Efficacy and Safety of a Recombinant Plant-Based Adjuvanted Covid-19 Vaccine.

BACKGROUND: Coronavirus-like particles (CoVLP) that are produced in plants and display the prefusion spike glycoprotein of the original strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are combined with an adjuvant (Adjuvant System 03 [AS03]) to form the candidate vaccine. METHODS: In this phase 3, multinational, randomized, placebo-controlled trial conducted at 85 centers, we assigned adults (≥18 years of age) in a 1:1 ratio to receive two intramuscular injections of the CoVLP+AS03 vaccine or placebo 21 days apart. The primary objective of the trial was to determine the efficacy of the CoVLP+AS03 vaccine in preventing symptomatic coronavirus disease 2019 (Covid-19) beginning at least 7 days after the second injection, with the analysis performed after the detection of at least 160 cases. RESULTS: A total of 24,141 volunteers participated in the trial; the median age of the participants was 29 years. Covid-19 was confirmed by polymerase-chain-reaction assay in 165 participants in the intention-to-treat population; all viral samples that could be sequenced contained variants of the original strain. Vaccine efficacy was 69.5% (95% confidence interval [CI], 56.7 to 78.8) against any symptomatic Covid-19 caused by five variants that were identified by sequencing. In a post hoc analysis, vaccine efficacy was 78.8% (95% CI, 55.8 to 90.8) against moderate-to-severe disease and 74.0% (95% CI, 62.1 to 82.5) among the participants who were seronegative at baseline. No severe cases of Covid-19 occurred in the vaccine group, in which the median viral load for breakthrough cases was lower than that in the placebo group by a factor of more than 100. Solicited adverse events were mostly mild or moderate and transient and were more frequent in the vaccine group than in the placebo group; local adverse events occurred in 92.3% and 45.5% of participants, respectively, and systemic adverse events in 87.3% and 65.0%. The incidence of unsolicited adverse events was similar in the two groups up to 21 days after each dose (22.7% and 20.4%) and from day 43 through day 201 (4.2% and 4.0%). CONCLUSIONS: The CoVLP+AS03 vaccine was effective in preventing Covid-19 caused by a spectrum of variants, with efficacy ranging from 69.5% against symptomatic infection to 78.8% against moderate-to-severe disease. (Funded by Medicago; ClinicalTrials.gov number, NCT04636697.).

Oral Valganciclovir Initiated Beyond 1 Month of Age as Treatment of Sensorineural Hearing Loss Caused by Congenital Cytomegalovirus Infection: A Randomized Clinical Trial.

OBJECTIVE: The objective of this study was to determine if valganciclovir initiated after 1 month of age improves congenital cytomegalovirus-associated sensorineural hearing loss. STUDY DESIGN: We conducted a randomized, double-blind, placebo-controlled phase 2 trial of 6 weeks of oral valganciclovir at US (n = 12) and UK (n = 9) sites. Patients of ages 1 month through 3 years with baseline sensorineural hearing loss were enrolled. The primary outcome was change in total ear hearing between baseline and study month 6. Secondary outcome measures included change in best ear hearing and reduction in cytomegalovirus viral load in blood, saliva, and urine. RESULTS: Of 54 participants enrolled, 35 were documented to have congenital cytomegalovirus infection and were randomized (active group: 17; placebo group: 18). Mean age at enrollment was 17.8 ± 15.8 months (valganciclovir) vs 19.5 ± 13.1 months (placebo). Twenty (76.9%) of the 26 ears from subjects in the active treatment group did not have worsening of hearing, compared with 27 (96.4%) of 28 ears from subjects in the placebo group (P = .09). All other comparisons of total ear or best ear hearing outcomes were also not statistically significant. Saliva and urine viral loads decreased significantly in the valganciclovir group but did not correlate with change in hearing outcome. CONCLUSIONS: In this randomized controlled trial, initiation of antiviral therapy beyond the first month of age did not improve hearing outcomes in children with congenital cytomegalovirus-associated sensorineural hearing loss. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01649869.

Factors Associated With Mortality and Hospice Use Among Medicare Beneficiaries With Heart Failure Who Received Home Health Services.

BACKGROUND: Although many Medicare beneficiaries with heart failure (HF) are discharged with home health services, little is known about mortality rates and hospice use in this group. OBJECTIVES: To identify risk factors for 6-month mortality and hospice use among patients hospitalized due to HF who receive home health care, which could inform efforts to improve palliative and hospice use for these patients. METHODS: A retrospective cohort analysis was conducted in a 100% national sample of Medicare fee-for-service beneficiaries with HF who were discharged to home health care between 2017 and 2018. Multivariable Cox regression models examined factors associated with 6-month mortality, and multivariable logistic regression models examined factors associated with hospice use at the time of death. RESULTS: A total of 285,359 Medicare beneficiaries were hospitalized with HF and discharged with home health care; 15.5% (44,174) died within 6 months. Variables most strongly associated with mortality included: age > 85 years (hazard ratio [HR] 1.66, 95% CI 1.61-1.71), urgent/emergency hospital admission (HR 1.68, 1.61-1.76), and "serious" condition compared to "stable" condition (HR 1.64, CI 1.52-1.78). Among 44,174 decedents, 48.2% (21,284) received hospice care at the time of death. Those with lower odds of hospice use at death included patients who were: < 65 years (odds ratio [OR] 0.65, CI 0.59-0.72); of Black (OR 0.64, CI 0.59-0.68) or Hispanic race/ethnicity (OR 0.79, CI 0.72-0.88); and Medicaid-eligible (OR 0.80, CI 0.76-0.85). CONCLUSIONS: Although many patients hospitalized for HF are at risk of 6-month mortality and may benefit from palliative and/or hospice services, our findings indicate under-use of hospice care and important disparities in hospice use by race/ethnicity and socioeconomic status.

Vaccination against COVID-19 - risks and benefits in children.

Countries in Europe and around the world have taken varying approaches to their policies on COVID-19 vaccination for children. The low risk of severe illness from COVID-19 means that even small risks from vaccination warrant careful consideration. Vaccination appears to result in a decreased risk of severe illness including the paediatric multi-system inflammatory syndrome known to be associated with COVID-19. These risks have already decreased significantly with the emergence of the Omicron variant and its subvariants, and due to widespread population immunity through previous infection. There is a relatively high risk of myocarditis following second doses of mRNA vaccines in adolescent males, although the general course of this condition appears mild.   Conclusion: COVID-19 vaccination only provides a transient reduction in transmission. Currently, insufficient evidence exists to determine the impact of vaccination on post-acute COVID syndromes in children, which are uncommon. What is Known: • Vaccines against COVID-19 have significantly reduced morbidity and mortality around the world. • Whilst countries have universally recommended vaccines for adults and continue to recommend them for vulnerable populations, there has been more variability in recommendations for children. What is New: • In the setting of near universal existing immunity from infection, the majority of the initial benefit in protecting against severe illness has been eroded. • The risks of myocarditis following mRNA vaccination for children is low, but an important consideration given the modest benefits.

Exploring the implementation of an educational film within antenatal care to reduce the risk of cytomegalovirus infection in pregnancy: A qualitative study.

BACKGROUND: Congenital cytomegalovirus (CMV) infection is a leading cause of sensorineural hearing loss and neuro-disability in childhood. In the absence of a licensed vaccine, adoption of hygiene-based measures may reduce the risk of CMV infection in pregnancy, however these measures are not routinely discussed with pregnant women as part of National Health Service (NHS) antenatal care in the United Kingdom (UK). METHODS: An exploratory qualitative study was conducted, underpinned by Normalization Process Theory (NPT), to investigate how an educational intervention comprising of a short film about CMV may best be implemented, sustained, and enhanced in real-world routine antenatal care settings. Video, semi-structured interviews were conducted with participants who were recruited using a purposive sample that comprised of midwives providing antenatal care from three NHS hospitals (n = 15) and participants from professional colleges and from organisations or charities providing, or with an interest in, antenatal education or health information in the UK (n = 15). FINDINGS: Midwives were reluctant to include CMV as part of early pregnancy discussions about reducing the risk of other infections due to lack of time, knowledge and absence of guidance or policies relating to CMV in antenatal education. However, the educational intervention was perceived to be a useful tool to encourage conversations and empower women to manage risk by all stakeholders, which would overcome some identified barriers. Macro-level challenges such as screening policies and lack of official guidelines to legitimise dissemination were identified. DISCUSSION: Successful implementation of education about CMV as part of routine NHS care in the UK will require an increase in awareness and knowledge about CMV amongst midwives. NPT revealed that 'coherence' and 'cognitive participation' between service members are vital to imbed CMV education in routine practice. 'Collective action' and 'reflexive monitoring' is required to sustain service changes.

Perspectives on supporting Veterans' social needs during hospital to home health transitions: findings from the Transitions Nurse Program.

BACKGROUND: Veterans who need post-acute home health care (HHC) are at risk for adverse outcomes and unmet social needs. Veterans' social needs could be identified and met by community-based HHC clinicians due to their unique perspective from the home environment, acuity of Veterans they serve, and access to Veterans receiving community care. To understand these needs, we explored clinician, Veteran, and care partner perspectives to understand Veterans' social needs during the transition from hospital to home with skilled HHC. METHODS: Qualitative data were collected through individual interviews with Veterans Health Administration (VHA) inpatient & community HHC clinicians, Veterans, and care partners who have significant roles facilitating Veterans' hospital to home with HHC transition. To inform implementation of a care coordination quality improvement intervention, participants were asked about VHA and HHC care coordination and Veterans' social needs during these transitions. Interviews were recorded, transcribed, and analyzed inductively using thematic analysis and results were organized deductively according to relevant transitional care domains (Discharge Planning, Transition to Home, and HHC Delivery). RESULTS: We conducted 35 interviews at 4 VHA Medical Centers located in Western, Midwestern, and Southern U.S. regions during March 2021 through July 2022. We organized results by the three care transition domains and related themes by VHA, HHC, or Veteran/care partner perspective. Our themes included (1) how social needs affected access to HHC, (2) the need for social needs screening during hospitalization, (3) delays in HHC for Veterans discharged from community hospitals, and (4) a need for closed-loop communication between VHA and HHC to report social needs. CONCLUSIONS: HHC is an underexplored space for Veterans social needs detection. While this research is preliminary, we recommend two steps forward from this work: (1) develop closed-loop communication and education pathways with HHC and (2) develop a partnership to integrate a social risk screener into HHC pathways.

Improving TRansitions ANd outcomeS for heart FailurE patients in home health CaRe (I-TRANSFER-HF): a type 1 hybrid effectiveness-implementation trial: study protocol.

BACKGROUND: Some of the most promising strategies to reduce hospital readmissions in heart failure (HF) is through the timely receipt of home health care (HHC), delivered by Medicare-certified home health agencies (HHAs), and outpatient medical follow-up after hospital discharge. Yet national data show that only 12% of Medicare beneficiaries receive these evidence-based practices, representing an implementation gap. To advance the science and improve outcomes in HF, we will test the effectiveness and implementation of an intervention called Improving TRansitions ANd OutcomeS for Heart FailurE Patients in Home Health CaRe (I-TRANSFER-HF), comprised of early and intensive HHC nurse visits combined with an early outpatient medical visit post-discharge, among HF patients receiving HHC. METHODS: This study will use a Hybrid Type 1, stepped wedge randomized trial design, to test the effectiveness and implementation of I-TRANSFER-HF in partnership with four geographically diverse dyads of hospitals and HHAs ("hospital-HHA" dyads) across the US. Aim 1 will test the effectiveness of I-TRANSFER-HF to reduce 30-day readmissions (primary outcome) and ED visits (secondary outcome), and increase days at home (secondary outcome) among HF patients who receive timely follow-up compared to usual care. Hospital-HHA dyads will be randomized to cross over from a baseline period of no intervention to the intervention in a randomized sequential order. Medicare claims data from each dyad and from comparison dyads selected within the national dataset will be used to ascertain outcomes. Hypotheses will be tested with generalized mixed models. Aim 2 will assess the determinants of I-TRANSFER-HF's implementation using a mixed-methods approach and is guided by the Consolidated Framework for Implementation Research 2.0 (CFIR 2.0). Qualitative interviews will be conducted with key stakeholders across the hospital-HHA dyads to assess acceptability, barriers, and facilitators of implementation; feasibility and process measures will be assessed with Medicare claims data. DISCUSSION: As the first pragmatic trial of promoting timely HHC and outpatient follow-up in HF, this study has the potential to dramatically improve care and outcomes for HF patients and produce novel insights for the implementation of HHC nationally. TRIAL REGISTRATION: This trial has been registered on ClinicalTrials.Gov (#NCT06118983). Registered on 10/31/2023, https://clinicaltrials.gov/study/NCT06118983?id=NCT06118983&rank=1 .

Food Desert Residence Is Not Associated With Dietary Adherence or Complication Rates in Patients With Isolated Mandibular Fractures.

BACKGROUND: Mandible fracture management requires postoperative dietary modifications to promote healing. Over 20 million Americans live in food deserts, low-income neighborhoods over one mile from a grocery store. The relationship between food desert residence (FDR) and adherence to postoperative dietary instructions remains unexplored. PURPOSE: This study's purpose is to evaluate the relationships between FDR, known risk factors, dietary adherence, and complications among patients with isolated mandible fractures. STUDY DESIGN, SETTING, SAMPLE: This retrospective cohort study was conducted at a level 1 trauma center and analyzed patients with mandible fractures between January 2015 and December 2020. Inclusion criteria included operative treatment of adult patients for mandible fractures; pregnant, incarcerated, and patients with incomplete data were excluded. PREDICTOR VARIABLE: FDR was the predictor variable of interest. FDR (coded yes or no) was generated by converting patient addresses to census tract GeoIDs and comparing them to the US Department of Agriculture Food Access Research Atlas. MAIN OUTCOME VARIABLES: The study examined two outcome variables: dietary adherence and postoperative complications. Dietary adherence was coded as adherent or nonadherent, indicating documented compliance with postoperative dietary modifications. Postoperative complications were coded as present or absent, reflecting infection, hardware failure, and mandible malunion or nonunion. COVARIATES: The covariates analyzed included age, sex, ethnicity, mechanism of injury, medical and psychiatric comorbidities (including diagnoses such as diabetes, hypertension, and schizophrenia), and tobacco use. ANALYSES: Relative risks (RRs) and multivariate logistic regression models were generated for both outcome variables. Two-tailed P values < 0.05 were considered statistically significant. RESULTS: During the study period, 143 patients had complete data allowing for FDR and dietary adherence determination, 124 of whom (86.7%) had complication data recorded. Of the cohort, 51/143 (35.7%) resided within a food desert, 30/143 (21.0%) exhibited dietary nonadherence, and 46/124 (37.1%) experienced complications. FDR was not associated with increased risk of dietary nonadherence (RR 0.92, 95% confidence interval [CI] 0.52 to 1.61, P = .76) or complications (RR 1.19, 95% CI 0.75 to 1.89; P = .46). On multivariate regression, dietary nonadherence was associated with increased complications (odds ratio 2.85, 95% CI 1.01 to 8.09, P = .049). CONCLUSION AND RELEVANCE: There was no association between FDR and dietary nonadherence or complications in mandible fracture patients. However, dietary nonadherence was associated with complications, highlighting the need for further research and intervention.

The Severity of Initial Unilateral Cleft Lip and Nasal Deformity Predicts Long-Term Postoperative Esthetic Outcome.

BACKGROUND: Infantile cleft lip and nasal severity influence the final esthetic result of the repair. Although various authors have described methods of cleft lip and nasal repair, there is a paucity of data that correlates cleft severity with esthetic outcomes. The aim of this study was to examine the correlation between presurgical severity of unilateral cleft deformity and long-term postoperative esthetic outcomes. METHODS: This retrospective study, based at a single institution, investigated patients with complete unilateral cleft lip, with or without cleft palate, who underwent repair by a single surgeon, had preoperative infantile facial casts, and had postoperative facial photographs at 6 to 11 years of age (N=31). Preoperative nostril width ratio and columellar angle measurements were taken from facial casts. Postoperative, long-term nasolabial appearance was rated by 5 blinded observers used a modified Kuijpers-Jagtman scale. Linear regression was used to determine the relationship between preoperative cleft severity and postoperative ratings. RESULTS: Preoperative nostril width ratio directly correlated with postoperative nasal form score (r=0.40; P=0.026); likewise, preoperative columellar angle predicted postoperative nasal form score (r=0.37; P=0.040). Preoperative cleft severity was not significantly correlated with vermillion border appearance. Cronbach α values of 0.91 (nasal form) and 0.79 (vermillion border) indicated good inter-rater reliability. Kappa values of 0.87 (nasal form) and 0.70 (vermillion border) indicated good intrarater reliability. CONCLUSIONS: Preoperative unilateral cleft nose severity directly correlates with long-term postoperative nasal appearance in childhood. Outcome studies should present and control for preoperative severity to allow more accurate assessment of repair techniques.

Respiratory Syncytial Virus Vaccination during Pregnancy and Effects in Infants.

BACKGROUND: Respiratory syncytial virus (RSV) is the dominant cause of severe lower respiratory tract infection in infants, with the most severe cases concentrated among younger infants. METHODS: Healthy pregnant women, at 28 weeks 0 days through 36 weeks 0 days of gestation, with an expected delivery date near the start of the RSV season, were randomly assigned in an overall ratio of approximately 2:1 to receive a single intramuscular dose of RSV fusion (F) protein nanoparticle vaccine or placebo. Infants were followed for 180 days to assess outcomes related to lower respiratory tract infection and for 364 days to assess safety. The primary end point was RSV-associated, medically significant lower respiratory tract infection up to 90 days of life, and the primary analysis of vaccine efficacy against the primary end point was performed in the per-protocol population of infants (prespecified criterion for success, lower bound of the 97.52% confidence interval [CI] of ≥30%). RESULTS: A total of 4636 women underwent randomization, and there were 4579 live births. During the first 90 days of life, the percentage of infants with RSV-associated, medically significant lower respiratory tract infection was 1.5% in the vaccine group and 2.4% in the placebo group (vaccine efficacy, 39.4%; 97.52% CI, -1.0 to 63.7; 95% CI, 5.3 to 61.2). The corresponding percentages for RSV-associated lower respiratory tract infection with severe hypoxemia were 0.5% and 1.0% (vaccine efficacy, 48.3%; 95% CI, -8.2 to 75.3), and the percentages for hospitalization for RSV-associated lower respiratory tract infection were 2.1% and 3.7% (vaccine efficacy, 44.4%; 95% CI, 19.6 to 61.5). Local injection-site reactions among the women were more common with vaccine than with placebo (40.7% vs. 9.9%), but the percentages of participants who had other adverse events were similar in the two groups. CONCLUSIONS: RSV F protein nanoparticle vaccination in pregnant women did not meet the prespecified success criterion for efficacy against RSV-associated, medically significant lower respiratory tract infection in infants up to 90 days of life. The suggestion of a possible benefit with respect to other end-point events involving RSV-associated respiratory disease in infants warrants further study. (Funded by Novavax and the Bill and Melinda Gates Foundation; ClinicalTrials.gov NCT02624947.).

Microbiotoxicity: antibiotic usage and its unintended harm to the microbiome.

PURPOSE OF REVIEW: Antibiotic use is associated with development of antimicrobial resistance and dysregulation of the microbiome (the overall host microbial community). These changes have in turn been associated with downstream adverse health outcomes. This review analyses recent important publications in a rapidly evolving field, contextualizing the available evidence to assist clinicians weighing the potential risks of antibiotics on a patient's microbiome. RECENT FINDING: Although the majority of microbiome research is observational, we highlight recent interventional studies probing the associations between antibiotic use, microbiome disruption, and ill-health. These studies include germ-free mouse models, antibiotic challenge in healthy human volunteers, and a phase III study of the world's first approved microbiome-based medicine. SUMMARY: The growing body of relevant clinical and experimental evidence for antibiotic-mediated microbiome perturbation is concerning, although further causal evidence is required. Within the limits of this evidence, we propose the novel term 'microbiotoxicity' to describe the unintended harms of antibiotics on a patient's microbiome. We suggest a framework for prescribers to weigh microbiotoxic effects against the intended benefits of antibiotic use.

A systematic review and meta-analysis of the prevalence of human cytomegalovirus shedding in seropositive pregnant women.

The detection of human cytomegalovirus (HCMV) in an individual's bodily fluid by culture techniques or through HCMV DNA detection by polymerase chain reaction, is known as HCMV shedding. Human cytomegalovirus shedding has the potential to transmit HCMV infection, where an individual can become infected with HCMV through contact with the bodily fluid of another individual containing HCMV. Human cytomegalovirus shedding can occur in primary infection and in non-primary infection for individuals with prior infection (HCMV seropositive). Human cytomegalovirus infection causes few or no symptoms in a pregnant woman, but can cause significant harm to her foetus if congenital CMV (cCMV) infection occurs. The association between HCMV shedding in HCMV seropositive pregnant women and the vertical transmission of HCMV to result in cCMV infection is poorly investigated, challenged by a limited understanding of the distribution of HCMV shedding in HCMV seropositive pregnant women. We systematically reviewed the published literature to describe the prevalence of HCMV shedding in HCMV seropositive women during pregnancy up to delivery. This analysis identified nine studies that met our eligibility criteria. In these studies, the prevalence of HCMV shedding in any bodily fluid of HCMV seropositive women during pregnancy and at delivery ranged from 0% to 42.5%. A meta-analysis, performed on six of the nine studies with suitable sample sizes, estimated a pooled prevalence of 21.5% [95% CI 12.7%,30.3%]. To our knowledge, this is the first review to systematically search the literature to summarise the prevalence of HCMV shedding in HCMV seropositive pregnant women. These estimates can help in the development of disease burden models and therapeutic or preventative strategies against cCMV infection in the context of non-primary maternal HCMV infection.

Care challenges of home health patients living with dementia: a pathway forward with palliative care.

BACKGROUND: Home health care (HHC) is a leading source of care support for older adults with serious illness, particularly patients living with dementia (PLWD). Demand for HHC is expected to continue to grow, driven by an aging population and preference for non-institutional care. HHC agencies are frequently under pressure to find effective approaches for improving care delivery and quality. One strategy that has the potential to improve the quality of life and patient satisfaction in HHC for PLWD is the integration of palliative care. Therefore, we sought to understand the experiences and needs of PLWD and their family caregivers specifically focusing on ways that HHC and palliative care may be integrated as part of the care transition from hospital to home, to better support PLWD and their families. METHODS: We conducted a descriptive qualitative study focusing on the perspectives of patients, caregivers, and healthcare team members about palliative care delivery for patients receiving HHC. Interviews were audio-recorded and professionally transcribed. In this analysis, we specifically report on dementia-related content using an iterative, team-based thematic analysis approach. RESULTS: We identified three themes: 1) 'Living in the Whirlwind' which describes the many competing demands on caregivers time and the associated feeling of loss of control, 2) 'Thinking Ahead' which describes the importance of thinking beyond the day-to-day tasks to begin planning for the future, and 3) 'Pathways Forward' which describes the integration of palliative care into HHC to provide enhanced support for PLWD and their caregivers. CONCLUSION: In this qualitative study, our formative work identified the importance of providing anticipatory guidance (e.g., safety, advance care planning) coupled with emotional and pragmatic care supports (e.g., finding resources, navigating insurance) to sustain caregivers who are struggling with the whirlwind.

Assessing the clinical viability of micro 3 pronuclei zygotes.

PURPOSE: What is the rate of euploidy and clinical viability of embryos resulting from micro 3 pronuclei zygotes? METHODS: Retrospective cohort analysis in a single, academic in vitro fertilization (IVF) center from March 2018 to June 2021. Cohorts were separated by fertilization as either a 2 pronuclear zygote (2PN) or micro 3 pronuclear zygote (micro 3PN). PGT-A was performed to identify embryonic ploidy rates in embryos created from micro 3PN zygotes. The clinical outcomes of all transferred euploid micro 3PN zygotes were evaluated from frozen embryo transfer (FET) cycles. RESULTS: During the designated study period, 75,903 mature oocytes were retrieved and underwent ICSI. Of these, 60,161 were fertilized as 2PN zygotes (79.3%) and 183 fertilized as micro 3PN zygotes (0.24%). Of the micro 3PN-derived embryos that underwent biopsy, 27.5% (n=11/42) were deemed euploid by PGT-A, compared to 51.4% (n=12,301/23,923) of 2PN-derived embryos, p=0.06. Four micro 3PN-derived embryos were transferred in subsequent single euploid FET cycles, which includes one live birth and one ongoing pregnancy. CONCLUSION: Micro 3PN zygotes that develop to the blastocyst stage and meet the criteria for embryo biopsy have the potential to be euploid by preimplantation genetic testing for aneuploidy (PGT-A) and if selected for transfer can achieve a live birth. Although there are a significantly lower number of micro 3PN embryos that make it to blastocyst biopsy, the potential to continue to culture abnormally fertilized oocytes may give these patients a chance at pregnancy that they previously did not have.

HIV-Associated Alterations of the Biophysical Features of Maternal Antibodies Correlate With Their Reduced Transfer Across the Placenta.

BACKGROUND: Human immunodeficiency virus (HIV) infection during pregnancy is associated with reduced transplacental transfer of maternal antibodies and increased risk of severe infections in children who are exposed and uninfected with HIV. The basis of this reduced transfer of maternal immunity has not yet been defined but could involve modifications in the biophysical features of antibodies. The objective of this study was to assess the impact of maternal HIV infection on the biophysical features of serum IgG and transplacental antibody transfer. METHODS: Maternal serum IgG subclass levels, Fc glycosylation, Fc receptor (FcR) binding, and transplacental transfer of pathogen-specific maternal IgG were measured in pregnant women with HIV (WWH) and pregnant women testing negative for HIV (WNH) in Cape Town, South Africa. RESULTS: Maternal antibody profiles were strikingly different between pregnant WWH and WNH. Antibody binding to FcγR2a and FcγR2b, IgG1 and IgG3 antibodies, and agalactosylated antibodies were all elevated in WWH, whereas digalactosylated and sialylated antibodies were reduced compared to pregnant WNH. Antibody features that were elevated in WWH were also correlated with reduced transplacental transfer of vaccine antigen-specific antibodies. CONCLUSIONS: HIV infection is associated with marked alterations of biophysical features of maternal IgG and reduced placental transfer, potentially impairing antimicrobial immunity.

"Our Hands Are Tied Until Your Doctor Gets Here": Nursing Perspectives on Inter-hospital Transfers.

BACKGROUND: The transfer of patients between hospitals (inter-hospital transfer, or IHT) is a common occurrence for patients, but guidelines to ensure safe and effective IHTs are lacking. Poor IHTs result in higher rates of mortality, longer lengths of stay, and higher hospitalization costs compared to admissions from the emergency department. Nurses are often the first point of contact for IHT patients and can provide valuable insights on key challenges to IHT processes. OBJECTIVE: To characterize the experiences of inpatient floor-level bedside nurses caring for IHT patients and identify care coordination challenges and solutions. DESIGN/PARTICIPANTS/APPROACH: Qualitative study using semi-structured focus groups and interviews conducted from October 2019 to July 2020 with 21 inpatient floor-level nurses caring for adult medicine patients at an academic hospital. Nurses were recruited using a purposive convenience sampling approach. A combined inductive and deductive coding approach guided by thematic analysis was used for data analysis. KEY RESULTS: Results from this study are mapped to the Agency for Healthcare Research and Quality Care Coordination Measurement Framework domains of communication, assessing needs and goals, and negotiating accountability. The following key themes characterize nurses' experiences with IHT related to these domains: (1) challenges with information exchange and team communication during IHT, (2) environmental and information preparation needed to anticipate transfers, and (3) determining responsibility and care plans after the IHT patient has arrived at the accepting facility. CONCLUSIONS: Nurses described the absence of standardized processes to coordinate care before or at the time of patient arrival. Challenges to communication and coordination during IHTs negatively impacted patient care and nursing professional satisfaction. To streamline care for IHT patients and reduce nursing stress, future IHT interventions should include standardized handoff reports, timely identification and easy access to admitting clinicians, and timely clinician evaluation and orders.

The Influence of the Rural Transitions Nurse Program for Veterans on Healthcare Utilization Costs.

BACKGROUND: The Veterans Affairs (VA) Healthcare System Rural Transitions Nurse Program (TNP) addresses barriers veterans face when transitioning from urban tertiary VA hospitals to home. Previous clinical evaluations of TNP have shown that enrolled veterans were more likely to follow up with their primary care provider within 14 days of discharge and experience a significant reduction in mortality within 30 days compared to propensity-score matched controls. OBJECTIVE: Examine changes from pre- to post-hospitalization in total, inpatient, and outpatient 30-day healthcare utilization costs for TNP enrollees compared to controls. DESIGN: Quantitative analyses modeling the changes in cost via multivariable linear mixed-effects models to determine the association between TNP enrollment and changes in these costs. PARTICIPANTS: Veterans meeting TNP eligibility criteria who were discharged home following an inpatient hospitalization at one of the 11 implementation sites from April 2017 to September 2019. INTERVENTION: The four-step TNP transitional care intervention. MAIN MEASURES: Changes in 30-day total, inpatient, and outpatient healthcare utilization costs were calculated for TNP enrollees and controls. KEY RESULTS: Among 3001 TNP enrollees and 6002 controls, no statistically significant difference in the change in total costs (p = 0.65, 95% CI: (- $675, $350)) was identified. However, on average, the increase in inpatient costs from pre- to post-hospitalization was approximately $549 less for TNP enrollees (p = 0.02, 95% CI: (- $856, - $246)). The average increase in outpatient costs from pre- to post-hospitalization was approximately $421 more for TNP enrollees compared to controls (p = 0.003, 95% CI: ($109, $671)). CONCLUSIONS: Although we found no difference in change in total costs between veterans enrolled in TNP and controls, TNP was associated with a smaller increase in direct inpatient medical costs and a larger increase in direct outpatient medical costs. This suggests a shifting of costs from the inpatient to outpatient setting.

Mind the Difference: Characterizing the Impact of Behavioral Health Disorders on Facial Trauma.

BACKGROUND: Patients with psychiatric diagnoses are at greater risk for traumatic injury than the general population. Current literature fails to characterize how premorbid behavioral health disorders (BHDs) complicate craniofacial trauma. This study aimed to describe the characteristics and outcomes of patients with premorbid BHD sustaining facial fractures. METHODS: All adults in the 2013-2016 Trauma Quality Improvement Program datasets with facial fractures were identified. Demographics, injury characteristics, fracture patterns, and in-hospital outcomes were compared in patients with and without premorbid BHDs. BHDs included major psychiatric illnesses, alcohol or drug use disorders, attention deficit hyperactivity disorder, or dementia. RESULTS: Twenty-five percent of the 240,104 subjects with facial fractures had at least one premorbid BHD. Assault (29.9% versus 23.9%, P< 0.001), self-inflicted injury (2.9% versus 1.2%, P< 0.001), and multiple facial fractures (40.2% versus 38.7%, P< 0.001) were more common among the BHD group. The BHD group displayed significantly higher rates of nearly all in-hospital complications, including pneumonia (4.3% versus 3.3%, P< 0.001), substance withdrawal (3.9% versus 0.3%, P< 0.001), unplanned intubation (1.5% versus 0.9%, P< 0.001) and unplanned transfer to the intensive care unit (ICU, 1.3% versus 0.8%, P< 0.001). BHD was strongly predictive of pneumonia, unplanned intubation, and unplanned ICU admission in multivariate analyses. CONCLUSIONS: Patients with BHD represent a subset of facial trauma characterized by different mechanisms and patterns of injury and premorbid health status. BHDs are associated with higher in-hospital complication rates and resource utilization. Understanding the relationship between craniofacial trauma and premorbid BHD creates opportunities to improve morbidity and resource utilization in this group.

Sustainment stories: a qualitative analysis of barriers to sustainment of the National Rural Transitions of Care Nurse Program.

BACKGROUND: Understanding how to successfully sustain evidence-based care coordination interventions across diverse settings is critical to ensure that patients continue to receive high quality care even after grant funding ends. The Transitions Nurse Program (TNP) is a national intervention in the Veterans Administration (VA) that coordinates care for high risk veterans transitioning from acute care VA medical centers (VAMCs) to home. As part of TNP, a VA facility receives funding for a full-time nurse to implement TNP, however, this funding ends after implementation. In this qualitative study we describe which elements of TNP sites planned to sustain as funding concluded, as well as perceived barriers to sustainment. METHODS: TNP was implemented between 2016 and 2020 at eleven VA medical centers. Three years of funding was provided to each site to support hiring of staff, implementation and evaluation of the program. At the conclusion of funding, each site determined if they would sustain components or the entirety of the program. Prior to the end of funding at each site, we conducted midline and exit interviews with Transitions nurses and site champions to assess plans for sustainment and perceived barriers to sustainment. Interviews were analyzed using iterative, team-based inductive deductive content analysis to identify themes related to planned sustainment and perceived barriers to sustainment. RESULTS: None of the 11 sites planned to sustain TNP in its original format, though many of the medical centers anticipated offering components of the program, such as follow up calls after discharge to rural areas, documented warm hand off to PACT team, and designating a team member as responsible for patient rural discharge follow up. We identified three themes related to perceived sustainability. These included: 1) Program outcomes that address leadership priorities are necessary for sustainment.; 2) Local perceptions of the need for TNP or redundancy of TNP impacted perceived sustainability; and 3) Lack of leadership buy-in, changing leadership priorities, and leadership turnover are perceived barriers to sustainment. CONCLUSIONS: Understanding perceived sustainability is critical to continuing high quality care coordination interventions after funding ends. Our findings suggest that sustainment of care coordination interventions requires an in-depth understanding of the facility needs and local leadership priorities, and that building adaptable programs that continually engage key stakeholders is essential.

Biological relevance of trophectoderm morphology: initial ß-hCG measurements correlate with trophectoderm grading on euploid frozen embryo transfers.

OBJECTIVE: To analyze the correlation between TE grading and initial ß-hCG serum level after single euploid embryo transfer. Secondarily, to explore the association between TE grading with subsequent IVF outcomes. DESIGN: Retrospective cohort analysis. SETTING: Single, academic, private infertility and assisted reproductive care institute. PATIENTS OR OTHER PARTICIPANTS: Infertility patients who underwent a single euploid embryo transfer that resulted in a positive pregnancy test. INTERVENTION(S): ß-hCG measurements. MAIN OUTCOME MEASURE(S): Correlation between TE grade with first ß-hCG measurement. Second outcome measurements included ongoing pregnancy, biochemical pregnancy loss, and clinical pregnancy loss rates. RESULTS: 2,798 cases were analyzed. A significant difference in initial ß-hCG measurement among groups (TE A: median 143.4 mIU/mL IQR 79.2-211.2; TE B: 119 mIU/mL IQR 57.1-177.8; TE C: 82.4 mIU/mL IQR 36.3-136.4, p ≤ 0.0001) was observed. There was a significant correlation found between the TE grade and ß-hCG measurements (p ≤ 0.0001, r2 = 0.10). TE grade was not associated with higher odds of biochemical pregnancy loss (TE A vs. TE B: aOR 1.01 CI95% 0.97-1.05; TE A vs. TE C: aOR 1.03 CI95% 0.98-1.08), or higher odds of clinical pregnancy loss (TE A vs. TE B: aOR 1.02 CI95% 0.98-1.05; TE A vs. TE C: aOR 1.03 CI95% 0.98-1.07). CONCLUSIONS: In patients with euploid embryos, TE grade correlates with the first pregnancy test measurement of ß-hCG. We propose this finding helps to appoint a relevant link between morphology assessment and early embryo development in vivo.