Cardiac manifestations and outcomes of COVID-19 vaccine-associated myocarditis in the young in the USA: longitudinal results from the Myocarditis After COVID Vaccination (MACiV) multicenter study.

Background: We aimed to study the clinical characteristics, myocardial injury, and longitudinal outcomes of COVID-19 vaccine-associated myocarditis (C-VAM). Methods: In this longitudinal retrospective observational cohort multicenter study across 38 hospitals in the United States, 333 patients with C-VAM were compared with 100 patients with multisystem inflammatory syndrome in children (MIS-C). We included patients ≤30 years of age with a clinical diagnosis of acute myocarditis after COVID-19 vaccination based on clinical presentation, abnormal biomarkers and/or cardiovascular imaging findings. Demographics, past medical history, hospital course, biochemistry results, cardiovascular imaging, and follow-up information from April 2021 to November 2022 were collected. The primary outcome was presence of myocardial injury as evidenced by late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) imaging. Findings: Patients with C-VAM were predominantly white (67%) adolescent males (91%, 15.7 ± 2.8 years). Their initial clinical course was more likely to be mild (80% vs. 23%, p < 0.001) and cardiac dysfunction was less common (17% vs. 68%, p < 0.0001), compared to MIS-C. In contrast, LGE on CMR was more prevalent in C-VAM (82% vs. 16%, p < 0.001). The probability of LGE was higher in males (OR 3.28 [95% CI: 0.99, 10.6, p = 0.052]), in older patients (>15 years, OR 2.74 [95% CI: 1.28, 5.83, p = 0.009]) and when C-VAM occurred after the first or second dose as compared to the third dose of mRNA vaccine. Mid-term clinical outcomes of C-VAM at a median follow-up of 178 days (IQR 114-285 days) were reassuring. No cardiac deaths or heart transplantations were reported until the time of submission of this report. LGE persisted in 60% of the patients at follow up. Interpretation: Myocardial injury at initial presentation and its persistence at follow up, despite a mild initial course and favorable mid-term clinical outcome, warrants continued clinical surveillance and long-term studies in affected patients with C-VAM. Funding: The U.S. Food and Drug Administration.

Oral Health Status and Dental Services Utilisation Among a Vulnerable Sample of Pregnant Women.

INTRODUCTION AND AIMS: Oral health conditions during pregnancy can negatively impact both mother and fetus, highlighting the importance of maintaining dental care. In Canada, significant disparities exist between general and dental healthcare access, with limited evidence on oral health status and dental care utilisation among pregnant women. This study aimed to provide initial insights into self-perceived oral health status and dental utilisation patterns among a vulnerable sample of pregnant women in southwestern Ontario. METHODS: This cross-sectional study recruited a convenient sample of pregnant women referred to the Family Medicine and Obstetrics Clinic, serving those without a family physician. Data were collected using a self-administered questionnaire adapted from the Canadian Health Measure Survey, the Canadian Community Health Survey, and the Survey of Maternal Health. Andersen and Newman's framework for health service utilisation was used as the theoretical framework. Descriptive and univariable analyses were conducted, followed by a forward stepwise selection of variables with p-values < 0.1 from the univariable analyses. RESULTS: One-hundred-fifty patients were approached and 130 (86.7%) completed the questionnaire. Of these, 96 (73.9%) reported their oral health as good/excellent while 34 (26.2%) reported having poor/fair oral health. Education level and quality of life were the strongest predictors of oral health status. While 101 (77.7%) visited a dentist within the last 2 years, only 35 (26.9%) had a dental visit during pregnancy. Toothbrushing frequency was the main predictor of time since last dental visit, with no other predictive factors once toothbrushing was considered. CONCLUSION: The study sample showed relatively positive self-perceived oral health and dental visit patterns. However, the low rate of dental visits during pregnancy highlights the need for better integration of dental care into prenatal care. To ensure maternal and child health, pregnant women should be a high priority in policies aimed at improving access to dental care.

Practice Patterns of Cardiovascular Magnetic Resonance Use in the Diagnosis of Pediatric Myocarditis: A Survey-Based Study.

BACKGROUND: Cardiovascular magnetic resonance (CMR) is used to diagnose myocarditis in adults and children based on the original Lake Louise Criteria (LLC) and more recently the revised LLC. The major change included in the revised LLC was the incorporation of parametric mapping, which significantly increases the sensitivity and specificity of diagnosis. Subsequently, scientific statements have recommended the use of parametric mapping in the diagnosis of myocarditis in children. However, there are some challenges to parametric mapping that are unique to the pediatric population. Our goal is to characterize clinical CMR and parametric mapping practice patterns for diagnosis of myocarditis in pediatric centers. METHODS: The Cardiovascular Magnetic Resonance Evaluation in Return to Athletes for Myocarditis in COVID-19 and Immunization Consortium created a REDCap survey to evaluate clinical practice patterns for diagnosis of myocarditis in pediatrics. This survey was distributed to the Society for Cardiovascular Magnetic Resonance community. RESULTS: 59 responses from 51 centers were received, with only one response from each center being utilized. Only 35% of centers (37% of North America, 31% of international) reported using CMR routinely in all patients with a suspicion for myocarditis. Diagnostic uncertainty was noted as the most important reason for CMR, while cost was noted as the least important consideration. The majority of centers reported using the revised LLC (37/51, 72%) compared to original LLC (7/51, 14%) or a hybrid criteria (6/51, 12%). When looking at the use of parametric mapping, only 5/47 (11%) for T1 mapping and 11/49 (22%) for T2 mapping reported having scanner-specific pediatric normative data. CONCLUSION: Routine CMR imaging for diagnosis of myocarditis in pediatrics is infrequently performed at surveyed centers despite the focus on a group of non-invasive cardiac imagers. While the majority reported using parametric mapping, few centers reporting having pediatric scanner-specific normative data. This highlights an important gap in the utilization of CMR that may aid in the diagnosis of myocardial disease.

Analysis of apheresis outcomes in a cohort of Chilean patients treated with autologous stem cell transplantation: A single center real-world experience.

Adequate stem cell harvesting is required for autologous hematopoietic transplantation. In deficient mobilizer patients, the collection of stem cells can be challenging because of the impossibility of achieving satisfactory CD34 cell counts with GCSF + - chemotherapy. Plerixafor is a potent and expensive drug that promotes the release of stem cells from the medullary niche to the peripheral blood and allows satisfactory harvests. We performed a retrospective analysis of 370 patients with myeloma and lymphoma harvested at our institution. 99 % of patients achieved satisfactory apheresis using Plerixafor in 45 %. Satisfactory harvests were obtained in patients mobilized with GCSF or plerixafor. In patients who used plerixafor, it was necessary to perform fewer apheresis procedures (P = 0.05). In multivariate analysis, the only factor that predicted the need for plerixafor was the presence of less than 30,000 CD34 / ul on the day of apheresis (OR 0.3. p < 0.001). Since we adopted the plerixafor protocol guided by CD34 counts, the number of patients with harvest failure has decreased. In conclusion, the rational and standardized use of plerixafor favors satisfactory harvest in patients who require autologous transplantation in South-American patients.

MoEDAL Search in the CMS Beam Pipe for Magnetic Monopoles Produced via the Schwinger Effect.

We report on a search for magnetic monopoles (MMs) produced in ultraperipheral Pb-Pb collisions during Run 1 of the LHC. The beam pipe surrounding the interaction region of the CMS experiment was exposed to 184.07 µb^{-1} of Pb-Pb collisions at 2.76 TeV center-of-mass energy per collision in December 2011, before being removed in 2013. It was scanned by the MoEDAL experiment using a SQUID magnetometer to search for trapped MMs. No MM signal was observed. The two distinctive features of this search are the use of a trapping volume very close to the collision point and ultrahigh magnetic fields generated during the heavy-ion run that could produce MMs via the Schwinger effect. These two advantages allowed setting the first reliable, world-leading mass limits on MMs with high magnetic charge. In particular, the established limits are the strongest available in the range between 2 and 45 Dirac units, excluding MMs with masses of up to 80 GeV at a 95% confidence level.

Exploring the feasibility of linking historical air pollution data to the Christchurch Health and Development study: A birth cohort study in Aotearoa, New Zealand.

Spatial life course epidemiological approaches offer promise for prospectively examining the impacts of air pollution exposure on longer-term health outcomes, but existing research is limited. An essential aspect, often overlooked is the comprehensiveness of exposure data across the lifecourse. The primary objective was to meticulously reconstruct historical estimates of air pollution exposure to include prenatal exposure as well as annual exposure from birth to 10 years (1977-1987) for each cohort member. We linked these data from a birth cohort of 1,265 individuals, born in Aotearoa/New Zealand in mid-1977 and studied to age 40, to historical air pollution data to create estimates of exposure from birth to 10 years (1977-1987). Improvements in air quality over time were found. However, outcomes varied by demographic and socioeconomic factors. Future research should examine how inequitable air pollution exposure is related to health outcomes over the life course.

Intra-organ cell specific mitochondrial quantitative interactomics.

Almost every organ consists of many cell types, each with its unique functions. Proteomes of these cell types are thus unique too. But it is reasonable to assume that interactome (inter and intra molecular interactions of proteins) are also distinct since protein interactions are what ultimately carry out the function. Podocytes and tubules are two cell types within kidney with vastly different functions: podocytes envelop the blood vessels in the glomerulus and act as filters while tubules are located downstream of the glomerulus and are responsible for reabsorption of important nutrients. It has been long known that for tubules mitochondria plays an important role as they require a lot of energy to carry out their functions. In podocytes, however, it has been assumed that mitochondria might not matter as much in both normal physiology and pathology1. Here we have applied quantitative cross-linking mass spectrometry to compare mitochondrial interactomes of tubules and podocytes using a transgenic mitochondrial tagging strategy to immunoprecipitate cell-specific mitochondria directly from whole kidney. We have uncovered that mitochondrial proteomes of these cell types are quite similar, although still showing unique features that correspond to known functions, such as high energy production through TCA cycle in tubules and requirements for detoxification in podocytes which are on the frontline of filtration where they encounter toxic compounds and therefore, as a non-renewing cell type they must have ways to protect themselves from cellular toxicity. But we gained much deeper insight with the interactomics data. We were able to find pathways differentially regulated in podocytes and tubules based on changing cross-link levels and not just protein levels. Among these pathways are betaine metabolism, lysine degradation, and many others. We have also demonstrated how quantitative interactomics could be used to detect different activity levels of an enzyme even when protein abundances of it are the same between cell types. We have validated this finding with an orthogonal activity assay. Overall, this work presents a new view of mitochondrial biology for two important, but functionally distinct, cell types within the mouse kidney showing both similarities and unique features. This data can continue to be explored to find new aspects of mitochondrial biology, especially in podocytes, where mitochondria has been understudied. In the future this methodology can also be applied to other organs to uncover differences in the function of cell types.

Rural-Urban Divide in the Prevalence and Correlates of Overweight and Obesity Among Women of Reproductive Age in Nigeria: A Multilevel Analysis of Repeated Cross-Sectional Data.

We examined rural and urban prevalence and correlates of overweight/obesity among women of reproductive age using survey data from Nigeria. Overweight and obesity prevalence increased from 16.1% and 6.1% in 2008 to 18.2% and 10.0% in 2018, while underweight prevalence consistently averaged at 12%. Regardless of the residential setting, age, marital status, education, occupation, wealth, and year were associated with higher risk of overweight/obesity, whereas breastfeeding showed a protective effect. Unique risk factors for overweight/obesity in urban areas were higher parity and female-headed households, while ethnicity, media exposure, and state of residence were unique risk factors in rural areas.

Prevalence and predictors of cigarette smoking among people with HIV in Western Jamaica.

With highly active antiretroviral therapy, HIV infection has become a treatable chronic disease. However, modifiable risk factors such as cigarette smoking continue to impact the morbidity and mortality of people with HIV (PWH). We assessed the prevalence and factors associated with cigarette smoking and motivation to quit among PWH in Western Jamaica. A cross-sectional study was conducted in which 392 adults seeking HIV care at health facilities in Western Jamaica completed an interviewer-administered questionnaire. Current smoking prevalence among participants was 17.4%. Current smoking was significantly associated with being male (OR = 2.99), non-Christian/non-Rastafarian (OR = 2.34), living or working with another smoker (aOR =1.86), being moderate to severely depressed (OR = 3.24), having an alcohol drinking problem (OR = 1.84), and never being asked by a healthcare provider if they smoked (OR = 3.24). Among the PWH who currently smoke, 36.7% are moderately to highly dependent on nicotine. One-third of people who smoke (33.8%) started smoking for the first time after HIV diagnosis, while 66.2% initiated smoking before; 88% were willing to quit smoking. These findings provide baseline information for designing and implementing a comprehensive smoking cessation program that considers the needs of PWH in Jamaica, with the potential of becoming a replicable model for other HIV-specialized healthcare settings in the Caribbean.

Patient information leaflets for placebo-controlled surgical trials: a review of current practice and recommendations for developers.

INTRODUCTION: Informed consent for participation in an RCT is an important ethical and legal requirement. In placebo surgical trials, further issues are raised, and to date, this has not been explored. Patient information leaflets (PILs) are a core component of the informed consent process. This study aimed to investigate the key content of PILs for recently completed placebo-controlled trials of invasive procedures, including surgery, to highlight areas of good practice, identify gaps in information provision for trials of this type and provide recommendations for practice. METHODS: PILs were sought from trials included in a recent systematic review of placebo-controlled trials of invasive procedures, including surgery. Trial characteristics and data on surgical and placebo interventions under evaluation were extracted. Directed content analysis was applied, informed by published regulatory and good practice guidance on PIL content and existing research on placebo-controlled surgical trials. Results were analysed using descriptive statistics and presented as a narrative summary. RESULTS: Of the 62 eligible RCTs, authors of 59 trials were contactable and 14 PILs were received for analysis. At least 50% of all PILs included content on general trial design. Explanations of how the placebo differs or is similar to the surgical intervention (i.e. fidelity) were reported in 6 (43%) of the included PILs. Over half (57%) of the PILs included information on the potential therapeutic benefits of the surgical intervention. One (7%) included information on potential indirect therapeutic benefits from invasive components of the placebo. Five (36%) presented the known risks of the placebo intervention, whilst 8 (57%) presented information on the known risks of the surgical intervention. A range of terms was used across the PILs to describe the placebo component, including 'control', 'mock' and 'sham'. CONCLUSION: Developers of PILs for placebo-controlled surgical trials should carefully consider the use of language (e.g. sham, mock), be explicit about how the placebo differs (or is similar) to the surgical intervention and provide balanced presentations of potential benefits and risks of the surgical intervention separately from the placebo. Further research is required to determine optimal approaches to design and deliver this information for these trials.

Exploring the existence, strength, and independence of relative age and maturation selection biases: a case study in Gaelic football talent development programmes.

BACKGROUND: Biological maturity and relative age player selection biases are well documented in youth sports. However, there has been limited examination of the relationship between these biases. AIM: This study investigated the presence, strength, and independence of relative age and biological maturity selection biases in Gaelic football. SUBJECTS AND METHODS: A total of 247 male players from U14 to U16, from two talent academies were assessed for relative age (decimal age (DA)) and biological maturity (discrepancy between biological and chronological age (BA-CA)). RESULTS: Relative age effects (RAE) were observed in the U14 (DA = 0.62, d = 0.40) and U15 squads (DA = 0.57. d = 0.26) only. A bias towards advanced maturity status was present at U14 (BA-CA = 0.60, d = 0.83), U15 (BA-CA = 0.78, d = 0.89), and U16 (BA-CA, d = 1.01). There was a trivial (U14, r(83) = -0.210; U15, r(88) = 0.060) and low (U16, r(76) = 0.352) correlation between relative age and maturity status. CONCLUSION: Substantial maturity selection biases and, to a lesser degree, relative age biases are evident in youth Gaelic football. Critically, these biases are independent constructs. Coaches and policy makers should be educated on the distinct influences of relative age and maturation, and on strategies to address these biases.

Obesity Predisposes Anthracycline-Treated Survivors of Childhood and Adolescent Cancers to Subclinical Cardiac Dysfunction.

Anthracyclines are effective chemotherapeutics used in approximately 60% of pediatric cancer cases but have a well-documented risk of cardiotoxicity. Existing cardiotoxicity risk calculators do not include cardiovascular risk factors present at the time of diagnosis. The goal of this study is to leverage the advanced sensitivity of strain echocardiography to identify pre-existing risk factors for early subclinical cardiac dysfunction among anthracycline-exposed pediatric patients. We identified 115 pediatric patients with cancer who were treated with an anthracycline between 2013 and 2019. Peak longitudinal left ventricular strain was retroactively calculated on 495 surveillance echocardiograms via the TOMTEC AutoSTRAIN software. Cox proportional hazards models were employed to identify risk factors for abnormal longitudinal strain (> - 16%) following anthracycline treatment. High anthracycline dose (≥ 250 mg/m2 doxorubicin equivalents) and obesity at the time of diagnosis (BMI > 95th percentile-for-age) were both significant predictors of abnormal strain with hazard ratios of 2.79, 95% CI (1.07-7.25), and 3.85, 95% CI (1.42-10.48), respectively. Among pediatric cancer survivors, patients who are obese at the time of diagnosis are at an increased risk of sub-clinical cardiac dysfunction following anthracycline exposure. Future studies should explore the incidence of symptomatic cardiomyopathy 10-15 years post-treatment among patients with early subclinical cardiac dysfunction.

Days alive and out of hospital for children born with single-ventricle heart disease.

BACKGROUND: This study describes the illness burden in the first year of life for children with single-ventricle heart disease, using the metric of days alive and out of hospital to characterize morbidity and mortality. METHODS: This is a retrospective single-centre study of single-ventricle patients born between 2005 and 2021 who had their initial operation performed at our institution. Patient demographics, anatomical details, and hospitalizations were extracted from our institutional single-ventricle database. Days alive and out of hospital were calculated by subtracting the number of days hospitalized from number of days alive during the first year of life. A multivariable linear regression with stepwise variable selection was used to determine independent risk factors associated with fewer days alive and out of hospital. RESULTS: In total, 437 patients were included. Overall median number of days alive and out of hospital in the first year of life for single-ventricle patients was 278 days (interquartile range 157-319 days). In a multivariable analysis, low birth weight (<2.5kg) (b = -37.55, p = 0.01), presence of a dominant right ventricle (b = -31.05, p = 0.01), moderate-severe dominant atrioventricular valve regurgitation at birth (b = -37.65, p < 0.05), index hybrid Norwood operation (b = -138.73, p < 0.01), or index heart transplant (b = -158.41, p < 0.01) were all independently associated with fewer days alive and out of hospital. CONCLUSIONS: Children with single-ventricle heart defects have significant illness burden in the first year of life. Identifying risk factors associated with fewer days alive and out of hospital may aid in counselling families regarding expectations and patient prognosis.

Measures of performance and proficiency in robotic assisted surgery: a systematic review.

Robotic assisted surgery (RAS) has seen a global rise in adoption. Despite this, there is not a standardised training curricula nor a standardised measure of performance. We performed a systematic review across the surgical specialties in RAS and evaluated tools used to assess surgeons' technical performance. Using the PRISMA 2020 guidelines, Pubmed, Embase and the Cochrane Library were searched systematically for full texts published on or after January 2020-January 2022. Observational studies and RCTs were included; review articles and systematic reviews were excluded. The papers' quality and bias score were assessed using the Newcastle Ottawa Score for the observational studies and Cochrane Risk Tool for the RCTs. The initial search yielded 1189 papers of which 72 fit the eligibility criteria. 27 unique performance metrics were identified. Global assessments were the most common tool of assessment (n = 13); the most used was GEARS (Global Evaluative Assessment of Robotic Skills). 11 metrics (42%) were objective tools of performance. Automated performance metrics (APMs) were the most widely used objective metrics whilst the remaining (n = 15, 58%) were subjective. The results demonstrate variation in tools used to assess technical performance in RAS. A large proportion of the metrics are subjective measures which increases the risk of bias amongst users. A standardised objective metric which measures all domains of technical performance from global to cognitive is required. The metric should be applicable to all RAS procedures and easily implementable. Automated performance metrics (APMs) have demonstrated promise in their wide use of accurate measures.

Treatment with PB125® Increases Femoral Long Bone Strength in 15-Month-Old Female Hartley Guinea Pigs.

Nuclear factor-erythroid 2-related factor-2 (Nrf2) is a transcription factor that serves as a master regulator of anti-inflammatory agents, phase I xenobiotic, and phase II antioxidant enzymes, all of which provide a cytoprotective role during disease progression. We hypothesized that oral administration of a purported phytochemical Nrf2-activator, PB125®, would increase long bone strength in aging Hartley guinea pigs, a model prone to musculoskeletal decline. Male (N = 56) and female (N = 56) guinea pigs were randomly assigned to receive daily oral treatment with either PB125® or vehicle control. Animals were treated for a consecutive 3-months (starting at 2-months of age) or 10-months (starting at 5-months of age) and sacrificed at 5-months or 15-months of age, respectively. Outcome measures included: (1) ANY-maze™ enclosure monitoring, (2) quantitative microcomputed tomography, and (3) biomechanical testing. Treatment with PB125® for 10 months resulted in increased long bone strength as determined by ultimate bending stress in female Hartley guinea pigs. In control groups, increasing age resulted in significant effects on geometric and structural properties of long bones, as well as a trending increase in ultimate bending stress. Furthermore, both age and sex had a significant effect on the geometric properties of both cortical and trabecular bone. Collectively, this work suggests that this nutraceutical may serve as a promising target and preventive measure in managing the decline in bone mass and quality documented in aging patients. Auxiliary to this main goal, this work also capitalized upon 5 and 15-month-old male and female animals in the control group to characterize age- and sex-specific differences on long bone geometric, structural, and material properties in this animal model.

Construction and validation of the area level deprivation index for health research: A methodological study based on Nepal Demographic and Health Survey.

Area-level factors may partly explain the heterogeneity in risk factors and disease distribution. Yet, there are a limited number of studies that focus on the development and validation of the area level construct and are primarily from high-income countries. The main objective of the study is to provide a methodological approach to construct and validate the area level construct, the Area Level Deprivation Index in low resource setting. A total of 14652 individuals from 11,203 households within 383 clusters (or areas) were selected from 2016-Nepal Demographic and Health survey. The index development involved sequential steps that included identification and screening of variables, variable reduction and extraction of the factors, and assessment of reliability and validity. Variables that could explain the underlying latent structure of area-level deprivation were selected from the dataset. These variables included: housing structure, household assets, and availability and accessibility of physical infrastructures such as roads, health care facilities, nearby towns, and geographic terrain. Initially, 26-variables were selected for the index development. A unifactorial model with 15-variables had the best fit to represent the underlying structure for area-level deprivation evidencing strong internal consistency (Cronbach's alpha = 0.93). Standardized scores for index ranged from 58.0 to 140.0, with higher scores signifying greater area-level deprivation. The newly constructed index showed relatively strong criterion validity with multi-dimensional poverty index (Pearson's correlation coefficient = 0.77) and relatively strong construct validity (Comparative Fit Index = 0.96; Tucker-Lewis Index = 0.94; standardized root mean square residual = 0.05; Root mean square error of approximation = 0.079). The factor structure was relatively consistent across different administrative regions. Area level deprivation index was constructed, and its validity and reliability was assessed. The index provides an opportunity to explore the area-level influence on disease outcome and health disparity.

Interfacing Whole Cell Biocatalysis with a Biocompatible Pictet-Spengler Reaction for One-Pot Syntheses of Tetrahydroisoquinolines and Tryptolines.

Biocatalytic processes are highly selective and specific. However, their utility is limited by the comparatively narrow scope of enzyme-catalysed transformations. To expand product scope, we are developing biocompatible processes that combine biocatalytic reactions with chemo-catalysis in single-flask processes. Here, we show that a chemocatalysed Pictet-Spengler annulation can be interfaced with biocatalysed alcohol oxidation. This two-step, one-pot cascade reaction converts tyramine and aliphatic alcohols to tetrahydroisoquinoline alkaloids in aqueous buffer at mild pH. Tryptamine derivatives are also efficiently converted to tryptolines. Optimization of stoichiometry, pH, reaction time, and whole-cell catalyst deliver the tetrahydroisouinolines and tryptolines in >90 % and >40 % isolated yield, respectively, with excellent regioselectivity.

Unfavourable beliefs about oral health and safety of dental care during pregnancy: a systematic review.

BACKGROUND: Oral conditions such as gingivitis and periodontitis are correlated with adverse pregnancy outcomes such as preeclampsia, preterm birth and low birth weight. Oral health-related unfavourable beliefs can have negative influences on oral health behaviours including hesitation in accessing preventative dental treatments and dental service utilization. The objective of this systematic review was to examine unfavourable beliefs that expectant or new mothers frequently hold about oral health and the safety of dental care during pregnancy. METHODS: An electronic database search on PubMed, Scopus, CINAHL, and MEDLINE (Ovid) followed by forward and backward citation tracing of the included studies was conducted. All English primary studies regardless of the year of publication were independently screened by two reviewers to identify studies addressing unfavourable beliefs about oral health and dental care during pregnancy. The CLARITY tool was applied to assess the risk of bias in the included studies. RESULTS: Out of a total of 5766 records, 39 quantitative and six qualitative studies met the inclusion criteria. The commonly held unfavourable beliefs were regarding the safety of dental services utilization and dental treatment procedures, the adverse impacts of pregnancy on oral health, and oral hygiene necessity during pregnancy. The most discussed unfavourable beliefs included "pregnant women lose their teeth because of pregnancy" (n = 18), "dental treatments are not safe and harm the fetus" (n = 17), and "the developing baby absorbs calcium from the mother's teeth" (n = 14). CONCLUSIONS: Unfavourable beliefs about oral health and dental care utilization are common among pregnant women and new mothers. The literature suggests that a low level of oral health knowledge and seeking information from social networks can contribute to such beliefs. This has implications for health promotion.

EV-301 long-term outcomes: 24-month findings from the phase III trial of enfortumab vedotin versus chemotherapy in patients with previously treated advanced urothelial carcinoma.

INTRODUCTION: This exploratory analysis evaluated efficacy and safety data for enfortumab vedotin versus chemotherapy over a median follow-up of ∼2 years from EV-301. MATERIALS AND METHODS: Patients with locally advanced/metastatic urothelial carcinoma with prior platinum-containing chemotherapy and disease progression during/after programmed cell death protein 1/ligand 1 inhibitor treatment were randomized to enfortumab vedotin or chemotherapy (docetaxel, paclitaxel, vinflunine). Endpoints were overall survival (primary), progression-free survival (PFS), objective response, and safety. RESULTS: In total, 608 patients were included (enfortumab vedotin, n = 301; chemotherapy, n = 307). With a median follow-up of 23.75 months, 444 deaths had occurred (enfortumab vedotin, n = 207; chemotherapy, n = 237). Risk of death was reduced by 30% with enfortumab vedotin versus chemotherapy [hazard ratio (HR) 0.70 (95% confidence interval [CI] 0.58-0.85); one-sided, log-rank P = 0.00015]; PFS improved with enfortumab vedotin [HR 0.63 (95% CI 0.53-0.76); one-sided, log-rank P < 0.00001]. Treatment-related adverse event rates were 93.9% for enfortumab vedotin and 91.8% for chemotherapy; grade ≥ 3 event rates were 52.4% and 50.5%, respectively. Grade ≥ 3 treatment-related decreased neutrophil count (14.1% versus 6.1%), decreased white blood cell count (7.2% versus 1.4%), and anemia (7.9% versus 2.7%) were more common with chemotherapy versus enfortumab vedotin; maculopapular rash (7.4% versus 0%), fatigue (6.8% versus 4.5%), and peripheral sensory neuropathy (5.1% versus 2.1%) were more common with enfortumab vedotin. Of special interest adverse events, treatment-related skin reactions occurred in 47.3% of patients receiving enfortumab vedotin and 15.8% of patients receiving chemotherapy; peripheral neuropathy occurred in 48.0% versus 31.6%, respectively, and hyperglycemia in 6.8% versus 0.3%. CONCLUSIONS: After a median follow-up of ∼2 years, enfortumab vedotin maintained clinically meaningful overall survival benefit versus chemotherapy, consistent with findings from the EV-301 primary analysis; PFS and overall response benefit remained consistent. Adverse events were manageable; no new safety signals were observed.