Foundation National Research Articles

Immigrant Generation, Ethnicity, and Early-life Education Outcomes: Evidence from the Born in Bradford Family Cohort Study

Abstract This paper examines the relationship between ethnicity and immigrant generation in relationship to early educational outcomes and their potential determinants. Using Born in Bradford, a large longitudinal birth cohort, and its linked education and health records, we investigated the associations between ethnicity, immigration generations and education measures (Early Years Foundation Stage Profile and National Curriculum Key Stage One). We looked at the children of both first- and second-generation immigrants and compared them with White British non-immigrant children. Logistic regressions were used to examine the explanatory factors of the differences. On the Early Years Foundation Stage Profile, children of first-generation Pakistani immigrants did less well than White British non-immigrant children. This was largely related to language barriers. There were no significant differences between the children of second-generation Pakistani families and children of White British non-immigrant families. In Key Stage One results, there were no differences in reading and maths between children of first-generation Pakistani immigrants and the White British children, however, children of first-generation Pakistani immigrants had better scores in Key Stage One writing. Children of second-generation Pakistani immigrants had better odds of achieving expected standards in most models for reading and writing (but not maths) than the White British children. This might be attributed to better socioeconomic circumstances. Immigrant generation is an independent predictor for early educational outcomes. There are different patterns associated with different immigrant generations. Early life policy interventions to help children of first-generation immigrant with their English language before school could improve these children’s school readiness.

Ethnic inequities in use of breast conserving surgery and radiation therapy in Aotearoa/New Zealand: which factors contribute?

PurposeAotearoa/New Zealand (NZ) faces ethnic inequities with respect to breast cancer survival and treatment. This study establishes if there are ethnic differences in (i) type of surgery and (ii) receipt of radiotherapy (RT) following breast conserving surgery (BCS), among women with early-stage breast cancer in NZ.MethodsThis analysis used Te Rēhita Mate Ūtaetae (Breast Cancer Foundation National Register), a prospectively maintained database of breast cancers from 2000 to 2020. Logistic regression models evaluated ethnic differences in type of surgery (mastectomy or BCS) and receipt of RT with sequential adjustment for potential contributing factors. Subgroup analyses by treatment facility type were undertaken.ResultsOf the 16,228 women included, 74% were NZ European (NZE), 10.3% were Māori, 9.4% were Asian and 6.2% were Pacific. Over one-third of women with BCS-eligible tumours received mastectomy. Asian women were more likely to receive mastectomy than NZE (OR 1.62; 95% CI 1.39, 1.90) as were wāhine Māori in the public system (OR 1.21; 95% CI 1.02, 1.44) but not in the private system (OR 0.78; 95% CI 0.51, 1.21). In women undergoing BCS, compared to NZE, Pacific women overall and wāhine Māori in the private system were, respectively, 36 and 38% less likely to receive RT (respective OR 0.64; 95% CI 0.50, 0.83 and 0.62; 95% CI 0.39, 0.98).ConclusionA significant proportion of women with early-stage breast cancer underwent mastectomy and significant ethnic inequities exist. Modern guidelines encourage BCS + RT. In NZ, this outcome must be carefully monitored by ethnicity to facilitate equitable surgical management of early-stage breast cancer.

Does diabetes affect breast cancer survival?

The objective of this study is to investigate the influence of diabetes on breast cancer-specific survival among women with breast cancer in Aotearoa/New Zealand. This study included women diagnosed with invasive breast cancer between 2005 and 2020, with their information documented in the Te Rēhita Mate Ūtaetae-Breast Cancer Foundation National Register. Breast cancer survival curves for women with diabetes and those without diabetes were generated using the Kaplan-Meier method. The hazard ratio (HR) of breast cancer-specific mortality for women with diabetes compared to women without diabetes was estimated using the Cox proportional hazards model. For women with diabetes, the 5-year and 10-year of cancer-specific survival were 87% (95% CI: 85%-88%) and 79% (95% CI: 76%-81%) compared to 89% (95% CI: 89%-90%) and 84% (95% CI: 83%-85%) for women without diabetes. The HR of cancer-specific mortality for patients with diabetes compared to those without diabetes was 0.99 (95% CI: 0.89-1.11) after adjustment for patient demographics, tumor characteristics, and treatments. Age at cancer diagnosis and cancer stage had the biggest impact on the survival difference between the two groups. When stratified by cancer stage, the cancer-specific mortality between the two groups was similar. While differences in survival have been identified for women with diabetes when compared to women without diabetes, these are attributable to age and the finding that women with diabetes tend to present with more advanced disease at diagnosis. We did not find any difference in survival between the two groups due to differences in treatment.

Comparing acute hospital outcomes for people with post-stroke aphasia who do and do not require an interpreter

ABSTRACT Background People with communication differences are known to have poorer hospital outcomes than their peers. However, the combined impact of aphasia and cultural/linguistic differences on care and outcomes after stroke remains unknown. Objectives To investigate the association between cultural/linguistic differences, defined as those requiring an interpreter, and the provision of acute evidence-based stroke care and in-hospital outcomes for people with aphasia. Methods Cross-sectional, observational data collected in the Stroke Foundation National Audit of Acute Services (2017, 2019, 2021) were used. Multivariable regression models compared evidence-based care and in-hospital outcomes (e.g., length of stay) by interpreter status. Models were adjusted for sex, hospital location, stroke type and severity, with clustering by hospital. Results Among 3122 people with aphasia (median age 78, 49% female) from 126 hospitals, 193 (6%) required an interpreter (median age 78, 55% female). Compared to people with aphasia not requiring an interpreter, those requiring an interpreter had similar care access but less often had their mood assessed (OR 0.50, 95% CI 0.32, 0.76), were more likely to have physiotherapy assessments (96% vs 90% p = 0.011) and carer training (OR 4.83, 95% CI 1.70, 13.70), had a 2 day longer median length of stay (8 days vs 6 days, p = 0.003), and were less likely to be independent on discharge (OR 0.54, 95% CI 0.33, 0.89). Conclusions Some differences exist in the management and outcomes for people with post-stroke aphasia who require an interpreter. Further research to explore their needs and the practical issues underpinning their clinical care pathways is required.

Walking the Walk: Inclusion of Lived Experience Experts in the Design of the National Hemophilia Foundation's National Research Blueprint for Those Living with Inherited Bleeding Disorders

BACKGROUND: The National Hemophilia Foundation's (NHF) vision of a world without inheritable blood disorders begins with research. To that end, we have initiated a multi-year project with the goal of building a transformational research enterprise through full community-engagement. Building this innovative research ecosystem has required us to rethink how we prioritize research questions mattering most to those impacted by and caring for people with inheritable bleeding disorders (Lived Experience Experts (LEEs)), how we democratize the research culture and structure to streamline efforts, and how we ensure research findings are disseminated, relevant, representative, and inclusive. As a result of the Research State of the Science Summit in September 2021, considerable progress has been made in identifying areas most urgently requiring attention to make the greatest impact for the future. Over the past year, members of the National Research Blueprint's (NRB) steering committee (SC) and working groups (WGs) have worked to produce the necessary components to launch, sustain, and expand a research network in which LEEs contribute at all levels. Inherent in this strategy is the involvement of the LEE in research prioritization, design, implementation, and analysis as an equal partner to the traditional research team members. To demonstrate the important role played by LEEs in this process, we report the demographic make-up of the members of the NRB SC and WGs to demonstrate the large LEE presense in this effort. METHODS: Based on the insights generated during the SOS, in addition to the SC, seven multi-disciplinary NRB WGs have been created: Community Engagement; Health Equity, Diversity, and Inclusion; Infrastructure; Lived Experience Experts (defined as individuals, their caregivers, and family members directly impacted by inheritable bleeding disorders, whose diverse and personal knowledge gives each individual the unique ability to translate lived experiences into meaningful system change); Policy; Research and Development; and Workforce (Figure 1). The WGs have been charged with addressing critical questions in the creation, sustainability, and eventual expansion of this LEE-focused research network. We collected basic demographic information for members of the SC and WGs. RESULTS: A total of 62 individuals are currently participating as members of either the NRB SC or WGs. Of these SC or WG members, 36 (58%) are female and 26 (42%) are male. Fourteen (23%) individuals are Black, Indigenous, or People of Color. Thirty SC or WG members are LEEs (48%). Twelve (33%) of the females are LEEs. Eighteen (60%) of the males are LEEs. A total of 29 (47%) of the SC and WG members are professional health-care providers (HCPs), defined as an individual with an academic degree allowing the provision of medical care to people. Twenty (69%) of the female SC or WG members are providers. Nine (31%) of the male SC or WG members are HCPs. Of the participating HCPs, 6 (21%) are LEEs including 2 (10%) who are female and four (44%) who are male (Table 1). CONCLUSIONS: The NHF's multi-year process of building the National Research Blueprint for inheritable bleeding disorders has prioritized the participation of people most familiar with bleeding disorders, the LEEs, from the beginning of the process. By including LEEs in all steps of development of this endeavor, each of the WGs have benefited from the exchange of ideas and insights from the LEEs, resulting in an innovative and inclusive approach to asking questions most impactful to those affected by inheritable bleeding disorders. Almost half of the members of the NRB SC and WGs are LEEs, who are also well represented among HCPs in dual roles. The NRB, driven by, for, and with LEEs, will redefine the inheritable bleeding disorders research landscape.

Relationship of business practices and characteristics to supervisors’ perceived effectiveness of disability recruitment

BACKGROUND: Employers are increasingly interested in the inclusion of employees with disabilities in the workplace. To be inclusive, employers need effective strategies for recruiting people with disabilities (PWD) that supervisors can endorse, as they are ultimately accountable for the success of all employees that they supervise, including people with disabilities. To date, little research has focused on effective practices for recruiting people with disabilities or the supervisors’ perspectives on successful disability recruitment practices. OBJECTIVE: This study presents results from the 2017 Kessler Foundation National Employment and Disability Survey-Supervisor Perspectives (KFNEDS-SP) that utilized a novel approach to investigating employer organizational characteristics and practices related to the recruitment of PWD. METHODS: The KFNEDS-SP is a web-based survey that used standard, replicable survey methods to collect data from a Qualtrics business-to-business panel of supervisors at U.S. organizations. Respondents included 6,530 supervisors ages 18 and older from private, nonprofit, and governmental organizations across industries. RESULTS: The results show that several organizational characteristics and practices are significantly associated with supervisor perceived effectiveness of disability recruitment processes. The degree of effort put forth to recruit people with disabilities, commitment from upper management in hiring and accommodating employees with disabilities, training hiring managers in accessible recruitment and interview practices for people with disabilities were all positively related to supervisors’ perceived effectiveness of their organizations’ disability recruitment processes. However, organizations that put a lot of effort into recruiting for diversity or had diversity hiring goals were less likely to be perceived by supervisors to have effective disability recruitment processes. CONCLUSION: Supervisors are at the center of an organization’s effort to include people with disabilities in the workplace and, as such, are good barometers of what works and does not work to support the recruitment, hiring and onboarding of people with disabilities. The results of this study point to several organizational characteristics and practices that individually and together are likely to support efforts to include people with disabilities in the workplace. Disability workforce intermediaries can use these findings to assist businesses successfully include people with disabilities in their workforce.

Adipo-myokine Irisin, a Promising Antioxidant against Nicotine Induced Oxidative Stress in BALB/c mice.

To determine the role of r-irisin in attenuating nicotine-induced oxidative stress by estimating serum oxidative stress markers and antioxidant enzymes in BALB/c mice. This 18 month experimental study was carried out at Foundation University Islamabad and National Institute of Health starting in 2020. Thirty healthy BALB/c mice were divided into three groups. Group-I (control group) received normal saline 1ml/kg body weight intra-peritoneally daily for 28 days. Experimental group, Group-II received nicotine 2mg/kg body weight intra-peritoneally, for 28 days to induce oxidative stress. Experimental Group-III was given r-irisin 0.5 μg/g body weight/day via tail vein injection, for the last 14 days in addition to intraperitoneal nicotine for 28 days. On 29th day, intra-cardiac blood samples were taken for estimation of serum antioxidant enzymes [Superoxide dismutase (SOD), Reduced Glutathione (GSH) and Catalases (CAT)], and Thiobarbituric Acid-Reactive Substances (TBARS) levels as lipid peroxidation marker using ELISA. SPSS version 24 was used for statistical analysis. Significant difference in parameters across groups was calculated using one way ANOVA. P-value of < 0.05 was considered significant. Group-II showed statistically significant increase in serum lipid peroxidation marker (TBARS) levels (p<0.001) and reduction in serum anti-oxidative enzymes (SOD, CAT, GSH) levels (p< 0.001) as compared to Group-I. In Group-III, with co administration of r-irisin, significant improvement in antioxidant enzymes levels and reduction in TBARS levels was observed (p< 0.001) as compared to Group-II. Irisin ameliorates nicotine induced oxidative stress by improving serum anti-oxidant enzyme levels and reducing serum lipid peroxidation marker.

First-trimester prediction of preterm pre-eclampsia and prophylaxis by aspirin: Effect on spontaneous and iatrogenic preterm birth.

To report the predictive performance for preterm birth (PTB) of the Fetal Medicine Foundation (FMF) triple test and National Institute for health and Care Excellence (NICE) guidelines used to screen for pre-eclampsia and examine the impact of aspirin in the prevention of PTB. Secondary analysis of data from the SPREE study and the ASPRE trial. Multicentre studies. In SPREE, women with singleton pregnancies had screening for preterm pre-eclampsia at 11-13 weeks of gestation by the FMF method and NICE guidelines. There were 16 451 pregnancies that resulted in delivery at ≥24 weeks of gestation and these data were used to derive the predictive performance for PTB of the two methods of screening. The results from the ASPRE trial were used to examine the effect of aspirin in the prevention of PTB in the population from SPREE. Comparison of performance of FMF method and NICE guidelines for pre-eclampsia in the prediction of PTB and use of aspirin in prevention of PTB. Spontaneous PTB (sPTB), iatrogenic PTB for pre-eclampsia (iPTB-PE) and iatrogenic PTB for reasons other than pre-eclampsia (iPTB-noPE). Estimated incidence rates of sPTB, iPTB-PE and iPTB-noPE were 3.4%, 0.8% and 1.6%, respectively. The corresponding detection rates were 17%, 82% and 25% for the triple test and 12%, 39% and 19% for NICE guidelines, using the same overall screen positive rate of 10.2%. The estimated proportions prevented by aspirin were 14%, 65% and 0%, respectively. Prediction of sPTB and iPTB-noPE by the triple test was poor and poorer by the NICE guidelines. Neither sPTB nor iPTB-noPE was reduced substantially by aspirin.

Relationship between emotional intelligence and disaster response self-efficacy: A comparative study in nurses

BackgroundNurses who constitute an important part of the health system play a critical role in all stages of disaster management, especially in providing care for disaster victims. It is essential for nurses to have adequate education and qualifications to reduce disaster-related mortality and morbidity rates in the community. The qualifications of nurses depend not only on their knowledge and skills but also on their emotional abilities such as empathy and stress management. Emotions can impact individuals' levels of self-efficacy in disaster response, and it may help explain the differences in self-efficacy among nurses. ObjectiveThis study aimed to investigate the relationship between emotional intelligence and disaster response self-efficacy, and compare the scores between hospital nurses and National Medical Rescue Team nurses. DesignA cross-sectional design. SettingsThis research was conducted at Bezmialem Foundation University Hospital and National Medical Rescue Team in Istanbul, Turkey. ParticipantsThis study included 565 nurses from two different institutions. MethodsA survey consisting of the Demographic Information Form, the Modified Schutte Emotional Intelligence Scale, and the Disaster Response Self-Efficacy Scale was administered to the nurses. The data collected from March to April of 2022 was analyzed using SPSS 25.0 program. The differences and relationships among variables were determined by using Chi-square tests, student's t-tests, Pearson correlation, and linear regression analyses. ResultsOf the 565 participants, 219 (38.8%) were hospital nurses and 346 (61.2%) were NMRT nurses. NMRT nurses scored significantly higher in emotional intelligence (131.45 ± 6.15 versus 129.75 ± 6.01) and disaster response self-efficacy (80.71 ± 11.38 versus 77.77 ± 11.33) than hospital nurses (p < 0.05). In addition, emotional intelligence was found to be significantly and positively correlated to disaster response self-efficacy (r = 0.885, p < 0.05). ConclusionsThe emotional intelligence and disaster response self-efficacy were positively correlated, and both levels of NMRT nurses higher than hospital nurses. These findings suggest that healthcare organizations should take the emotional intelligence of nurses as an important means to improve their disaster response selfefficacy. It can improve the quality of disaster response to obtain well self-efficacy by developing the emotional intelligence of nurses.

Percutaneous Closure of the Patent Ductus Arteriosus in Infants ≤2 kg: IMPACT Registry Insights.

Percutaneous patent ductus arteriosus (PDA) closure is becoming the standard of care for definitive closure in progressively smaller and younger neonates. The objective of this study was to assess safety and feasibility of percutaneous PDA closure in patients ≤2 kg. This was a cohort study using the IMPACT Registry (Improving Pediatric and Adult Congenital Treatments) from the American College of Cardiology Foundation's National Cardiovascular Data Registry. Patients who were ≤2 kg at the time of percutaneous PDA closure were included. The primary outcome was the composite of technical failure and/or major adverse event. A total of 1587 attempted PDA closures were included, with a 3% incidence of technical failure and 5.5% incidence of the composite outcome. Major adverse events were observed in 3.8% of the patients; the most common events were device embolization requiring retrieval and unplanned cardiac or vascular surgery in 1.3% and 1.3% of cases, respectively. The incidence of the composite outcome was associated with the need for arterial access (P < .001) as well as annual hospital volume of percutaneous PDA closures in infants ≤2 kg (P = .001). The incidence of the composite outcome has decreased overtime, whereas median weight at the time of procedure has also diminished. Percutaneous PDA closure appears to be safe and feasible procedures in infants ≤2 kg. The incidence of major adverse events has continued to decline over the years and seems to have a strong correlation with individual center case volumes and expertise.

First report of tumor-informed circulating tumor DNA in fibrolamellar carcinoma in adolescents and young adults: 51 patients.

3034 Background: Fibrolamellar Carcinoma (FLC) is an extremely rare form of primary liver cancer (50-200 cases/year), unrelated to hepatocellular carcinoma. The only established standard of care is surgery. However, recurrence is at least 80%, even with R0 surgery, suggesting that FLC is best thought of as a systemic disease instead of a surgical disease. Systemic therapies in retrospective studies of more than 25 show immunotherapy and chemotherapy combinations have promise. Circulating “tumor-informed” tumor DNA (ctDNA) is a tool for tracking microscopic systemic disease, serving as a marker of systemic involvement, has shown success in management of other cancers. FLC has never been studied using this technology. Our retrospective study of 51 patients over a 2.5-year period is the first attempt to understand if ctDNA can be helpful in the management of FLC. Methods: All patients consented to blood draws on a 1-3 monthly basis, according to the company (Signatera) protocol. All patients had regular imaging reviewed by the FibroFighters Foundation National Tumor Board. Complete response (CR), Partial response (PR) (&gt; 30% decrease), Progressive Disease (PD) (&gt; 20% increase), and Stable Disease (SD) (neither PD/PR/CR) were recorded according RECIST 1.1. The imaging closest in time to the blood draw was used for correlation purposes. “Negative” is defined as a value = 0.00. “Positive” is defined as a value &gt; 0.00. Results: Fifty-one FLC patients (26M, 25F, median age 23, range 10-56), 92% stage (III/IV), consented to ctDNA “blood biopsies,” (n=226 samples, mean 4.4/patient, range 1-11). Negative values correlated with no evidence of disease (NED) on imaging 78% of the time, positive values with disease 94% [PPV/NPV/sens/spec of 0.78/0.94/0.93/0.81]. NPV and sens increased to almost 100% with a ctDNA threshold of &gt; 1.0 at the expense of a lower PPV and spec. However, consecutive negative ctDNA values correlated with radiologic NED 86% [PPV/NPV/sens/spec = 0.86/0.84/0.77/0.91] without a single PD in this cohort (n=64). A “downward trend or slope” on consecutive values predicted Objective Response (CR+PR) and Disease Control (CR+PR+SD) at 68% and 96% [PPV/NPV/sens/spec of 0.68/0.49/0.36/0.78 and 0.96/0.26/0.36/0.94, respectively], while an “upward trend” performed less well to predict relapse [PPV/NPV/sens/spec = 0.54/0.98/0.94/0.81]. Conclusions: In this first exploration of 51 young FLC patients, and 226 tissue-informed cell free ctDNA data points, “Positive” and “Negative” values overall performed well for predicting RECIST 1.1 “disease” or “NED” respectively, especially for consecutive values of zero, where no progressions were observed in 64 distinct FLC scenarios. A downward trend or “slope” performed better than an upward trend to predict objective response (PR+CR) versus relapse (PD).

0459 Cardiovascular Endpoints for Obstructive Sleep Apnea with Twelfth Nerve Stimulation: Measures of Sleep-Related Function

Abstract Introduction Obstructive sleep apnea (OSA) is an increasingly prevalent sleep-related breathing disorder linked to cognitive dysfunction and daytime sleepiness. Positive airway pressure (PAP) therapy, the first-line treatment for OSA, may improve cognitive function and sleepiness, but responses vary. Hypoglossal nerve stimulation (HGNS) is a novel and effective PAP alternative, but its effect on mitigating cognitive decline secondary to OSA is unknown. In the first sham-controlled HGNS trial, we evaluated the effect of HGNS therapy on cognitive measures and patient-reported outcomes (PROs) in patients with moderate-severe OSA. Methods In a double-blind, sham-controlled, randomized crossover therapy trial, patients already stabilized on HGNS therapy underwent four weeks of active and four weeks of sham HGNS, each with a 1-week washout period. Sham therapy was defined as the lowest voltage at which HGNS was sensed by the patient or visualized by the clinician. Cognitive measures (Psychomotor Vigilance Test [PVT], Digit Symbol Substitution Task [DSST]) and sleep-related PROs (Epworth Sleepiness Scale [ESS], Snoring Visual Analog Scale [VAS], Insomnia Severity Index [ISI], Functional Outcomes of Sleep Questionnaire [FOSQ]) were assessed after each 4-week period and compared between active and sham therapy. Results Sixty randomized patients were included. On average, participants were elderly (67.3±9.9 years), overweight (BMI 28.7±4.6 kg/m2) and had severe OSA prior to HGNS therapy (AHI 33.1±14.9 events/hour). Patients’ AHI decreased to 23.0±15.6 events/hour with sham therapy (p=0.0001) and 18.1±14.8 events/hour with active therapy (p&amp;lt; 0.0001), with a 4.9 event/hour decrease between active and sham therapy (p=0.014). There were no significant differences in performance measures on PVT or DSST between active and sham HGNS. All sleep-related PROs were statistically significant with moderately large (effect sizes ~0.41-0.56) improvements following active HGNS. Conclusion The HGNS system permits a unique investigation of the therapy “on/off” effect on measures of cognitive function. In the first sham-controlled, randomized crossover trial of patients using HGNS, all sleep-related PROs, but not objective measures of cognition, were significantly different between sham and active (therapeutic) levels. These findings warrant additional investigation examining the relationship between subjective and objective measures of function in OSA. Support (if any) American Heart Association (17SDG33670349) American Sleep Medicine Foundation (176-JF-17) National Institutes of Health (P01-HL094307)

Multiphase Veteran Engagement to Develop a Spinal Cord Injury Employment Survey.

Spinal cord injury is a condition that adversely impacts employment and economic stability. The Kessler Foundation National Employment and Disability Survey (KFNEDS) was developed to understand the experience of striving to work among persons with disabilities. However, this survey was not intended to capture the employment experiences of veterans living with spinal cord injury. The aim of this study was to engage veterans living with a spinal cord injury to adapt the KFNEDS for veterans living with this specific disability. Describe the process and outcomes of actively engaging veterans living with spinal cord injury in the revision of the KFNEDS. In this multiphase qualitative study, we used an iterative veteran-centered approach to engage veterans living with an SCI in all project phases. We consulted with a Veterans' hospital's Veteran Engagement Group and convened a study-specific Community Action Board to engage in a collaborative partnership with the research team. We recruited 17 veterans living with a spinal cord injury, employed or looking for employment since their spinal cord injury, to participate in focus groups and cognitive interviews that informed the adaptation of the KFNEDS-VS. A provisional version of the KFNEDS-VS included 37 survey questions in the following sections: Disability Screen, Employment Screen, Disability, Employment Overall, Looking for Work, At Work, and Workplace Accommodations and Supports. Revisions included wording changes for clarity, veteran and spinal cord injury-specific content that was missing from the questions or response options, and removal of irrelevant questions. Engaging veterans in multiple phases of the study lead to the development of a relevant survey that captures the lived experience of veterans seeking, obtaining, and maintaining employment following spinal cord injury.

Reimagining Our Public Health Systems: The Robert Wood Johnson Foundation's National Commission to Transform Public Health Data Systems.

Reimagining Our Public Health Systems: The Robert Wood Johnson Foundation's National Commission to Transform Public Health Data Systems.

The evolution of financial literacy over time and its predictive power for financial outcomes: evidence from longitudinal data

AbstractWe administered the FINRA Foundation's National Financial Capability Study questionnaire to members of the RAND American Life Panel in 2012 and 2018. Using this unique, longitudinal data set, we investigate the evolution of financial literacy over time and shed light on the effect of financial knowledge on financial outcomes. Over a six-year observation period, financial literacy appears to be rather stable, with a slight tendency to decline at older ages. Importantly, financial literacy has significant predictive power for future financial outcomes, even after controlling for baseline outcomes and a wide set of demographics and individual characteristics that influence financial decision making.

Microbial biofilms are shaped by the constant dialogue between biological and physical forces in the extracellular matrix.

Microbial biofilms are shaped by the constant dialogue between biological and physical forces in the extracellular matrix.

Evaluation of Nanopore sequencing for Mycobacterium tuberculosis drug susceptibility testing and outbreak investigation: a genomic analysis

Mycobacterium tuberculosis whole-genome sequencing (WGS) has been widely used for genotypic drug susceptibility testing (DST) and outbreak investigation. For both applications, Illumina technology is used by most public health laboratories; however, Nanopore technology developed by Oxford Nanopore Technologies has not been thoroughly evaluated. The aim of this study was to determine whether Nanopore sequencing data can provide equivalent information to Illumina for transmission clustering and genotypic DST for M tuberculosis. In this genomic analysis, we analysed 151 M tuberculosis isolates from Madagascar, South Africa, and England, which were collected between 2011 and 2018, using phenotypic DST and matched Illumina and Nanopore data. Illumina sequencing was done with the MiSeq, HiSeq 2500, or NextSeq500 platforms and Nanopore sequencing was done on the MinION or GridION platforms. Using highly reliable PacBio sequencing assemblies and pairwise distance correlation between Nanopore and Illumina data, we optimise Nanopore variant filters for detecting single-nucleotide polymorphisms (SNPs; using BCFtools software). We then used those SNPs to compare transmission clusters identified by Nanopore with the currently used UK Health Security Agency Illumina pipeline (COMPASS). We compared Illumina and Nanopore WGS-based DST predictions using the Mykrobe software and mutation catalogue. The Nanopore BCFtools pipeline identified SNPs with a median precision of 99·3% (IQR 99·1-99·6) and recall of 90·2% (88·1-94·2) compared with a precision of 99·6% (99·4-99·7) and recall of 91·9% (87·6-98·6) using the Illumina COMPASS pipeline. Using a threshold of 12 SNPs for putative transmission clusters, Illumina identified 98 isolates as unrelated and 53 as belonging to 19 distinct clusters (size range 2-7). Nanopore reproduced 15 out of 19 clusters perfectly; two clusters were merged into one cluster, one cluster had a single sample missing, and one cluster had an additional sample adjoined. Illumina-based clusters were also closely replicated using a five SNP threshold and clustering accuracy was maintained using mixed Illumina and Nanopore datasets. Genotyping resistance variants with Nanopore was highly concordant with Illumina, having zero discordant SNPs across more than 3000 SNPs and four insertions or deletions (indels), across 60 000 indels. Illumina and Nanopore technologies can be used independently or together by public health laboratories performing M tuberculosis genotypic DST and outbreak investigations. As a result, clinical and public health institutions making decisions on which sequencing technology to adopt for tuberculosis can base the choice on cost (which varies by country), batching, and turnaround time. Academy for Medical Sciences, Oxford Wellcome Institutional Strategic Support Fund, and the Swiss South Africa Joint Research Award (Swiss National Science Foundation and South African National Research Foundation).

The association between mental disorders and subsequent years of working life: a Danish population-based cohort study

Mental disorders can affect workforce participation via a range of mechanisms. In this study, we aimed to estimate the association between different types of mental disorders and working years lost, defined as the number of years not actively working or enrolled in an educational programme. In this population-based cohort study, we included all people aged 18-65 years (mean 38·0 [SD 13·9]) in the Danish Civil Registration System from Jan 1, 1995 to Dec 31, 2016. Information on mental disorders was obtained from the Danish Psychiatric Central Research Register and information on labour market characteristics was obtained from administrative registers. Follow-up started at age 18 years, immigration to Denmark, or on Jan 1, 1995, whichever came later; and it ended at age 65 years, death, emigration from Denmark, disability pension, voluntary early retirement, or Dec 31, 2016 (whichever came earlier). As the main outcome, we estimated working years lost for those diagnosed with any mental disorder and 24 types of mental disorders, as well as for the general population of same age and sex. We decomposed total working years lost into periods of unemployment or sick leave, disability pension, voluntary early retirement, or death. Data on ethnicity were not available through administrative registers. A total of 5 163 321 individuals, 2 642 383 men and 2 520 938 women, were followed up for 65·4 million person-years. Overall, 488 775 (9·47%) individuals were diagnosed with a mental disorder. On average, individuals with mental disorders lost an additional 10·52 (95% CI 10·48-10·57) years of working life compared with the general Danish population. Receiving a disability pension (7·54 [7·49-7·59] years) and longer periods of unemployment (2·24 [2·21-2·27] years) accounted for most of this difference. Our findings foreground the substantial impact of mental disorders on workforce participation. There is a need to invest in programmes that reduce the burden of working years lost and assist people with mental disorders in returning to the workforce. Lundbeck Foundation and Danish National Research Foundation.

Efficacy and safety of methylphenidate and behavioural parent training for children aged 3–5 years with attention-deficit hyperactivity disorder: a randomised, double-blind, placebo-controlled, and sham behavioural parent training-controlled trial

There is insufficient evidence to support treatment recommendations for preschool children aged 3-5 years with attention-deficit hyperactivity disorder (ADHD). We aimed to investigate the efficacy and safety of methylphenidate and behavioural parent training in reducing the frequency and severity of symptoms and improving global functioning in preschool children with ADHD. We did an 8-week, randomised, double-blind, placebo-controlled and sham behavioural parent training-controlled clinical trial (the MAPPA Study) in children aged 3-5 years with moderate-to-severe ADHD. The trial was conducted at the Institute of Psychiatry, Hospital das Clinicas, University of São Paulo Medical School, São Paulo, Brazil. Participants were randomly assigned (1:1:1) to receive immediate-release methylphenidate plus educational intervention (sham behavioural parent training), placebo medication plus behavioural parent training, or placebo medication plus educational intervention. Randomisation was done by an independent research manager by use of a permuted block randomisation procedure. Parents, teachers, study staff, and evaluators remained masked to group allocation. Methylphenidate and placebo were titrated to a maximum dose of 1·25 mg/kg per day administered orally twice daily, and behavioural parent training and the educational intervention were delivered weekly through 90 min sessions with both the child and parent, conducted by two psychologists or learning therapists. The primary outcomes were parents' and teachers' composite scores of the Swanson, Nolan, and Pelham-IV scale (SNAP-IV-P/T), the Clinical Global Impressions Severity (CGI-S) scale, and the Children's Global Assessment Scale (CGAS). This trial is registered with ClinicalTrials.gov, NCT02807870, and is now complete. All participants were invited to participate in an open observational follow-up, which is ongoing. Between Aug 21, 2016, and Oct 21, 2019, 153 children were randomly assigned to receive methylphenidate plus the educational intervention (n=51), placebo plus behavioural parent training (n=51), or placebo plus the educational intervention (n=51). Nine (6%) children discontinued treatment. All participants were included in the intention-to-treat analysis. Children in the methylphenidate plus educational intervention group showed greater reductions in the SNAP-IV-P/T (endpoint mean difference -3·93 [95% CI -7·14 to -0·73], p=0·049; effect size -0·55 [95% CI -0·99 to -0·10]) and CGI-S scores (endpoint mean difference -0·49 [-0·82 to -0·17], p=0·0088; effect size -0·70 [-1·16 to -0·24]) and a greater increase in CGAS scores (endpoint mean difference 5·25 [95% CI 2·09 to 8·40], p=0·0036; effect size 0·80 [95% CI 0·32 to 1·28]) than children in the placebo plus educational intervention group. Children in the placebo plus behavioural parent training group did not have significantly different SNAP-IV-P/T scores (endpoint mean difference -3·18 [95% CI -6·38 to 0·02], p=0·077; effect size -0·44 [95% CI -0·89 to 0·003]) or CGI-S scores (endpoint mean difference -0·35 [-0·68 to -0·03], p=0·052; effect size -0·50 [-0·96 to -0·04]) compared to children in the placebo plus educational intervention group, but they had a greater increase in CGAS scores compared to the placebo plus educational intervention group (endpoint mean difference 3·69 [0·53 to 6·85], p=0·033; effect size 0·56 [0·08 to 1·04]). Children in the methylphenidate plus educational intervention versus placebo plus behavioural parent training group did not have statistically or clinically significant differences in primary outcomes. Children in the methylphenidate plus educational intervention group had more mild adverse events than the other two groups, and there were no between-group differences for moderate or severe adverse events. Methylphenidate was effective in reducing ADHD symptoms and improving functionality, and behavioural parent training was effective in improving functionality for preschool children with ADHD after 8 weeks of treatment. São Paulo Research Foundation and Brazilian National Council for Scientific and Technological Development.

Genomic characterisation of multidrug-resistant Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii in two intensive care units in Hanoi, Viet Nam: a prospective observational cohort study

Viet Nam has high rates of antimicrobial resistance (AMR) but little capacity for genomic surveillance. This study used whole genome sequencing to examine the prevalence and transmission of three key AMR pathogens in two intensive care units (ICUs) in Hanoi, Viet Nam. A prospective surveillance study of all adults admitted to ICUs at the National Hospital for Tropical Diseases and Bach Mai Hospital was done between June 19, 2017, and Jan 16, 2018. Clinical and environmental samples were cultured on selective media, characterised with MALDI TOF mass spectrometry, and sequenced with Illumina. Phylogenies based on the de-novo assemblies (SPAdes) were constructed with MAFFT (PARsnp), Gubbins, and RAxML. Resistance genes were detected with Abricate against the US National Center for Biotechnology Information database. 3153 Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii isolates from 369 patients were analysed. Phylogenetic analysis revealed predominant lineages within A baumannii (global clone 2, sequence types ST2 and ST571) and K pneumoniae (ST15, ST16, ST656, ST11, and ST147) isolates. Isolation from stool was most common with E coli (87·0%) followed by K pneumoniae (62·5%). Of the E coli, 85·0% carried a blaCTX-M variant, while 81·8% of K pneumoniae isolates carried blaNDM (54·4%), or blaKPC (45·1%), or both. Transmission analysis with single nucleotide polymorphisms identified 167 clusters involving 251 (68%) of 369 patients, in some cases involving patients from both ICUs. There were no clear differences between the lineages or AMR genes recovered between the two ICUs. This study represents the largest prospective surveillance study of key AMR pathogens in Vietnamese ICUs. Clusters of closely related isolates in patients across both ICUs suggests recent transmission before ICU admission in other health-care settings or in the community. UK Medical Research Council Newton Fund, Viet Nam Ministry of Science and Technology, Wellcome Trust, Academy of Medical Sciences, Health Foundation, and UK National Institute for Health and Care Research Cambridge Biomedical Research Centre.