Focusing HIV-1 Gag T-cell Responses to Highly Conserved Regions by DNA Vaccination in HVTN 119.

BACKGROUND: An HIV-1 DNA vaccine composed of seven highly conserved, structurally important elements (Conserved Elements, CE) of HIV p24Gag was tested in a phase I randomized, double-blind clinical trial (HVTN 119, NCT03181789) in people without HIV. A CE prime- CE+full-length p55Gag boost DNA vaccine was compared to p55Gag DNA vaccination only. METHODS: Two groups (n=25 each) received 4 DNA vaccinations [2xCE prime- 2xCE+p55Gag boost or 4x p55Gag] by intramuscular injection/electroporation, including IL-12 DNA adjuvant. The placebo group (n=6) received saline. Participants were followed for safety and tolerability. Immunogenicity was assessed for T cell and antibody responses. RESULTS: Both regimens were safe and generally well-tolerated. The p24CE vaccine was immunogenic (29% CD4+ and 4% CD8+ responders) and was significantly boosted by CE+p55Gag (64% CD4+, p=0.037; 42% CD8+, p=0.004). CE+p55Gag induced CD4+ responses to 5 of 7 CE, compared to only 2 CE by p55Gag DNA alone, with a higher reponse to CE5 in 30% of individuals (p=0.006). CE+p55Gag induced significantly higher mean CD4+ CE Tcell breadth (0.68 vs 0.22 CE; p=0.029) and a strong trend for increased CD4+ and CD8+ T-cell breadth (1.14 vs. 0.52 CE; p=0.051) compared to p55Gag alone. Both groups developed high p55Gag T-cell (91% each) and p24Gag antibody (91% vs. 80%) responses. p24CE vaccine-induced CD4+ CE T-cell responses correlated (p=0.007) with p24Gag antibody responses. CONCLUSION: The combination CE/CE+p55Gag DNA vaccine induced T-cell immune responses to conserved regions in p24Gag resulting in significant increases in breadth and epitope recognition throughout p55Gag. Vaccines able to focus immune responses by priming responses to highly conserved regions could be part of a comprehensive HIV vaccine strategy. CLINICAL TRIALS: gov NCT03181789 Study URL: https://www. CLINICALTRIALS: gov/search?term=NCT03181789 FUNDING. HIV vaccine trial network (HVTN), NIAID/NIH.

Antibiotic practice and stewardship in the management of neutropenic fever: a survey of US institutions.

OBJECTIVE: To describe neutropenic fever management practices among healthcare institutions. DESIGN: Survey. PARTICIPANTS: Members of the Society for Healthcare Epidemiology of America Research Network (SRN) representing healthcare institutions within the United States. METHODS: An electronic survey was distributed to SRN representatives, with questions pertaining to demographics, antimicrobial prophylaxis, supportive care, and neutropenic fever management. The survey was distributed from fall 2022 through spring 2023. RESULTS: 40 complete responses were recorded (54.8% response rate), with respondent institutions accounting for approximately 15.7% of 2021 US hematologic malignancy hospitalizations and 14.9% of 2020 US bone marrow transplantations. Most entities have institutional guidelines for neutropenic fever management (35, 87.5%) and prophylaxis (31, 77.5%), and first-line treatment included IV antipseudomonal antibiotics (35, 87.5% cephalosporin; 5, 12.5% penicillin; 0, 0% carbapenem).We observed significant heterogeneity in treatment course decisions, with roughly half (18, 45.0%) of respondents continuing antibiotics until neutrophil recovery, while the remainder having criteria for de-escalation prior to neutrophil recovery. Respondents were more willing to de-escalate prior to neutrophil recovery in patients with identified clinical (27, 67.5% with pneumonia) or microbiological (30, 75.0% with bacteremia) sources after dedicated treatment courses. CONCLUSIONS: We found substantial variation in the practice of de-escalation of empiric antibiotics relative to neutrophil recovery, highlighting a need for more robust evidence for and adoption of this practice. No respondents use carbapenems as first-line therapy, comparing favorably to prior survey studies conducted in other countries.

The Comparative Effects of Monotherapy with Topical Minoxidil, Oral Finasteride, and Topical Finasteride in Postmenopausal Women with Pattern Hair Loss: A Retrospective Cohort Study.

Introduction: Oral finasteride and topical minoxidil are long-standing androgenetic alopecia (AGA) treatments; topical finasteride is a more recent medicine. Few studies have compared their therapeutic effects in postmenopausal women. We compared the therapeutic impact of topical finasteride (1-4 sprays of 0.25% topical finasteride solution daily for 12 months), oral finasteride (2.5 mg oral finasteride once daily for 12 months), and topical minoxidil (1 mL of topical minoxidil 5% twice daily for 12 months) in postmenopausal women with AGA. Methods: We conducted Bayesian network meta-analyses of individual patient-level data insofar as four clinically relevant endpoints, namely, 12-month change in (1) total hair density, (2) hair diameter, (3) clinical photographs, and (4) patients' opinion of efficacy. Data were obtained through medical charts. Regimens' surface under the cumulative ranking distribution (SUCRA) values and relative effects - as per odds ratios - were computed. Results: As per SUCRA, the most and least effective regimens - across the four outcomes - were oral finasteride, and topical finasteride, respectively; however, no significant statistical differences were found (i.e., p > 0.05). Conclusion: Oral finasteride is ranked more effective than the topical forms of minoxidil and finasteride; however, more studies are needed to confirm this result.

SARS-CoV-2-Triggered Hemophagocytic Lymphohistiocytosis with Complications of Posterior Reversible Encephalopathy Syndrome.

In this article, we describe a novel case of SARS-CoV-2-associated-hemophagocytic lymphohistiocytosis (HLH) complicated by posterior reversible encephalopathy syndrome (PRES). Initially diagnosed with multisystem inflammatory response in children (MIS-C), the patient received a large corticosteroid dose days before the onset of neurological symptoms. After developing PRES, the patient was treated with antihypertensives, antiepileptics, dexamethasone, and anakinra, leading to neurologic normalization. We propose that given the challenging diagnostic picture of PRES developing in patients with HLH or MIS-C, institutionalized standards for blood pressure management during corticosteroid induction may significantly improve outcomes in patients being treated for hyperinflammatory syndromes who develop neurological symptoms.

An update on tinea capitis in children.

Tinea capitis presents a significant public health care challenge due to its contagious nature, and potential long-term consequences if unrecognized and untreated. This review explores the prevalence, risk factors, diagnostic methods, prevention strategies, impact on quality of life, and treatment options for pediatric tinea capitis. Epidemiological analysis spanning from 1990 to 1993 and 2020 to 2023 reveals prevalence patterns of pediatric tinea capitis influenced by geographic, demographic, and environmental factors. Notably, Trichophyton species is most prevalent in North America; however, Microsporum species remain the primary causative agent globally, with regional variations. Risk factors include close contact and environmental conditions, emphasizing the importance of preventive measures. Accurate diagnosis relies on clinical evaluation, microscopic examination, and fungal culture. Various treatment modalities including systemic antifungals show efficacy, with terbinafine demonstrating superior mycological cure rates particularly for Trichophyton species. Recurrent infections and the potential development of resistance can pose challenges. Therefore, confirming the diagnosis, appropriately educating the patient/caregiver, accurate drug and dose utilization, and compliance are important components of clinical cure. Untreated or poorly treated tinea capitis can lead to chronic infection, social stigma, and psychological distress in affected children. Prevention strategies focus on early detection and healthy lifestyle habits. Collaborative efforts between healthcare providers and public health agencies are important in treating pediatric tinea capitis and improving patient outcomes. Education and awareness initiatives play a vital role in prevention and community-level intervention to minimize spread of infection. Future research should explore diagnostic advances, novel treatments, and resistance mechanisms in order to mitigate the disease burden effectively.

Targeting Rural Adolescent Pregnancy: Modifiable Protective Factors and Contraceptive Use.

PURPOSE: Rural adolescent pregnancy is a serious public health issue, largely due to low contraceptive use. Existing data focuses on urban populations. Using a positive youth development framework, we examine associations between modifiable protective factors and birth control use in a rural population. METHODS: Prior to an evidence-based health education program, students in 10th grade health class in two low-to-middle income rural schools completed surveys. For contraceptive use at last sex, students could check all methods that applied which were collapsed into three rank-ordered categories: none, condoms only, and hormonal contraception. Predictor variables included sexual self-efficacy (six items, α = 0.66, "able to say no"), parent connectedness (five items, α = 0.94, "satisfaction with your parent/guardian?"), language acculturation (one item, "in your home do you speak…"), school connectedness (five items, α = 0.85, "I feel close to people at my school") and adverse childhood experiences (eight item score). These variables were entered into a multivariable logistic ordinal regression. RESULTS: The sample (N = 287) was 52% female, 48% LatinX and 49% white. Higher sexual self-efficacy and parent connectedness scores significantly increased the odds of using more effective birth control. Higher language acculturation (more likely to speak another language at home) suggested less likely to use more effective birth control. School connection and adverse childhood experiences were not significant in the final model. DISCUSSION: Contraception focused interventions in rural communities should address modifiable protective factors, such as self-efficacy and parent connection. Interventions need to be trauma-informed and language accessible.

A co-ordinated transcriptional programme in the maternal liver supplies long chain polyunsaturated fatty acids to the conceptus using phospholipids.

The long and very long chain polyunsaturated fatty acids (LC-PUFAs) are preferentially transported by the mother to the fetus. Failure to supply LC-PUFAs is strongly linked with stillbirth, fetal growth restriction, and impaired neurodevelopmental outcomes. However, dietary supplementation during pregnancy is unable to simply reverse these outcomes, suggesting imperfectly understood interactions between dietary fatty acid intake and the molecular mechanisms of maternal supply. Here we employ a comprehensive approach combining untargeted and targeted lipidomics with transcriptional profiling of maternal and fetal tissues in mouse pregnancy. Comparison of wild-type mice with genetic models of impaired lipid metabolism allows us to describe maternal hepatic adaptations required to provide LC-PUFAs to the developing fetus. A late pregnancy-specific, selective activation of the Liver X Receptor signalling pathway dramatically increases maternal supply of LC-PUFAs within circulating phospholipids. Crucially, genetic ablation of this pathway in the mother reduces LC-PUFA accumulation by the fetus, specifically of docosahexaenoic acid (DHA), a critical nutrient for brain development.

Perceived Weight Discrimination and General Coping Strategies.

BACKGROUND: Perceived weight discrimination is associated consistently with worse health outcomes. Coping strategies may be one mechanism of this association. The present research examined the association between perceived weight discrimination and strategies used to cope with general stress (not weight-specific) and whether these strategies accounted for part of the association with markers of health. METHOD: Participants (N = 1882) completed a cross-sectional survey with a comprehensive measure of coping strategies and reported on their perceived experience of weight discrimination and markers of physical, mental, and social health. RESULTS: Perceived weight discrimination was associated with greater use of disengaged coping strategies (ß = .19, p < .01) and was unrelated to active and support coping strategies. Disengaged coping mediated the association between weight discrimination and worse physical, mental, and social health (proportion of mediation ranged from 14 to 47%). This pathway was independent of body mass index (BMI). Individuals in the obesity weight category (BMI ≥ 30 kg/m2) were less likely to use active (ß = - .11, p < .01) and support (ß = - .09, p < .01) coping strategies, which did not consistently mediate the association with health. CONCLUSION: Perceived experiences of weight discrimination are associated with disengaged coping strategies to manage stressful experiences, and these strategies are one mechanism that may contribute to the worse health associated with unfair treatment due to weight.

Factors associated with participation in a walking intervention for veterans who smoke and have chronic pain.

This analysis was part of the Pain and Smoking Study (PASS), a randomized trial of a cognitive behavioral intervention (CBI) for Veterans with chronic pain who smoke. The objective of this study was to examine factors associated with participation in the walking component of the intervention. Demographics and clinical characteristics were obtained at baseline. Completion of two or more CBI counseling sessions was required to be included in analyses. Average daily step counts obtained via pedometer in the prior week were recorded in up to three telephone counseling sessions. Participants were then categorized as "sedentary" (≤ 4999 daily steps) or "not sedentary" (≥ 5000 daily steps). Multivariable logistic regression was used to model variance in activity categorization. Overall, 91.0% of participants were men, 70.5% were white, mean age was 58.4 years, mean BMI was 28.6, median pack years was 20.5, and 43.8% were depressed. Veterans reported moderate pain intensity (4.9/10) and pain interference (5.4/10). Pain locations included: lower extremity (67.4%), back (53.4%) and upper extremity (28.1%). Median daily steps were 2491 [IQR: 1720-3550] (sedentary) (n = 65), 7307 [IQR: 5952-8533] (not sedentary) (n = 24), and 3196 [IQR: 2237-5067] (overall) (n = 89). Veterans with older age (odds ratio (OR): 1.10, 95% confidence interval (CI): 1.04, 1.17) and presence of LE pain (OR: 5.98, 95% CI: 1.82, 19.65) had increased odds of being "sedentary." Integrated smoking cessation and chronic pain self-management interventions that include a walking component may need to consider the impact of age and pain location on participation.Trial registration: The trial is registered at www.ClinicalTrials.gov (NCT02971137). First posted on November 22, 2016.

Microfluidic device: A versatile biosensor platform to multiplex aptamer-based detection of malaria biomarkers.

Plasmodium falciparum malaria remains a dominant infectious disease that affects Africa than the rest of the world, considering its associated cases and death rates. It's a febrile illness that produces several reliable biomarkers, for example, P. falciparum lactate dehydrogenase (PfLDH), P. falciparum Plasmodium glutamate dehydrogenase (PfGDH), and P. falciparum histidine-rich proteins (HRP-II) in blood circulatory system that can easily be employed as targets in rapid diagnostic tests (RDTs). In recent times, several DNA aptamers have been developed via SELEX technology to detect some specific malaria biomarkers (PfLDH, PvLDH, HRP-II, PfGDH) in a biosensor mode with good binding affinity properties to overcome the trend of cross-reactivity, limited sensitivity and stability problems that have been observed with immunodiagnostics. In this review, we summarized existing diagnostic methods and relevant biomarkers to suggest promising approaches to develop sensitive and species-specific multiplexed diagnostic devices enabling effective detection of malaria in complex biological matrices and surveillance in the endemic region.

Hepatitis B Virus in People who Inject Drugs and Men who Have Sex With Men With HIV in India: A Cross-sectional Study.

Background: People with HIV (PWH) who are coinfected with hepatitis B virus (HBV) have a higher risk of mortality compared with PWH alone. Populations such as people who inject drugs (PWID) and men who have sex with men (MSM) are particularly at high risk for HBV acquisition; yet, limited epidemiological data from these populations exist on HBV prevalence from low- and middle-income country settings (LMICs). Methods: We characterized the prevalence and correlates of HBV serological markers in a sample of PWID and MSM with HIV recruited across 15 Indian cities using hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), and hepatitis B surface antibody (anti-HBs). Testing of stored specimens for the presence of these markers was performed on the Abbott ARCHITECT i1000 as per the manufacturer's instructions. Correlates of ever being infected with HBV (reactive for anti-HBc and/or HBsAg) and chronic HBV (reactive for HBsAg) among those ever infected were assessed using univariable and multivariable multilevel logistic regression models accounting for site-level clustering. Results: A total of 2198 (95%) of the 2314 participants recruited for the trial were screened for HBV markers. The median age among the PWID and MSM participants was 30 and 32 years, respectively. The prevalence of ever being infected with HBV was 75.6% vs 46.9% in PWID vs MSM, respectively (P < .01); prevalence of chronic infection was also higher in PWID vs MSM (14.1% vs 9.5%; P < .01). Correlates of ever being infected with HBV among PWID included unstable housing (adjusted odds ratio [aOR], 5.02) and sharing injection paraphernalia (aOR, 2.70), and among MSM, correlates included history of injection drug use (aOR, 4.87) and gender identity. The prevalence of isolated core (anti-HBc in the absence of anti-HBs) was 34.7% vs 29.4% in PWID vs MSM (P < .05). Vaccination serostatus was <10% in both populations. Conclusions: In this large sample of PWID and MSM with HIV, we observed a high prevalence of serology consistent with HBV infection and low vaccination, highlighting the need for routine screening and catch-up vaccination. The high prevalence of isolated anti-HBc reactivity highlights the need to understand the risk of reactivation with this serological pattern.

Association of Busulfan Exposure and Outcomes after HCT for Patients with an Inborn Error of Immunity.

Allogeneic HCT is a potentially curative treatment strategy for patients with inborn errors of immunities (IEIs). Objective of this study was to assess the optimal busulfan exposure prior to allogeneic HCT for patients with an IEI who received an intravenous busulfan-based conditioning regimen between 2000 and 2023. Patients from 17 international centers were included. Main outcome of interest was event-free survival (EFS). Patients were categorized into 4 IEI subgroups: combined-immunodeficiency (CID), severe combined immunodeficiency (SCID), neutrophil disorders and hemophagocytic lymphohistiocytosis (HLH)-related disorders. Busulfan exposure was calculated by individual centers (AUCCENTER) and was re-estimated using a validated model (AUCNONMEM). Overall, 562 patients were included: 173 (30.8%) CID, 154 (27.4%) SCID, 101 (18.0%) HLH-related disorders, and 134 (23.8%) neutrophil disorders. Median busulfan AUCNONMEM was 69.0 mg×h/L and correlated poorly with AUCCENTER (r2=0.54). Patients with SCID, HLH-related, and neutrophil disorders were analyzed together (n=389), because CID disease subtype was an effect modifier (p=0.03). Estimated 2-year EFS was 78.5%. In patients with the found optimal busulfan AUCNONMEM of 70-90 mg×h/L, 2-year EFS was superior to <70 mg×h/L (adj-HR 1.97, 95% CI 1.11-3.49, p=0.02), and >90 mg×h/L (adj-HR 5.05, 95% CI 2.43-10.49, p<0.0001). Full donor chimerism increased with higher busulfan AUCNONMEM, plateauing at 90 mg×h/L. For CID patients, optimal AUCNONMEM for donor chimerism was found to be >70 mg×h/L. Improved EFS and higher donor chimerism may be achieved by targeting a cumulative busulfan AUCNONMEM of 80 mg×h/L (range 70-90). Our study stresses the importance to uniformly using a validated population PK-model to estimate the AUCNONMEM.

Investigation of Pulmonary Saddle Embolism Caused by Metastasis-Induced Hypercoagulability Originating From Pancreatic Cancer.

An adult male cadaver, approximately 60 years of age, was dissected as part of an eight-week didactic course. It was found that the subject had evidence of pancreatic cancer with signs of metastasis as well as significant bilateral pulmonary artery clotting. In particular, a saddle embolism was observed, and the cause of death was listed as sudden pulmonary failure. Malignant tumors are often accompanied by hypercoagulable states and increased risk of thromboembolism. Because the clots showed lines of Zahn on histology, we can infer that this hypercoagulable state preceded death and may have been related to the presence of pancreatic carcinoma. There are few recorded cases of pulmonary saddle embolism being the fatal event in cases of underlying pancreatic cancer. The extensive clotting observed in the inferior vena cava and pulmonary arteries demonstrates to clinicians that patients, especially those with pancreatic cancer, are at higher risk for thromboembolic events. This case report also serves as a reminder that instances of pulmonary failure or sudden death because of pulmonary saddle embolism may be caused by underlying visceral neoplasms, such as pancreatic cancer.

Cellular zinc status alters chromatin accessibility and binding of p53 to DNA.

Zn2+ is an essential metal required by approximately 850 human transcription factors. How these proteins acquire their essential Zn2+ cofactor and whether they are sensitive to changes in the labile Zn2+ pool in cells remain open questions. Using ATAC-seq to profile regions of accessible chromatin coupled with transcription factor enrichment analysis, we examined how increases and decreases in the labile zinc pool affect chromatin accessibility and transcription factor enrichment. We found 685 transcription factor motifs were differentially enriched, corresponding to 507 unique transcription factors. The pattern of perturbation and the types of transcription factors were notably different at promoters versus intergenic regions, with zinc-finger transcription factors strongly enriched in intergenic regions in elevated Zn2+ To test whether ATAC-seq and transcription factor enrichment analysis predictions correlate with changes in transcription factor binding, we used ChIP-qPCR to profile six p53 binding sites. We found that for five of the six targets, p53 binding correlates with the local accessibility determined by ATAC-seq. These results demonstrate that changes in labile zinc alter chromatin accessibility and transcription factor binding to DNA.

Patterns of Prescription Medication Use Before Diagnosis of Early Age-Onset Colorectal Cancer: Population-Based Descriptive Study.

BACKGROUND: Colorectal cancer (CRC) is estimated to be the fourth most common cancer diagnosis in Canada (except for nonmelanoma skin cancers) and the second and third leading cause of cancer-related death in male and female individuals, respectively. OBJECTIVE: The rising incidence of early age-onset colorectal cancer (EAO-CRC; diagnosis at less than 50 years) calls for a better understanding of patients' pathway to diagnosis. Therefore, we evaluated patterns of prescription medication use before EAO-CRC diagnosis. METHODS: We used linked administrative health databases in British Columbia (BC), Canada, to identify individuals diagnosed with EAO-CRC between January 1, 2010, and December 31, 2016 (hereinafter referred to as "cases"), along with cancer-free controls (1:10), matched by age and sex. We identified all prescriptions dispensed from community pharmacies during the year prior to diagnosis and used the Anatomical Therapeutic Chemical Classification system Level 3 to group prescriptions according to the drug class. A parallel assessment was conducted for individuals diagnosed with average age-onset CRC (diagnosis at age 50 years and older). RESULTS: We included 1001 EAO-CRC cases (n=450, 45% female participants; mean 41.0, SD 6.1 years), and 12,989 prescriptions were filled in the year before diagnosis by 797 (79.7%) individuals. Top-filled drugs were antidepressants (first; n=1698, 13.1%). Drugs for peptic ulcer disease and gastroesophageal reflux disease (third; n=795, 6.1%) were more likely filled by EAO-CRC cases than controls (odds ratio [OR] 1.4, 95% CI 1.2-1.7) and with more frequent fills (OR 1.8, 95% CI 1.7-1.9). We noted similar patterns for topical agents for hemorrhoids and anal fissures, which were more likely filled by EAO-CRC cases than controls (OR 7.4, 95% CI 5.8-9.4) and with more frequent fills (OR 15.6, 95% CI 13.1-18.6). CONCLUSIONS: We observed frequent prescription medication use in the year before diagnosis of EAO-CRC, including for drugs to treat commonly reported symptoms of EAO-CRC.

Profound Properties of Protein-Rich, Platelet-Rich Plasma Matrices as Novel, Multi-Purpose Biological Platforms in Tissue Repair, Regeneration, and Wound Healing.

Autologous platelet-rich plasma (PRP) preparations are prepared at the point of care. Centrifugation cellular density separation sequesters a fresh unit of blood into three main fractions: a platelet-poor plasma (PPP) fraction, a stratum rich in platelets (platelet concentrate), and variable leukocyte bioformulation and erythrocyte fractions. The employment of autologous platelet concentrates facilitates the biological potential to accelerate and support numerous cellular activities that can lead to tissue repair, tissue regeneration, wound healing, and, ultimately, functional and structural repair. Normally, after PRP preparation, the PPP fraction is discarded. One of the less well-known but equally important features of PPP is that particular growth factors (GFs) are not abundantly present in PRP, as they reside outside of the platelet alpha granules. Precisely, insulin-like growth factor-1 (IGF-1) and hepatocyte growth factor (HGF) are mainly present in the PPP fraction. In addition to their roles as angiogenesis activators, these plasma-based GFs are also known to inhibit inflammation and fibrosis, and they promote keratinocyte migration and support tissue repair and wound healing. Additionally, PPP is known for the presence of exosomes and other macrovesicles, exerting cell-cell communication and cell signaling. Newly developed ultrafiltration technologies incorporate PPP processing methods by eliminating, in a fast and efficient manner, plasma water, cytokines, molecules, and plasma proteins with a molecular mass (weight) less than the pore size of the fibers. Consequently, a viable and viscous protein concentrate of functional total proteins, like fibrinogen, albumin, and alpha-2-macroglobulin is created. Consolidating a small volume of high platelet concentrate with a small volume of highly concentrated protein-rich PPP creates a protein-rich, platelet-rich plasma (PR-PRP) biological preparation. After the activation of proteins, mainly fibrinogen, the PR-PRP matrix retains and facilitates interactions between invading resident cells, like macrophages, fibroblast, and mesenchymal stem cells (MSCs), as well as the embedded concentrated PRP cells and molecules. The administered PR-PRP biologic will ultimately undergo fibrinolysis, leading to a sustained release of concentrated cells and molecules that have been retained in the PR-PRP matrix until the matrix is dissolved. We will discuss the unique biological and tissue reparative and regenerative properties of the PR-PRP matrix.

Identification of core competencies for exercise oncology professionals: A Delphi study of United States and Australian participants.

INTRODUCTION: Integration of exercise into standard oncology care requires a highly skilled workforce of exercise professionals; however, competency requirements have not kept pace with advancements in the field. Therefore, the aim of this study was to obtain consensus on core competencies required for an exercise professional to be qualified to work with adults undergoing active cancer treatment. MATERIALS AND METHODS: A three-round modified electronic Delphi process was used. In Round 1, an international group of 64 exercise oncology stakeholders (i.e., exercise oncology professionals (n = 29), clinical referrers (n = 21), and people with lived experience (n = 14)) responded to open-ended prompts eliciting perspectives regarding competencies needed for an exercise oncology professional to work with adults receiving active cancer treatment. Subsequently, only exercise oncology professionals participated, ranking the importance of competencies. In Round 2, professionals received summary feedback, ranked new competencies generated from open-ended responses, and reranked competencies not reaching consensus. In the final round, professionals finalized consensus ranking and rated frequency and mastery level for each. RESULTS: Consensus was reached on 103 core competencies required for exercise professionals to be qualified to deliver care to adults undergoing active cancer treatment. The core competencies represent 10 content areas and reflect the needs of clinical referrers and people with lived experience of receiving cancer treatment. CONCLUSIONS: The core competencies identified reflect significant advancements in the field of exercise oncology. Results will underpin the development of education, certification, and employment requirements for exercise oncology professionals, providing a critical step toward achieving routine integration of exercise into standard oncology care.

National rollout of a medication safety dashboard to improve testing for latent infections among biologic and targeted synthetic disease-modifying agent users within the Veterans Health Administration.

OBJECTIVE: To develop, deploy, and evaluate a national, electronic health record (EHR)-based dashboard to support safe prescribing of biologic and targeted synthetic disease-modifying agents (b/tsDMARDs) in the United States Veterans Affairs Healthcare System (VA). DATA SOURCES AND STUDY SETTING: We extracted and displayed hepatitis B (HBV), hepatitis C (HCV), and tuberculosis (TB) screening data from the EHR for users of b/tsDMARDs using PowerBI (Microsoft) and deployed the dashboard to VA facilities across the United States in 2022; we observed facilities for 44 weeks post-deployment. STUDY DESIGN: We examined the association between dashboard engagement by healthcare personnel and the percentage of patients with all screenings complete (HBV, HCV, and TB) at the facility level using an interrupted time series. Based on frequency of sessions, facilities were grouped into high- and low/none-engagement categories. We modeled changes in complete screening pre- and post-deployment of the dashboard. DATA COLLECTION METHODS: All VA facilities were eligible for inclusion; excluded facilities participated in design of the dashboard or had <20 patients receiving b/tsDMARDs. Session counts from facility personnel were captured using PowerBI audit log data. Outcomes were assessed weekly based on EHR data extracted via the dashboard itself. PRINCIPAL FINDINGS: Totally 117 facilities (serving a total of 41,224 Veterans prescribed b/tsDMARDs) were included. Before dashboard deployment, across all facilities, 61.5% of patients had all screenings complete, which improved to 66.3% over the course of the study period. The largest improvement (15 percentage points, 60.3%-75.3%) occurred among facilities with high engagement (post-intervention difference in outcome between high and low/none-engagement groups was 0.17 percentage points (pp) per week, 95% confidence interval (0.04 pp, 0.30 pp); p = 0.01). CONCLUSIONS: We observed significant improvements in screening for latent infections among facilities with high engagement with the dashboard, compared with those with fewer sessions.

An Ethical Framework for Disclosing the Training Status and Roles of Resident-Level Surgeons to Patients.

The concept of informed consent includes disclosure of all information that a reasonable patient would need to make a well-informed decision about whether to undergo a surgical procedure. This has traditionally been defined as including diagnosis, details about the procedure, prognosis, potential risks, and alternative treatments. The operating surgeon has final say and responsibility for the case, but the actual operation may be done (under supervision) by a surgeon in training. In this paper, we discuss the ethical dimensions of disclosing resident involvement, reviewing considerations such as established legal and professional standards, consequences for patients and for the surgical educators responsible for preparing future generations of surgeons, and patient rights. We conclude by offering a novel ethical framework intended to serve as a guide to disclosing resident involvement as part of the overall consent process.