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Setting the scene: cross-sectional country comparisons of associations between young adult care and education, employment, and health outcomes in Europe
Full text linkWith increasing demand for informal carers, young adults are taking up care of dependent adults. However, early adulthood is the period in which most people invest in human capital and transition to employment. Being neither in employment nor in training (NEET) during this period may have long-term effects, increasing the risk of poor mental health. This study explores data from the third wave of the European Health Survey to better understand the situation of young adult carers (18-29 years old) in Europe. Using multilevel regression models, results indicate that, overall, those who care for dependent adults are more likely to be in NEET status (intensive caring), perceive bad health, and report worse mental health. However, country-level care resources did not affect the gap between carers and non-carers. Hence, cultural differences, or other forms of support, arise as the main role of country differences in the health risks of young adult carers
Astrocyte Kir4.1 expression level territorially controls excitatory transmission in the brain.
Full text linkIntense brain activity elevates extracellular potassium, potentially leading to overexcitation and seizures. Astrocytes are crucial for restoring healthy potassium levels, and an emerging focus on their Kir4.1 channels has reopened the quest into the underlying mechanisms. We find that the Kir4.1 level in individual astrocytes sets the kinetics of their potassium and glutamate uptake current. Combining electrophysiology with multiplexed optical sensor imaging and FLIM reveals that rises in extracellular potassium would normally boost presynaptic Ca2+ entry and release probability at excitatory synapses unless such synapses are surrounded by the Kir4.1-overexpressing astrocytes. Inside the territories of Kir4.1-overexpressing astrocytes, high-frequency afferent stimulation fails to induce long-term synaptic potentiation, and the high-potassium waves of cortical spreading depolarization are markedly attenuated. Biophysical exploration explains how astrocytes can regulate local potassium homeostasis by engaging Kir4.1 channels. Our findings thus point to a fundamental astrocytic mechanism that can restrain the activity-driven rise of excitability in brain circuits
Role of the calcium-sensing receptor in regulating vascular function
Full text linkFunctional expression of the calcium-sensing receptor (CaSR) in calcitropic tissues, for example, parathyroid glands and kidneys, is important for maintaining Ca2+ homeostasis. It is also established that the CaSR is present in tissues previously thought to be noncalcitropic and this review discusses the role of the CaSR in vascular function, focusing mainly on contractility but also outlining its role in cell proliferation and calcification. Stimulation of the CaSR by extracellular Ca2+ concentration ([Ca2+]o) on perivascular sensory nerves and vascular endothelial cells is associated with vasodilatation through the release of vasoactive substances and stimulation of IKCa channels and nitric oxide synthesis, respectively, which mediate endothelium-derived hyperpolarizations and activation of BKCa channels and KATP channels in vascular smooth muscle cells (VSMCs). CaSR-induced vasoconstrictions are mediated by the CaSR expressed in VSMCs, which are coupled to the Gq/11 protein-coupled pathway. In addition, the CaSR expressed on VSMCs also regulates proliferation and calcification. Consequently, the CaSR has been implicated in regulating systemic and pulmonary blood pressure and calcimimetics and calcilytics are potential therapeutic targets for cardiovascular diseases, such as hypertension, pulmonary artery hypertension, and atherosclerosis
Management of dyslipidaemia in patients with comorbidities - facing the challenge Value and limitations of lipid lowering drugs in liver disease Effects/Interactions of lipid-lowering agents on/with the liver.
Full text linkOBJECTIVES: This review aims to examine the evidence on the benefits and risks of lipid lowering drugs in patients with liver disease. Elevated liver enzyme levels often lead to cautious discontinuation of these drugs, potentially withholding from patients their benefit in reducing cardiovascular disease morbidity and mortality. METHODS AND RESULTS: Using a literature search of PubMed, we examine the efficacy and safety profiles of various lipid lowering agents, including statins, ezetimibe, bempedoic acid, PCSK9 inhibitors, fibrates, and icosapent ethyl, focusing particularly on their potential side effects related to liver health. A major challenge in the assessment of drug-induced hepatotoxicity is the fact that it relies heavily on case reports rather than real world evidence. There is currently a lack of robust evidence on lipid-lowering therapy in people with pre-existing liver disease. Nevertheless, we have attempted to summarize the available data for all the drugs mentioned in order to provide guidance for the treatment of patients with liver dysfunction. CONCLUSION: This review highlights the need for further research to optimize treatment strategies for patients with coexisting liver and cardiovascular disease
Clinical and cost-effectiveness of detailed anomaly ultrasound screening in the first trimester: a mixed-methods study
Full text linkBackground
In the United Kingdom, pregnant women are offered two scans: at 11–14 and 18–20 weeks’ gestation. Current guidance supports fetal anatomical screening at the second scan, but evidence suggests earlier detection is possible.
Objectives
To determine clinical and cost-effectiveness of a detailed two-dimensional ultrasound scan in the first trimester for detection of fetal anomalies, in addition to usual practice.
Design
Systematic review and meta-analysis.
Nationwide survey.
Analysis of National Congenital Anomaly Disease Registry data.
Consensus procedure.
Prospective survey of parental opinions.
Probabilistic decision-analytic model for cost-effectiveness.
Value-of-information analysis.
Setting
United Kingdom National Health Service.
Participants
Pregnant women and partners.
Interventions
Detailed anomaly ultrasound at 11–14 weeks’ gestation, in addition to usual practice.
Main outcome measures
Diagnostic accuracy, protocol development, health economic modelling and value-of-information analysis.
Data sources
MEDLINE (OvidSP), EMBASE (OvidSP), Science Citation Index and Conference Proceedings Citation Index-Science (Web of Science Core Collection); National Congenital Anomaly Disease Registry; European Congenital Anomalies Registry; Surveys of National Health Service Trusts; screening sonographers, midwives and doctors; and parents; National Schedule of National Health Service Costs (2019–20).
Review methods
Systematic review and meta-analysis for diagnostic accuracy.
Results
First-trimester ultrasound detects 93.3% (95% confidence interval 90.4% to 95.7%) of a pre-selected group of eight major anomalies with specificity of 99.99% (95% confidence interval 99.98% to 99.99%) and positive predictive value of 96.5% (95% confidence interval 93.3 to 98.8, 416,877 fetuses, 40 studies). For major cardiac anomalies, the respective data are 55.8% (95% confidence interval 45.9% to 65.5%), 99.98% (95% confidence interval 99.97% to 99.99%) and 94.85% (95% confidence interval 91.63% to 97.32%, 306,872 fetuses, 45 studies). Of NHS trusts surveyed, 77% currently perform first-trimester anatomy assessment, with evidence of inequity of care; earlier screening resulted in more diagnoses before 16 weeks’ gestation. A consensus procedure (n = 172) developed an anatomical protocol and minimum targets for diagnosis. Parental survey (n = 1374) indicated that over 90% would opt for such screening. Modelling of singleton pregnancies undergoing earlier anomaly screening using two-dimensional ultrasound was associated with increased mean healthcare costs per woman (£11, 95% confidence interval £1 to £29) and maternal quality-adjusted life-years (0.002065, 95% confidence interval 0.000565 to 0.00358), an incremental cost per quality-adjusted life-year of £5270, with likelihood of being cost-effective at £20,000 per quality-adjusted life-year of over 95%. Additional modelling predicted reductions in infant healthcare costs and quality-adjusted life-years. Decision uncertainty was low. Value-of-information analysis of cost-effectiveness results showed no groups of parameters for which further research to reduce uncertainty would likely prove cost-effective.
Limitations
Study heterogeneity; the lack of a universal reference standard; simplifying assumptions relating to economic model structure; and estimation of some parameters are documented and justified. The rarity of the conditions made estimation of longer-term maternal and infant costs and quality-adjusted life-years challenging, resulting in likely under-estimation of healthcare costs.
Conclusions
With standardisation and training, first-trimester ultrasound screening for fetal anomalies is clinically effective with over 90% detection for eight major conditions and low false-positive rates. Decision uncertainty around implementation is low and a prospective study would not be an efficient investment. Adding first-trimester anomaly screening to the current screening likely represents a cost-effective use of resources and is acceptable to parents.
Future work
Focus on developing an implementation framework to modify the current United Kingdom Fetal Anomaly Screening Programme.
Study registration
This study is registered as PROSPERO CRD42018111781 and CRD42018112434.
Funding
This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/19/10) and is published in full in Health Technology Assessment; Vol. 29, No. 22. See the NIHR Funding and Awards website for further award information
Knowledge, Attitudes, and Practices of Iraqi Parents Regarding Antibiotic Use in Children and the Implications
Full text linkBackground: Antibiotic misuse is a major global health issue, particularly in low- and middle-income countries (LMICs), where inappropriate use contributes to antimicrobial resistance (AMR). Inappropriate antibiotic use is exacerbated in LMICs by pressure from parents on physicians and pharmacists to prescribe and dispense antibiotics for their children, often for viral infections. There is currently limited knowledge of key issues in Iraq to improve future antibiotic use. Consequently, we explored knowledge, attitudes, and practices (KAPs) of Iraqi parents regarding antibiotic use in their children to provide future direction. Methods: A cross-sectional survey was conducted between November 2023 and September 2024 among 1878 parents in four districts of Iraq. A structured questionnaire assessed parents’ KAPs towards antibiotic-related uses and practices. Data were analyzed using descriptive statistics and Chi-square tests to examine the associations between demographic variables and KAP indicators. Results: Among the participants, 83% were aware that antibiotics are ineffective for viral infections, and 75% recognized potential side effects from antibiotics. Despite this knowledge, 63% of parents admitted to administering antibiotics to their children without a prescription, with 42% discontinuing treatment once symptoms improved. Factors including cost, dosage, and taste influenced antibiotic selection. Parents with higher education and income levels were more likely to engage in self-medication. Pharmacists were the primary source of antibiotic information for 52% of respondents. Conclusions: Despite adequate knowledge, inappropriate practices such as self-medication and discontinuing treatment early were prevalent. Targeted educational campaigns, particularly among parents with higher education levels and incomes, are necessary to mitigate AMR in Iraq
Toxicant and Nicotine Exposure in Pregnant Smokers, Vapers, and Nicotine-Replacement Users: Cross-Sectional Study
No full textIntroduction
Given the increasing usage of vaping during pregnancy and limited longitudinal health-related data, there is an urgent need to assess the potential risks of vaping.
Aims and Methods
A cross-sectional study was conducted among pregnant UK adults (n = 140). Five study groups were purposively recruited: exclusive-smokers (n = 38), exclusive-vapers (former smokers) (n = 35), dual users of smoking and vaping (n = 25), dual users of smoking and nicotine replacement therapy (n = 10), and “never-users” of nicotine or tobacco products (n = 32). Sociodemographic, smoking, and vaping characteristics were assessed. Participants’ urine samples were analyzed for biomarkers of exposure to tobacco alkaloids, and toxicants, including 14 volatile organic compounds (VOCs), tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), heavy metals (cadmium, lead, chromium, nickel, copper, and tin) and a polycyclic aromatic hydrocarbon (2-naphthol). Regression analysis was used to compare biomarkers by group.
Results
Nicotine levels varied across product users, but not significantly. After controlling for confounders, for most VOCs, biomarker levels were similar for exclusive-vapers and never-users and significantly lower than for exclusive-smokers and any dual users. There were generally no significant differences between groups for 2-naphthol or heavy metals. For NNAL, cadmium and chromium, a high percentage of values were below the limit of detection, making analyses unreliable.
Conclusions
During pregnancy, former smokers who are established exclusive vapers, but not dual users, had levels of selected VOCs that were substantially lower than those for exclusive smokers and comparable with those who have never used nicotine or tobacco products.
Implications
Based on the biomarkers assessed in this study, during pregnancy, on average, exclusive-vapers are likely to have similar levels of exposure to selected VOCs as never-users and far lower levels than exclusive-smokers or dual-users (although dual-vaping and smoking may result in less exposure than exclusive-smoking). This provides preliminary information about exposure to vaping during pregnancy and suggests that, for some biomarkers, exclusive vaping is likely to result in lower exposures than exclusive smoking or dual-use. There may be exposure to other vaping toxicants that were not explored in this study. Studies are needed to assess pregnancy and birth outcomes as well as early life effects
Health outcomes of children with Prader-Willi or Angelman syndromes: a European population-based multicentre study.
Full text linkBackground/aim Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are rare imprinting disorders caused by the aberrant expression of 15q11.2-q13 imprinted genes. Due to their rarity, data on health outcomes during infancy are limited. This EUROlinkCAT study aimed to investigate major health outcomes of children with these chromosomal disorders.
Methods Data of children born in 1995–2014 and diagnosed with PWS (n=150) or AS (n=46), collected by 11 population-based congenital anomaly registries, were linked to local electronic healthcare and mortality databases and analysed.
Results Children with PWS had a survival rate of 94% (95% CI 89.5% to 98.7%) by 10 years of age. Nearly all children (99.5%, 95% CI 97.6% to 99.9%) with PWS required hospitalisation during the first year of life with a median length of stay of 25 days; a high proportion continued to need hospital care later in life (93.2% at 1–4 years and 79.6% at 5–9 years) with shorter stays (1.2 and 0.5 days per year, respectively). In comparison, no deaths occurred among children with AS by 10 years of age. Fewer children with AS required hospitalisation in the first year of life (59.0%, 95% CI 39.6% to 74.0%); as they grew older, the proportion admitted was 68% (95% CI 40.0% to 85.0%) at 5–9 years. Children with PWS and AS underwent first surgery at approximately 1.8 years and 2.5 years, respectively.
Conclusions This study provides valuable evidence for improving family counselling and promoting an adequate healthcare support system
Tremor Asymmetry and the Development of Bilateral Phase-Specific Deep Brain Stimulation for Postural Tremor.
Full text linkBackground
Tremor phase-locked deep brain stimulation (DBS) has been shown to modulate symptom severity in postural tremor, including essential and dystonic tremor, with less energy than existing systems. Previous studies focused on unilateral stimulation; it remains unknown how tremor asymmetry interacts with stimulation in the context of bilateral phase-locked DBS.
Methods
Archival limb acceleration from nine essential tremor patients was analyzed for asymmetries in tremor amplitude, frequency, and instability, and their relationship with continuous high-frequency DBS (cDBS). Bilateral phase-locked DBS was tested in one essential tremor and one dystonic tremor patient.
Results
Postural tremor is asymmetric, with larger tremor power linked to smaller amplitude and frequency stability in one hand. These asymmetries were significantly reduced during cDBS, with greater effects on larger amplitude tremors. Bilateral phasic DBS effects were also asymmetric.
Conclusions
This study enhances understanding of tremor asymmetry and its relationship with DBS, offering insights for patient-specific tremor treatments
The effect of early nipple stimulation on third stage of labour duration and estimated blood loss: A systematic review and meta-analysis
Full text linkBackground
Post-partum haemorrhage due to uterine atony remains a leading cause of maternal mortality worldwide with a high portion occurring in under resourced settings. The risk of post-partum haemorrhage increases with prolonged duration of the third stage of labour. Early nipple stimulation promotes the early release of oxytocin, which has beneficial effects on uterine tone. Therefore, this meta-analysis evaluates the impact of early nipple stimulation on the duration of the third stage of labour and estimated blood loss.
Aim
To assess whether early nipple stimulation following uncomplicated deliveries effects the duration of the third stage of labour and estimated blood loss.
Methods
A comprehensive search was conducted in PubMed, EMBASE, Cochrane, CiNAHL, Scopus and Web of Science, covering studies published up to February 5th 2024. Eligible studies included randomised control trials and observational studies involving women with singleton pregnancies and live foetuses who engaged in nipple stimulation in the third stage. Studies that reported the duration of the third stage of labour and/or estimated blood loss were included. Exclusion criteria comprised stillbirths, multiple pregnancies and the use of general anaesthesia. Data was analysed using a random-effects model. This review was registered with PROSPERO (CRD42023494605).
Results
Nine studies involving 789 mothers were included. Early nipple stimulation reduced blood loss and improved uterine tone. When synthetic oxytocin was not used, early nipple stimulation reduced the duration of the third stage of labour.
Conclusion
Early nipple stimulation may be a viable alternative to uterotonics in uncomplicated deliveries, especially in low-resource settings. Further high-quality primary research is indicated to build upon the preliminary findings of this current meta-analysis
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