Risk of Invasive Meningococcal Disease in Preterm Infants.

Background: Invasive meningococcal disease (IMD) is most common in the first year of life. We hypothesized that preterm infants may have a higher risk of IMD and more severe disease than term infants. We compared the incidence, demographics, clinical presentation, and outcomes of IMD in preterm compared with term infants during the first 5 years after implementation of a national meningococcal group B vaccine (4CMenB) for infants in England. Methods: The UK Health Security Agency conducts enhanced national IMD surveillance with detailed follow-up of all confirmed cases in England. Infants aged <1 year (uncorrected for gestational age) with IMD confirmed between 1 September 2015 and 31 August 2020 were included. Results: There were 393 infant IMD cases (incidence, 12.4/100 000 live births). Among 363 (92.4%) of the infants with known gestational age, the IMD incidence was higher in preterm (<37 weeks' gestation) than in term infants (18.3/100 000 vs 10.9/100 000; incidence rate ratio [IRR], 1.68 [95% confidence interval, 1.23-2.29]; P = .001). The IMD incidence was highest in those born at <32 weeks' gestation (32.9/100 000; incidence rate ratio for <32 weeks' gestation vs term, 3.01 [95% confidence interval, 1.73-5.24]; P ≤ .001). There were no differences in demographics, clinical presentation, rate of intensive care admission, or case-fatality rate, but preterm infants were more likely than term infants to have ≥1 reported sequela (14 of 39 [35.9%] vs 51 of 268 [19.0%]; P = .02). Conclusions: Preterm infants had a higher incidence of IMD than term infants and the IMD incidence was highest in infants born at <32 weeks' gestation. Preterm infants also had a higher risk of IMD sequelae.

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.

Consensus recommendation for prenatal, neonatal and postnatal management of congenital cytomegalovirus infection from the European congenital infection initiative (ECCI).

Congenital cytomegalovirus (cCMV) infection carries a significant burden with a 0.64% global prevalence and a 17-20% chance of serious long-term effects in children. Since the last guidelines, our understanding, particularly regarding primary maternal infections, has improved. A cCMV guidelines group was convened under the patronage of the European Society of Clinical Virology in April 2023 to refine these insights. The quality and validity of selected studies were assessed for potential biases and the GRADE framework was employed to evaluate quality of evidence across key domains. The resulting recommendations address managing cCMV, spanning prevention to postnatal care. Emphasizing early and accurate maternal diagnosis through serological tests enhances risk management and prevention strategies, including using valaciclovir to prevent vertical transmission. The guidelines also strive to refine personalized postnatal care based on risk assessments, ensuring targeted interventions for affected families.

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.

An implementation strategy postmortem method developed in the VA rural Transitions Nurse Program to inform spread and scale-up.

BACKGROUND: High-quality implementation evaluations report on intervention fidelity and adaptations made, but a practical process for evaluating implementation strategies is needed. A retrospective method for evaluating implementation strategies is also required as prospective methods can be resource intensive. This study aimed to establish an implementation strategy postmortem method to identify the implementation strategies used, when, and their perceived importance. We used the rural Transitions Nurse Program (TNP) as a case study, a national care coordination intervention implemented at 11 hospitals over three years. METHODS: The postmortem used a retrospective, mixed method, phased approach. Implementation team and front-line staff characterized the implementation strategies used, their timing, frequency, ease of use, and their importance to implementation success. The Expert Recommendations for Implementing Change (ERIC) compilation, the Quality Enhancement Research Initiative phases, and Proctor and colleagues' guidance were used to operationalize the strategies. Survey data were analyzed descriptively, and qualitative data were analyzed using matrix content analysis. RESULTS: The postmortem method identified 45 of 73 ERIC strategies introduced, including 41 during pre-implementation, 37 during implementation, and 27 during sustainment. External facilitation, centralized technical assistance, and clinical supervision were ranked as the most important and frequently used strategies. Implementation strategies were more intensively applied in the beginning of the study and tapered over time. CONCLUSIONS: The postmortem method identified that more strategies were used in TNP than planned and identified the most important strategies from the perspective of the implementation team and front-line staff. The findings can inform other implementation studies as well as dissemination of the TNP intervention.

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.

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.

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.

Qualitative interview study exploring the perspectives of pregnant women on participating in controlled human infection research in the UK.

INTRODUCTION: Pregnant women have been historically excluded from interventional research. While recent efforts have been made to improve their involvement, there remains a disparity in the evidence base for treatments available to pregnant women compared with the non-pregnant population. A significant barrier to the enrolment of pregnant women within research is risk perception and a poor understanding of decision-making in this population. OBJECTIVE: Assess the risk perception and influences on decision-making in pregnant women, when considering whether to enrol in a hypothetical interventional research study. DESIGN: Semistructured interviews were undertaken, and thematic analysis was undertaken of participant responses. PARTICIPANTS: Twelve pregnant women were enrolled from an antenatal outpatient clinic. RESULTS: Participants were unanimously positive about enrolling in the proposed hypothetical interventional study. Risk perception was influenced by potential risks to their fetus and their previous experiences of healthcare and research. Participants found the uncertainty in quantifying risk for new research interventions challenging. They were motivated to enrol in research by altruism and found less invasive research interventions more tolerable. CONCLUSION: It is vital to understand how pregnant women balance the perceived risks and benefits of interventional research. This may help clinicians and scientists better communicate risk to pregnant women and address the ongoing under-representation of pregnant women in interventional research.

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.

Learning from the experiences of pregnant women participating in a research study investigating human cytomegalovirus shedding: A qualitative study.

Transmission of human cytomegalovirus (CMV), from a pregnant woman to her fetus can cause congenital CMV infection, with life-long problems in some infected children. The presence of CMV in an infected individual's bodily fluid is known as shedding. An individual can become infected with CMV through contact with another individual who is shedding CMV in their bodily fluid, and the avoidance of contact with infected fluids may reduce the risk of infection. We explored the experiences of pregnant women taking part in a study investigating CMV shedding, to identify the potential facilitators and barriers towards engaging pregnant women with CMV risk-reduction measures. Twenty pregnant women participated in semi-structured, end-of-study, telephone interviews, analysed using thematic analysis. They participated in an observational study investigating CMV shedding in pregnant women previously infected with CMV living with young children. Participating women considered that CMV testing of themselves and their newborns was a benefit of participation, without raising additional concerns. They identified that their participation was contingent on a balance of convenience and inconvenience, and benefits and risks. Participation increased their awareness of their hygiene-based practices, leading to behavioural modifications that put them in contact with urine and saliva of their children without instructions to do so. These behavioural modifications might interfere with household routines. However, they recognised it to be a time-limited risk-reduction measure, and felt empowered by the knowledge they had gained through study participation and the support they had received from their partners. Participating women gained an increased awareness of their behaviour, resulting in behavioural modification without instructions to do this, in line with previous findings that trial participation can impact on participants' thinking about their behaviour with a possibility to influence change. Maternal research and risk-reduction measures should be centred around being informative, convenient, empowering, and supportive.

Online Well-Being Group Coaching Program for Women Physician Trainees: A Randomized Clinical Trial.

Importance: Physician burnout disproportionately affects women physicians and begins in training. Professional coaching may improve well-being, but generalizable evidence is lacking. Objective: To assess the generalizability of a coaching program (Better Together Physician Coaching) in a national sample of women physician trainees. Design, Setting, and Participants: A randomized clinical trial involving trainees in 26 graduate medical education institutions in 19 states was conducted between September 1, 2022, and December 31, 2022. Eligible participants included physician trainees at included sites who self-identified as a woman (ie, self-reported their gender identity as woman, including those who reported woman if multiple genders were reported). Intervention: A 4-month, web-based, group coaching program. Main Outcomes and Measures: The primary outcomes were change in burnout (measured using subscales for emotional exhaustion, depersonalization, and personal achievement from the Maslach Burnout Inventory). Secondary outcomes included changes in impostor syndrome, moral injury, self-compassion, and flourishing, which were assessed using standardized measures. A linear mixed model analysis was performed on an intent-to-treat basis. A sensitivity analysis was performed to account for the missing outcomes. Results: Among the 1017 women trainees in the study (mean [SD] age, 30.8 [4.0] years; 540 White participants [53.1%]; 186 surgical trainees [18.6%]), 502 were randomized to the intervention group and 515 were randomized to the control group. Emotional exhaustion decreased by an estimated mean (SE) -3.81 (0.73) points in the intervention group compared with a mean (SE) increase of 0.32 (0.57) points in the control group (absolute difference [SE], -4.13 [0.92] points; 95% CI, -5.94 to -2.32 points; P < .001). Depersonalization decreased by a mean (SE) of -1.66 (0.42) points in the intervention group compared with a mean (SE) increase of 0.20 (0.32) points in the control group (absolute difference [SE], -1.87 [0.53] points; 95%CI, -2.91 to -0.82 points; P < .001). Impostor syndrome decreased by a mean (SE) of -1.43 (0.14) points in the intervention group compared with -0.15 (0.11) points in the control group (absolute difference [SE], -1.28 (0.18) points; 95% CI -1.63 to -0.93 points; P < .001). Moral injury decreased by a mean (SE) of -5.60 (0.92) points in the intervention group compared with -0.92 (0.71) points in the control group (absolute difference [SE], -4.68 [1.16] points; 95% CI, -6.95 to -2.41 points; P < .001). Self-compassion increased by a mean (SE) of 5.27 (0.47) points in the intervention group and by 1.36 (0.36) points in the control group (absolute difference [SE], 3.91 [0.60] points; 95% CI, 2.73 to 5.08 points; P < .001). Flourishing improved by a mean (SE) of 0.48 (0.09) points in the intervention group vs 0.09 (0.07) points in the control group (absolute difference [SE], 0.38 [0.11] points; 95% CI, 0.17 to 0.60 points; P < .001). The sensitivity analysis found similar findings. Conclusions and Relevance: The findings of this randomized clinical trial suggest that web-based professional group-coaching can improve outcomes of well-being and mitigate symptoms of burnout for women physician trainees. Trial Registration: ClinicalTrials.gov Identifier: NCT05222685.

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.

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 Questionnaire-based Study Exploring Participant Perspectives in a Perinatal Human Challenge Trial.

BACKGROUND: Pregnant women have historically been excluded from most medical research, including human challenge studies. The proof-of-concept Lactamica 9 human challenge study investigated whether nasal inoculation of pregnant women with commensal bacteria leads to horizontal transmission to the neonate. Given the unique practical and ethical considerations of both human challenge studies and interventional research involving pregnant women and their newborns, we sought to investigate the motivations, concerns and experiences of these volunteers. METHODS: Pre- and post-participation questionnaires were given to all participants in the Lactamica 9 study. These fully anonymized qualitative and Semi-quantitative questionnaires used forced Likert scales, word association and free-text questions. RESULTS: Pre- and post-participation questionnaires were completed by 87.1% (27/31) and 62.5% (15/24) of eligible participants, respectively. Almost all pre-participation respondents agreed with altruistic motivations for participation, and most concerns were related to discomfort from study procedures, with few concerned about the theoretical risks of inoculation to themselves (5/27; 18.5%) or their baby (6/27; 22.2%). Participants most frequently associated the study intervention with the terms "bacteria," "natural," "protective" and "safe." For the post-participation questionnaire, 93.3% (14/15) found all study procedures acceptable, and qualitative feedback was almost entirely positive, with particular emphasis on the research team's flexibility, approachability and friendliness. CONCLUSIONS: The successful completion of the Lactamica 9 study demonstrates that human challenge research in healthy pregnant women can be acceptable and feasible. Participants' initial concerns of potential discomfort were outweighed by predominantly altruistic motivations and perception of the intervention as "natural."

Standardizing case definitions for monitoring the safety of maternal vaccines globally: GAIA definitions, a review of progress to date.

In 2014, the Global Alignment on Immunization safety Assessment in pregnancy consortium (GAIA) was formed, with the goal of developing a harmonized, globally-concerted approach to actively monitor the safety of vaccines in pregnancy. A total of 26 standardized definitions for the classification of adverse events have been developed. The aim of this review was to identify and describe studies undertaken to assess the performance of these definitions. A literature search was undertaken to identify published studies assessing the performance of the definitions, and reference lists were snowballed. Data were abstracted by two investigators and a narrative review of the results is presented. Four studies that have evaluated 13 GAIA case definitions (50%) were identified. Five case definitions have been assessed in high-income settings only. Recommendations have been made by the investigators to improve the performance of the definitions. These include ensuring consistency across definitions, removal of the potential for ambiguity or variations in interpretation and ensuring that higher-level criteria are acceptable at lower levels of confidence. Future research should prioritize the key case definitions that have not been assessed in low- and middle-income settings, as well as the 13 that have not undergone any validation.

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.