HIV-1 remission following CCR5Δ32/Δ32 haematopoietic stem-cell transplantation.

A cure for HIV-1 remains unattainable as only one case has been reported, a decade ago1,2. The individual-who is known as the 'Berlin patient'-underwent two allogeneic haematopoietic stem-cell transplantation (HSCT) procedures using a donor with a homozygous mutation in the HIV coreceptor CCR5 (CCR5Δ32/Δ32) to treat his acute myeloid leukaemia. Total body irradiation was given with each HSCT. Notably, it is unclear which treatment or patient parameters contributed to this case of long-term HIV remission. Here we show that HIV-1 remission may be possible with a less aggressive and toxic approach. An adult infected with HIV-1 underwent allogeneic HSCT for Hodgkin's lymphoma using cells from a CCR5Δ32/Δ32 donor. He experienced mild gut graft-versus-host disease. Antiretroviral therapy was interrupted 16 months after transplantation. HIV-1 remission has been maintained over a further 18 months. Plasma HIV-1 RNA has been undetectable at less than one copy per millilitre along with undetectable HIV-1 DNA in peripheral CD4 T lymphocytes. Quantitative viral outgrowth assays from peripheral CD4 T lymphocytes show no reactivatable virus using a total of 24 million resting CD4 T cells. CCR5-tropic, but not CXCR4-tropic, viruses were identified in HIV-1 DNA from CD4 T cells of the patient before the transplant. CD4 T cells isolated from peripheral blood after transplantation did not express CCR5 and were susceptible only to CXCR4-tropic virus ex vivo. HIV-1 Gag-specific CD4 and CD8 T cell responses were lost after transplantation, whereas cytomegalovirus-specific responses were detectable. Similarly, HIV-1-specific antibodies and avidities fell to levels comparable to those in the Berlin patient following transplantation. Although at 18 months after the interruption of treatment it is premature to conclude that this patient has been cured, these data suggest that a single allogeneic HSCT with homozygous CCR5Δ32 donor cells may be sufficient to achieve HIV-1 remission with reduced intensity conditioning and no irradiation, and the findings provide further support for the development of HIV-1 remission strategies based on preventing CCR5 expression.

Isatuximab Monotherapy for Desensitization in Highly Sensitized Patients Awaiting Kidney Transplant.

SIGNIFICANCE STATEMENT: There is no standardized desensitization regimen for kidney transplant candidates. CD38, expressed by plasma cells, could be targeted for desensitization to deplete plasma cells producing alloantibodies and donor-specific antibodies. Few studies and case reports are available regarding the use of CD38 antibodies for desensitization in patients awaiting kidney transplant. This study shows that isatuximab, a CD38-targeting therapy, was well tolerated in kidney transplant candidates, with a durable decrease in anti-HLA antibodies and partial desensitization activity. The short treatment period and long follow-up of this study allowed for the understanding of the mechanism and timing for any antibody rebound. Isatuximab could be further investigated as an option for adjunct therapy to existing desensitization for patients on the kidney transplant waitlist. BACKGROUND: Patients with calculated panel reactive antibody (cPRA) ≥80.00%, particularly those with cPRA ≥99.90%, are considered highly sensitized and underserved by the Kidney Allocation System. Desensitization removes circulating reactive antibodies and/or suppresses antibody production to increase the chances of a negative crossmatch. CD38 is expressed highly on plasma cells, thus is a potential target for desensitization. METHODS: This was an open-label single-arm phase 1/2 study investigating the safety, pharmacokinetics, and preliminary efficacy of isatuximab in patients awaiting kidney transplantation. There were two cohorts, cohorts A and B, which enrolled cPRA ≥99.90% and 80.00% to <99.90%, respectively. RESULTS: Twenty-three patients (12 cohort A, 11 cohort B) received isatuximab 10 mg/kg weekly for 4 weeks then every 2 weeks for 8 weeks. Isatuximab was well tolerated with pharmacokinetic and pharmacodynamic profiles that indicated similar exposure to multiple myeloma trials. It resulted in decreases in CD38 + plasmablasts, plasma cells, and NK cells and significant reductions in HLA-specific IgG-producing memory B cells. Overall response rate, on the basis of a predefined composite desensitization end point, was 83.3% and 81.8% in cohorts A and B. Most responders had decreases in anti-HLA antibodies that were maintained for 26 weeks after the last dose. Overall, cPRA values were minimally affected, however, with only 9/23 patients (39%) having cPRA decreases to target levels. By study cutoff (median follow-up of 68 weeks), six patients received transplant offers, of which four were accepted. CONCLUSIONS: In this open-label trial, isatuximab was well tolerated and resulted in a durable decrease in anti-HLA antibodies with partial desensitization activity. CLINICAL TRIAL REGISTRATION NUMBER: NCT04294459 .

Anti-HLA serologic response to CD38-targeting desensitization therapy is challenged by peripheral memory B cells in highly sensitized kidney transplant candidates.

High human leukocyte antigen (HLA) sensitization limits access to compatible transplantation. New CD38-targeting agents have been shown to reduce anti-HLA antibodies, although with important interpatient variability. Thus, pretreatment identification of responder and nonresponder (NR) patients is needed for treatment decision-making. We analyzed 26 highly sensitized (HS) patients from 2 desensitization trials using anti-CD38 monoclonal antibodies. Hierarchical clustering identified 3 serologic responder groups: high responders, low responders, and NR. Spectral flow cytometry and functional HLA-specific memory B cell (mBC) assessment were first conducted on peripheral blood mononuclear cells and bone marrow samples from 16 patients treated with isatuximab (NCT04294459). Isatuximab effectively depleted bone marrow plasma cells, peripheral CD38-expressing plasmablasts, plasma cells, transitional B cells, and class-switch mBCs, ultimately reducing frequencies of HLA-specific immunoglobulin G (IgG)-producing mBCs. Multidimensional spectral flow cytometry with partial least squares discriminant analysis revealed that pretreatment abundance of specific circulating mBC phenotypes, especially CD38neg class-switch mBCs, accurately distinguished between high serologic responders and low responders or NR (AUC 0.958, 0.860-1.000, P = .009), who also displayed significantly lower frequencies of HLA-specific IgG-producing mBCs (P < .0001). This phenotypical mBC signature predicting response to therapy was validated in an external HS patient cohort (n = 10) receiving daratumumab (NCT04204980). This study identifies critical circulating mBC subset phenotypes that distinguish HS patients with successful serologic responses to CD38-targeting desensitization therapies, potentially guiding treatment decision-making.

ChatGPT4 Outperforms Endoscopists for Determination of Postcolonoscopy Rescreening and Surveillance Recommendations.

BACKGROUND & AIMS: Large language models including Chat Generative Pretrained Transformers version 4 (ChatGPT4) improve access to artificial intelligence, but their impact on the clinical practice of gastroenterology is undefined. This study compared the accuracy, concordance, and reliability of ChatGPT4 colonoscopy recommendations for colorectal cancer rescreening and surveillance with contemporary guidelines and real-world gastroenterology practice. METHODS: History of present illness, colonoscopy data, and pathology reports from patients undergoing procedures at 2 large academic centers were entered into ChatGPT4 and it was queried for the next recommended colonoscopy follow-up interval. Using the McNemar test and inter-rater reliability, we compared the recommendations made by ChatGPT4 with the actual surveillance interval provided in the endoscopist's procedure report (gastroenterology practice) and the appropriate US Multisociety Task Force (USMSTF) guidance. The latter was generated for each case by an expert panel using the clinical information and guideline documents as reference. RESULTS: Text input of de-identified data into ChatGPT4 from 505 consecutive patients undergoing colonoscopy between January 1 and April 30, 2023, elicited a successful follow-up recommendation in 99.2% of the queries. ChatGPT4 recommendations were in closer agreement with the USMSTF Panel (85.7%) than gastroenterology practice recommendations with the USMSTF Panel (75.4%) (P < .001). Of the 14.3% discordant recommendations between ChatGPT4 and the USMSTF Panel, recommendations were for later screening in 26 (5.1%) and for earlier screening in 44 (8.7%) cases. The inter-rater reliability was good for ChatGPT4 vs USMSTF Panel (Fleiss κ, 0.786; 95% CI, 0.734-0.838; P < .001). CONCLUSIONS: Initial real-world results suggest that ChatGPT4 can define routine colonoscopy screening intervals accurately based on verbatim input of clinical data. Large language models have potential for clinical applications, but further training is needed for broad use.

A Preliminary Controlled Trial of Endoscopic Ultrasound-guided Fiducial Markers to Guide Pancreas Surgery.

OBJECTIVE: Endoscopic ultrasound (EUS) is routinely used for fiducial marker placement (FMP) to guide stereotactic radiation of pancreatic tumors, but EUS-FMP explicitly to guide surgery has not been studied in a prospective, controlled manner. Multipurpose EUS systems have been developed that facilitate simultaneous EUS-FMP at the time of biopsy. We aimed to evaluate the feasibility of EUS-FMP to guide pancreatic resection. METHODS: In this prospective trial, we enrolled patients with resectable pancreas masses undergoing tissue sampling and placed preloaded fiducials immediately after biopsy. Intraprocedure confirmation of carcinoma, neuroendocrine, and nonlymphomatous neoplasia by rapid on-site evaluation and lesion size <4 cm was required. The main outcomes were the feasibility and ease of preoperative placement and intraoperative detection of the markers using predefined Likert scales. RESULTS: In 20 patients, EUS-FMP was successful before planned surgery and placement was technically straightforward (Likert Scale: 9.1 ± 1.3; range: 1, most challenging to 10, most facile). Intraoperative detection was feasible and improved when compared with a pre-established comparator of 5 representing an equivalent lesion without a marker (Likert Scale: 7.8 ± 2.2; range: 1, most difficult to 10, most facile; P = 0.011). The mean tumor size on EUS was 1.7 ± 0.9 (range: 0.5 to 3.6) cm. CONCLUSION: EUS-FMP is feasible and safe for resectable pancreatic tumors before surgery and may assist in perioperative detection. Preloaded fiducials may be considered for placement at the time of initial referral for EUS-fine needle biopsy.

Improving electronic health record documentation and use to promote evidence-based pediatric care.

OBJECTIVE: Electronic health records (EHRs) often lack the necessary functionalities to support the full implementation of national clinical guidelines for pediatric care outlined in the American Academy of Pediatrics Bright Futures Guidelines. Using HealthySteps (HS), an evidence-based pediatric primary care program, as an exemplar, this study aimed to enhance pediatric EHRs, identify facilitators and barriers to EHR enhancements, and improve data quality for delivering clinical care as part of HS implementation and evidence building. METHODS: Three HS sites-each differing in location, setting, number of children served, and mix of child insurance coverage-participated in the study. Sites received technical assistance to support data collection and EHR updates. A comprehensive evaluation, including a process evaluation and outcomes monitoring, was conducted to gauge progress toward implementing study data requirements over time. Data sources included administrative records, surveys, and interviews. RESULTS: All sites enhanced their EHRs yet relied on supplemental data systems to track care coordination. Sites improved documentation of required data, demonstrating reductions in missing data and increases in extractable data between baseline and follow-up assessments. For example, the percentage of missing social-emotional screening results ranged from 0% to 8.0% at study conclusion. Facilitators and barriers to EHR enhancements included organizational supports, leadership, and capacity building. CONCLUSIONS: With significant investment of time and resources, practices modified their EHRs to better capture services aligned with HS and Bright Futures. However, more scalable digital solutions are necessary to support EHR updates to help drive improvements in clinical care and outcomes for children and families.

Supratherapeutic Infliximab Levels Do Not Predict Risk of Short-term Complications in Adults With Crohn's Disease.

BACKGROUND: It is uncertain if higher infliximab trough levels (TLs) confer a greater risk of infectious/noninfectious complications (IC/NIC). We aimed to assess the risk of IC and NIC in patients with different TLs. METHODS: We retrospectively evaluated a cohort of Crohn's disease (CD) patients treated with infliximab who underwent therapeutic drug monitoring (TDM), at a tertiary inflammatory bowel disease center, between January 1, 2010, and December 1, 2019. TDM was defined as checking of infliximab trough and antibody levels within a 48-hour period before administration. Patients with a minimum of 3-month assessment pre-TDM and post-TDM were included. In the case of multiple TDMs, the highest TL was considered, and patients were distributed across 4 predefined TL groups (A: <5 µg/mL, B: 5 to 10 µg/mL, C: 10 to 15 µg/mL, and D: ≥15 µg/mL). Rates of IC and NIC during the 3-month prior and following TDM were compared across the groups. In addition, duration of exposure, in terms of months up to TDM, was collected to analyze differences in rates of IC and NIC. RESULTS: Our study included 341 CD patients (median age: 35 y, 58% men). IC and NIC occurred in 52 (15%) and 30 (9%) patients, respectively. Rates of IC and NIC were similar across the 4 TL groups ( P =0.9 and 0.7, respectively for IC and NIC). On multivariable analysis, exposure to infliximab >40 months (as determined by receiver operating characteristic curve analysis) was associated with decreased odds for IC (adjusted odds ratio=0.51, P =0.04), but not NIC (adjusted odds ratio=0.72, P =0.46). CONCLUSIONS: In this large CD cohort, there was no association between infliximab TL and risk of short-term IC or NIC. Interestingly, a shorter duration of exposure predicted higher rates of IC. This supports the safety of targeting higher infliximab TLs when necessary and greater vigilance during the early stages of treatment.

Diversity, equity, and inclusion within the Society for Pediatric Anesthesia: A mixed methods assessment.

BACKGROUND: Leadership of the Society for Pediatric Anesthesia created the Diversity, Equity, and Inclusion committee in 2018 to prioritize diversity work. The Society for Pediatric Anesthesia-Diversity, Equity, and Inclusion committee implemented a baseline survey of the Society for Pediatric Anesthesia membership in 2020 to assess demographics, equity in leadership, inclusivity, and attitudes toward diversity work. The Society for Pediatric Anesthesia plays a significant role in shaping the future of pediatric anesthesiology and in supporting our diverse pediatric patients. METHODS: This study is an IRB-exempt, cross-sectional survey of the Society for Pediatric Anesthesia membership. Quantitative analysis provided descriptive statistics of demographics, practice characteristics, and involvement within the Society for Pediatric Anesthesia. Qualitative thematic analysis provided an in-depth assessment of perceptions of diversity, challenges faced, and prioritization of Diversity, Equity, and Inclusion efforts within the Society for Pediatric Anesthesia. RESULTS: Out of 3 242 Society for Pediatric Anesthesia members, 1 232 completed the survey representing 38% of overall membership. Respondents were 89.2% United States members, 52.7% female, 55.7% non-Hispanic White, 88.6% heterosexual, 95.7% non-military, 59.2% religious, and 2.1% have an Americans with Disabilities Act recognized disability. All major United States geographical areas were represented equally with 71% practicing in urban areas and 67% in academic settings. Ethnic/racial minorities were more likely to be international medical graduates (p < .001). Among United States members, 41.5% report being fluent in a language other than English, and 23.5% of those fluent in another language are certified to interpret. Compared to men, women are less likely to be in leadership roles (p < .003), but we found no difference in participation and leadership when stratified by race/ethnicity, geography, international medical graduate status, or sexuality. Racial/ethnic minorities (p < .028), women (p < .001), and lesbian, gay, bisexual, transgender, and queer members (p < .044) more frequently hold lower academic rank positions when compared to white, heterosexual, and male members. Half of respondents were unsure whether diversity, equity, and inclusion challenges existed within the Society for Pediatric Anesthesia while the other half demonstrated opposing views. Among those who reported diversity, equity, and inclusion challenges, the themes centered around persistent marginalization, the need for more inclusive policies and increased psychological safety, and lack of leadership diversity. CONCLUSIONS: Compared to the diversity of the pediatric population we serve, there are still significant gaps in demographic representation within the Society for Pediatric Anesthesia. As well, there is no consensus among Society for Pediatric Anesthesia membership regarding perceptions of diversity, equity, and inclusion in pediatric anesthesia in the United States. Among those who reported diversity challenges, opportunities for the Society for Pediatric Anesthesia and Anesthesiology Departments to better support minoritized members included bolstering workforce diversity efforts and awareness via more inclusive policies, improved psychological safety, and increasing diversity in leadership. If pediatric anesthesiology is like other specialties, gaining consensus and improving diversity in the workforce might advance pediatric anesthesia innovation, quality, and safety for children of all backgrounds in the United States.

Evaluating the Women's Empowerment and Leadership Initiative: Supporting mentorship, career satisfaction, and well-being among pediatric anesthesiologists.

The Society for Pediatric Anesthesia launched the Women's Empowerment and Leadership Initiative (WELI) in 2018 to empower highly productive women pediatric anesthesiologists to achieve equity, promotion, and leadership. WELI is focused on six career development domains: promotion and leadership, networking, conceptualization and completion of projects, mentoring, career satisfaction, and sense of well-being. We sought feedback about whether WELI supported members' career development by surveys emailed in November 2020 (baseline), May 2021 (6 months), and January 2022 (14 months). Program feedback was quantitatively evaluated by the Likert scale questions and qualitatively evaluated by extracting themes from free-text question responses. The response rates were 60.5% (92 of 152) for the baseline, 51% (82 of 161) for the 6-month, and 52% (96 of 185) for the 14-month surveys. Five main themes were identified from the free-text responses in the 6- and 14-month surveys. Members reported that WELI helped them create meaningful connections through networking, obtain new career opportunities, find tools and projects that supported their career advancement and promotion, build the confidence to try new things beyond their comfort zone, and achieve better work-life integration. Frustration with the inability to connect in-person during the coronavirus-19 pandemic was highlighted. Advisors further stated that WELI helped them improve their mentorship skills and gave them insight into early career faculty issues. Relative to the baseline survey, protégés reported greater contributions from WELI at 6 months in helping them clarify their priorities, increase their sense of achievement, and get promoted. These benefits persisted through 14 months. Advisors reported a steady increase in forming new meaningful relationships and finding new collaborators through WELI over time. All the members reported that their self-rated mentoring abilities improved at 6 months with sustained improvement at 14 months. Thus, programs such as WELI can assist women anesthesiologists and foster gender equity in career development, promotion, and leadership.

Toddlers at Elevated Likelihood for Autism: Exploring Sensory and Language Treatment Predictors.

Baseline child characteristics may predict treatment outcomes in children with or at elevated likelihood of developing autism (EL-ASD). Little is known about the role of child sensory and language features on treatment outcome. Participants were randomly assigned to a parent-mediated intervention or control condition. Analyses explored the relationship between baseline child sensory and language characteristics and changes in ASD symptoms over approximately 9 months. Higher baseline sensory hyporeactivity was significantly related to less improvement in social communication (SC) for the treatment group only. More baseline atypical vocalizations were significantly related to less improvement on SC across treatment and control groups. This work provides an initial framework to encourage the tailoring of interventions for EL-ASD children, suggesting sensory reactivity and atypical vocalizations may be useful behaviors to consider in treatment planning.

Increasing harms for bingo players: digitisation, commercialisation and regulatory inadequacy: a multi-site case study.

BACKGROUND: Bingo is often understood as a low-harm form of gambling. This view has been challenged by a growing body of literature identifying gambling harm to bingo players in a range of countries. In this study, we aimed to identify which conditions enabled, facilitated, intensified or mitigated gambling harm for bingo players in three populations in Victoria in the context of corporate, technological and regulatory changes. METHODS: Our qualitative study investigated experiences of bingo-related gambling harm in three populations in Victoria, Australia where bingo was popular and structural disadvantage common: Indigenous people in the east, Pacific people in the state's north and older people on low or fixed incomes in the capital. Data was generated through interviews with 53 bingo players and 13 stakeholders as well as 12 participant observations of bingo sessions. RESULTS: We found that while bingo is overwhelmingly positive for many players, a minority of bingo players and their families experience notable harm. Harm was generated through traditional paper-based bingo games, new technologies such as tablet-based bingo and by the widespread tactic of placing bingo sessions in close proximity to harmful electronic gambling machines. Overall, the risk of harm to bingo players appears to be escalating due to commercial, technological and regulatory changes. CONCLUSIONS: These changes can be better managed by regulators: reforms are needed to safeguard bingo's distinct character as a lower-risk form of gambling at a time when it, and its players, are under threat. Significantly, we found that harm to bingo players is intensified by factors external to gambling such as racialised poverty and adverse life events. Strategies that recognise these factors and grapple with gambling harm to bingo players are needed.

Acknowledging Anti-Blackness, Overlooking Anti-Asian Racism: Missed Developmental Opportunities for Chinese American Youth.

This paper explores the pathways and barriers to critical consciousness development for Chinese American youth. Thirty-five interviews conducted in 2020 with high-school-aged students in Chicago were analyzed to better understand young people's experiences developing an understanding of anti-Asian racism and anti-Blackness. Results indicated that participants overwhelmingly engaged in sustained conversations about Black Lives Matter and/or made efforts to address anti-Blackness within their families, but engaged in limited conversations about anti-Asian racism. Furthermore, conversations at home and school often failed to contextualize anti-Asian racism, specifically in relation to the experiences of other oppressed groups. Findings highlight a need for research on and practice with Chinese American adolescents to recognize the unique racial positioning of Asian Americans under White supremacy.

Sensory Features of Young Children From a Large Community Sample: Latent Factor Structures of the Sensory Experiences Questionnaire (Version 2.1, Short Form).

IMPORTANCE: Although three sensory factors (hyperresponsiveness [HYPO]; hyporesponsiveness [HYPER]; and sensory interests, repetitions, and seeking behaviors [SIRS]) have been demonstrated among a wide age range of clinical populations, they have not been well validated in the general population, especially with a large community sample of young children. OBJECTIVE: To validate the factor structure of the Sensory Experiences Questionnaire (Version 2.1, Short Form; SEQv2.1) in a community sample and to confirm the factor structure's existence in this sample. DESIGN: Caregivers completed the SEQv2.1, a parent-reported questionnaire designed to capture children's everyday sensory experiences. The latent factors of the SEQv2.1 were examined using confirmatory factor analysis. SETTING: North Carolina. PARTICIPANTS: Caregivers of 2,195 children age 3 yr were initially recruited through state birth records and were eligible to participate if the child did not have a history of serious medical problems and English was the family's primary language. OUTCOMES AND MEASURES: SEQv2.1. RESULTS: The SEQv2.1 showed validity in the community sample. Similar to previous research with clinical populations, the three broad patterns of sensory responsiveness were also confirmed in this large community sample of young children, but associations among the factors differed. CONCLUSIONS AND RELEVANCE: Validation of the three-sensory-factor structure in the general population suggests that these constructs are similar to those found with samples of participants with autism spectrum disorder and developmental disabilities. This finding underscores the importance of understanding the normative development of sensory features across a wider age range to better delineate qualitative differences underlying sensory features between clinical and general populations. What This Article Adds: Occupational therapists seeking to assess children's sensory features can use the SEQv2.1 not only with clinical samples but also with children in the general population.

Study To Evaluate the Performance of a Point-of-Care Whole-Blood HIV Viral Load Test (SAMBA II HIV-1 Semi-Q Whole Blood).

Remote areas of many low and middle income (LMI) countries have poor access to HIV viral load (HIV VL) testing. The SAMBA II (simple amplification-based assay) Semi-Q whole-blood test (Diagnostics for the Real World [DRW], Cambridge, UK) is a point-of-care assay, which uses leucodepletion technology to allow whole-blood testing in remote settings. A total of 1,540 consecutive HIV-positive clinic patients in Cameroon (250), United Kingdom (633), Ukraine (412), and Zimbabwe (245) donated venous blood (all countries) and finger prick blood (all except UK) for testing on SAMBA II. SAMBA II results were compared with simultaneous plasma results on the Abbott RealTime HIV-1 (Abbott Molecular, Des Plaines, IL) viral load assay and interpreted as either <1,000 RNA copies/ml or ≥1,000 RNA copies/ml. For 1,528 venous whole-blood samples tested on SAMBA II, overall percent agreement with the reference test at a cutoff HIV VL of ≥1,000 copies/ml was 96.9% (1,480/1,528; 95% confidence interval [CI], 95.9% to 97.7%), negative percent agreement was 97.7% (1,259/1,289; 95% CI, 96.7% to 98.4%), and positive percent agreement was 92.5% (221/239; 95% CI, 88.4% to 95.5%). For 854 finger prick samples, there was 95.0% (811/854; 95% CI, 93.3% to 96.3%) overall percent agreement, 98.0% (625/638; 95% CI, 96.5% to 98.9%) negative percent agreement, and 86.1% (186/216; 95% CI, 80.8% to 90.4%) positive percent agreement. These rose to 93.5% (82.1% to 98.6%), 97.6% (95.6% to 98.8%), and 95.6% (93.3% to 97.3%) after exclusion of aberrant results from the Ukraine center. These results show a high level of agreement between SAMBA-II and a laboratory-based assay. SAMBA-II has a performance that is suitable to use as a VL point-of-care assay in remote settings.

Empowering Women as Leaders in Pediatric Anesthesiology: Methodology, Lessons, and Early Outcomes of a National Initiative.

Research has shown that women have leadership ability equal to or better than that of their male counterparts, yet proportionally fewer women than men achieve leadership positions and promotion in medicine. The Women's Empowerment and Leadership Initiative (WELI) was founded within the Society for Pediatric Anesthesia (SPA) in 2018 as a multidimensional program to help address the significant career development, leadership, and promotion gender gap between men and women in anesthesiology. Herein, we describe WELI's development and implementation with an early assessment of effectiveness at 2 years. Members received an anonymous, voluntary survey by e-mail to assess whether they believed WELI was beneficial in several broad domains: career development, networking, project implementation and completion, goal setting, mentorship, well-being, and promotion and leadership. The response rate was 60.5% (92 of 152). The majority ranked several aspects of WELI to be very or extremely valuable, including the protégé-advisor dyads, workshops, nomination to join WELI, and virtual facilitated networking. For most members, WELI helped to improve optimism about their professional future. Most also reported that WELI somewhat or absolutely contributed to project improvement or completion, finding new collaborators, and obtaining invitations to be visiting speakers. Among those who applied for promotion or leadership positions, 51% found WELI to be somewhat or absolutely valuable to their application process, and 42% found the same in applying for leadership positions. Qualitative analysis of free-text survey responses identified 5 main themes: (1) feelings of empowerment and confidence, (2) acquisition of new skills in mentoring, coaching, career development, and project implementation, (3) clarification and focus on goal setting, (4) creating meaningful connections through networking, and (5) challenges from coronavirus disease 2019 (COVID-19) and the inability to sustain the advisor-protégé connection. We conclude that after 2 years, the WELI program has successfully supported career development for the majority of protégés and advisors. Continued assessment of whether WELI can meaningfully contribute to attainment of promotion and leadership positions will require study across a longer period. WELI could serve as a programmatic example to support women's career development in other subspecialties.

A qualitative analysis of caregiver perceptions of pediatric dental surgery under general anesthesia.

BACKGROUND: Dental surgery under general anesthesia (GA) is a common treatment for severe childhood caries and thus may serve as an event to motivate behavior change. The frequency of recurrent caries, however, indicates opportunities within current practice to change a child's oral health behaviors. AIM: To assess caregiver experiences related to their child's dental surgery to inform development of a behavioral intervention. DESIGN: Semi-structured interviews with caregivers of children receiving GA for dental surgery. Transcripts (n = 19) were analyzed using qualitative thematic methods. RESULTS: Children were 2-5 years of age, mean 3.8 years. Limited access to GA services was a source of caregiver frustration and a barrier to caries treatment. Surgical events elicited emotional reactions including guilt, anxiety, and a sense of caregiver accountability for development of severe caries. There was variation in caregiver awareness and/or motivation to change oral health behaviors. CONCLUSIONS: A child's dental surgery under GA is an emotionally challenging event yet may inspire hope and expectations for improvement. Surgery offers an opportunity to implement interventions at a time when caregivers may be open to assistance with behavior change, though stress and anxiety may create barriers. Behavioral interventions should be tailored to individual caregiver needs/barriers and stage of developmental readiness.

Qualitative and Quantitative Contrast-enhanced Endoscopic Ultrasound Improves Evaluation of Focal Pancreatic Lesions.

BACKGROUND & AIMS: Endoscopic ultrasound (EUS) is a sensitive method to evaluate the pancreas but its diagnostic capability for several diseases is limited. We compared the diagnostic yield of unenhanced EUS with that of contrast-enhanced EUS for focal pancreas lesions and identified and tested quantitative parameters of contrast enhancement. METHODS: We performed a prospective tandem-controlled trial in which 101 patients with focal pancreas lesions (48 with masses, 28 with cysts, and 25 with pancreatitis) underwent conventional EUS followed by contrast EUS using intravenous perflutren microspheres. The diagnosis at each stage was scored and compared with a standard (findings from surgical pathology analysis, cytologic, and/or 6-month clinical follow-up evaluations). Quantitative parameters were generated by time-intensity curve analysis. Solid lesions were divided into derivation and testing cohorts for a crossover validation analysis of the quantitative parameters. The primary outcome was diagnostic yield of unenhanced vs contrast EUS in analysis of focal pancreas lesions. RESULTS: Contrast increased the diagnostic yield of EUS from 64% (65/101 lesions accurately assessed) to 91% (92/101 lesions accurately assessed); the odds ratio [OR] was 7.8 (95% CI, 2.7-30.2) for accurate analysis of lesions by contrast-enhanced EUS relative to unenhanced EUS. The contrast increased accuracy of analysis of pancreas masses (OR, 6.0; 95% CI, 1.8-31.8), improving assessment of neuroendocrine and other (non-carcinoma) tumors. Contrast increased the diagnostic yield for pancreas cysts to 96% (27/28) compared with 71.4% (20/28) for unenhanced EUS (P = .02), due to improved differentiation of mural nodules vs debris. Time-intensity curve analysis revealed distinct patterns of relative peak enhancement (rPE) and in-slope (rIS) for different lesions following contrast injection: for adenocarcinomas, values were low rPE and low rIS; for neuroendocrine masses, values were high rPE and normal IS; and for chronic pancreatitis foci, values were normal rPE and low rIS. In the validation cohort, these parameters correctly characterized 91% of lesions and improved yield relative to unenhanced EUS (OR, 10; 95% CI, 1.4-34.0). CONCLUSIONS: Contrast-enhanced EUS improves the accuracy of analysis of focal pancreas lesions, compared with unenhanced EUS. Integration of practical quantitative parameters, specifically relative peak enhancement and in-slope, might increase the diagnostic accuracy of contrast EUS. ClinicalTrials.gov no: 02863770.

Performance Evaluation of the SAMBA II SARS-CoV-2 Test for Point-of-Care Detection of SARS-CoV-2.

Nucleic acid amplification for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in respiratory samples is the standard method for diagnosis. The majority of this testing is centralized and therefore has turnaround times of several days. Point-of-care (POC) testing with rapid turnaround times would allow more effective triage in settings where patient management and infection control decisions need to be made rapidly. The inclusivity and specificity of the Simple AMplification-Based Assay (SAMBA) II SARS-CoV-2 test were determined by both in silico analyses of the primers and probes and wet testing. The SAMBA II SARS-CoV-2 test was evaluated for performance characteristics. Clinical performance was evaluated in residual combined throat/nose swabs and compared to that of the Public Health England real-time PCR assay targeting the RdRp gene. The SAMBA II SARS-CoV-2 test has an analytical sensitivity of 250 copies/ml for detecting two regions of the genome (open reading frame 1ab [ORF1ab] and nucleocapsid protein [N]). The clinical performance was evaluated in 172 residual combined nose/throat swabs provided by the Clinical Microbiology and Public Health Laboratory, Addenbrooke's Hospital, Cambridge (CMPHL), which showed an estimated positive percent agreement of 98.9% (95% confidence interval [CI], 93.83 to 99.97) and negative percent agreement of 96.4% (95% CI, 89.92 to 99.26) compared to testing by the CMPHL. The data show that the SAMBA II SARS-CoV-2 test performs equivalently to the centralized testing methods, but with a shorter turnaround time of 86 to 101 min. Point-of-care tests such as SAMBA should enable rapid patient management and effective implementation of infection control measures.

Young First-Time Mothers' Parenting of Infants: The Role of Depression and Social Support.

OBJECTIVES: This study examines the contributions of social support and depressive symptoms on sensitive parenting behaviors, parenting attitudes and parenting stress among first-time young mothers. Additionally, the study tests the moderating role of depression in associations between various types and sources of social support and parenting outcomes. METHODS: Young (M = 17.4 years), low-income, African American mothers (n = 192) were interviewed and video-recorded interacting with their 4-month-old infants. RESULTS: Regression analyses showed that depressive symptoms (CES-D) were associated with less sensitivity observed during mother-infant interactions, less sensitive attitudes (AAPI) and greater parenting stress (PSI), but the role of social support was more nuanced. Direct infant care support from the mother's parent figure (typically her own mother) was related to more sensitive parenting behaviors and attitudes, while general support and direct infant care support from the father of the baby were related to reduced parenting stress. Depressive symptoms moderated the relationship between general support from the parent figure and parenting outcomes. Specifically, higher levels of general support contributed to more sensitive maternal behaviors and attitudes only when depressive symptoms were low. CONCLUSIONS FOR PRACTICE: For young mothers, their parent figure and the father of the baby can be important sources of support in promoting positive parenting and reducing parenting stress. Young mothers with depression, however, are at risk for problematic parenting and may have difficulty taking advantage of the support offered by their parent figure.