A Prospective Study to Assess the Relationship Between Nontechnical Skills for Surgeons (NOTSS) and Patient Outcomes.

BACKGROUND: Effective technical and nontechnical skills are necessary for surgeons to provide optimal patient care. The aim of this study was to assess the relationship between Nontechnical Skills for Surgeons (NOTSS) and postoperative outcomes among general surgery patients. METHOD: This prospective observational study was conducted at a single, large, urban, academic hospital in the USA from February to September 2022. Two raters (an observer and a nurse) assessed each participating surgeon during 3 to 5 different operations. Patient outcome data were collected from the Illinois Surgical Quality Improvement Collaborative (ISQIC) database. We used the American College of Surgeons National Quality Improvement Program (ACS NSQIP) method to calculate risk-adjusted complications. Robust linear regression models were used to assess the association between surgeons' nontechnical skills and risk-adjusted postoperative complications. RESULTS: Of the 45 surgeons who were observed in the study, 25 (55.5%) had patient outcome data captured by the ISQIC database. The adjusted analysis found that for every unit increase in the NOTSS score, there was a significant 5.1 (95% CI: -8.1; -2.0,p = 0.003), decrease in the adjusted risk of any postoperative complication, a significant 1.1 (95% CI: -1.8; -0.2, p = 0.01) decrease in the adjusted risk of mortality, and significant 1.1 (95% CI: -1.9; -0.4, p = 0.005) decrease in adjusted risks of returning to the operating room. CONCLUSION: Higher surgeons' nontechnical skills scores were associated with a decreased risk-adjusted rate of any postoperative complication, mortality, and return to the operating room. Strategies to improve postoperative patient outcomes should include the improvement of surgeons' nontechnical skills.

Comparison of Ultrasound Findings Associated with Adverse Fetal, Obstetric, and Neonatal Outcomes in Pregestational Type 1 And Type 2 Diabetes: A Systematic Review.

OBJECTIVE: We aimed to summarize the available evidence examining the association between prenatal ultrasound findings and adverse fetal, obstetric, and neonatal outcomes in pregnancies complicated by type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) and to evaluate whether the predictive value of ultrasound findings for adverse outcomes varies between T1DM and T2DM pregnancies. DATA SOURCES: We conducted a systematic review of the existing literature through August 12, 2024. METHODS OF STUDY SELECTION: We included articles in English that reported associations between ultrasound findings and fetal, obstetric, and neonatal outcomes in pregnant people with T1DM and T2DM. Two independent reviewers examined articles at the abstract level and, if eligible, at the full-text level; disagreements were adjudicated by a third reviewer. TABULATION, INTEGRATION, AND RESULTS: Of the 2,088 unique citations reviewed, 12 studies met the inclusion criteria describing associations between ultrasound findings and fetal, obstetric, and neonatal outcomes among a total of 1,165 pregnant people with T1DM and 489 pregnant people with T2DM. Most studies (10/12) examined the association between ultrasound measures of growth, including estimated fetal weight (EFW) and its individual components, abdominal wall thickness, head circumference to abdominal circumference (HC/AC) ratio, and birthweight, large for gestational age (LGA) or small for gestational age (SGA). Studies did not examine stillbirth, neonatal demise, or maternal outcomes other than cesarean section. CONCLUSION: This systematic review synthesizes the available literature on ultrasound risk markers of adverse fetal, obstetric, and neonatal outcomes separately in pregnant people with T1DM and T2DM. We identified very few studies that distinguished between pregnant people with T1DM and T2DM, and the majority focused on surrogate outcomes (e.g., LGA, SGA) of morbidity. Our findings highlight the need for further studies investigating these distinct diseases to provide evidence for antenatal management recommendations.

Unbiased care, unequal outcomes: a nursing telehealth intervention reveals systematic inequities in COVID-19 care delivery.

BACKGROUND: The Covid Connected Care Center (C4), a low-barrier telephone nurse hotline, was developed at an academic medical center to increase access to healthcare information and services across the state of Oregon, including to those without a usual source of care. Other studies have demonstrated that telephone triage services can positively influence health behaviors, but it is not known how this effect is maintained across racial/ethnic groups. The objective of this study was to show that the C4 reached throughout the state of Oregon, was valuable to callers, and that recommendations given affected callers' subsequent health-related behaviors. METHODS: This mixed-methods study, informed by the RE-AIM (Reach, Effectiveness, Addoption, Implementation and Maintenance) framework, assessed caller demographics and clinical care from March 30 2020 until September 8, 2021. Descriptive statistics, multivariable risk models and Zou's modified Poisson modeling were applied to electronic health record and call system data; An inductive approach was used for patient and staff experience surveys and semi-structured interviews. Approval was obtained from the OHSU Institutional Review Board (Study 00021413). RESULTS: 145,537 telephone calls and 92,100 text-based contacts (61% and 39%, respectively) were included. Callers tended to not have a usual source of primary care and utilized recommended services. Emergency department utilization was minimal (1.5%). Racial or ethnic disparities were not detected in the recommendations, but Black (RR 0.92, CI 0.86-0.98) and Multiracial (RR 0.90 CI 0.81-0.99) callers were less likely than non-Hispanic white callers to receive a COVID-19 test. Participants in the post-call survey (n = 50) would recommend this service to friends or family. Interviews with callers (n = 9) revealed this was because they valued assistance translating general recommendations into a personalized care plan. C4 staff interviewed (n = 9) valued the opportunity to serve the public. The C4 was a trusted resource to the public and reached the intended audiences. However, disparities in access to COVID-19 testing persisted. CONCLUSIONS: Nursing triage hotlines can guide caller behavior and be an effective part of a robust public health information infrastructure.

Fidelity of Enhanced Recovery Protocol Implementation With Assessment of Hospital-Specific Materials.

INTRODUCTION: Variability in implementation of enhanced recovery protocols (ERPs) often reduces the effects of an intervention on clinical outcomes. This study aimed to evaluate hospital-level implementation fidelity to a pediatric gastrointestinal surgery ERP by assessing site-specific implementation materials. METHODS: This document analysis study operationalized implementation fidelity as adherence to the creation of specified materials at each study site. During the 12-mo implementation phase within the stepped-wedge cluster randomized control trial, ENhanced Recovery In CHildren Undergoing Surgery, study sites were provided with materials (e.g., order sets), access to peer-counseling, and given key ERP elements spanning multiple phases of care. Sixteen of the 18 total study sites submitted implementation materials, including 14 anesthesia protocols, 11 order sets, and 16 sets of patient/family education materials. These materials were assessed and graded for fidelity using prespecified criteria. Hospital-level fidelity scores could range from 0 to a maximum score of 18, and were categorized as either high or low, based on whether the score was above or below/equal to the median. Descriptive statistics and Wilcoxon rank sum test were used for analysis. RESULTS: The overall hospital-level median fidelity score for inclusion of ERP elements in the implementation materials was 10.5. The median score was 12.8 at nine high-fidelity sites and was 5.6 at nine low-fidelity sites (P < 0.01). Higher adherence was noted for avoiding prolonged fasting (n = 16/18 hospitals; 89%) and preventing nausea and vomiting (n = 16/18 hospitals; 89%) in anesthesia protocols and/or order sets. Lower adherence was noted for incorporation of minimally invasive surgical techniques (n = 2/18 hospitals, 11%) and of preoperative optimization of medical comorbidities (n = 0/18 hospitals, 0%) in implementation materials. CONCLUSIONS: Despite substantial resources to promote ERP elements, there was wide variation in fidelity for incorporating ERPs into implementation materials among hospital sites. Development of high-fidelity implementation materials for complex ERPs for gastrointestinal surgery in children may require longer than 12 months. Additional implementation strategies, resources, and modification of implementation-focused materials may be needed.

Meta-analysis of genome-wide association studies of stable warfarin dose in patients of African ancestry.

Warfarin dose requirements are highly variable due to clinical and genetic factors. While genetic variants influencing warfarin dose have been identified in European and East Asian populations, more work is needed to identify African-specific genetic variants to help optimize warfarin dosing. We performed genome-wide association studies (GWAS) in four African cohorts from Uganda, South Africa, and Zimbabwe, totalling 989 warfarin-treated participants who reached stable dose and had international normalized ratios within therapeutic ranges. We also included two African American cohorts recruited by the International Warfarin Pharmacogenetics Consortium (n=316) and the University of Alabama at Birmingham (n=199). Following the GWAS, we performed standard error-weighted meta-analyses and then conducted stepwise conditional analyses to account for known loci (the CYP2C cluster SNP rs12777823 and CYP2C9 in chromosome 10; VKORC1 in chromosome 16). The genome-wide significance threshold was set at P<5×10-8. The meta-analysis, comprising 1,504 participants identified 242 significant SNPs across three genomic loci, with 99.6% of these located within known loci on chromosomes 10 (top SNP: rs58800757, P=4.27×10-13) and 16 (top SNP: rs9925964, P=9.97×10-16). Adjustment for the VKORC1 SNP -1639G>A revealed an additional locus on chromosome 2 (top SNPs rs116057875/rs115254730/rs115240773, P=3.64×10-8), implicating the MALL gene, that could indirectly influence warfarin response through interactions with caveolin-1. In conclusion, our meta-analysis of six cohorts of warfarin-treated patients of African ancestry reaffirmed the importance of CYP2C9 and VKORC1 in influencing warfarin dose requirements. We also identified a new locus (MALL), that still requires direct evidence of biological plausibility.

Implementing a pragmatic clinical trial to tailor opioids for chronic pain on behalf of the IGNITE ADOPT PGx investigators.

Chronic pain is a prevalent condition with enormous economic burden. Opioids such as tramadol, codeine, and hydrocodone are commonly used to treat chronic pain; these drugs are activated to more potent opioid receptor agonists by the hepatic CYP2D6 enzyme. Results from clinical studies and mechanistic understandings suggest that CYP2D6-guided therapy will improve pain control and reduce adverse drug events. However, CYP2D6 is rarely used in clinical practice due in part to the demand for additional clinical trial evidence. Thus, we designed the ADOPT-PGx (A Depression and Opioid Pragmatic Trial in Pharmacogenetics) chronic pain study, a multicenter, pragmatic, randomized controlled clinical trial, to assess the effect of CYP2D6 testing on pain management. The study enrolled 1048 participants who are taking or being considered for treatment with CYP2D6-impacted opioids for their chronic pain. Participants were randomized to receive immediate or delayed (by 6 months) genotyping of CYP2D6 with clinical decision support (CDS). CDS encouraged the providers to follow the CYP2D6-guided trial recommendations. The primary study outcome is the 3-month absolute change in the composite pain intensity score assessed using Patient-Reported Outcomes Measurement Information System (PROMIS) measures. Follow-up will be completed in July 2024. Herein, we describe the design of this trial along with challenges encountered during enrollment.

Exploratory qualitative study of firearm storage practices among surgeons in the USA: contexts and motivations.

BACKGROUND: A US survey of surgeons found that 32% store firearms unlocked and loaded. This study explored conditions and contexts impacting personal firearm storage methods among surgeons. METHODS: We conducted semi-structured interviews with English-speaking fellows of the American College of Surgeons who treated patients injured by firearms and who owned or lived in homes with firearms. Participants were recruited through email and subsequent snowball sampling from April 2022 to August 2022. All interviews were audio-recorded and transcribed verbatim. Thematic analysis was applied to transcripts to identify codes. A mixed deductive and inductive approach was used for data reduction and sorting. RESULTS: A total of 32 surgeons were interviewed; most were male and white. Dominant themes for firearm storage practices were based on (1) attitudes; (2) perceived norms; (3) personal agency; and (4) intention of firearm use. Personal agency often conflicted with attitudes and perceived norms for surgeons owning firearms for self-defence. CONCLUSIONS: Storage practices in this sample of firearm-owning surgeons were driven by intent for firearm use, coupled with attitudes, perceived norms and personal agency. Personal agency often conflicted with attitudes and perceived norms, especially for surgeons who owned their firearm for self-defence.

Comparison of pain after prophylactic anticoagulant injections to prevent venous thromboembolism.

Subcutaneous injection of unfractionated heparin (UH) or low molecular weight heparin (LMWH) is frequently utilized for venous thromboembolism chemoprophylaxis. We previously discovered that nurses believe patients experience more pain with UH compared to the LMWH enoxaparin; however, no published studies that are appropriately powered exist comparing pain associated with subcutaneous chemoprophylaxis. Our objective was to assess if differences exist in pain associated with subcutaneous administration of UH and enoxaparin. We conducted an observational study of patients who underwent major abdominal surgery between 11/2017-4/2019. All patients received one of three prophylactic regimens: (1) UH only, (2) Initial dose of UH followed by enoxaparin, or (3) enoxaparin only. Of the 74 patients observed, 40 patients received UH followed by enoxaparin, 17 received UH only, and 17 received enoxaparin only. There was a significant difference in patients' mean perceived pain between subcutaneous UH and enoxaparin injections (mean post-injection pain after UH 3.3 vs. enoxaparin 1.5; p < 0.001). There was no significant difference in perceived pain for patients who received consecutive UH or enoxaparin injections. Differences in pain associated with different chemoprophylaxis agents may be an unrecognized driver of patient refusals of VTE chemoprophylaxis and may lead to worse VTE outcomes.

Pregnancy and Parenthood Among US Surgical Residents.

Importance: The ability to pursue family planning goals is integral to gender equity in any field. Procedural specialties pose occupational risks to pregnancy. As the largest procedural specialty, general surgery provides an opportunity to understand family planning, workplace support for parenthood, obstetric outcomes, and the impact of these factors on workforce well-being, gender equity, and attrition. Objective: To examine pregnancy and parenthood experiences, including mistreatment and obstetric outcomes, among a cohort of US general surgical residents. Design, Setting, and Participants: This cohort study involved a cross-sectional national survey of general surgery residents in all programs accredited by the Accreditation Council for Graduate Medical Education after the 2021 American Board of Surgery In-Training Examination. Female respondents who reported a pregnancy and male respondents whose partners were pregnant during clinical training were queried about pregnancy- and parenthood-based mistreatment, obstetric outcomes, and current well-being (burnout, thoughts of attrition, suicidality). Main Outcomes and Measures: Primary outcomes included obstetric complications and postpartum depression compared between female residents and partners of male residents. Secondary outcomes included perceptions about support for family planning, pregnancy, or parenthood; assisted reproductive technology use; pregnancy/parenthood-based mistreatment; neonatal complications; and well-being, compared between female and male residents. Results: A total of 5692 residents from 325 US general surgery programs participated (81.2% response rate). Among them, 957 residents (16.8%) reported a pregnancy during clinical training (692/3097 [22.3%] male vs 265/2595 [10.2%] female; P < .001). Compared with male residents, female residents more frequently delayed having children because of training (1201/2568 [46.8%] females vs 1006/3072 [32.7%] males; P < .001) and experienced pregnancy/parenthood-based mistreatment (132 [58.1%] females vs 179 [30.5%] males; P < .001). Compared with partners of male residents, female residents were more likely to experience obstetric complications (odds ratio [OR], 1.42; 95% CI, 1.04-1.96) and postpartum depression (OR, 1.63; 95% CI, 1.11-2.40). Pregnancy/parenthood-based mistreatment was associated with increased burnout (OR, 2.03; 95% CI, 1.48-2.78) and thoughts of attrition (OR, 2.50; 95% CI, 1.61-3.88). Postpartum depression, whether in female residents or partners of male residents, was associated with resident burnout (OR, 1.93; 95% CI, 1.27-2.92), thoughts of attrition (OR, 2.32; 95% CI, 1.36-3.96), and suicidality (OR, 5.58; 95% CI, 2.59-11.99). Conclusions and Relevance: This study found that pregnancy/parenthood-based mistreatment, obstetric complications, and postpartum depression were associated with female gender, likely driving gendered attrition. Systematic change is needed to protect maternal-fetal health and advance gender equity in procedural fields.

Experiences With Unionization Among General Surgery Resident Physicians, Faculty, and Staff.

Importance: Labor unions are a mechanism for employee advocacy, but their role in surgery resident wellness is poorly characterized. Objective: To understand experiences with unionization among general surgery residents and residency program faculty and staff. Design, Setting, and Participants: This exploratory qualitative study included data from the Surgical Education Culture Optimization Through Targeted Interventions Based on National Comparative Data (SECOND) trial. In the exploratory phase of the SECOND trial (from March 6, 2019, to March 12, 2020), semistructured interviews about wellness were conducted with residents, faculty (attending physicians), and staff (program administrators) at 15 general surgery residency programs. Unionization was identified as an emergent theme in the interviews. Data analysis was performed from March 2019 to May 2023. Main Outcomes and Measures: The main outcome was resident and faculty experience with resident labor unions. In the qualitative analysis, lexical searches of interview transcripts identified content regarding resident labor unions. A codebook was developed inductively. Transcripts were coded by dyads, using a constant comparative approach, with differences reconciled by consensus. Results: A total of 22 interview transcripts were identified with relevant content. Of these, 19 were individual interviews conducted with residents (n = 10), faculty (n = 4), administrative staff (n = 1), a program director (n = 1), a department chair (n = 1), and designated institutional officials (n = 2), and 3 were from resident focus groups. Residents from all postgraduate year levels, including professional development (ie, research) years, were represented. Interviewees discussed resident unions at 2 programs (1 recently unionized and 1 with a decades-long history). Interviewees described the lack of voice and the lack of agency as drivers of unionization ("Residents…are trying to take control of their well-being"). Increased salary stipends and/or housing stipends were the most concretely identified union benefits. Unanticipated consequences of unionization were described by both residents and faculty, including (1) irrelevance of union-negotiated benefits to surgical residents, (2) paradoxical losses of surgery department-provided benefits, and (3) framing of resident-faculty relationships as adversarial. Union executives were noted to be nonphysician administrators whose participation in discussions about clinical education progression may increase the time and effort to remediate a resident and/or reduce educators' will to meaningfully intervene. Active surgical resident participation within the union allows for an understanding of surgical trainees' unique needs and reduced conflict. Conclusions and Relevance: In this qualitative study, unionization was a mechanism for resident voice and agency; the desire to unionize likely highlighted the lack of other such mechanisms in the training environment. However, these findings suggest that unionization may have had unintended consequences on benefits, flexibility, and teaching. Effective advocacy, whether within or outside the context of a union, was facilitated by participation from surgical residents. Future research should expand on this exploratory study by including a greater number of institutions and investigating the evolution of themes over time.

Interhospital Transfer of Patients With Acute Respiratory Failure in the United States: A Scoping Review.

OBJECTIVES: Interhospital transfer of patients with acute respiratory failure (ARF) is relevant in the current landscape of critical care delivery. However, current transfer practices for patients with ARF are highly variable, poorly formalized, and lack evidence. We aim to synthesize the existing evidence, identify knowledge gaps, and highlight persisting questions related to interhospital transfer of patients with ARF. DATA SOURCES: Ovid Medline, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Embase, CINAHL Plus, and American Psychological Association. STUDY SELECTION: We included studies that evaluated or described hospital transfers of adult (age > 18) patients with ARF between January 2020 and 2024 conducted in the United States. Using predetermined search terms and strategies, a total of 3369 articles were found across all databases. After deduplication, 1748 abstracts were screened by authors with 45 articles that advanced to full-text review. This yielded 16 studies that fit our inclusion criteria. DATA EXTRACTION: The studies were reviewed in accordance to Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews by three authors. DATA SYNTHESIS: Included studies were mostly retrospective analyses of heterogeneous patients with various etiologies and severity of ARF. Overall, transferred patients were younger, had high severity of illness, and were more likely to have commercial insurance compared with nontransferred cohorts. There is a paucity of data examining why patients get transferred. Studies that retrospectively evaluated outcomes between transferred and nontransferred cohorts found no differences in mortality, although transferred patients have a longer length of stay. There is limited evidence to suggest that patients transferred early in their course have improved outcomes. CONCLUSIONS: Our scoping review highlights the sparse evidence and the urgent need for further research into understanding the complexity behind ARF transfers. Future studies should focus on defining best practices to inform clinical decision-making and improve downstream outcomes.

A review of mitotane in the management of adrenocortical cancer.

IMPORTANCE: Mitotane (Lysodren, o,p'-DDD [1-(o-chlorophenyl)-1-(p-chlorophenyl)-2,2-dichloroethane)] is currently the only United States Food and Drug Administration and European Medicines Agency-approved product for the treatment of adrenocortical carcinoma. OBSERVATIONS: Mitotane is challenging to administer; however, its toxicities (specifically adrenal insufficiency) are well known, and the management of adverse consequences has established approaches. While often viewed through the prism of a cytotoxic agent, it can also interfere with hormone production making it a valuable asset in managing functional ACC. A recently completed prospective trial has shed some light on its use in the adjuvant setting, but further clarity is needed. Many think mitotane has a role in the advanced or metastatic setting, although prospective data are lacking and retrospective analyses are often difficult to interpret. CONCLUSIONS AND RELEVANCE: When used carefully and thoughtfully, especially in patients with hormonal excess, mitotane is an important component of the treatment armamentarium for ACC.

Are We Supporting Surgical Quality Improvement in Training and Beyond? A Qualitative Study of Surgical Trainees and Practicing Surgeons.

BACKGROUND: We conducted a qualitative study to describe surgeon and surgical trainee perspectives of quality improvement (QI) in training and practice to elucidate how surgeons and trainees interact with barriers and leverage facilitators to learn and conduct QI. STUDY DESIGN: Surgeons and surgical trainees of the American College of Surgeons were recruited via email and snowball sampling to participate in focus groups. Eligible individuals were English speaking surgical trainees or practicing surgeons. We developed a semi-structured focus group protocol to explore barriers and facilitators of quality training and improvement. An inductive thematic approach was used to identify actionable items. RESULTS: Thirty-two surgical trainees and surgeons participated in six focus groups. 28% of participants were trainees (8 residents, 1 fellow) and 72% were practicing surgeons, representing practice settings in university, community, and Veterans Affairs hospitals in urban and suburban regions. Thematic analysis revealed the central theme among trainees was that they lacked necessary support to effectively learn and conduct QI. Dominant sub-themes included lack of formal education, insufficient time, inconsistent mentorship, and maximizing self-sufficiency to promotes success. The central theme among surgeons was that effective QI initiatives require adequate resources and institutional support; however, surgeons in this study were ultimately constrained by institutional limitations. Sub-themes included difficulties in data acquisition and interpretation, financial limitations, workforce and staffing challenges, misaligned stakeholder priorities, and institutional culture. CONCLUSION: This qualitative evaluation further details gaps in QI demonstrated by previous quantitative studies. There is an opportunity to address these gaps with dedicated QI training and mentorship for surgical trainees and by creating a supportive environment with ample resources for surgeons.

Contemporary Evaluation of Work-Life Integration and Wellbeing in US Surgical Residents: A National Mixed-Methods Study.

BACKGROUND: The demands of surgical training present challenges for work-life integration (WLI). We sought to identify factors associated with work-life conflicts and to understand how programs support WLI. STUDY DESIGN: A cross-sectional national survey conducted after the 2020 American Board of Surgery In-Training Examination queried 4 WLI items. Multivariable regression models evaluated factors associated with (1) work-life conflicts and (2) well-being (career dissatisfaction, burnout, thoughts of attrition, suicidality). Semi-structured interviews conducted with faculty and residents from 15 general surgery programs were analyzed to identify strategies for supporting WLI. RESULTS: Of 7,233 residents (85.5% response rate) 5,133 had data available on work-life conflicts. 44.3% reported completing non-educational task-work at home, 37.6% were dissatisfied with time for personal life (e.g., hobbies), 51.6% with maintaining healthy habits (e.g., exercise), and 48.0% with performing routine health maintenance (e.g., dentist). In multivariable analysis, parents and female residents were more likely to report work-life conflicts (all p<0.05). After adjusting for other risk factors (e.g., duty-hour violations, and mistreatment), residents with work-life conflicts remained at increased risk for career dissatisfaction, burnout, thoughts of attrition, and suicidality (all p<0.05). Qualitative analysis revealed interventions for supporting WLI including (1) protecting time for health maintenance (e.g., therapy); (2) explicitly supporting life outside of work (e.g., prioritizing time with family); and (3) allowing meaningful autonomy in scheduling (e.g., planning for major life events). CONCLUSIONS: Work-life conflicts are common among surgical residents and are associated with poor resident well-being. Well-designed program-level interventions have the potential to support WLI in surgical residency.

CYP2C19 Genotype Is Associated With Adverse Cardiovascular Outcomes in Black Patients Treated With Clopidogrel Undergoing Percutaneous Coronary Intervention.

BACKGROUND: Cytochrome P450 2C19 (CYP2C19) intermediate and poor metabolizer patients exhibit diminished clopidogrel clinical effectiveness after percutaneous coronary intervention (PCI). However, outcome studies to date have lacked racial diversity. Thus, the impact of CYP2C19 genotype on cardiovascular outcomes in patients treated with clopidogrel who identify as Black or African American remains unclear. METHODS AND RESULTS: Adults among 5 institutions who self-identified as Black or African American, underwent PCI and clinical CYP2C19 genotyping, and were treated with clopidogrel were included. Data were abstracted from health records. Major atherothrombotic (composite of death, myocardial infarction, ischemic stroke, stent thrombosis, or revascularization for unstable angina) and bleeding event rates within 1 year after PCI were compared across CYP2C19 metabolizer groups using multivariable Cox regression adjusted for potential confounders and baseline variables meeting a threshold of P<0.10. The population included 567 Black patients treated with clopidogrel (median age, 62 years; 46% women; 70% with an acute coronary syndrome indication for PCI). Major atherothrombotic events rates were significantly higher among clopidogrel-treated intermediate and poor metabolizers (24 of 125 [19.2%]) versus patients treated with clopidogrel without a no function allele (43 of 442 [9.7%]; 35.1 versus 15.9 events per 100 person-years; adjusted hazard ratio, 2.00 [95% CI, 1.20-3.33], P=0.008). Bleeding event rates were low overall (23 of 567 [4.1%]) and did not differ among the metabolizer groups. CONCLUSIONS: Black patients with CYP2C19 intermediate and poor metabolizer phenotypes who are treated with clopidogrel exhibit increased risk of adverse cardiovascular outcomes after PCI in a real-world clinical setting. Bleeding outcomes should be interpreted cautiously. Prospective studies are needed to determine whether genotype-guided use of prasugrel or ticagrelor in intermediate and poor metabolizers improves outcomes in Black patients undergoing PCI.

Rationale and design for a pragmatic randomized trial to assess gene-based prescribing for SSRIs in the treatment of depression.

Specific selective serotonin reuptake inhibitors (SSRIs) metabolism is strongly influenced by two pharmacogenes, CYP2D6 and CYP2C19. However, the effectiveness of prospectively using pharmacogenetic variants to select or dose SSRIs for depression is uncertain in routine clinical practice. The objective of this prospective, multicenter, pragmatic randomized controlled trial is to determine the effectiveness of genotype-guided selection and dosing of antidepressants on control of depression in participants who are 8 years or older with ≥3 months of depressive symptoms who require new or revised therapy. Those randomized to the intervention arm undergo pharmacogenetic testing at baseline and receive a pharmacy consult and/or automated clinical decision support intervention based on an actionable phenotype, while those randomized to the control arm have pharmacogenetic testing at the end of 6-months. In both groups, depression and drug tolerability outcomes are assessed at baseline, 1 month, 3 months (primary), and 6 months. The primary end point is defined by change in Patient-Reported Outcomes Measurement Information System (PROMIS) Depression score assessed at 3 months versus baseline. Secondary end points include change inpatient health questionnaire (PHQ-8) measure of depression severity, remission rates defined by PROMIS score < 16, medication adherence, and medication side effects. The primary analysis will compare the PROMIS score difference between trial arms among those with an actionable CYP2D6 or CYP2C19 genetic result or a CYP2D6 drug-drug interaction. The trial has completed accrual of 1461 participants, of which 562 were found to have an actionable phenotype to date, and follow-up will be complete in April of 2024.

Integrated metabolomics analysis reveals mechanistic insights into variability in blood pressure response to thiazide diuretics and beta blockers.

Hypertensive patients with a higher proportion of genetic West African ancestry (%GWAA) have better blood pressure (BP) response to thiazide diuretics (TDs) and worse response to ß-blockers (BBs) than those with lower %GWAA, associated with their lower plasma renin activity (PRA). TDs and BBs are suggested to reduce BP in the long term through vasodilation via incompletely understood mechanisms. This study aimed at identifying pathways underlying ancestral differences in PRA, which might reflect pathways underlying BP-lowering mechanisms of TDs and BBs. Among hypertensive participants enrolled in the Pharmacogenomics Evaluation of Antihypertensive Responses (PEAR) and PEAR-2 trials, we previously identified 8 metabolites associated with baseline PRA and 4 metabolic clusters (including 39 metabolites) that are different between those with GWAA <45% versus ≥45%. In the current study, using Ingenuity Pathway Analysis (IPA), we integrated these signals. Three overlapping metabolic signals within three significantly enriched pathways were identified as associated with both PRA and %GWAA: ceramide signaling, sphingosine 1- phosphate signaling, and endothelial nitric oxide synthase signaling. Literature indicates that the identified pathways are involved in the regulation of the Rho kinase cascade, production of the vasoactive agents nitric oxide, prostacyclin, thromboxane A2, and endothelin 1; the pathways proposed to underlie TD- and BB-induced vasodilatation. These findings may improve our understanding of the BP-lowering mechanisms of TDs and BBs. This might provide a possible step forward in personalizing antihypertensive therapy by identifying patients expected to have robust BP-lowering effects from these drugs.

Characteristics of Patients With Cancer and COVID-19 Who Discontinued Cancer Treatment.

This cross-sectional study evaluates the prevalence of and characteristics associated with discontinuation of cancer treatment among patients who received a diagnosis of COVID-19 during their treatment planning.

Suicide Risk Screening for Head and Neck Cancer Patients: An Implementation Study.

OBJECTIVES: There is limited research on suicide risk screening (SRS) among head and neck cancer (HNC) patients, a population at increased risk for suicide. To address this gap, this single-site mixed methods study assessed oncology professionals' perspectives about the feasibility, acceptability, and appropriateness of an electronic SRS program that was implemented as a part of routine care for HNC patients. METHODS: Staff who assisted with SRS implementation completed (e.g., nurses, medical assistants, advanced practice providers, physicians, social workers) a one-time survey (N = 29) and interview (N = 25). Quantitative outcomes were assessed using previously validated feasibility, acceptability, and appropriateness measures. Additional qualitative data were collected to provide context for interpreting the scores. RESULTS: Nurses and medical assistants, who were directly responsible for implementing SRS, reported low feasibility, acceptability, and appropriateness, compared with other team members (e.g., physicians, social workers, advanced practice providers). Team members identified potential improvements needed to optimize SRS, such as hiring additional staff, improving staff training, providing different modalities for screening completion among individuals with disabilities, and revising the patient-reported outcomes to improve suicide risk prediction. CONCLUSION: Staff perspectives about implementing SRS as a part of routine cancer care for HNC patients varied widely. Before screening can be implemented on a larger scale for HNC and other cancer patients, additional implementation strategies may be needed that optimize workflow and reduce staff burden, such as staff training, multiple modalities for completion, and refined tools for identifying which patients are at greatest risk for suicide.

Use of CYP2D6 Inhibitors with CYP2D6 Opioids: Association with Emergency Department Visits for Pain.

Hydrocodone, tramadol, codeine, and oxycodone are commonly prescribed opioids that rely on activation by cytochrome P450 2D6 (CYP2D6). CYP2D6 inhibitors can significantly decrease CYP2D6 activity, leading to reduced generation of active metabolites, and impairing pain control. To understand this impact, we assessed emergency department (ED) visits in patients initiating these CYP2D6-dependent opioids while on CYP2D6-inhibitor antidepressants vs. antidepressants that do not inhibit CYP2D6. This retrospective cohort study included adult patients prescribed CYP2D6-dependent opioids utilizing electronic health records data from the University of Florida Health (2015-2021). The association between ED visits and inhibitor exposure was tested using multivariable logistic regression. The primary analysis had 12,118 patients (72% female; mean (SD) age, 55 (13.4)) in the hydrocodone/tramadol/codeine cohort and 5,547 patients (64% female; mean (SD) age, 53.6 (14.2)) in the oxycodone cohort. Hydrocodone/tramadol/codeine-treated patients exposed to CYP2D6-inhibitor antidepressants (n = 7,043) had a higher crude rate of pain-related ED visits than those taking other antidepressants (n = 5,075) (3.28% vs. 1.87%), with an adjusted odds ratio (aOR) of 1.75 (95% CI: 1.36 to 2.24). Similarly, in the oxycodone cohort, CYP2D6-inhibitor antidepressant-exposed individuals (n = 3,206) had a higher crude rate of ED visits than individuals exposed to other antidepressants (n = 2,341) (5.02% vs. 3.37%), with aOR of 1.70 (95% CI: 1.27-2.27). Similar findings were observed in secondary and sensitivity analyses. Our findings suggest patients with concomitant use of hydrocodone/tramadol/codeine or oxycodone and CYP2D6 inhibitors have more frequent ED visits for pain, which may be due to inadequate pain control.