Nucleation of fibronectin fibril assembly requires binding between heparin and the 13th type III module of fibronectin.

Fibronectin (FN), a critical component of the extracellular matrix, is assembled into fibrils through a cell-mediated process. Heparan sulfate (HS) binds to the III13 module of FN, and fibroblasts lacking this glycosaminoglycan exhibit reduced FN fibril assembly. To determine if HS depends on III13 to control FN assembly, we deleted both III13 alleles in NIH 3T3 cells using the CRISPR-Cas9 system. ΔIII13 cells assembled fewer FN matrix fibrils and less DOC-insoluble FN matrix than wildtype cells. Little if any mutant FN matrix was assembled when purified ΔIII13 FN was provided to Chinese hamster ovary (CHO) cells, showing that lack of III13 caused the deficiency in assembly by ΔIII13 cells. Addition of heparin promoted the assembly of wildtype FN by CHO cells, but it had no effect on the assembly of ΔIII13 FN. Furthermore, heparin binding stabilized the folded conformation of III13 and prevented it from self-associating with increasing temperature suggesting that stabilization by HS/heparin binding might regulate interactions between III13 and other FN modules. This effect would be particularly important at matrix assembly sites where our data show that ΔIII13 cells require both exogenous wildtype FN and heparin in the culture medium to maximize assembly site formation. Our results show that heparin-promoted growth of fibril nucleation sites is dependent on III13. We conclude that HS/heparin binds to III13 to promote and control the nucleation and development of FN fibrils.

Postrelease Risk of Overdose and All-Cause Death Among Persons Released From Jail or Prison: Minnesota, March 2020-December 2021.

Objectives. To determine mortality risk among those recently released from a Minnesota jail or prison. Methods. Using linked prison, jail, and death records, our retrospective cohort study followed 99 065 people who were released from Minnesota jails and prisons between March 1, 2020, and December 31, 2021. We explored differences between jail and prison exposures regarding mortality using standardized mortality ratios. Results. Adjusting for age and gender, we estimated that the rate of overdose death for people released from jail was 15.5 times that of the Minnesota general population. Overdose death rates for people released from prison were even higher at 28.3 times the rate of the Minnesota general population. Conclusions. Drug overdose was the leading cause of death for people reentering their communities from both jail and prison in Minnesota-with opioids being the leading cause of overdoses. Overdose death relative to the general population was double the estimates from earlier studies among people leaving prison. Providing seamless access to medications for opioid use disorder during and after incarceration is important to lower the risk of death following release. (Am J Public Health. 2024;114(9):913-922. https://doi.org/10.2105/AJPH.2024.307723).

Providers' knowledge and perception of xylazine in the unregulated drug supply: a sequential explanatory mixed-methods study.

BACKGROUND: Xylazine is increasingly prevalent in the unregulated opioid supply in the United States. Exposure to this adulterant can lead to significant harm, including prolonged sedation and necrotic wounds. In the absence of literature describing healthcare providers' experiences with treating patients who have been exposed to xylazine, we aimed to explore what gaps must be addressed to improve healthcare education and best practices. METHODS: From October 2023 to February 2024, we conducted a sequential explanatory mixed-methods study, with (1) a quantitative survey phase utilizing convenience sampling of healthcare providers treating patients in Connecticut and (2) a qualitative semi-structured interview phase utilizing purposive sampling of providers with experience treating patients with xylazine exposure. Summary statistics from the survey were tabulated; interview transcripts were analyzed using thematic analysis. RESULTS: Seventy-eight eligible healthcare providers participated in our survey. Most participants had heard of xylazine (n = 69, 95.8%) and had some knowledge about this adulterant; however, fewer reported seeing one or more patients exposed to xylazine (n = 46, 59.8%). After sampling from this subgroup, we conducted fifteen in-depth interviews. This qualitative phase revealed five themes: (1) while xylazine is novel and of concern, this is not necessarily exceptional (i.e., there are other emerging issues for patients who use drugs); (2) participants perceived that xylazine was increasingly prevalent in the drug supply, even if they were not necessarily seeing more patients with xylazine-related outcomes (XROs); (3) patients primarily presented with non-XROs, making it difficult to know when conversations about xylazine were appropriate; (4) patients with XROs may experience issues accessing healthcare; (5) providers and their patients are learning together about how to minimize XROs and reduce the sense of helplessness in the face of a novel adulterant. CONCLUSIONS: Xylazine-specific education for healthcare providers is currently insufficient. Improving this education, as well as resources (e.g., drug checking technologies) and data (e.g., research on prevention and treatment of XROs), is crucial to improve care for patients who use drugs.

Heparan sulfate is necessary for the early formation of nascent fibronectin and collagen I fibrils at matrix assembly sites.

Fibronectin (FN), an essential component of the extracellular matrix (ECM), is assembled via a cell-mediated process in which integrin receptors bind secreted FN and mediate its polymerization into fibrils that extend between cells, ultimately forming an insoluble matrix. Our previous work using mutant Chinese hamster ovary (CHO) cells identified the glycosaminoglycan heparan sulfate (HS) and its binding to FN as essential for the formation of insoluble FN fibrils. In this study, we investigated the contributions of HS at an early stage of the assembly process using knockdown of exostosin-1 (EXT1), one of the glycosyltransferases required for HS chain synthesis. NIH 3T3 fibroblasts with decreased EXT1 expression exhibited a significant reduction in both FN and type I collagen in the insoluble matrix. We show that FN fibril formation is initiated at matrix assembly sites, and while these sites were formed by cells with EXT1 knockdown, their growth was stunted compared with wild-type cells. The most severe defect observed was in the polymerization of nascent FN fibrils, which was reduced 2.5-fold upon EXT1 knockdown. This defect was rescued by the addition of exogenous soluble heparin chains long enough to simultaneously bind multiple FN molecules. The activity of soluble heparin in this process indicates that nascent fibril formation depends on HS more so than on the protein component of a specific HS proteoglycan. Together, our results suggest that heparin or HS is necessary for concentrating and localizing FN molecules at sites of early fibril assembly.

National Institutes of Health Diversity Supplement Awards by Medical School.

BACKGROUND: Increasing medical school faculty diversity is an urgent priority. National Institutes of Health (NIH) diversity supplements, which provide funding and career development opportunities to individuals underrepresented in research, are an important mechanism to increase faculty diversity. OBJECTIVE: Analyze diversity supplement utilization by medical schools. DESIGN: Retrospective cohort study. PARTICIPANTS: All R01 grant-associated diversity supplements awarded to medical schools from 2005 to 2020. Diversity supplements were identified using the publicly available NIH RePORTER database. MAIN MEASURES: Main measures were the number of R01-associated diversity supplements awarded to medical schools each year by medical school NIH funding status and the number of R01-associated diversity supplements awarded to individual medical schools in the NIH top 40 by funding status. We also examined the percentage of R01 grants with an associated diversity supplement by NIH funding status and individual medical school in the NIH top 40. KEY RESULTS: From 2005 to 2020, US medical school faculty received 1389 R01-associated diversity supplements. The number of diversity supplements awarded grew from 2012 to 2020, from ten to 187 for top 40 schools, and from seven to 83 for non-top 40 schools. The annual growth rate for diversity supplement awards at NIH top 40 schools (44.2%) was not significantly different than the annual growth rate among non-top 40 schools (36.2%; p = 0.68). From 2005 to 2020, the highest number of diversity supplements that an individual medical school received was 56 and the lowest number was four (mean = 24.6, SD = 11.7). The highest percentage of R01 grants with an associated diversity supplement received by a school was 4.5% and the lowest percentage was 0.79% (mean = 2.3%, SD = 0.98). CONCLUSION: Medical schools may be missing an opportunity to address the continuing shortage of individuals historically underrepresented in biomedical science and should consider additional mechanisms to enhance diversity supplement utilization.

Integrated Care Models: HIV and Substance Use.

PURPOSE OF REVIEW: Behaviors and practices associated with substance use contribute to lack of HIV virologic suppression and onward transmission. In the USA, many recent HIV outbreaks have been connected with substance use. Evidence-based strategies for integrating care of those at risk for and living with HIV and who use substances continue to evolve. This review, based on scientific and medical literature through March 2023, provides an overview and evaluation of initiatives for integrated care aimed to serve patients at risk for and with HIV and a substance use disorder. RECENT FINDINGS: Integrated care services can improve health outcomes for patients at risk for and with HIV and a substance use disorder; for instance, treatment for an opioid use disorder can help improve HIV viral suppression. Brick-and-mortar facilities can provide successful care integration with appropriate clinic leadership to support multidisciplinary care teams, up-to-date provider training, and sufficient pharmacy stock for substance use treatment. Delivering healthcare services to communities (e.g., mobile healthcare clinics and pharmacies, telehealth) may prove to be an effective way to provide integrated services for those with or at risk of HIV and substance use disorders. Incorporating technology (e.g., mobile phone applications) may facilitate integrated care. Other venues, including harm reduction programs and carceral settings, should be targets for integrated services. Venues providing healthcare should invest in integrated care and support legislation that increases access to services related to HIV and substance use.

"It's starting to weigh on me": Exploring the Experiences and Support Needs of Harm Reduction Staff in Connecticut using the Social-Ecological Model.

BACKGROUND: The experiences and perceived support needs of harm reduction workers in the USA have been understudied. While previous research has explored staff burnout and role-related stress, there is a research gap around potential supports for staff wellbeing and individual longevity in their roles. This is especially critical given the growing overdose crisis and the need for sustainable harm reduction programming. Thus, we sought to describe the experiences of harm reduction staff and identify the perceived support that could empower harm reduction staff to successfully navigate their roles. METHODS: Purposive sampling methods were used to recruit harm reduction staff working in Connecticut. Seventeen semi-structured, one-on-one interviews were conducted between December 2022 and March 2023. Participants were asked about their experiences with role-related stressors and supports. Informed by the Social-Ecological Model, transcripts were coded using both inductive and deductive codes, and themes were developed using thematic analysis approaches. RESULTS: Study participants described their experiences working in harm reduction and the numerous ways they already are or could be receiving support in their roles. These experiences were organized into eight themes according to the levels of the Social-Ecological Model. At the individual level, participants explained that support could help them navigate the variability of the physical environment, boundary setting, and self-care. Relationships between clients and co-workers were both identified as means of support at the interpersonal level, helping participants navigate difficult situations and feelings of stress. At the organizational level, study participants explained how they look to their organization to provide sufficient support by way of training, staffing, compensation, and benefits. Additionally, participants stressed the importance of having supervisors who valued their work and provided emotional support. Lastly, at the community level, participants discussed how support was needed to help them navigate complex systems while working with a stigmatized population in an often-stigmatized field. CONCLUSIONS: To best support harm reduction staff in their day-to-day roles, our findings underscore the need for support on multiple levels. Future research could explore how the provision of support to harm reduction staff impacts not only staff perceptions of support but also the success of clients accessing harm reduction services.

Associations between ergogenic supplement use and eating behaviors among university students.

Ergogenic supplements to improve athletic performance are commonly used among college athletes, but little is known about their association with eating disorder symptoms. The objective of this study was to examine associations between ergogenic supplement use and disordered eating attitudes and behaviors among university students, and to compare differences by sex. Undergraduate students from 10 top-ranked National College Athletics Association (NCAA) Division I colleges completed an online survey on supplement use, athletic activities, and eating attitudes and behaviors. Among 1633 university students, males (38.9%) reported higher rates of current supplement use than females (15.2%) (p < .001). In linear regression models adjusting for athletic status and body mass index, current supplement use was associated with higher Eating Disorders Examination-Questionnaire (EDE-Q) Global, Shape Concern, and Restraint scores in both males and females. Supplement use was associated with driven/compelled exercise (OR 2.00, 95% CI 1.33-2.99) in males and diuretic (OR 6.39, 95% CI 2.02-20.22) and diet pill use (OR 3.07, 95% CI 1.79-5.27) in females. Results suggest ergogenic supplement use is common in undergraduates and associated with disordered eating attitudes and behaviors. Clinicians should screen for disordered eating behaviors particularly in young adults who use ergogenic supplements.

Eating behavior and reasons for exercise among competitive collegiate male athletes.

PURPOSE: Research concerning eating disorders among adolescent and young adult male athletes is limited compared with female counterparts, but increasing evidence indicates that they may be at unique risk for unhealthy exercise and eating behavior. The current study aimed to characterize unhealthy exercise and eating behavior according to competitive athlete status, as well as per sport type. METHOD: Collegiate male athletes (N = 611), each affiliated with one of the 10 National College Athletics Association (NCAA) Division I schools in the United States, completed an online survey, reporting on eating and extreme weight control behaviors, and reasons for exercise. RESULTS: Competitive athletes endorsed increased driven exercise and exercising when sick. Baseball players, cyclists, and wrestlers emerged as the sports with the most players reporting elevated Eating Disorder Examination-Questionnaire scores in a clinical range, and basketball players reported the highest rates of binge eating. overall, baseball players, cyclists, rowers, and wrestlers appeared to demonstrate the greatest vulnerability for unhealthy eating and exercise behavior. CONCLUSION: Findings revealed differences between competitive and non-competitive male athletes. Among competitive athletes, results identified unique risk for unhealthy eating and exercise behavior across a variety of sport categories and support continued examination of these attitudes and behaviors in a nuanced manner. LEVEL II: Evidence obtained from well-designed controlled trials without randomization.

Two cases of imported respiratory diphtheria in Edinburgh, Scotland, October 2019.

We report two cases of respiratory toxigenic Corynebacterium diphtheriae infection in fully vaccinated UK born adults following travel to Tunisia in October 2019. Both patients were successfully treated with antibiotics and neither received diphtheria antitoxin. Contact tracing was performed following a risk assessment but no additional cases were identified. This report highlights the importance of maintaining a high index of suspicion for re-emerging infections in patients with a history of travel to high-risk areas outside Europe.

Interspecies Comparison of Control Data From Embryo-Fetal Development Studies in Sprague-Dawley Rats, New Zealand White Rabbits, and Göttingen Minipigs.

Species-dependent differences in relative incidence of spontaneous variations and malformations should be considered in the assessment of the translational value of reproductive and developmental safety assessments. The objective of this evaluation was to compare litter parameters and the frequency of external, visceral, and skeletal malformations and variations across species in the Sprague-Dawley rat, New Zealand White rabbit, and Göttingen minipig and to determine whether notable differences exist. Pregnant female rats (n = 824), rabbits (n = 540), and minipigs (n = 70) from vehicle control groups were included in the analysis, equating to 10,749 rat, 5,073 rabbit, and 378 pig fetuses collected at term by cesarean delivery. Preimplantation loss was more frequent than postimplantation loss in the rat and rabbit, whereas the opposite was observed in the minipig. Several external and visceral malformations and variations such as domed head, bent tail, abdominal edema, and anal atresia were observed in all 3 species. Visceral malformations of the heart and major blood vessels were remarkably more frequent in the minipig and rabbit, respectively; ventricular and atrium septum defects were observed in 1.9% and 2.1%, respectively, for the minipig fetuses, whereas they were observed in equal or less than 0.02% among the rat and rabbit fetuses evaluated in this study. Understanding species-dependent differences in spontaneous variations and malformations can be useful for the interpretation of embryo-fetal development study results. The current analysis identified relevant differences between commonly used species in reproductive toxicology with potential implications for data assessment.

Implementing the Trauma Evaluation and Management (TEAM) Course in Kenya.

BACKGROUND: Trauma training provides crucial knowledge and skills for health-care providers in low- and middle-income countries (LMICs). Although such training has been adapted for physicians and emergency personnel in LMICs, few courses have been offered for medical students. The Trauma Evaluation and Management (TEAM) course, developed by the American College of Surgeons, provides a valuable framework for providing this content to medical students in an LMIC-context. MATERIALS AND METHODS: We implemented the TEAM course at a single medical school in rural Kenya, for final-year medical students, utilizing the multimodal instruction and reference materials provided by the American College of Surgeons. We administered precourse and postcourse assessments, adapted the content for particular low-resource considerations, expanded the course to 2 d, and utilized a multidisciplinary and multinational group of surgical expert instructors. RESULTS: The entire final-year medical school class participated, and all completed pretesting and posttesting (100%, n = 61). Posttesting revealed significant improvement (P < 0.001), demonstrating successful knowledge acquisition, with the greatest improvements among the poorest performing decile on the pretest (P < 0.05). On narrative course feedback (100% completion, n = 61), participants appreciated instructors' interactive teaching style and the course's practical demonstrations, while requesting more time allotment for trauma training. CONCLUSIONS: We describe the feasibility of implementing TEAM training for final-year medical students in Kenya and demonstrate the course's effectiveness in this context as shown by knowledge acquisition. We plan for additional study to assess interval knowledge and skill retention. With refinement based on these results, we plan to repeat and expand trauma-education initiatives for medical students in LMICs.

A qualitative study of gender differences in the experiences of general surgery trainees.

BACKGROUND: Women surgeons continue to face unique challenges to professional advancement. Higher attrition rates and lower confidence among female surgical residents suggest that experiences during residency differ by gender. Few studies have investigated gender-specific experiences during training. This study identifies gender-based differences in the experiences of general surgery residents that could affect professional development. MATERIALS AND METHODS: Male and female general surgery residents at the University of Pittsburgh Medical Center participated in a semi-structured interview study exploring the significance of gender in training. Recurring themes were identified from transcribed interviews using inductive methods. Two individuals independently coded interviews. Themes were compared for male and female residents. Certain themes arose with greater frequency in reference to one gender over the other. RESULTS: Twenty-four male and eighteen female residents participated (87.5%) in the study. Fewer female residents self-identified as a "surgeon" (11.1% versus 37.5%, P < 0.001). Residents felt that patients and physicians more frequently disregarded female residents' professional role (P < 0.001). Female residents also more often mentioned perceiving aggressive behaviors from attendings and support staff (9% versus 1% and 10% versus 3%, respectively). Relative to men, women more often mentioned lack of mentorship (0% versus 8%), discomfort (4% versus 8%), feeling pressured to participate in unprofessional behaviors (2% versus 5%), and having difficulty completing tasks (5% versus 10%, P < 0.001). CONCLUSIONS: Women experience gender-based challenges during surgical training. Further investigation is needed to determine how these experiences affect professional development.

Next-generation sequencing and microarray-based interrogation of microRNAs from formalin-fixed, paraffin-embedded tissue: preliminary assessment of cross-platform concordance.

Next-generation sequencing is increasingly employed in biomedical investigations. Strong concordance between microarray and mRNA-seq levels has been reported in high quality specimens but information is lacking on formalin-fixed, paraffin-embedded (FFPE) tissues, and particularly for microRNA (miRNA) analysis. We conducted a preliminary examination of the concordance between miRNA-seq and cDNA-mediated annealing, selection, extension, and ligation (DASL) miRNA assays. Quantitative agreement between platforms is moderate (Spearman correlation 0.514-0.596) and there is discordance of detection calls on a subset of miRNAs. Quantitative PCR (q-RT-PCR) performed for several discordant miRNAs confirmed the presence of most sequences detected by miRNA-seq but not by DASL but also that miRNA-seq did not detect some sequences, which DASL confidently detected. Our results suggest that miRNA-seq is specific, with few false positive calls, but it may not detect certain abundant miRNAs in FFPE tissue. Further work is necessary to fully address these issues that are pertinent for translational research.

Students apply research methods to consumer decisions about cognitive enhancing drinks.

The goal of this class project was to provide students with a hands-on research experience that allowed autonomy, but eliminated duplication of effort and could be completed within one semester. Our resources were limited to a small supply budget and an introductory psychology subject pool. Six students from a behavioral neuroscience class tested claims made by a drink company that their product improves cognitive function. The students each chose a cognitive task for their part of the project. The tasks included the Donders Reaction Time Task, the Stroop Task, the Raven's Progressive Matrices, a short-term memory span test, the Rey-Osterrieth Complex Figure Test and a simple measure of prefrontal EEG activity. Participants were randomly assigned to an experimental or control drink. The experimental group received the putative cognitive enhancing drink and the control group received a placebo drink that was very similar in color and taste. The two drinks shared no active ingredients. Results suggest that the putative cognitive enhancing drink did not improve performance on any of the tasks and decreased performance on the short-term memory task. These findings are discussed in regard to implications for consumers as well as further research into supplements and their ability to improve cognitive performance. Each student presented his/her results at a university-wide research conference. This project provided a rich experience in which students had the opportunity to carry out a research project from conception to presentation.

Delays in Care by Race, Ethnicity, and Gender Before and During the COVID-19 Pandemic Using Cross-Sectional Data From the National Institutes of Health's All of Us Research Program.

PURPOSE: Delays in receiving medical care are an urgent problem. This study aims to determine whether the odds of, and reasons for, experiencing care delays differ by gender, race-ethnicity, and survey completion before versus during the COVID-19 pandemic. METHODS: We conducted a cross-sectional analysis of survey data from participants age ≥18 in the National Institutes of Health's All of Us Research Program collected from May 6, 2018, to January 1, 2022. Logistic regressions were performed to assess the association of gender, race-ethnicity, and survey completion date with any of nine reasons for delaying care in the past 12 months. RESULTS: Of 119,983 participants, 37.8% reported delaying care in the past 12 months. After adjusting for employment status, education, income, marital status, health insurance, and age, women of every race-ethnicity and Black and other race-ethnicity men were more likely than white men to report delays in care: Asian women (odds ratio [OR] 1.23; 95% confidence interval [CI] [1.13, 1.34]), Black men (OR 1.15; 95% CI [1.05, 1.25]) and women (OR 1.46; 95% CI [1.38, 1.54]), Hispanic women (OR 1.36; 95% CI [1.28, 1.44]), white women (OR 1.55; 95% CI [1.50, 1.60]), and other race-ethnicity men (OR 1.15; 95% CI [1.05, 1.27]) and women (OR 1.79; 95% CI [1.67, 1.91]). A small but statistically significant difference was seen in reports of care delays for non-pandemic-related reasons during versus before the COVID-19 pandemic (OR 0.88; 95% CI [0.83, 0.93]). CONCLUSIONS: In this study of a diverse group of U.S. participants, women and Black and other race-ethnicity men were more likely than white men to report delays in care, both before and during COVID-19. Addressing care delays may be necessary to ameliorate health disparities by race-ethnicity and gender.

Prevalence of Kratom Use Disorder Among Kratom Consumers.

OBJECTIVES: Kratom leaf products are increasingly consumed in the United States, with many consumers reporting they experience beneficial effects from kratom use. However, there is a growing concern for kratom's potential to result in dependence when used regularly. As such, we sought to assess, using Diagnostic and Statistical Manual of Mental Disorders , (DSM-5) , diagnostic criteria for substance use disorder, the prevalence of "kratom use disorder" (KUD) among kratom consumers. METHODS: Our cross-sectional study used an online, anonymous survey between February and May 2023. Through nonprobability sampling, we recruited people older than 18 years who currently consume kratom. Participants were asked about their kratom consumption patterns, adverse effects perceived to stem from kratom consumption, comorbid diagnoses, and components for a DSM-5 , substance use disorder, adapted for kratom. RESULTS: Among the total sample ( N = 2061), KUD criteria were met by 25.5% of participants ( n = 525); the most commonly reported symptoms were tolerance ( n = 427, 81.3%) and withdrawal ( n = 357, 68.0%). After adjusting for age, gender, daily frequency of kratom consumption, and history of either a substance use disorder or a mental health condition, those with a concurrent diagnosis of another substance use disorder had 2.83 times higher odds of meeting KUD criteria (95% CI, 2.19-3.67) compared with those without one. CONCLUSIONS: In this large cross-sectional study, most participants who met the criteria for a KUD diagnosis were categorized as having a mild or moderate KUD. Individual characteristics associated with KUD were related to being male, young, consuming kratom frequently, and having psychiatric and substance use disorder comorbidities.

Kratom addiction per DSM-5 SUD criteria, and kratom physical dependence: Insights from dosing amount versus frequency.

BACKGROUND: Kratom products are widely used in the United States, with inadequate understanding of how dosing amounts/frequencies relate to outcomes. METHODS: Between July-November 2022, we enrolled 395 active US adult kratom consumers into a remote study with a baseline survey. We examined self-reported typical dose amounts and frequencies across people and product types, and their associations with outcomes: multiple regression was used to examine whether amounts and frequencies (doses/day) were associated with acute effects, withdrawal symptoms, scores on the Subjective Opioid Withdrawal Scale (SOWS), and addiction (operationalized as DSM-5-based symptoms of kratom-use disorder, KUD). RESULTS: Participants were 54.9% male, aged 38.1 on average, and 81.3% White. Mean length of kratom use was 5.7 years. Most (95.9%) reported regularly using whole-leaf kratom products; 16 (4.1%) reported regular extract use. SOWS scores were mild to moderate on average (13.5, SD 11.9). KUD symptom counts were mostly in the mild/moderate range (80.7%). Withdrawal and KUD symptoms were more closely associated with dose frequency than dose amount. Men reported more acute effects, withdrawal symptoms with cessation, and KUD symptoms than women. CONCLUSIONS: Greater dose amount and frequency were systematically related to the number of withdrawal symptoms upon cessation and to KUD symptoms; the relationship was stronger for dose frequency than amount. Men may have more acute effects and more withdrawal and KUD symptoms than women. Although kratom may be used nonproblematically by some consumers, physical dependence (tolerance, withdrawal, or use to avoid withdrawal) and KUD become more likely with increasing dose frequency.

Use of Cannabinoids by People Who Consume Kratom in the United States.

OBJECTIVES: To estimate lifetime, past-year, and past-month prevalence of kratom, cannabis, and cannabidiol-only product use among adults 18 years and older in the United States, using 2 independent datasets. METHODS: Utilizing (a) the 2022 National Survey on Drug Use and Health (NSDUH) and (b) a 2022 online national convenience sample of adults who use kratom regularly (from our research group at the National Institute on Drug Abuse [NIDA]), we examined key demographic information as well as lifetime, past-year, and past-month substance use and preferences. RESULTS: Among the full sample of adults from the 2022 NSDUH, the prevalence of lifetime use was 49.69% for cannabis, 34.09% for cannabidiol-only products, and 1.93% for kratom. When solely examining participants who have used kratom, both independent datasets showed higher proportions of cannabis use over the lifetime-92.81% (95% confidence interval: 90.31-95.31) in the NSDUH subset and 92.16% (95% confidence interval: 89.37-94.95) in our NIDA sample. CONCLUSIONS: Our study demonstrates that people are co-using kratom with cannabis and/or cannabidiol-only products at the same time or during the same time period, though more research is needed to understand people's motivations and practices for such co-use. Co-use might result in herb-herb interactions that may impact research findings and clinical outcomes for people who use kratom.