Association Between Antibiotic Duration and Recurrence of Urinary Tract Infection in the Neonatal Critical Care Unit.

OBJECTIVES: Urinary tract infection (UTI) is the most common bacterial infection in infants. Current practice guidelines suggest a treatment duration of 7 to 14 days. Suboptimal therapy may increase the risk for recurrent UTIs leading to renal scarring and possibly chronic kidney disease. The primary objective is to evaluate the duration of therapy for UTIs and its association with the incidence of recurrent UTIs in a neonatal intensive care unit (NICU). The secondary objectives are to identify the risk factors and the most common organisms for recurrent UTIs. METHODS: Patients were identified via the diagnosis codes for UTIs and were included if admitted to the NICU and if they received antibiotics prior to hospital discharge. Patients were divided into 2 groups: antibiotic treatment for 7 days or fewer and antibiotic treatment for greater than 7 days. RESULTS: Eighty-six infants were included in the study. Twenty-six patients received antibiotics for 7 days or fewer, and 60 for more than 7 days. In the study, the median birth weight was 977 g and the median gestational age was 27.6 weeks. There was no significant difference in the rate of recurrent UTIs between the 2 groups (p = 0.66). However, in the subgroup analysis, the incidence was higher for patients receiving antibiotic therapy for fewer than 7 days versus 7 days (p = 0.03). CONCLUSION: There was no difference in recurrence of UTI between treatment groups (≤7 days versus >7 days), and recurrence was seen in a higher percentage of patients with a urinary tract anomaly.

Depression among currently married ever pregnant adolescents in Uttar Pradesh and Bihar: Evidence from understanding the lives of adolescents and young adults (UDAYA) survey, India.

Background: Depression is a major public health concern among Indian adolescents. Pre- and post-natal depression can often alter fetal development and have negative consequences on the physical and mental health of the mother. This paper aims to draw attention to the prevalence of depression and its correlates among currently married, ever-pregnant adolescents from two Indian States, i.e. Uttar Pradesh and Bihar. Methods: This study utilizes data from a subsample (n = 3116) of the prospective cohort study Understanding the Lives of Adolescents and Young Adults (UDAYA) among 10 to 19 year-old adolescents. Bivariate analysis was performed to assess the prevalence of depression by sociodemographic and behavioral characteristics. To further access the predictors associated with depression a logistic regression model was applied. Results: Around one-tenth (9%) of pregnant adolescents had depression. Regression analysis indicated that substance use, religion, autonomy, considering attempting suicide, premarital relationship, violence, dowry, adverse pregnancy outcome, menstrual problem, and parental pressure for the child immediately after marriage were significantly associated with depression. Conclusions: This study confirms the pre-existing annotation that teen pregnancy is linked with depression. Findings indicate that Adolescent mothers experiencing violence, and a history of adverse pregnancy outcomes are at increased risk of developing depression. These study findings call for an urgent need to address depression among adolescent mothers.

Therapeutic targeting of cellular senescence in diabetic macular edema: preclinical and phase 1 trial results.

Compromised vascular endothelial barrier function is a salient feature of diabetic complications such as sight-threatening diabetic macular edema (DME). Current standards of care for DME manage aspects of the disease, but require frequent intravitreal administration and are poorly effective in large subsets of patients. Here we provide evidence that an elevated burden of senescent cells in the retina triggers cardinal features of DME pathology and conduct an initial test of senolytic therapy in patients with DME. In cell culture models, sustained hyperglycemia provoked cellular senescence in subsets of vascular endothelial cells displaying perturbed transendothelial junctions associated with poor barrier function and leading to micro-inflammation. Pharmacological elimination of senescent cells in a mouse model of DME reduces diabetes-induced retinal vascular leakage and preserves retinal function. We then conducted a phase 1 single ascending dose safety study of UBX1325 (foselutoclax), a senolytic small-molecule inhibitor of BCL-xL, in patients with advanced DME for whom anti-vascular endothelial growth factor therapy was no longer considered beneficial. The primary objective of assessment of safety and tolerability of UBX1325 was achieved. Collectively, our data suggest that therapeutic targeting of senescent cells in the diabetic retina with a BCL-xL inhibitor may provide a long-lasting, disease-modifying intervention for DME. This hypothesis will need to be verified in larger clinical trials. ClinicalTrials.gov identifier: NCT04537884 .

Evaluating the relationship between ciprofloxacin prescription and non-susceptibility in Salmonella Typhi in Blantyre, Malawi: an observational study.

BACKGROUND: Ciprofloxacin is the first-line drug for treating typhoid fever in many countries in Africa with a high disease burden, but the emergence of non-susceptibility poses a challenge to public health programmes. Through enhanced surveillance as part of vaccine evaluation, we investigated the occurrence and potential determinants of ciprofloxacin non-susceptibility in Blantyre, Malawi. METHODS: We conducted systematic surveillance of typhoid fever cases and antibiotic prescription in two health centres in Blantyre, Malawi, between Oct 1, 2016, and Oct 31, 2019, as part of the STRATAA and TyVAC studies. In addition, blood cultures were taken from eligible patients presenting at Queen Elizabeth Central Hospital, Blantyre, as part of routine diagnosis. Inclusion criteria were measured or reported fever, or clinical suspicion of sepsis. Microbiologically, we identified Salmonella enterica serotype Typhi (S Typhi) isolates with a ciprofloxacin non-susceptible phenotype from blood cultures, and used whole-genome sequencing to identify drug-resistance mutations and phylogenetic relationships. We constructed generalised linear regression models to investigate associations between the number of ciprofloxacin prescriptions given per month to study participants and the proportion of S Typhi isolates with quinolone resistance-determining region (QRDR) mutations in the following month. FINDINGS: From 46 989 blood cultures from Queen Elizabeth Central Hospital, 502 S Typhi isolates were obtained, 30 (6%) of which had either decreased ciprofloxacin susceptibility, or ciprofloxacin resistance. From 11 295 blood cultures from STRATAA and TyVAC studies, 241 microbiologically confirmed cases of typhoid fever were identified, and 198 isolates from 195 participants sequenced (mean age 12·8 years [SD 10·2], 53% female, 47% male). Between Oct 1, 2016, and Aug 31, 2019, of 177 typhoid fever cases confirmed by whole-genome sequencing, four (2%) were caused by S Typhi with QRDR mutations, compared with six (33%) of 18 cases between Sept 1 and Oct 31, 2019. This increase was associated with a preceding spike in ciprofloxacin prescriptions. Every additional prescription of ciprofloxacin given to study participants in the preceding month was associated with a 4·2% increase (95% CI 1·8-7·0) in the relative risk of isolating S Typhi with a QRDR mutation (p=0·0008). Phylogenetic analysis showed that S Typhi isolates with QRDR mutations from September and October, 2019, belonged to two distinct subclades encoding two different QRDR mutations, and were closely related (4-10 single-nucleotide polymorphisms) to susceptible S Typhi endemic to Blantyre. INTERPRETATION: We postulate a causal relationship between increased ciprofloxacin prescriptions and an increase in fluoroquinolone non-susceptibility in S Typhi. Decreasing ciprofloxacin use by improving typhoid diagnostics, and reducing typhoid fever cases through the use of an efficacious vaccine, could help to limit the emergence of resistance. FUNDING: Wellcome Trust, Bill & Melinda Gates Foundation, and National Institute for Health and Care Research (UK).

Efficacy of typhoid conjugate vaccine: final analysis of a 4-year, phase 3, randomised controlled trial in Malawian children.

BACKGROUND: Randomised controlled trials of typhoid conjugate vaccines among children in Africa and Asia have shown high short-term efficacy. Data on the durability of protection beyond 2 years are sparse. We present the final analysis of a randomised controlled trial in Malawi, encompassing more than 4 years of follow-up, with the aim of investigating vaccine efficacy over time and by age group. METHODS: In this phase 3, double-blind, randomised controlled efficacy trial in Blantyre, Malawi, healthy children aged 9 months to 12 years were randomly assigned (1:1) by an unmasked statistician to receive a single dose of Vi polysaccharide conjugated to tetanus toxoid vaccine (Vi-TT) or meningococcal capsular group A conjugate (MenA) vaccine. Children had to have no previous history of typhoid vaccination and reside in the study areas for inclusion and were recruited from government schools and health centres. Participants, their parents or guardians, and the study team were masked to vaccine allocation. Nurses administering vaccines were unmasked. We did surveillance for febrile illness from vaccination until follow-up completion. The primary outcome was first occurrence of blood culture-confirmed typhoid fever. Eligible children who were randomly assigned and vaccinated were included in the intention-to-treat analyses. This trial is registered at ClinicalTrials.gov, NCT03299426. FINDINGS: Between Feb 21, 2018, and Sept 27, 2018, 28 130 children were vaccinated; 14 069 were assigned to receive Vi-TT and 14 061 to receive MenA. After a median follow-up of 4·3 years (IQR 4·2-4·5), 24 (39·7 cases per 100 000 person-years) children in the Vi-TT group and 110 (182·7 cases per 100 000 person-years) children in the MenA group were diagnosed with a first episode of blood culture-confirmed typhoid fever. In the intention-to-treat population, efficacy of Vi-TT was 78·3% (95% CI 66·3-86·1), and 163 (129-222) children needed to be vaccinated to prevent one case. Efficacies by age group were 70·6% (6·4-93·0) for children aged 9 months to 2 years; 79·6% (45·8-93·9) for children aged 2-4 years; and 79·3% (63·5-89·0) for children aged 5-12 years. INTERPRETATION: A single dose of Vi-TT is durably efficacious for at least 4 years among children aged 9 months to 12 years and shows efficacy in all age groups, including children younger than 2 years. These results support current WHO recommendations in typhoid-endemic areas for mass campaigns among children aged 9 months to 15 years, followed by routine introduction in the first 2 years of life. FUNDING: Bill & Melinda Gates Foundation.

Racial Disparities Among Predicted Bronchopulmonary Dysplasia Risk Outcomes in Premature Infants Born <30 Weeks Gestation.

Background and Objective: There is extensive literature to support eliminating race-based risk stratification. The National Institute of Child Health and Human Development (NICHD) calculator, used to predict risk of bronchopulmonary dysplasia (BPD), includes race as a variable. We sought to investigate how utilizing race in determination of risk for BPD may lead to inequitable care. Methods: The study included a retrospective cohort of infants born <30 weeks gestation between January 2016 and February 2022. The primary outcome was the difference in predictive risk of BPD for non-Hispanic Black compared to non-Hispanic White infants. The secondary outcome was the disparity in theoretical administration of post-natal corticosteroids when the calculator was applied to the cohort. Analysis included paired T-tests and Chi-Square. Results: Of the 273 infants studied, 154 were non-Hispanic Black (56%). There was no difference between the groups in gestation or respiratory support on day of life (DOL) 14 or 28. The predicted risk of moderate or severe BPD in non-Hispanic White babies was greater than non-Hispanic Black babies on both DOL 14 and 28 (p<0.01). When applied retrospectively to the cohort, the calculator resulted in differences in corticosteroid administration (risk >40%-non-Hispanic White 51.3% vs. non-Hispanic Black 35.7%, p=0.010; risk >50%-non-Hispanic White 42.9% vs. non-Hispanic Black 29.9%, p=0.026). Conclusion: When applied to our study cohort, the calculator resulted in a reduction in the predicted risk of BPD in non-Hispanic Black infants. If utilized to guide treatment, the calculator can potentially lead to disparities in care for non-Hispanic Black infants.

Neurally Adjusted Ventilatory Assist Versus Pressure Support Ventilation: A Comprehensive Review.

Mechanical ventilation serves as crucial life support for critically ill patients. Although it is life-saving prolonged ventilation carries risks and complications like barotrauma, Ventilator-associated pneumonia, sepsis, and many others. Optimizing patient-ventilator interactions and facilitating early weaning is necessary for improved intensive care unit (ICU) outcomes. Traditionally Pressure support ventilation (PSV) mode is widely used for weaning patients who are intubated and mechanically ventilated. Neurally adjusted ventilatory assist (NAVA) mode of the ventilator is an emerging ventilator mode that delivers pressure depending on the patient's respiratory drive, which in turn prevents over-inflation and improves the patient's ventilator interactions. Our article revises and compares the effectiveness of NAVA compared to PSV ventilation under different contexts. Overall we conclude that NAVA level of ventilation can be safely administered in a patient with acute respiratory failure, provided diaphragmatic paralysis is not considered. NAVA improves asynchrony index, wean-off time, and sleep quality and is associated with increased ventilator-free days. These results are based on small-scale studies with low power, and further studies are warranted in large-scale cohorts with more diverse populations to confirm these results.

Integration of transcriptomes of senescent cell models with multi-tissue patient samples reveals reduced COL6A3 as an inducer of senescence.

Senescent cells are a major contributor to age-dependent cardiovascular tissue dysfunction, but knowledge of their in vivo cell markers and tissue context is lacking. To reveal tissue-relevant senescence biology, we integrate the transcriptomes of 10 experimental senescence cell models with a 224 multi-tissue gene co-expression network based on RNA-seq data of seven tissues biopsies from ∼600 coronary artery disease (CAD) patients. We identify 56 senescence-associated modules, many enriched in CAD GWAS genes and correlated with cardiometabolic traits-which supports universality of senescence gene programs across tissues and in CAD. Cross-tissue network analyses reveal 86 candidate senescence-associated secretory phenotype (SASP) factors, including COL6A3. Experimental knockdown of COL6A3 induces transcriptional changes that overlap the majority of the experimental senescence models, with cell-cycle arrest linked to modulation of DREAM complex-targeted genes. We provide a transcriptomic resource for cellular senescence and identify candidate biomarkers, SASP factors, and potential drivers of senescence in human tissues.

Pediatric Dentists' and Guardians' Perceptions of Follow-Up Appointments After Dental Rehabilitation Under General Anesthesia.

Purpose: It has been suggested that follow-up visits for pediatric patients after full-mouth dental rehabilitation (FMDR) under general anesthesia (GA) are important to evaluate healing and restorative treatment, review oral hygiene instruction, provide nutritional counseling and address guardians' concerns. The purpose of this study was to evaluate pediatric dentists' current utilization of follow-up visits after GA and to evaluate pediatric dentists' and guardians' perceptions of their purpose and value. Methods: Three separate surveys were administered: (1) pediatric dentist survey, (2) guardian pre-appointment survey and (3) guardian post-appointment survey. The guardian surveys examined their perceptions of a follow-up visit before and after FMDR under GA. The pediatric dentist survey examined current utilization and perception of follow-up appointments. Results: Most clinicians (72 percent) reported scheduling a follow-up visit. Providers generally agreed that the post-operative appointments were important (69 percent). Of the guardians who attended the follow-up visit, 96.3 percent agreed that the post- operative visit was useful. Conclusion: Both pediatric dentists and guardians of patients undergoing FMDR under GA agreed that a follow-up visit after GA was valuable despite low complication rates.

Long-term trends of HIV/AIDS incidence in India: an application of joinpoint and age-period-cohort analyses: a gendered perspective.

Background: Monitoring the transmission patterns of human immunodeficiency virus (HIV) in a population is fundamental for identifying the key population and designing prevention interventions. In the present study, we aimed to estimate the gender disparities in HIV incidence and the age, period, and cohort effects on the incidence of HIV in India for identifying the predictors that might have led to changes in the last three decades. Data and methods: This study utilizes data from the Global Burden of Disease Study for the period 1990-2019. The joinpoint regression analysis was employed to identify the magnitude of the changes in age-standardized incidence rates (ASIRs) of HIV. The average annual percentage changes in the incidence were computed, and the age-period-cohort analysis was performed. Results: A decreasing trend in the overall estimates of age-standardized HIV incidence rates were observed in the period 1990-2019. The joinpoint regression analysis showed that the age-standardized incidence significantly declined from its peak in 1997 to 2019 (38.0 and 27.6 among males and females per 100,000 in 1997 to 5.4 and 4.6, respectively, in 2019). The APC was estimated to be 2.12 among males and 1.24 among females for the period 1990-2019. In recent years, although the gender gap in HIV incidence has reduced, females were observed to bear a proportionately higher burden of HIV incidence. Age effect showed a decline in HIV incidence by 91.1 and 70.1% among males and females aged between 15-19 years and 75-79 years. During the entire period from 1990-1994 to 2015-2019, the RR of HIV incidence decreased by 36.2 and 33.7% among males and females, respectively. Conclusion: India is experiencing a decline in new HIV infections in recent years. However, the decline is steeper for males than for females. Findings highlight the necessity of providing older women and young women at risk with effective HIV prevention. This study emphasizes the need for large-scale HIV primary prevention efforts for teenage girls and young women.

Forming the Perception of WIC Infant Feeding Recommendations: A Qualitative Study.

Nearly half of newborns in the United States are enrolled in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC). Promoting breastfeeding is a programmatic priority, although formula vouchers are provided for those who do not exclusively breastfeed. Previous literature suggests that participant perception of WIC's breastfeeding recommendations is a significant factor predicting breastfeeding initiation, duration, and exclusivity outcomes. However, little is known about how participants' perceptions of WIC's breastfeeding recommendations are formed. To address this knowledge gap, we conducted a qualitative pilot study in Nevada, interviewing 10 postpartum WIC mothers and 12 WIC staff who had interacted with participants regarding infant feeding. Results showed participants and staff reported various perceptions of what WIC recommends, the factors that contribute to these perceptions, and how these perceptions affect breastfeeding practices. Respondents also described that WIC has a negative legacy as the "free formula program," and that environmental factors, such as the recent formula recall, have had an impact on participants' infant feeding practices. More effective public campaigns and programmatic strategies are needed to target participants' prenatal self-efficacy and to communicate the availability of skilled lactation support in the early postpartum period to improve participants' perceptions of WIC's position on breastfeeding.

Protecting Low-Income Consumers in the Era of Digital Grocery Shopping: Implications for WIC Online Ordering.

The Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) is now expected to allow participants to redeem their food benefits online, i.e., via online ordering, rather than only in-store. However, it is unclear how this new benefit redemption model may impact participants' welfare since vendors may have an asymmetric information advantage compared with WIC customers. The WIC online ordering environment may also change the landscape for WIC vendors, which will eventually affect WIC participants. To protect WIC consumers' rights in the new online ordering model, policymakers need an appropriate legal and regulatory framework. This narrative review provides that framework by reviewing the literature, legal treatises, and reports on enforceable laws and regulations in the U.S. relevant to digital marketing. The results identify key issues that may arise with adopting WIC online ordering. This paper suggests "privacy, transparency, and fairness" as guiding principles to protect the welfare of WIC participants in WIC online ordering.

A Systematic Review of Marketing Practices Used in Online Grocery Shopping: Implications for WIC Online Ordering.

The Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) plans to allow participants to redeem their food package benefits online, i.e., online ordering. As grocery shopping online has become more common, companies have developed strategies to market food products to customers using online (or mobile) grocery shopping platforms. There is a significant knowledge gap in how these strategies may influence WIC participants who choose to shop for WIC foods online. This review examines the relevant literature to (1) identify food marketing strategies used in online grocery shopping platforms, (2) understand how these strategies influence consumer behavior and consumer diet, and (3) consider the implications for WIC participants. A total of 1862 references were identified from a systematic database search, of which 83 were included for full-text screening and 18 were included for data extraction and evidence synthesis. The included studies provide policymakers and other stakeholders involved in developing WIC online order processes with valuable information about the factors that shape healthy food choices in the online food retail environment. Findings indicate that some marketing interventions, such as nutrition labeling and food swaps, may encourage healthier food choices in the online environment and could potentially be tailored to reinforce WIC messaging about a healthy diet.

The burden of disease-specific multimorbidity among older adults in India and its states: evidence from LASI.

BACKGROUND: Around the world, advances in public health and changes in clinical interventions have resulted in increased life expectancy. Multimorbidity is becoming more of an issue, particularly in countries where the population is rapidly ageing. We aimed to determine the prevalence of multimorbidity and disease-specific multimorbidity and examine its association with demographic and socioeconomic characteristics among older adults in India and its states. METHODS: The individual data from the longitudinal ageing study in India (LASI) were used for this study, with 11 common chronic conditions among older adults aged 60 and above years (N = 31,464). Descriptive statistics were used to report the overall prevalence of multimorbidity and disease-specific burden of multimorbidity. Multinomial logistic regression has been used to explore the factors associated with multimorbidity. RESULTS: Prevalence of single morbidity was 30.3%, and multimorbidity was 32.1% among older people in India. Multimorbidity was higher among females and in urban areas and increased with age and among those living alone. Hypertension, arthritis and thyroid were highly prevalent among females and chronic lung diseases and stroke were highly prevalent among males. The older people in the state of Kerala had a high prevalence of multimorbidity (59.2%). Multimorbidity was found to be more likely in older age groups of 75-79 years (RR-1.69; CI: 1.53-1.87) and 80 years and above (RR-1.40; CI: 1.27-1.56) and in the Western (RR-2.16; CI: 1.90-2.44) and Southern regions (RR-2.89; CI: 2.57-3.24). Those who were living with a spouse (RR-1.60; CI: 1.15-2.23) were more likely to have multimorbidity. Disease-specific multimorbidity was high in chronic heart disease (91%) and low in angina (64.8%). CONCLUSIONS: The findings suggest that multimorbidity has a positive relationship with advancing age, and disease-specific burden of multimorbidity is higher among chronic heart patients. Comorbidity, especially among those who already have chronic heart disease, stroke, cholesterol or thyroid disorder can have severe consequences on physical functioning, therefore, disease-specific health management needs to be enhanced.

Evaluation of therapeutic radiographer contouring for magnetic resonance image guided online adaptive prostate radiotherapy.

BACKGROUND AND PURPOSE: The implementation of MRI-guided online adaptive radiotherapy has facilitated the extension of therapeutic radiographers' roles to include contouring, thus releasing the clinician from attending daily treatment. Following undergoing a specifically designed training programme, an online interobserver variability study was performed. MATERIALS AND METHODS: 117 images from six patients treated on a MR Linac were contoured online by either radiographer or clinician and the same images contoured offline by the alternate profession. Dice similarity coefficient (DSC), mean distance to agreement (MDA), Hausdorff distance (HD) and volume metrics were used to analyse contours. Additionally, the online radiographer contours and optimised plans (n = 59) were analysed using the offline clinician defined contours. After clinical implementation of radiographer contouring, target volume comparison and dose analysis was performed on 20 contours from five patients. RESULTS: Comparison of the radiographers' and clinicians' contours resulted in a median (range) DSC of 0.92 (0.86 - 0.99), median (range) MDA of 0.98 mm (0.2-1.7) and median (range) HD of 6.3 mm (2.5-11.5) for all 117 fractions. There was no significant difference in volume size between the two groups. Of the 59 plans created with radiographer online contours and overlaid with clinicians' offline contours, 39 met mandatory dose constraints and 12 were acceptable because 95 % of the high dose PTV was covered by 95 % dose, or the high dose PTV was within 3 % of online plan. A clinician blindly reviewed the eight remaining fractions and, using trial quality assurance metrics, deemed all to be acceptable. Following clinical implementation of radiographer contouring, the median (range) DSC of CTV was 0.93 (0.88-1.0), median (range) MDA was 0.8 mm (0.04-1.18) and HD was 5.15 mm (2.09-8.54) respectively. Of the 20 plans created using radiographer online contours overlaid with clinicians' offline contours, 18 met the dosimetric success criteria, the remaining 2 were deemed acceptable by a clinician. CONCLUSION: Radiographer and clinician prostate and seminal vesicle contours on MRI for an online adaptive workflow are comparable and produce clinically acceptable plans. Radiographer contouring for prostate treatment on a MR-linac can be effectively introduced with appropriate training and evaluation. A DSC threshold for target structures could be implemented to streamline future training.

Prevalence and correlates of adolescent pregnancy, motherhood and adverse pregnancy outcomes in Uttar Pradesh and Bihar.

Pregnancy during adolescence is a major risk factor for adverse pregnancy outcomes. Further, Motherhood during the adolescent period is identified as a major global health burden. Considering the widely known importance of the negative impact of adolescent pregnancy, motherhood at an early age, and adverse pregnancy outcomes, this paper aims to provide insight into correlates of teen pregnancy, adolescent motherhood and adverse pregnancy outcome. This study utilizes the data from UDAYA survey conducted in Uttar Pradesh and Bihar. The eligible sample size for the study was 4897 married adolescent girls between the ages of 15 and 19 years. Bivariate analysis with a chi-square test of association and Multivariable logistic regression analysis was performed to fulfill the aim of the study. Our study shows that a major proportion of married adolescents (61%) got pregnant before the age of 20 years and around 42% of all adolescent married women gave birth to a child before reaching the age of 20 years. Adolescents who married before the age of 18 years were 1.79 times more likely to experience pregnancy (OR: 1.79; CI: 1.39-2.30) and 3.21 times more likely to experience motherhood (OR: 3.21; CI: 2.33-4.43). In the present study, women who experienced physical violence were at higher risk for having an adverse pregnancy outcome (OR: 1.41; CI: 1.08-1.84) than those who did not experience physical violence. To conclude, regional and national level efforts focused on improving early marriage, education and empowering women and girls can be beneficial.

Interobserver variation of clinical oncologists compared to therapeutic radiographers (RTT) prostate contours on T2 weighted MRI.

The implementation of MRI-guided online adaptive radiotherapy has enabled extension of therapeutic radiographers' roles to include contouring. An offline interobserver variability study compared five radiographers' and five clinicians' contours on 10 MRIs acquired on a MR-Linac from 10 patients. All contours were compared to a "gold standard" created from an average of clinicians' contours. The median (range) DSC of radiographers' and clinicians' contours compared to the "gold standard" was 0.91 (0.86-0.96), and 0.93 (0.88-0.97) respectively illustrating non-inferiority of the radiographers' contours to the clinicians. There was no significant difference in HD, MDA or volume size between the groups.

Insights into the perinatal phenotype of Kabuki syndrome in infants identified by genome-wide sequencing.

Increasing use of unbiased genomic sequencing in critically ill infants can expand understanding of rare diseases such as Kabuki syndrome (KS). Infants diagnosed with KS through genome-wide sequencing performed during the initial hospitalization underwent retrospective review of medical records. Human phenotype ontology terms used in genomic analysis were aggregated and analyzed. Clinicians were surveyed regarding changes in management and other care changes. Fifteen infants met inclusion criteria. KS was not suspected prior to genomic sequencing. Variants were classified as Pathogenic (n = 10) or Likely Pathogenic (n = 5) by American College of Medical Genetics and Genomics Guidelines. Fourteen variants were de novo (KMT2D, n = 12, KDM6A, n = 2). One infant inherited a likely pathogenic variant in KMT2D from an affected father. Frequent findings involved cardiovascular (14/15) and renal (7/15) systems, with palatal defects also identified (6/15). Three infants had non-immune hydrops. No minor anomalies were universally documented; ear anomalies, micrognathia, redundant nuchal skin, and hypoplastic nails were common. Changes in management were reported in 14 infants. Early use of unbiased genome-wide sequencing enabled a molecular diagnosis prior to clinical recognition including infants with atypical or rarely reported features of KS while also expanding the phenotypic spectrum of this rare disorder.

The psychological impact of the COVID-19 pandemic on fertility care: a qualitative systematic review.

The objective of this systematic review was to characterise psychological impacts of the COVID-19 pandemic related to fertility care. We conducted a systematic search following PRISMA guidelines of five databases (EMBASE, Medline-OVID, CINAHL, Web of Science, and PsycINFO) from March 17th 2020 to April 10th 2021. Citing articles were also hand-searched using Scopus. Of the 296 original citations, we included fifteen studies that encompassed 5,851 patients seeking fertility care. Eleven studies only included female participants, while four included both male and female participants. The fifteen studies unanimously concluded that the COVID-19 pandemic caused negative psychological impacts on fertility care. Risk factors included female sex, single marital state, previous ART failure, prior diagnoses of anxiety or depression, and length of time trying to conceive. Specific concerns included the worry and frustration of clinic closure, concerns about pregnancy and COVID-19 infection, and advancing age. There were contrasting beliefs on whether the decision to stop fertility treatments during the COVID-19 pandemic was justified. In addition, we found that many patients preferred to resume fertility treatment, despite anxieties regarding the risk of the COVID-19 virus. We recommend that fertility providers screen patients for risk factors for poor mental health and tailor support for virtual care.

Typhoid conjugate vaccine effectiveness in Malawi: evaluation of a test-negative design using randomised, controlled clinical trial data.

BACKGROUND: Typhoid conjugate vaccines are being introduced in low-income and middle-income countries to prevent typhoid illness in children. Vaccine effectiveness studies assess vaccine performance after introduction. The test-negative design is a commonly used method to estimate vaccine effectiveness that has not been applied to typhoid vaccines because of concerns over blood culture insensitivity. The overall aim of the study was to evaluate the appropriateness of using a test-negative design to assess typhoid Vi polysaccharide-tetanus toxoid conjugate vaccine (Vi-TT) effectiveness using a gold standard randomised controlled trial database. METHODS: Using blood culture data from a randomised controlled trial of Vi-TT in Malawi, we simulated a test-negative design to derive vaccine effectiveness estimates using three different approaches and compared these to randomised trial efficacy results. In the randomised trial, 27 882 children aged 9 months to 12 years were randomly assigned (1:1) to receive a single dose of Vi-TT or meningococcal capsular group A conjugate vaccine between Feb 21 and Sept 27, 2018, and were followed up for blood culture-confirmed typhoid fever until Sept 30, 2021. FINDINGS: For all three test-negative design approaches, vaccine effectiveness estimates (test-negative design A, 80·3% [95% CI 66·2 to 88·5] vs test-negative design B, 80·5% [66·5 to 88·6] vs test-negative design C, 80·4% [66·9 to 88·4]) were almost identical to the randomised trial results (80·4% [95% CI 66·4 to 88·5]). Receipt of Vi-TT did not affect the risk of non-typhoid fever (vaccine efficacy against non-typhoid fever -0·4% [95% CI -4·9 to 3·9] vs -1% [-5·6 to 3·3] vs -2·5% [-6·4 to 1·3] for test-negative design A, test-negative design B, and test-negative design C, respectively). INTERPRETATION: This study validates the test-negative design core assumption for typhoid vaccine effectiveness estimation and shows the accuracy and precision of the estimates compared with the randomised controlled trial. These results show that the test-negative design is suitable for assessing typhoid conjugate vaccine effectiveness in post-introduction studies using blood culture surveillance. FUNDING: Bill & Melinda Gates Foundation.