. Results: Older age, less education, lower income, and female sex predicted enrolling via mail vs e-consent (p < .05's). In adjusted model, older age (AOR = 1.02, p = .016) and less education (AOR = 2.23, p < .001) remained predictive of mail enrollment. The $5 incentive (vs none) increased enrollment rate by 9% (AOR = 1.64, p = .007), with estimated cost of additional $59 per additional participant enrolled. Conclusions: As e-consent methods become more common, they have potential to reach many individuals but with perhaps diminished inclusion across all sociodemographic groups. Provision of an unconditional monetary incentive is possibly a cost-effective mechanism to increase recruitment efficiency for studies employing mail-based consenting procedures.

Patent Ductus Arteriosus Response to Treatment by Course and Associations with Perinatal and Clinical Factors.

OBJECTIVE: The objective of this study is to examine patent ductus arteriosus (PDA) response by treatment course and investigate associations with postmenstrual age (PMA), chronological age (CA), gestational age (GA), antenatal steroid exposure (ANS), birthweight (BW), weight at treatment initiation (WT), and PDA/left pulmonary artery (LPA) ratio. STUDY DESIGN: This is a single-center retrospective cohort study of preterm infants less than 37 weeks' GA born January 1, 2016 to December 31, 2018 who received acetaminophen and/or indomethacin for PDA treatment. Cox proportional hazards regression models were used to determine whether factors of interest were associated with PDA response to medical treatment. RESULTS: In total, 289 treatment courses were administered to 132 infants. Thirty-one (23%) infants experienced treatment-associated PDA closure. Ninety-four (71%) infants had evidence of PDA constriction following any treatment course. Ultimately, 84 (64%) infants experienced definitive PDA closure. For each 7-day increase in CA at the time of treatment initiation, the PDA was 59% less likely to close (p = 0.04) and 42% less likely to respond (i.e., constrict or close) to treatment (p < 0.01). PDA/LPA ratio was associated with treatment-associated PDA closure (p = 0.01). For every 0.1 increase in the PDA/LPA ratio, the PDA was 19% less likely to close in response to treatment. CONCLUSION: In this cohort, PDA closure is independent of PMA, GA, ANS, BW, and WT; however, CA at treatment initiation predicted both treatment-associated PDA closure and PDA response (i.e., constriction or closure), and PDA/LPA ratio was associated with treatment-associated closure. Most infants experienced PDA constriction rather than closure, despite receiving up to four treatment courses. KEY POINTS: · Detailed PDA responses for up to four treatment courses provide a novel perspective.. · Chronological age at the start of treatment predicted treatment-associated PDA closure and response.. · For each 7-day increase in chronological age, the PDA was 59% less likely to close..

The association between grandparents as caregivers and overdose mortality in Appalachia and non-Appalachia counties.

Objective: To assess the association of drug overdose mortality with grandparents serving as caregivers of children in Appalachia and non-Appalachia in the U.S. Methods: This study used a cross-sectional design, with percent of grandparents as caregivers and overdose mortality rates being of primary interest. County-level data were combined, and descriptive, bivariate, and multivariable statistics were applied. Multiple sociodemographic and geographic variables were included: median age of the population, percent of the population that is uninsured, percent of the population that is non-Hispanic white, teen birth rate, percent of high school dropouts, and rurality. Results: The percent of grandparents as caregivers increased as the overdose mortality rate increased (p < 0.01). For every 1% increase in the overdose mortality rate, the percent of grandparents as caregivers increased by 56% in Appalachian counties compared to 24% in non-Appalachian counties. After adjusting for sociodemographic characteristics, the interaction between overdose mortality and Appalachian vs. non-Appalachian counties was no longer significant (p = 0.3). Conclusions: Counties with higher overdose mortality rates had greater rates of grandparents as caregivers, with Appalachian counties experiencing greater rates of grandparents as caregivers than non-Appalachian counties. Sociodemographic characteristics that are often more prevalent in Appalachia may be driving the observed differences. Policy implications: Policies and programs are needed to support grandparents providing caregiving for children impacted by substance use disorders including reform to federal child welfare financing to support children, parents, and grandparent caregivers such as kinship navigation, substance use treatment and prevention services, mental health services and in-home supports.

The Impact of Older Age on Smoking Cessation Outcomes After Standard Advice to Quit.

Older adults are a high priority population for smoking cessation. This study observed the influence of older age on the relationship between quitting predictors and cessation. Secondary analysis was conducted of a primary care trial of adults who smoke cigarettes randomized to standard advice to quit or advice plus 2 week supply of nicotine replacement therapy. Logistic regressions assessed interactions of age (<60 vs. ≥ 60 years) by predictors in relation to quit attempts and 6-month cessation controlling for treatment. Predicting quit attempts, there was an interaction of age by motivation (p = .025) and trend of age by nicotine dependence (p = .057). Predicting 6-month cessation, an interaction of age by motivation was observed (p = .020) and a trend of age by dependence (p = .067). For those with high nicotine dependence, older adults had less successful outcomes compared to younger counterparts. Yet among participants unmotivated to quit, older adults had more successful outcomes than those younger.

Mask Adherence to Mask Mandate: College Campus Versus the Surrounding Community.

Adherence to masking recommendations and requirements continues to have a wide variety of impacts in terms of viral spread during the ongoing pandemic. As governments, schools, and private sector businesses formulate decisions around mask requirements, it is important to observe real-life adherence to policies and discern subsequent implications. The CDC MASCUP! observational study tracked mask-wearing habits of students on higher-education campuses across the country to collect stratified data about mask typologies, correct mask usage, and differences in behaviors at locations on a college campus and in the surrounding community. Our findings from a single institution include a significant adherence difference between on-campus (86%) and off-campus sites (72%) across the course of this study as well as a notable change in adherence at the on-campus sites with the expiration of a county-wide governmental mandate, despite continuance of a university-wide mandate. This study, completed on and around the campus of East Tennessee State University in Washington County TN, was able to pivotally extract information regarding increased adherence on campus versus the surrounding community. Changes were also seen when mask mandates were implemented and when they expired.

Long-Term Survival After Alcohol Septal Ablation for Hypertrophic Obstructive Cardiomyopathy: A 16-Year Experience.

BACKGROUND: Alcohol septal ablation (ASA) is an accepted treatment for medically refractory hypertrophic obstructive cardiomyopathy (HOCM). The procedural and medium-term outcomes have been reassuring. The iatrogenic targeted septal infarction has raised theoretical concerns about risk of arrhythmia and long-term survival. In this study, we describe the long-term survival in a large cohort of patients from a single referral center and the iterative improvement in procedural technique since its inception. METHODS: This cohort includes 580 consecutive patients who underwent 664 ASA procedures between the years 1999 and 2015. Procedural details and outcomes are described. Long-term survival is compared with expected survival of demographically similar controls. RESULTS: Fifty-four percent were women and 85% were Caucasian. At the time of ablation, mean age was 57 ± 15 years, septal thickness was 2.1 ± 0.5 cm, and left ventricular outflow tract (LVOT) gradient was 72 ± 40 mm Hg at rest and 102 ± 58 mm Hg with Valsalva provocation. Mean follow-up was 8.0 ± 4.3 years. LVOT gradient reduction >50% was achieved in 94% of patients with reduction in New York Heart Association functional class scores and increase in exercise treadmill duration. Procedural mortality was 0.9%. Over the 16-year period, survival estimates at 1, 5, 10, and 15 years were 98%, 92%, 84%, and 81%, respectively, which are comparable to demographically similar controls. The standardized mortality ratio was 0.84 (95% confidence interval, 0.66-1.06); P=.09. CONCLUSIONS: ASA appears to be a safe and effective treatment for symptomatic HOCM refractory to medical therapy with long-term survival comparable to a demographically similar United States population.

Evaluating N-acetylcysteine for early and end-of-treatment abstinence in adult cigarette smokers.

BACKGROUND: There is robust preclinical literature and preliminary clinical findings supporting the use of N-Acetylcysteine (NAC) to treat substance use disorders, including tobacco use disorder (TUD). However, randomized controlled trials have yielded mixed results and NAC's efficacy for TUD has not been established. The goals of this study were to assess the efficacy of NAC in promoting early and end-of-treatment abstinence and preventing relapse among adult smokers. METHODS: This randomized, double-blinded clinical trial enrolled adult, daily smokers (N = 114; ages 23-64; 51 % female; 65 % White; 29 % Black/African American; 7% Hispanic/Latinx), who were randomized 1:1 to receive NAC (n = 59) or placebo (n = 55) (1200 mg b.i.d.) for eight weeks. Participants received brief cessation counseling and incentives for abstinence during the first three days of the quit attempt. Primary outcomes: (i) carbon monoxide (CO)-confirmed abstinence during the first three days of the quit attempt. SECONDARY OUTCOMES: (ii) time to relapse; (iii) biologically confirmed abstinence at Week 8. RESULTS: No differences were found between NAC and placebo groups on measures of early abstinence (3-day quit attempt; 11 % for NAC vs. 15 % for placebo; all p > 0.11), time to relapse (p = 0.19), and end-of-treatment abstinence (7% for NAC vs. 11 % for placebo; all p > 0.40]. CONCLUSIONS: Results indicate that NAC is a well-tolerated pharmacotherapy but is unlikely to be efficacious as a monotherapy for TUD in adults. Considered in the collective context of other research, NAC may potentially be more useful in a younger population, as a combination pharmacotherapy, or in the presence of more intensive psychosocial treatment.