Associations Between Family History of Alcohol and/or Substance Use Problems and Frontal Cortical Development From 9 to 13 Years of Age: A Longitudinal Analysis of the ABCD Study.

Background: Previous investigations that have examined associations between family history (FH) of alcohol/substance use and adolescent brain development have been primarily cross-sectional. Here, leveraging a large population-based sample of youths, we characterized frontal cortical trajectories among 9- to 13-year-olds with (FH+) versus without (FH-) an FH and examined sex as a potential moderator. Methods: We used data from 9710 participants in the Adolescent Brain Cognitive Development (ABCD) Study (release 4.0). FH+ was defined as having ≥1 biological parents and/or ≥2 biological grandparents with a history of alcohol/substance use problems (n = 2433). Our primary outcome was frontal cortical structural measures obtained at baseline (ages 9-11) and year 2 follow-up (ages 11-13). We used linear mixed-effects models to examine the extent to which FH status qualified frontal cortical development over the age span studied. Finally, we ran additional interactions with sex to test whether observed associations between FH and cortical development differed significantly between sexes. Results: For FH+ (vs. FH-) youths, we observed increased cortical thinning from 9 to 13 years across the frontal cortex as a whole. When we probed for sex differences, we observed significant declines in frontal cortical thickness among boys but not girls from ages 9 to 13 years. No associations were observed between FH and frontal cortical surface area or volume. Conclusions: Having a FH+ is associated with more rapid thinning of the frontal cortex across ages 9 to 13, with this effect driven primarily by male participants. Future studies will need to test whether the observed pattern of accelerated thinning predicts future substance use outcomes.

Effects of parental mental health and family environment on impulsivity in preadolescents: a longitudinal ABCD study®.

Introduction: Impulsivity is a known risk factor for the development of substance use disorders and other psychiatric conditions that is influenced by both genetics and environment. Although research has linked parental mental health to children's impulsivity, potential mediators of this relationship remain understudied. The current investigation leverages the large national Adolescent Brain Cognitive Development (ABCD) Study to assess the mediating role of family conflict - an important social context for youth development - in the relationship between parental mental health and youth impulsivity. Methods: Data were from the first three annual waves of the ABCD study (Baseline N = 11,876 children, Mage = 9.9 years; 48% female; 52% White). Parental mental health conditions were self-reported internalizing, externalizing, and total problems. Youth completed the family conflict scale, and Urgency, Planning (lack of), Perseverance (lack of), Sensation Seeking, and Positive Urgency (UPPS-P) scale to measure impulsivity. To determine if within-family change in conflict from baseline to year 1 explained changes in the strength of relations between baseline parental mental health and year 2 youth impulsivity, longitudinal causal mediation analyses were conducted, controlling for demographic factors (i.e., age, sex, race, household income, parental education, marital status), as well as baseline levels of family conflict and outcomes. Separate mediation models were run for each mental health condition and each UPPS-P subscale. Results: Above and beyond bivariate relations, longitudinal mediation models, which included covariates, showed family conflict significantly (ps < 0.001) mediated relations between all three parental mental health conditions and all but one (i.e., sensation seeking) UPPS-P subscales. The proportion mediated through family conflict for internalizing problems and total problems on facets of impulsivity (except sensation seeking) ranged from 9% (for lack of perseverance) to 17% (for lack of planning). Proportion mediated via family conflict for externalizing problems on youth's impulsivity (except sensation seeking) was slightly higher, ranging between 13% (lack of perseverance) to 21% (lack of planning). Discussion: Family conflict may be an important intergenerational factor linking parental mental health and youth's impulsivity. Addressing parental mental health and family conflict may help curb increased impulsivity in youth, and in turn reduce adolescent substance use disorders.

The (in)visible Brazilians: A perspective review on the need for brain health and dementia research with Brazilian immigrants in the United States.

Introduction: The Brazilian population in the United States (U.S.), a Latinx subgroup, is rapidly growing and aging but remains underrepresented in U.S. health research. In addition to group-specific genetic and environmental risks, Brazilian immigrants and their offspring in the U.S. likely have cumulative risks for health inequities.It is estimated that 71% of Brazilian immigrants in the U.S. are undocumented, which may limit healthcare access/utilization. Furthermore, mental health is reported as a health priority by Brazilian immigrants in the U.S., and there is a lack of research on Alzheimer's disease and related dementia (AD/ADRD) in this population. Methods: We reviewed the scientific literature using traditional (e.g., PubMed) sources and databases generated by U.S. and Brazilian governments, as well as international organizations, and press articles. Results: This perspective review lists recommendations for researchers, health providers, and policymakers to promote greater inclusion of U.S. Brazilian populations in health research and care. The review identifies research areas in need of attention to address health inequities and promote mental/brain health in Brazilian immigrants and their offspring living in the U.S. These research areas are: 1) epidemiological studies to map the prevalence and incidence of mental/brain health conditions; 2) research on aging and AD/ADRD risk factors among Brazilian populations in the U.S.; and 3) the need for greater representation of U.S-residing Brazilian population in other relevant research areas involving genetics, neuropathology, and clinical trials. Conclusions: The recommendation and research efforts proposed should help to pave the way for the development of community-engagement research and to promote mental/brain health education, improvement of mental/brain health and AD/ADRD services, and the development of culturally-informed intervention to the U.S.-residing Brazilian communities. HIGHLIGHTS: The Brazilian population in the United States is growing but is underrepresented in U.S. health research.Approximately 71% of Brazilian immigrants in the United States are undocumented, with an increased risk for health inequities.Mental health is reported as a central health priority by Brazilian immigrants in the United States.There is a lack of research on Alzheimer's disease and other dementias (ADRD) in Brazilian immigrants in the United States.Epidemiological research is needed to map the prevalence/incidence of mental health conditions and ADRD risk factors among Brazilian immigrants in the United States.

A pilot study of volumetric and density tumor analysis of ACC patients treated with vorinostat in a phase II clinical trial.

Rationale and objectives: Adenoid cystic carcinoma (ACC) is a rare salivary gland cancer. The vast majority of clinical trials evaluating systemic therapy efficacy in solid tumors use the Response Evaluation Criteria in Solid Tumors (RECIST) to measure response that is limited to 2 dimensional only evaluations, not taking volume or density into account. The indolent behavior ACC represents a challenge toward an appropriate evaluation of therapy response. Objectives: 1) To describe and contrast volumetric and density changes at each time-point, including changes noted from baseline to best response, to currently used 2 dimensional-only criteria (RECIST) and 2) To report the coefficient of variation in volume measurement among three reviewers on a subset of ACC patients. Materials and methods: We retrospectively assessed a cohort of 18 prospectively treated patients with ACC in a phase 2 trial with vorinostat using a volumetric (viable tumor volume, VTV) and density criteria. Three independent and blinded observers segmented target lesions across a sample of randomly selected computed tomography (CT) exams to examine inter-observer variation. Results: We found that the average coefficient of variation among observers for all target lesions was 16.1%, with lung lesions displaying a smaller variation at 14.0% (p-value >0.17). We describe examples of decrease in volume and density in several lesions despite stable disease by RECIST. Conclusion: This pilot study demonstrates that two-dimensional criteria such as RECIST may not be the best criteria to assess response to therapy, especially with evolving tools within picture archiving and communication system (PACS) that can assess volumetric size, density and texture, however, this should be prospectively studied.

Particulate matter pollution and non-targeted analysis of polar compounds in three regions of Brazil.

Atmospheric Particulate Matter (PM) is a pollutant with diverse origins, exhibiting varying chemical compositions, and undergoes several molecular transformations in the atmosphere. In this study, PM samples (PM2.5, PM10 and TSP) were collected in five Brazilian cities (Camboriú-SC; Catalão-GO; Florianópolis-SC; Limeira-SP and Novo Hamburgo-RS) during the four seasons of the year. Analysis of Variance (ANOVA) was used to evaluate the differences between each city and season in PM concentration. PM10 average concentrations were higher in the city of Limeira, compared to the other (ANOVA p-values and Tukey's test). Moreover, Tukey's test demonstrated differences between the average PM10 concentrations in summer and winter. Regarding TSP and PM2.5, Tukey's test showed differences between winter and warm seasons (spring and summer). Moreover, polar compounds from the samples collected in the summer (February) and winter (August) periods were analyzed (Ultra-High-Performance Liquid Chromatography coupled to a Quadrupole Time-of-Flight Mass Spectrometer) following a non-targeted approach and annotated. This is the first study to carry out this type of analysis in these five Brazilian cities. Despite the differences in PM concentrations, profiles of polar organic compounds, showed similarities between samples/and, in general, the same compounds were present, albeit with different intensities. The annotated compounds are associated with vehicle emissions and plastics, which are considered important global air polluters. Therefore, there is an urgent necessity for comprehensive studies aimed at investigating the non-targeted compounds existing in the atmosphere. Such research can provide invaluable insights to policymakers, enabling them to formulate effective guidelines and policies to mitigate particulate matter concentration and enhance overall air quality.

How oxidized EGCG remodels α-synuclein fibrils into non-toxic aggregates: insights from computational simulations.

The misfolding and aggregation of the presynaptic protein α-synuclein (α-syn) is a pathological hallmark of Parkinson's disease (PD). Targeting α-syn has emerged as a promising therapeutic strategy for PD. Emerging in vitro evidence supports a dual action of epigallocatechin-3-gallate (EGCG) against amyloid neurotoxicity. EGCG can halt the formation of toxic aggregates by redirecting the amyloid fibril aggregation pathway toward non-toxic aggregates and remodeling the existing toxic fibrils into non-toxic aggregates. Moreover, EGCG oxidation can enhance fibril's remodeling by forming Schiff bases, leading to crosslinking of the fibril. However, this covalent modification is not required for amyloid remodeling, and establishing non-specific hydrophobic interactions with sidechains seems to be the main driver of amyloid remodeling by EGCG. Thioflavin (ThT) is a gold standard probe to detect amyloid fibrils in vitro, and oxidized EGCG competes with ThT for amyloid fibrils' binding sites. In this work, we performed docking and molecular dynamics (MD) simulations to gain insights into the intermolecular interactions of oxidized EGCG and ThT with a mature α-syn fibril. We find that oxidized EGCG moves within lysine-rich sites within the hydrophobic core of the α-syn fibril, forming aromatic and hydrogen-bonding (H-bond) interactions with different residues during the whole MD simulation time. In contrast, ThT, which does not remodel amyloid fibrils, was docked to the same sites but only via aromatic interactions. Our findings suggest that non-covalent interactions play a role in oxidized EGCG binding into the hydrophobic core, including H-bond and aromatic interactions with some residues in the amyloid remodeling processes. These interactions would ultimately lead to a disturbance of structural features as determinants for stabilizing this fibril into a compact and pathogenic Greek key topology.

Recreational cannabis legislation and binge drinking in U.S. adolescents and adults.

BACKGROUND: Recreational cannabis laws (RCLs) may have spillover effects on binge drinking. Our aims were to investigate binge drinking time trends and the association between RCLs and changes in binge drinking in the United States (U.S.). METHODS: We used restricted National Survey on Drug Use and Health data (2008-2019). We examined trends in the prevalence of past-month binge drinking by age groups (12-20, 21-30, 31-40, 41-50, 51+). Then, we compared model-based prevalences of past-month binge drinking before and after RCL by age group, using multi-level logistic regression with state random intercepts, an RCL by age group interaction term, and controlling for state alcohol policies. RESULTS: Binge drinking declined overall from 2008 to 2019 among people aged 12-20 (17.54% to 11.08%), and those aged 21-30 (43.66% to 40.22%). However, binge drinking increased among people aged 31+ (ages 31-40: 28.11% to 33.34%, ages 41-50: 25.48% to 28.32%, ages 51+: 13.28% to 16.75%). When investigating model-based prevalences after versus before RCL, binge drinking decreased among people aged 12-20 (prevalence difference=-4.8%; adjusted odds ratio (aOR)=0.77, [95% confidence interval (CI) 0.70-0.85]), and increased among participants aged 31-40 (+1.7%; 1.09[1.01-1.26]), 41-50 (+2.5; 1.15[1.05-1.26]) and 51+ (+1.8%; 1.17[1.06-1.30]). No RCL-related changes were noted in respondents ages 21-30. CONCLUSIONS: Implementation of RCLs was associated with increased past-month binge drinking in adults aged 31+ and decreased past-month binge drinking in those aged < 21. As the cannabis legislative landscape continues to change in the U.S., efforts to minimize harms related to binge drinking are critical.

Adverse Childhood Experiences and Risk Patterns of Alcohol and Cannabis Co-Use: A Longitudinal Study of Puerto Rican Youth.

PURPOSE: Adverse childhood experiences (ACEs) are common in Puerto Rican youths. Few large longitudinal studies of Latine youth examined what predicts co-use of alcohol and cannabis in late adolescence and young adulthood. We investigated the prospective association between ACEs with alcohol/cannabis co-use in Puerto Rican youth. METHODS: Participants from a longitudinal study of Puerto Rican youth (n = 2,004) were included. Using multinomial logistic regressions to test associations between prospectively reported ACEs (11 types, reported by parents and/or children, categorized as 0-1, 2-3, and 4+ ACEs) with young adult alcohol/cannabis use patterns in the past month (i.e., no lifetime use, low-risk [no binge drinking and cannabis use < 10], binge-drinking only, regular cannabis use only, and alcohol/cannabis co-use). Models were adjusted for sociodemographic variables. RESULTS: In this sample, 27.8% reported 4+ ACEs, 28.6% endorsed binge drinking, 4.9% regular cannabis use, and 5.5% alcohol/cannabis co-use. Compared to individuals with no lifetime use, those reporting 4+ (vs. 0-1) ACEs had greater odds of low-risk use (adjusted odds ratio [aOR] 1.60, 95% confidence interval [CI] = 1.04-2.45), regular cannabis use (aOR 3.13 95% CI = 1.44-6.77), and alcohol/cannabis co-use (aOR 3.57, 95% CI = 1.89-6.75). In relation to low-risk use, reporting 4+ ACEs (vs. 0-1) was associated with 1.96 odds (95% CI = 1.01-3.78) of regular cannabis use and 2.24 odds (95% CI = 1.29-3.89) of alcohol/cannabis co-use. DISCUSSION: Exposure to 4+ ACEs was associated with the occurrence of adolescent/young adulthood regular cannabis use and alcohol/cannabis co-use. Importantly, ACEs exposure differentiated young adults who were co-using compared to those engaged in low-risk use. Preventing ACE or interventions for Puerto Rican youth experiencing 4+ ACEs may mitigate negative consequences associated with alcohol/cannabis co-use.

Rivaroxaban to prevent major clinical outcomes in non-hospitalised patients with COVID-19: the CARE - COALITION VIII randomised clinical trial.

Background: COVID-19 progression is associated with an increased risk of arterial and venous thrombosis. Randomised trials have demonstrated that anticoagulants reduce the risk of thromboembolism in hospitalised patients with COVID-19, but a benefit of routine anticoagulation has not been demonstrated in the outpatient setting. Methods: We conducted a randomised, open-label, controlled, multicentre study, evaluating the use of rivaroxaban in mild or moderate COVID-19 patients. Adults ≥18 years old, with probable or confirmed SARS-CoV-2 infection, presenting within ≤7 days from symptom onset with no clear indication for hospitalization, plus at least 2 risk factors for complication, were randomised 1:1 either to rivaroxaban 10 mg OD for 14 days or to routine care. The primary efficacy endpoint was the composite of venous thromboembolic events, need of mechanical ventilation, acute myocardial infarction, stroke, acute limb ischemia, or death due to COVID-19 during the first 30 days. ClinicalTrials.gov: NCT04757857. Findings: Enrollment was prematurely stopped due to sustained reduction in new COVID-19 cases. From September 29th, 2020, through May 23rd, 2022, 660 patients were randomised (median age 61 [Q1-Q3 47-69], 55.7% women). There was no significant difference between rivaroxaban and control in the primary efficacy endpoint (4.3% [14/327] vs 5.8% [19/330], RR 0.74; 95% CI: 0.38-1.46). There was no major bleeding in the control group and 1 in the rivaroxaban group. Interpretation: On light of these findings no decision can be made about the utility of rivaroxaban to improve outcomes in outpatients with COVID-19. Metanalyses data provide no evidence of a benefit of anticoagulant prophylaxis in outpatients with COVID-19. These findings were the result of an underpowered study, therefore should be interpreted with caution. Funding: COALITION COVID-19 Brazil and Bayer S.A.

A surveillance program for long-term central venous access-associated infections in outpatient chemotherapy services.

OBJECTIVE: In this study, we described the first results of a surveillance system for infections associated with long-term central venous catheters (LT-CVC) in patients under outpatient chemotherapy. DESIGN: This was a multicentric, prospective study. SETTING: Outpatient chemotherapy services. PARTICIPANTS: The study included 8 referral cancer centers in the State of São Paulo. INTERVENTION: These services were invited to participate in a newly created surveillance program for patients under chemotherapy. Several meetings were convened to share previous experiences on LT-CVC infection surveillance and to define the surveillance method. Once the program was implemented, all bloodstream infection (LT-CVC BSIs), tunnel infection, and exit-site infections associated with LT-CVC were reported. Data from January to May 2021 were analyzed. The median monthly number of chemotherapy sessions per clinic was 925 (IQR, 270-5,855). We used Poisson regression to analyze the association of rates with the characteristics of the services. RESULTS: In total, 107 LT-CVC infections were reported, of which 95% were BSIs, mostly associated with totally implantable devices (76%). Infections occurred a median of 4 days after the last catheter manipulation and 116 after the LT-CVC insertion. Also, 102 microorganisms were isolated from LT-CVC BSIs; the most common pathogen was Staphylococcus epidermidis, at 22%. Moreover, 44 infections (44%) fulfilled the criteria for CVC-related LT-CVC BSI and 27 infections (27%) met the criteria for mucosal barrier injury. The 1-year cumulative LT-CVC BSI rate was 1.94 per 1,000 CVC days of use. The rates were higher in public hospitals (IRR, 6.00; P < .001) and in hospitals that already had in place surveillance for LT-CVC infections (IRR, 2.01; P < .01). CONCLUSION: Our study describes an applicable surveillance method for infections in cancer outpatients using LT-CVC.

Using PDX animal models to identify and stratify adenoid cystic carcinoma patients presenting an enhanced response to HDAC inhibitors.

Adenoid cystic carcinoma (ACC) patients face a highly infiltrative and metastatic disease characterized by poor survival rates and suboptimal response to available therapies. We have previously shown that sensitization of ACC tumors to chemotherapy using histone deacetylase inhibitors (HDACi) constitutes a promising therapeutic strategy to manage tumor growth. Here, we used patient-derived xenografts (PDX) from ACC tumors to evaluate the effects of in vivo administration of the HDAC inhibitor Entinostat combined with Cisplatin over tumor growth. RNA from PDX tumor samples receiving the proposed therapy were analyzed using NanoString technology to identify molecular signatures capable of predicting ACC response to the therapy. We also used an RNAseq dataset from 68 ACC patients to validate the molecular signature identified by the NanoString platform. We found that the administration of Entinostat combined with Cisplatin resulted in a potent tumor growth inhibition (TGI) ranging from 38% to 106% of the original tumor mass. Enhanced response to therapy is consistent with the reactivation of tumor suppressor genes, including SFRP1, and the downregulation of oncogenes like FGF8 and CCR7. Nanostring data from PDX tumors identified a genetic signature capable of predicting tumor response to therapy. We further stratified 68 ACC patients containing RNAseq data accordingly to the activity levels of the identified genetic signature. We found that 23% of all patients exhibit a genetic signature consistent with a high ACC tumor response rate to Entinostat and Cisplatin. Our study provides compelling preclinical data supporting the deployment of a powerful systemic anticancer therapy crafted and explicitly tested for ACC tumors.

Differential priority effects impact taxonomy and functionality of host-associated microbiomes.

Most multicellular eukaryotes host complex communities of microorganisms, but the factors that govern their assembly are poorly understood. The settlement of specific microorganisms may have a lasting impact on community composition, a phenomenon known as the priority effect. Priority effects of individual bacterial strains on a host's microbiome are, however, rarely studied and their impact on microbiome functionality remains unknown. We experimentally tested the effect of two bacterial strains (Pseudoalteromonas tunicata D2 and Pseudovibrio sp. D323) on the assembly and succession of the microbial communities associated with the green macroalga Ulva australis. Using 16S rRNA gene sequencing and qPCR, we found that both strains exert a priority effect, with strain D2 causing initially strong but temporary taxonomic changes and strain D323 causing weaker but consistent changes. Consistent changes were predominately facilitatory and included taxa that may benefit the algal host. Metagenome analyses revealed that the strains elicited both shared (e.g., depletion of type III secretion system genes) and unique (e.g., enrichment of antibiotic resistance genes) effects on the predicted microbiome functionality. These findings indicate strong idiosyncratic effects of colonizing bacteria on the structure and function of host-associated microbial communities. Understanding the idiosyncrasies in priority effects is key for the development of novel probiotics to improve host condition.

Cannabis Recreational Legalization and Prevalence of Simultaneous Cannabis and Alcohol Use in the United States.

BACKGROUND: Simultaneous cannabis/alcohol use, using both substances within a short time interval so that their effects overlap, has a greater risk of potential negative consequences than single-substance use and is more common in younger age. Relationships between recreational cannabis laws (RCLs) and changes in simultaneous cannabis/alcohol use prevalence remain untested. OBJECTIVE: To examine trends in simultaneous cannabis/alcohol use from 2008 to 2019, and investigate associations between implementation of RCLs (i.e., presence of active legal dispensaries or legal home cultivation) and simultaneous cannabis/alcohol use in the United States (U.S.). DESIGN: Repeated cross-sectional samples from the 2008-2019 U.S. National Survey on Drug Use and Health (NSDUH). PARTICIPANTS: Respondents (51% female) aged 12 and older. INTERVENTIONS: Changes in simultaneous cannabis/alcohol use before and after RCL implementation (controlling for medical cannabis law implementation) were compared in different age groups (12-20, 21-30, 31-40, 41-50, 51+), using adjusted multi-level logistic regression with state random intercepts and an RCL/age group interaction. MEASUREMENTS: Self-reported simultaneous cannabis/alcohol use. RESULTS: From 2008 to 2019, the overall prevalence of simultaneous cannabis/alcohol use declined among those aged 12-20 but increased in adults aged 21+. Model-based simultaneous cannabis/alcohol use prevalence increased after RCL implementation among respondents aged 21-30 years (+1.2%; aOR= 1.15 [95%CI = 1.04-1.27]), 31-40 years (+1.0; 1.15 [1.04-1.27]), and 41-50 years (+1.75; 1.63 [1.34-1.98]), but not in individuals aged <21 or 51+ years. CONCLUSIONS: Implementation of recreational cannabis policies resulted in increased simultaneous use of cannabis and alcohol, supporting the complementarity hypothesis, but only among adults aged 21+. Efforts to minimize harms related to simultaneous cannabis/alcohol use are critical, especially in states with RCLs. Future studies should investigate cultural norms, perceived harm, and motives related to simultaneous use.

Cognitive training and remediation interventions for substance use disorders: a Delphi consensus study.

AIMS: Substance use disorders (SUD) are associated with cognitive deficits that are not always addressed in current treatments, and this hampers recovery. Cognitive training and remediation interventions are well suited to fill the gap for managing cognitive deficits in SUD. We aimed to reach consensus on recommendations for developing and applying these interventions. DESIGN, SETTING AND PARTICIPANTS: We used a Delphi approach with two sequential phases: survey development and iterative surveying of experts. This was an on-line study. During survey development, we engaged a group of 15 experts from a working group of the International Society of Addiction Medicine (Steering Committee). During the surveying process, we engaged a larger pool of experts (n = 54) identified via recommendations from the Steering Committee and a systematic review. MEASUREMENTS: Survey with 67 items covering four key areas of intervention development: targets, intervention approaches, active ingredients and modes of delivery. FINDINGS: Across two iterative rounds (98% retention rate), the experts reached a consensus on 50 items including: (i) implicit biases, positive affect, arousal, executive functions and social processing as key targets of interventions; (ii) cognitive bias modification, contingency management, emotion regulation training and cognitive remediation as preferred approaches; (iii) practice, feedback, difficulty-titration, bias modification, goal-setting, strategy learning and meta-awareness as active ingredients; and (iv) both addiction treatment work-force and specialized neuropsychologists facilitating delivery, together with novel digital-based delivery modalities. CONCLUSIONS: Expert recommendations on cognitive training and remediation for substance use disorders highlight the relevance of targeting implicit biases, reward, emotion regulation and higher-order cognitive skills via well-validated intervention approaches qualified with mechanistic techniques and flexible delivery options.

Drug-drug interactions of immunosuppressants and other drugs in kidney post-transplant recipients

Introduction: Immunosuppressants (ISS) are the most crucial tools used in the therapeutic regimens of transplant recipients. Nevertheless, these drugs are not the only ones adopted by patients; therefore, knowing the possible drug-drug interactions (DDIs) between immunosuppressants and other drugs commonly used in kidney transplant recipients is essential to ensure the effectiveness and safety of treatments. In this way, the objective is analyzing the DDIs between the immunosuppressants and other commonly used medications on kidney transplant adult recipients with active medical records undergoing post-transplant follow-up for 4.4 years (mean). Methods: First, we performed a cross-sectional study based on patients' records, in which the patient's profile and drugs used were examined, and after we analyzed DDIs by the Micromedex Drug Interactions® database. Results: We analyzed 176 patients with a mean age of 47.6(± 12.5); most were male (67.7%), and the majority received a kidney from a deceased donor (81.4%). Patients were exposed to 15.0 (± 5.4) different medicines after the transplantation, and 7.4 (± 4.0) of these medicines were simultaneous. After analyzing the DDIs according to the severity of interaction, documentation quality interaction effect, clinical management and probable interaction mechanism, the most frequent interaction was with tacrolimus, classified as moderate, and the 3 major causes of interaction occurred with azathioprine according to the Micromedex database. The primary medicines involved with immunosuppressant interactions were proton pump inhibitors, ranitidine, domperidone, amlodipine, enalapril, allopurinol, cyclobenzaprine, amitriptyline, fluoxetine, and ciprofloxacin. These DDIs' effects were related to, mainly, increase their immunosuppressant activity. Conclusion: Although the immunosuppressants analyzed lacked many clinical DDIs significance with other medicines, the healthcare team needs to monitor their DDIs' effects to prevent and minimize side effects in transplanted recipients.

Comparing human to electronic observers to monitor hand hygiene compliance in an intensive care unit.

Objective: We sought to determine whether an electronic hand hygiene (HH) system could monitor HH compliance at similar rates to direct human observation. Methods: This 4-year proof-of-concept study was conducted in an intensive care unit (ICU) of a private tertiary-care hospital in São Paulo, Brazil, where electronic HH systems were installed in 2 rooms. HH compliance was reported respectively using direct observation and electronic counter devices with an infrared system for detecting HH opportunities. Results: In phase 1, HH compliance by human observers was 56.3% (564 of 1,001 opportunities), while HH compliance detected by the electronic observer was 51.0% (515 of 1,010 opportunities). In phase 2, human observers registered 484 HH opportunities with a HH compliance rate of 64.7% (313 of 484) versus 70.6% (346 of 490) simultaneously detected by the electronic system. In addition, an enhanced HH electronic system monitored activity 24 hours per day and HH compliance without the presence of a human observer was 40.3% (10,642 of 26,421 opportunities), providing evidence for the Hawthorne effect. Conclusions: The electronic HH monitoring system had good correlation with human HH observation, but compliance was remarkably lower when human observers were not present due to the Hawthorne effect (25%-30% absolute difference). Electronic monitoring systems can replace direct observation and can markedly reduce the Hawthorne effect.

Comparison of two electronic hand hygiene systems using real-time feedback via wireless technology to improve hand hygiene compliance in an intensive care unit.

Background: Most hand hygiene (HH) intervention studies use a quasi-experimental design, are primarily uncontrolled before-and-after studies, or are controlled before-and-after studies with a nonequivalent control group. Well-funded studies with improved designs and HH interventions are needed. Objectives: To evaluate healthcare worker (HCW) HH compliance with alcohol-based hand rub (ABHR) through direct observation (human observer), 2 electronic technologies, a radio frequency identification (RFID) badge system, and an invasive device sensor. Methods: In our controlled experimental study, 2,269 observations were made over a 6-month period from July 1 to December 30, 2020, in a 4-bed intensive care unit. We compared HH compliance between a basic feedback loop system with RFID badges and an enhanced feedback loop system that utilized sensors on invasive devices. Results: Real-time feedback by wireless technology connected to a patient's invasive device (enhanced feedback loop) resulted in a significant increase in HH compliance (69.5% in the enhanced group vs 59.1% in the basic group; P = .0001). Conclusion: An enhanced feedback loop system connected to invasive devices, providing real-time alerts to HCWs, is effective in improving HH compliance.

Do varsity college athletes have a greater likelihood of risky alcohol and cannabis use than non-athletes? Results from a National Survey in Brazil

Objective: We examined the prevalence of risky alcohol and cannabis use among Brazilian varsity college athletes and whether this group had a greater likelihood of risky use than non-athletes. Methods: In 2009, Brazilian college students (n=12,711) were recruited for a national stratified random survey. Their sociodemographic characteristics, mental health, substance use, and participation in varsity sports were assessed. Binary logistic regression models were used to examine the association between varsity athlete status and moderate to high-risk alcohol and cannabis use. Results: Among varsity athletes, 67.6 and 10.7% reported risky alcohol and cannabis use, respectively. Varsity athletes had greater odds of risky alcohol consumption than non-athletes (aOR = 2.02, 95%CI 1.08-3.78). Varsity athletes also had greater odds of risky cannabis use than non-athletes in unadjusted analyses (OR = 2.57, 95%CI 1.05-6.28), although this relationship was attenuated after covariate adjustment. Conclusions: Among college students in Brazil, varsity athletes had a higher prevalence of risky alcohol and cannabis use than non-athletes. The rates were considerably higher than those observed among samples of U.S. college athletes. Future research should examine the use of these substances among varsity college athletes in other middle-income countries since these findings will likely guide prevention and treatment efforts.

Simultaneous Alcohol/Cannabis Use and Driving Under the Influence in the U.S.

INTRODUCTION: Alcohol and cannabis are commonly involved in motor vehicle crashes and fatalities. This study examines whether simultaneous use of alcohol/cannabis is associated with higher odds of reporting driving under the influence of alcohol and cannabis in the U.S. METHODS: Drivers aged ≥16 years with any past-year alcohol and cannabis use in the 2016-2019 National Survey on Drug Use and Health (N=34,514) reported any past-year driving under the influence of alcohol-only, cannabis-only, both alcohol/cannabis, or not driving under the influence. Survey-weighted associations between simultaneous alcohol/cannabis use and each of the driving under the influence outcomes were computed adjusting for sociodemographics and daily alcohol/cannabis use. Analyses were conducted from November 2020 to September 2021. RESULTS: In 2016-2019, 42% of drivers with past-year alcohol and cannabis use reported driving under the influence (8% alcohol-only, 20% cannabis-only, 14% alcohol/cannabis). Simultaneous alcohol/cannabis use was associated with 2.88-times higher adjusted odds of driving under the influence of cannabis-only (95% CI=2.59, 3.19) and 3.51-times higher adjusted odds of driving under the influence of both alcohol/cannabis (95% CI=3.05, 4.05), compared to not driving under the influence. Associations with driving under the influence of alcohol-only were unexpectedly in the opposite direction (adjusted conditional odds ratio=0.59, 95% CI=0.45, 0.79). CONCLUSIONS: Overall, 2 in 5 drivers who used alcohol and cannabis reported driving under the influence of alcohol and/or cannabis. People reporting simultaneous alcohol/cannabis use were more likely to report cannabis-related driving under the influence. Prevention strategies should target individuals reporting simultaneous alcohol/cannabis use to reduce the occurrence of driving under the influence.

Do varsity college athletes have a greater likelihood of risky alcohol and cannabis use than non-athletes? Results from a National Survey in Brazil.

OBJECTIVE: We examined the prevalence of risky alcohol and cannabis use among Brazilian varsity college athletes and whether this group had a greater likelihood of risky use than non-athletes. METHODS: In 2009, Brazilian college students (n=12,711) were recruited for a national stratified random survey. Their sociodemographic characteristics, mental health, substance use, and participation in varsity sports were assessed. Binary logistic regression models were used to examine the association between varsity athlete status and moderate to high-risk alcohol and cannabis use. RESULTS: Among varsity athletes, 67.6 and 10.7% reported risky alcohol and cannabis use, respectively. Varsity athletes had greater odds of risky alcohol consumption than non-athletes (aOR = 2.02, 95%CI 1.08-3.78). Varsity athletes also had greater odds of risky cannabis use than non-athletes in unadjusted analyses (OR = 2.57, 95%CI 1.05-6.28), although this relationship was attenuated after covariate adjustment. CONCLUSIONS: Among college students in Brazil, varsity athletes had a higher prevalence of risky alcohol and cannabis use than non-athletes. The rates were considerably higher than those observed among samples of U.S. college athletes. Future research should examine the use of these substances among varsity college athletes in other middle-income countries since these findings will likely guide prevention and treatment efforts.