Year Of Life Research Articles

Abstract 4135333: Peripheral Perfusion Index: Normative Values From Electronically Reported Critical Congenital Heart Disease Screenin

Background: Critical Congenital Heart Disease (CCHD) screening is performed in an effort to reduce morbidity and mortality associated with CCHD by facilitating early detection. This screening consists of pulse oximetry and is most effective at identification of cyanotic cardiac lesions, with less sensitivity for left sided obstructive lesions. Research: Question Peripheral perfusion index (PPI) is obtained from the plethysmographic signal of a pulse oximeter and represents the ratio of pulsatile to non-pulsatile blood flow. As such, it is a surrogate for peripheral perfusion at the site of measurement. PPI has been postulated to be an adjunctive screening method for low perfusion states in neonates, including left sided obstructive lesions. To date, reference ranges of PPI values in neonates have not been published in the United States. This project utilized electronically reported CCHD screening results to establish normative PPI data in healthy neonates. Methods: In Minnesota, CCHD screening results are electronically sent to the Minnesota Department of Health (MDH) and are cross referenced against the Minnesota Birth Information System, which tracks infants who are identified to have a congenital birth defect within the first year of life. These data were provided by the MDH for infants born in Minnesota from Jan 2017 through Dec 2022. Infants were included in the analysis if they did not have a known critical congenital heart defect, were born between 35 and 42 weeks gestation, and were 24-48 hours of life at time of screening. Results: PPI data from 11,179 cases were included in the analysis. Overall, there is a trend towards increasing PPI with gestational age. Pre-ductal PPI trended higher than post-ductal PPI. There was no difference between PPI in males and females. Conclusions: These data reflect trends identified in international data. This is the largest dataset to date of PPI in healthy neonates and the first in the United States. Future studies will compare neonates with left sided obstructive lesions against these normative data. If PPI is found to predict left sided obstructive lesions in neonates, there may be utility in use of PPI in CCHD screening to facilitate earlier detection of these lesions.

Why Early Chatter Matters: The Role of Language in Shaping Futures

The words we learn early in life are building blocks for our brains, helping them grow and helping us understand the world better. As we learn new words and the concepts behind them, we support the foundation on which our future learning, relationships, and achievements are built. A rich early vocabulary opens the door to understanding complex ideas, solving problems, and expressing thoughts and emotions more clearly. Early language can even support distant future outcomes such as academic success in high school and employment as an adult. This article will discuss why early chatter is so powerful, how it supports future learning, and what factors are the most important contributors to developing vocabulary in the first few years of life.

Abstract 4138333: Childhood Oral Health Associates with the Incidence of Ischemic Heart Disease, Myocardial Infarction and Ischemic Stroke in Adulthood

Introduction: Cardiovascular disease remains a considerable source of years of life lost. Thus, identification of possible risk factors and prevention strategies continues to be important. In adults, oral diseases are associated with the risk of cardiovascular disease, including ischemic heart disease (IHD), myocardial infarction (MI) and ischemic stroke (IS). Few studies have examined the effect of oral health in childhood on the risk of cardiovascular disease in adulthood, thus overlooking a potentially important avenue of early detection of high-risk individuals. Hypothesis: We hypothesize that poor childhood oral health is associated with IHD, MI, and IS in adulthood. Methods: Using nationwide Danish registry data from the National Child Odontology Register, National Patient Register, and the Central Person Register we followed individuals born between 1963 and 1972. Follow-up started in 1995 or by age 30 (whichever occurred last), and ended in 2018, where study participants were aged 46 to 56. Using Cox-proportional hazards modelling we examined the association of childhood oral health, defined as the highest registered level of dental caries and gingivitis for any one individual, with the occurrence of IHD, MI, and IS in adulthood. The highest achieved level of education between ages 25 and 30 was used as Cox-strata. Results: The study consisted of n = 569.057 individuals, 51.2% male, 48.8% female. The incidence of IHD was 26% (1.17; 1.86) higher in females with high levels of caries in childhood compared to those with low-level caries, 19% (1.08; 1.40) higher in males. Severe caries in childhood was associated with a 58% (1.19; 2.09) higher incidence of MI in females, 19% (1.01;1.42) higher in males, and a 45% (1.19; 1.78) higher incidence of IS, 52% (1.27; 1.81) in males. Females had a 52% (1.19; 1.94) higher incidence of MI, and males a 32% (1.15; 1.52) higher incidence of IS, if they had high levels of gingivitis as children (table 1). Conclusion: Poor oral health in childhood is associated with an increased incidence of IHD, MI, and IS, pointing to a potential new avenue for early identification of and prevention amongst high-risk individuals.

Abstract 4135480: Effect of Time Since Heart Failure Diagnosis or Hospitalization on the Cost-effectiveness of Dapagliflozin in Patients with Heart Failure with Mildly Reduced or Preserved Ejection Fraction

Background: Previous studies have shown dapagliflozin, a sodium-glucose co-transporter-2 inhibitor (SGLT2i), to be a cost-effective treatment option for patients with heart failure (HF) with preserved or mildly reduced ejection fraction (HFpEF/HFmrEF) in multiple European settings. Research question: Is the cost-effectiveness of dapagliflozin treatment in HFpEF/HFmrEF modified by either the time since HFpEF/HFmrEF diagnosis or the time since the last hospitalization for heart failure (HHF) event? Methods: A Markov cohort transition model was built for the UK setting, informed by patient-level data from the randomized, placebo-controlled DELIVER trial. The patient population was subset according to categories of time since last HHF event (including no prior HHF) and time since HF diagnosis (further subset to those with no prior HHF). For each subgroup, disease evolution was characterized by transitions among health states defined by quartiles of the Kansas City Cardiomyopathy Questionnaire Total Symptom Scale. The risk of fatal (cardiovascular and non-cardiovascular) and non-fatal events of worsening HF were modelled, adjusting for baseline characteristics and time-updating health state. Incremental costs and quality-adjusted life-years (QALYs) were calculated for each subgroup to yield incremental cost-effectiveness ratios (ICERs). Results: The lowest ICERs were observed for subgroups with the shortest time from HF diagnosis (with and without prior HHF) or last HHF event (Figure 1). Across all subgroups, the calculated ICERs were below the UK willingness-to-pay (WTP) threshold of £20,000/QALY gained. Conclusions: In patients with HFpEF/HFmrEF, the cost-effectiveness of dapagliflozin improved (via lower ICERs) in the subgroups corresponding to earliest disease (least time since an HHF event or HF diagnosis) compared with groups of later disease and potentially delayed treatment initiation. These findings suggest early optimization of HF therapy with implementation of guideline-directed medical therapy, including SGLT2is, may improve economic value.

Abstract 4134744: Trends and Disparities in Mortality Among Patients with Hypertensive Heart Disease and Congestive Heart Failure in the United States from 1999 to 2020

Background: Hypertensive heart disease (HHD) poses a growing public health concern. Global data reveal a concerning rise in HHD prevalence, deaths, and disability-adjusted life years (DALYs) between 1990 and 2019. The Framingham Study highlights that hypertension is linked to approximately one-quarter of heart failure cases. This association is even stronger among older adults, in whom hypertension is responsible for up to 68% of heart failure cases. Methods: This study analyzed death certificates within the CDC WONDER database for patients in the United States from 1999 to 2020. We identified deaths among individuals aged 25 years and older caused by HHD and CHF using the International Classification of Diseases, Tenth Revision (ICD-10) code I11.0. Age-adjusted mortality rates (AAMRs) per 1,000,000 individuals and annual percent change (APC) were computed and categorized based on year, gender, race/ethnicity, and urbanization status. Results: Between 1999 and 2020, a total of 302,270 deaths were reported in patients due to HHD with CHF. Overall, AAMR increased from 37.3 to 134.9 per 1,000,000 population between 1999 and 2020, with a significant decrease from 1999 to 2004 (APC: -7.91; 95% CI: -20.16 to -1.04), followed by a significant increase from 2004 to 2007 (APC: 42.47; 95% CI: 21.27 to 55.62), a slight decrease from 2007 to 2014 (APC: -0.9; 95% CI: -9.38 to 2.39), and finally a steep increase from 2014 to 2020 (APC: 14.22; 95% CI: 10.87 to 20.84). Gender-based analysis revealed that men had slightly higher AAMRs than women (Men: 63.1; 95% CI: 62.8 to 63.5 vs. Women: 60.7; 95% CI: 60.5 to 61). Moreover, AAMRs were highest among non-Hispanic African Americans (109.6; 95% CI: 108.6 to 110.6), followed by non-Hispanic American Indian or Alaska Natives (66.6; 95% CI: 63.1 to 70.1), non-Hispanic Whites (58.5; 95% CI: 58.2 to 58.7), Hispanics (53.7; 95% CI: 52.9 to 54.5), and non-Hispanic Asian or Pacific Islanders (39; 95% CI: 38–39.9). In addition, non-metropolitan areas had higher AAMRs than metropolitan areas (non-metropolitan: 65.7; 95% CI: 65.2 to 66.3 vs. metropolitan: 62.1; 95% CI: 61.8 to 62.3) (Figure 1). Conclusions: Despite an initial decline, mortality from combined HHD and CHF has risen significantly since 1999. Notably, mortality was most pronounced among men, non-Hispanic African Americans, and individuals residing in non-metropolitan areas.

Forecasting the Worldwide Impact of Stroke for individuals aged 45 and above

Background:We aimed to assess the global impact of stroke in people aged 45 years and older between 1990 and 2030, focusing on morbidity, mortality and disability-adjusted life years (DALYs). Methods:Generalized additive models (GAM) were used to project disease burden from 2020 to 2030. Additionally, the association between sociodemographic index (SDI) and stroke burden was investigated, and regional differences were assessed by Mann U test-Whitney. Results:The overall age-standardized stroke incidence rate (ASIR) among adults aged 45 years and older is projected to increase from 2020 to 2030, with an estimated annual percentage change (EAPC) of 1.29. Conversely, the age-standardized death rate (ASDR) in EAPC is expected to decrease by -1.48, and the age-standardized DALY in EAPC is expected to decrease by -1.66. By 2030, men are expected to have higher ASIR (181.81) and ASDR (87.31) than women (ASIR: 151.85, ASDR: 65.20). Regional differences are large. East Asia is expected to have the highest ASIR in 2030 (265.55). Age estimates show that older age groups, particularly those aged 75 to 79, are at higher risk of stroke. In addition, there is a significant inverse relationship between SDI and stroke severity, with areas with higher SDI tending to have lower morbidity, mortality, and DALYs. Conclusion: From 1990 to 2030, ASIR is expected to upgrade, especially in East Asia and regions with lower SDI. Men will bear a greater burden than women.

Abstract 4146312: Global Burden and Trend of Atrial Fibrillation and Flutter in the 27 European Union Countries from 1990-2021: A Systematic analysis for the Global Burden of Disease Study 2021

Introduction: Atrial Fibrillation (Afib) and Flutter ranks as the fifth leading cause of death among all cardiovascular diseases (CVD). Given the scarcity of consistent previous estimates, this study is the first to assess the burden of Afib and Flutter in the European Union (EU) over the past three decades, including the initial two years of the COVID-19 pandemic. Methods: Using global burden of disease study 2021 meta tool, we estimated prevalence, incidence, deaths, disability adjusted life years (DALYs), years lived with disability (YLDs) due to Afib and Flutter by age, sex, year and location across the 27 EU countries from 1990-2021. Results: The total number of prevalence rose from 5 million (95% uncertainty interval: 3.9-6.4 million) in 1990 to 8.6 million (7.2-10.3 million) in 2021. The total percentage of change (TPC) in deaths increased by 130% (110%-143%), and YLDs by 69% (56%-84%) from 1990-2021. Austria saw the highest increase in age-standardized incidence rates (ASIR) at 83%, followed by Czechia at 50%. Sweden experienced the largest rise in mortality rates (ASMR) at 93%, with Estonia at 35%, and in YLD rates (ASYLDR), Austria led with a 90% increase followed by Sweden at 49%. In terms of age, individuals aged 55 and older recorded the highest death toll at 70,269 (57,793-77,019) and the highest incidence at 607,960 (397,686-868,122) in 2021. Regarding gender, males showed an increased TPC in overall burden compared to females, with males observing an increase and females a decreasing trend in ASIR (5% vs -7%), ASMR (7% vs -4%), and ASYLDR (7% vs -5%) from 1990-2021. Conclusion: Deaths due to Afib and Flutter accounted for 4.26% of all CVD in EU. The escalating prevalence and mortality rates of Afib and Flutter across the EU highlight an urgent need for comprehensive healthcare strategies. Effective management should focus on bolstering preventive measures, advancing diagnostic techniques, and enhancing patient care frameworks, particularly for the aging demographic most at risk. Strategic collaboration across sectors, including innovative public health initiatives and policy reinforcement, is essential to curb this growing trend and safeguard public health.

Abstract 4126628: Worse Cardiac Structure and Function is Associated with Decline in Multiple Domains of Cognitive Function: the Atherosclerosis Risk in Communities (ARIC) Study

Background: Cognitive impairment is cross-sectionally associated with worse cardiac structure/function. However, limited data exist regarding cardiac structure/function and longitudinal changes in cognitive function. Objective: Determine the association of cardiac structure and function with longitudinal changes in cognitive performance in late life. Methods: Among HF- and dementia-free participants in the community-based ARIC study who attended the 5th study visit (V5; 2011-2013), underwent protocol echocardiography, and completed a neurocognitive test battery at both V5 and study Visit 6 (V6; 2015-17), we assessed associations of cardiac structure and function measures with changes in both domain-specific and global cognitive scores between V5 and V6 using multivariable linear regression. Models were initially adjusted for demographics and education level, with additional models further adjusting for cardiovascular risk factors and disease at both V5 and V6. The neuropsychological test battery consisted of 10 neuropsychological tests that covered 3 domains of cognitive function: memory, executive functioning, and language. Factor scores were constructed for each cognitive domain, and their average represented a global composite score. Results: Among 2,988 included participants, mean age was 74±5 years, 60% were female, 20% reported Black race, and mean LVEF was 66±6%. Over a mean of 4.9±0.6 years (the V5 to V6 interval), raw scores declined for all neuropsychological tests. In fully adjusted models, worse diastolic function (larger LAVi) and LV remodeling (greater LV mass index) were associated with decline in executive function. Lower LVEF was associated with decline in language function, while worse LV longitudinal strain – a more sensitive measure of systolic dysfunction – was associated with decline in executive function, language function, and global cognition performance (all p<0.05; Table). Conclusion: Subclinical LV remodeling and dysfunction is associated with greater declines in cognitive function over 5 years in late life. Differential associations were observed by cognitive domains, with executive function decline most uniformly associated with impairments in cardiac structure/function.

Cost-effectiveness analysis of transcatheter aortic valve implantation versus surgical aortic valve replacement in patients with severe aortic stenosis at low risk of surgical mortality in Sweden

Background: Transcatheter aortic valve implantation (TAVI) has shown similar or improved clinical outcomes compared with surgical aortic valve replacement (SAVR) in patients with symptomatic severe aortic stenosis at low risk for surgical mortality. This cost-utility analysis compared TAVI with SAPIEN 3 versus SAVR in symptomatic severe aortic stenosis patients at low risk of surgical mortality from the perspective of the Swedish healthcare system. Methods: A published, two-stage, Markov-based cost-utility model that captured clinical outcomes from the Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated according to Recommended Therapies (SWEDEHEART) registry (2018–2020) was adapted from the perspective of the Swedish healthcare system using local general population mortality, utility and costs data. The model had a lifetime horizon. Model outputs included changes in direct healthcare costs and health-related quality of life from using TAVI as compared with SAVR. Results: TAVI with SAPIEN 3 resulted in lifetime costs per patient of 940,541 Swedish krona (SEK) and lifetime quality-adjusted life years (QALYs) per patient of 7.16, whilst SAVR resulted in lifetime costs and QALYs per patient of 821,380 SEK and 6.81 QALYs, respectively. Compared with SAVR, TAVI offered an incremental improvement of +0.35 QALY per patient at an increased cost of +119,161 SEK per patient over a lifetime horizon, resulting in an incremental cost-effectiveness ratio of 343,918 SEK per QALY gained. Conclusion: TAVI with SAPIEN 3 is a cost-effective option versus SAVR for patients with symptomatic severe aortic stenosis at low risk for surgical mortality treated in the Swedish healthcare setting. These findings may inform policy decisions in Sweden for the management of this patient group.

Cost‐Effectiveness Analysis of Risky Health Interventions: Moving Beyond Risk Neutrality

ABSTRACTCost‐effectiveness analysis for health interventions is traditionally conducted in a risk‐neutral way, insensitive to risk attitudes in the population, which are potentially non‐neutral. While the standard outcome metric of quality‐adjusted life years (QALYs) aims to be deferential to people's valuations of health states, cost‐effectiveness analysis of risky interventions using the QALY metric is not similarly deferential to people's risk attitudes. I argue that there is no good justification for this practice. Non‐neutral attitudes to risk, especially where they concern individually life‐changing interventions need not be irrational, and so imposing neutrality is not justifiable as a way of debiasing preferences. Many common justifications for deference to health state preferences extend to risk attitudes. But even if reasons for deference do not extend, imposition of risk neutrality as opposed to any other rationally permissible risk attitude is under‐motivated as default practice. Thus, either methods for measuring risk attitudes separately and incorporating them into cost‐effectiveness analysis should be used more widely or a richer set of information should be presented to political decision‐makers and the public to enable them to decide how to take into account the individual risks faced by members of the population, on top of aggregate effects on population health.

QOL-06. OPTIMIZING NEUROFIBROMATOSIS CARE: A COMPREHENSIVE ECONOMIC EVALUATION OF A SPECIALIZED EXPERTISE CENTER’S IMPACT ON PATIENT OUTCOMES

Abstract Neurofibromatosis type 1 (NF1), NF2-related schwannomatosis (NF2) and other schwannomatoses represent a spectrum of genetic disorders characterized by the development of tumors on nerve tissues, profoundly impacting patients’ quality of life and posing complex challenges. Recognizing the imperative for comprehensive care delivery, we undertook to implement a Neurofibromatosis Expertise Center (CE) at the Centre hospitalier de l’Université de Montréal (CHUM), Quebec, Canada. Employing a robust analysis framework, we aimed to assess the economic viability of the CE by quantifying the Quality-Adjusted Life Years (QALYs) gained through centralized multidisciplinary neurofibromatosis care (cost-utility ratio = CAD/QALY gained). Leveraging data from validated questionnaires including the SF-6D, our preliminary analysis revealed significant enhancements in patients’ quality of life across diverse domains, including physical pain, visible cutaneous lesions, cognitive dysfunction, hearing loss, malignancies, psychiatric comorbidities, unemployment, physical disability, and social isolation. Notably, among the respondents (N = 115), patients receiving CE services reported a 12% increase in general health compared to a 25% decline among those without CE services. Moreover, 28% of CE patients reported improved overall health compared to 12% of those without CE services. Using the Work Productivity and Activity Impairment questionnaire (WPAI-GH), we found that cohorts followed in CE for ≥ 1 year (N = 45) experienced less work productivity losses compared to the most recent cohort (N = 32), which presented scores exceeding 6 on a 1-to-10 scale. We hypothesize that the establishment of the CE will yield profound improvements in patient health outcomes and alleviate financial strains on the Ministère de la Santé et des Services Sociaux du Québec (MSSS). Therefore, our next steps include discussing a strategy for funding application to the MSSS to ensure the accessibility of necessary care for patients. Continuing data collection and analysis will also provide a more comprehensive overview of patient characteristics and needs.

“Discover your potential to raise your children”: A psychoeducational infancy parenting intervention in Spain

AbstractBackgroundThe quality of parenting has a significant impact on healthy development across the life cycle. Recent research has highlighted the financial return of evidence‐based parenting programs that are well designed and implemented.ObjectiveTo analyze the impact of a psychoeducational guidance intervention program aimed at improving parenting skills.MethodThirty‐five families with children aged between 0 and 3.5 years referred from the educational, social, and health departments of the Vitoria‐Gasteiz City Council (Spain) participated in the study. Using a longitudinal approach, the intervention took place over the course of three home visits: initial pretest assessment visit, feedback and orientation visit, and a final posttest assessment visit.ResultsStatistically significant pretest–posttest differences were observed in parenting skills, including cognitive and socio‐emotional development scaffolding, parental self‐efficacy, parental adaptive stress, and diversity of experiences.ConclusionsSeveral areas for improvement were detected in the context of an intervention based on customized guidance for individual families. The implementation process indicated issues to be improved in future program editions.ImplicationsOur findings provide family and public health policy makers with empirical support for the implementation of parenting programs designed to help families to acquire and improve parenting competencies to foster their children's comprehensive development, focused on the period between 0 and 3.5 years of life. Results of the study favor the propagation among Spanish professionals who work with families of the use of quality standards of the evidence‐based approach related to quality of implementation and assessment of the impact of parenting programs.

Endoscopic resection of a juvenile jejunum polyp which caused recurrent intestinal bleeding in a 12-month-old child: clinical observation

BACKGROUND: To verify a source of obscure gastrointestinal bleeding leading to iron deficiency anemia is a challenging diagnostic problem. Intestinal polyps can be one of such sources. Sporadic juvenile intestinal polyps are extremely rare at the first year of life. The authors present a clinical case which demonstrates endoscopic diagnostics and resection of a jejunum polyp in a 12-month-old child weighing 6.3 kg. We did not find similar publications in literature. CLINICAL CASE DESCRIPTION: A 12-month-old boy was admitted to our clinic with long-lasting complaints of dark stool and iron deficiency anemia. For the first time, gastrointestinal bleeding symptoms appeared at the age of one month. The child was repeatedly examined, but gastrointestinal bleeding source was not found. The child was prescribed symptomatic therapy for iron deficiency anemia including red blood cell transfusion. At current hospitalization in our clinic an intestinal polyp and transient small intestinal intussusception were suspected at ultrasound examination. The child underwent esophagogastroduodenoscopy, video capsule endoscopy, colonoscopy, laparoscopy. But the source of the bleeding was not found. During the repeated enteroscopy at 40 cm distally to the pylorus a sporadic juvenile jejunum polyp 17×15 mm was found and resected. The postoperative period was uneventful. In 1 month, there were no complaints as for the catamnesis, the child's stool had the usual characteristics, the indicators of "red blood" corresponded to the age norm. CONCLUSION: A sporadic juvenile jejunal polyp may be a cause of obscure recurrent intestinal bleeding in children. Modern intraluminal endoscopy allows not only to put diagnosis, but also to perform a minimally invasive surgical intervention.

Instability of revised Korean Developmental Screening Test classification in first year of life

Instability of revised Korean Developmental Screening Test classification in first year of life

Giardia lamblia risk factors and burden in children with acute gastroenteritis in a Nicaraguan birth cohort

Background Giardia lamblia is an intestinal protozoan estimated to cause ~200 million symptomatic infections annually, mainly in children in low- and middle-income countries associated with intestinal damage, increased permeability, and malabsorption. Methods and results We describe here the epidemiology, incidence, clinical characteristics, and risk factors of acute gastroenteritis episodes (AGE) with G. lamblia detection (GAGE) using a birth cohort of 443 Nicaraguan children followed weekly until 36 months of life. From June 2017 to July 2021, 1385 AGE samples were tested by qPCR. G. lamblia was detected in 104 (7.5%) of AGE episodes. In all, 69 (15.6%) children experienced at least one GAGE episode, and 25 of them (36.2%) experienced more than one episode. The incidence rate of the first episode of GAGE was 6.8/100 child-years (95% CI, 4.5–9.1). During GAGE, bloody stools, vomiting, and fever were uncommon, and children were less likely to be treated at a primary care clinic, suggesting that GAGE is typically mild and most cases did not receive medical attention, which could facilitate higher parasite loads with increased possibilities of establishing chronic carriage. GAGE was more common in children 12–24 months of age (13.9/100 child-years [95% CI, 10.7–17.1]) as compared to other age groups. In our birth-cohort, children living in a home with an indoor toilet (aHR, 0.52 [95%CI, 0.29–0.92]), and being breastfed in the first year of life (aHR: 0.10 [95%IC, 0.02, 0.57]) had a lower incidence of GAGE. In contrast, being breastfed for ≤ 6 months was associated with a higher incidence if the children were living in houses without indoor toilets and earthen floors (HR, 7.79 [95% CI, 2.07, 29.3]). Conclusion Taken together, GAGE is more frequent under poor household conditions. However, breastfeeding significantly reduces the incidence of GAGE in those children.

Clinical, biochemical and molecular characteristics of classic homocystinuria in Saudi Arabia and the impact of newborn screening on prevention of the complications: A tertiary center experience

AbstractBackgroundClassic homocystinuria (HCU) is a rare inborn metabolic disease that is generally asymptomatic at birth. If untreated, it can cause a wide range of complications including intellectual disability, lens dislocation, and thromboembolism. This study aimed to describe the natural history and the molecular findings of patients with HCU, and to assess the importance of early diagnosis.MethodsThis study retrospectively collected data on patients attending the metabolic unit at Prince Sultan Military Medical City, Riyadh, Saudi Arabia from 2011 to 2024. Demographic, clinical, and molecular data was extracted from the electronic medical records.ResultsAmong the 33 patients with HCU enrolled, 5/33 (15%) were diagnosed by newborn screening and the rest were diagnosed on clinical grounds. The complication profile was vast, with neuropsychiatric, musculoskeletal, ophthalmic, and thromboembolic morbidities complicating the disease course in 28/33 (85%) of the patients. None of the newborn screened patients had complications while all of the non‐newborn screened patients had at least one complication, p < 0.0001. The majority of parents in this cohort were highly consanguineous, with 90% had first or second cousin marriage. Seven previously reported variants were detected in this cohort and one novel variant was found in three patients (c.828+2‐828+ 3 delins ACACTTGCATCC, p.?). The known pathogenic variant (c.969G>A, p. (Trp323*)) was seen in most of the patients, with all of them coming from one tribe.ConclusionsThis cohort gives further evidence that the newborn screening for HCU is likely to prevent the complications associated with the disease at least in the first few years of life. Therefore, newborn screening for HCU should be encouraged. Our molecular studies revealed the presence of a founder variant, detected in patients from a single tribe. This suggests that specific mutation testing may be cost‐effective for individuals from certain ethnicities.

Impact of department chair gender on paid parental leave across American anaesthesiology residencies

BackgroundResidency training and parenthood are conflicting pursuits for many residents, as both often occur during similar years of life. Online policy about paid parental leave for residents is important for...

Improving diets and multimorbidity prevention

In 2023, the UK government announced a Major Conditions Strategy, publishing ‘The case for change and our strategic framework’, which set out the focus on cancers, diabetes, dementia, mental ill health, musculoskeletal disorders, CVD and chronic respiratory diseases. Together, these conditions account for 60% of total disability-adjusted life years lost to early death or ill health in England, and one in four adults has at least two (multimorbidity). This review considers some of the key dietary risks for these major conditions and population policies that may improve diets and reduce risks. UK Government dietary recommendations, based on independent risk assessment and advice from the Scientific Advisory Committee on Nutrition, are encapsulated in the national food model, the Eatwell Guide. Based on key sources of dietary data – chiefly consumption data from the National Diet and Nutrition Survey and consumer purchase data from Kantar – most people do not meet dietary recommendations. This review considers how science and evidence inform health improvement policy. This includes policies that encourage healthier food choices, such as labelling and public procurement standards to those that minimise the impact of the less healthy choice such as sugar and salt reduction and reformulation. The review also considers nutritional approaches to managing some non-communicable diseases. Given the role nutrition and excess weight play in the onset, prognosis and quality of life for those living with one or more of the major conditions, there are huge potential gains from even small dietary improvements across population groups.

Estimates and trends in the global burden of glaucoma influenced by metabolic risk factors from Global Burden of Disease Study between 1990 to 2019

Purpose Glaucoma is an irreversible eye disease that causes blindness, which not only causes visual impairment and economic burden to patients, but also increases the social burden. This study aimed to estimate the global burden of glaucoma due to metabolic risk over the past 30 years. Methods The number and rate of deaths, disability-adjusted life years (DALYs), and age-standardized rates (ASRs) for metabolic risk factors-induced glaucoma were extracted. The estimated annual percentage changes (EAPCs) for ASRs were calculated using a generalized linear model with a Gaussian distribution to quantify the temporal trends in the global burden of metabolic risk factor-attributed glaucoma. The strength and direction of the association between the sociodemographic index (SDI) and the DALY rate were measured using Spearman's rank-order correlation. Results Approximately 0.07% of the global DALYs of glaucoma in 1990 were associated with metabolic risk factors, which increased to 0.1% in 2019. From 1990 to 2019, the global DALY cases of glaucoma caused by metabolic risk factors and the global burden of DALYs increased, whereas the DALY rate decreased with a higher SDI regional grade. The ASR of glaucoma disability loss years with a metabolic high risk increased with age, reaching the highest in the >85-year-old age group. Conclusion The burden of glaucoma caused by metabolic risk factors has increased over the past three decades, especially in regions with a low SDI and in old-age groups.

Cost-effectiveness analysis of lorlatinib and crizotinib in the first-line treatment of anaplastic lymphoma kinase-positive non-small cell lung cancer

ABSTRACT Objectives To assess the economic value of lorlatinib and crizotinib in the first-line treatment of anaplastic lymphoma kinase-positive non-small cell lung cancer at medical insurance negotiation prices from the viewpoint of China’s health system. Methods Based on data from the phase III clinical trial, a three-state partitioned survival model was established. In combination with parameters such as treatment costs, utility values, incidence of adverse reactions, and discount rates, the total incremental cost-effectiveness ratio (ICER) was simulated. Results The results of the fundamental analysis indicated that the patients in the lorlatinib group expended 709,671 yuan more than did the patients in the crizotinib group did but gained 3.09 quality-adjusted life years (QALYs). The ICER value was 229,782.6 yuan/QALY, which was lower than three times the per capita gross domestic product (GDP) of China. Conclusions Compared with crizotinib, lorlatinib may be a cost-effective first-line treatment choice for advanced ALK-positive NSCLC in China.