Knowledge of medications for opioid use disorder and associated stigma among primary care professionals.

BACKGROUND: Medications for opioid use disorder (MOUD) are the gold standard. However, significant barriers limit their use in the primary care setting, including limited knowledge of the medications and stigmatizing attitudes. In this study, we assess knowledge levels among primary care-aligned professionals (PCPs) currently in practice, and whether knowledge of MOUD is associated with stigma and treatment attitudes. PARTICIPANTS AND METHODS: Using rosters from the state of Ohio licensing boards, we surveyed 403 physicians, nurse practitioners, and physician associates in 2022, on the mechanism of different MOUD, as well as stigma and treatment attitudes. To assess MOUD knowledge, we employed descriptive and bivariate statistics. We fit four linear regression models, which controlled for empathy towards patients with OUD and provider demographics to assess the relationship between MOUD knowledge and four endpoints: stigma, perceived controllability of opioid use, perceived vulnerability to opioid use disorder, and support for abstinence-only treatment. RESULTS: 43% of participants correctly identified the mechanism of all 3 medications whereas 13% of participants did not identify the mechanism of any MOUD correctly. MOUD knowledge was higher among physicians as compared to nurse practitioners and physician associates. Lower MOUD knowledge was associated with more negative attitudes towards patients with OUD and MOUD treatment. CONCLUSION: Expanding access to MOUD treatment requires a trained and willing health-care professional (HCP) workforce. Our findings highlight considerable variation in clinician knowledge of MOUD and suggest that knowledge levels are also related to negative attitudes towards patients with OUD and MOUD. Training interventions that increase knowledge, as well as focus on stigma reduction, are critical for reducing the longstanding treatment gap for opioid use disorder.

Prevalence of the cefazolin inoculum effect (CzIE) in nasal colonizing methicillin-susceptible Staphylococcus aureus in patients from intensive care units in Colombia and use of a modified rapid nitrocefin test for detection.

The cefazolin inoculum effect (CzIE) has been associated with poor clinical outcomes in patients with methicillin-susceptible Staphylococcus aureus (MSSA) infections. We aimed to investigate the point prevalence of the CzIE among nasal colonizing MSSA isolates from ICU patients in a multicenter study in Colombia (2019-2023). Patients underwent nasal swabs to assess for S. aureus colonization on admission to the ICU, and some individuals had follow-up swabs. We performed cefazolin MIC by broth microdilution using standard and high inoculum and developed a modified nitrocefin-based rapid test to detect the CzIE. Whole-genome sequencing was carried out to characterize BlaZ types and allotypes, phylogenomics, and Agr-typing. A total of 352 patients were included; 46/352 (13%) patients were colonized with S. aureus and 22% (10/46) and 78% (36/46) with MRSA and MSSA, respectively. Among 36 patients who contributed with 43 MSSA colonizing isolates, 21/36 (58%) had MSSA exhibiting the CzIE. BlaZ type A and BlaZ-2 were the predominant type and allotype in 56% and 52%, respectively. MSSA belonging to CC30 were highly associated with the CzIE, and single-nucleotide polymorphism (SNP) analyses supported possible transmission of MSSA exhibiting the CzIE among some patients of the same unit. The modified nitrocefin rapid test had 100%, 94.4%, and 97.7% sensitivity, specificity, and accuracy, respectively. We found a high point prevalence of the CzIE in MSSA colonizing the nares of critically ill patients in Colombia. A modified rapid test was highly accurate in detecting the CzIE in this patient population.

Thromboembolic Complications in Continuous Versus Interrupted Anticoagulation During Venovenous Extracorporeal Membrane Oxygenation: A Multicenter Study.

OBJECTIVES: Continuous, therapeutic anticoagulation is the standard of care for patients on extracorporeal membrane oxygenation (ECMO). The risks of hemorrhage exacerbated by anticoagulation must be weighed with the thrombotic risks associated with ECMO. We hypothesized increased thrombotic events in patients who had interrupted (vs. continuous) anticoagulation during venovenous ECMO. DESIGN: This is a retrospective, observational study. SETTING: Enrollment of individuals took place at three adult ECMO centers in Minnesota from 2013 to 2022. PATIENTS: This study consists of 346 patients supported with venovenous ECMO. INTERVENTIONS: Anticoagulation administration was collected from electronic health records, including frequency and duration of anticoagulation interruptions (IAs) and timing and type of thrombotic events, and data were analyzed using descriptive statistics. MEASUREMENTS AND MAIN RESULTS: A total of 156 patients had IA during their ECMO run and 190 had continuous anticoagulation. Risk adjusted logistic regression demonstrated that individuals in the IA group were not statistically more likely to experience a thrombotic complication (odds ratio [OR], 0.69; 95% CI, 0.27-1.70) or require ECMO circuit change (OR, 1.36; 95% CI, 0.52-3.49). Subgroup analysis demonstrated greater frequency of overall thrombotic events with increasing frequency and duration of anticoagulation being interrupted (p = 0.001). CONCLUSIONS: Our multicenter analysis found a similar frequency of thrombotic events in patients on ECMO when anticoagulation was interrupted vs. administered continuously. Further investigation into the impact of the frequency and duration of these interruptions is warranted.

Development of brain metastases in non-small-cell lung cancer: high-risk features.

Aim: Brain metastases (BM) are a common site of disease progression and treatment failure in non-small-cell lung cancer (NSCLC) and can be identified in up to 30-50% of patients. Although they are common, there is no standardized screening protocol for development of BM in NSCLC. Multiple clinical variables predict increased BM occurrence, and, when present, should be used to initiate screening MRI.Materials & methods: We performed a single center retrospective review of NSCLC patients, examining BM development and overall survival. Available clinical, radiographic and molecular data were reviewed for association with BM and overall survival. A predictive model for BM development was created for multivariate analysis.Results: Risk factors for new BM development in NSCLC included younger age, larger primary lung tumor, Karnofsky performance score (KPS) <70, pre-existing liver or bone metastases, large cell histology and family history of cancer. Factors associated with decreased OS were larger primary lung tumor, extracranial metastases at time of diagnosis, large cell histology and poorly-differentiated carcinoma histology.Conclusion: There are multiple high risk features for developing BM in NSCLC. Each of these factors should routinely be investigated, and presence should prompt brain MRI to allow earlier diagnosis and treatment of BM.

non-small-cell lung cancer has a high rate of cancer spread and brain metastases (cancer spread to the brain). There is currently no standardized protocol for when to obtain imaging of the brain to inspect for metastases. Our study reviewed over 1000 patients with non-small-cell lung cancer to determine which factors predisposed to development of brain metastases, and which factors impacted survival. Risk factors for development of brain metastases included younger age, larger primary lung tumor, poor functional status, liver or bone metastases, large cell histology and family cancer history. Lung cancer patients with any of these risk factors should be screened for brain metastases. Factors associated with decreased overall survival were larger primary lung tumor, extracranial metastases at time of diagnosis, large cell histology and poorly-differentiated carcinoma histology.

A rapid review protocol of physiotherapy and occupational therapy telerehabilitation to inform ethical and equity concerns.

Background: Telerehabilitation (TR) has emerged as a feasible and promising approach for delivering rehabilitation services remotely, utilizing technology to bridge the gap between healthcare providers and patients. As new modalities of virtual care and health technologies continue to emerge, it is crucial to stay informed about the growing landscape of virtual care to ensure that telehealth service delivery is ethical and equitable, and improves the quality of services and patient outcomes. Objective: The primary objective of this article is to present the protocol of a rapid review to examine the equity-related aspects surrounding the implementation of TR. This includes a comprehensive analysis of the ethical dimensions and fairness concerns linked to this practice. Methods: A rapid review protocol was developed in accordance with Cochrane Rapid Reviews Methods Guidance. Medline and EMBASE databases were searched between January 2010 and March 2023. Study selection and data extraction will be conducted in two phases (Phase I) by two independent reviewers and subsequently (Phase II) by a single reviewer. Our study will utilize the PROGRESS-Plus and Equitable virtual rehabilitation in the metaverse era framework to identify dimensions where potential inequities may exist within TR interventions. Results: This rapid review is anticipated to enhance our knowledge of TR in the fields of physiotherapy and occupational therapy, with a specific focus on its influence on ethical and equitable practices and providing a foundation for informed decision-making and improved patient care. Conclusion: This rapid review will contribute to the advancement of our understanding of TR within physiotherapy and occupational therapy. Through synthesizing existing evidence, this study not only addresses current gaps in knowledge but also offers valuable insights for future research and clinical practice in TR services.

Updated Risk Score Algorithms for Acute HIV Infection Detection at a Sexually Transmitted Infections Clinic in Lilongwe, Malawi.

BACKGROUND: Detection of acute (pre-seroconversion) HIV infection (AHI), the phase of highest transmission risk, requires resource-intensive RNA- or antigen-based detection methods that can be infeasible for routine use. Risk score algorithms can improve the efficiency of AHI detection by identifying persons at highest risk of AHI for prioritized RNA/antigen testing, but prior algorithms have not considered geospatial information, potential differences by sex, or current antibody testing paradigms. METHODS: We used elastic net models to develop sex-stratified risk score algorithms in a case-control study of persons (136 with AHI, 250 without HIV) attending a sexually transmitted infections (STI) clinic in Lilongwe, Malawi from 2015 to 2019. We designed algorithms for varying clinical contexts according to three levels of data availability: 1) routine demographic and clinical information, 2) behavioral and occupational data obtainable through patient interview, and 3) geospatial variables requiring external datasets or field data collection. We calculated sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) to assess model performance and developed a web application to support implementation. RESULTS: The highest-performing AHI risk score algorithm for men (AUC=0.74) contained five variables (condom use, body aches, fever, rash, genital sores/ulcers) from the first two levels of data availability. The highest-performing algorithm for women (AUC=0.81) contained fifteen variables from all three levels of data availability. A risk score cut-point of 0.26 had an AHI detection sensitivity of 93% and specificity of 27% for males, and a cut-point of 0.15 had 97% sensitivity and 44% specificity for females. Additional models are available in the web application. CONCLUSION: Risk score algorithms can facilitate efficient AHI detection in STI clinic settings, creating opportunities for HIV transmission prevention interventions during this critical period of elevated transmission risk.

The War on Drugs, Racialized Capitalism, and Health Care Utilization Among White People Who Use Drugs in 22 Rural Appalachian Counties.

Objectives. To analyze War on Drugs encounters and their relationships to health care utilization among White people who use drugs (PWUD) in 22 Appalachian rural counties in Kentucky, West Virginia, Ohio, and North Carolina. Methods. We recruited White PWUD using chain referral sampling in 2018 to 2020. Surveys asked about criminal-legal encounters, unmet health care needs, and other covariates. We used generalized estimating equations to regress unmet need on criminal-legal encounters in multivariable models. Results. In this sample (n = 957), rates of stop and search, arrest, incarceration, and community supervision were high (44.0%, 26.8%, 36.3%, and 31.1%, respectively), as was unmet need (68.5%). Criminal-legal encounters were unrelated to unmet need (stops: adjusted prevalence ratio [APR] = 1.13; 95% confidence interval [CI] = 0.97, 1.32; arrest: APR = 0.95; 95% CI = 0.78, 1.15; incarceration: APR = 1.01; 95% CI = 0.89, 1.14; community supervision: APR = 0.99; 95% CI = 0.90, 1.09). Conclusions. Contrasting with findings from predominantly Black urban areas, criminal-legal encounters and unmet need were unrelated among White Appalachian PWUD. Research should explore whether and under what conditions White supremacy's benefits might buffer adverse impacts of the War on Drugs in Appalachia. (Am J Public Health. 2024;114(10):1086-1096. https://doi.org/10.2105/AJPH.2024.307744).

The Human Cytomegalovirus vGPCR UL33 is Essential for Efficient Lytic Replication in Epithelial Cells.

Human cytomegalovirus (HCMV) is a ß-herpesvirus which is ubiquitous in the human population. HCMV has the largest genome of all known human herpesviruses, and thus encodes a large array of proteins that affect pathogenesis in different cell types. Given the large genome and the ability of HCMV to replicate in a range of cells, investigators have begun to identify viral proteins required for cell type-specific replication. There are four proteins encoded in the HCMV genome that are homologous to human G protein-coupled receptors (GPCRs); these viral-encoded GPCRs (vGPCRs) are UL33, UL78, US27, and US28. In the current study, we find that deletion of all four vGPCR genes from a clinical isolate of HCMV severely attenuates lytic replication in both primary human salivary gland epithelial cells, as well as ARPE-19 retinal epithelial cells as evidenced by significant decreases in immediate early gene expression and virus production. Deletion of UL33 from the HCMV genome also results in a failure to efficiently replicate in epithelial cells, and this defect is manifested by decreased levels of immediate early, early, and late gene expression, as well as reduced viral production. We find that similar to US28, UL33 constitutively activates Gαq-dependent PLC-ß signaling to high levels in these epithelial cells. We also find that UL33 transcription is more complicated than originally believed, and there is the potential for the virus to utilize various 5' UTRs to create novel UL33 proteins that are all capable of constitutive Gαq signaling. Taken together, these studies suggest that UL33 driven signaling is important for lytic HCMV replication in cells of epithelial origin.

An Automated Text Messaging Intervention to Reduce Substance Use Self-Stigma (Project RESTART): Protocol for a Feasibility and Acceptability Pilot Study.

BACKGROUND: Stigma is a barrier to treatment and harm reduction seeking in people who use drugs. Most stigma reduction interventions offer psychotherapy or psychoeducation in group-based clinical settings, failing to reach people who are not in treatment. SMS text messaging is an effective and acceptable modality for delivering health information to people who use drugs and may be a suitable conduit for providing information and advice to understand and cope with stigma. OBJECTIVE: This paper presents the protocol for a study that aims to determine the feasibility, acceptability, and preliminary effectiveness of a 4-week automated SMS text message intervention to increase stigma resistance and reduce self-stigma in people who use drugs. METHODS: We designed a novel automated SMS text message intervention to address the four personal-level constructs of stigma resistance: (1) not believing stigma and catching and challenging stigmatizing thoughts, (2) empowering oneself through learning about substance use and one's recovery, (3) maintaining one's recovery and proving stigma wrong, and (4) developing a meaningful identity and purpose apart from one's substance use. Theory-based messages were developed and pilot-tested in qualitative elicitation interviews with 22 people who use drugs, resulting in a library of 56 messages. In a single-group, within-subjects, community-based pilot trial, we will enroll 30 participants in the Resisting Stigma and Revaluating Your Thoughts (RESTART) intervention. Participants will receive 2 daily SMS text messages for 4 weeks. Implementation feasibility will be assessed through recruitment, enrollment, retention, and message delivery statistics. User feasibility and acceptability will be assessed at follow-up using 23 survey items informed by the Theoretical Framework of Acceptability. Primary effectiveness outcomes are changes in self-stigma (Substance Abuse Self-Stigma Scale) and stigma resistance (Stigma Resistance Scale) from baseline to follow-up measured via a self-administered survey. Secondary outcomes are changes in hope (Adult Dispositional Hope Scale) and self-esteem (Rosenberg Self-Esteem Scale). Feasibility and acceptability will be assessed with descriptive statistics; effectiveness outcomes will be assessed with paired 2-tailed t tests, and group differences will be explored using ANOVA. Overall, 12 participants will also be selected to complete acceptability interviews. RESULTS: This pilot study was funded by the National Institute on Drug Abuse in April 2023 and received regulatory approval in January 2024 by the University of North Carolina-Chapel Hill Institutional Review Board. Recruitment and enrollment began in March 2024. Follow-up visits are expected to conclude by May 2024. Results will be disseminated in relevant peer-reviewed journals. CONCLUSIONS: To the best of our knowledge, this is the first study to address substance use stigma via a self-help SMS text messaging program. Results will add to the nascent literature on stigma reduction in people who use drugs. This protocol may interest researchers who are considering text messaging to address psychosocial needs in hard-to-reach populations. TRIAL REGISTRATION: ClinicalTrials.gov NCT06281548; https://clinicaltrials.gov/ct2/show/NCT06281548. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/59224.

Behavioral and Health Outcome Differences by Heroin or Methamphetamine Preference Among People in Rural US Communities Who Use Both Substances.

Background: The United States' (US) opioid overdose epidemic has evolved into a combined stimulant/opioid epidemic, a pattern driven in part by mitigating opioid overdose risk, variable substance availability, and personal preferences. This study aimed to investigate the association between self-reported substance preference (heroin or methamphetamine) and behavioral/health outcomes among individuals who used both heroin and methamphetamine in the rural US. Methods: The Rural Opioid Initiative is a consortium of 8 research cohorts from 10 states and 65 rural counties that recruited individuals reporting past 30-day injection of any substance or opioid substance use by any route from 1/2018 to 3/2020. Analyses were restricted to participants ⩾18 years, who self-reported either heroin or methamphetamine as their preferred substance and past 30-day use of both heroin and methamphetamine. We examined cross-sectional associations between preferred substance (heroin versus methamphetamine) and behavioral and health outcomes using random effects meta-analysis with adjusted regression models. Results: Among 1239 participants, 61% (n = 752) reported heroin as their preferred substance. Adjusting for age, sex, and race/ethnicity, methamphetamine preference was associated with lower prevalence ratios for current naloxone possession (adjusted prevalence ratio [aPR] = 0.68; 95% Confidence Interval [95% CI] = 0.59-0.78; P-value ⩽ .001), of ever being told they had the hepatitis C virus (HCV; aPR = 0.72; 95% CI: 0.61-0.85; P-value ⩽ .001) and a personal history of overdose (aPR = 0.81; 95% CI = 0.73-0.90; P-value ⩽ .001). Conclusion: In our study analyzing associations between preferred substance and various behavioral and health outcomes amongst people who use both heroin and methamphetamine, a majority of participants preferred heroin. Methamphetamine preference was associated with lower prevalence of naloxone possession, ever being told they had HCV, and prior history of an overdose. This study underscores the need for targeted harm reduction services for people who prefer methamphetamine in rural areas.

fRAP 2.0: a community engagement method applied to cervical cancer disparities among Hispanic women.

focused Rapid Assessment Process (fRAP) 2.0 is a community engagement approach combining geospatial mapping with rapid qualitative assessment in cyclical fashion within communities to capture multifactorial and multilevel features impacting primary care problems. fRAP 2.0 offers primary care researchers a methodology framework for exploring complex community features that impact primary healthcare delivery and outcomes. The fRAP 2.0 study design expands the fRAP from a sequential design to a cyclical process of geospatial mapping and rapid qualitative assessment in search of modifiable contextual factors. Research participants are stakeholders from various socioecological levels whose perspectives inform study outcomes that they may use to then become the agents of change for the very problems they helped explore. Here, we present a proof-of-concept study for fRAP 2.0 examining disparities in cervical cancer mortality rates among Hispanic women in Texas. The primary outcomes of interest are features at the community level, medical health system level and regional government policy levels that offer opportunities for collaborative interventions to improve cervical cancer outcomes. In this study, geospatial mapping of county and ZIP code-level variables impacting postdiagnosis cervical cancer care at community, medical and policy levels were created using publicly available data and then overlaid with maps created with Texas Cancer Registry data for cervical cancer cases in three of the largest population counties. Geographically disparate areas were then qualitatively explored using participant observation and ethnographic field work, alongside 39 key informant interviews. Roundtable discussion groups and stakeholder engagement existed at every phase of the study. Applying the fRAP 2.0 method, we created an action-oriented roadmap of next steps to improve cervical cancer care disparities in the three Texas counties with emphasis on the high disparity county. We identified local change targets for advocacy and the results helped convene a stakeholder group that continues to actively create on-the-ground change in the high-disparity county to improve cervical cancer outcomes for Hispanic women.

Feasibility and Acceptability of a Prospective Syphilis Sexual Network Study for Sexual Minority Men.

BACKGROUND: In preparation for a prospective syphilis network study of sexual minority men, we conducted a mixed-methods formative study with the following objectives: a) assess acceptability of respondent driven sampling (RDS), b) assess acceptability of study procedures, c) social network seed selection, and d) pilot an ecological momentary assessment (EMA) study to assess social networking, sexual and substance use behavior. METHODS: We conducted in-depth interviews with eight providers serving sexual minority men and five focus group discussions with 34 sexual minority men, prioritizing four target populations: young Black sexual minority men, 2) on PrEP, 3) living with HIV, 4) not engaged in care. The 4-week EMA pilot was conducted with 40 sexual minority men. EMA survey responses were analyzed to evaluate how different compensation levels influenced response rates. Brief exit surveys were used to assess EMA app acceptability. RESULTS: Primary themes identified through qualitative data collection: 1) importance of developing trust and maintaining confidentiality during proposed recruitment activities, 2) importance of compensating participants appropriately for study activities, and 3) cultural considerations for increasing visibility and participation of young Black sexual minority men. All EMA participants reported being "completely comfortable" reporting sexual behavior through the app. Most (78%) preferred the app to in-person interviews. Several participants identified technical issues with the app, including not receiving push notifications and spontaneous closure. CONCLUSIONS: This mixed-methods formative study allowed for adjustments to and tailoring of the planned network study, including recruitment protocols, compensation type and amount, and EMA survey wording and response items.

A Brief Alcohol Intervention (BAI) to reduce alcohol use and improve PrEP outcomes among men who have sex with men in Vietnam: study protocol for a randomized controlled trial.

BACKGROUND: In Vietnam and other global settings, men who have sex with men (MSM) have become the population at greatest risk of HIV infection. Although HIV pre-exposure prophylaxis (PrEP) has been implemented as a prevention strategy, PrEP outcomes may be affected by low persistence and adherence among MSM with unhealthy alcohol use. MSM have a high prevalence of unhealthy alcohol use in Vietnam, which may affect PrEP outcomes. METHODS: Design: We will conduct a two-arm hybrid type 1 effectiveness-implementation randomized controlled trial of a brief alcohol intervention (BAI) compared to the standard of care (SOC) at the Sexual Health Promotion (SHP) clinic Hanoi, Vietnam. PARTICIPANTS: Sexually active MSM (n=564) who are newly initiating PrEP or re-initiating PrEP and have unhealthy alcohol use will be recruited and randomized 1:1 to the SOC or BAI arm. A subgroup of participants (n=20) in each arm will be selected for longitudinal qualitative interviews; an additional subset (n=48) in the BAI arm will complete brief quantitative and qualitative interviews after completion of the BAI to assess the acceptability of the intervention. Additional implementation outcomes will be assessed through interviews with clinic staff and stakeholders (n=35). INTERVENTION: Study participants in both arms will receive standard care for PrEP clients. In the BAI arm, each participant will receive two face-to-face intervention sessions and two brief booster phone sessions, based on cognitive behavioral therapy and delivered in motivational interviewing informed style, to address their unhealthy alcohol use. OUTCOMES: Effectiveness (PrEP and alcohol use) and cost-effectiveness outcomes will be compared between the two arms. Intervention implementation outcomes (acceptability, feasibility, adoption) will be assessed among MSM participants, clinic staff, and stakeholders. DISCUSSION: This proposed trial will assess an alcohol intervention for MSM with unhealthy alcohol use who initiate or re-initiate PrEP, while simultaneously preparing for subsequent implementation. The study will measure the effectiveness of the BAI for increasing PrEP persistence through reducing unhealthy alcohol use in a setting where excessive alcohol consumption is a normative behavior. If effective, implementation-focused results will inform future scale-up of the BAI in similar settings. TRIAL REGISTRATION: NCT06094634 on clinicaltrials.gov. Registered 16 October 2023.

Long-term Outcomes of Liver Transplantation for Inborn Errors of Metabolism in Children.

BACKGROUND: Liver transplantation for inborn errors of metabolism is increasingly common and has historically had positive outcomes. However, this therapeutic modality is not without risks, and patient post-transplant quality of life should be part of the consideration. METHODS: This retrospective, observational cohort study included all pediatric patients receiving liver transplant from 2010 through 2020 at a single center. Recipients were split into 2 groups based on metabolic or non-metabolic indications for liver transplant. Ten-year patient survival and graft survival were analyzed. The PedsQL Transplant Module and RAND 36-Item Health Survey 1.0 were administered prospectively to those recipients with metabolic indications. RESULTS: Ten-year patient survival was statistically significantly higher in the metabolic group than in the non-metabolic (p < .05), and there was no difference in 10-year graft survival between groups. Of the 12 patients in the metabolic group who completed the PedsQL Transplant Module or RAND 36-Item Health Survey 1.0, the median score was 88, similar to the score seen in healthy children. CONCLUSIONS: Liver transplantation for inborn errors of metabolism provides excellent long-term outcomes in terms of patient and graft survival, while maintaining a high quality of life.

Cefiderocol heteroresistance associated with mutations in TonB-dependent receptor genes in Pseudomonas aeruginosa of clinical origin.

The siderophore-cephalosporin cefiderocol (FDC) presents a promising treatment option for carbapenem-resistant (CR) P. aeruginosa (PA). FDC circumvents traditional porin and efflux-mediated resistance by utilizing TonB-dependent receptors (TBDRs) to access the periplasmic space. Emerging FDC resistance has been associated with loss of function mutations within TBDR genes or the regulatory genes controlling TBDR expression. Further, difficulties with antimicrobial susceptibility testing (AST) and unexpected negative clinical treatment outcomes have prompted concerns for heteroresistance, where a single lineage isolate contains resistant subpopulations not detectable by standard AST. This study aimed to evaluate the prevalence of TBDR mutations among clinical isolates of P. aeruginosa and the phenotypic effect on FDC susceptibility and heteroresistance. We evaluated the sequence of pirR, pirS, pirA, piuA, or piuD from 498 unique isolates collected before the introduction of FDC from four clinical sites in Portland, OR (1), Houston, TX (2), and Santiago, Chile (1). At some clinical sites, TBDR mutations were seen in up to 25% of isolates, and insertion, deletion, or frameshift mutations were predicted to impair protein function were seen in 3% of all isolates (n = 15). Using population analysis profile testing, we found that P. aeruginosa with major TBDR mutations were enriched for a heteroresistant phenotype and undergo a shift in the susceptibility distribution of the population as compared to susceptible strains with wild-type TBDR genes. Our results indicate that mutations in TBDR genes predate the clinical introduction of FDC, and these mutations may predispose to the emergence of FDC resistance.

Developing Leaders in Surgical Residency: A Curriculum for Success.

OBJECTIVE: As surgical residents continue in their training, they are expected to not only take part in more complicated procedures, but to also serve as leaders in their respective care teams. While surgical skills are intensively taught in surgical residency programs, leadership is often learned informally, to the detriment of residents. Our curriculum was developed and implemented to provide foundational knowledge for surgical residents as they take on senior roles so that they may successfully act as leaders. This educational workshop was effective and efficient and can be applied at other residency programs that seek to improve the leadership skills of their residents. DESIGN: Implementation of a 3-day program focused on leadership, surgical skills, and career development to provide rising PGY-4 surgical residents with the abilities necessary for successful training. SETTING: This program was implemented at the University of Minnesota General Surgery residency program. PARTICIPANTS: Rising PGY-4 general surgery residents. RESULTS: The program consisted of a 3-day workshop which all rising PGY-4 residents participating in before transitioning into their respective roles. The program was led by the general surgery faculty. CONCLUSIONS: Curricula focused on developing leadership skills in residents can be effectively applied in a time-efficient manner that can benefit the residents as they move into official leadership roles on the care team.

Comparing the acute responses between a manual and automated blood flow restriction system.

The purpose of this study was to compare acute responses between manual and automated blood flow restriction (BFR) systems. Methods: A total of 33 individuals completed this study. On visit 1, arterial occlusion pressure (AOP, mm Hg), cardiovascular responses, and discomfort (RPE-D) were measured with each BFR system at rest. On visit 2, unilateral bicep curls were completed [30% one-repetition maximum; 50% AOP] with one system per arm. Muscle thickness (MT, cm) and maximal force (N) were assessed before (pre), immediately (post-0), 5 min (post-5), and 10 min (post-10) post-exercise. Ratings of perceived exertion (RPE-E) and ratings of perceived discomfort (RPE-D) were assessed throughout the exercise. AOP and repetitions were compared with Bayesian paired t-tests. Other outcomes were compared with Bayesian RMANOVAs. BF10 represents the likelihood of the best model vs. the null. The results are presented as mean ± SD. Results: Supine cardiovascular responses and RPE-D were similar for manual and automated (all BF10 ≤ 0.2). Supine AOP for manual (157 ± 20) was higher than that of automated (142 ± 17; BF10 = 44496.0), but similar while standing (manual: 141 ± 17; automated: 141 ± 22; BF10 = 0.2). MT (time, BF10 = 6.047e + 40) increased from Pre (3.9 ± 0.7) to Post-0 (4.4 ± 0.8; BF10 = 2.969e + 28), with Post-0 higher than Post-5 (4.3 ± 0.8) and Post-10 (4.3 ± 0.8; both BF10 ≥ 275.2). Force (time, BF10 = 1.246e + 29) decreased from Pre (234.5 ± 79.2) to Post-0 (149.8 ± 52.3; BF10 = 2.720e + 22) and increased from Post-0 to Post-5 (193.3 ± 72.7; BF10 = 1.744e + 13), with Post-5 to Post-10 (194.0 ± 70.6; BF10 = 0.2) being similar. RPE-E increased over sets. RPE-D was lower for manual than automated. Repetitions per set were higher for manual (Set 1: 37 ± 18; Set 4: 9 ± 5) than automated (Set 1: 30 ± 7; Set 4: 7 ± 3; all BF10 ≥ 9.7). Conclusion: Under the same relative pressure, responses are mostly similar between BFR systems, although a manual system led to lower exercise discomfort and more repetitions.

Prevalence of the Cefazolin Inoculum Effect (CzIE) in Nasal Colonizing Methicillin-Susceptible Staphylococcus aureus in Patients from Intensive Care Units in Colombia and Use of a Modified Rapid Nitrocefin Test for Detection.

The cefazolin inoculum effect (CzIE) has been associated with poor clinical outcomes in patients with MSSA infections. We aimed to investigate the point prevalence of the CzIE among nasal colonizing MSSA isolates from ICU patients in a multicenter study in Colombia (2019-2023). Patients underwent nasal swabs to assess for S. aureus colonization on admission to the ICU and some individuals had follow-up swabs. We performed cefazolin MIC by broth-microdilution using standard and high-inoculum and developed a modified nitrocefin-based rapid test to detect the CzIE. Whole genome sequencing was carried out to characterize BlaZ types and allotypes, phylogenomics and Agr-typing. All swabs were subjected to 16S-rRNA metabarcoding sequencing to evaluate microbiome characteristics associated with the CzIE. A total of 352 patients were included; 46/352 (13%) patients were colonized with S. aureus; 22% (10/46) and 78% (36/46) with MRSA and MSSA, respectively. Among 36 patients that contributed with 43 MSSA colonizing isolates, 21/36 (58%) had MSSA exhibiting the CzIE. BlaZ type A and BlaZ-2 were the predominant type and allotype in 56% and 52%, respectively. MSSA belonging to CC30 were highly associated with the CzIE and SNP analyses supported transmission of MSSA exhibiting the CzIE among some patients of the same unit. The modified nitrocefin rapid test had 100%, 94.4% and 97.7% sensitivity, specificity and accuracy, respectively. We found a high prevalence point prevalence of the CzIE in MSSA colonizing the nares of critically-ill patients in Colombia. A modified rapid test was highly accurate in detecting the CzIE in this patient population.