Identifying incarceration status in the electronic health record using large language models in emergency department settings.

Background: Incarceration is a significant social determinant of health, contributing to high morbidity, mortality, and racialized health inequities. However, incarceration status is largely invisible to health services research due to inadequate clinical electronic health record (EHR) capture. This study aims to develop, train, and validate natural language processing (NLP) techniques to more effectively identify incarceration status in the EHR. Methods: The study population consisted of adult patients (≥ 18 y.o.) who presented to the emergency department between June 2013 and August 2021. The EHR database was filtered for notes for specific incarceration-related terms, and then a random selection of 1,000 notes was annotated for incarceration and further stratified into specific statuses of prior history, recent, and current incarceration. For NLP model development, 80% of the notes were used to train the Longformer-based and RoBERTa algorithms. The remaining 20% of the notes underwent analysis with GPT-4. Results: There were 849 unique patients across 989 visits in the 1000 annotated notes. Manual annotation revealed that 559 of 1000 notes (55.9%) contained evidence of incarceration history. ICD-10 code (sensitivity: 4.8%, specificity: 99.1%, F1-score: 0.09) demonstrated inferior performance to RoBERTa NLP (sensitivity: 78.6%, specificity: 73.3%, F1-score: 0.79), Longformer NLP (sensitivity: 94.6%, specificity: 87.5%, F1-score: 0.93), and GPT-4 (sensitivity: 100%, specificity: 61.1%, F1-score: 0.86). Conclusions: Our advanced NLP models demonstrate a high degree of accuracy in identifying incarceration status from clinical notes. Further research is needed to explore their scaled implementation in population health initiatives and assess their potential to mitigate health disparities through tailored system interventions.

Structure and function of Semaphorin-5A glycosaminoglycan interactions.

Integration of extracellular signals by neurons is pivotal for brain development, plasticity, and repair. Axon guidance relies on receptor-ligand interactions crosstalking with extracellular matrix components. Semaphorin-5A (Sema5A) is a bifunctional guidance cue exerting attractive and inhibitory effects on neuronal growth through the interaction with heparan sulfate (HS) and chondroitin sulfate (CS) glycosaminoglycans (GAGs), respectively. Sema5A harbors seven thrombospondin type-1 repeats (TSR1-7) important for GAG binding, however the underlying molecular basis and functions in vivo remain enigmatic. Here we dissect the structural basis for Sema5A:GAG specificity and demonstrate the functional significance of this interaction in vivo. Using x-ray crystallography, we reveal a dimeric fold variation for TSR4 that accommodates GAG interactions. TSR4 co-crystal structures identify binding residues validated by site-directed mutagenesis. In vitro and cell-based assays uncover specific GAG epitopes necessary for TSR association. We demonstrate that HS-GAG binding is preferred over CS-GAG and mediates Sema5A oligomerization. In vivo, Sema5A:GAG interactions are necessary for Sema5A function and regulate Plexin-A2 dependent dentate progenitor cell migration. Our study rationalizes Sema5A associated developmental and neurological disorders and provides mechanistic insights into how multifaceted guidance functions of a single transmembrane cue are regulated by proteoglycans.

Equity and use of telehealth modalities among people living with HIV during the COVID-19 pandemic.

Background: COVID-19 forced a rapid transition to telehealth. Little is known about the use of telephone versus video visits among people living with or at risk for HIV (PWH). Setting: We studied electronic health record data from an urban HIV clinic. Our sample included visit- and person-level data. Visit-level data came from appointments scheduled from 30 March 2020 to 31 May 2020. Person-level data came from patients 18+ years of age who completed at least one telephone or video visit during the period of interest. Methods: We performed a cross-sectional analysis. Our primary outcome was telehealth modality (telephone or video). We compared visit completion status by telehealth modality. We evaluated associations between patient characteristics and telehealth modality using logistic regression. Results: In total, 1742 visits included information on telehealth modality: 1432 telephone (82%) and 310 (18%) video visits. 77% of telephone visits were completed compared to 75% of video visits (p = 0.449). The clinic recorded 643 completed telehealth visits in April and 623 in May 2020. The proportion of telephone visits decreased from 84% in April to 79% in May (p = 0.031). Most patients participated in telephone versus video visits (415 vs. 88 patients). Older age (adjusted odds ratio [AOR] 3.28; 95% confidence interval [CI], 1.37-7.82) and Black race (AOR 2.42; 95% CI, 1.20-4.49) were positively associated with telephone visits. Patient portal enrollment (AOR 0.06; 95% CI, 0.02-0.16) was negatively associated with telephone visits. Conclusion: PWH used telephone more than video visits, suggesting that telephone visits are a vital healthcare resource for this population.

Rewiring of mitochondrial metabolism in therapy-resistant cancers: permanent and plastic adaptations.

Deregulation of tumor cell metabolism is widely recognized as a "hallmark of cancer." Many of the selective pressures encountered by tumor cells, such as exposure to anticancer therapies, navigation of the metastatic cascade, and communication with the tumor microenvironment, can elicit further rewiring of tumor cell metabolism. Furthermore, phenotypic plasticity has been recently appreciated as an emerging "hallmark of cancer." Mitochondria are dynamic organelles and central hubs of metabolism whose roles in cancers have been a major focus of numerous studies. Importantly, therapeutic approaches targeting mitochondria are being developed. Interestingly, both plastic (i.e., reversible) and permanent (i.e., stable) metabolic adaptations have been observed following exposure to anticancer therapeutics. Understanding the plastic or permanent nature of these mechanisms is of crucial importance for devising the initiation, duration, and sequential nature of metabolism-targeting therapies. In this review, we compare permanent and plastic mitochondrial mechanisms driving therapy resistance. We also discuss experimental models of therapy-induced metabolic adaptation, therapeutic implications for targeting permanent and plastic metabolic states, and clinical implications of metabolic adaptations. While the plasticity of metabolic adaptations can make effective therapeutic treatment challenging, understanding the mechanisms behind these plastic phenotypes may lead to promising clinical interventions that will ultimately lead to better overall care for cancer patients.

Laparoscopic administration of bupivacaine at the uterosacral ligaments during benign laparoscopic and robotic hysterectomy: a randomized controlled trial.

BACKGROUND: Postoperative pain continues to be an undermanaged part of the surgical experience. Multimodal analgesia has been adopted in response to the opioid epidemic, but opioid prescribing practices remain high after minimally invasive hysterectomy. Novel adjuvant opioid-sparing analgesia to optimize acute postoperative pain control is crucial in preventing chronic pain and minimizing opioid usage. OBJECTIVE: This study aimed to determine the effect of direct laparoscopic uterosacral bupivacaine administration on opioid usage and postoperative pain in patients undergoing benign minimally invasive (laparoscopic and robotic) hysterectomy. STUDY DESIGN: This was a single-blinded, triple-arm, randomized controlled trial at an academic medical center between March 15, 2021, and April 8, 2022. The inclusion criteria were patients aged >18 years undergoing benign laparoscopic or robotic hysterectomy. The exclusion criteria were non-English-speaking patients, patients with an allergy to bupivacaine or actively using opioid medications, patients undergoing transversus abdominis plane block, and patients undergoing supracervical hysterectomy or combination cases with other surgical services. Patients were randomized in a 1:1:1 fashion to the following uterosacral administration before colpotomy: no administration, 20 mL of normal saline, or 20 mL of 0.25% bupivacaine. All patients received incisional infiltration with 10 mL of 0.25% bupivacaine. The primary outcome was 24-hour oral morphine equivalent usage (postoperative day 0 and postoperative day 1). The secondary outcomes were total oral morphine equivalent usage in 7 days, last day of oral morphine equivalent usage, numeric pain scores from the universal pain assessment tool, and return of bowel function. Patients reported postoperative pain scores, total opioid consumption, and return of bowel function via Qualtrics surveys. Patient and surgical characteristics and primary and secondary outcomes were compared using chi-square analysis and 1-way analysis of variance. Multiple linear regression was used to identify predictors of opioid use in the first 24 hours after surgery and total opioid use in the 7 days after surgery. RESULTS: Of 518 hysterectomies screened, 410 (79%) were eligible, 215 (52%) agreed to participate, and 180 were ultimately included in the final analysis after accounting for dropout. Most hysterectomies (70%) were performed laparoscopically, and the remainder were performed robotically. Most hysterectomies (94%) were outpatient. Patients randomized to bupivacaine had higher rates of former and current tobacco use, and patients randomized to the no-administration group had higher rates of previous surgery. There was no difference in first 24-hour oral morphine equivalent use among the groups (P=.10). Moreover, there was no difference in numeric pain scores (although a trend toward significance in discharge pain scores in the bupivacaine group), total 7-day oral morphine equivalent use, day of last opioid use, or return of bowel function among the groups (P>.05 for all). The predictors of increased 24-hour opioid usage among all patients included only increased postanesthesia care unit oral morphine equivalent usage. The predictors of 7-day opioid usage among all patients included concurrent tobacco use and mood disorder, history of previous laparoscopy, estimated blood loss of >200 mL, and increased oral morphine equivalent usage in the postanesthesia care unit. CONCLUSION: Laparoscopic uterosacral administration of bupivacaine at the time of minimally invasive hysterectomy did not result in decreased opioid usage or change in numeric pain scores.

Personal Health Libraries for People Returning From Incarceration: Protocol for a Qualitative Study.

BACKGROUND: Individuals released from carceral facilities have high rates of hospitalization and death, especially in the weeks immediately after their return to community settings. During this transitional process, individuals leaving incarceration are expected to engage with multiple providers working in separate, complex systems, including health care clinics, social service agencies, community-based organizations, and probation and parole services. This navigation is often complicated by individuals' physical and mental health, literacy and fluency, and socioeconomic status. Personal health information technology, which can help people access and organize their health information, could improve the transition from carceral systems to the community and mitigate health risks upon release. Yet, personal health information technologies have not been designed to meet the needs and preferences of this population nor tested for acceptability or use. OBJECTIVE: The objective of our study is to develop a mobile app to create personal health libraries for individuals returning from incarceration to help bridge the transition from carceral settings to community living. METHODS: Participants were recruited through Transitions Clinic Network clinic encounters and professional networking with justice-involved organizations. We used qualitative research methods to assess the facilitators and barriers to developing and using personal health information technology for individuals returning from incarceration. We conducted individual interviews with people just released from carceral facilities (n=~20) and providers (n=~10) from the local community and carceral facilities involved with the transition for returning community members. We used rigorous rapid qualitative analysis to generate thematic output characterizing the unique circumstances impacting the development and use of personal health information technology for individuals returning from incarceration and to identify content and features for the mobile app based on the preferences and needs of our participants. RESULTS: As of February 2023, we have completed 27 qualitative interviews with individuals recently released from carceral systems (n=20) and stakeholders (n=7) who support justice-involved individuals from various organizations in the community. CONCLUSIONS: We anticipate that the study will characterize the experiences of people transitioning from prison and jails to community settings; describe the information, technology resources, and needs upon reentry to the community; and create potential pathways for fostering engagement with personal health information technology. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/44748.

Enhanced Identification of Hispanic Ethnicity Using Clinical Data: A Study in the Largest Integrated United States Health Care System.

BACKGROUND: Collection of accurate Hispanic ethnicity data is critical to evaluate disparities in health and health care. However, this information is often inconsistently recorded in electronic health record (EHR) data. OBJECTIVE: To enhance capture of Hispanic ethnicity in the Veterans Affairs EHR and compare relative disparities in health and health care. METHODS: We first developed an algorithm based on surname and country of birth. We then determined sensitivity and specificity using self-reported ethnicity from the 2012 Veterans Aging Cohort Study survey as the reference standard and compared this to the research triangle institute race variable from the Medicare administrative data. Finally, we compared demographic characteristics and age-adjusted and sex-adjusted prevalence of conditions in Hispanic patients among different identification methods in the Veterans Affairs EHR 2018-2019. RESULTS: Our algorithm yielded higher sensitivity than either EHR-recorded ethnicity or the research triangle institute race variable. In 2018-2019, Hispanic patients identified by the algorithm were more likely to be older, had a race other than White, and foreign born. The prevalence of conditions was similar between EHR and algorithm ethnicity. Hispanic patients had higher prevalence of diabetes, gastric cancer, chronic liver disease, hepatocellular carcinoma, and human immunodeficiency virus than non-Hispanic White patients. Our approach evidenced significant differences in burden of disease among Hispanic subgroups by nativity status and country of birth. CONCLUSIONS: We developed and validated an algorithm to supplement Hispanic ethnicity information using clinical data in the largest integrated US health care system. Our approach enabled clearer understanding of demographic characteristics and burden of disease in the Hispanic Veteran population.

Educating Mental Health Trainees About Measurement-Based Care: A Scoping Review.

OBJECTIVE: Measurement-based care (MBC) refers to the routine use of symptom rating scales to guide treatment decisions. Although effective, it is an underused approach to enhance patient care. A significant barrier to integration of MBC is insubstantial foundational training. This scoping review aims to survey the literature on MBC educational curricula for mental health trainees. METHODS: Investigators searched Ovid Medline, PsycINFO, Embase, Cochrane Central, and Ebsco CINAHL through June 2021 to select records that described studies of MBC educational programs for undergraduate, graduate, or postgraduate learners in mental healthcare. RESULTS: From 1270 unique records, 1263 were excluded in abstract/title and full-text screening. This scoping review included seven articles, of which most were empirical or case studies and took place in the USA. These curricula involved many delivery formats, including lectures and in-service training. Measured learner outcomes include those that are learner-focused (i.e. learner reaction, or attitudinal/behavioral change) and organizational-focused (i.e. increased clinical use of MBC). Mechanisms of positive outcomes are posited to include enhanced stakeholder support and continual curriculum improvement. CONCLUSIONS: MBC curricula can be taught in various formats to diverse learners in mental healthcare. Contextual factors, such as dedicated resources, MBC champions, supervisor training, online measurement feedback systems, simple measures, and gathering and disseminating feedback may facilitate curricular success by fostering stakeholder support and continual program improvement. To address literature gaps, future research in MBC education should involve educational frameworks in designing curriculum and address the use of quality improvement approaches in the implementation of MBC education.

Image-dependence of the detectability of optogenetic stimulation in macaque inferotemporal cortex.

Artificial activation of neurons in early visual areas induces perception of simple visual flashes.1,2 Accordingly, stimulation in high-level visual cortices is expected to induce perception of complex features.3,4 However, results from studies in human patients challenge this expectation. Stimulation rarely induces any detectable visual event, and never a complex one, in human subjects with closed eyes.2 Stimulation of the face-selective cortex in a human patient led to remarkable hallucinations only while the subject was looking at faces.5 In contrast, stimulations of color- and face-selective sites evoke notable hallucinations independent of the object being viewed.6 These anecdotal observations suggest that stimulation of high-level visual cortex can evoke perception of complex visual features, but these effects depend on the availability and content of visual input. In this study, we introduce a novel psychophysical task to systematically investigate characteristics of the perceptual events evoked by optogenetic stimulation of macaque inferior temporal (IT) cortex. We trained macaque monkeys to detect and report optogenetic impulses delivered to their IT cortices7,8,9 while holding fixation on object images. In a series of experiments, we show that detection of cortical stimulation is highly dependent on the choice of images presented to the eyes and it is most difficult when fixating on a blank screen. These findings suggest that optogenetic stimulation of high-level visual cortex results in easily detectable distortions of the concurrent contents of vision.

Breast cancer screening during the COVID-19 pandemic: moving from disparities to health equity.

The COVID-19 pandemic created unprecedented disruptions to routine health care in the United States. Screening mammography, a cornerstone of breast cancer control and prevention, was completely halted in the spring of 2020, and screening programs have continued to face challenges with subsequent COVID-19 waves. Although screening mammography rates decreased for all women during the pandemic, a number of studies have now clearly documented that reductions in screening have been greater for some populations than others. Specifically, minoritized women have been screened at lower rates than White women across studies, although the specific patterns of disparity vary depending on the populations and communities studied. We posit that these disparities are likely due to a variety of structural and contextual factors, including the differential impact of COVID-19 on communities. We also outline key considerations for closing gaps in screening mammography. First, practices, health systems, and communities must measure screening mammography use to identify whether gaps exist and which populations are most affected. Second, we propose that strategies to close disparities in breast cancer screening must be multifaceted, targeting the health system or practice, but also structural factors at the policy level. Health disparities arise from a complex set of conditions, and multimodal solutions that address the complex, multifactorial conditions that lead to disparities may be more likely to succeed and are necessary for promoting health equity.

Complement factor B is critical for sub-RPE deposit accumulation in a model of Doyne honeycomb retinal dystrophy with features of age-related macular degeneration.

EFEMP1 R345W is a dominant mutation causing Doyne honeycomb retinal dystrophy/malattia leventinese (DHRD/ML), a rare blinding disease with clinical pathology similar to age-related macular degeneration (AMD). Aged Efemp1  R345W/R345W knock-in mice (Efemp1ki/ki) develop microscopic deposits on the basal side of retinal pigment epithelial cells (RPE), an early feature in DHRD/ML and AMD. Here, we assessed the role of alternative complement pathway component factor B (FB) in the formation of these deposits. RNA-seq analysis of the posterior eyecups revealed increased unfolded protein response, decreased mitochondrial function in the neural retina (by 3 months of age) and increased inflammatory pathways in both neural retina and posterior eyecups (at 17 months of age) of Efemp1ki/ki mice compared with wild-type littermate controls. Proteomics analysis of eye lysates confirmed similar dysregulated pathways as detected by RNA-seq. Complement activation was increased in aged Efemp1ki/ki eyes with an approximately 2-fold elevation of complement breakdown products iC3b and Ba (P < 0.05). Deletion of the Cfb gene in female Efemp1ki/ki mice partially normalized the above dysregulated biological pathway changes and oral dosing of a small molecule FB inhibitor from 10 to 12 months of age reduced sub-RPE deposits by 65% (P = 0.029). In contrast, male Efemp1ki/ki mice had fewer sub-RPE deposits than age-matched females, no elevation of ocular complement activation and no effect of FB inhibition on sub-RPE deposits. The effects of FB deletion or inhibition on Efemp1ki/ki mice supports systemic inhibition of the alternative complement pathway as a potential treatment of dry AMD and DHRD/ML.

Behavioral detectability of optogenetic stimulation of inferior temporal cortex varies with the size of concurrently viewed objects.

We have previously demonstrated that macaque monkeys can behaviorally detect a subtle optogenetic impulse delivered to their inferior temporal (IT) cortex. We have also shown that the ability to detect the cortical stimulation impulse varies depending on some characteristics of the visual images viewed at the time of brain stimulation, revealing the visual nature of the perceptual events induced by stimulation of the IT cortex. Here we systematically studied the effect of the size of viewed objects on behavioral detectability of optogenetic stimulation of the central IT cortex. Surprisingly, we found that behavioral detection of the same optogenetic impulse highly varies with the size of the viewed object images. Reduction of the object size in four steps from 8 to 1 degree of visual angle significantly decreased detection performance. These results show that identical stimulation impulses delivered to the same neural population induce variable perceptual events depending on the mere size of the objects viewed at the time of brain stimulation.

Utilization and cost of cell salvage in minimally invasive myomectomy.

OBJECTIVE: To assess the utilization and cost of intraoperative cell salvage (ICS) in minimally invasive myomectomy. STUDY DESIGN: Retrospective cohort study of patients who underwent minimally invasive myomectomy at a quaternary care academic hospital. Patients were classified into: ICS setup vs no ICS setup, ICS setup with reinfusion vs ICS setup without reinfusion. RESULTS: Of 382 patients who underwent minimally invasive myomectomy, 67 (17.5 %) had ICS setup, 30 (44.8 %) of those patients reinfused. Median volume of reinfusion per patient was 300 mL (range 125-1000 mL). Patients who ultimately underwent ICS reinfusion, compared to those with ICS setup only, had significantly larger mean maximum fibroid size (9.8 cm vs 8.0 cm, p = 0.02), higher median total specimen weight (367 vs 304 g, p = 0.03), higher median estimated blood loss (575 vs 300 mL, p < 0.0001), longer mean operative time (261 vs 215 min, p = 0.04). No perioperative complications were associated with ICS. Higher costs are associated with universal use or complete lack of ICS; lowest cost is associated with ICS setup only for those ultimately reinfused. CONCLUSION: ICS might reduce requirements for allogeneic blood transfusions in patients undergoing minimally invasive myomectomy, and may contribute to cost savings. Uterine and maximum fibroid sizes are possible preoperative indicators for patients who require cell salvage reinfusion.

Implementing Centering Parenting Model With an Urban Pediatric Population to Measure and Improve Clinical Outcomes and Parent Satisfaction.

INTRODUCTION: For CenteringParenting-a patient-centered, group family approach to child health-this study aimed to determine how the CenteringParenting model affects clinical outcomes compared with the traditional well-child care model and how the CenteringParenting model affect parent satisfaction as compared with the traditional well-child care model. This study was conducted at the Children's Health Center in West Reading, PA-a single-site pediatric practice that serves primarily an inner city with a population currently at 95,112. METHOD: Quantitative data collection was obtained from a retrospective chart review for both groups of patients to obtain outcome data. Phone interviews were completed, and participants were asked to respond to a series of questions using a 5-point Likert scale and several open-ended questions. All statistical analyses for this research were performed using SPSS (version 25.0; IBM Corp., Armonk, NY). Two groups were coded as the centering group and control group. Significance testing was performed using chi-square analysis for categorical data and t test for continuous data. RESULTS: CenteringParenting children are more likely to be UTD with their scheduled visits and vaccines than those receiving the traditional model of well-child care. Maternal depression screenings were more likely to be completed and documented and open discussions about maternal depression. Parents involved with group visits found it to be great care, liked being with other parents, learned a lot, and would recommend it to other parents. DISCUSSION: Limitations of the study include being a new site offering the CHI program for group well-child visits. As the program has continued to progress over the years, it has continued to grow and is now offered in both English and Spanish. Another limitation was not having trained breastfeeding professionals such as lactation counselors, consultants, or breastfeeding resource nurses. Future research is needed to study the implementation of breastfeeding in minority populations. In addition, a more in-depth study about triage calls and if parents feel more comfortable calling if they have a better connection to their provider and health care team. This issue was not addressed or questioned in this research and would be very beneficial to understand in the future how it relates to CPGs.

National Institutes of Health Diversity Supplement Awards by Medical School.

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

Multiple switching between the biosimilar adalimumab PF-06410293 and reference adalimumab in patients with active rheumatoid arthritis: a phase 3, open-label, randomised, parallel-group study.

BACKGROUND: An adalimumab biosimilar with an interchangeability designation could increase access to effective treatment for more patients. We aimed to assess the interchangeability of adalimumab biosimilar PF-06410293 (adalimumab-afzb) and reference adalimumab using a multi-switch study design. METHODS: We did an open-label, randomised, parallel-group study at 61 community (n=29), hospital (n=12), and academic (n=20) sites in ten countries (Bulgaria, Bosnia and Herzegovina, Czech Republic, Lithuania, Poland, Russia, Serbia, South Africa, Ukraine, and USA). Eligible patients were aged 18-70 years and met the 2010 American College of Rheumatology-European League Against Rheumatism classification criteria for rheumatoid arthritis for at least 4 months with moderately to severely active rheumatoid arthritis, based on their physician's evaluation. Eligible patients had been receiving methotrexate for at least 12 weeks and been on a stable dose for at least 4 weeks before the first dose of study medication. All patients received subcutaneous reference adalimumab (40 mg/0·4 mL [100 mg/mL] every 2 weeks) for 10 weeks before randomisation. At week 10, patients were randomly assigned (1:1) to either three switches between subcutaneous reference adalimumab (40 mg/0·4 mL [100 mg/mL] every 2 weeks) and adalimumab-afzb (40 mg/0·8 mL [50 mg/mL] every 2 weeks; switching group), or continuous dosing with subcutanous reference adalimumab (40 mg/0·4 mL [100 mg/mL] every 2 weeks; non-switching group) with stratification by bodyweight groups. Patients, investigators, and site personnel were not masked to treatment allocation. Primary endpoints were maximum observed serum concentration (Cmax) and area under plasma concentration-time curve (AUCτ) during weeks 30-32 in the pharmacokinetic population. Interchangeability was based on geometric mean ratios and corresponding 90% CIs within prespecified equivalence margins of 80-125% for both primary endpoints. Safety was analysed in all patients who received at least one dose of adalimumab-afzb or reference adalimumab. This trial is registered with ClinicalTrials.gov, NCT04230213. FINDINGS: Of the 569 patients assessed for eligibility between Jan 13, 2020, and June 22, 2021, 445 were enrolled, and 427 completed the first 10 weeks and were randomly assigned (213 to the switching group and 214 to the non-switching group). Participants had a median age of 56 years (IQR 46-63), 354 (83%) of 427 patients were women and 73 (17%) were men, and 422 (99%) were White. In the pharmacokinetic population (n=380), no clinically meaningful differences were observed in mean steady-state pharmacokinetic parameters between the switching and non-switching groups (geometric mean AUC 2237 µg × h/mL in the switching group and 2125 µg × h/mL in the non-switching group; Cmax 8·21 µg/mL in the switching group and 8·00 µg/mL in the non-switching group). Geometric mean ratios and 90% CIs for AUCτ (105·31, 89·16-124·39) and Cmax (102·56, 89·78-117·17) were within prespecified equivalence margins. No meaningful differences were observed in the proportion of patients who had serious adverse events (three [1%] of 213 patients in the switching group vs eight [4%] of 214 patients in the non-switching group), grade 3 or higher adverse events of special interest, discontinuations due to adverse events (eight [4%] vs nine [4%]), or immunogenic reactions in antidrug antibody-positive patients. No deaths were reported during the study. INTERPRETATION: The risk of multiple switches between reference adalimumab and adalimumab-afzb with respect to diminished efficacy (using pharmacokinetics as a surrogate) or safety is not greater than the risk of using reference adalimumab alone. FUNDING: Pfizer. VIDEO ABSTRACT.

Risk Factors for Postoperative Narcotic Use in Benign, Minimally-Invasive Gynecologic Surgery.

Background and Objectives: To evaluate postoperative opioid use after benign minimally-invasive gynecologic surgery and assess the impact of a patient educational intervention regarding proper opioid use/disposal. Methods: Educational pamphlets were provided preoperatively. Patients underwent hysterectomy, myomectomy, or other laparoscopic procedures. Opioid prescriptions were standardized with 25 tablets oxycodone 5mg for hysterectomy/myomectomy, 10 tablets oxycodone 5mg for LSC (oral morphine equivalents were maintained for alternatives). Pill diaries were reviewed and patient surveys completed during postoperative visits. Results: Of 106 consented patients, 65 (61%) completed their pill diaries. Median opioid use was 35 OME for hysterectomy (∼5 oxycodone tablets; IQR 11.25-102.5), 30 OME for myomectomy (∼4 tablets; IQR 15-75), and 18.75 OME for laparoscopy (∼3 tablets; IQR 7.5-48.75). Median last post-operative day (d) of use was 3d for hysterectomy (IQR 2, 8), 4d for myomectomy (IQR 1, 7), and 2d for laparoscopy (IQR 0.5-3.5). One patient (myomectomy) required a refill of 5mg oxycodone. No difference was found between total opioid use and presence of pelvic pain, chronic pain disorders, or psychiatric co-morbidities. Overall satisfaction with pain control (>4 on a 5-point Likert scale) was 91% for hysterectomy, 100% for myomectomy, 83% for laparoscopy. Of the 33 patients who read the pamphlet, 32(97%) felt it increased their awareness. Conclusion: Most patients required <10 oxycodone 5mg tablets, regardless of procedure with excellent patient satisfaction. A patient education pamphlet is a simple method to increase knowledge regarding the opioid epidemic and facilitate proper medication disposal.

Informatics in Undergraduate Medical Education: Analysis of Competency Frameworks and Practices Across North America.

BACKGROUND: With the advent of competency-based medical education, as well as Canadian efforts to include clinical informatics within undergraduate medical education, competency frameworks in the United States have not emphasized the skills associated with clinical informatics pertinent to the broader practice of medicine. OBJECTIVE: By examining the competency frameworks with which undergraduate medical education in clinical informatics has been developed in Canada and the United States, we hypothesized that there is a gap: the lack of a unified competency set and frame for clinical informatics education across North America. METHODS: We performed directional competency mapping between Canadian and American graduate clinical informatics competencies and general graduate medical education competencies. Directional competency mapping was performed between Canadian roles and American common program requirements using keyword matching at the subcompetency and enabling competency levels. In addition, for general graduate medical education competencies, the Physician Competency Reference Set developed for the Liaison Committee on Medical Education was used as a direct means of computing the ontological overlap between competency frameworks. RESULTS: Upon mapping Canadian roles to American competencies via both undergraduate and graduate medical education competency frameworks, the difference in focus between the 2 countries can be thematically described as a difference between the concepts of clinical and management reasoning. CONCLUSIONS: We suggest that the development or deployment of informatics competencies in undergraduate medical education should focus on 3 items: the teaching of diagnostic reasoning, such that the information tasks that comprise both clinical and management reasoning can be discussed; precision medical education, where informatics can provide for more fine-grained evaluation; and assessment methods to support traditional pedagogical efforts (both at the bedside and beyond). Assessment using cases or structured assessments (eg, Objective Structured Clinical Examinations) would help students draw parallels between clinical informatics and fundamental clinical subjects and would better emphasize the cognitive techniques taught through informatics.

Human NOP2/NSUN1 regulates ribosome biogenesis through non-catalytic complex formation with box C/D snoRNPs.

5-Methylcytosine (m5C) is a base modification broadly found on various RNAs in the human transcriptome. In eukaryotes, m5C is catalyzed by enzymes of the NSUN family composed of seven human members (NSUN1-7). NOP2/NSUN1 has been primarily characterized in budding yeast as an essential ribosome biogenesis factor required for the deposition of m5C on the 25S ribosomal RNA (rRNA). Although human NOP2/NSUN1 has been known to be an oncogene overexpressed in several types of cancer, its functions and substrates remain poorly characterized. Here, we used a miCLIP-seq approach to identify human NOP2/NSUN1 RNA substrates. Our analysis revealed that NOP2/NSUN1 catalyzes the deposition of m5C at position 4447 on the 28S rRNA. We also find that NOP2/NSUN1 binds to the 5'ETS region of the pre-rRNA transcript and regulates pre-rRNA processing through non-catalytic complex formation with box C/D snoRNAs. We provide evidence that NOP2/NSUN1 facilitates the recruitment of U3 and U8 snoRNAs to pre-90S ribosomal particles and their stable assembly into snoRNP complexes. Remarkably, expression of both WT and catalytically inactive NOP2/NSUN1 in knockdown background rescues the rRNA processing defects and the stable assembly of box C/D snoRNP complexes, suggesting that NOP2/NSUN1-mediated deposition of m5C on rRNA is not required for ribosome synthesis.