Matching study design to prescribing intention: The prevalent new-user design for studying abuse-deterrent formulations of opioids.

PURPOSE: In drug studies, research designs requiring no prior exposure to certain drug classes may restrict important populations. Since abuse-deterrent formulations (ADF) of opioids are routinely prescribed after other opioids, choice of study design, identification of appropriate comparators, and addressing confounding by "indication" are important considerations in ADF post-marketing studies. METHODS: In a retrospective cohort study using claims data (2006-2018) from a North Carolina private insurer [NC claims] and Merative MarketScan [MarketScan], we identified patients (18-64 years old) initiating ADF or non-ADF extended-release/long-acting (ER/LA) opioids. We compared patient characteristics and described opioid treatment history between treatment groups, classifying patients as traditional (no opioid claims during prior six-month washout period) or prevalent new users. RESULTS: We identified 8415 (NC claims) and 147 978 (MarketScan) ADF, and 10 114 (NC claims) and 232 028 (MarketScan) non-ADF ER/LA opioid initiators. Most had prior opioid exposure (ranging 64%-74%), and key clinical differences included higher prevalence of recent acute or chronic pain and surgery among patients initiating ADFs compared to non-ADF ER/LA initiators. Concurrent immediate-release opioid prescriptions at initiation were more common in prevalent new users than traditional new users. CONCLUSIONS: Careful consideration of the study design, comparator choice, and confounding by "indication" is crucial when examining ADF opioid use-related outcomes.

Second sensor to improve near-infrared spectroscopy flap monitor utility: A prospective study.

OBJECTIVE: This study assesses whether use of continuous noninvasive near-infrared spectroscopy (NIRS) sensor on head and neck free flap (FF) with a second sensor on nonoperated tissue improves distinction between systemic hypoperfusion and FF compromise. METHODS: Single-institution, prospective study of patients undergoing head and neck FF reconstruction from December 2018 to April 2020. FFs were continuously monitored using NIRS on a monitor paddle with a second (control) sensor on the shoulder. Crude StO2 and percent change in StO2 were compared between the FF and control sensors on each patient, and percent change and percent difference between the control and the monitor paddle were documented to assess for congruity. Sentinel events (e.g., hypotension and hematoma) were documented to assess the association with change in StO2. These events and timing of StO2 changes were noted to assess associations with change in StO2. RESULTS: A total of 48 patients had complete data. Donor sites included 35 soft-tissue FFs and 13 fibula FFs. Average StO2 was 73.7 ± 5.5 for FFs and 71.4 ± 5.0 for control sensors. There were seven sentinel events during the study. At the time of the events, StO2 dropped significantly more for the FF than the control sensor (FF = 52.2% drop; control = 6.2% drop; p = .016). NIRS signal denoted change prior to changes in implantable arterial Doppler in all cases. CONCLUSIONS: The addition of a second sensor when using NIRS as a primary modality for FF monitoring may improve distinction between FF compromise events and systemic hypoperfusion. By increasing accuracy of the monitor, there is a potential for decreased resident burden and decreased use of higher level of care nursing, which could reduce overall costs.

The impact of ActiGraph's low-frequency extension filter on measurement of children's physical activity.

This study examines differences in accelerometer-based measurements of children's movement with and without applying ActiGraph's low-frequency extension (LFE) filter. Thirty children wore ActiGraph GT9X devices during structured physical activity (PA) periods. Raw accelerometry data for each activity period were processed with and without the LFE filter applied. For each activity period, paired t-tests were used to compare vector magnitude counts and minutes spent in moderate-to-vigorous physical activity (MVPA) with and without the LFE filter applied. Repeated measures MANOVA models were used for compositional data analysis of the percentage of time spent in sedentary behaviour and light, moderate, and vigorous PA with and without the LFE filter applied. Applying the LFE filter significantly increased vector magnitude counts and estimated minutes spent in MVPA for all activity periods when compared to the normal filter. For brisk walking, the LFE filter had a significant impact on the composition of time spent in sedentary behaviour and PA intensities. Children's activity data processed with the LFE filter may not be compatible with cut-points for activity levels developed with the normal filter, and caution should be taken when comparing children's activity levels or movement data between studies that do and do not use the LFE filter.

American Society of Emergency Radiology Multicenter Blunt Splenic Trauma Study: CT and Clinical Findings.

Background Treatment of blunt splenic trauma (BST) continues to evolve with improved imaging for detection of splenic vascular injuries. Purpose To report on treatments for BST from 11 trauma centers, the frequency and clinical impact of splenic vascular injuries, and factors influencing treatment. Materials and Methods Patients were retrospectively identified as having BST between January 2011 and December 2018, and clinical, imaging, and outcome data were recorded. Patient data were summarized descriptively, both overall and stratified by initial treatment received (nonoperative management [NOM], angiography, or surgery). Regression analyses were used to examine the primary outcomes of interest, which were initial treatment received and length of stay (LOS). Results This study evaluated 1373 patients (mean age, 42 years ± 18; 845 men). Initial treatments included NOM in 849 patients, interventional radiology (IR) in 240 patients, and surgery in 284 patients. Rates from CT reporting were 22% (304 of 1373) for active splenic hemorrhage (ASH) and 20% (276 of 1373) for contained vascular injury (CVI). IR management of high-grade injuries increased 15.6%, from 28.6% (eight of 28) to 44.2% (57 of 129) (2011-2012 vs 2017-2018). Patients who were treated invasively had a higher injury severity score (odds ratio [OR], 1.04; 95% CI: 1.02, 1.05; P < .001), lower temperature (OR, 0.97; 95% CI: 0.97, 1.00; P = .03), and a lower hematocrit (OR, 0.96; 95% CI: 0.93, 0.99; P = .003) and were more likely to show ASH (OR, 8.05; 95% CI: 5.35, 12.26; P < .001) or CVI (OR, 2.70; 95% CI: 1.64, 4.44; P < .001) on CT images, have spleen-only injures (OR, 2.35; 95% CI: 1.45, 3.8; P < .001), and have been administered blood product for fewer than 24 hours (OR, 2.35; 95% CI: 1.58, 3.51; P < .001) compared with those chosen for NOM, after adjusting for key demographic and clinical variables. After adjustment, factors associated with a shorter LOS were female sex (OR, 0.84; 95% CI: 0.73, 0.96; P = .009), spleen-only injury (OR, 0.72; 95% CI: 0.6, 0.86; P < .001), higher admission hematocrit (OR, 0.98; 95% CI: 0.6, 0.86; P < .001), and presence of ASH at CT (OR, 0.74; 95% CI: 0.62, 0.88; P < .001). Conclusion Contained vascular injury and active splenic hemorrhage (ASH) were frequently reported, and rates of interventional radiologic management increased during the study period. ASH was associated with a shorter length of stay, and patients with ASH had eight times the odds of undergoing invasive treatment compared with undergoing nonoperative management. © RSNA, 2021 See also the editorial by Patlas in this issue.

High-fat feeding disrupts daily eating behavior rhythms in obesity-prone but not in obesity-resistant male inbred mouse strains.

Abnormal meal timing, like skipping breakfast and late-night snacking, is associated with obesity in humans. Disruption of daily eating rhythms also contributes to obesity in mice. When fed a high-fat diet, male C57BL/6J mice have disrupted eating behavior rhythms and they become obese. In contrast to obesity-prone C57BL/6J mice, some inbred strains of mice are resistant to high-fat diet-induced obesity. In this study, we sought to determine whether there are distinct effects of high-fat feeding on daily eating behavior rhythms in obesity-prone and obesity-resistant male mice. Male obesity-prone (C57BL/6J and 129X1/SvJ) and obesity-resistant (SWR/J and BALB/cJ) mice were fed low-fat diet or high-fat diet for 6 wk. Consistent with previous studies, obesity-prone male mice gained more weight and adiposity during high-fat diet feeding than obesity-resistant male mice. The amplitude of the daily rhythm of eating behavior was markedly attenuated in male obesity-prone mice fed high-fat diet, but not in obesity-resistant males. In contrast, high-fat feeding did not differentially affect locomotor activity rhythms in obesity-prone and obesity-resistant male mice. Together, these data suggest that regulation of the daily rhythm of eating may underlie the propensity to develop diet-induced obesity in male mice.

Age and sex are associated with the plasma lipidome: findings from the GOLDN study.

BACKGROUND: Developing an understanding of the biochemistry of aging in both sexes is critical for managing disease throughout the lifespan. Lipidomic associations with age and sex have been reported, but prior studies are limited by measurements in serum rather than plasma or by participants taking lipid-lowering medications. METHODS: Our study included lipidomic data from 980 participants aged 18-87 years old from the Genetics of Lipid-Lowering Drugs and Diet Network (GOLDN). Participants were off lipid-lowering medications for at least 4 weeks, and signal intensities of 413 known lipid species were measured in plasma. We examined linear age and sex associations with signal intensity of (a) 413 lipid species; (b) 6 lipid classes (glycerolipids, glycerophospholipids, sphingolipids, sterol lipids, fatty acids, and acylcarnitines); and (c) 15 lipid subclasses; as well as with the particle sizes of three lipoproteins. RESULTS: Significant age associations were identified in 4 classes, 11 subclasses, 147 species, and particle size of one lipoprotein while significant sex differences were identified in 5 classes, 12 subclasses, 248 species, and particle sizes of two lipoproteins. For many lipid species (n = 97), age-related associations were significantly different between males and females. Age*sex interaction effects were most prevalent among phosphatidylcholines, sphingomyelins, and triglycerides. CONCLUSION: We identified several lipid species, subclasses, and classes that differ by age and sex; these lipid phenotypes may serve as useful biomarkers for lipid changes and associated cardiovascular risk with aging in the future. Future studies of age-related changes throughout the adult lifespan of both sexes are warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT00083369 ; May 21, 2004.

Remote monitoring of head and neck free flaps using near infrared spectroscopic tissue oximetry.

PURPOSE: Near infrared spectroscopy (NIRS) measures tissue oximetry and perfusion of free tissue transfer with the advantage of remote wireless monitoring for free tissue transfer. It has been widely used in breast and extremity reconstruction but has had limited adoption in the head and neck. MATERIALS AND METHODS: A retrospective review of head and neck microvascular reconstruction by three different surgical services over 15 months at one tertiary care hospital was performed. Demographics, flap type, monitoring technique, complications, and flap outcomes were recorded. Monitoring techniques were (1) implantable/handheld Doppler or (2) NIRS. Flap monitoring outcomes were evaluated using multivariate analysis. RESULTS: 119 flaps were performed by four surgeons with a success rate of 92% (109/119). Flaps were monitored with Doppler (40%) or NIRS (60%). There was no difference in flap success based on monitoring technique. An ROC analysis identified that the optimal cutoff in immediate StO2 for classifying flap success at discharge was 68%. CONCLUSIONS: NIRS was successfully implemented in a high-volume head and neck reconstructive practice. NIRS remote monitoring allowed for flap surveillance without requiring in-hospital presence and was able to identify both arterial and venous compromise.

A fair comparison of tree-based and parametric methods in multiple imputation by chained equations.

Multiple imputation by chained equations (MICE) has emerged as a leading strategy for imputing missing epidemiological data due to its ease of implementation and ability to maintain unbiased effect estimates and valid inference. Within the MICE algorithm, imputation can be performed using a variety of parametric or nonparametric methods. Literature has suggested that nonparametric tree-based imputation methods outperform parametric methods in terms of bias and coverage when there are interactions or other nonlinear effects among the variables. However, these studies fail to provide a fair comparison as they do not follow the well-established recommendation that any effects in the final analysis model (including interactions) should be included in the parametric imputation model. We show via simulation that properly incorporating interactions in the parametric imputation model leads to much better performance. In fact, correctly specified parametric imputation and tree-based random forest imputation perform similarly when estimating the interaction effect. Parametric imputation leads to slightly higher coverage for the interaction effect, but it has wider confidence intervals than random forest imputation and requires correct specification of the imputation model. Epidemiologists should take care in specifying MICE imputation models, and this paper assists in that task by providing a fair comparison of parametric and tree-based imputation in MICE.

Maternal diet during lactation and breast-feeding practices have synergistic association with child diet at 6 years.

OBJECTIVE: Children breast-fed during infancy consume more fruits and vegetables than formula-fed children. This pattern is likely due, in part, to infant learning from flavours of the mother's diet transmitted through breast milk, but more research is needed to understand associations between early flavour exposures and later dietary patterns. We examined whether breast-feeding and maternal fruit and vegetable consumption during nursing were synergistically associated with higher child fruit and vegetable consumption. DESIGN: Prospective cohort study of breast-feeding duration, maternal diet postpartum and child diet. Complete breast-feeding and maternal diet data were available for 1396 mother-child dyads; multiple imputation was used for missing data in other variables. In separate multivariable logistic regression models, we estimated the adjusted odds of high child fruit or vegetable consumption at 12 months or 6 years as a function of breast-feeding duration, maternal fruit or vegetable consumption during nursing, and their interaction. SETTING: The Infant Feeding Practices Study II and Year 6 Follow-Up. PARTICIPANTS: Mother-child dyads followed from birth to 6 years during 2005-2012 in the USA. RESULTS: Longer breast-feeding duration was associated with high child fruit and vegetable consumption at 12 months. At 6 years, the interaction between breast-feeding duration and maternal vegetable consumption was associated with high child vegetable consumption. CONCLUSIONS: Higher maternal vegetable consumption and longer breast-feeding duration were synergistically associated with high child vegetable consumption at 6 years, independent of sociodemographic characteristics and fruit and vegetable availability. Exposures to vegetable flavours through breast milk may promote later child vegetable consumption.

Estradiol regulates daily rhythms underlying diet-induced obesity in female mice.

The circadian system is a critical regulator of metabolism and obesity in males, but its role in regulating obesity in females is poorly understood. Because there are sex differences in the development of obesity and susceptibility to obesity-related disorders, we sought to determine the role of estrogens in regulating the circadian mechanisms underlying diet-induced obesity. When fed high-fat diet, C57BL/6J male mice gain weight, whereas females are resistant to diet-induced obesity. Here, we demonstrate that estradiol regulates circadian rhythms in females to confer resistance to diet-induced obesity. We found that ovariectomized females with undetectable circulating estrogens became obese and had disrupted daily rhythms of eating behavior and locomotor activity when fed a high-fat diet. The phase of the liver molecular circadian rhythm was also altered by high-fat diet feeding in ovariectomized mice. Estradiol replacement in ovariectomized females a fed high-fat diet rescued these behavioral and tissue rhythms. Additionally, restoring the daily rhythm of eating behavior in ovariectomized females with time-restricted feeding inhibited diet-induced obesity and insulin resistance. Together, these data suggest that the circadian system is a target for treating obesity and its comorbidities in women after menopause, when circulating levels of estrogens are too low to protect their circadian rhythms.

Leveraging Methylome-Environment Interaction to Detect Genetic Determinants of Disease.

OBJECTIVE: The association between DNA methylation and a trait of interest may depend on an environmental exposure, and incorrectly accounting for this dependence can lead to a reduction in power of the standard tests used in epigenome-wide association studies. We present the M-ME test to jointly test for the main effect of DNA methylation and methylation-environment interaction. METHODS: Through simulation, we compare the power and type 1 error of the M-ME test to a standard marginal test (M test) and a standard interaction test (ME test) under 1,800 different underlying models. These models allow for methylation-environment correlation and measurement error in the exposure. RESULTS: In many true underlying models, either the M test or the ME test has very low power, but the M-ME test has optimal or nearly optimal power to detect a DNA methylation effect in all models considered, including those with methylation- environment dependence and measurement error in the exposure. Type 1 error inflation occurs in the tests when the exposure is measured with error and correlated with DNA methylation. CONCLUSION: The M-ME test is an attractive choice for studies aiming to detect any DNA methylation association when little is known about the epigenetic associations a priori.

The Implementation of Recommender Systems for Mental Health Recovery Narratives: Evaluation of Use and Performance.

BACKGROUND: Recommender systems help narrow down a large range of items to a smaller, personalized set. NarraGive is a first-in-field hybrid recommender system for mental health recovery narratives, recommending narratives based on their content and narrator characteristics (using content-based filtering) and on narratives beneficially impacting other similar users (using collaborative filtering). NarraGive is integrated into the Narrative Experiences Online (NEON) intervention, a web application providing access to the NEON Collection of recovery narratives. OBJECTIVE: This study aims to analyze the 3 recommender system algorithms used in NarraGive to inform future interventions using recommender systems for lived experience narratives. METHODS: Using a recently published framework for evaluating recommender systems to structure the analysis, we compared the content-based filtering algorithm and collaborative filtering algorithms by evaluating the accuracy (how close the predicted ratings are to the true ratings), precision (the proportion of the recommended narratives that are relevant), diversity (how diverse the recommended narratives are), coverage (the proportion of all available narratives that can be recommended), and unfairness (whether the algorithms produce less accurate predictions for disadvantaged participants) across gender and ethnicity. We used data from all participants in 2 parallel-group, waitlist control clinical trials of the NEON intervention (NEON trial: N=739; NEON for other [eg, nonpsychosis] mental health problems [NEON-O] trial: N=1023). Both trials included people with self-reported mental health problems who had and had not used statutory mental health services. In addition, NEON trial participants had experienced self-reported psychosis in the previous 5 years. Our evaluation used a database of Likert-scale narrative ratings provided by trial participants in response to validated narrative feedback questions. RESULTS: Participants from the NEON and NEON-O trials provided 2288 and 1896 narrative ratings, respectively. Each rated narrative had a median of 3 ratings and 2 ratings, respectively. For the NEON trial, the content-based filtering algorithm performed better for coverage; the collaborative filtering algorithms performed better for accuracy, diversity, and unfairness across both gender and ethnicity; and neither algorithm performed better for precision. For the NEON-O trial, the content-based filtering algorithm did not perform better on any metric; the collaborative filtering algorithms performed better on accuracy and unfairness across both gender and ethnicity; and neither algorithm performed better for precision, diversity, or coverage. CONCLUSIONS: Clinical population may be associated with recommender system performance. Recommender systems are susceptible to a wide range of undesirable biases. Approaches to mitigating these include providing enough initial data for the recommender system (to prevent overfitting), ensuring that items can be accessed outside the recommender system (to prevent a feedback loop between accessed items and recommended items), and encouraging participants to provide feedback on every narrative they interact with (to prevent participants from only providing feedback when they have strong opinions).

Higher First 30-Day Dose of Buprenorphine for Opioid Use Disorder Treatment Is Associated With Decreased Mortality.

OBJECTIVE: Buprenorphine is a medication for opioid use disorder that reduces mortality. This study aims to investigate the less well-understood relationship between the dose in the early stages of treatment and the subsequent risk of death. METHODS: We used Kentucky prescription monitoring data to identify adult Kentucky residents initiating transmucosal buprenorphine medication for opioid use disorder (January 2017 to November 2019). Average daily buprenorphine dose for days covered in the first 30 days of treatment was categorized as ≤8 mg, >8 to ≤16 mg, and >16 mg. Patients were followed for 365 days after the first 30 days of buprenorphine treatment. Endpoints were opioid-involved overdose death and death from other causes. Causes and dates of death were obtained using Kentucky death certificate records. Associations were evaluated using multivariable Fine and Gray models adjusting for patient baseline characteristics. RESULTS: In the cohort of 49,857 patients, there were 227 opioid-involved overdose deaths and 459 deaths from other causes. Compared with ≤8 mg, the adjusted subdistribution hazard ratio (aSHR) of opioid-involved overdose death decreased by 55% (aSHR, 0.45; 95% confidence interval [CI], 0.34-0.60) and 64% (aSHR, 0.36; 95% CI, 0.25-0.52) for patients receiving doses of >8 to ≤16 mg and >16 mg, respectively. The incidence of death from other causes was lower in patients receiving >8 to ≤16 mg (aSHR, 0.78; 95% CI, 0.62-0.98) and >16 mg (aSHR, 0.62; 95% CI, 0.47-0.80) versus ≤8 mg dose. CONCLUSIONS: Higher first 30-day buprenorphine doses were associated with reduced opioid-involved overdose death and death from other causes, supporting benefit of higher dosing in reducing mortality.

Peer review of clinical and translational research manuscripts: Perspectives from statistical collaborators.

Research articles in the clinical and translational science literature commonly use quantitative data to inform evaluation of interventions, learn about the etiology of disease, or develop methods for diagnostic testing or risk prediction of future events. The peer review process must evaluate the methodology used therein, including use of quantitative statistical methods. In this manuscript, we provide guidance for peer reviewers tasked with assessing quantitative methodology, intended to complement guidelines and recommendations that exist for manuscript authors. We describe components of clinical and translational science research manuscripts that require assessment including study design and hypothesis evaluation, sampling and data acquisition, interventions (for studies that include an intervention), measurement of data, statistical analysis methods, presentation of the study results, and interpretation of the study results. For each component, we describe what reviewers should look for and assess; how reviewers should provide helpful comments for fixable errors or omissions; and how reviewers should communicate uncorrectable and irreparable errors. We then discuss the critical concepts of transparency and acceptance/revision guidelines when communicating with responsible journal editors.

Better together? Comparing physical activity of parents walking outdoors with and without their child.

This study compares the physical activity levels and enjoyment of parents (n â€‹= â€‹50; age â€‹= â€‹41.8 â€‹± â€‹4.0 years) during outdoor, self-paced walking sessions while walking alone and when walking with their 6-to-12-year-old child. Step counts, moderate-to-vigorous physical activity (MVPA), vigorous physical activity, and enjoyment were compared using paired t-tests. Regression modeling was used to examine the impact of children's age and adults' and children's body mass index on the disparity in step counts experienced by adults. Adults attained high percentages of time spent in MVPA while walking alone (99.8%) and when walking with their child (96.6%). However, more of this time was categorized as vigorous physical activity when walking alone (13.6% vs. 3.0%, p â€‹= â€‹0.006). Adults' step counts decreased by an average of 6.4% while walking with their child compared to walking alone (p â€‹< â€‹0.001). This reduction was greater for parents of younger children (p â€‹= â€‹0.004). In obese adults, the reduction in step counts experienced while walking with their child was not as great as the reduction experienced by normal-weight adults (p â€‹= â€‹0.042). Although adults obtained higher step counts and vigorous physical activity while walking alone, they enjoyed walking more with their child (p â€‹< â€‹0.001). Health practitioners should be aware of this tradeoff when making recommendations for parent-child co-participation in physical activity, and parents may wish to supplement their physical activity obtained while walking with their child(ren) with additional activities that result in vigorous physical activity.

Building a strong collaborative biostatistics workforce: Strategies for effective intra-unit professional development activities.

Ongoing professional development is important for collaborative biostatisticians, as it enables them to remain current with the latest advances in statistical methodology and software, refine their analytical skills, and expand their domain knowledge, thereby facilitating their ability to contribute effectively to biomedical research. Although external opportunities for professional development, such as attending conferences and workshops, are widely recognized and valued in the field of biostatistics, there has been comparatively little attention given to internal opportunities for enhancing the skills and knowledge of biostatisticians which can be implemented with lower financial and time investment than external offerings. The purpose of this paper is to offer guidance for ongoing internal professional development activities that can be employed by collaborative biostatistics units in universities and academic medical centers to complement structured curricula and initial training. Specific examples of activities are provided so that collaborative biostatisticians and/or managers of biostatistical units can flexibly combine components to create an appropriately scaled, customized program that meets the needs of themselves or of the unit.

Changes in transmucosal buprenorphine utilization for opioid use disorder treatment during the COVID-19 pandemic in Kentucky.

PURPOSE: With surging opioid-involved overdoses, maintaining access to opioid use disorder (OUD) treatment is critical during the COVID-19 pandemic. We examined changes in transmucosal buprenorphine prescribing for OUD treatment in Kentucky after the national COVID-19 emergency declaration, with a focus on rural-urban differences. METHODS: Using 2019-2020 prescription monitoring data, we performed segmented regression analysis for an interrupted time series design to evaluate changes in weekly rates (per 100,000 residents) of dispensed prescriptions, unique individuals with dispensed prescriptions, and average days' supply for dispensed prescriptions of transmucosal buprenorphine. FINDINGS: The weekly rates of dispensed prescriptions and unique individuals with dispensed prescriptions were higher for rural residents than urban residents. After the national COVID-19 emergency declaration, rural and urban residents experienced similar immediate drops in the rate of dispensed prescriptions (rural -33.4; urban -24.3) and unique patients with dispensed prescriptions (rural -25.0; urban -17.1), followed by similar sustained increases. Both measures surpassed the prepandemic levels in mid-June 2020. Patients residing in urban areas received averagely longer prescriptions at baseline (urban: 11.0 days; rural: 10.5 days). The average weekly days' supply increased in the week after the national emergency declaration, but the estimated increase was higher (P = .004) for urban (0.8 days) versus rural (0.5 days) residents. CONCLUSIONS: Transmucosal buprenorphine utilization increased during the COVID-19 pandemic after experiencing interruption during the initial weeks of the pandemic. Future studies should evaluate the contribution of the relaxed telemedicine buprenorphine prescribing regulations during the COVID-19 national emergency on initiation and maintenance of buprenorphine treatment.

Medicaid expansion and access to naloxone in metropolitan and nonmetropolitan areas.

PURPOSE: The opioid crisis remains a major public health concern in the United States. Naloxone is used to reverse opioid overdoses. This study examined Medicaid expansion on naloxone prescriptions in retail pharmacies in metropolitan (metro) and nonmetropolitan (nonmetro) areas (2011-2017). METHODS: We used population average models to evaluate the association of Medicaid expansion at the state level on the number of naloxone prescriptions dispensed and the percentage paid by Medicaid, including adjustment for opioid-related and state-level policy covariates. Difference-in-difference modeling was performed as a sensitivity analysis. FINDINGS: States that expanded Medicaid had higher unadjusted naloxone dispensing rates and Medicaid-paid percentage of naloxone in metro and nonmetro areas. Medicaid expansion was not associated with the number of naloxone dispensed in either metro (adjusted rate ratio (ARR) = 1.26, 95% CI: [0.80, 1.97]) or nonmetro (ARR = 0.67, 95% CI: [0.37, 1.19]) areas after covariate adjustment. In metro areas, Medicaid expansion was associated with a significant increase of 3.86 percentage points (95% CI: [0.09, 7.63]) in the Medicaid-paid percentage of naloxone dispensing compared to nonexpansion states, but this association was not significant in nonmetro areas. There was also a significant time by Medicaid expansion interaction on the Medicaid-paid percentage of naloxone dispensed (metro: estimate = 0.74, 95% CI: [0.36, 1.12]; nonmetro: estimate = 0.68, 95% CI: [0.17, 1.18]). CONCLUSIONS: Medicaid expansion increased naloxone access by increasing the Medicaid-paid percentage of naloxone prescriptions in metro areas. States with Medicaid expansion had a faster rate of increase in the Medicaid-paid percentage of naloxone than states without Medicaid expansion in nonmetro areas.

Associations Among PTSD, Cognitive Functioning, and Health-Promoting Behavior in Post-9/11 Veterans.

INTRODUCTION: PTSD is associated with negative health behaviors that increase chronic disease risk, yet health behaviors and their determinants are not well investigated in this context. One understudied mechanism of health behaviors is cognitive functioning. Deficits in cognitive functioning may undermine engagement in health-promoting behavior, thereby increasing the negative impact of PTSD. We tested three hypotheses: (1) Greater PTSD symptom severity is associated with less health-promoting behavior; (2) greater PTSD symptom severity is associated with poorer cognitive functioning across verbal memory, processing speed, attention, and executive functioning domains; and (3) verbal memory and executive functioning exhibit indirect effects on the relationship between PTSD and health-promoting behavior. MATERIALS AND METHODS: We examined associations between PTSD symptom severity (Clinician-Administered PTSD Scale for DSM-IV), cognitive functioning, and health-promoting behavior (Health-Promoting Lifestyle Profile II) in 124 post-9/11 veterans (average age = 37.82; 85.5% male; 63.7% White; 18.5% Black; 26.6% Hispanic). Cognitive domains examined included verbal memory (California Verbal Learning Test), processing speed (Digit Symbol Coding), attention and working memory (Digit Span), and executive functions (Trail Making Test and Stroop Interference). RESULTS: Regression analyses indicated that greater PTSD symptom severity was associated with less health-promoting behavior (B = -.0101, SE = 0.0016, P < .0001; R2 = 0.3052). Path analyses revealed that verbal learning and memory partially accounted for this relationship (R2 = 0.037- 0.043; P < .05). CONCLUSIONS: Therapeutic targeting of these relationships may have implications for the prevention of long-term disease impact in veterans; longitudinal research is needed to elucidate the potential impact on chronic disease.

Optimizing team science in an academic medical center: A qualitative examination of investigator perspectives.

Introduction: Optimizing the effectiveness of a team-based approach to unite multiple disciplines in advancing specific translational areas of research is foundational to improving clinical practice. The current study was undertaken to examine investigators' experiences of participation in transdisciplinary team science initiatives, with a focus on challenges and recommendations for improving effectiveness. Methods: Qualitative interviews were conducted with investigators from twelve multidisciplinary teams awarded pilot research funding by the University of Kentucky College of Medicine to better understand the barriers and facilitators to effective team science within an academic medical center. An experienced qualitative researcher facilitated one-on-one interviews, which lasted about one hour. Structured consensus coding and thematic analysis were conducted. Results: The sample was balanced by gender, career stage (five were assistant professor at the time of the award, seven were senior faculty), and training (six were PhDs; six were MD physicians). Key themes at the team-level centered on the tension between clinical commitments and research pursuits and the limitations for effective team functioning. Access to tangible support from home departments and key university centers was identified as a critical organizational facilitator of successful project completion. Organizational barriers centered on operationalizing protected time for physicians, gaps in effective mentoring, and limitations in operational support. Conclusions: Prioritizing tailored mentoring and career development support for early career faculty, and particularly physician faculty, emerged as a key recommendation for improving team science in academic medical centers. The findings contribute to establishing best practices and policies for team science in academic medical centers.