Coupling of mRNA Structure Rearrangement to Ribosome Movement during Bypassing of Non-coding Regions.

Nearly half of the ribosomes translating a particular bacteriophage T4 mRNA bypass a region of 50 nt, resuming translation 3' of this gap. How this large-scale, specific hop occurs and what determines whether a ribosome bypasses remain unclear. We apply single-molecule fluorescence with zero-mode waveguides to track individual Escherichia coli ribosomes during translation of T4's gene 60 mRNA. Ribosomes that bypass are characterized by a 10- to 20-fold longer pause in a non-canonical rotated state at the take-off codon. During the pause, mRNA secondary structure rearrangements are coupled to ribosome forward movement, facilitated by nascent peptide interactions that disengage the ribosome anticodon-codon interactions for slippage. Close to the landing site, the ribosome then scans mRNA in search of optimal base-pairing interactions. Our results provide a mechanistic and conformational framework for bypassing, highlighting a non-canonical ribosomal state to allow for mRNA structure refolding to drive large-scale ribosome movements.

Temporal Trends of Neonatal Surgical Conditions in Texas and Accessibility to Pediatric Surgical Care.

INTRODUCTION: Texas consistently accounts for approximately 10% of annual national births, the second highest of all US states. This temporal study aimed to evaluate incidences of neonatal surgical conditions across Texas and to delineate regional pediatric surgeon accessibility. METHODS: The Texas Birth Defects Registry was queried from 1999 to 2018, based on 11 well-established regions. Nine disorders (30,476 patients) were identified as being within the operative scope of pediatric surgeons: biliary atresia (BA), pyloric stenosis (PS), Hirschsprung's disease, stenosis/atresia of large intestine/rectum/anus, stenosis/atresia of small intestine, tracheoesophageal fistula/esophageal atresia, gastroschisis, omphalocele, and congenital diaphragmatic hernia. Annual and regional incidences were compared (/10,000 births). Statewide pediatric surgeons were identified through the American Pediatric Surgical Association directory. Regional incidences of neonatal disorder per surgeon were evaluated from 2010 to 2018 as a surrogate for provider disparity. RESULTS: PS demonstrated the highest incidence (14.405/10,000), while BA had the lowest (0.707/10,000). Overall, incidences of PS and BA decreased significantly, while incidences of Hirschsprung's disease and small intestine increased. Other diagnoses remained stable. Regions 2 (48.24/10,000) and 11 (47.79/10,000) had the highest incidence of neonatal conditions; Region 6 had the lowest (34.68/10,000). Three rural regions (#2, 4, 9) lacked pediatric surgeons from 2010 to 2018. Of regions with at least one surgeon, historically underserved regions (#10, 11) along the Texas-Mexico border consistently had the highest defect per surgeon rates. CONCLUSIONS: There are temporal and regional differences in incidences of neonatal conditions treated by pediatric surgeons across Texas. Improving access to neonatal care is a complex issue that necessitates collaborative efforts between state legislatures, health systems, and providers.

Multiple Parallel Pathways of Translation Initiation on the CrPV IRES.

The complexity of eukaryotic translation allows fine-tuned regulation of protein synthesis. Viruses use internal ribosome entry sites (IRESs) to minimize or, like the CrPV IRES, eliminate the need for initiation factors. Here, by exploiting the CrPV IRES, we observed the entire process of initiation and transition to elongation in real time. We directly tracked the CrPV IRES, 40S and 60S ribosomal subunits, and tRNA using single-molecule fluorescence spectroscopy and identified multiple parallel initiation pathways within the system. Our results distinguished two pathways of 80S:CrPV IRES complex assembly that produce elongation-competent complexes. Following 80S assembly, the requisite eEF2-mediated translocation results in an unstable intermediate that is captured by binding of the elongator tRNA. Whereas initiation can occur in the 0 and +1 frames, the arrival of the first tRNA defines the reading frame and strongly favors 0 frame initiation. Overall, even in the simplest system, an intricate reaction network regulates translation initiation.

mRNA- and factor-driven dynamic variability controls eIF4F-cap recognition for translation initiation.

mRNA 5' cap recognition by eIF4F is a key element of eukaryotic translational control. Kinetic differences in eIF4F-mRNA interactions have long been proposed to mediate translation-efficiency differences between mRNAs, and recent transcriptome-wide studies have revealed significant heterogeneity in eIF4F engagement with differentially-translated mRNAs. However, detailed kinetic information exists only for eIF4F interactions with short model RNAs. We developed and applied single-molecule fluorescence approaches to directly observe real-time Saccharomyces cerevisiae eIF4F subunit interactions with full-length polyadenylated mRNAs. We found that eIF4E-mRNA association rates linearly anticorrelate with mRNA length. eIF4G-mRNA interaction accelerates eIF4E-mRNA association in proportion to mRNA length, as does an eIF4F-independent activity of eIF4A, though cap-proximal secondary structure still plays an important role in defining the final association rates. eIF4F-mRNA interactions remained dominated by effects of eIF4G, but were modulated to different extents for different mRNAs by the presence of eIF4A and ATP. We also found that eIF4A-catalyzed ATP hydrolysis ejects eIF4E, and likely eIF4E•eIF4G from the mRNA after initial eIF4F•mRNA complex formation, suggesting a mechanism to prepare the mRNA 5' end for ribosome recruitment. Our results support a role for mRNA-specific, factor-driven eIF4F association rates in kinetically controlling translation.

Risk factors for pediatric intracranial neoplasms in the Kids' Inpatient Database (KID).

INTRODUCTION: In children and adolescents brain and central nervous system (CNS) tumors are the leading types of cancers. Past studies have found differing rates of intracranial cancers among races and identified additional cancer risk factors. This study aims to see if these differences can be substantiated with further investigation of the latest version (2019) of the Kids' Inpatient Database (KID). METHODS: A total of 7,818 pediatric patients <21 years old in KID with ICD-10 codes consisting of malignant neoplasms of the brain, brainstem, and cerebral meninges (C700, C709-C719) were queried. Modifiable risk factors evaluated include: hospital region, insurance type, hospital city size, the average income of patient zip code, and location/teaching status of a hospital. Non-modifiable risk factors were race and sex at birth. Dependent variables were tested in Excel and GraphPad Prism 9 using a Chi-squared test with Yates' continuity correction and Tukey's one-way and two-way ANOVAs. RESULTS: Mortality rates of females (2.88%) compared to males (1.99%) were significant (p<0.05). Mortality was (4.17%) in Black patients compared to (1.68%) for White (p<0.0001), Hispanic mortality (2.95%) compared to White (p<0.01), and mortality of Asian/Pacific Islander (3.86%) compared to White (p<0.01). Black patients had significantly higher mortality than White, Hispanic, Asian/Pacific Islander, Native American, and other races overall (p<0.01). There was no significant difference in the mortality rates between children's hospitals and large hospitals for any race. After accounting for patient race, mortality was still not significantly different for patients with Medicaid insurance compared to non-Medicaid insurance types. Of the children treated at children's hospitals, the most transferred in from outside hospitals were Native American (20.00%) followed by Asian/PI (15.09%) then Hispanic patients (13.67%). A significant difference between races was also seen regarding length of stay (p<0.001) and number of charges (p<0.001). CONCLUSION: These findings confirm prior studies suggesting gender and race are significant factors in mortality rates for children with intracranial neoplasms. However, the findings do not identify the root causes of these discrepancies but may serve as an impetus for clinicians, healthcare administrators, and governmental leaders to improve national resource allocation to better care for pediatric patients with intracranial neoplasms.

Satisfactory 5-year functional outcomes following primary ACL reconstructions from the UK National Ligament Registry.

PURPOSE: The aim of this study was to describe the 10-year findings from the UK National Ligament Registry (NLR). METHODS: A retrospective review was performed for prospectively collected data on the NLR between January 2013 and December 2022. All patients who underwent primary ACL reconstruction (ACLR) on the registry were included. Surgical characteristics were analysed, including surgeon grade and case volume, concomitant knee procedures, venous thromboembolic prophylaxis, graft characteristics, femoral and tibial tunnel drilling, and fixation methods. Clinical outcomes were collected preoperatively and at 6 months, 1 year, 2 years and 5 years following the index procedure. RESULTS: During the study period, 17,492 unilateral ACLR procedures were recorded. Autograft was used in 98%, most commonly a combined semitendinosus and gracilis graft (77%) or patella tendon graft (31%). Allograft was used in only 1% of the patients. In 52% of cases, ACLR was associated with an additional procedure, with isolated medial meniscal surgery being the most common (21%). Femoral tunnel drilling was mostly performed through an anteromedial portal (73%) and tibial tunnel drilling using an outside-in technique (92%). The most common method of femoral graft fixation was with an Endobutton fixed loop suspensory device (77%), while interference screws predominated for tibial tunnel fixation (86%). Patients who underwent ACLR surgery showed significant improvement in their functional outcome scores at six months, 1 year, 2 years and 5 years postoperatively. CONCLUSION: Data from the NLR shows a detailed description of the current trends and evolution of ACLR in the United Kingdom over the last 10 years. Satisfactory functional outcomes were observed 5 years postoperatively. This study provides useful information on the prevalence of ACL-associated injuries and current surgical techniques with the aim of improving the quality of clinical care and patients' outcomes. Moreover, it provides surgeons with a benchmark against which to compare current practices and functional outcomes following ACLR across the United Kingdom. LEVEL OF EVIDENCE: Level III.

Ten-year results from the UK National Ligament Registry: Patient characteristics and factors predicting nonresponders for completion of outcome scores.

PURPOSE: The aim of this study was to report the demographic and mechanism of injury data in the UK National Ligament Registry (NLR) at 10 years and determine factors leading to poor compliance with completion of Patient-Reported Outcome Scores (PROMs). METHODS: A retrospective review was performed for prospectively collected data on the NLR between January 2013 and December 2022. All patients who underwent primary anterior cruciate ligament reconstruction (ACLR) were included. Patient demographics, mechanism of injury and patient compliance with completing PROMs were analysed. Patient characteristics were further analysed in relation to compliance with completing the different PROMs at the predefined time points. Patients were identified as nonresponders if they had not completed either 1- or 2-year postoperative Knee injury and Osteoarthritis Outcome Score (KOOS). RESULTS: A total of 17,492 patients were included in this study. The average age for patients undergoing ACLR between 2013 and 2022 was 29.4 (SD, 10.3). Seventy percent were men and 30% women. Football was the most common activity associated with an ACL injury. Patient compliance with recording PROMs was 55% preoperatively and 37%, 32% and 24% at 1-, 2- and 5-year postoperative follow-up, respectively. Nonresponders represented 54% of eligible patients. Multivariate analyses showed that sex, age, smoking, time interval between injury and surgery and low socioeconomic status were associated with low compliance with postoperative PROM completion (p < 0.001). CONCLUSION: This study reports the demographic characteristics for patients on the NLR since 2013. Male sex, young age, increased waiting time between injury and surgery, smoking and lower socioeconomic class were predictors of low compliance with completion of postoperative PROMs on the UK NLR. Understanding the factors that affect patient compliance with PROMs improves our ability to provide targeted interventions and information to specific patient populations with the aim of enhancing inclusiveness and representation of population in the registry. LEVEL OF EVIDENCE: Level III.

Safe driving recommendations following lower extremity orthopedic surgery: a systematic review.

PURPOSE: We analyzed the published literature on return-to-driving (RTD) recommendations following lower extremity orthopedic surgery, including knee and hip arthroplasty and ankle and foot surgery. METHODS: We conducted a PubMed MEDLINE database search for the relevant literature spanning from 1988 to 2022. Data were extracted from the selected articles independently by six investigators, and the mean, standard deviation, and range of RTD recommendations for each surgical region and procedure were calculated. RESULTS: The 34 studies included in our review evaluated brake response time, reaction time, movement time, braking force, and other parameters. Average RTD recommendations in weeks were: hip surgeries, 4.1 (± 2.7); foot surgeries, 6.67 (± 0.94); Achilles surgeries, 6.67 (± 0.25); ankle surgeries, 4 (± 2); knee surgeries, 5.42 (± 0.77); and multiple lower extremity surgeries, 3.85 (± 0.15). CONCLUSION: Our findings can assist physicians in providing informed recommendations to patients, promoting safe driving practices, and optimizing postoperative recovery. LEVEL OF EVIDENCE: Therapeutic, Level III: Retrospective comparative study.

Rehabilitation versus surgical reconstruction for non-acute anterior cruciate ligament injury (ACL SNNAP): a pragmatic randomised controlled trial.

BACKGROUND: Anterior cruciate ligament (ACL) rupture is a common debilitating injury that can cause instability of the knee. We aimed to investigate the best management strategy between reconstructive surgery and non-surgical treatment for patients with a non-acute ACL injury and persistent symptoms of instability. METHODS: We did a pragmatic, multicentre, superiority, randomised controlled trial in 29 secondary care National Health Service orthopaedic units in the UK. Patients with symptomatic knee problems (instability) consistent with an ACL injury were eligible. We excluded patients with meniscal pathology with characteristics that indicate immediate surgery. Patients were randomly assigned (1:1) by computer to either surgery (reconstruction) or rehabilitation (physiotherapy but with subsequent reconstruction permitted if instability persisted after treatment), stratified by site and baseline Knee Injury and Osteoarthritis Outcome Score-4 domain version (KOOS4). This management design represented normal practice. The primary outcome was KOOS4 at 18 months after randomisation. The principal analyses were intention-to-treat based, with KOOS4 results analysed using linear regression. This trial is registered with ISRCTN, ISRCTN10110685, and ClinicalTrials.gov, NCT02980367. FINDINGS: Between Feb 1, 2017, and April 12, 2020, we recruited 316 patients. 156 (49%) participants were randomly assigned to the surgical reconstruction group and 160 (51%) to the rehabilitation group. Mean KOOS4 at 18 months was 73·0 (SD 18·3) in the surgical group and 64·6 (21·6) in the rehabilitation group. The adjusted mean difference was 7·9 (95% CI 2·5-13·2; p=0·0053) in favour of surgical management. 65 (41%) of 160 patients allocated to rehabilitation underwent subsequent surgery according to protocol within 18 months. 43 (28%) of 156 patients allocated to surgery did not receive their allocated treatment. We found no differences between groups in the proportion of intervention-related complications. INTERPRETATION: Surgical reconstruction as a management strategy for patients with non-acute ACL injury with persistent symptoms of instability was clinically superior and more cost-effective in comparison with rehabilitation management. FUNDING: The UK National Institute for Health Research Health Technology Assessment Programme.

Balloon catheters versus vaginal prostaglandins for labour induction (CPI Collaborative): an individual participant data meta-analysis of randomised controlled trials.

BACKGROUND: Induction of labour is one of the most common obstetric interventions globally. Balloon catheters and vaginal prostaglandins are widely used to ripen the cervix in labour induction. We aimed to compare the effectiveness and safety profiles of these two induction methods. METHODS: We did an individual participant data meta-analysis comparing balloon catheters and vaginal prostaglandins for cervical ripening before labour induction. We systematically identified published and unpublished randomised controlled trials that completed data collection between March 19, 2019, and May 1, 2021, by searching the Cochrane Library, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, and PubMed. Further trials done before March 19, 2019, were identified through a recent Cochrane review. Data relating to the combined use of the two methods were not included, only data from women with a viable, singleton pregnancy were analysed, and no exclusion was made based on parity or membrane status. We contacted authors of individuals trials and participant-level data were harmonised and recoded according to predefined definitions of variables. Risk of bias was assessed with the ROB2 tool. The primary outcomes were caesarean delivery, indication for caesarean delivery, a composite adverse perinatal outcome, and a composite adverse maternal outcome. We followed the intention-to-treat principle for the main analysis. The primary meta-analysis used two-stage random-effects models and the sensitivity analysis used one-stage mixed models. All models were adjusted for maternal age and parity. This meta-analysis is registered with PROSPERO (CRD42020179924). FINDINGS: Individual participant data were available from 12 studies with a total of 5460 participants. Balloon catheters, compared with vaginal prostaglandins, did not lead to a significantly different rate of caesarean delivery (12 trials, 5414 women; crude incidence 27·0%; adjusted OR [aOR] 1·09, 95% CI 0·95-1·24; I2=0%), caesarean delivery for failure to progress (11 trials, 4601 women; aOR 1·20, 95% CI 0·91-1·58; I2=39%), or caesarean delivery for fetal distress (10 trials, 4441 women; aOR 0·86, 95% CI 0·71-1·04; I2=0%). The composite adverse perinatal outcome was lower in women who were allocated to balloon catheters than in those allocated to vaginal prostaglandins (ten trials, 4452 neonates, crude incidence 13·6%; aOR 0·80, 95% CI 0·70-0·92; I2=0%). There was no significant difference in the composite adverse maternal outcome (ten trials, 4326 women, crude incidence 22·7%; aOR 1·02, 95% CI 0·89-1·18; I2=0%). INTERPRETATION: In induction of labour, balloon catheters and vaginal prostaglandins have comparable caesarean delivery rates and maternal safety profiles, but balloon catheters lead to fewer adverse perinatal events. FUNDING: Australian National Health and Medical Research Council and Monash Health Emerging Researcher Fellowship.

Survey of Physician Practices, Attitudes, and Knowledge Regarding Recombinant Zoster Vaccine.

BACKGROUND: Herpes zoster vaccination rates remain low despite longstanding national recommendations to vaccinate immunocompetent adults aged ≥ 50 years. The Advisory Committee on Immunization Practice (ACIP) updated its recommendations for recombinant zoster vaccine (RZV) in October 2021 to include immunocompromised adults aged ≥19 years. OBJECTIVE: To assess practices, attitudes, and knowledge about RZV, barriers to recommending RZV, and likelihood of recommending RZV to patients with various immunocompromising conditions. DESIGN: Mail and internet-based survey conducted from May through July 2020. PARTICIPANTS: General internists and family physicians throughout the USA. MAIN MEASURES: Survey responses. KEY RESULTS: The response rate was 66% (632/955). Many physicians were already recommending RZV to immunocompromised populations, including adults ≥50 years with HIV (67% of respondents) and on recombinant human immune modulator therapy (56%). Forty-seven percent of respondents both stocked/administered RZV and referred patients elsewhere, frequently a pharmacy, for vaccination; 42% did not stock RZV and only referred patients. The majority agreed pharmacies do not inform them when RZV has been given (64%). Physicians were generally knowledgeable about RZV; however, 25% incorrectly thought experiencing side effects from the first dose of RZV that interfere with normal activities was a reason to not receive the second dose. The top reported barrier to recommending RZV was experience with patients declining RZV due to cost concerns (67%). Most physicians reported they would be likely to recommend RZV to immunocompromised patients. CONCLUSION: Most primary care physicians welcome updated ACIP RZV recommendations for immunocompromised adults. Knowledge gaps, communication issues, and financial barriers need to be addressed to optimize vaccination delivery.

Understanding the Factors Influencing Health Care Provider Recommendations about Adolescent Vaccines: A Proposed Framework.

Health care provider recommendations are among the most important factors influencing parents' decisions to vaccinate their adolescents. However, delivery of high-quality health care provider recommendations for vaccination is not universal. There is wide variation in the strength, timeliness and consistency of the delivery of recommendations for all adolescent vaccines. The factors that influence health care providers' recommendations are multi-level and can be conceptualized in much the same way as vaccine acceptance among parents. Health care providers are influenced by their own attitudes and beliefs about a vaccine and also by the patient they are treating and by the community in which they practice as well as state and national level vaccine policy. We propose a multi-level framework for understanding the factors that influence health care providers' recommendations at the individual, interpersonal and community level to both develop and adapt interventions to improve providers' recommendations.

Direct readout of heterochromatic H3K9me3 regulates DNMT1-mediated maintenance DNA methylation.

In mammals, repressive histone modifications such as trimethylation of histone H3 Lys9 (H3K9me3), frequently coexist with DNA methylation, producing a more stable and silenced chromatin state. However, it remains elusive how these epigenetic modifications crosstalk. Here, through structural and biochemical characterizations, we identified the replication foci targeting sequence (RFTS) domain of maintenance DNA methyltransferase DNMT1, a module known to bind the ubiquitylated H3 (H3Ub), as a specific reader for H3K9me3/H3Ub, with the recognition mode distinct from the typical trimethyl-lysine reader. Disruption of the interaction between RFTS and the H3K9me3Ub affects the localization of DNMT1 in stem cells and profoundly impairs the global DNA methylation and genomic stability. Together, this study reveals a previously unappreciated pathway through which H3K9me3 directly reinforces DNMT1-mediated maintenance DNA methylation.

The Impact of Altitude at Birth on Perinatal Respiratory Support for Neonates with Trisomy 21.

OBJECTIVE: Both high altitude and trisomy 21 (T21) status can negatively impact respiratory outcomes. The objective of this study was to examine the association between altitude and perinatal respiratory support in neonates with T21 compared with those without T21. STUDY DESIGN: This retrospective cohort study used the United States all-county natality files that included live, singleton, in-hospital births from 2015 to 2019. Descriptive statistics for neonates with and without the primary outcome of sustained assisted ventilation (>6 hours) were compared using t-tests and Chi-squared analyses. Multivariable logistic regression was used to determine the association between respiratory support and the presence of T21, and included an interaction term to determine whether the association between respiratory support and the presence of T21 was modified by elevation at delivery. RESULTS: A total of 17,939,006 neonates, 4,059 (0.02%) with T21 and 17,934,947 (99.98%) without, were included in the study. The odds of requiring sustained respiratory support following delivery were 5.95 (95% confidence interval [CI]: 5.31, 6.66), 4.06 (95% CI: 2.39, 6.89), 2.36 (95% CI: 1.64, 3.40), and 5.04 (95% CI: 1.54, 16.54) times as high for neonates with T21 than without T21 when born at low, medium, high, and very high elevations, respectively. The odds of requiring immediate ventilation support following delivery were 5.01 (95% CI: 4.59, 5.46), 5.90 (95% CI: 4.16, 8.36), 2.86 (95% CI: 2.15, 3.80), and 12.08 (95% CI: 6.78, 21.51) times as high for neonates with T21 than without T21 when born at low, medium, high, and very high elevation, respectively. CONCLUSION: Neonates with T21 have increased odds of requiring respiratory support following delivery when compared with neonates without T21 at all categories of altitude. However, the odds ratios did not increase monotonically with altitude which indicates additional research is critical in understanding the effects of altitude on neonates with T21. KEY POINTS: · Neonates with T21 have an increased need for perinatal respiratory support at all altitudes.. · The odds of needing perinatal respiratory support did not increase monotonically with elevation.. · Additional research is critical to understanding the effects of altitude on neonates with T21..

Measles Experience, Practice, and Knowledge by Pediatricians in the Context of Resurgent US Outbreaks.

OBJECTIVE: To assess measles experience, practice, and knowledge by pediatricians in the context of resurgent US outbreaks in 2018-2019. STUDY DESIGN: A nationally representative network of pediatricians were surveyed by email and mail from January to April 2020. RESULTS: The response rate was 67% (297 of 444). In the 3 years preceding the survey, 52% of the respondents reported awareness of measles cases in/near their community. Most thought that media reports about recent measles outbreaks had decreased delay/refusal of measles, mumps, and rubella (MMR) vaccine (6% "greatly decreased"; 66% "moderately decreased"). More than 60% of the pediatricians responded correctly for 6 of 9 true/false measles knowledge items. Less than 50% responded correctly for 3 true/false items, including statements about pretravel MMR recommendations for a preschooler and measles isolation precautions. The most common resources that the pediatricians would "sometimes" or "often/always" consult for measles information were those from the American Academy of Pediatrics (72%), a state or local public health department (70%), and the Centers for Disease Control and Prevention (63%). More than 90% of the pediatricians reported correct clinical practice for MMR vaccination of a 9-month-old before international travel. More than one-third of the respondents did not have a plan for measles exposures in their clinic. Pediatricians aware of measles cases in/near their community in the previous 3 years and those working in a hospital/clinic or Health Maintenance Organization setting were more likely to have a plan for measles exposures. CONCLUSIONS: During this time of heightened risk for measles outbreaks, there are opportunities to strengthen the knowledge and implementation of measles pretravel vaccination and infection prevention and control recommendations among pediatricians.

The predictive value of anti-Müllerian hormone for natural conception leading to live birth in subfertile couples.

RESEARCH QUESTION: What is the predictive value of serum anti-Müllerian hormone (AMH) level for natural conception and its clinical effect on subfertile couples? DESIGN: A retrospective cohort of ovulatory women seeking fertility consultation in a private fertility clinic. Couples who had an immediate indication for IVF were excluded. All natural conceptions leading to live birth before the start of assisted reproductive technology were followed within 12 months of the initial consultation. A prediction model was developed by updating the Hunault model with serum AMH to predict the probabilities of achieving a natural conception leading to live birth. RESULTS: A total of 325 couples were included in the final analysis. The estimated cumulative proability of achieving natural conception leading to live birth within 12 months was 20.9% (95% CI 12.9% to 28.2%). The categorical net reclassification improvement of AMH is 7.6%. For couples with a predicted chance of natural conception changed from poor (<30%) by the reference model to good (≥30%) by the updated model, the cumulative natural conception rate leading to live birth was 52.0%. For couples who had predicted chance of natural conception changed from good to poor by the updated model, the rate was 18.9%. CONCLUSIONS: The addition of serum AMH to the routine fertility work-up may improve prognosis-based treatment policy and help to prevent unnecessary costs and stress for couples. Prospective validation of the updated model with AMH is required before clinical application.

MomsTalkShots, tailored educational app, improves vaccine attitudes: a randomized controlled trial.

BACKGROUND: Many pregnant women and parents have concerns about vaccines. This analysis examined the impact of MomsTalkShots, an individually tailored educational application, on vaccine attitudes of pregnant women and mothers. METHODS: MomsTalkShots was the patient-level component of a multi-level intervention to improve maternal and infant vaccine uptake that also included provider- and practice-level interventions. The impact of these interventions was studied using a two-by-two factorial design, randomizing at both the patient- and the practice-level. Study staff recruited pregnant women from a diverse set of prenatal care practices in Colorado and Georgia between June 2017 and July 2018. All participants (n = 2087) received a baseline survey of maternal and infant vaccine intentions and attitudes, and two follow-up surveys at least 1 month and 1 year after their infant's birth, respectively. Half of participants (n = 1041) were randomly assigned to receive educational videos through MomsTalkShots, algorithmically tailored to their vaccine intentions, attitudes, and demographics. Since the practice/provider intervention did not appear impactful, this analysis focused on MomsTalkShots regardless of the practice/provider intervention. RESULTS: By 1 month post-birth, MomsTalkShots increased perceived risk of maternal influenza disease (61% among MomsTalkShots recipients vs 55% among controls; Odds Ratio: 1.61, 95% Confidence Interval: 1.23-2.09), confidence in influenza vaccine efficacy (73% vs 63%; OR: 1.97, 95%CI: 1.47-2.65), and perceived vaccine knowledge (55% vs 48%; OR: 1.39, 95%CI: 1.13-1.72). Among those intending not to vaccinate at baseline, MomsTalkShots increased perceived risk of maternal influenza disease (38% vs 32%; OR: 2.07, 95%CI: 1.15-3.71) and confidence in influenza vaccine efficacy (44% vs 28%; OR: 2.62, 95%CI: 1.46-4.69). By 1 year post-birth, MomsTalkShots increased perceived vaccine knowledge (62% vs 50%; OR: 1.74, 95%CI: 1.36-2.24) and trust in vaccine information from obstetricians and pediatricians (64% vs 55%; OR: 1.53, 95%CI: 1.17-2.00). Among those uncertain about vaccinating at baseline, MomsTalkShots increased perceived vaccine knowledge (47% vs 12%; OR: 6.89, 95%CI: 1.52-31.25) and reduced infant vaccine safety concerns (71% vs 91%; OR: 0.24, 95%CI: 0.06-0.98). CONCLUSIONS: MomsTalkShots improved pregnant women's and mothers' knowledge and perceptions of maternal and infant vaccines and the diseases they prevent, and offers a scalable tool to address vaccine hesitancy. TRIAL REGISTRATION: Registered at Clinicaltrials.gov on 13/09/2016 (registration number: NCT02898688).

Effectiveness of Hyaluronic Acid Gel and Intrauterine Devices in Prevention of Intrauterine Adhesions after Hysteroscopic Adhesiolysis in Infertile Women.

STUDY OBJECTIVE: To compare the recurrence rate, post-treatment American Fertility Society (AFS) score, ongoing pregnancy rate, and endometrial thickness of 3 secondary prevention therapies in preventing recurrent intrauterine adhesions (IUAs) and increasing pregnancy rates in infertile women after hysteroscopic adhesiolysis. DESIGN: A retrospective study. SETTING: A private fertility hospital. PATIENTS: A total of 200 consecutive infertile women, with the desire to have a baby and were diagnosed as having IUAs detected by hysterosalpingogram, who underwent hysteroscopic adhesiolysis for IUAs from January, 2018 to May, 2020. INTERVENTIONS: Women who underwent hysteroscopic adhesiolysis received hormone therapy, and one of the 3 secondary preventions: hyaluronic acid (HA) gel alone, intrauterine devices (IUDs) alone, or HA gel + IUD. MEASUREMENTS AND MAIN RESULTS: Of the 200 women included in the final analysis, 121 received HA alone, 59 were treated with IUD alone, and 20 received HA gel + IUD combination. The mean post-treatment AFS score for IUAs was significantly lower in the HA gel + IUD group than the HA alone or the IUD alone groups (adjusted p = .01 and p = .02, respectively). Multivariable analysis revealed a significantly lower recurrence rate in the women after treatment with HA gel + IUD than HA alone (adjusted odds ratio, 0.19; 95% credible interval [CreI], 0.03-0.88). Women treated with HA gel + IUD also had reduced post-treatment AFS scores compared with HA alone (ß coefficients, -0.83; 95% CreI, -1.64 to -0.01). For ongoing pregnancy rates after in vitro fertilization, the adjusted odds ratio for HA gel + IUD vs HA alone was 2.03 (95% CreI, 0.44-11.00) and for IUD alone vs HA alone was 1.13 (95% CreI, 0.41-3.29), indicating nonsignificant differences. There were no differences observed in endometrial thickness on the day of embryo transfer among the 3 groups. CONCLUSION: The investigation of the primary outcome in reducing the recurrence rate IUA after treatment demonstrated that a combination of HA gel + IUD provides greater prevention of recurrent IUAs and may decrease post-treatment AFS scores for infertile women undergoing hysteroscopic adhesiolysis. However, for the secondary outcome of increasing pregnancy rates, there was no improvement in the ongoing pregnancy rates after in vitro fertilization.

The Risk of Resurgence in Vaccine-Preventable Infections Due to Coronavirus Disease 2019-Related Gaps in Immunization.

Nationally, immunization delivery has decreased significantly during the coronavirus disease 2019 (COVID-19) pandemic. Internationally, >60 national vaccine programs have been disrupted or suspended. As a result of these immunization declines, the global community is at risk for a resurgence in vaccine-preventable infections including measles, pertussis, and polio-all highly contagious diseases that result in significant morbidity and mortality in children. Measles outbreaks have already occurred in many countries that suspended their vaccination programs. Outbreaks in the United States are likely to occur when social distancing stops and children return to school. Healthcare providers have acted quickly to institute multiple risk mitigation strategies to restore vaccine administration. However, childhood immunization rates remain below pre-COVID-19 levels. Partnerships between healthcare providers, community leaders, and local, state, regional, and national public health departments are needed to reassure families that vaccine delivery during COVID-19 is safe and to identify and catch up those children who are underimmunized.